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This Sporting Life was directed by Lindsay Anderson.
|
[
{
"docid": "This_Sporting_Life",
"text": "This Sporting Life is a 1963 British feature film based on the 1960 novel of the same name by David Storey , which won the 1960 Macmillan Fiction Award . It recounts the story of a rugby league footballer , Frank Machin , in Wakefield , a mining area of Yorkshire , whose romantic life is not as successful as his sporting life . Storey , a former professional rugby league footballer , also wrote the screenplay . The film stars Richard Harris , Rachel Roberts , William Hartnell and Alan Badel . It was directed by Lindsay Anderson . The film was Richard Harris 's first starring role , and won him a Best Actor Award at the 1963 Cannes Film Festival . He was also nominated for an Oscar for Best Actor in a Leading Role . Rachel Roberts won her second BAFTA award for This Sporting Life and an Oscar nomination for best actress . Harris was nominated for the BAFTA that year as well . The film opened at the Odeon Leicester Square in London 's West End on 7 February 1963 .",
"title": ""
}
] |
[
{
"docid": "This_Sporting_Life_(novel)",
"text": "This Sporting Life is a 1960 novel by the English writer David Storey . It is set in Northern England and follows a man who tries to make it as a Rugby league player . It was the debut novel of Storey , himself a former player for Leeds . The book was the basis for Lindsay Anderson 's 1963 film This Sporting Life .",
"title": ""
},
{
"docid": "O_Lucky_Man!",
"text": "O Lucky Man ! is a 1973 British comedy-drama fantasy film , intended as an allegory on life in a capitalist society . Directed by Lindsay Anderson , it stars Malcolm McDowell as Mick Travis , whom McDowell had first played as a disaffected public schoolboy in his first film performance in Anderson 's film if ... ( 1968 ) . The film was entered into the 1973 Cannes Film Festival .",
"title": ""
},
{
"docid": "David_Sherwin",
"text": "David Sherwin ( born 1942 ) is a British screenwriter best known for his collaborations with director Lindsay Anderson and actor Malcolm McDowell on the films if ... ( 1968 ) ( for which Sherwin was nominated for a BAFTA Award for Best Screenplay ) , O Lucky Man ! ( 1973 ) and Britannia Hospital ( 1982 ) . Sherwin attended Tonbridge School , which provided much of the inspiration for the content of if ... In 1996 , Sherwin published a memoir , Going Mad in Hollywood : And Life with Lindsay Anderson , ( Andre Deutsch ) ISBN 978-0-233-98966-2 .",
"title": ""
},
{
"docid": "Celebrities_Anonymous",
"text": "Celebrities Anonymous is a 2009 American independent comedy film directed by Dennis Hemphill Jr. , starring Lindsay Zir , Joey Kern , Dianna Agron and Jamie Anderson . The film was produced by Lindsay Zir .",
"title": ""
},
{
"docid": "If....",
"text": "if ... . is a 1968 British drama film produced and directed by Lindsay Anderson satirising English public school life . Famous for its depiction of a savage insurrection at a fictitious boys ' boarding school , the X certificate film was made at the time of the May 1968 protests in France by a director who was strongly associated with the 1960s counterculture . The film stars Malcolm McDowell in his first screen role and his first appearance as Anderson 's `` everyman '' character Mick Travis . Richard Warwick , Christine Noonan , David Wood , and Robert Swann also star . if ... . won the Palme d'Or at the 1969 Cannes Film Festival . In 1999 , the British Film Institute named it the 12th greatest British film of the 20th Century ; in 2004 , the magazine Total Film named it the 16th greatest British film of all time .",
"title": ""
},
{
"docid": "In_Celebration",
"text": "In Celebration is a 1975 film directed by Lindsay Anderson . It is based in the 1969 stage production of the same name by David Storey which was also directed by Anderson . The movie was produced and released as part of the American Film Theatre , which adapted theatrical works for a subscription-driven cinema series . It was meant to be shown theatrically with tickets sold in advance .",
"title": ""
},
{
"docid": "The_Life's_Romance_of_Adam_Lindsay_Gordon",
"text": "The Life 's Romance of Adam Lindsay Gordon is a 1916 Australian feature-length film directed by W. J. Lincoln , based on the life of poet Adam Lindsay Gordon . Unlike many Australian silent movies , part of the film survives today .",
"title": ""
},
{
"docid": "John_Anderson_(sportscaster)",
"text": "John Anderson ( born May 13 , 1965 ) is a sports journalist from Green Bay , Wisconsin , and a host of the ESPN TV program SportsCenter since June 1999 . Since Brian Kenny 's departure to the MLB Network , he mostly appears on the 6-8pm edition with Lindsay Czarniak . He also co-hosted the TV series Wipeout .",
"title": ""
},
{
"docid": "Sequence_(journal)",
"text": "Sequence was a short-lived but influential British film journal founded in 1947 by Lindsay Anderson , Gavin Lambert and Karel Reisz . Anderson had returned to Oxford after his time with the army Intelligence Corps in Delhi , Lambert was a schoolfriend of Anderson from Cheltenham College who had dropped out of English at Magdalen College on discovering that he would have to study Middle English under C. S. Lewis , while Reisz was a chemistry graduate from Emmanuel College , Cambridge who later said `` I met Lindsay Anderson on a Green Line bus . I was going to the British Film Institute to look at some film for my editing book and he was going to see Ford 's The Iron Horse . '' Founded as the Film Society Magazine , the organ of the Oxford Film Society , in 1947 , with Penelope Houston as its first editor , the journal quickly changed its name to Sequence , and produced fourteen issues between 1947 and 1952 , the last few being edited by Reisz and Anderson . The British Free Cinema movement , co-founded in 1956 by Lindsay Anderson , Karel Reisz , Tony Richardson and Lorenza Mazzetti , drew on the principles first expressed by the journal . Articles from Sequence by Anderson were published in Lindsay Anderson : The Collected Writings edited by Paul Ryan ( London : Plexus , 2004 ) .",
"title": ""
},
{
"docid": "Julian_Wintle",
"text": "Julian Wintle ( 1913 -- 1980 ) was a British film and TV producer who battled with haemophilia throughout his life . He is best remembered for his work on TV 's The Avengers , where he oversaw the transition of the series to film , the introduction of Emma Peel , and the subsequent international success , in what is considered by many to be the series `` classic '' years ( 1965 -- 67 ) . Wintle was a member of the Bryanston Consortium from 1959 to 1963 . For several years , in the early 1960s he was head of Beaconsfield Film Studios , and a director of Independent Artists Ltd. , which produced Lindsay Anderson 's This Sporting Life ( 1963 ) among other projects . His sons are the musician and publisher Christopher Wintle and the writer Justin Wintle . He was the subject of a biography by Anne Francis , Julian Wintle . A Memoir , London , Dukeswood , 1984 . This contains an extensive filmography with many films listed for which he was executive producer .",
"title": ""
},
{
"docid": "Lindsay_Anderson",
"text": "Lindsay Gordon Anderson ( 17 April 1923 -- 30 August 1994 ) was a British feature film , theatre and documentary director , film critic , and leading light of the Free Cinema movement and the British New Wave . He is most widely remembered for his 1968 film if ... , which won the Palme d'Or at Cannes Film Festival and was Malcolm McDowell 's cinematic debut . He is also notable , though not a professional actor , for playing a minor role in the Academy Award winning film Chariots of Fire . Malcolm McDowell produced a 2007 documentary about his experiences with Lindsay Anderson , Never Apologize .",
"title": ""
},
{
"docid": "Glory!_Glory!",
"text": "Glory ! Glory ! is a 1989 televangelism comedy film directed by Lindsay Anderson and starring Ellen Greene that originally aired on HBO in two parts .",
"title": ""
},
{
"docid": "Lindsay_Anderson_(footballer)",
"text": "Lindsay Anderson ( 2 September 1883 -- 12 November 1962 ) was a former Australian rules footballer who played with Melbourne in the Victorian Football League ( VFL ) .",
"title": ""
},
{
"docid": "In_Celebration_(play)",
"text": "In Celebration is a 1969 play by the English writer David Storey . It is set in a Nottinghamshire mining town and tells the story of three brothers who visit their parents for their 40th wedding anniversary . According to Storey , the three brothers are based on aspects of himself : `` One was a very passive nature , the second was a kind of conformist nature , and the third was a kind of bolshie nature that did n't want to have anything to do with the other two . '' The play took three days to write . It premiered in 1969 at the Royal Court Theatre , where it was directed by Lindsay Anderson and ran for twelve weeks . Anderson also directed a 1975 film adaptation with the same title .",
"title": ""
},
{
"docid": "John_Howlett",
"text": "John Howlett is an English author and screenwriter living in Rye , East Sussex . He started his writing career by co-writing the screenplay of the 1968 feature film if ... '' , directed by Lindsay Anderson .",
"title": ""
},
{
"docid": "The_Long_and_the_Short_and_the_Tall_(play)",
"text": "The Long and the Short and the Tall is a play written by British playwright Willis Hall . Set in the Second World War , the play premiered at the Royal Court Theatre in London in January 1959 ; it was directed by Lindsay Anderson and starred Peter O'Toole and Robert Shaw . It was Anderson 's first major production for the Royal Court , transferring to London 's West End in April 1959 . The play 's name comes from the lyrics of the 1917 song `` Bless 'Em All '' . A film adaptation was released in 1961 . Directed by Leslie Norman , it stars Laurence Harvey , Richard Harris , Richard Todd and David McCallum . A TV drama followed in 1979 which starred Michael Kitchen , Mark McManus and Richard Morant .",
"title": ""
},
{
"docid": "The_Wreck_(1913_film)",
"text": "The Wreck is an Australian film directed by W. J. Lincoln based on a poem by Adam Lindsay Gordon about the ride to help by a farmhand who has witnessed a shipwreck . It is considered a lost film . The movie was made in 1913 but not released until 1915 . W. J. Lincoln later made a film of Gordon 's life , The Life 's Romance of Adam Lindsay Gordon ( 1916 ) .",
"title": ""
},
{
"docid": "Look_Back_in_Anger_(1980_film)",
"text": "Look Back in Anger is a 1980 British film starring Malcolm McDowell , Lisa Banes and Fran Brill , and directed by Lindsay Anderson and David Hugh Jones . The film is based on John Osborne 's play Look Back in Anger .",
"title": ""
},
{
"docid": "The_Pleasure_Garden_(1953_film)",
"text": "The Pleasure Garden is a short film written and directed by James Broughton in 1953 . Among its crew was Peter Price as sound editor . Cast members included the subsequent director Lindsay Anderson and Broughton 's artistic collaborator Kermit Sheets .",
"title": ""
},
{
"docid": "Repsol_Sport_Centre",
"text": "Repsol Sport Centre , formerly known as the Talisman Centre and Lindsay Park Sports Centre , is a multi-sports complex in Calgary , Alberta , Canada . The name of the facility was changed in March 2002 , after the City of Calgary sold the naming rights for 10 million dollars to Talisman Energy for 20 years which was later bought out by Repsol and resulted in another name change . Repsol Sport Centre operates under a dual mandate as directed by The City of Calgary to support both Members and Sport Partner Athletes . ◾ To provide training and competition facilities and services for the development of Calgary 's high performance athletes in their respective dryland and aquatic sports . ◾ To provide facilities , programs and services for the wellness and recreational sporting needs of the citizens of Calgary . The complex attracts over 1.8 million visitors annually . The complex itself is run by the non-profit Lindsay Park Sports Society , a 13-member board and Civic Partner of the City of Calgary .",
"title": ""
},
{
"docid": "Devil's_Due_(film)",
"text": "Devil 's Due is a 2014 American found footage supernatural horror film directed by Matt Bettinelli-Olpin and Tyler Gillett , and written by Lindsay Devlin . The film stars Allison Miller , Zach Gilford , and Sam Anderson . The film was released on January 17 , 2014 .",
"title": ""
},
{
"docid": "The_Changing_Room",
"text": "The Changing Room is a 1971 play by David Storey , set in a men 's changing room before , during and after a rugby league football game . It premiered at the Royal Court Theatre on 9 November 1971 , directed by Lindsay Anderson . The 1973 Broadway production , directed by Michael Rudman , won several awards including the New York Drama Critics ' Circle award for Best Play and the Tony Award for Best Featured Actor for John Lithgow .",
"title": ""
},
{
"docid": "David_Gladwell",
"text": "David Gladwell ( born 1935 ) is a British film editor and director . His most notable films as editor include If ... ( 1968 ) and O Lucky Man ! ( 1973 ) both by director Lindsay Anderson . In 1981 , Gladwell directed the adaptation of the Doris Lessing novel Memoirs of a Survivor starring Julie Christie .",
"title": ""
},
{
"docid": "Love_of_Life_Orchestra",
"text": "Collaborators on their recording Extended Niceties have included Arto Lindsay and David Byrne Early members of the band included Laurie Anderson ( electric violin ) , Blue Gene Tyranny ( keyboards ) , Ken Deifik ( harmonica ) , Scott Johnson guitar , Rhys Chatham ( flute ) , Peter Zummo ( trombone ) , Arthur Russell ( cello ) , Kathy Acker ( vocals ) , and Jill Kroesen ( vocals ) .",
"title": ""
},
{
"docid": "Wakefield_Express",
"text": "The Wakefield Express is the newspaper serving the City of Wakefield district in West Yorkshire , England . It was established in 1852 and was the subject of a centenary film directed by Lindsay Anderson in 1952 . The newspaper is owned by Johnston Press and edited by Mark Bradley . After 155 years of publication as a broadsheet , it changed to a tabloid format in March 2007 .",
"title": ""
},
{
"docid": "The_Long_and_the_Short_and_the_Tall",
"text": "The Long and the Short and the Tall may refer to : The Long and the Short and the Tall ( play ) , a 1959 play , directed by Lindsay Anderson , starring Peter O ' Toole and Robert Shaw The Long and the Short and the Tall ( film ) , a 1961 film , directed by Leslie Norman , starring Laurence Harvey , David McCallum , Richard Harris and Richard Todd `` Bless 'Em All '' ( also known as `` The Long And The Short And The Tall '' ) , a 1917 song by Fred Godfrey , first recorded by George Formby in 1940",
"title": ""
},
{
"docid": "WQME",
"text": "WQME is a medium market Contemporary-Christian format radio station in Anderson , Indiana broadcasting on 98.7 FM . It is a Class A FM station with an Effective Radiated Power of 4,500 watts . It is owned by Anderson University . WQME offers several nationally syndicated programs , including New Life Live ! , Family Life Today , and CBH Viewpoint . The station also offers Hey Howard , Soul 2 Soul , Direct Connection , and Homecoming Radio . Other programs include After Midnight , a program for young adults ; Talk 'N Sports with Dave Edwards , featuring interviews with local athletes and coaches ; and Consider this with Big Joe Clark , a show focused on personal finance and the economy . WQME 's staff includes General Manager Donald Boggs and Program Director Matt Rust , who also hosts the Morning Show on weekday mornings . Other staff include Jerry Morton , engineer ; Norma Armogum , certified traffic director ; and Becky Melson , bookkeeper .",
"title": ""
},
{
"docid": "Mick_Travis",
"text": "Michael Arnold `` Mick '' Travis is a character played by Malcolm McDowell in three films directed by British film director Lindsay Anderson and written by David Sherwin . Travis features not so much as a single character with a character arc , but as an everyman character whose role changes according to the needs of the storyteller . In 1968 's if ... , his first appearance ( and McDowell 's film debut ) , Travis first appears as a disaffected public school boy whose anti-establishment attitude and experiences lead to armed insurrection at a private school . The film was made at Cheltenham College , Lindsay Anderson 's old school , and many of the scenes drew heavily on his experience in the Officers Training Corps at Cheltenham , which he had joined in May 1937 . It also draws heavily upon Tonbridge School , where the two screenwriters both went , and several characters , including the child-abusing chaplain , are based on real people who taught at Tonbridge . In O Lucky Man ! , cowritten by Sherwin and McDowell , Travis becomes a picaresque character , often compared to Voltaire 's ingénu character Candide , in a satirical drama that starts with Travis 's first job as a mobile coffee salesman and , after many adventures involving arms-sale scandals , experiments in human-animal genetics by the mad scientist Doctor Millar ( played with relish by Graham Crowden ) , and a sojourn with the musician Alan Price , ends in his rebirth as a film star , thanks to a slap by a film director played in a cameo by Anderson -- the scene was a depiction of McDowell 's first audition in which McDowell was slapped ( according to script , which he had not read ) by Christine Noonan , who played ` the girl ' in if ... . and briefly appeared ( in two roles ) in O Lucky Man ! In Britannia Hospital , written by Sherwin , Travis is a reporter attempting to make an investigative documentary about a hospital where Doctor Millar , the mad geneticist from O Lucky Man ! is continuing his unspeakable experiments . While spying on an experiment to create a new human being from assembled body parts , Travis is captured by the hospital staff . A power cut renders the experiment 's human head unusable , so Millar decapitates Travis and attaches his head to the creature . On being given life , the creature ( played by McDowell ) attacks Millar , forcing Millar to stab and dismember it .",
"title": ""
},
{
"docid": "1969_Cannes_Film_Festival",
"text": "The 22nd Cannes Film Festival was held from 8 to 23 May 1969 . At this festival a new non-competitive section called `` Directors ' Fortnight '' is added , in response to the cancellation of the 1968 festival . The Grand Prix du Festival International du Film went to the If ... . by Lindsay Anderson . The festival opened with Sweet Charity , directed by Bob Fosse .",
"title": ""
},
{
"docid": "Craig_Anderson_(actor)",
"text": "Craig Anderson is an Australian director and actor best known for his comedic turns in the Australian television series ' Double the Fist , Review with Myles Barlow , Laid , and award winning short films Life in a Datsun , Demon Datsun , Life in a Volkswagen . Anderson has also directed the horror feature Red Christmas starring Dee Wallace . Anderson has a First Class Honors in Performance and Theory from the University of Western Sydney and has almost completed a PhD on which looks at various Epistemologies of Comedy . In 2000 , Anderson began a successful career as an MC and judge at film festivals including the Newcastle Film Festival , the Shootout Film Festival held annually in Newcastle , and the Funny Bone 500 . In November 2008 Anderson featured in three episodes of the ABC TV show Review With Myles Barlow . Double the Fist co-star Bryan Moses also featured in three episodes of the series . In addition Anderson served as associate producer and first assistant director on the series During 2011 Anderson produced and directed several web series ( Bernie , Late Night Angel Weenie Baby ) that screened on various Sydney Morning Herald digital spaces , and ABC 's iView . Anderson is currently in development on a new comedy series for ABC entitled Love.Sick . He will be working with Stevo Petckovic and Melinda Clomovska of which he worked previously on for the short film A Family Affair ( which was a finalist at Tropfest 2011 ) . The six episode series about untold love stories is set to air in September 2012 . In 2013 Craig was the subject of a six-part Observational Documentary series Next Stop Hollywood , which followed him around Hollywood during pilot series . In 2014 Craig shared directing duties on Australia 's first Indigenous sketch Comedy series Black Comedy . In 2014 he ( and fellow director Bec Cole ) were nominated for an AACTA award for Best Direction in TV .",
"title": ""
}
] |
163773
|
Wishful Drinking is based on a show developed by Carrie Fisher and Joshua Ravetch.
|
[
{
"docid": "Wishful_Drinking",
"text": "Wishful Drinking is an autobiographical humor book by American actress and author Carrie Fisher , published by Simon & Schuster in 2008 . Fisher 's book was based on her one-woman stage show , which she developed with writer/director Joshua Ravetch . The show debuted at The Geffen Playhouse with Ravetch directing . It enjoyed a successful Broadway run and then toured in other cities . In 2010 , HBO filmed a feature-length documentary of the stage play .",
"title": ""
}
] |
[
{
"docid": "Joshua_Ravetch",
"text": "Joshua Ravetch is an American writer/director born in Los Angeles , California who co-created and directed Carrie Fisher 's one-woman show Wishful Drinking , which had a successful run on Broadway . He also co-wrote and directed Dick Van Dyke in his first-ever one man show , `` Step in Time ! A Musical Memoir , '' which premiered at The Geffen Playhouse . Ravetch , a graduate of the Stella Adler Conservatory in Manhattan , took over Ms. Adler 's signature script-interpretation classes before assuming the post as artistic director at the Stella Adler Conservatory West .",
"title": ""
},
{
"docid": "Joshua_Mark_Thomas",
"text": "Joshua Mark Thomas is an accomplished interior designer and photographer . He was born in Montana , possibly Proctor , on August 21 , 1973 to Mark & Dianne Thomas . After various moves throughout the country , including to New York , Los Angeles , and Las Vegas , he settled in Atlanta , Georgia , where he attended the Savannah College of Art & Design . Joshua 's early career including the design and manufacture of detailed , high-end dresses and costumes for ballroom dancers , and his clients included many of the countries top dancers who are still performing professionally today . He was an on-air cast member of HGTV 's Designed to Sell for all Atlanta seasons and is the current photographer for HGTV 's Curb Appeal . Joshua 's textile work has also been featured on The Today Show , HGTV 's Designed to Sell , and with various John Gidding Design Inc. projects , including at the upscale furniture store , Artefacto ( currently in their Atlanta , GA Style House ) . His work has also recently been in Loft Life magazine , which shows both his textiles as part of the Artefacto Style House and his photography , as credited in the article , in Jezebel magazine , where he 's shown as part of the Designed to Sell cast , and in Atlanta Woman 's Magazine , which shows his textile work as part of Designed to Sell , as well as crediting his photography work . In 2009 , his work ( both photography and textiles ) was featured in the remodel of Carrie Fisher 's dressing room at Studio 54 for her production of Wishful Drinking . He also owns a textile and design firm named J Thomas Design and a fine art photography business , J Thomas Fine Art . His textile work has appeared on almost every episode of seasons 25 - 28 of Designed to Sell .",
"title": ""
},
{
"docid": "Carrie_Fisher",
"text": "Carrie Frances Fisher ( October 21 , 1956 -- December 27 , 2016 ) was an American actress , writer and humorist who first became known for playing Princess Leia in the Star Wars film series . Her other film roles included Shampoo ( 1975 ) , The Blues Brothers ( 1980 ) , Hannah and Her Sisters ( 1986 ) , The ` Burbs ( 1989 ) , and When Harry Met Sally ... ( 1989 ) . Fisher wrote several semi-autobiographical novels , including Postcards from the Edge and the screenplay for the film of the book , as well as an autobiographical one-woman play , and its non-fiction book , Wishful Drinking , based on the play . She worked on other writers ' screenplays as a script doctor . In later years , she earned praise for speaking publicly about her experiences with bipolar disorder and drug addiction . The daughter of the singer Eddie Fisher and actress Debbie Reynolds , Fisher and her mother appear in Bright Lights : Starring Carrie Fisher and Debbie Reynolds , a 2016 documentary about their relationship . It premiered at the 2016 Cannes Film Festival . Fisher died of cardiac arrest on December 27 , 2016 , at age 60 , four days after experiencing a medical emergency during a transatlantic flight from London to Los Angeles . Her final film , Star Wars : The Last Jedi , is scheduled to be released on December 15 , 2017 .",
"title": ""
},
{
"docid": "One_November_Yankee",
"text": "One November Yankee is a play by American writer Joshua Ravetch . It was first performed at The Pasadena Playhouse before opening at The NoHo Arts Center in 2012 . The play starred two time Emmy winner , and TV 's Hot Lips Houlihan from M * A * S * H * , Loretta Swit , and LA Law 's Harry Hamlin . The set was designed by Dana Moran Williams . The film rights were picked up by Pam Williams Productions as a feature film for Ravetch to adapt and direct .",
"title": ""
},
{
"docid": "Joshua_Fisher_(musician)",
"text": "Joshua Fisher ( born 1989 ) is a singer-songwriter from Lewisham in South London , currently living in Norwich , England . His debut EP , `` Atlas '' was scheduled to be released on 25 October 2010 by independent London based label Polymorph Records . `` Atlas '' features four songs , which have been co-produced by Roger Pusey -- former Producer of iconic recordings on The Smiths albums Hatful of Hollow and `` Louder Than Bombs '' . Joshua cites Nick Drake , Bright Eyes and The Waterboys among his influences .",
"title": ""
},
{
"docid": "The_Princess_Diarist",
"text": "The Princess Diarist is a 2016 memoir written by Carrie Fisher , based on diaries she kept as a young woman around the time she starred in the 1977 film Star Wars . The book is the third memoir Fisher wrote , in addition to four novels and a one-woman Broadway show . It is Fisher 's final book , as she died five weeks after its release on December 27 , 2016 . The book describes Fisher 's affair with co-star Harrison Ford in `` cringe-worthy '' , albeit educational , detail . At the time of the relationship , Ford was married with two children and in his early 30s .",
"title": ""
},
{
"docid": "Wish_You_Were_Here_(1952_song)",
"text": "`` Wish You Were Here '' is a popular song with music and lyrics by Harold Rome , the title tune from his 1952 show , Wish You Were Here ( musical ) . It was introduced in the show and on the RCA Victor cast album by Jack Cassidy . The best-known version was recorded by Eddie Fisher becoming a # 1 hit in 1952 on RCA Victor 47-4830 ( 45 rpm ) and 20-4830 ( 78 rpm ) .",
"title": ""
},
{
"docid": "Joshua_Francis_Fisher",
"text": "Joshua Francis Fisher ( February 17 , 1807 Philadelphia - January 21 , 1873 ) was a United States author and philanthropist .",
"title": ""
},
{
"docid": "Friends_of_Peter_G.",
"text": "`` Friends of Peter G. '' is the tenth episode of the ninth season of the animated comedy series Family Guy . It aired on Fox in the United States on February 13 , 2011 . The episode follows Peter and Brian as they are forced to join Alcoholics Anonymous , due to their excessive drinking , much to their chagrin . Soon , however , Peter crashes his car while driving home drunk , and is approached by Death , who shows him what his life will be like if he continues to drink alcohol , as well if he had never drunk at all . The episode was written by Brian Scully and directed John Holmquist . It received mostly mixed reviews from critics for its storyline and many cultural references . According to Nielsen ratings , it was viewed in 5.99 million homes in its original airing . The episode featured guest performances by H. Jon Benjamin , Adam Carolla , Carrie Fisher , Phil LaMarr , Jessica Stroup and Laura Vandervoort , along with several recurring guest voice actors for the series . It was first announced at the 2010 San Diego Comic-Con International .",
"title": ""
},
{
"docid": "Kitty_Fisher",
"text": "Kitty Fisher ( 1741 -- 1767 ) was a prominent British courtesan . From her teen years onwards , Fisher carefully developed her public image , which was boosted by attention from Sir Joshua Reynolds and other artists . By emphasizing Fisher 's beauty , audacity , and charm , portraits and newspaper and magazine articles promoted her reputation and prompted spectators to view her with redoubled awe . She was one of the world 's first celebrities famous not for being an actress , musician or member of the royalty , but simply for being famous . Her life exemplifies the emergence of mass media publishing and fame in an era when capitalism , commercialism , global markets , and rising emphasis on public opinion were transforming England .",
"title": ""
},
{
"docid": "Testament_of_Man",
"text": "The Testament of Man ( 1943-1960 ) , a twelve-volume series of novels by the American author Vardis Fisher , traces the physical , psychological and spiritual evolution of Western civilization from Australopithecus to the present . The series explores a pantheon of subjects : myth , ritual , language , family , sex and especially sin , guilt and religion . Each work emphasizes a particular pathway that Fisher considered of paramount importance in the development of the modern world and our current views . `` Enlightened minds must wonder what the world would be like today if the torrent -LSB- that carries us along -RSB- had taken another channel at any one of a dozen moments in history . What if Greek values had triumphed in that war more than twenty − one centuries ago ? '' Fisher traced a specific pathway in which ape-like creatures segued to Middle Eastern tribes , followed by the development of Judaism and Christianity . The task consumed two decades after prodigious preparation . By his own account , Fisher read more than 2,000 books and essays on a wide range of subjects - religion , anthropology , archaeology , music , food , psychology , evolution and climate . In The Great Confession , `` Part III : The Orphans '' Fisher describes his research in detail . In order to get into the mind of the ape-man , he lived like one , dwelling in caves , walking , eating , hunting and sleeping as he imagined they had . He observed apes in zoos and conducted behavioral experiments with animals . For example , he concluded that contrary to popular belief , animals did not generally recognize people by scent . He was convinced that Western religion developed out of fear , particularly that of the father . Judaism was the only ancient religion without a mother figure . All volumes in the series are based on similar themes and characters , or personas . One theme is the role of gender in the rise of human civilization . He holds that female 's feelings run deeper ; she was more practical since her first duties were to home , food and children . The man , uninvolved with family , is egotistical , shallow and alone , yet this solitude gives rise to intellectual breakthroughs that radically changed ancient beliefs . One recurrent character is the misunderstood male genius , the neurotic thinker who suddenly grasps a unique thought that becomes increasingly influential to future generations . An intellectually strong woman often appears . She understands better than the male and assists in his quest into the unknown . Fisher 's interest in men 's long subjugation of women is a dominant theme throughout . The controversial subject matter met with frequent , scathing denunciation that centered on three elements - his treatment of religion , sexual content and anthropological conclusions . Many reviewers objected to Fisher 's penchant for interrupting the story with explanatory comments for the reader . Particularly reviled was his treatment of historical and Biblical characters , religion in general , and Christianity and Judaism specifically . The Valley of Vision ( 1951 ) , a novel of Solomon and his court , evoked a fierce review in TIME : The project was viewed as a financial risk and had trouble finding a publisher despite Fisher 's fame as a popular Western novelist . When he presented Jesus Came Again : A Parable ( 1956 ) , Caxton Press refused to publish it due to the heretical nature of the story . They thought the tale of a misunderstood , neurotic Jesus ( `` Joshua '' ) who was all too human , and not the man who satisfied the universal yearnings of the times for a Messiah , was too controversial . The project was picked up by Swallow Publishing , which printed the rest of the series . Fisher considered religion not as a cultural , collective phenomenon but as the consequences of individual insight due to sexual longings , loneliness and genius .",
"title": ""
},
{
"docid": "Harriet_Frank_Jr.",
"text": "Harriet Frank Jr. ( born March 2 , 1917 ) is an American film writer and producer . Working alongside her husband , Irving Ravetch , Frank received numerous awards during her lengthy career , including the New York Film Critics Circle Awards and the Writers Guild of America Award , and several nominations . Frank and Ravetch are considered one of the all-time great screenwriting couples , and many of their works are recognised classics of their genres . Frank began her writing career after World War II , under Metro-Goldwyn-Mayer 's young writer 's training program , where she first met her future husband . She married Ravetch in 1946 but worked independently for ten years , finally collaborating with him in 1957 , a relationship that continued for the remainder of her career . During 33 years of collaboration , they created the screenplays for a variety of films , mainly adaptations of the works of American authors . Frank and Ravetch maintained a close working relationship with director Martin Ritt throughout their career , collaborating with him on eight occasions ; after initially being suggested by Ravetch to direct The Long , Hot Summer ( 1958 ) , Ritt would eventually draw the couple out of inactivity on three occasions , hiring them to write the screenplays for Norma Rae ( 1979 ) , Murphy 's Romance ( 1985 ) and Stanley & Iris ( 1990 ) . The latter was both the last film directed by Ritt ( who died later that year ) and the last for which Frank and Ravetch wrote the screenplay .",
"title": ""
},
{
"docid": "Wish_(Joshua_Redman_album)",
"text": "Wish is a 1993 album by jazz saxophonist Joshua Redman .",
"title": ""
},
{
"docid": "Wishing_well",
"text": "A wishing well is a term from European folklore to describe wells where it was thought that any spoken wish would be granted . The idea that a wish would be granted came from the idea that water housed deities or had been placed there as a gift from the gods , since water was a source of life and often a scarce commodity . The Germanic and Celtic peoples considered springs and wells sacred places . Sometimes the places were marked with wooden statues possibly of the god associated with the pool . Germanic peoples were known to throw the armour and weapons of defeated enemies into bogs and other pools of water as offerings to their gods . Water was seen to have healing powers and therefore wells became popular with many people drinking , bathing or just simply wishing over it . Some people believe that the guardians or dwellers of the well would grant them their wish if they paid a price . After uttering the wish , one would generally drop coins in the well . That wish would then be granted by the guardian or dweller , based upon how the coin would land at the bottom of the well . If the coin landed heads up , the guardian of the well would grant the wish , but the wish of a tails up coin would be ignored . It was thus potentially lucky to throw coins in the well , but it depended on how they landed . The tradition of dropping pennies in ponds and fountains stems from this . Coins would be placed there as gifts for the deity to show appreciation . This may be a leftover from ancient mythology such as Mímir 's Well from Nordic myths , also known as the `` Well of Wisdom '' , a well that could grant you infinite wisdom provided you sacrificed something you held dear . Odin was asked to sacrifice his right eye which he threw into the well to receive not only the wisdom of seeing the future but the understanding of why things must be . Mímir is the Nordic god of wisdom , and his well sits at the roots of Yggdrasil , the World Tree which draws its water from the well . Another theory is people may have unknowingly discovered the biocidal properties of both copper and silver ; the two metals traditionally used in coins . Throwing coins made of either of these metals could help make the water safer to drink . Wells that were frequented by those that threw coins in may have been less affected by a range of bacterial infections making them seem more fortunate and may have even appeared to have cured people suffering from repeated infections . In November 2006 the `` Fountain Money Mountain '' reported that tourists throw just under 3 million pounds sterling per year into wishing wells .",
"title": ""
},
{
"docid": "Eddie_Fisher_(singer)",
"text": "Edwin John `` Eddie '' Fisher ( August 10 , 1928 -- September 22 , 2010 ) was an American singer and actor . He was the most successful pop singles artist during the first half of the 1950s , selling millions of records and hosting his own TV show . Fisher divorced his first wife , actress Debbie Reynolds , to marry Reynolds ' best friend , actress Elizabeth Taylor , after Taylor 's husband , film producer Mike Todd , was killed in a plane crash . The scandalous affair was widely reported , bringing unfavorable publicity to Fisher . He later married Connie Stevens . Fisher fathered Carrie Fisher and Todd Fisher with Reynolds , and Joely Fisher and Tricia Leigh Fisher with Stevens .",
"title": ""
},
{
"docid": "Caffeinated_drink",
"text": "A caffeinated drink , or caffeinated beverage , is a drink that contains caffeine , a stimulant that is legal and popular in most developed countries . The most common naturally caffeinated beverages are coffee and tea , which in one form or another ( usually served hot , but sometimes iced ) feature in most world cultures . Other drinks are artificially caffeinated as part of their production process . These include certain soft drinks ( primarily cola drinks ) , and also energy drinks designed as a stimulant , and to perpetuate activity at times when the user might ordinarily be asleep . The consumption of caffeinated drinks is often intended entirely or partly for the physical and mental effects of caffeine . Examples include the consumption of tea or coffee with breakfast in many westernized societies , in order to ` wake oneself up ' , or the deliberate consumption of energy drinks by students wishing to study through the night , or revellers seeking to maintain an alert attitude during social recreation . Caffeine can cause a physical dependence , if consumed in excessive amounts . The need for caffeine can be identified when individuals feel headaches , fatigue and muscle pain 24 hours after their last energy drink . Some commercially distributed drinks contain guarana , a South American berry with a caffeine content about twice that of coffee beans . Many caffeinated drinks also have decaffeinated counterparts , for those who enjoy the taste , but wish to limit their caffeine intake because of its physical effects , or due to religious or medical perceptions of the drug and its effects . In recent years , some alcoholic beverage companies have begun to manufacture caffeinated alcoholic beverages . The manufacturing of such beverages has been met with much controversy .",
"title": ""
},
{
"docid": "Joshua_Fisher",
"text": "Joshua Fisher ( 1707 -- February 1 , 1783 ) was a prominent Philadelphia merchant involved in transatlantic trade and mapmaking as applied to nautical charts . He made the first nautical chart of the Delaware River and Delaware Bay , and established the first merchant packet line between London and Philadelphia .",
"title": ""
},
{
"docid": "The_Joshua_Light_Show",
"text": "The Joshua Light Show , created by Joshua White , was a liquid light show . It was known for its psychedelic art and served as a lighting backdrop behind many live band performances during the late 1960s and early 1970s . Joshua White studied electrical engineering , theatrical lighting , and magic lantern techniques at Carnegie Tech and also film making at University of Southern California . Performances were held every weekend . The light shows used multiple image-making devices including film projectors , slide projectors , overhead projectors , color wheels , watercolors , oil colors , and glass crystals . These all would be arranged on two levels for their performances . The Joshua Light Show based their shows on four elements ; projection of pure color , concrete imagery , variety of color effects and shaping of the light .",
"title": ""
},
{
"docid": "Kev_Seed",
"text": "Kevin `` Kev '' Seed ( born 27 July 1968 ) is an English radio DJ . He has presented shows on Rock FM and Radio City , and most recently , the former Breakfast Presenter for Wish FM . In April 2016 , it was announced he would be joining the presenting line-up at Wirral Radio . Seed first joined Radio City in 1990 . Two years later , he moved to the Preston-based station Rock FM for five years . In 1997 , he re-joined Radio City and presented The Kev Seed Breakfast Show for 11 years before moving to the Drivetime show ( 4pm -- 7pm ) in August 2008 . He presented the early evening Drivetime show on the Liverpool radio station Radio City 96.7 until October 2008 , when he was suspended and then sacked after pleading guilty to a drink-driving charge . Although he appealed , it was reported on 11 November that the station management had upheld their decision . In October 2009 , Seed started his new job as the Breakfast Presenter for Wish FM , the Radio Station for Wigan & St Helens , a year after leaving Radio City . He is also to begin presenting a show on 107.6 Juice FM from 29 November . He now no longer presents on either stations . As of 2014 , he is voice of Sainsbury 's on various radio stations .",
"title": ""
},
{
"docid": "NG_Knight_Ramune_&_40",
"text": "For the final OVA , see Knights of Ramune . was a Japanese television series of 1990 . It was one of the Lamune group of television shows and OVAs , and the `` NG '' in the title stands for `` new generation '' . In all there were 3 OVA series ( NG Knight Lamune & 40 EX , NG Knight Lamune & 40 DX , VS Knight Lamune & 40 Fresh ) and a sequel anime television series ( VS Knight Lamune & 40 Fire ) . This show is not related to the anime series Lamune of 2005 . The original concept for the show was developed by Takehiko Ito , much of the story was written by Satoru Akahori , and the mecha design was done by Rei Nakahara . ( Collectively this team is known as `` B3 '' . ) All anime and OVA in the series were produced by Starchild Records , and the show was broadcast on TV Tokyo from April 6 , 1990 to January 4 , 1991 as well as on Nickelodeon India until June 3 , 2013 . The main storyline of the series involves a boy named Baba Lamune who is sucked into the video game `` King Sccasher . '' Lamune is a blood relative of the hero `` Lamuness , '' and in the program he is destined to save the world from the evil Don Harumage . `` Lamune '' is the name of a popular , lemon-flavored Japanese carbonated drink , and most character names in the series are based on drinks , such as the character Milk . The name `` Scassher '' is based on the name of a competitor to Lamune , namely `` Lemon Squash '' , a drink not franchised in America whose name is based on that of `` Orange Crush '' , which is .",
"title": ""
},
{
"docid": "Jeffrey_V._Ravetch",
"text": "Jeffrey Victor Ravetch ( born 1951 ) is a professor and head of the Laboratory of Molecular Genetics and Immunology at The Rockefeller University .",
"title": ""
},
{
"docid": "Happily_Ever_After_(Magic_Kingdom)",
"text": "Happily Ever After is a fireworks and projection mapping show which debuted at the Magic Kingdom on May 12 , 2017 . Unlike its predecessor , Wishes : A Magical Gathering of Disney Dreams , the show includes projection mapping across Cinderella Castle , lasers , and searchlights , in addition to pyrotechnics . The show includes characters and music from a wide array of Disney films . The music also includes a theme song from Angie Keilhauer and Jordan Fisher .",
"title": ""
},
{
"docid": "Fisher's_Lane_Bridge",
"text": "Fisher 's Lane Bridge is a historic stone arch bridge that carries Fisher 's Lane west of Ramona Avenue across Tacony Creek in Tacony Creek Park in Philadelphia , Pennsylvania . The closed-spandrel stone arch bridge has a single span of 54 ft and is 27.7 ft wide . It is currently open to traffic . Though claimed by some to have been re-built in 1796 , a still-legible cornerstone in the bridge masonry shows the year 1759 .",
"title": ""
},
{
"docid": "Irving_Ravetch",
"text": "Irving Dover Ravetch ( November 14 , 1920 -- September 19 , 2010 ) was an American screenwriter and film producer who frequently collaborated with his wife Harriet Frank , Jr. .",
"title": ""
},
{
"docid": "Passenger_Fatty-Seven",
"text": "`` Passenger Fatty-Seven '' is the tenth episode of the fifteenth season of the animated sitcom Family Guy , and the 279th episode overall . It aired on Fox in the United States on January 8 , 2017 , and is written by Alex Carter and directed by Greg Colton . The episode 's title is a play on the film Passenger 57 . This episode was dedicated in memory of cast member Carrie Fisher , who died on December 27 , 2016 after going into cardiac arrest while on a flight to Los Angeles on December 23 , 2016 . A slide showing her picture with the words `` In Loving Memory '' on top and `` Carrie Fisher 1956-2016 '' below was shown before the start of the episode .",
"title": ""
},
{
"docid": "Superstar_USA",
"text": "The WB 's Superstar USA is a television show which spoofed the popular show American Idol . Essentially that show 's polar opposite , Superstar USA told contestants they were looking for the best singer when they were actually looking for the worst . Hosted by Brian McFayden ( Ryan Seacrest 's double ) , people first audition before three judges ( the sarcastic Briggs , who also produces the show and could be considered the `` Simon '' of the show ; rapper Tone Lōc , the show 's answer to Randy Jackson ; and singer Vitamin C , put into Paula Abdul 's role ) in four cities across the United States . Finalists were chosen based on the lie that they were the most likely to be able to parlay their win into a successful recording contract based on talent . However , the audition process was the opposite of American Idol as good singers were mocked and told no , while bad singers were given gushing praise and passed to the next round . Said finalists were subjected to makeovers where they were encouraged to emulate pop stars . Contestants would then be falsely encouraged and praised by the judges as well as the stylists , choreographers and vocal coaches ; in particular , they would be encouraged to try and stretch their vocal range far beyond what they could actually reach . Contestants with charismatic personalities , such as the singer/songwriter pro-cheerleader Nina `` Diva '' , were heavily encouraged to follow all of the producer driven directives . Eventually the contest was `` won '' by a singer named Jamie Foss , a buxom young blonde girl ( who bore a resemblance to Jessica Simpson ) who could barely carry a tune . Throughout the competition she was constantly mocked by judges with thinly veiled references to the largeness of her breasts . She was awarded $ 50,000 in cash and a $ 50,000 budget to produce a record , which has not yet surfaced . The truth was revealed to her on stage in front of the audience she had just sung for , but Foss did not seem very upset with the truth . One producer , worried that the live audience members would not be able to respectfully compose themselves during the final performances , deceived the audience by falsely informing them that the singers were all terminally ill young people , who were having a wish fulfilled by a charitable organization . The Los Angeles Times reported the organization named by the producer was the Make a Wish Foundation , which later received an apology from the WB . In an interview with USA Today , executive producer Mike Fleiss straightened out the details : `` First of all , it was me . But I did not say ` Make-A-Wish . ' I said , ` Who 's heard of the One Wish Foundation ? ' and people raised their hands . There is no One Wish Foundation . It was a prank on top of a prank . It was the only way to get it to work . ''",
"title": ""
},
{
"docid": "Celia_Fisher",
"text": "Celia B. Fisher , is an American developmental psychologist , the Marie Ward Doty University Chair and Professor of Psychology , and founding director of the Fordham University Center for Ethics Education . In addition , she is currently the director of the Fordham HIV Prevention Research Ethics Training Institute , which provides training on research ethics issues and offers financial support for a mentored research project that will contribute to evidence - based research ethics practices . Fisher is past chair of the Environmental Protection Agency 's Human Studies Review Board , a past member of the DHHS Secretary 's Advisory Committee on Human Research Protections ( SACHRP ; and co-chair of the SACHRP Subcommittee on Children 's Research ) and a founding editor of the journal Applied Developmental Science . She chaired the American Psychological Association 's Ethics Code Task Force and the New York State Licensing Board for Psychology , and served on the National Institute of Mental Health Data Safety and Monitoring Board , and the Institute of Medicine 's Committee on Clinical Research Involving Children . She is author of Decoding the Ethics Code : A Practical Guide for Psychologists ; co-editor of eight books , including The Handbook of Ethical Research with Ethnocultural Populations and Communities and Research with High-Risk Populations : Balancing Science , Ethics , and Law ; and author of over 100 theoretical and empirical publications in the areas of ethics in medical and social science research and practice and life-span development . Fisher is the recipient of the Lifetime Achievement Award of Excellence in Human Research Protection from the Health Improvement Institute ( HII ) . Her federally funded research programs focus on ethical issues and well-being of vulnerable populations , including ethnic minority youth and families , active drug users , college students at risk for drinking problems , and adults with impaired consent capacity .",
"title": ""
},
{
"docid": "Bright_Lights:_Starring_Carrie_Fisher_and_Debbie_Reynolds",
"text": "Bright Lights : Starring Carrie Fisher and Debbie Reynolds ( on-screen title is simply Bright Lights ) is a 2016 documentary about the relationship between entertainer Debbie Reynolds ( in her final film appearance ) and her actress/daughter Carrie Fisher . It premiered at the 2016 Cannes Film Festival and on January 7 , 2017 on HBO . A few weeks before the film 's premiere broadcast , both Fisher and Reynolds died . On December 23 , Fisher went into cardiac arrest and succumbed four days later , while Reynolds had a severe stroke from which she died on the following day , December 28 .",
"title": ""
},
{
"docid": "Joshua_Pearce",
"text": "Joshua M. Pearce is an academic engineer at Michigan Tech known for his work on protocrystallinity , photovoltaic technology , open-source-appropriate technology , and open-source hardware including RepRap 3D printers . Dr. Pearce received his Ph.D. at The Pennsylvania State University , where his work on protocrystallinity helped develop low-cost amorphous silicon solar photovoltaic technology . His solar research continues . For example , his research group published a levelized cost of electricity study on solar energy showed solar electricity was economically competitive with fossil fuels over wide geographic regions . His research into BDRF modeling of reflectors showed potential solar systems output increases of 30 % . However , he is also a vocal advocate of an open-source approach to technical development . For his work related to open-source nanotechnology , Ars Technica compared him to American software freedom activist Richard Stallman . He applied open-source 3-D printing and electronics to scientific equipment design , where he has claimed both superior innovation and lower costs . Reviewing his book Open-Source Lab , 3-D Printing Industry wrote , `` This is a manual that every scientist should read and it holds a message so powerful and disruptive that the Anarchist Cookbook is a fairy tale in comparison . '' His research has shown that printing household items with a RepRap is less costly and better for the environment than purchasing conventionally manufactured goods . Similarly , his group developed the recyclebot , a waste plastic extruder , which drops the cost of 3D printing filament from $ 35/kg to ten cents per kg while making recycling even more environmentally beneficial . In 2013 his group released an open-source 3D printer capable of printing in steel , which cost less than US$ 1,200 . in order to encourage more rapid technological development according to Scientific American . This cost reduction was significant as the New York Times reported commercial metal printers at the time cost over US$ 500,000 . Following the same approach , Dr. Pearce developed the early work on open-source-appropriate technology , which is technology that is designed with special consideration to the environmental , ethical , cultural , social , political , and economical aspects of the community it is intended for that are designed in the same fashion as free and open-source software . For example , he further developed inexpensive methods such as SODIS to disinfect drinking water in the developing world , using sunlight , water bottles , and salt . Recently , the MIT Sloan Management Review reported that Dr. Pearce has combined many of his research areas developing solar powered 3-D printers to drive sustainable development .",
"title": ""
},
{
"docid": "Polymorph_Records",
"text": "Polymorph Records is a record label based in London , England . In 2010 they released the debut single by Jamie West , called `` Give Me Everything You Got '' . Their most recent release is by singer-songwriter Joshua Fisher who released his debut EP `` Atlas '' on 25 October 2010 . It was co-produced by Roger Pusey . Their latest signing is Jake Benson , a young singer from London .",
"title": ""
}
] |
187
|
British male students are bullied more than British female students.
|
[
{
"docid": "16855829",
"text": "Bullying is still prevalent in schools and is clearly stressful for victims. 1 2 It may also have undesirable consequences for bullies, with antisocial behaviour persisting into adulthood. Victims are generally reported to be weaker than the bullies. 2 3 This would suggest that very short pupils are more likely to be victims and less likely to be the aggressors. The Wessex growth study allowed us to examine the prevalence of bullying, as experienced or perpetrated by pupils of different heights. Ninety two short normal adolescents who had been below the third centile for height at school entry4 and 117 controls matched for age and sex completed a bullying questionnaire, derived from work by Whitney and Smith.5 There were no refusals or any significant differences in sex or social class between the groups. Mean age (range) was 14.7 (13.4-15.7) years. Mean height SD scores were: short pupils −1.90 (−3.53 to −0.01), controls 0.31 (−1.41 …",
"title": "Bullying in school: are short pupils at risk? Questionnaire study in a cohort."
}
] |
[
{
"docid": "2867345",
"text": "BACKGROUND A sexual dimorphism exists in the incidence and prevalence of coronary artery disease--men are more commonly affected than are age-matched women. We explored the role of the Y chromosome in coronary artery disease in the context of this sexual inequity. METHODS We genotyped 11 markers of the male-specific region of the Y chromosome in 3233 biologically unrelated British men from three cohorts: the British Heart Foundation Family Heart Study (BHF-FHS), West of Scotland Coronary Prevention Study (WOSCOPS), and Cardiogenics Study. On the basis of this information, each Y chromosome was tracked back into one of 13 ancient lineages defined as haplogroups. We then examined associations between common Y chromosome haplogroups and the risk of coronary artery disease in cross-sectional BHF-FHS and prospective WOSCOPS. Finally, we undertook functional analysis of Y chromosome effects on monocyte and macrophage transcriptome in British men from the Cardiogenics Study. FINDINGS Of nine haplogroups identified, two (R1b1b2 and I) accounted for roughly 90% of the Y chromosome variants among British men. Carriers of haplogroup I had about a 50% higher age-adjusted risk of coronary artery disease than did men with other Y chromosome lineages in BHF-FHS (odds ratio 1·75, 95% CI 1·20-2·54, p=0·004), WOSCOPS (1·45, 1·08-1·95, p=0·012), and joint analysis of both populations (1·56, 1·24-1·97, p=0·0002). The association between haplogroup I and increased risk of coronary artery disease was independent of traditional cardiovascular and socioeconomic risk factors. Analysis of macrophage transcriptome in the Cardiogenics Study revealed that 19 molecular pathways showing strong differential expression between men with haplogroup I and other lineages of the Y chromosome were interconnected by common genes related to inflammation and immunity, and that some of them have a strong relevance to atherosclerosis. INTERPRETATION The human Y chromosome is associated with risk of coronary artery disease in men of European ancestry, possibly through interactions of immunity and inflammation. FUNDING British Heart Foundation; UK National Institute for Health Research; LEW Carty Charitable Fund; National Health and Medical Research Council of Australia; European Union 6th Framework Programme; Wellcome Trust.",
"title": "Inheritance of coronary artery disease in men: an analysis of the role of the Y chromosome"
},
{
"docid": "12789595",
"text": "It is becoming “a truth universally acknowledged” that the education of undergraduate medical students will be enhanced through the use of computer assisted learning. Access to the wide range of online options illustrated in the figure must surely make learning more exciting, effective, and likely to be retained. This assumption is potentially but by no means inevitably correct. ### Box 1: Why fund computer assisted learning? Computer assisted learning is inevitable —Individual lecturers and departments are already beginning to introduce a wide range of computer based applications, sometimes in a haphazard way. Planned and coordinated development is better than indiscriminate expansion It is convenient and flexible —Courses supported by computer assisted learning applications may require fewer face to face lectures and seminars and place fewer geographical and temporal constraints on staff and students. Students at peripheral hospitals or primary care centres may benefit in particular Unique presentational benefits —Computer presentation is particularly suited to subjects that are visually intensive, detail oriented, and difficult to conceptualise, such as complex biochemical processes or microscopic images.1 Furthermore, “virtual” cases may reduce the need to use animal or human tissue in learning Personalised learning —Each learner can progress at his or her preferred pace. They can repeat, interrupt, and resume at will, which may have particular advantages for weaker students Economies of scale —Once an application has been set up, the incremental cost of offering it to additional students is relatively small Competitive advantage —Potential applicants may use the quality of information technology to discriminate between medical schools. A “leading edge” virtual campus is likely to attract good students Achieves the ultimate goal of higher education —The goal is to link people into learning communities. Computer applications, especially the internet and world wide web, are an extremely efficient way of doing this2 Expands pedagogical horizons —The most controversial argument for … RETURN TO TEXT",
"title": "Computer assisted learning in undergraduate medical education."
},
{
"docid": "17374970",
"text": "AIM To determine attrition and predictors of academic success among medical students at University of Split, Croatia. METHODS We analysed academic records of 2054 students enrolled during 1979-2008 period. RESULTS We found that 26% (533/2054) of enrolled students did not graduate. The most common reasons for attrition were 'personal' (36.4%), transfer to another medical school (35.6%), and dismissal due to unsatisfactory academic record (21.2%). Grade point average (GPA) and study duration of attrition students were significantly associated with parental education. There were 1126 graduates, 395 men and 731 women. Their average graduation GPA was 3.67±0.53 and study duration 7.6±2.44 years. During 5-year curriculum only 6.4% (42/654) of students graduated in time, and 55% (240/472) of students graduated in time after curriculum was extended to 6 years. Variables predicting whether a student will graduate or not were high school grades, entrance exam score and year of enrollment. Significant predictors of graduation grades were high school grades and entrance exam score. Entrance exam score predicted length of studying. CONCLUSION Preadmission academic qualifications and year of enrollment predict academic success in medical school. More attention should be devoted to high attrition.",
"title": "Predictors of Attrition and Academic Success of Medical Students: A 30-Year Retrospective Study"
},
{
"docid": "24159217",
"text": "CONTEXT No randomized controlled studies have been conducted to date on the effectiveness of psychological interventions for children with symptoms of posttraumatic stress disorder (PTSD) that has resulted from personally witnessing or being personally exposed to violence. OBJECTIVE To evaluate the effectiveness of a collaboratively designed school-based intervention for reducing children's symptoms of PTSD and depression that has resulted from exposure to violence. DESIGN A randomized controlled trial conducted during the 2001-2002 academic year. SETTING AND PARTICIPANTS Sixth-grade students at 2 large middle schools in Los Angeles who reported exposure to violence and had clinical levels of symptoms of PTSD. INTERVENTION Students were randomly assigned to a 10-session standardized cognitive-behavioral therapy (the Cognitive-Behavioral Intervention for Trauma in Schools) early intervention group (n = 61) or to a wait-list delayed intervention comparison group (n = 65) conducted by trained school mental health clinicians. MAIN OUTCOME MEASURES Students were assessed before the intervention and 3 months after the intervention on measures assessing child-reported symptoms of PTSD (Child PTSD Symptom Scale; range, 0-51 points) and depression (Child Depression Inventory; range, 0-52 points), parent-reported psychosocial dysfunction (Pediatric Symptom Checklist; range, 0-70 points), and teacher-reported classroom problems using the Teacher-Child Rating Scale (acting out, shyness/anxiousness, and learning problems; range of subscales, 6-30 points). RESULTS Compared with the wait-list delayed intervention group (no intervention), after 3 months of intervention students who were randomly assigned to the early intervention group had significantly lower scores on symptoms of PTSD (8.9 vs 15.5, adjusted mean difference, - 7.0; 95% confidence interval [CI], - 10.8 to - 3.2), depression (9.4 vs 12.7, adjusted mean difference, - 3.4; 95% CI, - 6.5 to - 0.4), and psychosocial dysfunction (12.5 vs 16.5, adjusted mean difference, - 6.4; 95% CI, -10.4 to -2.3). Adjusted mean differences between the 2 groups at 3 months did not show significant differences for teacher-reported classroom problems in acting out (-1.0; 95% CI, -2.5 to 0.5), shyness/anxiousness (0.1; 95% CI, -1.5 to 1.7), and learning (-1.1, 95% CI, -2.9 to 0.8). At 6 months, after both groups had received the intervention, the differences between the 2 groups were not significantly different for symptoms of PTSD and depression; showed similar ratings for psychosocial function; and teachers did not report significant differences in classroom behaviors. CONCLUSION A standardized 10-session cognitive-behavioral group intervention can significantly decrease symptoms of PTSD and depression in students who are exposed to violence and can be effectively delivered on school campuses by trained school-based mental health clinicians.",
"title": "A mental health intervention for schoolchildren exposed to violence: a randomized controlled trial."
},
{
"docid": "24510595",
"text": "PURPOSE Patients with daily or near-daily headaches are commonly seen in neurology practices and in headache subspecialty centers, but there is little information on the prevalence of this condition in the general population. We present the first US-based study describing the prevalence and characteristics of frequent headache in the general population. METHODS In Baltimore County, Maryland, 13 343 individuals 18 to 65 years of age were selected by random-digit dialing and interviewed by telephone about their headaches. Subjects reporting 180 or more headaches per year were classified as having frequent headache. Three mutually exclusive subtypes of frequent headache were identified: frequent headache with migrainous features, chronic tension-type headache, and unclassified frequent headache. RESULTS The overall prevalence of frequent headache was 4.1% (5.0% female, 2.8% male; 1.8:1 female to male ratio). Frequent headache was 33% more common in Caucasians (4.4%) than in African Americans (3.3%). In both males and females, prevalence was highest in the lowest educational category. Among frequent headache sufferers, more than half (52% female, 56% male) met criteria for chronic tension-type headache, almost one third (33% female, 25% male) met criteria for frequent headache with migrainous features, and the remainder (15% female, 19% male) were unclassified. Overall, 30% of female and 25% of male frequent headache sufferers met International Headache Society (IHS) criteria for migraine (with or without aura). CONCLUSIONS Frequent headache is common in the general population and is more prevalent in Caucasians and in those with less than a high school education. Chronic tension-type headache is more common than frequent headache with migrainous features, though the latter is more disabling. Although more common in females than males, the female preponderance of frequent headache is less marked than in migraine. The sex ratio varies by frequent headache subtype.",
"title": "Prevalence of frequent headache in a population sample."
},
{
"docid": "36558211",
"text": "OBJECTIVES To explore the different characteristics of high and low fat consumers, in particular their macronutrient intake and body mass index. DESIGN Reanalysis of data from the Dietary and Nutritional Survey of British Adults. Comparisons were made between groups defined as high and low fat consumers on the basis of 7-day weighed food records considered to be valid for energy intake. Individuals were classified in two ways according to the percentage energy from fat (FAT%) and the absolute amount of fat consumed (FATg). The criteria for classification of the high FAT% being > 45% (high fat) and < or = 35% (low fat). For the FATg group the threshold for the high fat group was > 138 g/day (men) and > 102 g/day (women), and for the low fat group < 85 g/day (men) and < 70 g/day (women). SETTING Dietary data was collected from private households in Great Britain between 1986 and 1987. SUBJECTS From the total population of 2197, individuals who were slimming, ill or had an EI: BMR of < 1.2 were excluded in order to use data which was most likely to represent habitual energy intakes. From the remaining 1240 subjects, 10.8% of this sample (6.1% of the total population) were classified as low fat consumers (76 men and 58 women) and 15.4% high fat (8.7% of the total population, 93 men and 98 women). MAIN OUTCOME MEASURES Macronutrient consumption and body mass index (BMI). RESULTS 30% of the subjects changed fat group classification when the criteria of defining high and low fat groups altered from FAT% to FATg. Nutrient intakes differed according to definition of the groups. The high fat FATg group ate significantly more of all nutrients than the low fat FATg group. However, this was not seen for the FAT% analysis, with the high fat group eating more fat and less carbohydrate. The average BMI tended to be higher in the high fat than the low fat groups, particularly in the FATg analysis. However, the high fat group contained a wide range of BMIs. Further exploration of BMI in the high fat groups, showed that age (an 11-year difference) was the only variable to distinguish individuals in the top and bottom quartiles of BMI. CONCLUSIONS High and low fat consumers differ according to a number of variables, and this is affected by how these groups are defined (FAT% or FATg). High fat consumers tend to have a higher BMI than low fat consumers, but not all high fat consumers are overweight or obese.",
"title": "High and low fat consumers, their macronutrient intake and body mass index: further analysis of the National Diet and Nutrition Survey of British Adults."
},
{
"docid": "2295434",
"text": "myfood24 Is an online 24-h dietary assessment tool developed for use among British adolescents and adults. Limited information is available regarding the validity of using new technology in assessing nutritional intake among adolescents. Thus, a relative validation of myfood24 against a face-to-face interviewer-administered 24-h multiple-pass recall (MPR) was conducted among seventy-five British adolescents aged 11-18 years. Participants were asked to complete myfood24 and an interviewer-administered MPR on the same day for 2 non-consecutive days at school. Total energy intake (EI) and nutrients recorded by the two methods were compared using intraclass correlation coefficients (ICC), Bland-Altman plots (using between and within-individual information) and weighted κ to assess the agreement. Energy, macronutrients and other reported nutrients from myfood24 demonstrated strong agreement with the interview MPR data, and ICC ranged from 0·46 for Na to 0·88 for EI. There was no significant bias between the two methods for EI, macronutrients and most reported nutrients. The mean difference between myfood24 and the interviewer-administered MPR for EI was -230 kJ (-55 kcal) (95 % CI -490, 30 kJ (-117, 7 kcal); P=0·4) with limits of agreement ranging between 39 % (3336 kJ (-797 kcal)) lower and 34 % (2874 kJ (687 kcal)) higher than the interviewer-administered MPR. There was good agreement in terms of classifying adolescents into tertiles of EI (κ w =0·64). The agreement between day 1 and day 2 was as good for myfood24 as for the interviewer-administered MPR, reflecting the reliability of myfood24. myfood24 Has the potential to collect dietary data of comparable quality with that of an interviewer-administered MPR.",
"title": "Agreement between an online dietary assessment tool (myfood24) and an interviewer-administered 24-h dietary recall in British adolescents aged 11-18 years."
},
{
"docid": "6710713",
"text": "OBJECTIVE To determine whether there are risk factors in a doctor's time at medical school that are associated with subsequent professional misconduct. DESIGN Matched case-control study. Setting Records from medical schools and the General Medical Council (GMC). PARTICIPANTS 59 doctors who had graduated from any one of eight medical schools in the United Kingdom in 1958-97 and had a proved finding of serious professional misconduct in GMC proceedings in 1999-2004 (cases); 236 controls (four for each case) were selected by systematic sampling from matching graduation cohorts. Case-control status was revealed by the GMC after completion of data entry. MAIN OUTCOME MEASURE Odds ratios for being a \"case,\" with multivariable conditional logistic regression of potential risk factors including pre-admission characteristics and progress during the course. These data were obtained from anonymised copies of the students' progress files held by their original medical schools. RESULTS Univariate conditional logistic regression analysis found that cases were more likely to be men, to be of lower estimated social class, and to have had academic difficulties during their medical course, especially in the early years. Multivariable analysis showed that male sex (odds ratio 9.80, 95% confidence interval 2.43 to 39.44, P=0.001), lower social class (4.28, 1.52 to 12.09, P=0.006), and failure of early or preclinical examinations (5.47, 2.17 to 13.79, P<0.001) were independently associated with being a case. CONCLUSIONS This small study suggests that male sex, a lower socioeconomic background, and early academic difficulties at medical school could be risk factors for subsequent professional misconduct. The findings are preliminary and should be interpreted with caution. Most doctors with risk factors will not come before the GMC's disciplinary panels.",
"title": "Risk factors at medical school for subsequent professional misconduct: multicentre retrospective case-control study"
},
{
"docid": "84580585",
"text": "This volume and its companion, Volume 350, are specifically designed to meet the needs of graduate students and postdoctoral students as well as researchers, by providing all the up-to-date methods necessary to study genes in yeast. Procedures are included that enable newcomers to set up a yeast laboratory and to master basic manipulations. Relevant background and reference information given for procedures can be used as a guide to developing protocols in a number of disciplines. Specific topics addressed in this book include cytology, biochemistry, cell fractionation, and cell biology.",
"title": "Guide to yeast genetics and molecular biology"
},
{
"docid": "31543713",
"text": "The recent development of microarray technology has led statisticians and bioinformaticians to develop new statistical methodologies for comparing different biological samples. The objective is to identify a small number of differentially expressed genes from among thousands. In quantitative proteomics, analysis of protein expression using two-dimensional gel electrophoresis shows some similarities with transcriptomic studies. Thus, the goal of this study was to evaluate different data analysis methodologies widely used in array analysis using different proteomic data sets of hundreds of proteins. Even with few replications, the significance analysis of microarrays method appeared to be more powerful than the Student's t test in truly declaring differentially expressed proteins. This procedure will avoid wasting time due to false positives and losing information with false negatives.",
"title": "Data analysis methods for detection of differential protein expression in two-dimensional gel electrophoresis."
},
{
"docid": "34818263",
"text": "As time passes, the AIDS pandemic continues to spike, affecting an estimated 38.6 million people worldwide. In response, a satellite health clinic is being d esigned by two Cal Poly students to serve the Maasai people living in the Kajiado district in Southern Kenya. The Maasai have traditionally lived as pastoralists, surviving off of their cattle with which they share their water, increasing the risk for contamination. However, as the population of Kenya increases, the land the Maasai have traditionally used for grazing is shrink ing. For this reason, some have turned to farming to maintain their liveli hood. These factors have contributed to the desertification and deforestation of their region. As the lifestyle of the Maasai evolves, they rely more on maize than meat and dairy products for their nutrients. All of these changes have contributed to the evolution of the Maasai culture. We will address these changes in order to better understand the Maasai, as well as highlight pos sible further aid needed to support their survival.",
"title": "Current Health and Environmental Status of the Maasai People in Sub-Saharan Africa"
},
{
"docid": "3413083",
"text": "BACKGROUND Following widespread rollout of chlamydia testing to non-specialist and community settings in the UK, many individuals receive a chlamydia test without being offered comprehensive STI and HIV testing. We assess sexual behaviour among testers in different settings with a view to understanding their need for other STI diagnostic services. METHODS A probability sample survey of the British population undertaken 2010-2012 (the third National Survey of Sexual Attitudes and Lifestyles). We analysed weighted data on chlamydia testing (past year), including location of most recent test, and diagnoses (past 5 years) from individuals aged 16-44 years reporting at least one sexual partner in the past year (4992 women, 3406 men). RESULTS Of the 26.8% (95% CI 25.4% to 28.2%) of women and 16.7% (15.5% to 18.1%) of men reporting a chlamydia test in the past year, 28.4% of women and 41.2% of men had tested in genitourinary medicine (GUM), 41.1% and 20.7% of women and men respectively tested in general practice (GP) and the remainder tested in other non-GUM settings. Women tested outside GUM were more likely to be older, in a relationship and to live in rural areas. Individuals tested outside GUM reported fewer risk behaviours; nevertheless, 11.0% (8.6% to 14.1%) of women and 6.8% (3.9% to 11.6%) of men tested in GP and 13.2% (10.2% to 16.8%) and 9.6% (6.5% to 13.8%) of women and men tested in other non-GUM settings reported 'unsafe sex', defined as two or more partners and no condom use with any partner in the past year. Individuals treated for chlamydia outside GUM in the past 5 years were less likely to report an HIV test in that time frame (women: 54.5% (42.7% to 65.7%) vs 74.1% (65.9% to 80.9%) in GUM; men: 23.9% (12.7% to 40.5%) vs 65.8% (56.2% to 74.3%)). CONCLUSIONS Most chlamydia testing occurred in non-GUM settings, among populations reporting fewer risk behaviours. However, there is a need to provide pathways to comprehensive STI care to the sizeable minority at higher risk.",
"title": "Patterns of chlamydia testing in different settings and implications for wider STI diagnosis and care: a probability sample survey of the British population"
},
{
"docid": "36033696",
"text": "OBJECTIVE The purpose of this project was to educate inpatients with psychotic disorders, many of whom were taking second-generation antipsychotics, about lifestyle changes they can make to combat weight gain. METHOD All inpatients on a Veterans Affairs acute inpatient schizophrenia treatment unit were invited to a 30-minute, didactic presentation given by a medical student and a psychology student under the supervision of the primary investigator. The topics covered included the health benefits of maintaining an ideal body weight by selecting foods according to the USDA Food Pyramid, determining adequate food portions, choosing healthy meals outside the home, and beginning and adhering to an exercise program. Subjects completed a 13-item quiz concerning their knowledge of food and nutrition before and after the presentation to determine its efficacy in teaching patients the material. RESULTS Fifty patients completed both the pre- and post-presentation tests. The mean percentage of correct answers on the pre-test was 85.6%, which rose to 89.3% on the post-test. This difference of 3.7% was statistically significant (t = 2.43, df = 49, p < 0.02), and the mean percent of improvement was 6.1%. CONCLUSIONS This study demonstrates that psychotic individuals are able to benefit from educational presentations about nutrition and a healthy lifestyle. A statistically significant improvement in test scores suggests that subjects gained an understanding of basic concepts related to food choices and fitness.",
"title": "A wellness class for inpatients with psychotic disorders."
},
{
"docid": "45027320",
"text": "BACKGROUND The aim of this study was to examine the clustering of four major lifestyle risk factors (smoking, heavy drinking, lack of fruit and vegetables consumption, and lack of physical activity), and to examine the variation across different socio-demographic groups in the English adult population. METHODS The study population was derived from the 2003 Health Survey for England (n=11,492). Clustering was examined by comparing the observed and expected prevalence of the different possible combinations. A multinomial multilevel regression model was conducted to examine the socio-demographic variation in the clustering of the four risk factors. RESULTS The study found that, when using British health recommendations, a majority of the English population have multiple lifestyle risk factors at the same time. Clustering was found at both ends of the lifestyle spectrum and was more pronounced for women than for men. Overall, multiple risk factors were more prevalent among men, lower social class households, singles, and people who are economically inactive, but less prevalent among home owners and older age groups. CONCLUSIONS The clustering of multiple risk factors provides support for multiple-behavior interventions as opposed to single-behavior interventions.",
"title": "The prevalence and clustering of four major lifestyle risk factors in an English adult population."
},
{
"docid": "13445579",
"text": "BACKGROUND AND PURPOSE IAs are found in 2.3% of adults; the mean age at detection is 52 years. Prevalence is <0.5% in young adults. Early studies suggest that 10%-50% of patients with aortic coarctation have IAs. Screening recommendations are variable. We sought to examine the prevalence of IAs through screening with MRA. MATERIALS AND METHODS Consecutive patients older than 16 years of age with coarctation undergoing brain MRA between May 1999 and October 2007 were included. MRA was performed by using a 1.5T scanner with a 3D time-of-flight protocol; simultaneous MR imaging was performed of the heart and aorta. Cerebral MRAs were double-reported by a neuroradiologist. Statistics are described as mean ± SD and median ± range. Continuous variables were compared by using Student t tests and Mann-Whitney U tests (categoric variables, by using the Fisher exact test). RESULTS One hundred seventeen MRAs were double-reported. The median age was 29 ± 11 years (range, 16-59 years). IAs were found in 12 patients (10.3%). The mean diameter of IAs was 3.9 mm (range, 2.0-8.0 mm). Patients with aneurysms were older (median, 37 years; range, 16-50 years) than those without (median, 23 years; range, 16-59 years; Z = -2.01, P = .04). Hypertension was more common in those with IAs (IA 83% versus no IA 43%, P = .01). There was no association between ascending aortopathy, bicuspid aortic valves, and IAs. CONCLUSIONS Patients with coarctation have a higher prevalence of IAs, occurring at an earlier age than in population studies. Whether routine screening is appropriate for this group of patients is unclear. Hypertension is likely to be an important pathophysiologic factor.",
"title": "Results of screening for intracranial aneurysms in patients with coarctation of the aorta."
},
{
"docid": "13900610",
"text": "BACKGROUND Self-harm and suicide are common in prisoners, yet robust information on the full extent and characteristics of people at risk of self-harm is scant. Furthermore, understanding how frequently self-harm is followed by suicide, and in which prisoners this progression is most likely to happen, is important. We did a case-control study of all prisoners in England and Wales to ascertain the prevalence of self-harm in this population, associated risk factors, clustering effects, and risk of subsequent suicide after self-harm. METHODS Records of self-harm incidents in all prisons in England and Wales were gathered routinely between January, 2004, and December, 2009. We did a case-control comparison of prisoners who self-harmed and those who did not between January, 2006, and December, 2009. We also used a Bayesian approach to look at clustering of people who self-harmed. Prisoners who self-harmed and subsequently died by suicide in prison were compared with other inmates who self-harmed. FINDINGS 139,195 self-harm incidents were recorded in 26,510 individual prisoners between 2004 and 2009; 5-6% of male prisoners and 20-24% of female inmates self-harmed every year. Self-harm rates were more than ten times higher in female prisoners than in male inmates. Repetition of self-harm was common, particularly in women and teenage girls, in whom a subgroup of 102 prisoners accounted for 17,307 episodes. In both sexes, self-harm was associated with younger age, white ethnic origin, prison type, and a life sentence or being unsentenced; in female inmates, committing a violent offence against an individual was also a factor. Substantial evidence was noted of clustering in time and location of prisoners who self-harmed (adjusted intra-class correlation 0·15, 95% CI 0·11-0·18). 109 subsequent suicides in prison were reported in individuals who self-harmed; the risk was higher in those who self-harmed than in the general prison population, and more than half the deaths occurred within a month of self-harm. Risk factors for suicide after self-harm in male prisoners were older age and a previous self-harm incident of high or moderate lethality; in female inmates, a history of more than five self-harm incidents within a year was associated with subsequent suicide. INTERPRETATION The burden of self-harm in prisoners is substantial, particularly in women. Self-harm in prison is associated with subsequent suicide in this setting. Prevention and treatment of self-harm in prisoners is an essential component of suicide prevention in prisons. FUNDING Wellcome Trust, National Institute for Health Research, National Offender Management Service, and Department of Health.",
"title": "Self-harm in prisons in England and Wales: an epidemiological study of prevalence, risk factors, clustering, and subsequent suicide"
},
{
"docid": "21641088",
"text": "Obesity is a multifactorial disease with a marked genetic component. The situation is further complicated by the heterogeneity of obesity demonstrated by the topographical distribution of body fat, e.g. upper body (central) and lower body (gluteal) obesity. Furthermore, the distribution of fat shows a stronger heritable tendency compared with total body fat. Central obesity is characterized by hyperinsulinaemia and insulin resistance, a feature in common with non-insulin dependent diabetes mellitus, hypertension and atherosclerosis. In order to study the molecular genetics of central obesity we have examined 56 severely obese (mean body mass index 40), unrelated British Caucasoid young non-diabetic women for associations of restriction fragment length polymorphism of candidate genes with anthropometric measurements and indices of insulin secretion and resistance. The candidate genes examined were insulin receptor, insulin sensitive glucose transporter and insulin. An association of the class 3 allele of the hypervariable region in the 5' flanking region of the insulin gene was found with upper segment obesity (P = 0.005). Furthermore, the class 3 allele was also associated with fasting hyperinsulinaemia (P = 0.01), stimulated insulin secretion (P = 0.01) and insulin resistance as calculated from the homeostatic model of assessment (HOMA; P = 0.008). No such associations were found with the other candidate genes studied. This data suggests that polymorphisms in the 5' flanking region of the insulin gene may affect expression of the gene and thereby modulate insulin production in severely obese female subjects.",
"title": "Central obesity and hyperinsulinaemia in women are associated with polymorphism in the 5' flanking region of the human insulin gene."
},
{
"docid": "9211173",
"text": "BACKGROUND Ovarian clear-cell and endometrioid carcinomas may arise from endometriosis, but the molecular events involved in this transformation have not been described. METHODS We sequenced the whole transcriptomes of 18 ovarian clear-cell carcinomas and 1 ovarian clear-cell carcinoma cell line and found somatic mutations in ARID1A (the AT-rich interactive domain 1A [SWI-like] gene) in 6 of the samples. ARID1A encodes BAF250a, a key component of the SWI–SNF chromatin remodeling complex. We sequenced ARID1A in an additional 210 ovarian carcinomas and a second ovarian clear-cell carcinoma cell line and measured BAF250a expression by means of immunohistochemical analysis in an additional 455 ovarian carcinomas. RESULTS ARID1A mutations were seen in 55 of 119 ovarian clear-cell carcinomas (46%), 10 of 33 endometrioid carcinomas (30%), and none of the 76 high-grade serous ovarian carcinomas. Seventeen carcinomas had two somatic mutations each. Loss of the BAF250a protein correlated strongly with the ovarian clear-cell carcinoma and endometrioid carcinoma subtypes and the presence of ARID1A mutations. In two patients, ARID1A mutations and loss of BAF250a expression were evident in the tumor and contiguous atypical endometriosis but not in distant endometriotic lesions. CONCLUSIONS These data implicate ARID1A as a tumor-suppressor gene frequently disrupted in ovarian clear-cell and endometrioid carcinomas. Since ARID1A mutation and loss of BAF250a can be seen in the preneoplastic lesions, we speculate that this is an early event in the transformation of endometriosis into cancer. (Funded by the British Columbia Cancer Foundation and the Vancouver General Hospital–University of British Columbia Hospital Foundation.).",
"title": "ARID1A mutations in endometriosis-associated ovarian carcinomas."
},
{
"docid": "12561083",
"text": "BACKGROUND Several studies have demonstrated that women with nonobstructive coronary disease have a high rate of subsequent investigations, rehospitalizations for recurrent chest pain, and repeat coronary angiography. The sex specificity of this finding is unclear. We therefore undertook an evaluation of sex differences in rehospitalization for acute coronary syndrome (ACS) or chest pain in patients with \"angiographically normal\" coronaries. METHODS A retrospective cohort study using prospectively collected angiographic and clinical data on all patients in British Columbia, Canada, presenting for their first cardiac catheterization with suspected ischemic heart disease but angiographically normal coronaries. RESULTS Among 32,856 patients, 7.1% of men versus 23.3% of women were angiographically normal (P < .001). Among angiographically normal patients, women were older and more likely to present with hypertension, prior stroke, chronic obstructive pulmonary disease, and peripheral vascular disease than men, but Canadian Cardiovascular Society class of angina did not vary by sex. Within 1 year, 1.0% died, (19 women, 18 men, P = .27) and 0.6% had a stroke (13 women, 9 men, P = .91). Readmission to hospital for ACS or chest pain requiring catheterization was significantly higher in women compared to men (adjusted OR 4.06; 95% CI 1.15-14.31). CONCLUSIONS In a contemporary, population-based cohort presenting for cardiac catheterization for suspected ischemia, women with angiographically normal coronaries were >4 times more likely to be readmitted to hospital for ACS/chest pain within 180 days compared to men. The observed sex difference has important social and economic implications and suggests that traditional diagnostic methods may not be optimal for women.",
"title": "Angina with \"normal\" coronary arteries: sex differences in outcomes."
},
{
"docid": "18557974",
"text": "High plasma total homocysteine (tHcy) concentration is reported to be a risk factor for vascular diseases. We investigated the extent to which serum folate and plasma tHcy respond to a high intake of natural folate from food. Thirty-seven healthy females volunteered t o participate in a crossover dietary intervention. The study included a baseline period and two 5-week diet periods (low- and high-folate diets) with a 3-week washout in between. The low-folate diet contained one serving of both vegetables and fruit/d, while during the high-folate diet the subjects ate at least seven servings of vegetables, berries, and citrus fruit/d. Serum and erythrocyte (RBC) folate, serum vitamin B (12), and plasma tHcy concentrations were measured at the base-line and at the end of each diet period. The mean concentrations of serum and RBC folate were 11.0 (SD 3.0) nmol/l and 412 (SD 120) nmol/l at the end of the low-folate diet and 78 (95 % CI 62, 94) % and 14 (95 % CI 8, 20) % higher in response to the high-folate diet (P< 0.001). The serum concentration of vitamin B12 remained unchanged during the intervention. The mean plasma tHcy concentration was 8.0 pmol/ at the end of the low-folate diet and decreased by 13 (95% CI 9, 18) % in response to the high-folate diet (P<0.001). In conclusion, a diet high in fresh berries, citrus fruit, and vegetables effectively increases serum and RBC folate and decreases plasma homocysteine.",
"title": "British Journal of Nutrition (2003), 89, 295–301 q The Authors 2003 DOI: 10.1079/BJN2002776 Plasma homocysteine concentration is decreased by dietary intervention*"
},
{
"docid": "143381103",
"text": "This article provides psychometric information on the second edition of the Beck Depression Inventory (BDI-II; A. T. Beck, R. A. Steer, & G. K. Brown, 1996), with respect to internal consistency, factorial validity, and gender differences. Both measures demonstrated high internal reliability in the full student sample. Significant differences between the mean BDI and BDI-II scores necessitated the development of new cutoffs for analogue research on the BDI-II. Results from exploratory and confirmatory factor analyses indicated that a 2-factor solution optimally summarized the data for both versions of the inventory and accounted for a cumulative 41% and 46% of the common variance in BDI and BDI-II responses, respectively. These factor solutions were reliably cross-validated, although the importance of each factor varied by gender. The authors conclude that the BDI-II is a stronger instrument than the BDI in terms of its factor structure.",
"title": "A psychometric evaluation of the Beck Depression Inventory–II."
},
{
"docid": "23439808",
"text": "We hypothesized that serum cystatin C can be a more predictable marker of arterial stiffness than serum creatinine and creatinine-based glomerular filtration rate (GFR). The aim of this study is to evaluate whether serum cystatin C is related to arterial stiffness independently of serum creatinine in subjects for whom serum creatinine is normal. A total of 2,018 individuals (1,120 males, 898 females) were enrolled. Mean brachial-ankle pulse wave velocity (baPWV) was used as a marker of arterial stiffness and sex-specific analysis was performed. A positive relationship between baPWV and serum cystatin C (Y=1109.0548+329.9102X, r2=0.056, p<0.001) was found in males. Stepwise multivariate regression analysis in males showed that age, waist circumference, heart rate, cystatin C level, triglyceride level, and fasting glucose were independent contributors to baPWV. In females, a positive relationship between baPWV and serum cystatin C (Y=1035.7828+402.2970X, r2=0.090, p<0.001) was found. Stepwise multivariate regression analysis showed that age, heart rate, cystatin C level, fasting glucose and insulin level were independent contributors to baPWV. Age, heart rate, fasting glucose and serum cystatin C were the significant variables in both genders that contributed to baPWV. In conclusion, this study confirmed that serum cystatin C was related to pulse wave velocity even in subjects with normal serum creatinine. This finding suggested that cystatin C could be a more predictable marker of arterial stiffness than serum creatinine and creatinine-based GFR.",
"title": "Serum Cystatin C Is Related to Pulse Wave Velocity Even in Subjects with Normal Serum Creatinine"
},
{
"docid": "34228604",
"text": "Females live longer than males in many species, including humans. We have traced a possible explanation for this phenomenon to the beneficial action of estrogens, which bind to estrogen receptors and increase the expression of longevity-associated genes, including those encoding the antioxidant enzymes superoxide dismutase and glutathione peroxidase. As a result, mitochondria from females produce fewer reactive oxygen species than those from males. Administering estrogens has serious drawbacks, however--they are feminizing (and thus cannot be administered to males) and may increase the incidence of serious diseases such as uterine cancer in postmenopausal women. Phytoestrogens, which are present in soy or wine, may have some of the favorable effects of estrogens without their undesirable effects. Study of gender differences in longevity may help us to understand the basic processes of aging and to devise practical strategies to increase the longevity of both females and males.",
"title": "Why females live longer than males: control of longevity by sex hormones."
},
{
"docid": "6503534",
"text": "A group of 27 Italian patients was screened for α-L-iduronidase mucopolysaccharidosis type I mutations. Mutations were found in 18 patients, with 28 alleles identified. The two most common mutations in northern Europeans (W402X and Q70X) accounted for 11% and 13% of the alleles, respectively. The R89Q mutation, uncommon in Europeans, was found only in one patient, accounting for 1 of 54 alleles (1.9%). The other mutations, P533R, A327P and G51D, accounted for 11%, 5.6% and 9.3% of the total alleles, respectively. Interestingly, the high frequency of the P533R mutation seems to be confined to Sicily and is higher than the 3% reported in a British/Australian study.",
"title": "Mutations among Italian mucopolysaccharidosis type I patients"
},
{
"docid": "10209731",
"text": "STUDY OBJECTIVE The aim of the study was to analyse differences in mortality from the main cardiovascular diseases (ischaemic heart disease, hypertensive disease, and cerebrovascular disease) among Chinese, Malays, and Indians in Singapore. DESIGN The study was a survey using national death registration data in Singapore for the five years 1980 to 1984. The underlying cause of death, coded according to the ninth revision of the International Classification of Diseases, was taken for the analyses. SETTING The study was confined to the independent island state of Singapore, population 2.53 million (Chinese 76.5%, Malays 14.8%, Indians 6.4%, Others 2.3%). Death registration is thought to be complete. SUBJECTS All registered deaths in the age range 30-69 years during the study period were analysed by ethnic group. MEASUREMENT AND MAIN RESULTS Indians had higher mortality from ischaemic heart disease than the other ethnic groups in both sexes, with age-standardised relative risks of Indian v Chinese (males 3.8, females 3.4), Indian v Malay (males 1.9, females 1.6), and Malay v Chinese (males 2.0, females 2.2). The excess mortality in Indians declined with age. For hypertensive disease Malays had the highest mortality, with age-standardised relative risks of Malay v Chinese (males 3.4, females 4.4), Malay v Indian (males 2.0, females 2.5), and Indian v Chinese (males 1.6, females 1.6). For cerebrovascular disease there was little ethnic difference except for lower rates in Chinese females, with age-standardised relative risks of Malay v Chinese (males 1.1, females 1.9), Malay v Indian (males 1.0, females 1.1), and Indian v Chinese (males 1.1, females 1.7). CONCLUSIONS There are significant differences in mortality from the three main cardiovascular diseases in the different ethnic groups in Singapore.",
"title": "Cardiovascular diseases in Chinese, Malays, and Indians in Singapore. I. Differences in mortality."
},
{
"docid": "3552753",
"text": "BACKGROUND In the assessment of severity in community acquired pneumonia (CAP), the modified British Thoracic Society (mBTS) rule identifies patients with severe pneumonia but not patients who might be suitable for home management. A multicentre study was conducted to derive and validate a practical severity assessment model for stratifying adults hospitalised with CAP into different management groups. METHODS Data from three prospective studies of CAP conducted in the UK, New Zealand, and the Netherlands were combined. A derivation cohort comprising 80% of the data was used to develop the model. Prognostic variables were identified using multiple logistic regression with 30 day mortality as the outcome measure. The final model was tested against the validation cohort. RESULTS 1068 patients were studied (mean age 64 years, 51.5% male, 30 day mortality 9%). Age >/=65 years (OR 3.5, 95% CI 1.6 to 8.0) and albumin <30 g/dl (OR 4.7, 95% CI 2.5 to 8.7) were independently associated with mortality over and above the mBTS rule (OR 5.2, 95% CI 2.7 to 10). A six point score, one point for each of Confusion, Urea >7 mmol/l, Respiratory rate >/=30/min, low systolic(<90 mm Hg) or diastolic (</=60 mm Hg) Blood pressure), age >/=65 years (CURB-65 score) based on information available at initial hospital assessment, enabled patients to be stratified according to increasing risk of mortality: score 0, 0.7%; score 1, 3.2%; score 2, 3%; score 3, 17%; score 4, 41.5% and score 5, 57%. The validation cohort confirmed a similar pattern. CONCLUSIONS A simple six point score based on confusion, urea, respiratory rate, blood pressure, and age can be used to stratify patients with CAP into different management groups.",
"title": "Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study."
},
{
"docid": "9310407",
"text": "INTRODUCTION Isotonic crystalloids play a central role in perioperative fluid management. Isooncotic preparations of colloids (for example, human albumin or hydroxyethyl starch) remain nearly completely intravascular when infused to compensate for acute blood losses. Recent data were interpreted to indicate a comparable intravascular volume effect for crystalloids, challenging the occasionally suggested advantage of using colloids to treat hypovolemia. General physiological knowledge and clinical experience, however, suggest otherwise. METHODS In a prospective study, double-tracer blood volume measurements were performed before and after intended normovolemic hemodilution in ten female adults, simultaneously substituting the three-fold amount of withdrawn blood with Ringer's lactate. Any originated deficits were substituted with half the volume of 20% human albumin, followed by a further assessment of blood volume. To assess significance between the measurements, repeated measures analysis of variance (ANOVA) according to Fisher were performed. If significant results were shown, paired t tests (according to Student) for the singular measurements were taken. P < 0.05 was considered to be significant. RESULTS A total of 1,097 ± 285 ml of whole blood were withdrawn (641 ± 155 ml/m(2) body surface area) and simultaneously replaced by 3,430 ± 806 ml of Ringer's lactate. All patients showed a significant decrease in blood volume after hemodilution (-459 ± 185 ml; P < 0.05) that did not involve relevant hemodynamical changes, and a significant increase in interstitial water content (+2,157 ± 606 ml; P < 0.05). The volume effect of Ringer's lactate was 17 ± 10%. The infusion of 245 ± 64 ml of 20% human albumin in this situation restored blood volume back to baseline values, the volume effect being 184 ± 63%. CONCLUSIONS Substitution of isolated intravascular deficits in cardiopulmonary healthy adults with the three-fold amount of Ringer's lactate impedes maintenance of intravascular normovolemia. The main side effect was an impressive interstitial fluid accumulation, which was partly restored by the intravenous infusion of 20% human albumin. We recommend to substitute the five-fold amount of crystalloids or to use an isooncotic preparation in the face of acute bleeding in patients where edema prevention might be advantageous.",
"title": "The intravascular volume effect of Ringer's lactate is below 20%: a prospective study in humans"
},
{
"docid": "20610390",
"text": "OBJECTIVES To investigate incidence, mortality and case survival trends for cancer of unknown primary site (CUP) and consider clinical implications. METHOD South Australian Cancer Registry data were used to calculate age-standardised incidence and mortality rates from 1977 to 2004. Disease-specific survivals, socio-demographic, histological and secular predictors of CUP, compared with cancers of known primary site, and of CUP histological types, using multivariable logistic regression were investigated. RESULTS Incidence and mortality rates increased approximately 60% between 1977--80 and 1981--84. Rates peaked in 1993--96. Male to female incidence and mortality rate ratios approximated 1.3:1. Incidence and mortality rates increased with age. The odds of unspecified histological type, compared with the more common adenocarcinomas, were higher for males than females, non-metropolitan residents, low socio-economic areas, and for 1977--88 than subsequent diagnostic periods. CUP represented a higher proportion of cancers in Indigenous patients. Case survival was 7% at 10 years from diagnosis. Factors predictive of lower case survival included older age, male sex, Indigenous status, lower socio-economic status, and unspecified histology type. CONCLUSION Results point to poor CUP outcomes, but with a modest improvement in survival. The study identifies socio-demographic groups at elevated risk of CUP and of worse treatment outcomes where increased research and clinical attention are required.",
"title": "Exploring the epidemiological characteristics of cancers of unknown primary site in an Australian population: implications for research and clinical care."
},
{
"docid": "60515890",
"text": "\" The Mouse Brain in Stereotaxic Coordinates\" is the most widely used and cited atlas of the mouse brain in print. It provides researchers and students with both accurate stereotaxic coordinates for laboratory use, and detailed delineations and indexing of structures for reference. The accompanying DVD provides drawings of brains structures that can be used as templates for making figures for publication. The 3rd edition is both a major revision and an expansion of previous editions. Delineations and photographs in the horizontal plane of section now complement the coronal and sagittal series, and all the tissue sections are now shown in high resolution digital color photography. The photographs of the sections and the intermediate sections are also provided on the accompanying DVD in high-resolution JP 2000 format. The delineations of structures have been revised, and naming conventions made consistent with Paxinos and Watson's \"Rat Brain in Stereotaxic Coordinates, 6th Edition\". The 3rd edition of this atlas is now in more practical 14\"x11\" format for convenient lab use. This edition is in full color throughout. It includes a CD of all plates and diagrams, as well as Adobe Illustrator files of the diagrams, and a variety of additional useful material. Coronal and sagittal diagrams are completely reworked and updated. Rhombomeric borders are included in sagittal figures, for the first time in mammals. Microscopic plates are scanned with a new method in much higher quality.",
"title": "The Mouse Brain in Stereotaxic Coordinates"
},
{
"docid": "2052720",
"text": "OBJECTIVE To investigate the association between gastric cancer and prior infection with Helicobacter pylori. DESIGN Case-control comparison of prevalence of IgG antibodies to H pylori in blood samples collected prospectively, before diagnosis of gastric cancer in the cases. Presence of H pylori antibody (greater than 10 micrograms IgG/ml) determined by enzyme linked immunosorbent assay (ELISA). SUBJECTS 29 men with a subsequent diagnosis of gastric cancer and 116 aged matched controls selected from over 22,000 middle aged men participating in two ongoing cohort studies (the British United Provident Association study and the Caerphilly collaborative heart disease study), who had provided blood samples during 1975-1982. RESULTS 20 of the 29 cases (69%) and 54 of the 116 controls (47%) were positive for H pylori specific antibody. The median specific IgG concentration was significantly higher in the cases than controls (90 micrograms/ml v 3.6 micrograms/ml, p less than 0.01). The estimated odds ratio for the risk of gastric cancer in those with a history of infection with H pylori was 2.77 (95% confidence interval 1.04 to 7.97, 2p = 0.039). CONCLUSIONS H pylori infection may be an important cause of gastric cancer; between 35% and 55% of all cases may be associated with such an infection.",
"title": "Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation."
}
] |
315
|
Decrease of p62 in prostate tumor stroma results in defective autophagy.
|
[
{
"docid": "3701541",
"text": "Hepatic stellate cells (HSCs) play critical roles in liver fibrosis and hepatocellular carcinoma (HCC). Vitamin D receptor (VDR) activation in HSCs inhibits liver inflammation and fibrosis. We found that p62/SQSTM1, a protein upregulated in liver parenchymal cells but downregulated in HCC-associated HSCs, negatively controls HSC activation. Total body or HSC-specific p62 ablation potentiates HSCs and enhances inflammation, fibrosis, and HCC progression. p62 directly interacts with VDR and RXR promoting their heterodimerization, which is critical for VDR:RXR target gene recruitment. Loss of p62 in HSCs impairs the repression of fibrosis and inflammation by VDR agonists. This demonstrates that p62 is a negative regulator of liver inflammation and fibrosis through its ability to promote VDR signaling in HSCs, whose activation supports HCC.",
"title": "p62/SQSTM1 by Binding to Vitamin D Receptor Inhibits Hepatic Stellate Cell Activity, Fibrosis, and Liver Cancer."
}
] |
[
{
"docid": "26735905",
"text": "The tumor microenvironment plays a critical role in cancer progression, but the precise mechanisms by which stromal cells influence the epithelium are poorly understood. Here we show that p62 levels were reduced in the stroma of several tumors and that its loss in the tumor microenvironment or stromal fibroblasts resulted in increased tumorigenesis of epithelial prostate cancer cells. The mechanism involves the regulation of cellular redox through an mTORC1/c-Myc pathway of stromal glucose and amino acid metabolism, resulting in increased stromal IL-6 production, which is required for tumor promotion in the epithelial compartment. Thus, p62 is an anti-inflammatory tumor suppressor that acts through the modulation of metabolism in the tumor stroma.",
"title": "Metabolic reprogramming of stromal fibroblasts through p62-mTORC1 signaling promotes inflammation and tumorigenesis."
},
{
"docid": "25576204",
"text": "Malignant cells often display defects in autophagy, an evolutionarily conserved pathway for degrading long-lived proteins and cytoplasmic organelles. However, as yet, there is no genetic evidence for a role of autophagy genes in tumor suppression. The beclin 1 autophagy gene is monoallelically deleted in 40-75% of cases of human sporadic breast, ovarian, and prostate cancer. Therefore, we used a targeted mutant mouse model to test the hypothesis that monoallelic deletion of beclin 1 promotes tumorigenesis. Here we show that heterozygous disruption of beclin 1 increases the frequency of spontaneous malignancies and accelerates the development of hepatitis B virus-induced premalignant lesions. Molecular analyses of tumors in beclin 1 heterozygous mice show that the remaining wild-type allele is neither mutated nor silenced. Furthermore, beclin 1 heterozygous disruption results in increased cellular proliferation and reduced autophagy in vivo. These findings demonstrate that beclin 1 is a haplo-insufficient tumor-suppressor gene and provide genetic evidence that autophagy is a novel mechanism of cell-growth control and tumor suppression. Thus, mutation of beclin 1 or other autophagy genes may contribute to the pathogenesis of human cancers.",
"title": "Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene."
},
{
"docid": "8702697",
"text": "AIMS Tumor microenvironment is a strong determinant for the acquisition of metastatic potential of cancer cells. We have recently demonstrated that cancer-associated fibroblasts (CAFs) elicit a redox-dependent epithelial-mesenchymal transition (EMT) in prostate cancer (PCa) cells, driven by cycloxygenase-2/hypoxia-inducible factor-1 (HIF-1)/nuclear factor-κB pathway and enhancing tumor aggressiveness. Here, we investigated the involvement of microRNAs (miRNAs) in tumor-stroma interplay to identify possible tools to counteract oxidative stress and metastasis dissemination. RESULTS We found that miR-205 is the most downmodulated miRNA in PCa cells upon CAF stimulation, due to direct transcriptional repression by HIF-1, a known redox-sensitive transcription factor. Rescue experiments demonstrated that ectopic miR-205 overexpression in PCa cells counteracts CAF-induced EMT, thus impairing enhancement of cell invasion, acquisition of stem cell traits, tumorigenicity, and metastatic dissemination. In addition, miR-205 blocks tumor-driven activation of surrounding fibroblasts by reducing pro-inflammatory cytokine secretion. INNOVATION Overall, such findings suggest miR-205 as a brake against PCa metastasis by blocking both the afferent and efferent arms of the circuit between tumor cells and associated fibroblasts, thus interrupting the pro-oxidant and pro-inflammatory circuitries engaged by reactive stroma. CONCLUSION The evidence that miR-205 replacement in PCa cells is able not only to prevent but also to revert the oxidative/pro-inflammatory axis leading to EMT induced by CAFs sets the rationale for developing miRNA-based approaches to prevent and treat metastatic disease.",
"title": "miR-205 hinders the malignant interplay between prostate cancer cells and associated fibroblasts."
},
{
"docid": "24349992",
"text": "Loss of stromal fibroblast caveolin-1 (Cav-1) is a powerful single independent predictor of poor prognosis in human breast cancer patients, and is associated with early tumor recurrence, lymph node metastasis and tamoxifen-resistance. We developed a novel co-culture system to understand the mechanism(s) by which a loss of stromal fibroblast Cav-1 induces a \"lethal tumor micro-environment. \" Here, we propose a new paradigm to explain the powerful prognostic value of stromal Cav-1. In this model, cancer cells induce oxidative stress in cancer-associated fibroblasts, which then acts as a \"metabolic\" and \"mutagenic\" motor to drive tumor-stroma co-evolution, DNA damage and aneuploidy in cancer cells. More specifically, we show that an acute loss of Cav-1 expression leads to mitochondrial dysfunction, oxidative stress and aerobic glycolysis in cancer associated fibroblasts. Also, we propose that defective mitochondria are removed from cancer-associated fibroblasts by autophagy/mitophagy that is induced by oxidative stress. As a consequence, cancer associated fibroblasts provide nutrients (such as lactate) to stimulate mitochondrial biogenesis and oxidative metabolism in adjacent cancer cells (the \"Reverse Warburg Effect\"). We provide evidence that oxidative stress in cancer-associated fibroblasts is sufficient to induce genomic instability in adjacent cancer cells, via a bystander effect, potentially increasing their aggressive behavior. Finally, we directly demonstrate that nitric oxide (NO) over-production, secondary to Cav-1 loss, is the root cause for mitochondrial dysfunction in cancer associated fibroblasts. In support of this notion, treatment with anti-oxidants (such as N-acetyl-cysteine, metformin and quercetin) or NO inhibitors (L-NAME) was sufficient to reverse many of the cancer-associated fibroblast phenotypes that we describe. Thus, cancer cells use \"oxidative stress\" in adjacent fibroblasts (i) as an \"engine\" to fuel their own survival via the stromal production of nutrients and (ii) to drive their own mutagenic evolution towards a more aggressive phenotype, by promoting genomic instability. We also present evidence that the \"field effect\" in cancer biology could also be related to the stromal production of ROS and NO species. eNOS-expressing fibroblasts have the ability to downregulate Cav-1 and induce mitochondrial dysfunction in adjacent fibroblasts that do not express eNOS. As such, the effects of stromal oxidative stress can be laterally propagated, amplified and are effectively \"contagious\"--spread from cell-to-cell like a virus--creating an \"oncogenic/mutagenic\" field promoting widespread DNA damage.",
"title": "Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells."
},
{
"docid": "10463997",
"text": "Objectives: Autophagy is a highly regulated process that has an important role in the control of a wide range of cellular functions, such as organelle recycling, nutrient availability and tissue differentiation. A recent study has shown an increased autophagic activity in the adipose tissue of obese subjects, and a role for autophagy in obesity-associated insulin resistance was proposed. Body mass reduction is the most efficient approach to tackle insulin resistance in over-weight subjects; however, the impact of weight loss in adipose tissue autophagy is unknown. Subjects:Adipose tissue autophagy was evaluated in mice and humans. Results:First, a mouse model of diet-induced obesity and diabetes was maintained on a 15-day, 40% caloric restriction. At baseline, markers of autophagy were increased in obese mice as compared with lean controls. Upon caloric restriction, autophagy increased in the lean mice, whereas it decreased in the obese mice. The reintroduction of ad libitum feeding was sufficient to rapidly reduce autophagy in the lean mice and increase autophagy in the obese mice. In the second part of the study, autophagy was evaluated in the subcutaneous adipose tissue of nine obese-non-diabetic and six obese-diabetic subjects undergoing bariatric surgery for body mass reduction. Specimens were collected during the surgery and approximately 1 year later. Markers of systemic inflammation, such as tumor necrosis factor-1α, interleukin (IL)-6 and IL-1β were evaluated. As in the mouse model, human obesity was associated with increased autophagy, and body mass reduction led to an attenuation of autophagy in the adipose tissue. Conclusion:Obesity and caloric overfeeding are associated with the defective regulation of autophagy in the adipose tissue. The studies in obese-diabetic subjects undergoing improved metabolic control following calorie restriction suggest that autophagy and inflammation are regulated independently.",
"title": "Defective regulation of adipose tissue autophagy in obesity"
},
{
"docid": "31882215",
"text": "We describe robust induction of autophagy during the reprogramming of mouse fibroblasts to induced pluripotent stem cells by four reprogramming factors (Sox2, Oct4, Klf4 and c-Myc), henceforth 4F. This process occurs independently of p53 activation, and is mediated by the synergistic downregulation of mechanistic target of rapamycin complex 1 (mTORC1) and the induction of autophagy-related genes. The 4F coordinately repress mTORC1, but bifurcate in their regulation of autophagy-related genes, with Klf4 and c-Myc inducing them but Sox2 and Oct4 inhibiting them. On one hand, inhibition of mTORC1 facilitates reprogramming by promoting cell reshaping (mitochondrial remodelling and cell size reduction). On the other hand, mTORC1 paradoxically impairs reprogramming by triggering autophagy. Autophagy does not participate in cell reshaping in reprogramming but instead degrades p62, whose accumulation in autophagy-deficient cells facilitates reprogramming. Our results thus reveal a complex signalling network involving mTORC1 inhibition and autophagy induction in the early phase of reprogramming, whose delicate balance ultimately determines reprogramming efficiency.",
"title": "Autophagy and mTORC1 regulate the stochastic phase of somatic cell reprogramming"
},
{
"docid": "27647593",
"text": "Cancer cells do not exist as pure homogeneous populations in vivo. Instead they are embedded in \"cancer cell nests\" that are surrounded by stromal cells, especially cancer associated fibroblasts. Thus, it is not unreasonable to suspect that stromal fibroblasts could influence the metabolism of adjacent cancer cells, and visa versa. In accordance with this idea, we have recently proposed that the Warburg effect in cancer cells may be due to culturing cancer cells by themselves, out of their normal stromal context or tumor microenvironment. In fact, when cancer cells are co-cultured with fibroblasts, then cancer cells increase their mitochondrial mass, while fibroblasts lose their mitochondria. An in depth analysis of this phenomenon reveals that aggressive cancer cells are \"parasites\" that use oxidative stress as a \"weapon\" to extract nutrients from surrounding stromal cells. Oxidative stress in fibroblasts induces the autophagic destruction of mitochondria, by mitophagy. Then, stromal cells are forced to undergo aerobic glycolysis, and produce energy-rich nutrients (such as lactate and ketones) to \"feed\" cancer cells. This mechanism would allow cancer cells to seed anywhere, without blood vessels as a food source, as they could simply induce oxidative stress wherever they go, explaining how cancer cells survive during metastasis. We suggest that stromal catabolism, via autophagy and mitophagy, fuels the anabolic growth of tumor cells, promoting tumor progression and metastasis. We have previously termed this new paradigm \"The Autophagic Tumor Stroma Model of Cancer Metabolism\", or the \"Reverse Warburg Effect\". We also discuss how glutamine addiction (glutaminolysis) in cancer cells fits well with this new model, by promoting oxidative mitochondrial metabolism in aggressive cancer cells.",
"title": "Stromal-epithelial metabolic coupling in cancer: integrating autophagy and metabolism in the tumor microenvironment."
},
{
"docid": "10024681",
"text": "Deregulation of microRNA (miRNA) expression can have a critical role in carcinogenesis. Here we show in prostate cancer that miRNA-205 (miR-205) transcription is commonly repressed and the MIR-205 locus is hypermethylated. LOC642587, the MIR-205 host gene of unknown function, is also concordantly inactivated. We show that miR-205 targets mediator 1 (MED1, also called TRAP220 and PPARBP) for transcriptional silencing in normal prostate cells, leading to reduction in MED1 mRNA levels, and in total and active phospho-MED1 protein. Overexpression of miR-205 in prostate cancer cells negatively affects cell viability, consistent with a tumor suppressor function. We found that hypermethylation of the MIR-205 locus was strongly related with a decrease in miR-205 expression and an increase in MED1 expression in primary tumor samples (n=14), when compared with matched normal prostate (n=7). An expanded patient cohort (tumor n=149, matched normal n=30) also showed significant MIR-205 DNA methylation in tumors compared with normal, and MIR-205 hypermethylation is significantly associated with biochemical recurrence (hazard ratio=2.005, 95% confidence interval (1.109, 3.625), P=0.02), in patients with low preoperative prostate specific antigen. In summary, these results suggest that miR-205 is an epigenetically regulated tumor suppressor that targets MED1 and may provide a potential biomarker in prostate cancer management.",
"title": "Epigenetic-induced repression of microRNA-205 is associated with MED1 activation and a poorer prognosis in localized prostate cancer"
},
{
"docid": "8425533",
"text": "A defining feature of mitochondria is their maternal mode of inheritance. However, little is understood about the cellular mechanism through which paternal mitochondria, delivered from sperm, are eliminated from early mammalian embryos. Autophagy has been implicated in nematodes, but whether this mechanism is conserved in mammals has been disputed. Here, we show that cultured mouse fibroblasts and pre-implantation embryos use a common pathway for elimination of mitochondria. Both situations utilize mitophagy, in which mitochondria are sequestered by autophagosomes and delivered to lysosomes for degradation. The E3 ubiquitin ligases PARKIN and MUL1 play redundant roles in elimination of paternal mitochondria. The process is associated with depolarization of paternal mitochondria and additionally requires the mitochondrial outer membrane protein FIS1, the autophagy adaptor P62, and PINK1 kinase. Our results indicate that strict maternal transmission of mitochondria relies on mitophagy and uncover a collaboration between MUL1 and PARKIN in this process.",
"title": "Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1"
},
{
"docid": "23509593",
"text": "BACKGROUND Prostate development and maintenance in the adult results from an interaction of stromal and glandular components. Androgens can drive this process by direct action on the stroma. We investigated whether there was a direct link between androgens and another key regulator of stromal cells, intracellular Ca2+ ([Ca2+ ]i ). METHODS Prostate stromal cells were freshly obtained and cultures derived from patients with benign prostatic hyperplasia. Gene expression in dihydrotestosterone treated and untreated cells was compared using Affymetrix gene expression arrays and Ca2+ regulated features were identified by Gene Ontology (GO). Changes in [Ca2+]i were determined in Fluo-4 loaded cells. Androgen regulation was confirmed by chromatin immunoprecipitaion. RESULTS Stromal cell cultures were sorted for expression of integrin α1 β1 , which enriched for cells expressing the androgen receptor (AR). We identified key functional categories, within the androgen-induced gene expression signature, focusing on genes involved in calcium signaling. From this analysis, stromal interaction molecule-1 (STIM1) was identified as a significantly differentially expressed gene with four relevant associated GO terms. DNA sequence analysis showed that the promoter region of STIM1 contained putative androgen response element sequences in which AR binding ability of STIM1 was confirmed. Androgens directly regulated STIM1 expression and STIM1 effects on store-operated calcium entry were inhibited by STIM1 knock-down. Reduced STIM1 expression in prostate stromal cells led to a reduction in basal Ca2+ levels, the amount of Ca2+ released by thapsigargin and a reduction in store filling following TG-induced store depletion. CONCLUSIONS These results indicate that androgens modulate [Ca2+]i through the direct regulation of the STIM1 gene by AR binding to the STIM1 promoter.",
"title": "The calcium sensor STIM1 is regulated by androgens in prostate stromal cells."
},
{
"docid": "24632480",
"text": "Aberrant protein misfolding may contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS) but the detailed mechanisms are largely unknown. Our previous study has shown that autophagy is altered in the mouse model of ALS. In the present study, we systematically investigated the correlation of the autophagic alteration with the motor neurons (MNs) degeneration in the ALS mice. We have demonstrated that the autophagic protein marker LC3-II is markedly and specifically increased in the spinal cord MNs of the ALS mice. Electron microscopy and immunochemistry studies have shown that autophagic vacuoles are significantly accumulated in the dystrophic axons of spinal cord MNs of the ALS mice. All these changes in the ALS mice appear at the age of 90 d when the ALS mice display modest clinical symptoms; and they become prominent at the age of 120 d. The clinical symptoms are correlated with the progression of MNs degeneration. Moreover, we have found that p62/SQSTM1 is accumulated progressively in the spinal cord, indicating that the possibility of impaired autophagic flux in the SOD1(G93A) mice. Furthermore, to our surprise, we have found that treatment with autophagy enhancer rapamycin accelerates the MNs degeneration, shortens the life span of the ALS mice, and has no obvious effects on the accumulation of SOD1 aggregates. In addition, we have demonstrated that rapamycin treatment in the ALS mice causes more severe mitochondrial impairment, higher Bax levels and greater caspase-3 activation. These findings suggest that selective degeneration of MNs is associated with the impairment of the autophagy pathway and that rapamycin treatment may exacerbate the pathological processing through apoptosis and other mechanisms in the ALS mice.",
"title": "Rapamycin treatment augments motor neuron degeneration in SOD1(G93A) mouse model of amyotrophic lateral sclerosis."
},
{
"docid": "41710132",
"text": "The tumor suppressor PML (promyelocytic leukemia protein) regulates cellular senescence and terminal differentiation, two processes that implicate a permanent exit from the cell cycle. Here, we show that the mechanism by which PML induces a permanent cell cycle exit and activates p53 and senescence involves a recruitment of E2F transcription factors bound to their promoters and the retinoblastoma (Rb) proteins to PML nuclear bodies enriched in heterochromatin proteins and protein phosphatase 1α. Blocking the functions of the Rb protein family or adding back E2Fs to PML-expressing cells can rescue their defects in E2F-dependent gene expression and cell proliferation, inhibiting the senescent phenotype. In benign prostatic hyperplasia, a neoplastic disease that displays features of senescence, PML was found to be up-regulated and forming nuclear bodies. In contrast, PML bodies were rarely visualized in prostate cancers. The newly defined PML/Rb/E2F pathway may help to distinguish benign tumors from cancers, and suggest E2F target genes as potential targets to induce senescence in human tumors.",
"title": "Regulation of E2Fs and senescence by PML nuclear bodies."
},
{
"docid": "7548577",
"text": "In the yeast Saccharomyces cerevisiae, glycogen is accumulated as a carbohydrate reserve when cells are deprived of nutrients. Yeast mutated in SNF1, a gene encoding a protein kinase required for glucose derepression, has diminished glycogen accumulation and concomitant inactivation of glycogen synthase. Restoration of synthesis in an snf1 strain results only in transient glycogen accumulation, implying the existence of other SNF1-dependent controls of glycogen storage. A genetic screen revealed that two genes involved in autophagy, APG1 and APG13, may be regulated by SNF1. Increased autophagic activity was observed in wild-type cells entering the stationary phase, but this induction was impaired in an snf1 strain. Mutants defective for autophagy were able to synthesize glycogen upon approaching the stationary phase, but were unable to maintain their glycogen stores, because subsequent synthesis was impaired and degradation by phosphorylase, Gph1p, was enhanced. Thus, deletion of GPH1 partially reversed the loss of glycogen accumulation in autophagy mutants. Loss of the vacuolar glucosidase, SGA1, also protected glycogen stores, but only very late in the stationary phase. Gph1p and Sga1p may therefore degrade physically distinct pools of glycogen. Pho85p is a cyclin-dependent protein kinase that antagonizes SNF1 control of glycogen synthesis. Induction of autophagy in pho85 mutants entering the stationary phase was exaggerated compared to the level in wild-type cells, but was blocked in apg1 pho85 mutants. We propose that Snf1p and Pho85p are, respectively, positive and negative regulators of autophagy, probably via Apg1 and/or Apg13. Defective glycogen storage in snf1 cells can be attributed to both defective synthesis upon entry into stationary phase and impaired maintenance of glycogen levels caused by the lack of autophagy.",
"title": "Antagonistic Controls of Autophagy and Glycogen Accumulation by Snf1p, the Yeast Homolog of AMP-Activated Protein Kinase, and the Cyclin-Dependent"
},
{
"docid": "1084345",
"text": "Chaperone-mediated autophagy (CMA), a selective mechanism for degradation of cytosolic proteins in lysosomes, contributes to the removal of altered proteins as part of the cellular quality-control systems. We have previously found that CMA activity declines in aged organisms and have proposed that this failure in cellular clearance could contribute to the accumulation of altered proteins, the abnormal cellular homeostasis and, eventually, the functional loss characteristic of aged organisms. To determine whether these negative features of aging can be prevented by maintaining efficient autophagic activity until late in life, in this work we have corrected the CMA defect in aged rodents. We have generated a double transgenic mouse model in which the amount of the lysosomal receptor for CMA, previously shown to decrease in abundance with age, can be modulated. We have analyzed in this model the consequences of preventing the age-dependent decrease in receptor abundance in aged rodents at the cellular and organ levels. We show here that CMA activity is maintained until advanced ages if the decrease in the receptor abundance is prevented and that preservation of autophagic activity is associated with lower intracellular accumulation of damaged proteins, better ability to handle protein damage and improved organ function.",
"title": "Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function"
},
{
"docid": "24581365",
"text": "CONTEXT The appropriate therapy for men with clinically localized prostate cancer is uncertain. A recent study suggested an increasing prostate cancer mortality rate for men who are alive more than 15 years following diagnosis. OBJECTIVE To estimate 20-year survival based on a competing risk analysis of men who were diagnosed with clinically localized prostate cancer and treated with observation or androgen withdrawal therapy alone, stratified by age at diagnosis and histological findings. DESIGN, SETTING, AND PATIENTS A retrospective population-based cohort study using Connecticut Tumor Registry data supplemented by hospital record and histology review of 767 men aged 55 to 74 years with clinically localized prostate cancer diagnosed between January 1, 1971, and December 31, 1984. Patients were treated with either observation or immediate or delayed androgen withdrawal therapy, with a median observation of 24 years. MAIN OUTCOME MEASURES Probability of mortality from prostate cancer or other competing medical conditions, given a patient's age at diagnosis and tumor grade. RESULTS The prostate cancer mortality rate was 33 per 1000 person-years during the first 15 years of follow-up (95% confidence interval [CI], 28-38) and 18 per 1000 person-years after 15 years of follow-up (95% CI, 10-29). The mortality rates for these 2 follow-up periods were not statistically different, after adjusting for differences in tumor histology (rate ratio, 1.1; 95% CI, 0.6-1.9). Men with low-grade prostate cancers have a minimal risk of dying from prostate cancer during 20 years of follow-up (Gleason score of 2-4, 6 deaths per 1000 person-years; 95% CI, 2-11). Men with high-grade prostate cancers have a high probability of dying from prostate cancer within 10 years of diagnosis (Gleason score of 8-10, 121 deaths per 1000 person-years; 95% CI, 90-156). Men with Gleason score of 5 or 6 tumors have an intermediate risk of prostate cancer death. CONCLUSION The annual mortality rate from prostate cancer appears to remain stable after 15 years from diagnosis, which does not support aggressive treatment for localized low-grade prostate cancer.",
"title": "20-year outcomes following conservative management of clinically localized prostate cancer."
},
{
"docid": "25513319",
"text": "Metabolic pathway reprogramming is a hallmark of cancer cell growth and survival and supports the anabolic and energetic demands of these rapidly dividing cells. The underlying regulators of the tumor metabolic program are not completely understood; however, these factors have potential as cancer therapy targets. Here, we determined that upregulation of the oncogenic transcriptional coregulator steroid receptor coactivator 2 (SRC-2), also known as NCOA2, drives glutamine-dependent de novo lipogenesis, which supports tumor cell survival and eventual metastasis. SRC-2 was highly elevated in a variety of tumors, especially in prostate cancer, in which SRC-2 was amplified and overexpressed in 37% of the metastatic tumors evaluated. In prostate cancer cells, SRC-2 stimulated reductive carboxylation of α-ketoglutarate to generate citrate via retrograde TCA cycling, promoting lipogenesis and reprogramming of glutamine metabolism. Glutamine-mediated nutrient signaling activated SRC-2 via mTORC1-dependent phosphorylation, which then triggered downstream transcriptional responses by coactivating SREBP-1, which subsequently enhanced lipogenic enzyme expression. Metabolic profiling of human prostate tumors identified a massive increase in the SRC-2-driven metabolic signature in metastatic tumors compared with that seen in localized tumors, further implicating SRC-2 as a prominent metabolic coordinator of cancer metastasis. Moreover, SRC-2 inhibition in murine models severely attenuated the survival, growth, and metastasis of prostate cancer. Together, these results suggest that the SRC-2 pathway has potential as a therapeutic target for prostate cancer.",
"title": "Coactivator SRC-2-dependent metabolic reprogramming mediates prostate cancer survival and metastasis."
},
{
"docid": "982650",
"text": "BACKGROUND & AIMS Tumor cells survive hypoxic conditions by inducing autophagy. We investigated the roles of microRNAs (miRNAs) in regulating autophagy of hepatocellular carcinoma (HCC) cells under hypoxic conditions. METHODS We used gain- and loss-of-function methods to evaluate the effect of miRNAs on autophagy in human HCC cell lines (Huh7 and Hep3B) under hypoxic conditions. Autophagy was quantified by immunoblot, immunofluoresence, and transmission electron microscopy analyses, and after incubation of cells with bafilomycin A1. We used a luciferase reporter assay to confirm associations between miRNAs and their targets. We analyzed growth of HCC xenograft tumors in nude mice. RESULTS miR-375 was down-regulated in HCC cells and tissues; it inhibited autophagy under hypoxic conditions by suppressing the conversion of LC3I to LC3II and thereby autophagic flux. The ability of miR-375 to inhibit autophagy was independent of its ability to regulate 3'-phosphoinositide-dependent protein kinase-1-AKT-mammalian target of rapamycin signaling, but instead involved suppression of ATG7, an autophagy-associated gene. miR-375 bound directly to a predicted site in the 3' untranslated region of ATG7. Up-regulating miR-375 or down-regulating ATG7 inhibited mitochondrial autophagy of HCC cells, reduced the elimination of damaged mitochondria under hypoxia, increased release of mitochondrial apoptotic proteins, and reduced viability of HCC cells. In mice, xenograft tumors that expressed miR-375 had fewer autophagic cells, larger areas of necrosis, and grew more slowly than tumors from HCC cells that expressed lower levels of miR-375. CONCLUSIONS miR-375 inhibits autophagy by reducing expression of ATG7 and impairs viability of HCC cells under hypoxic conditions in culture and in mice. miRNAs that inhibit autophagy of cancer cells might be developed as therapeutics.",
"title": "miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions."
},
{
"docid": "6790197",
"text": "PURPOSE To accurately identify gene expression alterations that differentiate neoplastic from normal prostate epithelium using an approach that avoids contamination by unwanted cellular components and is not compromised by acute gene expression changes associated with tumor devascularization and resulting ischemia. EXPERIMENTAL DESIGN Approximately 3,000 neoplastic and benign prostate epithelial cells were isolated using laser capture microdissection from snap-frozen prostate biopsy specimens provided by 31 patients who subsequently participated in a clinical trial of preoperative chemotherapy. cDNA synthesized from amplified total RNA was hybridized to custom-made microarrays composed of 6,200 clones derived from the Prostate Expression Database. Expression differences for selected genes were verified using quantitative reverse transcription-PCR. RESULTS Comparative analyses identified 954 transcript alterations associated with cancer (q < 0.01%), including 149 differentially expressed genes with no known functional roles. Gene expression changes associated with ischemia and surgical removal of the prostate gland were absent. Genes up-regulated in prostate cancer were statistically enriched in categories related to cellular metabolism, energy use, signal transduction, and molecular transport. Genes down-regulated in prostate cancers were enriched in categories related to immune response, cellular responses to pathogens, and apoptosis. A heterogeneous pattern of androgen receptor expression changes was noted. In exploratory analyses, androgen receptor down-regulation was associated with a lower probability of cancer relapse after neoadjuvant chemotherapy followed by radical prostatectomy. CONCLUSIONS Assessments of tumor phenotypes based on gene expression for treatment stratification and drug targeting of oncogenic alterations may best be ascertained using biopsy-based analyses where the effects of ischemia do not complicate interpretation.",
"title": "Prostate cancer-associated gene expression alterations determined from needle biopsies."
},
{
"docid": "27270151",
"text": "In the past decade, insightful preclinical research has led to important breakthroughs in our understanding of pancreatic cancer. Even though the vast majority of pancreatic cancers are KRAS mutated, not all pancreatic cancer tumors are \"KRAS equal\"; there seems to be varying dependencies on the KRAS pathway. While KRAS-targeting therapies have been disappointing in the clinic, 'synthetic lethal' approaches hold promise in this setting. The pancreatic cancer stromal microenvironment appears to have contradictory roles. While there is evidence to suggest that stromal barrier prevents drug delivery, in other circumstances, stroma can play a protective role and its disruption enhances tumor dissemination. Clinical trials aimed at manipulating the various stromal components are in progress. BRCA mutation-related pancreatic tumors illustrate a unique subtype with enhanced susceptibility to DNA damaging agents and PARP-inhibition. DNA repair defects in cancer extend beyond germ line BRCA mutation and may extend the indications for DNA repair-targeting agents. Immune strategies are an area of active investigation in pancreatic cancer. Although the initial trials of single-agent checkpoint inhibitors have been negative, combinational approaches using immune-modifying agents and vaccines appear promising and goal is to identify an 'immune-therapy responsive' profile in pancreatic cancer.",
"title": "Changing the course of pancreatic cancer--Focus on recent translational advances."
},
{
"docid": "38243984",
"text": "PURPOSE The goal of this study was to evaluate prospectively the engraftment rate, factors influencing engraftment, and predictability of clinical outcome of low-passage xenografts from patients with resectable pancreatic ductal adenocarcinoma (PDA) and to establish a bank of PDA xenografts. EXPERIMENTAL DESIGN Patients with resectable PDA scheduled for resection at the Johns Hopkins Hospital were eligible. Representative pieces of tumor were implanted in nude mice. The status of the SMAD4 gene and content of tumor-generating cells were determined by immunohistochemistry. Gene expression was carried out by using a U133 Plus 2.0 array. Patients were followed for progression and survival. RESULTS A total of 94 patients with PDA were resected, 69 tumors implanted in nude mice, and 42 (61%) engrafted. Engrafted carcinomas were more often SMAD4 mutant, and had a metastatic gene expression signature and worse prognosis. Tumors from patients resistant to gemcitabine were enriched in stroma-related gene pathways. Tumors sensitive to gemcitabine were enriched in cell cycle and pyrimidine gene pathways. The time to progression for patients who received treatment with gemcitabine for metastatic disease (n = 7) was double in patients with xenografts sensitive to gemcitabine. CONCLUSION A successful xenograft was generated in 61% of patients attempted, generating a pool of 42 PDA xenografts with significant biological information and annotated clinical data. Patients with PDA and SMAD4 inactivation have a better engraftment rate. Engraftment is a poor prognosis factor, and engrafted tumors have a metastatic gene expression signature. Tumors from gemcitabine-resistant patients were enriched in stromal pathways.",
"title": "Tumor engraftment in nude mice and enrichment in stroma- related gene pathways predict poor survival and resistance to gemcitabine in patients with pancreatic cancer."
},
{
"docid": "25738896",
"text": "The thymic transcription factor autoimmune regulator (Aire) prevents autoimmunity in part by promoting expression of tissue-specific self-antigens, which include many cancer antigens. For example, AIRE-deficient patients are predisposed to vitiligo, an autoimmune disease of melanocytes that is often triggered by efficacious immunotherapies against melanoma. Therefore, we hypothesized that Aire deficiency in mice may elevate immune responses to cancer and provide insights into how such responses might be triggered. In this study, we show that Aire deficiency decreases thymic expression of TRP-1 (TYRP1), which is a self-antigen in melanocytes and a cancer antigen in melanomas. Aire deficiency resulted in defective negative selection of TRP-1-specific T cells without affecting thymic numbers of regulatory T cells. Aire-deficient mice displayed elevated T-cell immune responses that were associated with suppression of melanoma outgrowth. Furthermore, transplantation of Aire-deficient thymic stroma was sufficient to confer more effective immune rejection of melanoma in an otherwise Aire wild-type host. Together, our work showed how Aire deficiency can enhance immune responses against melanoma and how manipulating TRP-1-specific T-cell negative selection may offer a logical strategy to enhance immune rejection of melanoma.",
"title": "Aire deficiency promotes TRP-1-specific immune rejection of melanoma."
},
{
"docid": "17671145",
"text": "The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptor-related orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an AR-ROR response element (RORE) to stimulate AR gene transcription. ROR-γ antagonists suppress the expression of both AR and its variant AR-V7 in prostate cancer (PCa) cell lines and tumors. ROR-γ antagonists also markedly diminish genome-wide AR binding, H3K27ac abundance and expression of the AR target gene network. Finally, ROR-γ antagonists suppressed tumor growth in multiple AR-expressing, but not AR-negative, xenograft PCa models, and they effectively sensitized CRPC tumors to enzalutamide, without overt toxicity, in mice. Taken together, these results establish ROR-γ as a key player in CRPC by acting upstream of AR and as a potential therapeutic target for advanced PCa.",
"title": "ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer"
},
{
"docid": "32766786",
"text": "PURPOSE In the initial report of the Lupron Depot Neoadjuvant Prostate Cancer Study Group patients who received 3 months of androgen deprivation had a significant decrease in the positive margin rate. We monitored these patients for 5 years and to our knowledge present the longest followup of any neoadjuvant trial. MATERIALS AND METHODS A multi-institutional prospective randomized trial was performed between February 1992 and April 1994 involving patients with stage cT2b prostate cancer, including 138 who received 3 months of leuprolide plus flutamide before radical prostatectomy and 144 who underwent radical prostatectomy only. Patients were followed every 6 months with serum prostate specific antigen (PSA) testing for 5 years. Biochemical recurrence was defined as PSA greater than 0.4 ng./ml. RESULTS At 5 years there was no difference in the biochemical recurrence rate. PSA was less than 0.4 ng./ml. in 64.8% of the patients in the neoadjuvant androgen ablation plus prostatectomy and 67.6% in the prostatectomy only group (p = 0.663). CONCLUSIONS Although 3 months of androgen deprivation before radical prostatectomy resulted in an apparently significant decrease in positive surgical margins, a 5-year followup does not indicate any difference in the recurrence rate. Until studies document improvement in biochemical or clinical recurrence with longer periods of treatment, induction androgen deprivation before radical prostatectomy is not indicated.",
"title": "Neoadjuvant androgen ablation before radical prostatectomy in cT2bNxMo prostate cancer: 5-year results."
},
{
"docid": "14131683",
"text": "An increasingly recognized resistance mechanism to androgen receptor (AR)-directed therapy in prostate cancer involves epithelial plasticity, in which tumor cells demonstrate low to absent AR expression and often have neuroendocrine features. The etiology and molecular basis for this 'alternative' treatment-resistant cell state remain incompletely understood. Here, by analyzing whole-exome sequencing data of metastatic biopsies from patients, we observed substantial genomic overlap between castration-resistant tumors that were histologically characterized as prostate adenocarcinomas (CRPC-Adeno) and neuroendocrine prostate cancer (CRPC-NE); analysis of biopsy samples from the same individuals over time points to a model most consistent with divergent clonal evolution. Genome-wide DNA methylation analysis revealed marked epigenetic differences between CRPC-NE tumors and CRPC-Adeno, and also designated samples of CRPC-Adeno with clinical features of AR independence as CRPC-NE, suggesting that epigenetic modifiers may play a role in the induction and/or maintenance of this treatment-resistant state. This study supports the emergence of an alternative, 'AR-indifferent' cell state through divergent clonal evolution as a mechanism of treatment resistance in advanced prostate cancer.",
"title": "Divergent clonal evolution of castration resistant neuroendocrine prostate cancer"
},
{
"docid": "33507866",
"text": "A critical regulator of autophagy is the Class III PI3K Vps34 (also called PIK3C3). Although Vps34 is known to play an essential role in autophagy in yeast, its role in mammals remains elusive. To elucidate the physiological function of Vps34 and to determine its precise role in autophagy, we have generated Vps34(f/f) mice, in which expression of Cre recombinase results in a deletion of exon 4 of Vps34 and a frame shift causing a deletion of 755 of the 887 amino acids of Vps34. Acute ablation of Vps34 in MEFs upon adenoviral Cre infection results in a diminishment of localized generation of phosphatidylinositol 3-phosphate and blockade of both endocytic and autophagic degradation. Starvation-induced autophagosome formation is blocked in both Vps34-null MEFs and liver. Liver-specific Albumin-Cre;Vps34(f/f) mice developed hepatomegaly and hepatic steatosis, and impaired protein turnover. Ablation of Vps34 in the heart of muscle creatine kinase-Cre;Vps34(f/f) mice led to cardiomegaly and decreased contractility. In addition, while amino acid-stimulated mTOR activation was suppressed in the absence of Vps34, the steady-state level of mTOR signaling was not affected in Vps34-null MEFs, liver, or cardiomyocytes. Taken together, our results indicate that Vps34 plays an essential role in regulating functional autophagy and is indispensable for normal liver and heart function.",
"title": "Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function."
},
{
"docid": "946756",
"text": "A protein of molecular size 62,000 daltons (p62) was detected in HeLa cell nuclear extracts by UV cross-linking to mRNA precursors. p62 binds specifically to the polypyrimidine tract of the 3' splice site region of introns. p62 purified to homogeneity binds the polypyrimidine tract of pre-mRNAs. This binding does not require the AG dinucleotide at the 3' splice site. Alterations in the polypyrimidine tract that reduce the binding of p62 yield a corresponding reduction in the efficiency of formation of a U2 snRNP/pre-mRNA complex and splicing. The p62 protein is retained in the spliceosome, where it remains bound to the pre-mRNA. This polypyrimidine tract binding protein (pPTB) is proposed to be a critical component in recognition of the 3' splice site during splicing.",
"title": "Identification and purification of a 62,000-dalton protein that binds specifically to the polypyrimidine tract of introns."
},
{
"docid": "52925737",
"text": "BACKGROUND Exosomes are extracellular vesicles that mediate cellular communication in health and diseases. Neutrophils could be polarized to a pro-tumor phenotype by tumor. The function of tumor-derived exosomes in neutrophil regulation remains unclear. METHODS We investigated the effects of gastric cancer cell-derived exosomes (GC-Ex) on the pro-tumor activation of neutrophils and elucidated the underlying mechanisms. RESULTS GC-Ex prolonged neutrophil survival and induced expression of inflammatory factors in neutrophils. GC-Ex-activated neutrophils, in turn, promoted gastric cancer cell migration. GC-Ex transported high mobility group box-1 (HMGB1) that activated NF-κB pathway through interaction with TLR4, resulting in an increased autophagic response in neutrophils. Blocking HMGB1/TLR4 interaction, NF-κB pathway, and autophagy reversed GC-Ex-induced neutrophil activation. Silencing HMGB1 in gastric cancer cells confirmed HMGB1 as a key factor for GC-Ex-mediated neutrophil activation. Furthermore, HMGB1 expression was upregulated in gastric cancer tissues. Increased HMGB1 expression was associated with poor prognosis in patients with gastric cancer. Finally, gastric cancer tissue-derived exosomes acted similarly as exosomes derived from gastric cancer cell lines in neutrophil activation. CONCLUSION We demonstrate that gastric cancer cell-derived exosomes induce autophagy and pro-tumor activation of neutrophils via HMGB1/TLR4/NF-κB signaling, which provides new insights into mechanisms for neutrophil regulation in cancer and sheds lights on the multifaceted role of exosomes in reshaping tumor microenvironment.",
"title": "Tumor-derived exosomes induce N2 polarization of neutrophils to promote gastric cancer cell migration"
},
{
"docid": "25915873",
"text": "PURPOSE Therapies to target prostate cancer bone metastases have only limited effects. New treatments are focused on the interaction between cancer cells, bone marrow cells and the bone matrix. Osteoclasts play an important role in the development of bone tumors caused by prostate cancer. Since Src kinase has been shown to be necessary for osteoclast function, we hypothesized that dasatinib, a Src family kinase inhibitor, would reduce osteoclast activity and prostate cancer (PC-3) cell-induced osteoclast formation. RESULTS Dasatinib inhibited RANKL-induced osteoclast differentiation of bone marrow-derived monocytes with an EC(50) of 7.5 nM. PC-3 cells, a human prostate cancer cell line, were able to differentiate RAW 264.7 cells, a murine monocytic cell line, into osteoclasts, and dasatinib inhibited this differentiation. In addition, conditioned medium from PC-3 cell cultures was able to differentiate RAW 264.7 cells into osteoclasts and this too, was inhibited by dasatinib. Even the lowest concentration of dasatinib, 1.25 nmol, inhibited osteoclast differentiation by 29%. Moreover, dasatinib inhibited osteoclast activity by 58% as measured by collagen 1 release. EXPERIMENTAL DESIGN We performed in vitro experiments utilizing the Src family kinase inhibitor dasatinib to target osteoclast activation as a means of inhibiting prostate cancer bone metastases. CONCLUSION Dasatinib inhibits osteoclast differentiation of mouse primary bone marrow-derived monocytes and PC-3 cell-induced osteoclast differentiation. Dasatinib also inhibits osteoclast degradation activity. Inhibiting osteoclast differentiation and activity may be an effective targeted therapy in patients with prostate cancer bone metastases.",
"title": "Dasatinib inhibits both osteoclast activation and prostate cancer PC-3-cell-induced osteoclast formation."
},
{
"docid": "22180793",
"text": "The transition from androgen-dependent to castration-resistant prostate cancer (CRPC) is a lethal event of uncertain molecular etiology. Comparing gene expression in isogenic androgen-dependent and CRPC xenografts, we found a reproducible increase in N-cadherin expression, which was also elevated in primary and metastatic tumors of individuals with CRPC. Ectopic expression of N-cadherin in nonmetastatic, androgen-dependent prostate cancer models caused castration resistance, invasion and metastasis. Monoclonal antibodies against the ectodomain of N-cadherin reduced proliferation, adhesion and invasion of prostate cancer cells in vitro. In vivo, these antibodies slowed the growth of multiple established CRPC xenografts, blocked local invasion and metastasis and, at higher doses, led to complete regression. N-cadherin–specific antibodies markedly delayed the time to emergence of castration resistance, markedly affected tumor histology and angiogenesis, and reduced both AKT serine-threonine kinase activity and serum interleukin-8 (IL-8) secretion. These data indicate that N-cadherin is a major cause of both prostate cancer metastasis and castration resistance. Therapeutic targeting of this factor with monoclonal antibodies may have considerable clinical benefit.",
"title": "Monoclonal antibody targeting of N-cadherin inhibits prostate cancer growth, metastasis and castration resistance"
},
{
"docid": "12009265",
"text": "CONTEXT Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements. A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship. No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer. OBJECTIVE To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men. DESIGN, SETTING, AND PARTICIPANTS The Physicians' Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. A total of 14,641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled. INTERVENTION Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily. MAIN OUTCOME MEASURES Prostate and total cancer. RESULTS During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers. Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41). There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80). Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers. Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results. Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk. CONCLUSIONS In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer. These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00270647.",
"title": "Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial."
}
] |
121768
|
Matt Smith acted only on stage.
|
[
{
"docid": "Matt_Smith_(actor)",
"text": "Matthew Robert `` Matt '' Smith ( born 28 October 1982 ) is an English actor . He is best known for his role as the Eleventh Doctor in the BBC science fiction series Doctor Who , for which he received a BAFTA Award nomination in 2011 . Smith initially aspired to be a professional footballer , but spondylolysis forced him out of the sport . After joining the National Youth Theatre and studying Drama and Creative Writing at the University of East Anglia , he became an actor in 2003 , performing in plays like Murder in the Cathedral , Fresh Kills , The History Boys , and On the Shore of the Wide World in London theatres . Extending his repertoire into West End theatre , he has since performed in the stage adaptation of Swimming with Sharks with Christian Slater , followed a year later by a critically acclaimed performance as Henry in That Face . Smith 's first television role came in 2006 as Jim Taylor in the BBC adaptations of Philip Pullman 's The Ruby in the Smoke and The Shadow in the North , while his first major role in television came as Danny in the 2007 BBC series Party Animals . Smith , who was announced as the eleventh incarnation of the Doctor in January 2009 , is the youngest person to play the character in the British television series . He left the series at the end of the 2013 Christmas Day special , `` The Time of the Doctor '' . He portrayed both the physical embodiment and a holographic version of Skynet in Terminator Genisys ( 2015 ) . Since 2016 , he portrays Prince Philip , Duke of Edinburgh in Peter Morgan 's Netflix biographical drama series The Crown , opposite Claire Foy as Elizabeth II .",
"title": ""
}
] |
[
{
"docid": "The_Death_of_Bessie_Smith",
"text": "The Death of Bessie Smith is a one-act play by American playwright Edward Albee , written in 1959 and premiered in West Berlin the following year . The play consists of a series of conversations between Bernie and his friend Jack , Jack and an off-stage Bessie , and black and white staff of a ` whites-only ' hospital in Memphis , Tennessee on the death date of the famous blues singer , Bessie Smith , who died in a car wreck .",
"title": ""
},
{
"docid": "List_of_awards_and_nominations_received_by_Maggie_Smith",
"text": "This is the list of awards and nominations received by Maggie Smith , whose acting career in motion pictures , television , and on stage spans over 60 years . Among her major competitive awards , Smith has won two Oscars , five BAFTAs ( including a record four for Best Actress ) , four Emmys and a Tony Award . Other significant awards include three Golden Globes , five Screen Actors Guild Awards , and a record five Best Actress Evening Standard Theatre Awards . Smith is one of only 14 actresses to have achieved the Triple Crown of Acting , which is competitive Academy Award , Emmy Award and Tony Award wins . Overall in her career to date she has won 58 competitive awards from 157 nominations . She has also received numerous honorary awards , including the BAFTA Special Award ( 1993 ) , the BAFTA Fellowship ( 1996 ) and the Special Olivier Award ( 2010 ) .",
"title": ""
},
{
"docid": "Matt_Thompson_(film_director)",
"text": "Matt Thompson ( born in Roseville , California on 19 May 1984 ) , is an American film director , producer , screenwriter and actor . He also directed some music videos and commercials and acted on stage productions . Born to Tim and Cindy Thompson , he grew up in Sacramento , California and graduated from Granite Bay High School , starting his acting debut at 18 and has appeared in many movies since . In 2009 he made his feature directorial debut with the feature film Listen to Your Heart ( 2010 film ) starring Cybill Shepherd , Kent Moran , Alexia Rasmussen and Ernie Sabella . He also played lead role of Stanley Kowalski in the stage presentation of A Streetcar Named Desire . He was named as one of 15 people to watch early in their careers by Sacramento Magazine in its March 2010 cover story .",
"title": ""
},
{
"docid": "Bec_Gilbert",
"text": "Rebecca Louise `` Bec '' Gilbert ( previously O'Connor ) is a fictional character from the Australian drama series Winners & Losers , played by Zoe Tuckwell-Smith . She made her debut screen appearance in the pilot episode `` Covert Aggression in Netball '' , which was broadcast on the Seven Network on 22 March 2011 . Tuckwell-Smith auditioned for the role of Bec . At the callback , she was introduced to Blair McDonough , who was cast as Bec 's partner , before she was given the role . Having previously appeared in guest parts , Winners & Losers marks Tuckwell-Smith 's major television acting debut . The series revolves around four `` losers '' who are reunited at their school reunion and then win the Oz Lotto . Bec was portrayed as being `` bright '' , `` rational '' and `` hard-working '' . Tuckwell-Smith thought Bec was a typical girl next door , but with a bit more complexity . She liked her character 's generosity and how she did not change after winning the Lotto . Reuniting with her friends -- Jenny ( Melissa Bergland ) , Frances ( Virginia Gay ) and Sophie ( Melanie Vallejo ) -- brought out Bec 's more playful side . Unlike the other girls , Bec was not given a cruel nickname at school and she knew that if she did not hang out with Jenny , she may have been popular . However , Bec stuck up for Jenny against the bullies from an early age and they remained best friends years after school . At the start of the first season , Bec had been with McDonough 's character , Matt O'Connor , for ten years , and engaged for four . Matt later called off their engagement and Bec had a brief relationship with Doug Graham ( Tom Wren ) . Bec and Matt reunited and married in the season finale episode , which also saw Bec learn that she was pregnant with Doug 's baby . Tuckwell-Smith liked that the writers had made Doug the father of Bec 's baby , calling it a great opportunity for drama . The actress also enjoyed playing out a pregnancy on-screen for the first time and liked the change it brought out in Bec 's personality . Bec spent the majority of the third season dealing with Matt 's death and learning that he had an affair . Bec and Tuckwell-Smith have received a mostly positive reception from television critics . Tuckwell-Smith departed the show on 12 August 2014 .",
"title": ""
},
{
"docid": "Mike_Smith_(A&R_man)",
"text": "Mike Smith started as an A&R man at MCA Publishing as a scout in 1988 , where he signed Blur , Levitation and scouted The Smashing Pumpkins . He then moved to EMI Publishing in 1992 , where he went on to sign acts , such as PJ Harvey , Elastica , Supergrass , Teenage Fan Club , Doves , Starsailor , The Beta Band , The Avalanches , Gorillaz , The White Stripes , The Libertines , The Scissor Sisters , The Arcade Fire , and Arctic Monkeys , as well as resigning Blur and progressing to the position of Head of A&R . He also worked with artists such as Robbie Williams , The Verve and Beth Orton . Smith moved to Columbia Records UK in 2006 to work as the Managing Director . In 2006 , he signed Mark Ronson and Calvin Harris . In 2007 , signings included The Ting Tings , MGMT , The Hugs , The Gossip and Glasvegas . The following year , he signed Miike Snow and Lissie to the label and in 2009 , Magnetic Man , Miles Kane and Paul Epworth . Band of Horses , Katy B , The Vaccines and Ryan Adams were all signed in 2010 and in the following year , he signed Madeon and The Civil Wars . Acts he also looked after included Kings of Leon , Bruce Springsteen , Bob Dylan , Foo Fighters , Matt Cardle , Ke $ ha , Sleigh Bells , and Kasabian . In April 2012 , Mike left Columbia to take up the role of President of Music at Mercury Records where he oversaw the signings of Iggy Azalea , The Vamps ( British band ) and Slaves ( UK band ) , as well as signing Duke Dumont and The Strypes . With the formation of Virgin / EMI Records in 2013 , from the merger of Virgin Records and Mercury Records , he signed The Chemical Brothers , The Libertines and Squeeze . Since 2010 , Mike has been a trustee of the charity , New Deal of The Mind , which works to encourage job creation within the creative industries . Mike has been sketching the musicians he has spent his lifetime watching and in 2009 , staged an exhibition of prints made from these drawings at Richard Goodall Gallery in Manchester . This was followed up in 2011 with a comprehensive show of his paintings , light boxes and prints at Somerset House . A further exhibition of the work was staged at Metropolis Group studios .",
"title": ""
},
{
"docid": "Dad's_Garage_Theatre_Company",
"text": "Dad 's Garage Theatre Company , located at 569 Ezzard St in the Old 4th Ward in Atlanta , Georgia , was founded in 1995 by Chris Blair , Marc Cram , Sean Daniels , John Gregorio , David Keeton , Joseph Limbaugh , Matt Stanton , and Matt Young . The small theater company has since achieved international recognition for original stage productions and Improvisational comedy . The current Artistic Director , Kevin Gillese , is a former director at Rapid Fire Theatre . Lara Smith is the current Managing Director .",
"title": ""
},
{
"docid": "Tom_and_Matt_Smith",
"text": "Tom Smith ( along with son Matt Smith ) are father and son jazz musicians best known for their work in the United States , Eastern Europe and China . Tom Smith ( father ) is a long time American university jazz professor , trombonist , researcher , wind symphony conductor , program creator and multiple Senior Fulbright Professor of Music at the Romanian National University of Music and Tibiscus University , with Senior Fulbright Professional Specialist appointments at University KwaZulu-Natal ( Durban , South Africa ) and the Serbian Academy of Music in Belgrade , as well as numerous American high school and community college positions , alongside an extended professorship at Pfeiffer University , and a three-year appointment as the first full-time American jazz studies professor at a Chinese university . In May 2013 , he became the 21st inductee into the DownBeat Jazz Education Hall of Fame . Tom was introduced to fine arts at an early age by his father , a noted trombonist , best known for his work with New Orleans traditional jazz artist Murphy Campo . Tom Smith was the longest continuous member of the North Carolina Artist-in-Residence Program ( 1984 -- 1992 ) , while based at three separate North Carolina community colleges . A widely acknowledged pioneer of the American community jazz movement ( having founded over fifty large community jazz ensembles ) his best known group was the Unifour Jazz Ensemble , an eighteen-piece big band and first entirely state funded big band in the United States , that placed seventh in the 1988 Down Beat Readers Poll . In that same poll , Smith placed fifth in the trombone category . As an improvising soloist , he has performed and toured with Louie Bellson , Clark Terry , McCoy Tyner , Joe Henderson , Chris Potter , the New York Voices , Nicholas Payton , Herb Ellis , Donald Byrd , Darius Brubeck and the Manhattan Transfer . Smith is also a noted music historian and researcher . In 2001 he and his research partner Gary Westbrook received recognition for identifying the musical fingerprint for identification of unknown personnel on early recordings . This and subsequent research has received widespread media exposure via National Public Radio 's Weekly Edition and Tech TV . In 2014 , Tom received the Brubeck Award for Jazz Research . Since 2002 , his works in global jazz education have drawn wide attention . Called by a former Fulbright Executive Director the premminent jazz Fulbright Scholar in the program 's history , Smith is the only foreigner to have been awarded The Romanian National Radio Prize . In 2005 , he founded and coordinated the Romanian Jazz Education Seminar , the first summer music camp staged in Romania , and cofounded the first western styled jazz music college in that country ( 2004 ) . In 2006 , his Fulbright work in South Africa included extensive assistance with township based initiatives , alongside devising a strategy to link university jazz education with local Zulu musicians . In 2008 , Smith was the recipient of the International Association for Jazz Education Jazz Ambassador Award , having already been awarded Outstanding Service to Jazz Education honors in 1998 , 2000 , 2001 , 2002 , 2003 , 2005 and 2006 . In 2009 , Tom received his eighth Fulbright Award ( a record for musician professors ) and accepted residency at the Serbia Academy of Music ( University of Arts ) drafting the curriculum for their jazz program . Later , he accepted guest jazz studies appointments in Budva , Montenegro . In 2010 , Tom and his wife Sarah relocated to Northeast China where he developed a jazz music strategy for teaching English to native Mandarin speakers . In 2011 he was appointed a professor of music at Ningbo University ( Zhejiang Province , China ) assigned to establish the first entirely functional jazz program on the Chinese mainland , that led to formation of numerous instrumental groups and a 40-member jazz choir . In 2013 , Tom was awarded the Camellia Award , for noteworthy artistic contributions towards social betterment for the Greater Ningbo Region . Website : tomsmithjazz.wix.com/music Matt Smith ( son ) ( born 1990 ) is an award winning jazz drum set musician , percussionist , hip hop mixologist , and radio/television personality who in 2006 , at age 16 , won the WFD World 's Fastest Drummer Extreme Sport Drumming competition in the Fastest Hands category . Matt is the son and grandson of two accomplished jazz musicians . He was introduced to the drums at age 9 , when Louie Bellson ( one of his father 's performing acquaintances ) gave him his first pair of drum sticks . Matt 's official début occurred at age 12 , when he performed for a jazz combo on Romanian National Television . At age 14 , he recorded a début album under his own name ( Coltrane Redeux ) featuring an all star European jazz lineup . In 2005 , Matt entered the Louie Bellson National Drumset Competition , and became the youngest finalist in that competition 's history.From 2005-2008 he held a number of speed drumming world records , and in 2007 , set the world speed endurance record when he performed 5,132 single strokes in five consecutive minutes . On June 26 , 2008 Matt set a traditional grip world speed record , when he recorded 1132 single strokes played in 1 minute - a record formerly held by Dream Theater drummer Mike Mangini . Since 2005 , Matt has performed and been interviewed on numerous American media outlets , including PBS , CBS Radio and CNN . In 2008 , a PBS news segment featuring Matt and drummer Johnny Rabb was nominated for an Arts and Entertainment News Documentary Emmy Award At age 18 , with speed drumming activities behind him , Matt began performing with a variety of diverse world class bands showcasing jazz , rock , hip hop , pop , funk and blues . In 2008 he was named a runner-up in the Rising Star category of the Drum Magazine Readers Poll . Matt is a 2009 graduate of the Atlanta Institute of Music , and from 2009-2011 resided in Europe , where he began production of nu jazz recordings , and performed with a diverse lineup of artists that included jazz pianist Darius Brubeck and Linkin Park singer Mike Shinoda.In 2011 , he signed on as house drummer with Euro blues headliner A. G. Weinberger on the weekly television show Acadeaua . In 2011 Matt relocated to Nashville , TN , where he works as a touring and session drummer .",
"title": ""
},
{
"docid": "The_Clock_Maker",
"text": "The Clock Maker is an American comic book published by Image Comics starting in January 2003 . The comic was written by Jim Krueger and pencilled by Matt Smith ( Act I ) and Jason Baroody ( Act II ) . The title was launched during a new superhero comics initiative at Image . The story is about a giant clockworks hidden within a hollow mountain in Switzerland . Hundreds of men that never age maintain the old behemoth 's operation . The clock is the cause and sustainer of the Earth 's revolutions -- and more , it is the gateway to Heaven itself . The first four issues were published as double-sized editions with a 1:1 reproduction ratio , meaning the original art was not resized when it was published . The books were folded in half to fit on standard news racks , and in the current sized protective polymer bags . The back cover of the fourth issue advertised a fifth , coming in June 2003 , however that issue was never published . Act II was never printed in the serial format , but only as a 48-page graphic novel ( ISBN 1-58240-377-5 ) in 2004 . Act three was intended to be published in the same manner , but , to this date , has never surfaced . Krueger maintains that the book will be out `` in the near future '' and that a collection will also be forthcoming .",
"title": ""
},
{
"docid": "Doctrine_of_the_Trinity_Act_1813",
"text": "The Doctrine of the Trinity Act 1813 ( 53 Geo . III c. 160 . sometimes called the Trinitarian Act 1812 ) was an Act of the Parliament of the United Kingdom . It amended the Blasphemy Act 1697 in respect of its Trinitarian provisions . The Blasphemy Act applied only to those educated in or having made profession of the Christian religion . The Act , passed July 21 , was also variously known as the Unitarian Relief Act ( Trinity Act ) , The Unitarian Toleration Bill , and Mr William Smith 's Bill , after Whig politician William Smith . The Act granted toleration for Unitarian worship , as previously the Toleration Act 1688 had only granted toleration to those Protestant dissenters who accepted the Trinity . The Blasphemy Act was repealed in 1967 , implicitly taking the Doctrine of the Trinity Act with it .",
"title": ""
},
{
"docid": "Maggie_Smith",
"text": "Dame Margaret Natalie Smith , ( born 28 December 1934 ) , known as Maggie Smith , is an English actress . She has had an extensive , varied career in stage , film and television spanning over sixty-five years . Smith has appeared in over 50 films and is one of Britain 's most recognisable actresses . A prominent figure in British culture for six decades , she was made a Dame by Queen Elizabeth II in 1990 for services to the performing arts , and received the Companion of Honour from the Queen in 2014 for services to drama . Smith began her career on stage at the Oxford Playhouse in 1952 and made her Broadway debut in New Faces of ' 56 . For her work on the London stage , she has won a record five Best Actress Evening Standard Awards ; for The Private Ear and The Public Eye ( 1962 ) , Hedda Gabler ( 1970 ) , Virginia ( 1981 ) , The Way of the World ( 1984 ) and Three Tall Women ( 1994 ) . She received Tony Award nominations for Private Lives ( 1975 ) and Night and Day ( 1979 ) , before winning the 1990 Tony Award for Best Actress in a Play for Lettice and Lovage . Other stage roles include Stratford Shakespeare Festival productions of Antony and Cleopatra ( 1976 ) and Macbeth ( 1978 ) , and West End productions of A Delicate Balance ( 1997 ) and The Breath of Life ( 2002 ) . On screen , Smith first drew praise for the crime film Nowhere to Go ( 1958 ) , for which she received her first BAFTA Award nomination . She has won two Academy Awards , winning Best Actress for The Prime of Miss Jean Brodie ( 1969 ) and Best Supporting Actress for California Suite ( 1978 ) . She is one of only six actresses to have won in both categories . She has won a record four BAFTA Awards for Best Actress , including for A Private Function ( 1984 ) and The Lonely Passion of Judith Hearne ( 1988 ) , a BAFTA for Best Supporting Actress for Tea With Mussolini ( 1999 ) , and three Golden Globe Awards . A six-time Oscar nominee , her other nominations were for Othello ( 1965 ) , Travels with My Aunt ( 1972 ) , A Room with a View ( 1986 ) , and Gosford Park ( 2001 ) . Smith played Professor Minerva McGonagall in the Harry Potter film series ( 2001 -- 11 ) . Other notable films include Love and Pain and the Whole Damn Thing ( 1973 ) , Death on the Nile ( 1978 ) , Clash of the Titans ( 1981 ) , Evil Under the Sun ( 1982 ) , Hook ( 1991 ) , Sister Act ( 1992 ) , The Best Exotic Marigold Hotel ( 2012 ) and The Lady in the Van ( 2015 ) . She won an Emmy Award in 2003 for My House in Umbria , to become one of the few actresses to have achieved the Triple Crown of Acting , and starred as Lady Violet Crawley , Dowager Countess of Grantham on Downton Abbey ( 2010 -- 15 ) , for which she won three Emmys , her first non-ensemble Screen Actors Guild Award and her third Golden Globe . Her honorary awards include the BAFTA Special Award ( 1993 ) , the BAFTA Fellowship ( 1996 ) , and the Special Olivier Award ( 2011 ) . She received the Stratford Shakespeare Festival 's Legacy Award in 2012 , and the Evening Standard Icon Award in 2013 .",
"title": ""
},
{
"docid": "Matt_Smith",
"text": "Matt or Matthew Smith may refer to :",
"title": ""
},
{
"docid": "Matt_Smith_(TV_reporter)",
"text": "Matt Smith is a British broadcaster .",
"title": ""
},
{
"docid": "Matt_Harrington_(actor)",
"text": "Matt Harrington is an American stage actor , best known for his work in the Broadway production of Matilda the Musical , in which he replaced Tony Award winner Gabriel Ebert in the role of Mr. Wormwood . Prior to performing in Matilda , Harrington was the only American actor to appear on stage in both productions of the critically acclaimed Broadway repertory of Twelfth Night and Richard III , starring Mark Rylance , at the Belasco Theatre . The productions originated at Shakespeare 's Globe in London and ultimately transferred to Broadway after a successful West End run .",
"title": ""
},
{
"docid": "Matt_\"Money\"_Smith",
"text": "Matt `` Money '' Smith ( born April 26 , 1973 ) is a United States sports radio personality . On January 8 , 2007 Smith began co-hosting The Petros and Money Show , with Petros Papadakis , which currently runs Monday-Friday from 2pm to 6pm .",
"title": ""
},
{
"docid": "List_of_awards_and_nominations_received_by_Doctor_Who",
"text": "Doctor Who is a British science fiction television programme produced and aired by the BBC . Originally shown from 1963 until 1989 , but was revived in 2005 . In 26 years , its original 1963 -- 1989 run won only two awards , a RTS Television Award and a Writer 's Guild of Great Britain Award . However , the revived series has received recognition from critics and the public , winning many awards . It has been nominated for a variety of different awards including 29 BAFTA TV Awards ( eight wins for the series ) , 27 Hugo Awards ( 6 wins ) , 16 Saturn Awards ( 3 wins ) , 24 National Television Awards ( 16 wins ) , 5 Writer 's Guild of Great Britain Awards ( two wins ) , and a total of 23 awards from BBC itself ( 14 wins ) . Amongst the wins for the series are a BAFTA TV Award for Best Drama Series , the most prestigious award for British television series ; it was the very first ( and to date only ) science fiction work to win . Matt Smith became the first Doctor Who actor to earn a BAFTA TV nomination in 2011 , receiving a Best Actor nomination for his role as the Eleventh Doctor , while Michelle Gomez became the first BAFTA TV-nominated Doctor Who actress in 2016 for her supporting role as Missy . It also won the only Saturn Award for Best International Series , and five Hugo Awards for Best Dramatic Presentation , Short Form . The series have received a record of 26 nominations in this last category in nine years only , making it the second television series in history after Star Trek to have more than two episodes nominated for a Hugo Award in a single year . Star Trek , the second most nominated series , only received 8 nominations overall . One of the most critically acclaimed aspects of Doctor Who is its acting quality : Christopher Eccleston , David Tennant and Matt Smith have all won awards playing the Doctor , while Billie Piper , Catherine Tate and Karen Gillan have won awards playing companions , and Carey Mulligan and Alex Kingston won awards playing supporting characters . Both Billie Piper and David Tennant have received awards ; nine ( in two years in the series ) and sixteen ( three regular years , two other years during special episodes ) respectively . The series has earned a broad range of nominations including recognition of its writing quality and its visual effects .",
"title": ""
},
{
"docid": "Ian_Smith_(footballer,_born_1952)",
"text": "Ian Lennox Taylor Smith ( born 2 April 1952 ) , sometimes listed as Ian Taylor-Smith , is a Scottish former footballer who played in the Scottish Football League for Queens Park , Heart of Midlothian and Queen of the South , and in the Football League for Birmingham City . He played as a forward . Smith was born in Edinburgh . He studied medicine , and eventually qualified as a doctor , combining this with playing football on an amateur or semi-professional basis . He spent time with several clubs in both Scotland and England , playing league football only where it did not interfere with his medical career . While with Birmingham City , he scored regularly for the reserve team and was highly rated , but his work at the Queen Elizabeth Medical Centre restricted him to only two first-team appearances . His father , Jimmy , played professionally for Clyde and St Mirren in the 1930s , and his son , Matt , turned professional with Oldham Athletic in 2011 .",
"title": ""
},
{
"docid": "Matt_Smith_(guitarist)",
"text": "Matt Smith is an Australian jazz guitarist . He is most widely known as the guitarist in the Australian rock pop band Thirsty Merc but also plays guitar for Sydney afrobeat/reggae band The Strides . Matt joined Thirsty Merc in January 2010 after helping record the band 's third album , Mousetrap Heart , in Los Angeles in late 2009 .",
"title": ""
},
{
"docid": "Matt_Smith_(voice_actor)",
"text": "Matthew `` Matt '' Smith ( born February 28 , 1968 in Toronto ) is a Canadian voice actor who works with Ocean Productions in Vancouver .",
"title": ""
},
{
"docid": "Gulliver_Smith",
"text": "Kevin Gullifer Hopkins-Smith ( born Kevin Gullifer Smith ca. 1950November 2014 ) , who performed as Little Gulliver and Gulliver Smith ( also styled as Gullifer Smith ) , was an Australian singer and songwriter from the early 1960s to mid-2000s . He was the front man and founding mainstay vocalist of Company Caine . In 1976 he and Ross Wilson co-wrote `` A Touch of Paradise '' for Wilson 's group , Mondo Rock , which appeared on their third album , Nuovo Mondo ( July 1982 ) . It was covered by John Farnham on his album , Whispering Jack ( October 1986 ) , and was issued as its third single in February 1987 , which reached the top 30 on the Kent Music Report Singles Chart . Gulliver Smith died on 12 November 2014 from kidney failure , and was survived by his wife Stephanie Hopkins-Smith ( nee Hopkins ) and their three sons . According to Australian musicologist , Ian McFarlane , `` Smith drew on vintage rock 'n' roll , Professor Longhair-styled New Orleans R&B , psychedelia and soul for inspiration . He was known for his outrageous stage act , which incorporated an inventive free-form approach and much evangelist-styled ad-libbing . Later on , he added a satirical Zappaesque component to his on-stage banter and lyrics . ''",
"title": ""
},
{
"docid": "Matt_Smith_(footballer,_born_1989)",
"text": "Mathieu James `` Matt '' Smith ( born 7 June 1989 ) is an English professional footballer who plays as a striker for Championship club Queens Park Rangers .",
"title": ""
},
{
"docid": "Matt_Smith_(rugby_union_player_born_1989)",
"text": "Matt Smith ( born 26 October 1989 in Hexham ) is a rugby union footballer who plays lock for the Leeds Carnegie and England Students .",
"title": ""
},
{
"docid": "Matt_Smith_(rugby_union_player_born_1996)",
"text": "Matt Smith ( born 5 October 1996 in Scotland ) is a Scottish rugby union player who plays for Glasgow Warriors at the Flanker position .",
"title": ""
},
{
"docid": "Broderick_Smith",
"text": "Broderick Smith ( born 17 February 1948 in Hertfordshire , England ) a.k.a. Brod Smith is a singer-songwriter , harmonica , guitar and banjo player . He was a member of 1970s bands Carson and The Dingoes , 1980s Broderick Smith 's Big Combo and performed solo . He also acted on stage in the 1973 Australian version of the rock opera Tommy and in minor roles in 1990s Television series Blue Heelers , Snowy River : The McGregor Saga and State Coroner . Smith has been involved in writing about 200 songs and has run workshops on songwriting , harmonica and vocals . He is also the father of King Gizzard and the Lizard Wizard harmonica/keyboard player Ambrose Kenny-Smith .",
"title": ""
},
{
"docid": "The_Crash_of_the_Elysium",
"text": "The Crash of the Elysium is a one-hour theatrical work created originally for children by the British company Punchdrunk , centred on the unexplained disappearance of a Victorian steamer named the Elysium and its investigation by the Eleventh Doctor from the television series Doctor Who . It premiered at MediaCityUK in Salford from 1 to 17 July 2011 as part of the Manchester International Festival , with a central narrative idea from Steven Moffat and written by Tom MacRae . It features the Weeping Angels and footage of Matt Smith as the Doctor specially recorded for the show . Its target audience is children from 6 to 12 , with adults allowed in if accompanied by a child on `` family '' shows . A number of adults-only shows were subsequently added following requests from the public . On 16 July 2011 , Matt Smith made a surprise visit to the show , appearing in character in place of the final video sequence . The show was remounted in Ipswich in 2012 as part of London 2012 's Olympics festival . Alfred Hickling of The Guardian awarded the production five out of five stars .",
"title": ""
},
{
"docid": "Matt_Smith_(comics)",
"text": "Matt Smith ( born 31 October 1972 ) is the current and longest-serving editor of long-running British science fiction weekly anthology comic 2000 AD , and the sister title Judge Dredd Megazine . He has also written two novels .",
"title": ""
},
{
"docid": "Matt_Smith_(Australian_politician)",
"text": "Matthew John `` Matt '' Smith ( born 18 March 1978 ) is an Australian Liberal politician who served in the Tasmanian House of Assembly from 1998 to 2002 . Smith was elected to the Tasmanian House of Assembly in 1998 as a member for the seat of Franklin . He became the youngest member of any parliament in Australia upon election in 1998 at 20 years of age . Smith stepped down shortly before the 2002 election after his father was charged with stealing from his employer and a court was told some of the money may have been used to fund his campaign . His father was later acquitted of all charges .",
"title": ""
},
{
"docid": "Matt_Smith_(footballer,_born_1982)",
"text": "Matthew Terence `` Matt '' Smith ( born 14 October 1982 ) is an English-born Australian football ( soccer ) player who plays for Bangkok Glass in the Thai League T1 . Born in England , Smith emigrated to Australia where he started his professional football career with North Queensland Fury during the 2009/10 A-League season and then signed a two-year contract with Brisbane Roar at the start of the A-League 2010/11 season . He has played for the Australian national team .",
"title": ""
},
{
"docid": "Christmas_Eve_(opera)",
"text": "Christmas Eve ( Ночь перед Рождеством , Noch ' pered Rozhdestvom ) , is an opera in four acts with music and libretto by Nikolai Rimsky-Korsakov . Composed between 1894 and 1895 , Rimsky-Korsakov based his opera on a short story , `` Christmas Eve '' , from Nikolay Gogol 's Evenings on a Farm Near Dikanka . The story had been used as the basis for an opera at least three times previously , including for Tchaikovsky 's Vakula the Smith ( 1874 ) . Oliver Knussen writes that `` Rimsky is only interested in recreating the atmosphere of the folk-tale , fleshing it out for his stage pageant in a comparable way to Humperdinck in Hansel .",
"title": ""
},
{
"docid": "Matthew_Dow_Smith",
"text": "Matthew Dow Smith ( sometimes credited as Matt Smith or Matthew Smith ) is an American comic book artist .",
"title": ""
},
{
"docid": "Matt_Smith_(broadcaster)",
"text": "Matt Smith ( born 26 April 1967 ) is a British broadcaster , who worked with ITV Sport between 2001-2015 . He currently presents BT Sport 's Premier League , FA Cup , Champions League , Europa League , Conference Football , England Under 21 .",
"title": ""
}
] |
PLAIN-1513
|
lima beans
| [{"docid":"MED-4509","text":"Hypercholesterolemia is a major modifiable risk factor for cardiovascul(...TRUNCATED) | [{"docid":"MED-3170","text":"Background Few studies have focused on the cognitive morbidity of neuro(...TRUNCATED) |
753
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Malaria has a high vectorial capacity.
| [{"docid":"1173667","text":"Experience gained from the Global Malaria Eradication Program (1955-72) (...TRUNCATED) | [{"docid":"25938221","text":"A specific retinopathy has been described in African children with cere(...TRUNCATED) |
734
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MEK inhibitors are effective treatments in RAS-driven mouse models of cancer.
| [{"docid":"4961038","text":"Somatic mutations that activate phosphoinositide 3-kinase (PI3K) have be(...TRUNCATED) | [{"docid":"2272614","text":"Activating mutations in the EGF receptor (EGFR) are associated with clin(...TRUNCATED) |
5497
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What kinds of exchange-traded funds (ETFs) should specifically be avoided?
| [{"docid":"210257","text":"\"As with ANY investment the first answer is....do not invest in any that(...TRUNCATED) | [{"docid":"332924","text":"\"I recommend avoiding trading directly in commodities futures and option(...TRUNCATED) |
PLAIN-2625
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Turmeric Curcumin Reprogramming Cancer Cell Death
| [{"docid":"MED-2781","text":"Our previous study demonstrated that curcumin, an active compound of Cu(...TRUNCATED) | [{"docid":"MED-1819","text":"Gemcitabine is a first line cancer drug widely used for the treatment o(...TRUNCATED) |
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