tbuckley/cabot-search huggingface dataset:
Effectiveness and Safety of Antidepressants for Children and Adolescents
Authors: Sally Nicola Merry, Sarah Elisabeth Hetrick, Karolina Stasiak
Journal: JAMA Psychiatry (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Effect of trastuzumab/AT-101 combination on apoptosis and cytotoxicity in HER2-positive breast cancer cells: A novel combination to effect resistance to anti-HER2 therapy through inhibition of PI3K signaling.
Authors: Burcak Karaca, Emir Bozkurt, Harika Atmaca, Zeki Surmeli, Atike Pinar, Ulus Ali Sanli, Ruchan Uslu
Journal: Journal of Clinical Oncology (2014)

e13512 Background: Trastuzumab is a humanized monoclonal antibody approved for the treatment of breast cancer with HER2 amplification and/or overexpression. AT-101, the (-/-) enantiomer of gossypol, is a natural polyphenolic compound extracted from the cotton plant with potent cytotoxic effects on various tumor types. In the present study, we have investigated the possible synergistic cytotoxic and apoptotic effects of AT-101 in combination with Trastuzumab in HER2-positive human breast cancer cell lines, MDA-MB-453 and SKBR3. We have further investigated the effect of the combination treatment on the PI3K signaling pathway to elucidate the molecular targets of the combination treatment Methods: Cytotoxicity was assessed by XTT cell viability assay. Apoptosis was shown by using Cell Death Detection ELISA Plus Kit and verified by measuring caspase 3/7 enzyme activity. In order to investigate the molecular mechanism of combination treatment-induced apoptotic activity, cells were pretreated with PI3K inhibitor (LY294002) before Trastuzumab/AT-101 combination treatment, and then DNA fragmentation analysis was done. Results: Combination of Trastuzumab with AT-101 showed strong synergistic cytotoxicity in both breast cancer cells at 72 h, as compared with any agent alone. Combined treatment also induced DNA fragmentation and caspase 3/7 activation in breast cancer cells. PI3K inhibitor LY294002 inhibited the apoptotic effect of combination treatment in both breast cancer cell lines indicating that this combination inhibits the PI3K signaling pathway leading to apoptotic cell death. Conclusions: PI3K pathway is mostly found in Her-2resistance; thus this novel combination of Trastuzumab and AT-101 might be promising for overcoming anti-Her-2 resistance.
MerTK Cleavage on Resident Cardiac Macrophages Compromises Repair After Myocardial Ischemia Reperfusion Injury
Authors: Matthew DeBerge, Xin Yi Yeap, Shirley Dehn, Shuang Zhang, Lubov Grigoryeva, Sol Misener, Daniel Procissi, Xin Zhou, Daniel C. Lee, William A. Muller, Xunrong Luo, Carla Rothlin, Ira Tabas, Edward B. Thorp
Journal: Circulation Research (2017)

Clinical benefits of reperfusion after myocardial infarction are offset by maladaptive innate immune cell function, and therapeutic interventions are lacking.We sought to test the significance of phagocytic clearance by resident and recruited phagocytes after myocardial ischemia reperfusion.In humans, we discovered that clinical reperfusion after myocardial infarction led to significant elevation of the soluble form of MerTK (myeloid-epithelial-reproductive tyrosine kinase; ie, soluble MER), a critical biomarker of compromised phagocytosis by innate macrophages. In reperfused mice, macrophage Mertk deficiency led to decreased cardiac wound debridement, increased infarct size, and depressed cardiac function, newly implicating MerTK in cardiac repair after myocardial ischemia reperfusion. More notably, Mertk(CR) mice, which are resistant to cleavage, showed significantly reduced infarct sizes and improved systolic function. In contrast to other cardiac phagocyte subsets, resident cardiac MHCIILOCCR2- (major histocompatibility complex II/C-C motif chemokine receptor type 2) macrophages expressed higher levels of MerTK and, when exposed to apoptotic cells, secreted proreparative cytokines, including transforming growth factor-β. Mertk deficiency compromised the accumulation of MHCIILO phagocytes, and this was rescued in Mertk(CR) mice. Interestingly, blockade of CCR2-dependent monocyte infiltration into the heart reduced soluble MER levels post-ischemia reperfusion.Our data implicate monocyte-induced MerTK cleavage on proreparative MHCIILO cardiac macrophages as a novel contributor and therapeutic target of reperfusion injury.
Impact of leucovorin on mucositis and skin reactions in pts with peripheral t-cell lymphoma (PTCL) and cutaneous t-cell lymphoma (CTCL) treated with pralatrexate.
Authors: Francine M. Foss, Terri L. Parker, Anlong Li
Journal: Journal of Clinical Oncology (2016)

7558 Background: Pralatrexate (Pral,) is a novel folic acid analog with activity in T cell lymphomas. In the clinical trial of Pral in relapsed PTCL, treatment modification occurred frequently due to mucositis, and/or skin reactions. Leucovorin (Leuc) administration has been shown to minimize mucositis without sacrificing efficacy in patients (pts) with PTCL (Haddad, 2011), and CTCL pts (Koch, 2013).The aim of this study was to define the potential clinical benefits of Leuc with Pral on frequency of mucositis and skin reactions in pts with relapsed/refractory PTCL and CTCL Methods: A retrospective review of consecutive pts treated with Pral was conducted. Pts either received Pral or Pral-Leuc with Leuc given at a dose of 50 mg orally q 6 h x 4 doses the day following Pral. All patients treated before 2013 received Pral without Leucovorin and those treated after 2013 received Pral-Leuc. Thirty-four pts (17 female, 17 males) were identified, including 7 with PTCL (6 stage IV, 1 stage III) and 27 with CTCL (11 Stage IIB, 9 Stage IV). The age range was 27-89 years (median 54 years). Results: Pral dosing ranged from 10-30 mg/m2 weekly x 3 q28 days or every q other week. In the Pral group (n = 24), 46% (n = 11) of pts reported mucositis and 48% (n = 10) had skin reactions.Three pts who had initiated therapy only with Pral and developed mucositis were then given Leuc on subsequent cycles and mouth sores did not recur, In the Pral-Leuc group (n = 10), one pt had mucositis. The incidence of skin reactions was the same for Pral and Pral-Leuc. Response or disease stabilization (CR, PR, SD) were seen in 21 of 27 pts with CTCL and 4 of 7 with PTCL. The mean number of cycles of Pralatrexate was 7 (range 2-18). Two pts with CTCL and one with PTCL discontinued therapy before response assessment due to intolerability or pt withdrawal. Conclusions: Addition of Leuc significantly reduced the incidence of mucositis in pts with PTCL and CTCL but interestingly did not change the incidence of skin reactions, suggesting alternative mechanisms of the drug to induce skin rash in these patients. Response rates were similar in the Pral-Leuc group and the Pral group, suggesting no impact of Leucovorin on clinical efficacy.
Low-Density Lipoprotein Cholesterol Lowering for the Primary Prevention of Cardiovascular Disease Among Men With Primary Elevations of Low-Density Lipoprotein Cholesterol Levels of 190 mg/dL or Above
Authors: Antonio J. Vallejo-Vaz, Michele Robertson, Alberico L. Catapano, Gerald F. Watts, John J. Kastelein, Chris J. Packard, Ian Ford, Kausik K. Ray
Journal: Circulation (2017)

Background: Patients with primary elevations of low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL are at a higher risk of atherosclerotic cardiovascular disease as a result of long-term exposure to markedly elevated LDL-C levels. Therefore, initiation of statin therapy is recommended for these individuals. However, there is a lack of randomized trial evidence supporting these recommendations in primary prevention. In the present analysis, we provide hitherto unpublished data on the cardiovascular effects of LDL-C lowering among a primary prevention population with LDL-C ≥190 mg/dL. Methods: We aimed to assess the benefits of LDL-C lowering on cardiovascular outcomes among individuals with primary elevations of LDL-C ≥190 mg/dL without preexisting vascular disease at baseline. We performed post hoc analyses from the WOSCOPS (West of Scotland Coronary Prevention Study) randomized, placebo-controlled trial, and observational posttrial long-term follow-up, after excluding individuals with evidence of vascular disease at baseline. WOSCOPS enrolled 6595 men aged 45 to 64 years, who were randomly assigned to pravastatin 40 mg/d or placebo. In the present analyses, 5529 participants without evidence of vascular disease were included, stratified by LDL-C levels into those with LDL-C &lt;190 mg/dL (n=2969; mean LDL-C 178±6 mg/dL) and those with LDL-C ≥190 mg/dL (n=2560; mean LDL-C 206±12 mg/dL). The effect of pravastatin versus placebo on coronary heart disease and major adverse cardiovascular events were assessed over the 4.9-year randomized controlled trial phase and on mortality outcomes over a total of 20 years of follow-up. Results: Among 5529 individuals without vascular disease, pravastatin reduced the risk of coronary heart disease by 27% ( P =0.002) and major adverse cardiovascular events by 25% ( P =0.004) consistently among those with and without LDL-C ≥190 mg/dL ( P -interaction &gt;0.9). Among individuals with LDL-C ≥190 mg/dL, pravastatin reduced the risk of coronary heart disease by 27% ( P =0.033) and major adverse cardiovascular events by 25% ( P =0.037) during the initial trial phase and the risk of coronary heart disease death, cardiovascular death, and all-cause mortality by 28% ( P =0.020), 25% ( P =0.009), and 18% ( P =0.004), respectively, over a total of 20 years of follow-up. Conclusions: The present analyses provide robust novel evidence for the short- and long-term benefits of lowering LDL-C for the primary prevention of cardiovascular disease among individuals with primary elevations of LDL-C ≥190 mg/dL.
Assessment of Hematological Data in a Cohort of European Children with Sickle Cell Anemia Treated with Hydroxyurea: Can European Centers Apply Today the Lessons from the Twitch Study?
Authors: Mariane De Montalembert, Malika Benkerrou, Regine Grosse, Uwe Kordes, Valentine Brousse, Corinne Pondarré, Corinne Armari-alla, Narcisse Elenga, Marcin Wlodarski, Stephan Lobitz
Journal: Blood (2016)
TV: Help, I'm a Doctor
Authors: A. Ellis
Journal: BMJ (2002)

Rating:![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> BBC 1, 28 August at 7.55 pm “Help! I'm a Doctor” follows the progress of medical students on a new, revolutionary course at St George's Hospital Medical School, London. The methods used by the course, from selection to teaching to exams, are controversial, and the programme helps explain this new ethos. In a “Doctors To Be” style we follow some fascinating characters through their first year. It's a watchable programme that deals with many controversies of the course, spiced with the experiences of some lovable and some irritating students. The course lasts four years, in contrast to the traditional five in Britain, and selection methods are unique as A levels are totally ignored. The only requirement is that applicants have a degree in any subject they wish. In light of the current shortages of doctors, we are told that “St George's believe that they … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
The Harms of Empirical Bowel Regimens
Authors: Arjun Gupta, Deepak Agrawal, Carol Croft
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
ニューロン発達中の軸索形成を指示する細胞内蛋白質の生体磁気送達のためのミセルナノ複合体【Powered by NICT】
Authors: Suarato Giulia, Lee Seong-Il, Li Weiyi, Rao Sneha, Khan Tanvir, Meng Yizhi, Shelly Maya
Journal: Biomaterials (2017)
Evaluating the impact of Affordable Care Act repeal on America's opioid epidemic
Authors: Leana S. Wen, Evan B. Behrle, Alexander C. Tsai
Journal: PLoS Medicine (2017)

In this month's Editorial, Health Commissioner of the City of Baltimore Leana S. Wen and co-authors discuss why the United States needs Medicaid to address its epidemic of opioid abuse.
The Comparative Proteinase and Peptidase Activities of Rat Hepatoma and Normal and Regenerating Rat Liver
Authors: Mary E. Maver, G. Burroughs Mider, J. M. Johnson, J. W. Thompson
Journal: JNCI Journal of the National Cancer Institute (1941)

Journal Article The Comparative Proteinase and Peptidase Activities of Rat Hepatoma and Normal and Regenerating Rat Liver Get access Mary E. Maver, Mary E. Maver senior biochemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Burroughs Mider, G. Burroughs Mider research fellow National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar J. M. Johnson, J. M. Johnson senior chemist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar J. W. Thompson J. W. Thompson associate pharmacologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 3, December 1941, Pages 277–282, https://doi.org/10.1093/jnci/2.3.277 Published: 01 December 1941
Identification of genes implicated in angiogenesis using an automated text mining process
Authors: Jayanthi Jagannathan, John M. Maris, Peter S. White
Journal: Cancer Research (2006)

1562  Angiogenesis is the process of building of new blood vessels. In a healthy body, this process is required for wound healing and in cancer, it is essential for solid tumor growth. Having as much knowledge about genes implicated as possibly playing a role in the process of angiogenesis is extremely useful in developing agents to target these as a therapy for controlling cancer. The richest source of gene annotation data exists in the biomedical literature and is constantly expanding (>2,000 new articles/month). However, the unstructured nature of biomedical text poses a challenge for the efficient extraction of useful information. Here, we have demonstrated a method based on text mining to automatically identify a set of genes implicated in angiogenesis. A subset of MEDLINE abstracts selected as being relevant for angiogenesis were annotated with a named entity tagger that can automatically identify mentions of genes and proteins. The tagged genes were normalized against an exhaustive human gene lexicon that was built to contain all gene names and all their aliases. The normalized genes were ranked according to frequency of mention. The resulting gene list was validated by comparing it to a list of angiogenes compiled manually by experts, as well as to online resources listing angiogenesis-related genes. The final gene list contained 2,460 unique official gene names. All but 2 of the genes in the manual list were also identified by the text-mined list [99.2% recall (sensitivity)]. The text-mined list was relevance ranked based on the number of documents in which each gene was mentioned, and the 247 highest-ranking genes were compared with the comparably-sized manual list for precision. All of the 100 highest-ranked text-mined genes were identified as being legitimately associated with angiogenesis after further literature review. Furthermore, article recall was 17-fold higher than for articles linked to genes in Entrez Gene, and gene recall was 95-fold higher than for genes assigned to angiogenesis-related GO terms through AMIGO, demonstrating the current under-annotation of these resources for human genes. The methodâ€™s performance was assessed using a gene expression array-based classifier distinguishing angiogenic from non-angiogenic tumor samples (human). The findings suggest clearly the usefulness of this method in assimilating and annotating genes involved in a biological process from descriptive text.
Modeling bone marrow: A novel 3-D culture system for characterization of the multiple myeloma stem cell niche
Authors: Julia Kirshner, Andrew Belch, Tony Reiman, Linda Pilarski
Journal: Cancer Research (2007)

3052   Bone marrow (BM) is a complex tissue responsible for initial steps of B cell development but is also a site of tumorigenesis. Multiple myeloma (MM), an incurable cancer of the BM plasma cells is responsible for 19% of deaths from hematological malignancies. While considerable progress has been made towards understanding and curing this disease, to date, there is no culture system which can recapitulate the complex interactions between the extracellular matrix (ECM) and the various cells of the BM. Here we describe the design of an in vitro 3-dimensional (3-D) model recapitulating the BM microevironment. The 3-D tissue culture model system presented here mimics in vivo microenvironment of the BM where cells from the BM aspirates are grown in the ECM closely resembling that of the human BM. We show that various cells found in the BM establish individual niches mimicking the in vivo condition. The organization of the reconstructed BM from the MM patients differs from that established by cells from the normal donors. The malignancy of the MM is sustained in the 3-D culture. Thus this is a good model for pre-clinical analysis of novel therapeutics. Finally, this model provides an avenue for the identification and characterization of the microevironmental niche responsible for harboring the drug resistant MM stem cell.
Trends in Dementia Incidence in a Birth Cohort Analysis of the Einstein Aging Study
Authors: Carol A. Derby, Mindy J. Katz, Richard B. Lipton, Charles B. Hall
Journal: JAMA Neurology (2017)

Trends in dementia incidence rates have important implications for planning and prevention. To better understand incidence trends over time requires separation of age and cohort effects, and few prior studies have used this approach.To examine trends in dementia incidence and concomitant trends in cardiovascular comorbidities among individuals aged 70 years or older who were enrolled in the Einstein Aging Study between 1993 and 2015.In this birth cohort analysis of all-cause dementia incidence in persons enrolled in the Einstein Aging Study from October 20, 1993, through November 17, 2015, a systematically recruited, population-based sample of 1348 participants from Bronx County, New York, who were 70 years or older without dementia at enrollment and at least one annual follow-up was studied. Poisson regression was used to model dementia incidence as a function of age, sex, educational level, race, and birth cohort, with profile likelihood used to identify the timing of significant increases or decreases in incidence.Birth year and age.Incident dementia defined by consensus case conference based on annual, standardized neuropsychological and neurologic examination findings, using criteria from the DSM-IV.Among 1348 individuals (mean [SD] baseline age, 78.5 [5.4] years; 830 [61.6%] female; 915 [67.9%] non-Hispanic white), 150 incident dementia cases developed during 5932 person-years (mean [SD] follow-up, 4.4 [3.4] years). Dementia incidence decreased in successive birth cohorts. Incidence per 100 person-years was 5.09 in birth cohorts before 1920, 3.11 in the 1920 through 1924 birth cohorts, 1.73 in the 1925 through 1929 birth cohorts, and 0.23 in cohorts born after 1929. Change point analyses identified a significant decrease in dementia incidence among those born after July 1929 (95% CI, June 1929 to January 1930). The relative rate for birth cohorts before July 1929 vs after was 0.13 (95% CI, 0.04-0.41). Prevalence of stroke and myocardial infarction decreased across successive birth cohorts, whereas diabetes prevalence increased. Adjustment for these cardiovascular comorbidities did not explain the decreased dementia incidence rates for more recent birth cohorts.Analyses confirm decreasing dementia incidence in this population-based sample. Whether decreasing incidence will contribute to reduced burden of dementia given the aging of the population is not known.
Left Atrial Fibrosis and Risk of Cerebrovascular and Cardiovascular Events in Patients With Atrial Fibrillation
Authors: Jordan B. King, Peyman N. Azadani, Promporn Suksaranjit, Adam P. Bress, Daniel M. Witt, Frederick T. Han, Mihail G. Chelu, Michelle A. Silver, Joseph Biskupiak, Brent D. Wilson, Alan K. Morris, Eugene G. Kholmovski, Nassir Marrouche
Journal: Journal of the American College of Cardiology (2017)