tbuckley/cabot-search huggingface dataset:
Early Allogeneic Stem Cell Transplantation and Use of Asparaginase during Induction Chemotherapy Appear to Improve Otherwise Poor Outcomes in Adult T-Cell Acute Lymphoblastic Leukemia/Lymphoma (T-ALL/T-LBL) Patients: A Multi-Institutional Review
Authors: Uma Borate, Amanda Redden Hathaway, Deniz Peker, Bradford E Jackson, Vamsi K Kota, Bijal D Shah, Ling Zhang, Anand Jillella, Martha Arellano, Leonard T. Heffner, Harry P Erba
Journal: Blood (2015)
IQGAP2 is a novel interferon-alpha antiviral effector gene acting non-conventionally through the NF-κB pathway
Authors: Cynthia Brisac, Shadi Salloum, Victor Yang, Esperance A.K. Schaefer, Jacinta A. Holmes, Stephane Chevaliez, Jian Hong, Charlie Carlton-Smith, Nadia Alatrakchi, Annie Kruger, Wenyu Lin, Raymond T. Chung
Journal: Journal of Hepatology (2016)
Glucocorticoid receptors in depression: relationship to the dexamethasone suppression test
Authors: G J Gormley, M T Lowy, A T Reder, V D Hospelhorn, J P Antel, H Y Meltzer
Journal: American Journal of Psychiatry (1985)

Cytoplasmic glucocorticoid receptor content wa quantitated in lymphocytes from unmedicated depressed patients and control subjects before and after a standardized dexamethasone suppression test. Depressed patients (N = 11) had significantly lower (32%) basal cytoplasmic glucocorticoid receptor content than the control group (N = 14). Suppression of serum cortisol (5.0 micrograms/dl or less) in both control and depressed subjects (N = 16) following dexamethasone (1 mg) was associated with a decrease in lymphocyte cytoplasmic glucocorticoid receptor number, whereas no such change occurred in cortisol nonsuppressors (N = 9). Changes in receptor concentration were positively correlated with postdexamethasone serum cortisol levels and with the inhibitory effect of dexamethasone on mitogen-induced lymphocyte proliferation.
Improved sorafenib activity on hepatocellular carcinoma in Notch3 silenced in vivo and in vitro models.
Authors: Michele Baglioni, Catia Giovannini, Laura Gramantieri, Marco Baron Toaldo, Cristiano Ventrucci, Stefania D'Adamo, Mario Cipone, Pasquale Chieco, Luigi Bolondi
Journal: Journal of Clinical Oncology (2012)

3061 Background: Sorafenib is the only approved drug for the treatment of the advanced stage of HCC. Although its efficacy has been proven with randomized clinical trials, the clinical benefit seen in overall survival for advanced HCC patients treated with sorafenib could be improved. New molecules or combination of novel targeted agents to improve sorafenib efficacy for advanced stage HCC patients are needed. Notch genes are a family of receptors involved in many cell fate regulations, their expression has been found altered in many tumors, including HCC. The aim of this study was to study the combination of sorafenib and Notch3 signaling inhibition to improve sorafenib’s therapeutic effect. Methods: HepG2 and Huh7 cellular models were used for Notch3 stable silencing by retroviral introduction of specific interfering RNAs Xenograft models in both Notch3 stable shRNA cell lines have been developed using NOD/SCID mice. Animals bearing tumors were treated with 60 mg/kg of sorafenib for 21 consecutive days. Notch3, p21 and pGSK3β Ser9 protein expression were also analyzed in 20 human HCCs. Results: Notch3 silencing (shN3) in HuH7 and HepG2 cell lines treated with sorafenib showed an increase in cell death (3.8 to 5 fold increase) when shN3 cell lines were compared with their relative controls (GL2). A difference in tumor growth was observed between GL2 negative control vs shN3 xenografts in both HepG2 and Huh7 after 21 days of sorafenib treatment. Two tailed student’s t test (shN3 vs GL2) P=0,04 and P=0,01 for Huh7 and HepG2 respectively. Molecular investigations have shown the involvement of p21 and GSK3β in the enhanced response to sorafenib in Notch 3 silenced models. A significant inverse correlation between Notch3 and pGSK3β Ser9 proteins accumulation (Spearman ρ= -0.666) (p &lt; 0.01) and a direct correlation between Notch3 and p21 proteins expression (Spearman ρ= 0.681) (p &lt; 0.01) was found in HCC samples obtained from patients. Conclusion: Our preclincal findings outline the effect of combined Notch3 inhibition and sorafenib. The molecular mechanisms responsible for sorafenib induced cell death associated with Notch3 silencing relays on inhibition of p21/CDKN1A and GSK3β Ser9 . This study is supported by a grant from Bayer Healthcare, Italy.
Eighteen-year follow-up in the Veterans Affairs Cooperative Study of Coronary Artery Bypass Surgery for stable angina. The VA Coronary Artery Bypass Surgery Cooperative Study Group.
Journal: Circulation (1992)

The 18-year effect of bypass surgery compared with medical therapy on survival, incidence of myocardial infarction, and relief of angina was evaluated in 686 randomized patients with stable angina in the Veterans Affairs Cooperative Study of Coronary Artery Bypass Surgery.The primary treatment comparisons were made according to intent to treat; 44% of the entire medical cohort had bypass surgery during a median follow-up of 16.8 years. Overall 18-year survival rates were 33% for medicine compared with 30% for surgery (p = 0.60). Survival rates for high-risk patients without left main disease, which had shown a significant advantage for surgical therapy up to 11 years, were 23% medicine versus 24% surgery for patients with three-vessel disease and impaired left ventricular function (p = 0.49) and 22% versus 25% for those with multiple clinical risk factors (p = 0.12). For patients with two-vessel disease, who had significantly better survival with medical therapy at 11 years, rates were similar at 18 years in the two treatment groups (34% medicine versus 30% surgery, p = 0.09). Cumulative 18-year myocardial infarction rates (fatal plus nonfatal) were 41% in medical and 49% in surgical patients (13% perioperative infarction rate), p = 0.15. Nonfatal infarction rates were lower with medical than with surgical therapy (32% versus 44%, p = 0.015), but fatal infarction rates were similar (14% medicine versus 13% surgery, p = 0.62). The combined rate of myocardial infarction or death was also lower with medical therapy (75% versus 82%, p = 0.016). In contrast, surgery reduced mortality after myocardial infarction by 35% at 10 years (p less than 0.001) but only by 13% at 18 years (p = 0.09). The percent of medical and surgical patients who were angina-free was 3% versus 22% (p less than 0.001) at 1 year and 4% versus 12% (p less than 0.001) at 5 years compared with rates of 6% versus 5% (p greater than 0.50) at 10 years and 3% versus 4% (p greater than 0.50) at 15 years.The benefits of coronary artery bypass surgery on survival, symptoms, and postinfarction mortality were transient and lasted fewer than 11 years. The benefits began to diminish after 5 years, when graft closure accelerated. Surgery was effective in reducing mortality only for patients with a poor natural history. Low-risk patients, who had a good prognosis with medical therapy, derived no survival benefit with surgical therapy at any time during the follow-up period. Regardless of risk, surgery also did not reduce the incidence of myocardial infarction or the combined incidence of infarction or death.
Now and then
Authors: Ike Iheanacho
Journal: BMJ (2007)

He died in 1993. His book was published more than 40 years ago, has long been out of print, and isn't widely known. So, how could he still be saying anything relevant about a field as dynamic as drugs?

Brian Inglis's Drugs, Doctors and Disease: A Survey of the Pharmaceutical Industry appeared midway between the thalidomide scandal and the UK's Medicines Act 1968, which provided a crucial brake on drug company activities. It is worth reflecting on just how bad things had been. Facing little or no regulation, drug companies were running riot. Products were inadequately tested before launch, misleading promotion flourished unchecked, and cartels kept some drug prices obscenely high. And, importantly, no safety culture existed that ensured disclosure of unwanted effects of treatments.

Authorities in the United States had decided that enough was enough. In particular, a congressional inquiry chaired by Senator Estes Kefauver prompted groundbreaking legislation to control approval, marketing, and promotion of medicines. Brian Inglis admired the work of the Kefauver subcommittee, and his book was in part a push for a similar investigation in the United Kingdom.

Like many of the best commentators on the drug industry he was neither a healthcare professional nor a scientist. And like many of the best writers on anything he was Irish. He was also a historian, journalist, and television presenter. The academic's intellectual rigour and the skills of a natural communicator glow throughout Drugs, Doctors, and Disease. But being scholarly, lucid, and concise doesn't account for the book's enduring value.

It is the stunning quality of the author's insights that makes the text so compellingly brilliant, despite the huge changes in circumstances four decades on. A few examples? He emphasised the dangers of resistance to drugs, related to inappropriate advertising and misuse of antibacterial drugs. He debunked attempts to present promotion as the supply of unbiased information, drew attention to inadequate training of medical students in pharmacology and therapeutics, poured scorn on doctors' self deception that they were (uniquely) immune to advertising, and cautioned against the too cosy relationships that develop between the industry and those meant to regulate it. None of these issues (and many others he raised) can be considered remotely out of date.

Also, he was not especially interested in knocking drug companies. Rightly, he found much to praise about the industry but was highly critical of the environment in which it was allowed to operate.

In short, he showed how society gets the industry it deserves—a truly timeless message. In the 1960s governments, regulators, doctors, and the general public could plausibly plead ignorance to such a suggestion. What excuse do we have now?
The Two-Question Method in Other High-Stress Settings
Authors: Pelle G. Lindqvist, Charlotte Hellsten
Journal: JAMA Internal Medicine (2016)

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
Specificity of the TRH test for major depression in patients with serious cocaine abuse
Authors: C A Dackis, T W Estroff, D R Sweeney, A L Pottash, M S Gold
Journal: American Journal of Psychiatry (1985)

The authors administered the thyrotropin-releasing hormone (TRH) test to 17 patients with severe cocaine abuse and without major depression. The results suggest that the test is not specific for major depression when serious cocaine abuse is present.
123I-MIBG Scintigraphy in the Subacute State of Takotsubo Cardiomyopathy
Authors: Thomas Emil Christensen, Lia Evi Bang, Lene Holmvang, Dorthe Charlotte Skovgaard, Ditte Bang Oturai, Helle Søholm, Jakob Hartvig Thomsen, Hedvig Bille Andersson, Adam Ali Ghotbi, Nikolaj Ihlemann, Andreas Kjaer, Philip Hasbak
Journal: JACC. Cardiovascular imaging (2016)
The Prognostic Value of MYC, BCL2 and BCL6 Translocations and Protein Expressions in Young Patients with High-Risk Diffuse Large B-Cell Lymphoma Treated with R-CHOEP
Authors: Mette Ølgod Pedersen, Anne Ortved Gang, Estrid Hoegdall, Helle Knudsen, Anne F. Lauritzen, Signe Ledou Nielsen, Tobias Wirenfeldt Klausen, Michael Pedersen, Peter de Nully Brown, Peter H Norgaard
Journal: Blood (2014)
B cell regulation of the anti-tumor response and role in carcinogenesis
Authors: Marc Schwartz, Yu Zhang, Joseph D. Rosenblatt
Journal: Journal for ImmunoTherapy of Cancer (2016)

The balance between immune effector cells such as T cells and natural killer cells, and immunosuppressive Treg cells, dendritic, myeloid and monocytic sub-populations in the tumor microenvironment acts to calibrate the immune response to malignant cells. Accumulating evidence is pointing to a role for B cells in modulating the immune response to both solid tumors and hematologic cancer. Evidence from murine autoimmune models has defined B regulatory cell (Breg) subsets that express cytokines such as IL-10, TGF-β, and/or express immune regulatory ligands such as PD-L1, which can suppress T cell and/or natural killer cell responses. Multiple murine tumor models exhibit decreased tumor growth in B cell deficient or B cell depleted mice. In several of these models, B cells inhibit T cell mediated tumor immunity and/or facilitate conversion of T cells to CD4(+)CD25(+)FoxP3(+) T regs, which act to attenuate the innate and/or adaptive antitumor immune response. Mechanisms of suppression include the acquisition of inhibitory ligand expression, and phosphorylation of Stat3, and induction of IL-10 and TGF-β, resulting in a Breg phenotype. Breg suppressive activity may affect diverse cell subtypes, including T effector cells, NK cells, myeloid derived suppressor cells (MDSC) and/or tumor associated macrophages. B cells may also directly promote tumorigenesis through recruitment of inflammatory cells, and upregulation of pro-angiogenic genes and pro-metastatic collagenases. Breg infiltration has now been identified in a variety of solid tumor malignancies including but not limited to ovarian, gastric, non-small cell lung cancer, pancreatic, esophageal, head and neck, and hepatocellular carcinomas. Increasing evidence suggests that recruitment of B cells and acquisition of suppressive activity within the tumor bed may be an important mechanism through which B cells may modulate innate and/or adaptive anti-tumor immunity. B cell depletion in the clinic using anti-CD20 antibodies and/or inhibitors of BTK and/or other signaling pathways, may be a useful strategy for augmenting the anti-tumor immune response.
Recent Trends in Cardiovascular Mortality in the United States and Public Health Goals
Authors: Stephen Sidney, Charles P. Quesenberry, Marc G. Jaffe, Michael Sorel, Mai N. Nguyen-Huynh, Lawrence H. Kushi, Alan S. Go, Jamal S. Rana
Journal: JAMA Cardiology (2016)

Heart disease (HD) and cancer are the 2 leading causes of death in the United States. During the first decade of the 21st century, HD mortality declined at a much greater rate than cancer mortality and it appeared that cancer would overtake HD as the leading cause of death.To determine whether changes in national trends had occurred in recent years in mortality rates due to all cardiovascular disease (CVD), HD, stroke, and cancer and to evaluate the gap between mortality rates from HD and cancer.The Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research data system was used to determine national trends in age-adjusted mortality rates due to all CVD, HD, stroke, and cancer from January 1, 2000, to December 31, 2011, and January 1, 2011, to December 31, 2014, overall, by sex, and by race/ethnicity. The present study was conducted from December 30, 2105, to January 18, 2016.Comparison of annual rates of change and trend in gap between HD and cancer mortality rates.The rate of the decline in all CVD, HD, and stroke mortality decelerated substantially after 2011, and the rate of decline for cancer mortality remained relatively stable. Reported as percentage (95% CI), the annual rates of decline for 2000-2011 were 3.79% (3.61% to 3.97%), 3.69% (3.51% to 3.87%), 4.53% (4.34% to 4.72%), and 1.49% (1.37% to 1.60%) for all CVD, HD, stroke, and cancer mortality, respectively; the rates for 2011-2014 were 0.65% (-0.18% to 1.47%), 0.76% (-0.06% to 1.58%), 0.37% (-0.53% to 1.27%), and 1.55% (1.07% to 2.04%), respectively. Deceleration of the decline in all CVD mortality rates occurred in males, females, and all race/ethnicity groups. For example, the annual rates of decline for total CVD mortality for 2000-2011 were 3.69% (3.48% to 3.89%) for males and 3.98% (3.81% to 4.14%) for females; for 2011-2014, the rates were 0.23% (-0.71% to 1.16%) and 1.17% (0.41% to 1.93%), respectively. The gap between HD and cancer mortality persisted.Deceleration in the decline of all CVD, HD, and stroke mortality rates has occurred since 2011. If this trend continues, strategic goals for lowering the burden of CVD set by the American Heart Association and the Million Hearts Initiative may not be reached.
The Copenhagen Consensus Conference 2016: children, youth, and physical activity in schools and during leisure time
Authors: Jens Bangsbo, Peter Krustrup, Joan Duda, Charles Hillman, Lars Bo Andersen, Maureen Weiss, Craig A Williams, Taru Lintunen, Ken Green, Peter Riis Hansen, Patti-Jean Naylor, Ingegerd Ericsson, Glen Nielsen, Karsten Froberg, Anna Bugge, Jesper Lundbye-Jensen, Jasper Schipperijn, Symeon Dagkas, Sine Agergaard, Jesper von Seelen, Charlotte Østergaard, Thomas Skovgaard, Henrik Busch, Anne-Marie Elbe
Journal: British Journal of Sports Medicine (2016)

From 4 to 7 April 2016, 24 researchers from 8 countries and from a variety of academic disciplines gathered in Snekkersten, Denmark, to reach evidence-based consensus about physical activity in children and youth, that is, individuals between 6 and 18 years. Physical activity is an overarching term that consists of many structured and unstructured forms within school and out-of-school-time contexts, including organised sport, physical education, outdoor recreation, motor skill development programmes, recess, and active transportation such as biking and walking. This consensus statement presents the accord on the effects of physical activity on children's and youth's fitness, health, cognitive functioning, engagement, motivation, psychological well-being and social inclusion, as well as presenting educational and physical activity implementation strategies. The consensus was obtained through an iterative process that began with presentation of the state-of-the art in each domain followed by plenary and group discussions. Ultimately, Consensus Conference participants reached agreement on the 21-item consensus statement.
EGFR mutation status of cell free serum DNA and clinical efficacy of afatinib in pretreated non-small cell lung cancer (NSCLC) harboring EGFR mutations.
Authors: Satoru Kitazono, Hironari Nishizawa, Hiroshi Kobayashi, Tomoyo Oguri, Yuichi Tambo, Noriko Yanagitani, Atsushi Horiike, Fumiyoshi Ohyanagi, Takeshi Horai, Makoto Nishio
Journal: Journal of Clinical Oncology (2015)

e19087 Background: EGFR mutation status of cell free serum DNA is a potentially useful biomarker to decide the subsequence treatment after 1stgeneration EGFR-TKI. The purpose of this study is to examine the relationship between serum EGFR mutation status and clinical efficacy of afatinib in NSCLC harboring active EGFR mutations and previously treated with gefitinib or erlotinib. Methods: Serum samples were collercted before afatinib treatment from patients with NSCLC harboring EGFR active mutations and treated gefitinib or erlotinib. DNA was extracted from 2ml of the serum and EGFR mutation status was examined by using cobas EGFR Mutation Test. Assessment of response and resistance to afatinib was studied in the patients. Results: Between May 2014 and Dec 2014, total of 22 serum samples were collected from 22 patients who were previously treated with gefitinib (n = 17) or erlotinib (n = 13) and progressed. EGFR mutations in the serum were detected in 5 of 22 patients (22.7%, CI 7.8-45.4%), Exon19 deletion was detected in 4/9, Exon21 L858R in 1/12, and Exon21 L861Q in 0/1. T790M was detected in 3 patients (combined with Exon19 deletion in 2 patients, with L858R in 1). Although overall response rate (ORR) was similar in serum EGFR wild type patients compared to serum EGFR mutated patients (17.6% and 20.0%), disease control rate (DCR) in serum EGFR mutated patients was higher than in the wild type (80.0% vs 47.0%). On the other hand, patients who harboring T790M did not response to afatinib treatment. Conclusions: Serum EGFR mutation analysis may be useful to predict the efficacy of afatinib in patients who were previously treated with gefitinib or erlotinib. Usefulness of plasma EGFR typing by using more sensitive and quantitative PCR such as digital droplet PCR is under examination.
Posaconazole for Primary Antifungal Prophylaxis in AML Patients: A Real Life Single Center Experience and a Comparison with the Historical Cohort
Authors: Paola Minetto, Fabio Guolo, Malgorzata Mikulska, Giordana Pastori, Livia Giannoni, Elisa Furfaro, Franca Miletich, Valerio Del Bono, Filippo Ballerini, Marino Clavio, Maurizio Miglino, Roberto Lemoli, Claudio Viscoli, Marco Gobbi
Journal: Blood (2014)
Baseline Characteristics Of Patients With Chronic Myeloid Leukemia In a Prospective Observational Study (SIMPLICITY)
Authors: Jorge E. Cortes, Rüdiger Hehlmann, Carlo Gambacorti-Passerini, Stuart Goldberg, H. Jean Khoury, Michael Mauro, Mauricette Michallet, Ron Paquette, Bengt Simonsson, Aimee Foreman, Hesham Mohamed, Teresa Zyczynski, Ishan Hirji, Catherine Davis
Journal: Blood (2013)
Do New pN Subclassifications Proposed by IASLC’s Lung Cancer Staging Project Agree with ypN Categories after Trimodality Therapy for Initial N2 Disease?
Authors: Hakyoung Kim, Yong Chan Ahn, Hongryull Pyo, Dongryul Oh, Jae Myoung Noh, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Yong Soo Choi, Jhingook Kim, Jae Ill Zo, Young Mog Shim, Minju Lee, Jungho Han
Journal: Journal of Thoracic Oncology (2016)