tbuckley/cabot-search huggingface dataset:
Modélisation en temps réel des épidémies de grippe : une analyse de régression linéaire
Authors: J. D. Mooney, E. Holmes, P Christie
Journal: Eurosurveillance (2002)

Les epidemies saisonnieres de grippe mobilisent d’enormes ressources des services de sante. Or elles sont connues pour leur variabilite d’un hiver a l’autre. En utilisant les donnees historiques du systeme ecossais de surveillance sentinelle de la grippe depuis 1972, un modele potentiel de prediction des epidemies de grippe a ete etabli en utilisant une analyse de regression lineaire simple. Il a ete applique avec un certain succes au cours de la saison hivernale 1999–2000.
What is the most effective treatment for frozen shoulder?
Authors: Amar Rangan, Nigel Hanchard, Catriona McDaid
Journal: BMJ (2016)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following What is the most effective treatment for frozen shoulder? Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Low-Dose FCR Is a Safe and Effective Treatment Option for Elderly/Comorbid Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Updated Results of Project Q-Lite By Czech CLL Study Group
Authors: Lukas Smolej, Yvona Brychtova, Michael Doubek, Eduard Cmunt, Martin Spacek, David Belada, Monika Motyckova, Irena Zygulova, Dagmar Adamova, Vit Prochazka, Martin Simkovic, Katerina Klaskova, Tomas Kozak
Journal: Blood (2014)
Association Between Depressive Disorders and Incident Acute Myocardial Infarction in Human Immunodeficiency Virus–Infected Adults
Authors: Tasneem Khambaty, Jesse C. Stewart, Samir K. Gupta, Chung-Chou H. Chang, Roger J. Bedimo, Matthew J. Budoff, Adeel A. Butt, Heidi Crane, Cynthia L. Gibert, David A. Leaf, David Rimland, Hilary A. Tindle, Kaku A. So-Armah, Amy C. Justice, Matthew S. Freiberg
Journal: JAMA Cardiology (2016)

With the advent of highly effective antiretroviral therapy and improved survival, human immunodeficiency virus (HIV)-infected people are living longer and are now at an increased risk for cardiovascular disease (CVD). There is an urgent need to identify novel risk factors and primary prevention approaches for CVD in HIV. Although depression is prevalent in HIV-infected adults and is associated with future CVD in the general population, its association with CVD events has not been examined in the HIV-infected population.
Macronutrient Intake–Associated <i>FGF21</i> Genotype Modifies Effects of Weight-Loss Diets on 2-Year Changes of Central Adiposity and Body Composition: The POUNDS Lost Trial
Authors: Yoriko Heianza, Wenjie Ma, Tao Huang, Tiange Wang, Yan Zheng, Steven R. Smith, George A. Bray, Frank M. Sacks, Lu Qi
Journal: Diabetes Care (2016)

Fibroblast growth factor 21 (FGF21) is involved in the regulation of energy balance and adipose metabolism. Our previous genome-wide association study identified genetic variants in the FGF21 region associated with macronutrient intake preference. We investigated whether the FGF21 genotype modified effects of weight-loss diets varying in macronutrient intake on changes in adiposity in a 2-year randomized diet intervention trial.We genotyped FGF21 rs838147 in 715 overweight or obese individuals who were assigned to one of four diets varying in macronutrient contents. A DEXA scan was performed to evaluate body composition.We observed a significant interaction between the FGF21 genotype and carbohydrate/fat intake on 2-year changes in waist circumference (WC), percentage of total fat mass, and percentage of trunk fat (P = 0.049, P = 0.001, and P = 0.003 for interaction, respectively). In response to the low-carbohydrate/high-fat diet, carrying the carbohydrate intake-decreasing C allele of rs838147 was marginally associated with less reduction in WC (P = 0.08) and significantly associated with less reduction of total fat mass (P = 0.01) and trunk fat (P = 0.02). Opposite genetic associations with these outcomes were observed among the high-carbohydrate/low-fat diet group; carrying the C allele was associated with a greater reduction of WC, total body fat mass, and trunk fat.Our data suggest that FGF21 genotypes may interact with dietary carbohydrate/fat intake on changes in central adiposity and body fat composition. A low-calorie, high-carbohydrate/low-fat diet was beneficial for overweight or obese individuals carrying the carbohydrate intake-decreasing allele of the FGF21 variant to improve body composition and abdominal obesity.
Broad neutralization of hepatitis C virus‐resistant variants by Civacir hepatitis C immunoglobulin
Authors: Rajiv G. Tawar, Laura Heydmann, Charlotte Bach, Jörg Schüttrumpf, Shailesh Chavan, Barnabas J. King, C. Patrick McClure, Jonathan K. Ball, Patrick Pessaux, François Habersetzer, Ralf Bartenschlager, Mirjam B. Zeisel, Thomas F. Baumert
Journal: Hepatology (2016)

Hepatitis C virus (HCV)-induced end-stage liver disease is the major indication for liver transplantation (LT). However, reinfection of the liver graft is still common, especially in patients with detectable viral load at the time of LT. Limited data are available on direct-acting antivirals in the transplant setting for prevention of graft infection. The human hepatitis C immunoglobulin (HCIG) Civacir is an investigational drug that is currently being developed in an ongoing phase 3 clinical trial assessing its safety and efficacy at preventing HCV recurrence after liver transplantation (LT) in the United States. Using well-characterized patient-derived HCV variants selected during LT, we studied the molecular mechanism of action of Civacir. Inhibition of HCV infection was studied using infectious HCV models including HCV pseudoparticles (HCVpp) and cell culture-derived HCV (HCVcc) containing patient-derived viral envelope glycoproteins from 22 HCV variants isolated from patients before and after LT. The human hepatitis C immune globulin Civacir is an investigational drug that is currently being developed in an ongoing phase 3 clinical trial assessing safety and efficacy to prevent HCV recurrence after LT in the United States. Using well-characterized patient-derived HCV variants selected during LT, we studied the molecular mechanism of action of Civacir. Inhibition of HCV infection was studied using infectious HCV models including HCV pseudoparticles and cell culture-derived HCV containing patient-derived viral envelope glycoproteins from 22 HCV variants isolated from patients before and after liver transplantation. Additionally, we studied neutralization of different HCV genotypes and of direct-acting antiviral-resistant viruses. Our results indicate that Civacir potently, broadly, and dose-dependently neutralizes all tested patient variants in HCV pseudoparticles and cell culture-derived HCV assays including variants displaying resistance to host neutralizing antibodies and antiviral monoclonal antibodies. The half-maximal inhibitory concentrations were independent of the phenotype of the viral variant, indicating that virus neutralization by Civacir is not affected by viral selection. Furthermore, Civacir is equally active against tested direct-acting antiviral-resistant HCV isolates in cell culture.Collectively, these results demonstrate broad neutralizing activity of Civacir against resistant viruses, likely due to synergy between anti-HCV antibodies derived from different plasma donors, and support its further clinical development for prevention of liver graft infection. (Hepatology 2016;64:1495-1506).
TGF-β receptor maintains CD4 T helper cell identity during chronic viral infections
Authors: Gavin M. Lewis, Ellen J. Wehrens, Lara Labarta-Bajo, Hendrik Streeck, Elina I. Zuniga
Journal: Journal of Clinical Investigation (2016)

Suppression of CD8 and CD4 T cells is a hallmark in chronic viral infections, including hepatitis C and HIV. While multiple pathways are known to inhibit CD8 T cells, the host molecules that restrict CD4 T cell responses are less understood. Here, we used inducible and CD4 T cell-specific deletion of the gene encoding the TGF-β receptor during chronic lymphocytic choriomeningitis virus infection in mice, and determined that TGF-β signaling restricted proliferation and terminal differentiation of antiviral CD4 T cells. TGF-β signaling also inhibited a cytotoxic program that includes granzymes and perforin expression at both early and late stages of infection in vivo and repressed the transcription factor eomesodermin. Overexpression of eomesodermin was sufficient to recapitulate in great part the phenotype of TGF-β receptor-deficient CD4 T cells, while SMAD4 was necessary for CD4 T cell accumulation and differentiation. TGF-β signaling also restricted accumulation and differentiation of CD4 T cells and reduced the expression of cytotoxic molecules in mice and humans infected with other persistent viruses. These data uncovered an eomesodermin-driven CD4 T cell program that is continuously suppressed by TGF-β signaling. During chronic viral infection, this program limits CD4 T cell responses while maintaining CD4 T helper cell identity.
Sometimes Wrong, Always In Doubt
Authors: Steven Yule, Stanley W. Ashley
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Interindividual Variation in DNA Methylation at a Putative POMC Metastable Epiallele Is Associated with Obesity
Authors: Peter Kühnen, Daniela Handke, Robert A. Waterland, Branwen J. Hennig, Matt Silver, Anthony J. Fulford, Paula Dominguez-Salas, Sophie E. Moore, Andrew M. Prentice, Joachim Spranger, Anke Hinney, Johannes Hebebrand, Frank L. Heppner, Lena Walzer, Carsten Grötzinger, Jörg Gromoll, Susanna Wiegand, Annette Grüters, Heiko Krude
Journal: Cell Metabolism (2016)
The effect of selenium on the oncogenic protein β-catenin in human colorectal cancers.
Authors: M. Saifo, Y. M. Rustum, R. G. Azrak
Journal: Journal of Clinical Oncology (2010)

e13553 Background: β-catenin is a multifunctional oncogenic protein leads to many types of human cancers by affecting cell growth and adhesion. Recently, Wnt/β-catenin signaling pathway is implicated in the self-renewal of stem cells. Cancer stem cells (CSCs) contribute to tumor bulk, recurrence and resistance to chemotherapy. In colorectal carcinomas, Wnt/β-catenin signaling pathway is activated due to a mutation in the tumor suppresser gene, APC. This study is to determine whether pharmacological doses of a selenium-containing compound, methylseleninic acid (MSeA), have an effect on the expression of β-catenin in colorectal carcinomas. Methods: Two human colorectal cancer cell lines, HCT-8 and HT-29,were treated with MSeA alone, SN-38 alone (the active metabolite of irinotecan, a topoisomearse I inhibitor) and in sequential combination of MSeA/SN-38. MSeA was applied at various doses and exposure times. SN-38 was used at concentration that inhibits 50% of cell growth. After treatments, the effect on intracellular level of β-catenin was detected using western blot analyses. The effect on cell growth/death was measured using Sulforhodamine B (SRB) assay. Results: Untreated HCT-8 and HT-29 cells expressed β-catenin. MSeA inhibited intracellular level of β-catenin in dose and time dependent manners. The reduced level of β-catenin after MSeA treatments was associated with inhibition of tumor cell growth and enhancement of cell death. SN-38 alone had no effect onβ-catenin level. The sequential combination of MSeA/SN-38 resulted in more inhibition of β-catenin when compared to all other treatment groups. Conclusions: In colorectal carcinomas, MSeA is a potent inhibitor of β-catenin that consequently led to cell growth inhibition and death. Sequential combination of MSeA/SN-38 resulted in further increase in β-catenin inhibition, thus offering the potential for reversal of drug resistance and tumor relapse. Based on these results and given the important role of Wnt/β-catenin signaling pathway in CSCs, MSeA is an excellent candidate regimen for future therapeutic combinations to reduce tumor bulk, reverse drug resistance and eradicate CSCs, thus preventing tumor relapse and increasing cure rates. No significant financial relationships to disclose.
Response by Sharkey et al to Letter Regarding Article, “Giant J Waves and ST-Segment Elevation Associated With Acute Gastric Distension”
Authors: Scott W. Sharkey, Quirino Orlandi, Maria Teresa Olivari
Journal: Circulation (2016)

In Response:In his letter, Dr Littmann notes similarities in ECG findings between our case report 1 and those previously reported in critically ill patients without acute myocardial infarction and labeled as the "spiked helmet" sign. 2,3The spike represents the QRS complex, and the helmet represents an upward deflection of the ECG baseline beginning before and ending after the QRS complex.Dr Littmann has postulated the upward ECG shift represents a mechanical mechanism resulting from cardio-synchronous diaphragmatic contraction or "pulsatile epidermal stretch." 2,3 We have examined the ECG tracings from Dr Littmann's publications and respectfully disagree with his suggestion that our case represents an example of the spiked helmet sign.The spiked helmet tracings demonstrate ST-segment elevation but without a well-defined J wave as was present in our case.In our case, the availability of serial 12-lead ECG tracings is useful in revealing the temporal increase in both the J-wave amplitude and the associated ST-segment elevation.As Dr Littmann noted, the ECG baseline in our case shifts upward in leads V 4 through V 6 before the QRS onset.However, the slope of this shift is gradual, in contrast to the slope of the upward shift immediately following the QRS complex, likely representing different physiologic processes.We think that the ST-segment elevation, especially prominent in leads V 4 through V 6 , represents the J wave, whereas the gradual upward slope before the QRS onset represents continuation of ventricular repolarization with a superimposed P wave and atrial repolarization.In our case and the cases of Dr Littmann, sinus tachycardia was present with consequent shortening of the time available for ventricular and atrial repolarization, another possible influence on the ECG changes.Regardless of mechanism, our case and the spiked helmet examples reported by Dr Littmann illustrate the importance of careful examination of the ECG in critically ill patients.In both conditions, the unusual ECG appearance differs from that of patients with acute myocardial infarction caused by coronary artery obstruction.
Clinical Characteristics and Prognosis in South-American Patients with Myelodysplastic Syndrome: A Multicenter Study
Authors: Carolina Belli, Ronald Feitosa Pinheiro, Maria Gabriela Flores, Silvia M. M. Magalhaes, Laura Kornblihtt, Alicia Enrico, Juliana Cordeiro, Ana Lisa Basquiera, Marcela Cavalcante de Andrade Silva, Roberta da Silva Tanizawa, Noemi Pintos, Graciela Alfonso, Jorge Arbelbide, Francisco Sakamoto, Nora Watman, Ximena Valladares Ticona, Irene B Larripa, Soledad S. Undurraga, Elvira RP Velloso
Journal: Blood (2014)
Caring for the Uninsured and Underinsured
Authors: William R. Herman
Journal: JAMA (1991)

<h3>To the Editor.</h3> —While your editorial<sup>1</sup>noted that costs and access—in that order—are the most important problems of medical care in the United States, most of the contributors to your May 15 issue ignored or minimized costs. Maybe that's because it's easier and less hostile to propose spending money—5% more than at present by Rashi Fein,<sup>2</sup>$25 billion more by Karen Davis,<sup>3</sup>and perhaps $50 billion more by advocates of the Pepper report.<sup>4</sup>No doubt, because it's easier to spend money, one of the proposals in your journal will be accepted, thereby making the cost situation even worse. Medical costs are the fundamental problem, terrorizing individuals, corporations, and governments in different ways. After reviewing the medical care policies and programs of five other nations (Great Britain, the Netherlands, Sweden, Germany, and Canada), I believe we should be able to provide comprehensive, quality medical care for virtually
The Cost-effectiveness of Misoprostol
Authors: J. Jacobs
Journal: JAMA (1991)

<h3>To the Editor.—</h3> I find it disconcerting that the only two studies of the economic impact of misoprostol could provide such disparate results. Hillman and Bloom<sup>1</sup>conclude that misoprostol is actually cost-reducing; they report that the drug more than pays for itself through reduced morbidity. In contrast, Edelson et al<sup>2</sup>estimate that (for the general population of NSAID users) it is necessary to spend $667 400 to save a year of life via a reduction in fatal gastrointestinal tract (GI) bleeds. I confess that I had some difficulty following the calculations in the article by Edelson et al. It appears, however, that the following assumptions are used to estimate the effectiveness of misoprostol. The annual rate of GI tract bleeds in NSAID users is 45 per 1000; the risk ofdeath for patients who suffer a GI tract bleed is 11.2 per 1000. Misoprostol reduces the risk of
Ofranogene obadenovec (VB-111), an anti-cancer gene therapy in combination with bevacizumab to improve overall survival compared to bevacizumab monotherapy in patients with rGBM: A phase 2 historically controlled trial.
Authors: Andrew Jacob Brenner, Yael Chava Cohen, James J. Vredenburgh, Katherine B Peters, Lakshmi Nayak, Deborah T. Blumenthal, Felix Bokstein, Eyal Breitbart, Livnat Bangio, Naamit Sher, Andrea R Leubitz, Shlomit Yust-Katz, Idit Peretz, Laurence S Freedman, Liraz Olmer, Patrick Y. Wen
Journal: Journal of Clinical Oncology (2016)

2074 Background: Ofranergene obadenovec (VB-111) is a gene-therapy specifically targeting angiogenic endothelial cells thereby leading to tumor starvation. Safety and efficacy of VB-111 in combination with bevacizumab (BEV) were evaluated in recurrent Glioblastoma (rGBM) patients in this Phase 2 study and were compared to pooled BEV data generated using meta-analysis. Methods: VB-111 was administered at 1x1013 viral particles bimonthly until progression, followed by BEV standard of care (limited exposure cohort). The protocol was amended to add BEV 10mg/Kg biweekly combined with VB-111 bimonthly, until further progression (continuous exposure cohort). A systematic literature review identified reports of rGBM BEV monotherapy published between 1.1.2009 and 30.11.2015. Data were pooled in a meta-analysis and served as historical controls for comparison of VB-111 extended exposure cohort. Results: 46 patients at 4 sites received up to 13 doses of VB-111. Upon further progression, 24 received VB-111 with BEV, 22 were treated with BEV as standard of care. VB-111 was safe and well-tolerated alone and combined with BEV. Median OS was 59 weeks for continuous exposure versus 33 weeks for limited exposure cohort (p = 0.048). Eight reports of BEV monotherapy were identified, with a total of 694 rGBM patients. VB-111 continuous exposure had superior OS compared to the pooled meta-analysis of BEV monotherapy, 59 versus 39 weeks (p = 0.0295, log-rank test), with a Hazard Ratio of 0.62 (95% CI: 0.40-0.96). Of 46 patients who received VB-111, 25 patients spiked a fever post- dosing of VB-111 at least once, which was associated with increased median OS of 64 weeks versus 34 weeks among patients without fever (p = 0.03). Conclusions: VB-111 was safe and well-tolerated alone and combined with BEV in rGBM patients. VB-111 continuous exposure significantly increased OS compared to a historical BEV meta-analysis controls, and compared to VB-111 limited exposure. Toxicities were as expected in this population. The GLOBE phase 3 randomized controlled trial of VB-111 in rGBM is currently underway. Clinical trial information: NCT01260506.
Sunitinib malate for metastatic castration resistant prostate cancer following docetaxel-based chemotherapy
Authors: P. O. Periman, G. Sonpavde, D. M. Bernold, D. J. Weckstein, A. Williams, F. Zhan, K. A. Boehm, L. Asmar, T. E. Hutson
Journal: Journal of Clinical Oncology (2008)

5157 Background: Sunitinib malate is a multitargeted tyrosine kinase inhibitor approved multinationally for renal cell carcinoma and gastrointestinal stromal tumors. Effective options are lacking for progressive CRPC (castration-resistant prostate cancer) following conventional chemotherapy. This phase II trial was conducted to examine the efficacy and toxicity of sunitinib in metastatic CRPC progressing after prior chemotherapy. Methods: Key inclusion: histologically confirmed adenocarcinoma (metastatic stage IV), clinical or PSA progression, currently on androgen ablation treatment, with 1- 2 prior chemotherapy regimens including docetaxel. Other standard (drug specific) inclusion/exclusion criteria applied. The primary objective was clinical progression-free survival (PFS) with a 12-week PFS >30% as a goal. Secondary objectives: PSA response, objective response, quality of life, pain, survival, and toxicities. Sunitinib 50 mg/day was administered orally 4 weeks on / 2 weeks off in 6-week cycles. Patients (pts) were treated to a maximum of 8 cycles or until clinically progressive disease or intolerable toxicity. A planned interim analysis of the first 19 pts is presented here; accrual goals (n=36) have been met. Results: The median age was 69 years. The median clinical PFS (as per RECIST, bone events, pain, obstruction, ECOG) for these pts was 2.8 months (95% CI, 2.2, 6.1) with a 12-week PFS attained in 48.3%. A 50% PSA response was seen in 1 pt, and 30% PSA response was seen in 3 pts, with an additional 2 pts with unconfirmed 30% PSA responses. Grade 3–4 therapy related toxicities were infrequent with only Grade 3 anemia occurring in 2 pts; 7 pts died due to disease progression with 2 deaths deemed possibly related to sunitinib (non- neutropenic sepsis and hemorrhagic stroke, n=1 each). Conclusions: Single-agent sunitinib malate demonstrated significant antitumor activity with manageable toxicities in men with metastatic CRPC that had progressed following 1–2 prior regimens including docetaxel. Accrual is complete and final efficacy and toxicity data on all pts will be presented. These data warrant further evaluation of sunitinib in metastatic CRPC. Supported, in part, by a grant from Pfizer, Inc., New York, NY. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, GlaxoSmithKline, Pfizer Oncology, Wyeth Bayer, GlaxoSmithKline, Pfizer Oncology, Wyeth Bayer, GlaxoSmithKline, Pfizer Oncology, Wyeth