tbuckley/cabot-search huggingface dataset:
Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: Updated criteria and genotype assignment web resource
Authors: Donald B. Smith, Jens Bukh, Carla Kuiken, A. Scott Muerhoff, Charles M. Rice, Jack T. Stapleton, Peter Simmonds
Journal: Hepatology (2013)

The 2005 consensus proposal for the classification of hepatitis C virus (HCV) presented an agreed and uniform nomenclature for HCV variants and the criteria for their assignment into genotypes and subtypes. Since its publication, the available dataset of HCV sequences has vastly expanded through advancement in nucleotide sequencing technologies and an increasing focus on the role of HCV genetic variation in disease and treatment outcomes. The current study represents a major update to the previous consensus HCV classification, incorporating additional sequence information derived from over 1,300 (near-)complete genome sequences of HCV available on public databases in May 2013. Analysis resolved several nomenclature conflicts between genotype designations and using consensus criteria created a classification of HCV into seven confirmed genotypes and 67 subtypes. There are 21 additional complete coding region sequences of unassigned subtype. The study additionally describes the development of a Web resource hosted by the International Committee for Taxonomy of Viruses (ICTV) that maintains and regularly updates tables of reference isolates, accession numbers, and annotated alignments (http://talk.ictvonline.org/links/hcv/hcv-classification.htm). The Flaviviridae Study Group urges those who need to check or propose new genotypes or subtypes of HCV to contact the Study Group in advance of publication to avoid nomenclature conflicts appearing in the literature. While the criteria for assigning genotypes and subtypes remain unchanged from previous consensus proposals, changes are proposed in the assignment of provisional subtypes, subtype numbering beyond "w," and the nomenclature of intergenotypic recombinant.This study represents an important reference point for the consensus classification of HCV variants that will be of value to researchers working in clinical and basic science fields.
Are implementation science advances and digital technology developments important in sports medicine? Sports Medicine Australia thinks so
Authors: Jacqueline Tran, Caroline F Finch
Journal: British Journal of Sports Medicine (2014)

The rate of growth of scientific knowledge gains pace year-on-year. Over 20 million journal articles have been indexed in MEDLINE from 1947 to 2012, with the number of publications increasing by an average of 5.2% per year.1 So how might our global community of researchers, clinicians and practitioners pool our collective knowledge to effect improvement in clinical practice?

In this issue of BJSM , curated on behalf of Sports Medicine Australia (SMA), we explore the power of better understanding of intervention implementation and in embracing the new digital technologies. For several years, BJSM has had a major focus on implementation science developments and their applications.2 Rigorously controlled studies will always have their place in the literature, but as outlined previously by Finch3 and Peters et al ( see page 731 ), implementation research seeks to investigate: How can efficacious interventions work harmoniously within the dynamics of the real world? Hanson et al ( see page 682 ) stress that research alone is not enough and that more connection with that real world is needed. One dynamic of our modern age is that of digital technology, providing new opportunities for researchers, clinicians and …
A case of dermatomyositis that developed after delivery: the involvement of pregnancy in the induction of dermatomyositis
Authors: H. Kanoh, T. Izumi, M. Seishima, M. Nojiri, Y. Ichiki, Y. Kitajima
Journal: British Journal of Dermatology (1999)

Journal Article A case of dermatomyositis that developed after delivery: the involvement of pregnancy in the induction of dermatomyositis Get access H. Kanoh, H. Kanoh Department of Dermatology, Ogaki Municipal Hospital, 4‐86 Minaminokawa‐cho, Ogaki 503‐8502, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Izumi, T. Izumi Department of Dermatology, Ogaki Municipal Hospital, 4‐86 Minaminokawa‐cho, Ogaki 503‐8502, Japan Search for other works by this author on: Oxford Academic Google Scholar M. Seishima, M. Seishima Department of Dermatology, Ogaki Municipal Hospital, 4‐86 Minaminokawa‐cho, Ogaki 503‐8502, Japan Search for other works by this author on: Oxford Academic Google Scholar M. Nojiri, M. Nojiri Department of Dermatology, Gifu University School of Medicine, 40 Tsukasamachi, Gifu 500‐8705, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Ichiki, Y. Ichiki Department of Dermatology, Gifu University School of Medicine, 40 Tsukasamachi, Gifu 500‐8705, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Kitajima Y. Kitajima Department of Dermatology, Gifu University School of Medicine, 40 Tsukasamachi, Gifu 500‐8705, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 141, Issue 5, 1 November 1999, Pages 897–900, https://doi.org/10.1046/j.1365-2133.1999.03165.x Published: 01 November 1999
Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease.
Authors: J A Vita, C B Treasure, E G Nabel, J M McLenachan, R D Fish, A C Yeung, V I Vekshtein, A P Selwyn, P Ganz
Journal: Circulation (1990)

In animals, acetylcholine dilates normal arteries and produces vasoconstriction in the presence of hypercholesterolemia, hypertension, or atherosclerosis, reflecting endothelial cell dysfunction. In patients with angiographically smooth coronary arteries, acetylcholine has been reported to produce both vasodilation and constriction. To test the hypothesis that the acetylcholine response relates to risk factors for coronary artery disease, acetylcholine 10(-8) to 10(-6) M was infused into the left anterior descending or circumflex coronary artery, and diameter changes were assessed with quantitative angiography in 34 patients with angiographically smooth coronary arteries. The acetylcholine response ranged from +37% (dilation) to -53% (constriction) at the peak acetylcholine dose. All coronary arteries dilated in response to nitroglycerin (26 +/- 17%), suggesting an abnormality of endothelial function in the patients with a constrictor response to acetylcholine. By multiple stepwise regression analysis, serum cholesterol (p less than 0.01), male gender (p less than 0.001), family history (p less than 0.05), age (p less than 0.05), cholesterol level (p less than 0.01), and total number of risk factors (p less than 0.0001) were independently associated with the acetylcholine response. Thus, coronary risk factors are associated with loss of endothelium-dependent vasodilation. The development of vasoconstriction is likely to be an abnormality of endothelial function that precedes atherosclerosis or an early marker of atherosclerosis not detectable by angiography.
A model of human cytokine regulation based on transfection of gamma interferon gene fragments directly into isolated peripheral blood T lymphocytes.
Authors: J C Chrivia, T Wedrychowicz, H A Young, K J Hardy
Journal: The Journal of Experimental Medicine (1990)

An approach has been optimized permitting measurement of human cytokine reporter gene expression after transient transfection directly into purified human peripheral blood T lymphocytes. Comparing the expression of interleukin 2 (IL-2) CAT with a series of specially engineered gamma interferon (IFN-gamma) constructs, a fundamental difference in the molecular mechanisms regulating these two cytokines has been suggested. A potent, tissue-specific, constitutive-acting positive regulatory element was located between sequences -215 and -53 in the human IFN-gamma gene. Deletion analyses suggested that sequences slightly upstream, between positions -251 to -215, exerted a powerful dominant suppressive influence over that positive element. Negative elements appear to play a major role in controlling the regulation of human IFN-gamma gene expression. We thus propose a model of cytokine gene regulation in which selective derepression may be an important fundamental mechanism of induction and/or positive modulation.
Cutaneous manifestations associated with antiphospholipid antibodies in patients with suspected primary antiphospholipid syndrome: a case-control study.
Authors: L Naldi, F Locati, L Marchesi, S Cortelazzo, G Finazzi, M Galli, A Brevi, T Cainelli, T Barbui
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVE: To study the association of a variety of dermatological manifestations related to vascular abnormalities with antiphospholipid antibodies in patients with suspected primary antiphospholipid syndrome. METHOD: Case-control study. Consecutive patients referred to the coagulation and haemostasis service of a general hospital for the first determination of antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibodies) and newly diagnosed disorders (for example, thrombocytopenia, thrombotic disorders, and unexplained repeated abortions) were selected. Patients were examined by two dermatologists according to predefined criteria, and information about general characteristics and relevant dermatological and medical histories were collected using an ad hoc questionnaire. The study was limited to patients without evidence of systemic lupus erythematosus. A total of 35 patients was examined; 13 subjects were positive for lupus anticoagulant or anticardiolipin antibodies, or both (cases), and 22 were negative (controls). RESULTS: Moderate to severe livedo reticularis and acrocyanosis were significantly associated with antiphospholipid antibodies, with relative risks of 13.1 (95% confidence interval 1.1 to 149.0) and 8.6 (95% confidence interval 1.1 to 65.1). Capillaritis was also associated with the antibodies. Histories of Raynaud9s phenomenon and superficial thrombophlebitis were more common in cases than controls. CONCLUSIONS: This study provides quantitative evidence of the association of antiphospholipid antibodies with several cutaneous diseases in which vascular abnormalities seem to play a major part. The study suggests that these manifestations might appear early in the development of the antiphospholipid syndrome.
Clinical efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis and poor prognostic factors
Authors: R Westhovens, M Robles, A C Ximenes, S Nayiager, J Wollenhaupt, P Durez, J Gomez-Reino, W Grassi, B Haraoui, W Shergy, S-H Park, H Genant, C Peterfy, J-C Becker, A Covucci, R Helfrick, J Bathon
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Objectives:</h3> To assess the efficacy and safety of abatacept in methotrexate-naive patients with early rheumatoid arthritis (RA) and poor prognostic factors. <h3>Methods:</h3> In this double-blind, phase IIIb study, patients with RA for 2 years or less were randomly assigned 1 : 1 to receive abatacept (∼10 mg/kg) plus methotrexate, or placebo plus methotrexate. Patients were methotrexate-naive and seropositive for rheumatoid factor (RF), anti-cyclic citrullinated protein (CCP) type 2 or both and had radiographic evidence of joint erosions. The co-primary endpoints were the proportion of patients achieving disease activity score in 28 joints (DAS28)-defined remission (C-reactive protein) and joint damage progression (Genant-modified Sharp total score; TS) at year 1. Safety was monitored throughout. <h3>Results:</h3> At baseline, patients had a mean DAS28 of 6.3, a mean TS of 7.1 and mean disease duration of 6.5 months; 96.5% and 89.0% of patients were RF or anti-CCP2 seropositive, respectively. At year 1, a significantly greater proportion of abatacept plus methotrexate-treated patients achieved remission (41.4% vs 23.3%; p&lt;0.001) and there was significantly less radiographic progression (mean change in TS 0.63 vs 1.06; p = 0.040) versus methotrexate alone. Over 1 year, the frequency of adverse events (84.8% vs 83.4%), serious adverse events (7.8% vs 7.9%), serious infections (2.0% vs 2.0%), autoimmune disorders (2.3% vs 2.0%) and malignancies (0.4% vs 0%) was comparable for abatacept plus methotrexate versus methotrexate alone. <h3>Conclusions:</h3> In a methotrexate-naive population with early RA and poor prognostic factors, the combination of abatacept and methotrexate provided significantly better clinical and radiographic efficacy compared with methotrexate alone and had a comparable, favourable safety profile.
PTEN Loss Mitigates the Response of Medulloblastoma to Hedgehog Pathway Inhibition
Authors: Ciara Metcalfe, Bruno Alicke, Ailey Crow, Marlea Lamoureux, Gerrit J.P. Dijkgraaf, Franklin Peale, Stephen E. Gould, Frederic J. de Sauvage
Journal: Cancer Research (2013)

Abstract Medulloblastoma is a cancer of the cerebellum, for which there is currently no approved targeted therapy. Recent transcriptomics approaches have demonstrated that medulloblastoma is composed of molecularly distinct subgroups, one of which is characterized by activation of the Hedgehog pathway, which in mouse models is sufficient to drive medulloblastoma development. There is thus considerable interest in targeting the Hedgehog pathway for therapeutic benefit in medulloblastoma, particularly given the recent approval of the Hedgehog pathway inhibitor vismodegib for metastatic and locally advanced basal cell carcinoma. Like other molecularly targeted therapies, however, there have been reports of acquired resistance to vismodegib, driven by secondary Hedgehog pathway mutations and potentially by activation of the phosphatidylinositol 3-kinase (PI3K) pathway. Given that acquired resistance to vismodegib may occur as a result of inappropriate PI3K pathway activation, we asked if loss of the PI3K pathway regulator, phosphatase and tensin homologue (Pten), which has been reported to occur in patients within the Hedgehog subgroup, would constitute a mechanism of innate resistance to vismodegib in Hedgehog-driven medulloblastoma. We find that Hedgehog pathway inhibition successfully restrains growth of Pten-deficient medulloblastoma in this mouse model, but does not drive tumor regression, as it does in Pten-wild-type medulloblastoma. Combined inhibition of the Hedgehog and PI3K pathways may lead to superior antitumor activity in PTEN-deficient medulloblastoma in the clinic. Cancer Res; 73(23); 7034–42. ©2013 AACR.
Prospective Study of Potentially Virulent Strains of <i>Helicobacter pylori</i> and Coronary Heart Disease in Middle-Aged Men
Authors: Peter Whincup, John Danesh, Mary Walker, Lucy Lennon, Andrew Thomson, Paul Appleby, Chris Hawkey, John Atherton
Journal: Circulation (2000)

Background —Studies are needed to test claims that potentially virulent strains of Helicobacter pylori are more strongly related to coronary heart disease (CHD) than are other strains. Methods and Results —We measured serum IgG antibodies to mixed H pylori antigens and separately to the virulence-associated H pylori antigen CagA (cytotoxin-associated gene product A) in 505 CHD cases and in 1025 age-matched controls “nested” in a prospective study of 7735 British men (mean duration of follow-up in controls, 16 years). Of the 505 cases, 401 (79%) were seropositive for H pylori antibodies compared with 740 (72%) of the 1025 controls, yielding an odds ratio for CHD of 1.55 (95% CI 1.19 to 2.03), which fell to 1.30 (95% CI 0.88 to 1.90) after adjustments were made for standard vascular risk factors and indicators of socioeconomic status. Of the CHD cases, 240 (48%) were seropositive for IgG antibodies to CagA compared with 450 (44%) of the controls. When CagA-seropositive individuals were compared with H pylori –seronegative individuals, the odds ratio for CHD was 1.42 (95% CI 1.06 to 1.91), which fell to 1.10 (95% CI 0.71 to 1.71) after adjustments. In an analysis restricted to the 1141 (75%) H pylori –seropositive participants, the odds ratio for CHD was 1.0 (95% CI 0.78 to 1.29) in CagA–seropositive men. No strong associations were observed between H pylori seropositivity and blood lipids, blood pressure, markers of systemic inflammation, or plasma homocysteine. Conclusions — H pylori infection is not strongly related to the incidence of CHD in late middle-aged men, and CagA-positive strains appear to be no more strongly related to the disease than other strains. However, further studies are required to confirm or refute the existence of any moderate associations, particularly at younger ages.
Toward a Fourth Generation of Disparities Research to Achieve Health Equity
Authors: Stephen B. Thomas, Sandra Crouse Quinn, James Butler, Craig S. Fryer, Mary A. Garza
Journal: Annual Review of Public Health (2011)

Achieving health equity, driven by the elimination of health disparities, is a goal of Healthy People 2020. In recent decades, the improvement in health status has been remarkable for the U.S. population as a whole. However, racial and ethnic minority populations continue to lag behind whites with a quality of life diminished by illness from preventable chronic diseases and a life span cut short by premature death. We examine a conceptual framework of three generations of health disparities research to understand (a) data trends, (b) factors driving disparities, and (c) solutions for closing the gap. We propose a new, fourth generation of research grounded in public health critical race praxis, utilizing comprehensive interventions to address race, racism, and structural inequalities and advancing evaluation methods to foster our ability to eliminate disparities. This new generation demands that we address the researcher's own biases as part of the research process.
High versus Low Blood-Pressure Target in Patients with Septic Shock
Authors: Pierre Asfar, Ferhat Meziani, Jean-François Hamel, Fabien Grelon, Bruno Megarbane, Nadia Anguel, Jean-Paul Mira, Pierre-François Dequin, Soizic Gergaud, Nicolas Weiss, François Legay, Yves Le Tulzo, Marie Conrad, René Robert, Frédéric Gonzalez, Christophe Guitton, Fabienne Tamion, Jean-Marie Tonnelier, Pierre Guezennec, Thierry Van Der Linden, Antoine Vieillard-Baron, Eric Mariotte, Gaël Pradel, Olivier Lesieur, Jean-Damien Ricard, Fabien Hervé, Damien du Cheyron, Claude Guerin, Alain Mercat, Jean-Louis Teboul, Peter Radermacher
Journal: New England Journal of Medicine (2014)

The Surviving Sepsis Campaign recommends targeting a mean arterial pressure of at least 65 mm Hg during initial resuscitation of patients with septic shock. However, whether this blood-pressure target is more or less effective than a higher target is unknown.In a multicenter, open-label trial, we randomly assigned 776 patients with septic shock to undergo resuscitation with a mean arterial pressure target of either 80 to 85 mm Hg (high-target group) or 65 to 70 mm Hg (low-target group). The primary end point was mortality at day 28.At 28 days, there was no significant between-group difference in mortality, with deaths reported in 142 of 388 patients in the high-target group (36.6%) and 132 of 388 patients in the low-target group (34.0%) (hazard ratio in the high-target group, 1.07; 95% confidence interval [CI], 0.84 to 1.38; P=0.57). There was also no significant difference in mortality at 90 days, with 170 deaths (43.8%) and 164 deaths (42.3%), respectively (hazard ratio, 1.04; 95% CI, 0.83 to 1.30; P=0.74). The occurrence of serious adverse events did not differ significantly between the two groups (74 events [19.1%] and 69 events [17.8%], respectively; P=0.64). However, the incidence of newly diagnosed atrial fibrillation was higher in the high-target group than in the low-target group. Among patients with chronic hypertension, those in the high-target group required less renal-replacement therapy than did those in the low-target group, but such therapy was not associated with a difference in mortality.Targeting a mean arterial pressure of 80 to 85 mm Hg, as compared with 65 to 70 mm Hg, in patients with septic shock undergoing resuscitation did not result in significant differences in mortality at either 28 or 90 days. (Funded by the French Ministry of Health; SEPSISPAM ClinicalTrials.gov number, NCT01149278.).
Acacetin, a Natural Flavone, Selectively Inhibits Human Atrial Repolarization Potassium Currents and Prevents Atrial Fibrillation in Dogs
Authors: Gui-Rong Li, Hong-Bing Wang, Guo-Wei Qin, Man-Wen Jin, Qiang Tang, Hai-Ying Sun, Xin-Ling Du, Xiu-Ling Deng, Xiao-Hua Zhang, Jing-Bo Chen, Lei Chen, Xiao-Hui Xu, Lik-Cheung Cheng, Shui-Wah Chiu, Hung-Fat Tse, Paul M. Vanhoutte, Chu-Pak Lau
Journal: Circulation (2008)

The development of atrium-selective antiarrhythmic agents is a current strategy for inhibiting atrial fibrillation (AF). The present study investigated whether the natural flavone acacetin from the traditional Chinese medicine Xuelianhua would be an atrium-selective anti-AF agent. The effects of acacetin on human atrial ultrarapid delayed rectifier K(+) current (I(Kur)) and other cardiac ionic currents were studied with a whole-cell patch technique. Acacetin suppressed I(Kur) and the transient outward K(+) current (IC(50) 3.2 and 9.2 mumol/L, respectively) and prolonged action potential duration in human atrial myocytes. The compound blocked the acetylcholine-activated K(+) current; however, it had no effect on the Na(+) current, L-type Ca(2+) current, or inward-rectifier K(+) current in guinea pig cardiac myocytes. Although acacetin caused a weak reduction in the hERG and hKCNQ1/hKCNE1 channels stably expressed in HEK 293 cells, it did not prolong the corrected QT interval in rabbit hearts. In anesthetized dogs, acacetin (5 mg/kg) prolonged the atrial effective refractory period in both the right and left atria 1 to 4 hours after intraduodenal administration without prolongation of the corrected QT interval, whereas sotalol at 5 mg/kg prolonged both the atrial effective refractory period and the corrected QT interval. Acacetin prevented AF induction at doses of 2.5 mg/kg (50%), 5 mg/kg (85.7%), and 10 mg/kg (85.7%). Sotalol 5 mg/kg also prevented AF induction (60%). The present study demonstrates that the natural compound acacetin is an atrium-selective agent that prolongs the atrial effective refractory period without prolonging the corrected QT interval and effectively prevents AF in anesthetized dogs after intraduodenal administration. These results indicate that oral acacetin is a promising atrium-selective agent for the treatment of AF.
Medical Charities Collection
Authors: R. C. Smith
Journal: BMJ (1971)

nize these deficiencies, and that they will press very hard for the development of academic departments in the next quinquennium.Once the demands from the medical schools have been recognized the University Grants Committee will have to act, and we can then hope for an adequate response from the Treasury and Government.In the mean- time, it is up to the heads of the profession to sustain the pressure and reiterate our case vigorously on all suitable occasions.-Iam, etc.,