tbuckley/cabot-search huggingface dataset:
A comparison of two molecular methods for diagnosing leptospirosis from three different sample types in patients presenting with fever in Laos
Authors: K. Woods, C. Nic-Fhogartaigh, C. Arnold, L. Boutthasavong, W. Phuklia, C. Lim, A. Chanthongthip, S.M. Tulsiani, S.B. Craig, M.-A. Burns, S.L. Weier, V. Davong, S. Sihalath, D. Limmathurotsakul, D.A.B. Dance, N. Shetty, M. Zambon, P.N. Newton, S. Dittrich
Journal: Clinical Microbiology and Infection (2017)

To compare two molecular assays (rrs quantitative PCR (qPCR) versus a combined 16SrRNA and LipL32 qPCR) on different sample types for diagnosing leptospirosis in febrile patients presenting to Mahosot Hospital, Vientiane, Laos.Serum, buffy coat and urine samples were collected on admission, and follow-up serum ∼10 days later. Leptospira spp. culture and microscopic agglutination tests (MAT) were performed as reference standards. Bayesian latent class modelling was performed to estimate sensitivity and specificity of each diagnostic test.In all, 787 patients were included in the analysis: 4/787 (0.5%) were Leptospira culture positive, 30/787 (3.8%) were MAT positive, 76/787 (9.7%) were rrs qPCR positive and 20/787 (2.5%) were 16SrRNA/LipL32 qPCR positive for pathogenic Leptospira spp. in at least one sample. Estimated sensitivity and specificity (with 95% CI) of 16SrRNA/LipL32 qPCR on serum (53.9% (33.3%-81.8%); 99.6% (99.2%-100%)), buffy coat (58.8% (34.4%-90.9%); 99.9% (99.6%-100%)) and urine samples (45.0% (27.0%-66.7%); 99.6% (99.3%-100%)) were comparable with those of rrs qPCR, except specificity of 16SrRNA/LipL32 qPCR on urine samples was significantly higher (99.6% (99.3%-100%) vs. 92.5% (92.3%-92.8%), p <0.001). Sensitivities of MAT (16% (95% CI 6.3%-29.4%)) and culture (25% (95% CI 13.3%-44.4%)) were low. Mean positive Cq values showed that buffy coat samples were more frequently inhibitory to qPCR than either serum or urine (p <0.001).Serum and urine are better samples for qPCR than buffy coat, and 16SrRNA/LipL32 qPCR performs better than rrs qPCR on urine. Quantitative PCR on admission is a reliable rapid diagnostic tool, performing better than MAT or culture, with significant implications for clinical and epidemiological investigations of this global neglected disease.
Authors of US dermatology guidelines did not declare conflicts of interest
Authors: Jacqui Wise
Journal: BMJ (2017)

Doctors who wrote US dermatology guidelines received sizeable industry payments and did not fully disclose them, according to an analysis published in JAMA Dermatology .1

The study authors say the findings raise worries about potential financial conflicts of interest in the dermatology guideline development process.

Before the Affordable Care Act was passed in 2010, any financial ties that doctors had to industry were only apparent through self disclosure, but now all industry payments of more than $10 (£7.58; €8.5) are publicly available on the Open Payments …
Differential binding affinity of mutated peptides for MHC class I is a predictor of survival in advanced lung cancer and melanoma
Authors: E. Ghorani, R. Rosenthal, N. McGranahan, J.L. Reading, M. Lynch, K.S. Peggs, C. Swanton, S.A. Quezada
Journal: Annals of Oncology (2017)

Cancer mutations generate novel (neo-)peptides recognised by T cells, but the determinants of recognition are not well characterised. The difference in predicted class I major histocompatibility complex (MHC-I) binding affinity between wild-type and corresponding mutant peptides (differential agretopicity index; DAI) may reflect clinically relevant cancer peptide immunogenicity. Our aim was to explore the relationship between DAI, measures of immune infiltration and patient outcomes in advanced cancer.
R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma
Authors: Thierry Lamy, Gandhi Damaj, Pierre Soubeyran, Emmanuel Gyan, Guillaume Cartron, Krimo Bouabdallah, Rémy Gressin, Jérôme Cornillon, Anne Banos, Katell Le Du, Mohamed Benchalal, Marie-Pierre Moles, Steven Le Gouill, Joel Fleury, Pascal Godmer, Hervé Maisonneuve, Eric Deconinck, Roch Houot, Kamel Laribi, Jean Pierre Marolleau, Olivier Tournilhac, Bernard Branger, Anne Devillers, Jean Philippe Vuillez, Thierry Fest, Philippe Colombat, Valérie Costes, Vanessa Szablewski, Marie C. Béné, Vincent Delwail
Journal: Blood (2017)
Targeting the Lysosome for Cancer Therapy
Authors: Christina G. Towers, Andrew Thorburn
Journal: Cancer Discovery (2017)

Abstract Summary: Lysosomes are the recycling centers of the cell where organelles and proteins are degraded during autophagy and macropinocytosis; they also serve as signaling hubs that control the activity of mTORC1. In this issue, Rebecca and colleagues report the development of a new type of lysosomal inhibitor for cancer therapy that can inhibit multiple lysosomal activities that are needed for tumor cell survival and growth. Cancer Discov; 7(11); 1218–20. ©2017 AACR. See related article by Rebecca et al., p. 1266.
Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor Therapy
Authors: Gregory P. Hess, Pradeep Natarajan, Kamil F. Faridi, Anna Fievitz, Linda Valsdottir, Robert W. Yeh
Journal: Circulation (2017)

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are a novel class of medications for patients with familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease requiring additional lipid lowering beyond dietary measures and statin use. Because of the drugs' high cost, rates of prescription approval by payers may be low. We aimed to identify payer approval and rejection rates for PCSK9i prescriptions and the potential factors influencing these rates.This is a retrospective, descriptive cohort study using nationwide pharmacy claims linked to electronic medical records from a nationwide data warehouse. The data set includes >220 million patients from all 50 states and all payer types with 5140 distinct health plans. PCSK9i prescriptions were submitted for 51 466 patients in the pharmacy data set. The main outcome was approval or rejection of PCSK9i prescription claims. Factors associated with approval and rejection of these medications in the United States were assessed.Among patients who were prescribed a PCSK9i, 47.0% were approved for coverage by the payer. Variables that were associated with PCSK9i approval included age >65 years (P<0.01), history of atherosclerotic cardiovascular disease (P<0.01), prescription by a cardiologist or nonprimary care provider (P<0.01), statin intolerance (P=0.03), longer statin duration (P=0.01), and noncommercial payers (P<0.01). Higher low-density lipoprotein cholesterol levels were not associated with higher approval rates. Commercial third-party payers had the lowest approval rates (24.4%) and Medicare had the highest (60.9%).Rates of approval for PCSK9i therapy are low, even for patients who appear to meet labeled indications. Although a combination of clinical characteristics increases the likelihood of approval, payer type is the most significant factor.
Abstract #4377: Inhibition of Tumor Growth by 15-Lipoxygenase-2 through inactivation of PDGF pathway
Authors: Xiangyang Bai, Hong Wu, Dian Wang
Journal: Cancer Research (2009)

15-LOX-2 has been considered as a tumor suppressor in many epithelium-derived cancer including carcinoma of prostate, esophagus, and head and neck. However, the molecular mechanism for the tumor inhibition by 15-LOX-2 remains to be unclear In this study, we generated lentiviral 15-LOX-2 expression vector and then examined the expression profiles of 84 genes that are commonly involved in cancer metastasis, cell cycle, adhesion, signal transduction and angiogenesis in prostate cancer cells LNCaP and PC3 transfected with the 15-LOX-2 expression vector. We identified significant downregulation of PDGF-A. This observation was further confirmed by Q-PCR and Western blot analysis. Knockdown of PDGF-A expression by its specific inhibitor siRNA produced a similar degree of growth inhibition to that by 15-LOX-2 expression in the above cells. Addition of functional PDGF-A protein attenuated the growth inhibition by 15-LOX-2. Furthermore, we have evaluated the key intermediates (ERK and AKT) of the MAPK pathway and PI3K pathway, which are well-known downstream pathways of PDGF. We noted significant downregulations of phospharylated ERK and AKT in the cells transfected with 15-LOX-2 expression vector. Finally we observed a significant reduction of nuclear transfection factor PPAP\#947; in the cells containing 15-LOX-2 expression vector. All together, our results suggested that 15-LOX-2 inhibited tumor growth of prostate cancer cells, at least partially, through inactivation of PDGF-A pathway.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4377.
Spatial and Temporal Scales of Range Expansion in Wild Phaseolus vulgaris
Authors: Andrea Ariani, Jorge Carlos Berny Mier y Teran, Paul Gepts
Journal: Molecular Biology and Evolution (2017)

The wild progenitor of common-bean has an exceptionally large distribution from northern Mexico to northwestern Argentina, unusual among crop wild progenitors. This research sought to document major events of range expansion that led to this distribution and associated environmental changes. Through the use of genotyping-by-sequencing (∼20,000 SNPs) and geographic information systems applied to a sample of 246 accessions of wild Phaseolus vulgaris, including 157 genotypes of the Mesoamerican, 77 of the southern Andean, and 12 of the Northern Peru-Ecuador gene pools, we identified five geographically distinct subpopulations. Three of these subpopulations belong to the Mesoamerican gene pool (Northern and Central Mexico, Oaxaca, and Southern Mexico, Central America and northern South America) and one each to the Northern Peru-Ecuador (PhI) and the southern Andean gene pools. The five subpopulations were distributed in different floristic provinces of the Neotropical seasonally dry forest and showed distinct distributions for temperature and rainfall resulting in decreased local potential evapotranspiration (PhI and southern Andes groups) compared with the two Mexican groups. Three of these subpopulations represent long-distance dispersal events from Mesoamerica into Northern Peru-Ecuador, southern Andes, and Central America and Colombia, in chronological order. Of particular note is that the dispersal to Northern Peru-Ecuador markedly predates the dispersal to the southern Andes (∼400 vs. ∼100 ky), consistent with the ancestral nature of the phaseolin seed protein and chloroplast sequences observed in the PhI group. Seed dispersal in common bean can be, therefore, described at different spatial and temporal scales, from localized, annual seed shattering to long-distance, evolutionarily rare migration.
Glucocorticoid resistance is reverted by LCK inhibition in pediatric T-cell acute lymphoblastic leukemia
Authors: Valentina Serafin, Giorgia Capuzzo, Gloria Milani, Sonia Anna Minuzzo, Marica Pinazza, Roberta Bortolozzi, Silvia Bresolin, Elena Porcù, Chiara Frasson, Stefano Indraccolo, Giuseppe Basso, Benedetta Accordi
Journal: Blood (2017)
Management and long-term outcomes of sarcoidosis-associated pulmonary hypertension
Authors: Athénaïs Boucly, Vincent Cottin, Hilario Nunes, Xavier Jaïs, Abdelatif Tazi, Grégoire Prévôt, Martine Reynaud-Gaubert, Claire Dromer, Catherine Viacroze, Delphine Horeau-Langlard, Christophe Pison, Emmanuel Bergot, Julie Traclet, Jason Weatherald, Gérald Simonneau, Dominique Valeyre, David Montani, Marc Humbert, Olivier Sitbon, Laurent Savale
Journal: European Respiratory Journal (2017)

Studies reporting the effects of modern strategies with pulmonary arterial hypertension (PAH)-targeted therapies in sarcoidosis-associated pulmonary hypertension (S-APH) are limited. Clinical and haemodynamic data from newly diagnosed patients with severe S-APH (mean pulmonary artery pressure (mPAP) &gt;35 mmHg or mPAP 25–35 mmHg with cardiac index &lt;2.5 L·min −1 ·m −2 ) were collected from the French Pulmonary Hypertension Registry between 2004 and 2015. Data from 126 patients with severe S-APH were analysed (mean± sd age 57.5±11.6 years, 74% radiological stage IV). 97 patients (77%) received PAH-targeted therapy and immunosuppressive therapy was initiated or escalated in 33 patients at the time of pulmonary hypertension diagnosis. Four months after PAH-targeted therapy initiation, mean± sd pulmonary vascular resistance decreased from 9.7±4.4 to 6.9±3.0 Wood units (p&lt;0.001), without significant improvement in exercise capacity. Among the 11 patients treated only with immunosuppressive therapy, a haemodynamic improvement was observed in four patients, including two with compressive lymph nodes. After a median follow-up of 28 months, 39 patients needed PAH-targeted therapy escalation, nine underwent lung transplantation and 42 had died. Survival at 1, 3 and 5 years was 93%, 74% and 55%, respectively. PAH-targeted therapy improved short-term pulmonary haemodynamics in severe S-APH without change in exercise capacity. Immunosuppressive therapy improved haemodynamics in selected patients. Pulmonary hypertension in sarcoidosis remains associated with a poor prognosis.
Abstract 12228: Understanding the Gender Gap in Patients Undergoing Atrial Fibrillation Ablation: Women Delay Ablation Until Functionally Limited and Symptoms Are Severe
Authors: Lauren E Bolger, Amith Mandavilli, Samuel F Sears, James P Hummel, Eugene H Chung, J P Mounsey, Anil K Gehi
Journal: Circulation (2016)

Introduction: The incidence of atrial fibrillation (AF) is nearly equivalent in men and women. Yet, existing literature indicates a gender gap in patients with atrial fibrillation presenting for ablation. We examine this discrepancy among patients undergoing AF ablation at The University of North Carolina hospital. Hypothesis: We hypothesized that gender differences in AF symptoms and functional capacity could account for the gender gap in patients undergoing AF ablation. Methods: A study of 178 consecutive patients presenting for AF ablation was conducted between October 2014 and May 2015. Prior to undergoing ablation, consenting patients completed the Duke Activity Status Index (DASI) evaluating functional capacity and the Atrial Fibrillation Effect on Quality-of-Life Questionnaire Tool (AFEQT) assessing AF-specific quality of life, symptom severity, treatment concern, and daily activities. Questionnaire data was analyzed with baseline demographics and comorbidities for gender differences. Results: Of 178 patients completing the baseline questionnaire, the proportion of men pursuing ablation (n=129, 72.5%) largely outweighed that of women (n=49, 27.5%). There were no gender differences in baseline demographics with the exception of significantly higher prevalence of obstructive sleep apnea (p&lt;0.001) and persistent AF in men (p&lt;0.05). Women presented for AF ablation with significantly lower functional capacity (p&lt;0.001), higher AF symptom severity (p&lt;0.05) and lower overall AF quality of life (p&lt;0.05) in comparison to men (Table). Conclusions: Our findings suggest that women do not present for AF ablation until symptoms are severe and functional capacity is low, likely contributing to the gender gap in AF ablation referrals. Whether this disparity is due to patient or provider factors requires further evaluation. Education of patients and providers regarding the potential efficacy and risks of ablation may help to bridge this gender gap.
TCT-273 Comparison of Silent Cerebral İnfarct Between Right Versus Left Radial Approach in Elective Percutaneous Coronary Intervention/Coronary Angiography
Authors: Hüseyin Göksülük, Sadi Gulec, Yusuf Atmaca, Cansın Kaya, Başar Candemir, Nil Özyüncü, seda kürklü, Çetin Erol
Journal: Journal of the American College of Cardiology (2017)
Receipt of Selected Preventive Health Services for Women and Men of Reproductive Age — United States, 2011–2013
Authors: Karen Pazol, Cheryl L. Robbins, Lindsey I. Black, Katherine A. Ahrens, Kimberly Daniels, Anjani Chandra, Anjel Vahratian, Lorrie E. Gavin
Journal: MMWR Surveillance Summaries (2017)

Receipt of key preventive health services among women and men of reproductive age (i.e., 15-44 years) can help them achieve their desired number and spacing of healthy children and improve their overall health. The 2014 publication Providing Quality Family Planning Services: Recommendations of CDC and the U.S. Office of Population Affairs (QFP) establishes standards for providing a core set of preventive services to promote these goals. These services include contraceptive care for persons seeking to prevent or delay pregnancy, pregnancy testing and counseling, basic infertility services for those seeking to achieve pregnancy, sexually transmitted disease (STD) services, and other preconception care and related preventive health services. QFP describes how to provide these services and recommends using family planning and other primary care visits to screen for and offer the full range of these services. This report presents baseline estimates of the use of these preventive services before the publication of QFP that can be used to monitor progress toward improving the quality of preventive care received by women and men of reproductive age.
Abstract 20055: Etiology of Atrial Fibrillation Recurrence After Previous Successful Pulmonary Vein Isolation With Cryoablation; A Two-center Review of Redo AF Ablation Data
Authors: John Harding, Robert Sangrigoli, Muhanad Al-Zubaidi, Andrew Williams, Roger Tseng, Wilber Su
Journal: Circulation (2016)

Background: Cryoballoon ablation has been effective in treating atrial fibrillation (AF) with high rate of pulmonary vein isolation (PVI). Repeat ablation for failed prior cryoballoon PVI may revea...
International management platform for children’s interstitial lung disease (chILD-EU)
Authors: Matthias Griese, Elias Seidl, Meike Hengst, Simone Reu, Hans Rock, Gisela Anthony, Nural Kiper, Nagehan Emiralioğlu, Deborah Snijders, Lutz Goldbeck, Reiner Leidl, Julia Ley-Zaporozhan, Ingrid Krüger-Stollfuss, Birgit Kammer, Traudl Wesselak, Claudia Eismann, Andrea Schams, Doerthe Neuner, Morag MacLean, Andrew G Nicholson, McCann Lauren, Annick Clement, Ralph Epaud, Jacques de Blic, Michael Ashworth, Paul Aurora, Alistair Calder, Martin Wetzke, Matthias Kappler, Steve Cunningham, Nicolaus Schwerk, Andy Bush
Journal: Thorax (2017)

Background Children’s interstitial lung diseases (chILD) cover many rare entities, frequently not diagnosed or studied in detail. There is a great need for specialised advice and for internationally agreed subclassification of entities collected in a register. Our objective was to implement an international management platform with independent multidisciplinary review of cases at presentation for long-term follow-up and to test if this would allow for more accurate diagnosis. Also, quality and reproducibility of a diagnostic subclassification system were assessed using a collection of 25 complex chILD cases. Methods A web-based chILD management platform with a registry and biobank was successfully designed and implemented. Results Over a 3-year period, 575 patients were included for observation spanning a wide spectrum of chILD. In 346 patients, multidisciplinary reviews were completed by teams at five international sites (Munich 51%, London 12%, Hannover 31%, Ankara 1% and Paris 5%). In 13%, the diagnosis reached by the referring team was not confirmed by peer review. Among these, the diagnosis initially given was wrong (27%), imprecise (50%) or significant information was added (23%). The ability of nine expert clinicians to subcategorise the final diagnosis into the chILD-EU register classification had an overall exact inter-rater agreement of 59% on first assessment and after training, 64%. Only 10% of the ‘wrong’ answers resulted in allocation to an incorrect category. Subcategorisation proved useful but training is needed for optimal implementation. Conclusions We have shown that chILD-EU has generated a platform to help the clinical assessment of chILD. Trial registration number Results, NCT02852928 .
Prediction of Type 2 Diabetes by Hemoglobin A1c in Two Community-Based Cohorts
Authors: Aaron Leong, Natalie Daya, Bianca Porneala, James J. Devlin, Dov Shiffman, Michael J. McPhaul, Elizabeth Selvin, James B. Meigs
Journal: Diabetes Care (2017)

Hemoglobin A1c (HbA1c) can be used to assess type 2 diabetes (T2D) risk. We asked whether HbA1c was associated with T2D risk in four scenarios of clinical information availability: 1) HbA1c alone, 2) fasting laboratory tests, 3) clinic data, and 4) fasting laboratory tests and clinic data.We studied a prospective cohort of white (N = 11,244) and black (N = 2,294) middle-aged participants without diabetes in the Framingham Heart Study and Atherosclerosis Risk in Communities study. Association of HbA1c with incident T2D (defined by medication use or fasting glucose [FG] ≥126 mg/dL) was evaluated in regression models adjusted for 1) age and sex (demographics); 2) demographics, FG, HDL, and triglycerides; 3) demographics, BMI, blood pressure, and T2D family history; or 4) all preceding covariates. We combined results from cohort and race analyses by random-effects meta-analyses. Subsidiary analyses tested the association of HbA1c with developing T2D within 8 years or only after 8 years.Over 20 years, 3,315 individuals developed T2D. With adjustment for demographics, the odds of T2D increased fourfold for each percentage-unit increase in HbA1c. The odds ratio (OR) was 4.00 (95% CI 3.14, 5.10) for blacks and 4.73 (3.10, 7.21) for whites, resulting in a combined OR of 4.50 (3.35, 6.03). After adjustment for fasting laboratory tests and clinic data, the combined OR was 2.68 (2.15, 3.34) over 20 years, 5.79 (2.51, 13.36) within 8 years, and 2.23 (1.94, 2.57) after 8 years.HbA1c predicts T2D in different common scenarios and is useful for identifying individuals with elevated T2D risk in both the short- and long-term.