tbuckley/cabot-search huggingface dataset:
Serum metabolites detect the presence of advanced fibrosis in derivation and validation cohorts of patients with non-alcoholic fatty liver disease
Authors: Cyrielle Caussy, Veeral H Ajmera, Puneet Puri, Cynthia Li-Shin Hsu, Shirin Bassirian, Mania Mgdsyan, Seema Singh, Claire Faulkner, Mark A Valasek, Emily Rizo, Lisa Richards, David A Brenner, Claude B Sirlin, Arun J Sanyal, Rohit Loomba
Journal: Gut (2018)

Non-invasive and accurate diagnostic tests for the screening of disease severity in non-alcoholic fatty liver disease (NAFLD) remain a major unmet need. Therefore, we aimed to examine if a combination of serum metabolites can accurately predict the presence of advanced fibrosis.This is a cross-sectional analysis of a prospective derivation cohort including 156 well-characterised patients with biopsy-proven NAFLD and two validation cohorts, including (1) 142 patients assessed using MRI elastography (MRE) and(2) 59 patients with biopsy-proven NAFLD with untargeted serum metabolome profiling.In the derivation cohort, 23 participants (15%) had advanced fibrosis and 32 of 652 analysed metabolites were significantly associated with advanced fibrosis after false-discovery rate adjustment. Among the top 10 metabolites, 8 lipids (5alpha-androstan-3beta monosulfate, pregnanediol-3-glucuronide, androsterone sulfate, epiandrosterone sulfate, palmitoleate, dehydroisoandrosterone sulfate, 5alpha-androstan-3beta disulfate, glycocholate), one amino acid (taurine) and one carbohydrate (fucose) were identified. The combined area under the receiver operating characteristic curve (AUROC) of the top 10 metabolite panel was higher than FIB--4 and NAFLD Fibrosis Score (NFS) for the detection of advanced fibrosis: 0.94 (95% CI 0.897 to 0.982) versus 0.78 (95% CI0.674 to 0.891), p=0.002 and versus 0.84 (95% CI 0.724 to 0.929), p=0.017, respectively. The AUROC of the top 10 metabolite panel remained excellent in the independent validation cohorts assessed by MRE or liver biopsy: c-statistic of 0.94 and 0.84, respectively.A combination of 10 serum metabolites demonstrated excellent discriminatory ability for the detection of advanced fibrosis in an derivation and two independent validation cohorts with greater diagnostic accuracy than the FIB-4-index and NFS. This proof-of-concept study demonstrates that a non-invasive blood-based diagnostic test can provide excellent performance characteristics for the detection of advanced fibrosis.
Durable Remission Achieved from Bcma-Directed CAR-T Therapy Against Relapsed or Refractory Multiple Myeloma
Authors: Yarong Liu, Zhi Chen, Hongliang Fang, Runhong Wei, Kang Yu, Songfu Jiang, Weijun Fu, Hua Jiang, Juan Du, Feng He, Ronglin Xie, Jing Chen, Baofeng Wei, Jin Tao, Pin Wang
Journal: Blood (2018)
Smoking, but not alcohol, is associated with risk of psoriasis in a Taiwanese population-based cohort study
Authors: Ying-Xiu Dai, Shih-Chun Wang, Yiing-Jenq Chou, Yun-Ting Chang, Tzeng-Ji Chen, Chung-Pin Li, Chen-Yi Wu
Journal: Journal of the American Academy of Dermatology (2018)
Abstract P297: Long-Term Benefit Comparison of Absolute Risk Reduction versus Absolute Risk to Prioritize Statin Therapy
Authors: Ciaran N Kohli-Lynch, Andrew E Moran, George Thanassoulis, Allan D Sniderman, Yiyi Zhang, Michael Pencina, Mark J Pletcher, Eric Vittinghoff
Journal: Circulation (2018)

Introduction: Individuals with no established cardiovascular disease (CVD) are currently recommended preventive statin therapy based on 10-year absolute risk (AR) of CVD, and individuals with a 10-year AR ≥7.5% are recommended statins. However, individuals with elevated LDL cholesterol experience greater absolute CVD absolute risk reduction (ARR) from statin therapy compared with those with the same 10-year AR but with lower LDL. A previous study showed that ARR-based statin treatment would prevent more CVD events than AR-based treatment in the 10 years following treatment initiation. Objective: This study aimed to quantify the long-term benefits of treating patients based on ARR rather than AR. Methods: A microsimulation version of the CVD Policy Model, a decision-analytic state transition model, simulated intermediate-strength statin therapy in 40,000 CVD-free US adults (50% female) under a variety of treatment strategies. The model predicts health outcomes for individuals based on their age, sex, and risk factor profile, accounting for the competing risk of non-CVD mortality. Individuals entered the model aged 40 years, and a time horizon of 40 years was employed. Life year gains and CVD events prevented compared to no treatment were estimated for a range of 10-year ARR and AR treatment initiation thresholds. Results: At the same numbers of patient-years of treatment (PYoT), ARR consistently produced more life year gains than AR (Figure). A 10-year ARR threshold of ≥2.62% would lead to approximately the same PYoT as standard of care (10-year AR ≥7.5%) while preventing 60 additional CVD events and producing 421 additional life year gains in the cohort. Conclusion: Treating patients with statins based on ARR would yield significant health gains in the U.S. population compared to standard AR-based treatment strategies. The ARR strategy may also achieve greater adherence and uptake as it focuses on individuals with elevated levels of a modifiable risk factor.
Factors Associated With Successful Medication Discontinuation After a Randomized Clinical Trial of Relapse Prevention in First-Episode Psychosis
Authors: Christy L. M. Hui, William G. Honer, Edwin H. M. Lee, W. C. Chang, Sherry K. W. Chan, Eric Y. H. Chen
Journal: JAMA Psychiatry (2018)

This follow-up study of a randomized clinical trial examines a cohort of patients who had participated in the trial 10 years ago to establish what factors were associated with successful discontinuation of antipsychotic medication regimens.
The Anti-Trans Memo — Abandoning Doctors and Patients
Authors: Jocelyn Samuels, Mara Keisling
Journal: New England Journal of Medicine (2018)

A proposed redefinition of gender as a "biological, immutable condition determined by a person's genitalia at birth" would have damaging repercussions for vulnerable communities that have faced discrimination from health care providers, hospitals, insurers, and others.
Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo
Authors: Marc Aurel Busche, Susanne Wegmann, Simon Dujardin, Caitlin Commins, Julia Schiantarelli, Naomi Klickstein, Tarun V. Kamath, George A. Carlson, Israel Nelken, Bradley T. Hyman
Journal: Nature Neuroscience (2018)
Effects of sacubitril/valsartan on neprilysin targets and the metabolism of natriuretic peptides in chronic heart failure: a mechanistic clinical study
Authors: Hélène Nougué, Théo Pezel, François Picard, Malha Sadoune, Mattia Arrigo, Florence Beauvais, Jean‐Marie Launay, Alain Cohen‐Solal, Nicolas Vodovar, Damien Logeart
Journal: European Journal of Heart Failure (2018)
Functional Annotation of <i>TNNT2</i> Variants of Uncertain Significance With Genome-Edited Cardiomyocytes
Authors: Wenjian Lv, Lyon Qiao, Nataliya Petrenko, Wenjun Li, Anjali T. Owens, Chris McDermott-Roe, Kiran Musunuru
Journal: Circulation (2018)
Assessment of the Medicare Advantage Risk Adjustment Model for Measuring Veterans Affairs Hospital Performance
Authors: Todd H. Wagner, Peter Almenoff, Joseph Francis, Josephine Jacobs, Christine Pal Chee
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Policymakers and consumers are eager to compare hospitals on performance metrics, such as surgical complications or unplanned readmissions, measured from administrative data. Fair comparisons depend on risk adjustment algorithms that control for differences in case mix. <h3>Objective</h3> To examine whether the Medicare Advantage risk adjustment system version 21 (V21) adequately risk adjusts performance metrics for Veterans Affairs (VA) hospitals. <h3>Design, Setting, and Participants</h3> This cohort analysis of administrative data from all 5.5 million veterans who received VA care or VA-purchased care in 2012 was performed from September 8, 2015, to October 22, 2018. Data analysis was performed from January 22, 2016, to October 22, 2018. <h3>Exposures</h3> A patient's risk as measured by the V21 model. <h3>Main Outcomes and Measures</h3> The main outcome was total cost, and the key independent variable was the V21 risk score. <h3>Results</h3> Of the 5 472 629 VA patients (mean [SD] age, 63.0 [16.1] years; 5 118 908 [93.5%] male), the V21 model identified 694 706 as having a mental health or substance use condition. In contrast, a separate classification system for psychiatric comorbidities identified another 1 266 938 patients with a mental health condition. The V21 model missed depression not otherwise specified (396 062 [31.3%]), posttraumatic stress disorder (345 338 [27.3%]), and anxiety (129 808 [10.2%]). Overall, the V21 model underestimated the cost of care by $2314 (6.7%) for every person with a mental health diagnosis. <h3>Conclusions and Relevance</h3> The findings suggest that current aspirations to engender competition by comparing hospital systems may not be appropriate or fair for safety-net hospitals, including the VA hospitals, which treat patients with complex psychiatric illness. Without better risk scores, which is technically possible, outcome comparisons may potentially mislead consumers and policymakers and possibly aggravate inequities in access for such vulnerable populations.
A Global, Randomized, Placebo-Controlled, Phase 3 Study of Ibrutinib Plus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (RCHOP) in Patients with Previously Untreated Non-Germinal Center B-Cell-like (GCB) Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Anas Younes, Laurie H Sehn, Peter Johnson, Pier Luigi Zinzani, Xiaonan Hong, Jun Zhu, Olga Samoilova, Cheolwon Suh, Itaru Matsumura, Andres Lopez-Hernandez, Ulrich Dührsen, Catherine Thieblemont, Jodi Carey, Grace Liu, S. Martin Shreeve, Steven Sun, Jessica Vermeulen, Louis M. Staudt, Wyndham H. Wilson
Journal: Blood (2018)
Apixaban, Dalteparin, in Active Cancer Associated Venous Thromboembolism, the ADAM VTE Trial
Authors: Robert D. McBane, Waldemar E. Wysokinski, Jennifer Le-Rademacher, Aneel A. Ashrani, Alfonso J Tafur, Krishna Gundabolu, Juliana Perez-Botero, Usha Perepu, Daniel M. Anderson, Charles Kuzma, Roberto leon Ferre, Stanislav Henkin, Charles Lenz, Charles Loprinzi
Journal: Blood (2018)
Final Results of Phase I/II Study of Combination of Sorafenib, Vorinostat, and Bortezomib in Acute Myeloid Leukemia with FLT3-ITD Mutation or Poor-Risk Cytogenetics
Authors: Antoine N Saliba, H. Scott Boswell, Larry D Cripe, Mohammad Issam Abu Zaid, Jill Weisenbach, Hamid Sayar
Journal: Blood (2017)
Clinical Outcomes of Lentiglobin Gene Therapy for Transfusion-Dependent β-Thalassemia Following Completion of the Northstar HGB-204 Study
Authors: John E.J. Rasko, Alexis A. Thompson, Janet L. Kwiatkowski, Suradej Hongeng, Gary J. Schiller, Usanarat Anurathapan, Marina Cavazzana, P. Joy Ho, Manfred Schmidt, Morris Kletzel, Philippe Leboulch, Elliott Vichinsky, Briana Deary, Ying Chen, Mohammed Asmal, Mark C. Walters
Journal: Blood (2018)
Abstract 17287: Effect of Inhaled Nitric Oxide During LVAD-Based Resuscitation in Pigs: Echocardiography and Deformation Imaging Evaluation
Authors: Rashad Zayat, Andreas Ebeling, Nima Hatam, Christoph Nix, Anne Brücken, Gernot Marx, Rüdiger Autschbach, Matthias Derwall
Journal: Circulation (2017)

Introduction: We have previously shown that primary survival after cardiac arrest (CA) can be improved by optimizing circulation during CPR using a minimal invasive left ventricular assist device (Impella 2.5, iCPR). Whether inhaled nitric oxid (iNO) will improve protection of the right ventricle (RV) is still unknown. Hypothesis: iNO preserves RV-function following CA by increasing transpulmonary flow (TPF). Methods: Ventricular fibrillation (VF) was electrically induced in 6 anesthetized pigs. Animals were left untreated for 10 min before iCPR was attempted. 3 pigs (iNO) had iNO starting 30 min post ROSC. In addition to invasive hemodynamic monitoring, all animals received transesophageal echocardiography at baseline, during untreated cardiac arrest, at the initiation of iCPR, 30 min, and 5 h following ROSC. Results: LV unloading was sufficient in both groups (LV-end-diastolic volume (mL): baseline and 5h after ROSC: iNO group: 58.4±8.4, 62.7±12.2; Control: 48.3±6.2, 52.9±7.6) (Fig. 1a). Preservation of...
Improvements in Histologic Features and Diagnosis Associated With Improvement in Fibrosis in Nonalcoholic Steatohepatitis: Results From the Nonalcoholic Steatohepatitis Clinical Research Network Treatment Trials
Authors: Elizabeth M. Brunt, David E. Kleiner, Laura A. Wilson, Arun J. Sanyal, Brent A. Neuschwander‐Tetri
Journal: Hepatology (2018)

Hepatocellular injury and inflammation are believed to be the primary drivers of fibrogenesis that ultimately lead to cirrhosis in patients with nonalcoholic steatohepatitis (NASH). This study sought associations between observed improvements in fibrosis with improvement in specific histologic features, nonalcoholic fatty liver disease activity score (NAS) ≥2, diagnostic category, and primary histologically based outcomes of two adult NASH treatment trials. The primary outcome for the study was fibrosis improvement from baseline to end of treatment, defined as a 1‐point or more improvement in fibrosis stage. This is a retrospective analysis of biopsy data collected from the NASH Clinical Research Network Pathology Committee of Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with NASH Trial (PIVENS) and Farnesoid X Receptor Ligand Obeticholic Acid in NASH Treatment Trial (FLINT) baseline and final biopsies. Treatment group–adjusted univariable and multivariable logistic regression models related improvement in fibrosis to improvements in other histologic variables, resolution of steatohepatitis, and improvement in the NAS ≥2. In PIVENS 221 subjects had baseline and 96‐week biopsies, and in FLINT 200 subjects had baseline and 72‐week biopsies. Improvement in fibrosis was found in 38% of PIVENS and 29% of FLINT biopsies; fibrosis improvement was more likely in treated than placebo subjects in both studies. Controlling for treatment group, fibrosis improvement was associated most strongly with resolution of NASH (PIVENS, odds ratio [OR], 3.9; 95% confidence interval [CI] 2.0‐7.6; P &lt; 0.001; FLINT, OR, 8.0; 95% CI 3.1‐20.9; P &lt; 0.001), and improved NAS by ≥2 (PIVENS, OR, 2.4; 95% CI 1.3‐4.3; P = 0.003; FLINT, OR, 4.2; 95% CI 2.1‐8.3; P &lt; 0.001). Improvement in histologic features associated with improved fibrosis for both studies included steatosis, ballooning, Mallory‐Denk bodies, and portal, but not lobular, inflammation. Conclusion: These findings support a strong link between histologic resolution of steatohepatitis with improvement in fibrosis in NASH.
STAT1 gain-of-function compromises skin host defense in the context of IFN-γ signaling
Authors: Hanna Niehues, Berenice Rösler, Danique A. van der Krieken, Ivonne M.J.J. van Vlijmen-Willems, Diana Rodijk-Olthuis, Malou Peppelman, Joost Schalkwijk, Ellen H.J. van den Bogaard, Patrick L.J.M. Zeeuwen, Frank L. van de Veerdonk
Journal: Journal of Allergy and Clinical Immunology (2018)
Targeting human CD141+ DC using CLEC9A antibodies for cancer immunotherapy
Authors: K.-A. Masterman, F.E. Pearson, K. Tullett, O. Haigh, C. Walpole, G. Daraj, M.H. Lahoud, I. Leal Rojas, K. Radford
Journal: Annals of Oncology (2018)

Background: Dendritic cells (DC) are a heterogeneous cell population, with specialist subtypes driving specific immune responses. In mice, the cDC1 subset (also referred to as Batf3-dependent DC, XCR1+ DC, CD8+ DC in lymphoid tissues and CD103+ DC in peripheral tissues) is essential for the induction of tumour immune responses and for the efficacy of checkpoint inhibitor blockade and adoptive T cell immunotherapies. Vaccines that can deliver antigens (Ag) directly to DCs in vivo are more effective than cell-based therapies in mouse models and are promising approaches to translate to humans. CD141+ DC are the human cDC1 equivalent and specifically express the C-type lectin-like receptor CLEC9A, that facilitates cross-presentation of dead cell Ag. Targeting tumour-associated Ag (TAA) to human CD141+ DC using CLEC9A antibody (Ab) is therefore an attractive strategy to induce or boost tumour immune responses. Methods: NYESO1 and WT1 are well characterised, highly immunogenic TAA expressed by a broad array of tumour types. We developed recombinant human chimaeric IgG4 Ab specific for human CLEC9A genetically fused to NYESO1 or WT1. For comparison we developed TAA fusions with chimaeric IgG4 Ab specific for human DEC-205, which is expressed by many human leukocytes, and β-galactosidase as an irrelevant isotype control. CLEC9A-NYESO1 and CLEC9A-WT1 Abs retained their binding specificity for CD141+ DC. Following uptake of CLEC9A-WT1, CD141+ DC cross-presented a WT-1 HLA-A24-restricted epitope for recognition by specific CD8+ cytotoxic T cells. Likewise, a HLA-A2-restricted NYESO1 epitope was cross-presented Ag specific CD8+ T cells by CD141+ DC following uptake of CLEC9A-NYESO1. Results: For both TAA, the CLEC9A Abs were more efficient at delivery of Ag for cross-presentation than DEC-205 or isotype control Abs. Moreover, using a humanised mouse model in which functional human CD141+ DC and Ag-specific T cells develop, CLEC9A-TAA Ab induced priming of Ag-specific T cells. Conclusions: Our data advocate further development of human CLEC9A targeting Abs as cancer vaccines. Legal entity responsible for the study: Mater Research Institute. Funding: Department of Defense, USA. Disclosure: All authors have declared no conflicts of interest.
P086 Toward the Standardization of Bioinformatics Methods for the Accurate Assessment of Tumor Mutational Burden (TMB)
Authors: H. Chang, S. Srinivasan, A. Sasson, R. Golhar, D. Greenawalt, S. Kirov, J. Szustakowski, V. Ip
Journal: Journal of Thoracic Oncology (2018)
Long-Term Exposure to Ultrafine Particles and Incidence of Cardiovascular and Cerebrovascular Disease in a Prospective Study of a Dutch Cohort
Authors: George S. Downward, Erik J.H.M. van Nunen, Jules Kerckhoffs, Paolo Vineis, Bert Brunekreef, Jolanda M.A. Boer, Kyle P. Messier, Ananya Roy, W. Monique M. Verschuren, Yvonne T. van der Schouw, Ivonne Sluijs, John Gulliver, Gerard Hoek, Roel Vermeulen
Journal: Environmental Health Perspectives (2018)

Background: There is growing evidence that exposure to ultrafine particles (UFP; particles smaller than 100 nm) may play an underexplored role in the etiology of several illnesses, including cardiovascular disease (CVD). Objectives: We aimed o investigate the relationship between long-term exposure to ambient UFP and incident cardiovascular and cerebrovascular disease (CVA). As a secondary objective, we sought to compare effect estimates for UFP with those derived for other air pollutants, including estimates from two-pollutant models. Methods: Using a prospective cohort of 33,831 Dutch residents, we studied the association between long-term exposure to UFP (predicted via land use regression) and incident disease using Cox proportional hazard models. Hazard ratios (HR) for UFP were compared to HRs for more routinely monitored air pollutants, including particulate matter with aerodynamic diameter ≤10μm (PM10), PM with aerodynamic diameter ≤2.5 (PM2.5), and NO2. Results: Long-term UFP exposure was associated with an increased risk for all incident CVD [HR=1.18 per 10,000 particles/cm3; 95% confidence interval (CI): 1.03, 1.34], myocardial infarction (MI) (HR=1.34; 95% CI: 1.00, 1.79), and heart failure (HR=1.76; 95% CI: 1.17, 2.66). Positive associations were also estimated for NO2 (HR for heart failure=1.22; 95% CI: 1.01, 1.48 per 20 μg/m3) and coarse PM (PMcoarse; HR for all CVD=1.21; 95% CI: 1.01, 1.45 per 10 μg/m3). CVD was not positively associated with PM2.5 (HR for all CVD=0.95; 95% CI: 0.75, 1.28 per 5 μg/m3). HRs for UFP and CVAs were positive, but not significant. In two-pollutant models (UFP+NO2 and UFP+PMcoarse), positive associations tended to remain for UFP, while HRs for PMcoarse and NO2 generally attenuated towards the null. Conclusions: These findings strengthen the evidence that UFP exposure plays an important role in cardiovascular health and that risks of ambient air pollution may have been underestimated based on conventional air pollution metrics. https://doi.org/10.1289/EHP3047
Abstract 15498: The Impact of Complete Versus Incomplete Revascularization on the Outcomes of Patients With Single Vessel and Multivessel Disease Undergoing Chronic Total Occlusion Percutaneous Coronary Intervention
Authors: Barbara A Danek, Aris Karatasakis, Peter Tajti, Dimitris Karmpaliotis, Khaldoon Alaswad, Farouc Jaffer, Robert Yeh, Santiago Garcia, David Kandzari, Nicholas Lembo, Mitul Patel, Ehtisham Mahmud, James Choi, Anthony Doing, William Lombardi, Ray Michael Wyman, Catalin Toma, Oleg Krestyaninov, Jeffrey Moses, Ajay Kirtane, Raja Hatem, Ziad Ali, Manish Parikh, Judit Karacsonyi, Yader Sandoval, Bavana Rangan, Houman Khalili, Subhash Banerjee, Emmanouil S Brilakis
Journal: Circulation (2017)

Introduction: The impact of complete revascularization during chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is unknown. Methods: We examined the characteristics of 1,693 CT...
The Digitization of Patient Care: A Review of the Effects of Electronic Health Records on Health Care Quality and Utilization
Authors: Hilal Atasoy, Brad N. Greenwood, Jeffrey Scott McCullough
Journal: Annual Review of Public Health (2018)

Electronic health records (EHRs) adoption has become nearly universal during the past decade. Academic research into the effects of EHRs has examined factors influencing adoption, clinical care benefits, financial and cost implications, and more. We provide an interdisciplinary overview and synthesis of this literature, drawing on work in public and population health, informatics, medicine, management information systems, and economics. We then chart paths forward for policy, practice, and research.
Abstract 20517: Coronary Artery Disease in Eisenmenger Syndrome
Authors: Joseph T Poterucha, Nandan S Anavekar, Alexander C Egbe
Journal: Circulation (2016)

Background: A long held maxim in congenital heart disease is that patients (pts) with cyanotic congenital defects do not develop coronary artery disease (CAD) due to hypothetical protective effects...