tbuckley/cabot-search huggingface dataset:
Integrative Analysis of Histopathological Images and Genomic Data Predicts Clear Cell Renal Cell Carcinoma Prognosis
Authors: Jun Cheng, Jie Zhang, Yatong Han, Xusheng Wang, Xiufen Ye, Yuebo Meng, Anil Parwani, Zhi Han, Qianjin Feng, Kun Huang
Journal: Cancer Research (2017)

Abstract In cancer, both histopathologic images and genomic signatures are used for diagnosis, prognosis, and subtyping. However, combining histopathologic images with genomic data for predicting prognosis, as well as the relationships between them, has rarely been explored. In this study, we present an integrative genomics framework for constructing a prognostic model for clear cell renal cell carcinoma. We used patient data from The Cancer Genome Atlas (n = 410), extracting hundreds of cellular morphologic features from digitized whole-slide images and eigengenes from functional genomics data to predict patient outcome. The risk index generated by our model correlated strongly with survival, outperforming predictions based on considering morphologic features or eigengenes separately. The predicted risk index also effectively stratified patients in early-stage (stage I and stage II) tumors, whereas no significant survival difference was observed using staging alone. The prognostic value of our model was independent of other known clinical and molecular prognostic factors for patients with clear cell renal cell carcinoma. Overall, this workflow and the shared software code provide building blocks for applying similar approaches in other cancers. Cancer Res; 77(21); e91–100. ©2017 AACR.
TCT-91 Antithrombotic therapy post transcatheter aortic valve replacement in patients with no indication for anticoagulation
Authors: M. Chadi Alraies, Homam Moussa Pacha, Kyle Buchanan, Arie Steinvil, Toby Rogers, Edward Koifman, Fahed Darmoch, Petros Okubagzi, Rebecca Torguson, Linzhi Xu, Itsik Ben-Dor, Augusto Pichard, Lowell Satler, Ron Waksman
Journal: Journal of the American College of Cardiology (2017)
PS01.11: Comparison of Initial (T0) Screens in UI Health's Minority-Based Lung Cancer Screening Program to that of the National Lung Screening Trial (NLST)
Authors: Lawrence E. Feldman, Mary Pasquinelli, Juan Alban, Arkadiusz Z. Dudek, Robert Winn, Karriem Watson, Martha G. Menchaca, Matthew Koshy, Kevin Kovitz
Journal: Journal of Thoracic Oncology (2016)
Abstract 20092: Acute Decompensated Valvular Heart Failure Results in Shorter Hospital Stays but Higher Readmission Rates Compared to Non-Valvular Heart Failure: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Michael Sola, Melissa Caughey, Aamir Husain, Patricia Chang, Cassandra Ramm, Michael Yeung, Amil Shah, Kunihiro Matsushita, Dalane Kitzman, John Vavalle
Journal: Circulation (2016)

Introduction: Among patients hospitalized with acute decompensated heart failure (ADHF), the prevalence of valvular disease is unknown. Furthermore, differences in length of stay (LOS) and readmiss...
Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis
Authors: Philip Mease, Stephen Hall, Oliver FitzGerald, Désirée van der Heijde, Joseph F. Merola, Francisco Avila-Zapata, Dorota Cieślak, Daniela Graham, Cunshan Wang, Sujatha Menon, Thijs Hendrikx, Keith S. Kanik
Journal: New England Journal of Medicine (2017)

Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who previously had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs).
TCT-275 Radial hemostasis is facilitated with a potassium ferrate hemostatic patch (Statseal): preliminary results from the randomized controlled Statseal with TR Band Assessment Trial (STAT)
Authors: Arnold Seto, William Rollefson, Mitul Patel, William Suh, Daniel Amador, Omid Behnamfar, Vinisha Garg, Mauricio Cohen
Journal: Journal of the American College of Cardiology (2017)
Abstract 15260: Function of G Protein-Coupled Receptor 146 in Regulation of Blood Lipid Levels
Authors: Haojie Yu, Leonardo M Ferreira, Fang Xia, Tao Chen, Sekar Kathiresan, Chad A Cowan
Journal: Circulation (2016)

Background and Hypothesis: Cardiovascular diseases (CVDs) remain the leading cause of death globally. Abundant data indicate that cholesterol-carrying low-density lipoproteins (LDLs) are essential ...
Cancer incidence and mortality among young adults aged 20–39 years worldwide in 2012: a population-based study
Authors: Miranda M Fidler, Sumit Gupta, Isabelle Soerjomataram, Jacques Ferlay, Eva Steliarova-Foucher, Freddie Bray
Journal: The Lancet Oncology (2017)

To date, the burden of cancer among young adults has rarely been studied in depth. Our aim was to describe the scale and profile of cancer incidence and mortality worldwide among 20-39 year-olds, highlighting major patterns by age, sex, development level, and geographical region.
Compensação por acidente e infecções pelo VIH adquiridas no exercício da profissão em profissionais de saúde na Alemanha
Authors: J Jarke
Journal: Eurosurveillance (1999)

Ate ao final de 1997, foram notificados em todo o mundo duzentos e oitenta e seis casos de transmissao de VIH no exercicio da profissao (1). Um terco destes casos (95), geralmente associados a uma seroconversao apos uma exposicao profissional especifica, foram classificados como infeccoes adquiridas no exercicio da profissao comprovadas. As restantes infeccoes (191) foram classificadas como tendo sido possivelmente adquiridas no exercicio da profissao. Tres das 95 comprovadas (2,3) e 22 das 191 infeccoes pelo VIH possivelmente adquiridas no exercicio da profissao ocorreram em profissionais de saude na Alemanha (1).
Deep mechanisms of social affect – Plastic parental brain mechanisms for sensitivity versus contempt
Authors: James E. Swain, S. Shaun Ho
Journal: Behavioral and Brain Sciences (2017)

Abstract Insensitive parental thoughts and affect, similar to contempt, may be mapped onto a network of basic emotions moderated by attitudinal representations of social-relational value. Brain mechanisms that reflect emotional valence of baby signals among parents vary according to individual differences and show plasticity over time. Furthermore, mental health problems and treatments for parents may affect these brain systems toward or away from contempt, respectively.
TCT-137 Gender Differences in Fractional Flow Reserve after Percutaneous Coronary Intervention
Authors: Rutger van Bommel, Roberto Diletti, Miguel Lemmert, Jeroen Wilschut, Peter P.T. De Jaegere, Felix Zijlstra, Joost Daemen, Nicolas Van Mieghem
Journal: Journal of the American College of Cardiology (2017)
Human herpes virus 8-unrelated CD5 negative primary effusion lymphoma (PEL)-like lymphoma with IGH-CCND1 translocation
Authors: Genju Koh, Kiyoaki Uryu, Yoshio Ichihashi, Nobuko Matsuura, Yoshie Iwasaki, Yuuki Kubo, Hiromasa Harada
Journal: Annals of Oncology (2017)
Racial and Ethnic Disparities in Cancer Survival: The Contribution of Tumor, Sociodemographic, Institutional, and Neighborhood Characteristics
Authors: Libby Ellis, Alison J. Canchola, David Spiegel, Uri Ladabaum, Robert Haile, Scarlett Lin Gomez
Journal: Journal of Clinical Oncology (2017)

Purpose Racial/ethnic disparities in cancer survival in the United States are well documented, but the underlying causes are not well understood. We quantified the contribution of tumor, treatment, hospital, sociodemographic, and neighborhood factors to racial/ethnic survival disparities in California. Materials and Methods California Cancer Registry data were used to estimate population-based cancer-specific survival for patients diagnosed with breast, prostate, colorectal, or lung cancer between 2000 and 2013 for each racial/ethnic group (non-Hispanic black, Hispanic, Asian American and Pacific Islander, and separately each for Chinese, Japanese, and Filipino) compared with non-Hispanic whites. The percentage contribution of factors to overall racial/ethnic survival disparities was estimated from a sequence of multivariable Cox proportional hazards models. Results In baseline models, black patients had the lowest survival for all cancer sites, and Asian American and Pacific Islander patients had the highest, compared with whites. Mediation analyses suggested that stage at diagnosis had the greatest influence on overall racial/ethnic survival disparities accounting for 24% of disparities in breast cancer, 24% in prostate cancer, and 16% to 30% in colorectal cancer. Neighborhood socioeconomic status was an important factor in all cancers, but only for black and Hispanic patients. The influence of marital status on racial/ethnic disparities was stronger in men than in women. Adjustment for all covariables explained approximately half of the overall survival disparities in breast, prostate, and colorectal cancer, but it explained only 15% to 40% of disparities in lung cancer. Conclusion Overall reductions in racial/ethnic survival disparities were driven largely by reductions for black compared with white patients. Stage at diagnosis had the largest effect on racial/ethnic survival disparities, but earlier detection would not entirely eliminate them. The influences of neighborhood socioeconomic status and marital status suggest that social determinants, support mechanisms, and access to health care are important contributing factors.
Mutations in NOTCH1 PEST Domain Orchestrate CCL19-Driven Homing of Chronic Lymphocytic Leukemia (CLL) Cells By Modulating the Tumor Suppressor Gene DUSP22
Authors: Francesca Arruga, Branimir Gizdic, Cinzia Bologna, Simona Cignetto, Roberta Buonincontri, Sara Serra, Tiziana Vaisitti, Nicoletta Vitale, Giulia Garaffo, Elisabetta Mereu, Fary Diop, Francesco Neri, Marta Coscia, John N. Allan, Roberto Piva, Salvatore Oliviero, Richard R. Furman, Davide Rossi, Gianluca Gaidano, Silvia Deaglio
Journal: Blood (2016)
Supervised exercise training as an adjunct therapy for venous leg ulcers: a randomized controlled feasibility trial
Authors: M. Klonizakis, G.A. Tew, A. Gumber, H. Crank, B. King, G. Middleton, J.A. Michaels
Journal: British Journal of Dermatology (2017)

Venous leg ulcers (VLUs) are typically painful and heal slowly. Compression therapy offers high healing rates; however, improvements are not usually sustained. Exercise is a low-cost, low-risk and effective strategy for improving physical and mental health. Little is known about the feasibility and efficacy of supervised exercise training used in combination with compression therapy patients with VLUs.To assess the feasibility of a 12-week supervised exercise programme as an adjunct therapy to compression in patients with VLUs.This was a two-centre, two-arm, parallel-group, randomized feasibility trial. Thirty-nine patients with venous ulcers were recruited and randomized 1 : 1 either to exercise (three sessions weekly) plus compression therapy or compression only. Progress/success criteria included exercise attendance rate, loss to follow-up and patient preference. Baseline assessments were repeated at 12 weeks, 6 months and 1 year, with healing rate and time, ulcer recurrence and infection incidents documented. Intervention and healthcare utilization costs were calculated. Qualitative data were collected to assess participants' experiences.Seventy-two per cent of the exercise group participants attended all scheduled exercise sessions. No serious adverse events and only two exercise-related adverse events (both increased ulcer discharge) were reported. Loss to follow-up was 5%. At 12 months, median ulcer healing time was lower in the exercise group (13 vs. 34·7 weeks). Mean National Health Service costs were £813·27 for the exercise and £2298·57 for the control group.The feasibility and acceptability of both the supervised exercise programme in conjunction with compression therapy and the study procedures is supported.
Red Blood Cells Homeostatically Bind Mitochondrial DNA through TLR9 to Maintain Quiescence and to Prevent Lung Injury
Authors: Meghan J. Hotz, Danielle Qing, Michael G. S. Shashaty, Peggy Zhang, Hilary Faust, Neal Sondheimer, Stefano Rivella, G. Scott Worthen, Nilam S. Mangalmurti
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Potentially hazardous CpG-containing cell-free mitochondrial DNA (cf-mtDNA) is routinely released into the circulation and is associated with morbidity and mortality in critically ill patients. How the body avoids inappropriate innate immune activation by cf-mtDNA remains unknown. Because red blood cells (RBCs) modulate innate immune responses by scavenging chemokines, we hypothesized that RBCs may attenuate CpG-induced lung inflammation through direct scavenging of CpG-containing DNA.Objectives: To determine the mechanisms of CpG-DNA binding to RBCs and the effects of RBC-mediated DNA scavenging on lung inflammation.Methods: mtDNA on murine RBCs was measured under basal conditions and after systemic inflammation. mtDNA content on human RBCs from healthy control subjects and trauma patients was measured. Toll-like receptor 9 (TLR9) expression on RBCs and TLR9-dependent binding of CpG-DNA to RBCs were determined. A murine model of RBC transfusion after CpG-DNA–induced lung injury was used to investigate the role of RBC-mediated DNA scavenging in mitigating lung injury in vivo.Measurements and Main Results: Under basal conditions, RBCs bind CpG-DNA. The plasma-to-RBC mtDNA ratio is low in naive mice and in healthy volunteers but increases after systemic inflammation, demonstrating that the majority of cf-mtDNA is RBC-bound under homeostatic conditions and that the unbound fraction increases during inflammation. RBCs express TLR9 and bind CpG-DNA through TLR9. Loss of TLR9-dependent RBC-mediated CpG-DNA scavenging increased lung injury in vivo.Conclusions: RBCs homeostatically bind mtDNA, and RBC-mediated DNA scavenging is essential in mitigating lung injury after CpG-DNA. Our data suggest a role for RBCs in regulating lung inflammation during disease states where cf-mtDNA is elevated, such as sepsis and trauma.
TCT-761 A Predictive Score for Successful Antegrade Crossing of Infrapopliteal Chronic Total Occlusions During Endovascular Intervention
Authors: Omar Jawaid, Damianos Kokkinidis, Aaron Strobel, T. Raymond Foley, Bejan Alvandi, Robert Sturm, Ho-Hin Choy, Gagan Singh, Stephen Waldo, Ehrin Armstrong
Journal: Journal of the American College of Cardiology (2017)
Predominance of G9P[8] rotavirus strains throughout France, 2014–2017
Authors: J. Kaplon, N. Grangier, S. Pillet, A. Minoui-Tran, A. Vabret, N. Wilhelm, N. Prieur, M. Lazrek, S. Alain, Y. Mekki, V. Foulongne, J. Guinard, V. Avettand-Fenoel, A. Schnuriger, A. Beby-Defaux, G. Lagathu, P. Pothier, A. de Rougemont
Journal: Clinical Microbiology and Infection (2017)
DnaJ Homolog Subfamily B Member 9 Is a Putative Autoantigen in Fibrillary GN
Authors: Nicole K. Andeen, Han-Yin Yang, Dao-Fu Dai, Michael J. MacCoss, Kelly D. Smith
Journal: Journal of the American Society of Nephrology (2017)

Fibrillary GN is a rare form of GN of uncertain pathogenesis that is characterized by the glomerular accumulation of randomly arranged, nonbranching fibrils (12-24 nm) composed of Ig and complement proteins. In this study, we used mass spectrometry to comprehensively define the glomerular proteome in fibrillary GN compared with that in controls and nonfibrillary GN renal diseases. We isolated glomeruli from formalin-fixed and paraffin-embedded biopsy specimens using laser capture microdissection and analyzed them with liquid chromatography and data-dependent tandem mass spectrometry. These studies identified DnaJ homolog subfamily B member 9 (DNAJB9) as a highly sampled protein detected only in fibrillary GN cases. The glomerular proteome of fibrillary GN cases also contained IgG1 as the dominant Ig and proteins of the classic complement pathway. In fibrillary GN specimens only, immunofluorescence and immunohistochemistry with an anti-DNAJB9 antibody showed strong and specific staining of the glomerular tufts in a distribution that mimicked that of the immune deposits. Our results identify DNAJB9 as a putative autoantigen in fibrillary GN and suggest IgG1 and classic complement effector pathways as likely mediators of the destructive glomerular injury in this disease.
MicroRNA-709 Mediates Acute Tubular Injury through Effects on Mitochondrial Function
Authors: Yan Guo, Jiajia Ni, Shuang Chen, Mi Bai, Jiajuan Lin, Guixia Ding, Yue Zhang, Pingping Sun, Zhanjun Jia, Songming Huang, Li Yang, Aihua Zhang
Journal: Journal of the American Society of Nephrology (2017)

Mitochondrial dysfunction has important roles in the pathogenesis of AKI, yet therapeutic approaches to improve mitochondrial function remain limited. In this study, we investigated the pathogenic role of microRNA-709 (miR-709) in mediating mitochondrial impairment and tubular cell death in AKI. In a cisplatin-induced AKI mouse model and in biopsy samples of human AKI kidney tissue, miR-709 was significantly upregulated in the proximal tubular cells (PTCs). The expression of miR-709 in the renal PTCs of patients with AKI correlated with the severity of kidney injury. In cultured mouse PTCs, overexpression of miR-709 markedly induced mitochondrial dysfunction and cell apoptosis, and inhibition of miR-709 ameliorated cisplatin-induced mitochondrial dysfunction and cell injury. Further analyses showed that mitochondrial transcriptional factor A (TFAM) is a target gene of miR-709, and genetic restoration of TFAM attenuated mitochondrial dysfunction and cell injury induced by cisplatin or miR-709 overexpression in vitro Moreover, antagonizing miR-709 with an miR-709 antagomir dramatically attenuated cisplatin-induced kidney injury and mitochondrial dysfunction in mice. Collectively, our results suggest that miR-709 has an important role in mediating cisplatin-induced AKI via negative regulation of TFAM and subsequent mitochondrial dysfunction. These findings reveal a pathogenic role of miR-709 in acute tubular injury and suggest a novel target for the treatment of AKI.
Aetiology, timing and clinical predictors of early vs. late readmission following index hospitalization for acute heart failure: insights from ASCEND-HF
Authors: Marat Fudim, Christopher M. O'Connor, Allison Dunning, Andrew P. Ambrosy, Paul W. Armstrong, Adrian Coles, Justin A. Ezekowitz, Stephen J. Greene, Marco Metra, Randall C. Starling, Adriaan A. Voors, Adrian F. Hernandez, G. Michael Felker, Robert J. Mentz
Journal: European Journal of Heart Failure (2017)
Overcoming mutational complexity in acute myeloid leukemia by inhibition of critical pathways
Authors: Yoriko Saito, Yoshiki Mochizuki, Ikuko Ogahara, Takashi Watanabe, Leah Hogdal, Shinsuke Takagi, Kaori Sato, Akiko Kaneko, Hiroshi Kajita, Naoyuki Uchida, Takehiro Fukami, Leonard D. Shultz, Shuichi Taniguchi, Osamu Ohara, Anthony G. Letai, Fumihiko Ishikawa
Journal: Science Translational Medicine (2017)

Targeting leukemogenic mutations identified by functional single-cell genomics eliminated human AML in vivo.
Development of novel backbones for the treatment of peripheral T-cell lymphoma (PTCL): The pralatrexate/romidepsin doublet.
Authors: Jennifer Effie Amengual, Renee Lichtenstein, Celeste Rojas, Ahmed Sawas, Changchun Deng, Donald Steven Colbourn, Emily Lichtenstein, Karen Khan, Michael J. Smith, Heather Dials, Owen A. O'Connor
Journal: Journal of Clinical Oncology (2016)

2552 Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of lymphomas in which only 20-25% of patients experience long-term survival with CHOP chemotherapy. Recently several drugs have been approved for this entity including pralatrexate (P), romidepsin (R), and belinostat which have response rates ranging from 26%-29% as single agents. Based on our demonstration of synergy of P+R in preclinical models of TCL, we initiated a study on the safety and efficacy of P+R in a phase I-II study for relapsed or refractory lymphomas (NCT01947140). Methods: A 3+3 dose-escalation study started at P 10mg/m2 and R 12mg/m2 with escalation to P 25 mg/m2 and R 14 mg/m2. Patients were treated on 1 of 3 dosing schedules (weekly x 3 Q28D; weekly x 2 Q21D and QOW Q28D). The primary objective was to determine MTD and DLT; the secondary objective included describing ORR (CR+PR). Patients were required to have relapsed lymphoma of any subtype, ECOG PS < 2, and adequate organ and marrow function. There was no upper limit to the number of prior therapies or transplantation. Results: Twenty-five patients were enrolled and were evaluable for toxicity. Median age was 52 yrs (23-73) and 60% were male. The median number of prior therapies was 3 (range 1-16). Histologies included HL (N = 3), B-cell (N = 7 of which FL = 4) and T-cell (N = 15). The median number of cycles completed was 4 (range 1-8+ ongoing). There were 3 DLTs in cohort 4 (P 20mg/m2 & R 12mg/m2given weekly x 2 Q21D) consisting of 2 Grade 3 oral mucositis and 1 Grade 4 sepsis. The QOW Q28D schedule had no DLTs at equivalent and higher doses. The grade 3/4 toxicities reported in > 5% of patients were: neutropenia (32%), thrombocytopenia (32%), anemia (24%), oral mucositis (16%), hyponatremia (8%), pneumonia (8%) and sepsis (8%). Twenty-one patients were evaluable for response, 2 patients are currently on therapy. The ORR in the total, non-PTCL and PTCL populations was 52%; 33% (no CR) and 77% (38% CR) respectively. Presently 1 patient is awaiting safety and response analysis. Conclusions: These data support the lineage specific activity of the P+R combination, which is being expanded to a multicenter Phase II for PTCL. Clinical trial information: NCT01947140.
Multi-trigger and viral wheeze: describing symptoms or defining diseases?
Authors: Daan Caudri
Journal: European Respiratory Journal (2017)

Preschool wheeze is a highly prevalent clinical problem [1] which, while typically mild, can present within a wide spectrum of severity and is associated with considerable healthcare costs [2]. The natural history is favourable and the majority of preschool wheezers will outgrow their symptoms regardless of any intervention [3–5]. However, a solid evidence base with which to guide clinicians as to which preschool wheezers would benefit from treatment, if any, is lacking. Multi-trigger and viral wheeze track over time but it is unclear whether they represent separate disease entities <http://ow.ly/El7w30eO9fb>
Research integrity has become complacent and lacks transparency, MPs hear
Authors: Adrian O’Dowd
Journal: BMJ (2017)

Experts have told MPs that research is suffering from complacency, a lack of transparency, poor statistical skills, and too much weight being given to “exciting” research.

The concerns were raised during an evidence session of the parliamentary science and technology committee’s inquiry into research integrity, held on 24 October.

MPs asked witnesses for their opinion on the current state of research integrity, to which Ottoline Leyser, former chair of the steering group on the culture of scientific research at the Nuffield Council on Bioethics, said that a culture had developed “where people are rewarded for being right and being exciting.”

She added, “Those things have nothing to do with science and the research method that we want to espouse. These norms of science that everybody would agree to if you pushed them are being not …