tbuckley/cabot-search huggingface dataset:
Vemurafenib in Patients with Erdheim-Chester Disease (ECD) and Langerhans Cell Histiocytosis (LCH) Harboring BRAFV600 Mutations: A Cohort of the Histology-Independent VE-Basket Study
Authors: Eli L. Diamond, Vivek Subbiah, Craig Lockhart, Jean-Yves Blay, Jason E. Faris, Igor Puzanov, Ian Chau, Noopur S. Raje, Jürgen S. Wolf, Joe Erinjeri, Jean Torrisi, Gary Ulaner, Mario Lacouture, Susan Robson, Martina Makrutzki, Elena Elez, Josep Tabernero, Omar Abdel-Wahab, Jose Baselga, David M. Hyman
Journal: Blood (2016)
Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes
Authors: Aidin Rawshani, Araz Rawshani, Stefan Franzén, Björn Eliasson, Ann-Marie Svensson, Mervete Miftaraj, Darren K. McGuire, Naveed Sattar, Annika Rosengren, Soffia Gudbjörnsdottir
Journal: New England Journal of Medicine (2017)

Long-term trends in excess risk of death and cardiovascular outcomes have not been extensively studied in persons with type 1 diabetes or type 2 diabetes.We included patients registered in the Swedish National Diabetes Register from 1998 through 2012 and followed them through 2014. Trends in deaths and cardiovascular events were estimated with Cox regression and standardized incidence rates. For each patient, controls who were matched for age, sex, and county were randomly selected from the general population.Among patients with type 1 diabetes, absolute changes during the study period in the incidence rates of sentinel outcomes per 10,000 person-years were as follows: death from any cause, -31.4 (95% confidence interval [CI], -56.1 to -6.7); death from cardiovascular disease, -26.0 (95% CI, -42.6 to -9.4); death from coronary heart disease, -21.7 (95% CI, -37.1 to -6.4); and hospitalization for cardiovascular disease, -45.7 (95% CI, -71.4 to -20.1). Absolute changes per 10,000 person-years among patients with type 2 diabetes were as follows: death from any cause, -69.6 (95% CI, -95.9 to -43.2); death from cardiovascular disease, -110.0 (95% CI, -128.9 to -91.1); death from coronary heart disease, -91.9 (95% CI, -108.9 to -75.0); and hospitalization for cardiovascular disease, -203.6 (95% CI, -230.9 to -176.3). Patients with type 1 diabetes had roughly 40% greater reduction in cardiovascular outcomes than controls, and patients with type 2 diabetes had roughly 20% greater reduction than controls. Reductions in fatal outcomes were similar in patients with type 1 diabetes and controls, whereas patients with type 2 diabetes had smaller reductions in fatal outcomes than controls.In Sweden from 1998 through 2014, mortality and the incidence of cardiovascular outcomes declined substantially among persons with diabetes, although fatal outcomes declined less among those with type 2 diabetes than among controls. (Funded by the Swedish Association of Local Authorities and Regions and others.).
RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury
Authors: Julius C. Fischer, Michael Bscheider, Gabriel Eisenkolb, Chia-Ching Lin, Alexander Wintges, Vera Otten, Caroline A. Lindemans, Simon Heidegger, Martina Rudelius, Sébastien Monette, Kori A. Porosnicu Rodriguez, Marco Calafiore, Sophie Liebermann, Chen Liu, Stefan Lienenklaus, Siegfried Weiss, Ulrich Kalinke, Jürgen Ruland, Christian Peschel, Yusuke Shono, Melissa Docampo, Enrico Velardi, Robert R. Jenq, Alan M. Hanash, Jarrod A. Dudakov, Tobias Haas, Marcel R. M. van den Brink, Hendrik Poeck
Journal: Science Translational Medicine (2017)

Activation of the RIG-I or STING pathways results in a type I interferon response that protects gut integrity after irradiation- or immune-induced tissue injury.
TCTAP C-171 Heavily Calcified Unprotected Left Main and Left Anterior Descending Lesions Treated Using Tri-level Rotational Atherectomy
Authors: Prem Nathan Arumuganathan, Kamaraj Selvaraj, Abd Kahar Bin Abd Ghapar, Abdul Muizz Bin Abd Malek, Abdul Raqib Abd Ghani
Journal: Journal of the American College of Cardiology (2017)
Noninvasive FFR Derived From Coronary CT Angiography
Authors: Michael T. Lu, Maros Ferencik, Rhonda S. Roberts, Kerry L. Lee, Alexander Ivanov, Elizabeth Adami, Daniel B. Mark, Farouc A. Jaffer, Jonathon A. Leipsic, Pamela S. Douglas, Udo Hoffmann
Journal: JACC. Cardiovascular imaging (2017)
Abstract 15139: Coronary Arterial Stenosis Assessment versus Different Coronary Atherosclerotic Plaque Burden Indices by Computed Tomography Angiography for Detecting Hemodynamically Significant Coronary Artery Disease - Insights From the CORE320 International Study
Authors: Tiago A Magalhçes, Satoru Kishi, Richard George, Jeffrey Brinker, Julie Miller, Melvin Clouse, Christopher Cox, Andrea Vavere, Johan Reiber, Pieter Kitslaar, Carlos Rochitte, Joao Lima, Armin Arbab-Zadeh
Journal: Circulation (2013)

Purpose: The aim of this study is to investigate the diagnostic performance of semi-automatically derived indices of coronary atherosclerotic plaque burden by coronary CT angiography (CTA) for assessment of flow-limiting stenosis using a combined outcome of Quantitative Coronary Angiography (QCA) and Single-Photon Emission Computed Tomography (SPECT) as the reference.

Methods: Three-hundred-seventy-three patients with suspected CAD referred for invasive angiography in the CORE320 multicenter study underwent a cardiac 320-slice CT scanning. Per-patient coronary atherosclerotic plaque burden was assessed using a novel arterial contour detection algorithm (MEDIS™, Netherlands), by subtracting lumen volume from vessel wall volume for the entire coronary tree using a 19-segment coronary model. To estimate severity of plaque burden, we used three indexed parameters: 1) Length normalized total atheroma volume (lenght normTAV) - total plaque volume)/(total coronary length); 2) Normalized total atheroma volume (TAVnorm) - (total plaque volume)/(total coronary length) x mean coronary length in study population); 3) percent atheroma volume (PAV) - (total plaque volume)/(total vessel volume) x 100. Area under Receiver-Operation Characteristics Curve (AUC) estimated the diagnostic accuracy of these indices to predict flow-limiting stenosis, defined as the presence of at least one >50% stenosis with related perfusion deficit by SPECT.

Results: The diagnostic accuracy of coronary plaque burden assessed by PAV was similar to coronary CTA to predict flow-limiting stenosis (AUC 0,79 [0.75-0.83] vs 0,82 [0.77-0.86] respectively, p= 0.28). Plaque burden assessed by length normTAV and TAVnorm had the same diagnostic performance to predict disease (AUC 0.73 [0.68 - 0.77]), being inferior to coronary CTA (p = 0.002).

Conclusions: Semi-automatically derived coronary atherosclerotic plaque burden index by CTA offers robust information to predict flow-limiting stenosis. Percent atheroma volume had the best performance to predict flow-limiting stenosis among all plaque burden indices, with no difference when compared to CTA stenosis assessment.
Low- Molecular Weight Heparins (LMWH) Versus Vitamin K Antagonists (VKAs) in the Treatment and Secondary Prevention of Cancer-Associated Venous Thromboembolism (VTE): A Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCTs)
Authors: Kyaw Zin Thein, Lukman Tijani, Thein H. Oo
Journal: Blood (2016)
A stemness-related ZEB1–MSRB3 axis governs cellular pliancy and breast cancer genome stability
Authors: Anne-Pierre Morel, Christophe Ginestier, Roxane M Pommier, Olivier Cabaud, Emmanuelle Ruiz, Julien Wicinski, Mojgan Devouassoux-Shisheboran, Valérie Combaret, Pascal Finetti, Christelle Chassot, Christiane Pinatel, Frédérique Fauvet, Pierre Saintigny, Emilie Thomas, Caroline Moyret-Lalle, Joël Lachuer, Emmanuelle Despras, Jean-Luc Jauffret, François Bertucci, Jérôme Guitton, Anne Wierinckx, Qing Wang, Nina Radosevic-Robin, Frédérique Penault-Llorca, David G Cox, Frédéric Hollande, Stéphane Ansieau, Julie Caramel, Daniel Birnbaum, Arnaud M Vigneron, Agnès Tissier, Emmanuelle Charafe-Jauffret, Alain Puisieux
Journal: Nature Medicine (2017)
Genomic Responses of Mouse Synovial Fibroblasts During Tumor Necrosis Factor–Driven Arthritogenesis Greatly Mimic Those in Human Rheumatoid Arthritis
Authors: Evangelos Ntougkos, Panagiotis Chouvardas, Fani Roumelioti, Caroline Ospelt, Mojca Frank‐Bertoncelj, Andrew Filer, Christopher D. Buckley, Steffen Gay, Christoforos Nikolaou, George Kollias
Journal: Arthritis & Rheumatology (2017)

Aberrant activation of synovial fibroblasts is a key determinant in the pathogenesis of rheumatoid arthritis (RA). The aims of this study were to produce a map of gene expression and epigenetic changes occurring in this cell type during disease progression in the human tumor necrosis factor (TNF)-transgenic model of arthritis and to identify commonalities with human synovial fibroblasts.We used deep sequencing to probe the transcriptome, the methylome, and the chromatin landscape of cultured mouse arthritogenic synovial fibroblasts at 3 stages of disease, as well as synovial fibroblasts stimulated with human TNF. We performed bioinformatics analyses at the gene, pathway, and network levels, compared mouse and human data, and validated selected genes in both species.We found that synovial fibroblast arthritogenicity was reflected in distinct dynamic patterns of transcriptional dysregulation, which was especially enriched in pathways of the innate immune response and mesenchymal differentiation. A functionally representative subset of these changes was associated with methylation, mostly in gene bodies. The arthritogenic state involved highly active promoters, which were marked by histone H3K4 trimethylation. There was significant overlap between the mouse and human data at the level of dysregulated genes and to an even greater extent at the level of pathways.This study is the first systematic examination of the pathogenic changes that occur in mouse synovial fibroblasts during progressive TNF-driven arthritogenesis. Significant correlations with the respective human RA synovial fibroblast data further validate the human TNF-transgenic mouse as a reliable model of the human disease. The resource of data generated in this work may serve as a framework for the discovery of novel pathogenic mechanisms and disease biomarkers.
Monitored Anesthesia Care vs Intubation for Vertebrobasilar Stroke Endovascular Therapy
Authors: Ashutosh P. Jadhav, Mehdi Bouslama, Amin Aghaebrahim, Leticia C. Rebello, Matthew T. Starr, Diogo C. Haussen, Manasa Ranginani, Matthew K. Whalin, Tudor G. Jovin, Raul G. Nogueira
Journal: JAMA Neurology (2017)

No consensus regarding the ideal sedation treatment for stroke endovascular therapy has been reached, and practices remain largely based on local protocols and clinician preferences. Most studies have focused on anterior circulation strokes; therefore, little is known regarding the optimal anesthesia type for vertebrobasilar occlusion strokes.To compare clinical and angiographic outcomes between monitored anesthesia care (MAC) and general anesthesia (GA) in patients presenting with vertebrobasilar occlusion strokes.Retrospective, matched, case-control study of consecutive vertebrobasilar occlusion strokes treated with endovascular therapy at 2 academic institutions. The study took place between September 2005 and September 2015 at University of Pittsburgh Medical Center Stroke Institute, Pittsburgh, Pennsylvania, and between September 2010 and September 2015 at the Marcus Stroke and Neuroscience Center at Grady Memorial Hospital, Atlanta, Georgia. Patients requiring emergent intubation prior to endovascular therapy were excluded. The remaining patients were categorized into (1) MAC and (2) elective intubation for the procedure (elective GA). Patients who converted from MAC to GA during the procedure were included in the MAC group. The 2 groups were matched for age, baseline National Institutes of Health Stroke Scale score, and glucose levels. Baseline characteristics and outcomes were compared.The primary outcome measure was the shift in the degree of disability among the 2 groups as measured by the modified Rankin scale at 90 days.A total of 215 patients underwent endovascular therapy for vertebrobasilar occlusion strokes during the study period. Thirty-nine patients were excluded owing to emergent pre-endovascular therapy intubation. Sixty-three patients had MAC (36%) and 113 patients had GA (64%). The conversion rate from MAC to GA was 13% (n = 8). After matching, 61 pairs of patients (n = 122) underwent primary analysis. The 2 groups were well balanced in terms of baseline characteristics. Median age was 69 years (interquartile range, 60-75 years) in the MAC group vs 67 years (interquartile range, 55.5-78.5 years) in the GA group (P = .83). Fifty-four percent of the patients in the MAC group were men vs 41% in the GA group (P = .44). When compared with the elective GA group, patients who underwent the procedure with MAC had similar rates of successful reperfusion, good clinical outcomes, hemorrhagic complications, and mortality. The modality of anesthesia was not associated with any significant changes in the modified Rankin scale score distribution (MAC: OR, 1.52; 95% CI, 0.80-2.90; P = .19).In endovascular therapy for acute posterior circulation stroke, MAC is feasible and appears to be as safe and effective as GA. Future clinical trials are warranted to confirm our findings.
A Markov chain model of a longitudinal breast cancer data set.
Authors: Paul K. Newton, Jorge J. Nieva, Peter Kuhn, Larry Norton, Elizabeth Anne Comen, Jeremy Mason, Neethi Venkatappa, Maxine S. Jochelson
Journal: Journal of Clinical Oncology (2014)

11040 Background: Cancer cell migration patterns are critical for understanding metastases and clinical evolution. Breast cancer spreads from one organ system to another via hematogenous and lymphatic routes. Although patterns of spread may superficially seem random and unpredictable we explored the possibility that this is not the case. Methods: Based on a data set of 453 breast cancer patients from Memorial Sloan Kettering Cancer Center—all non-metastatic at time of diagnosis—we created a Markov chain model of metastasis. This describes the probabilities of metastasis occurring at a given anatomic site together with the probability of spread to additional sites, based on observations. Results: Using actual data, we have learned (i) how to create the Markov transition matrix governing the probabilities of cancer progression from site to site; (ii) how to create a systemic network diagram governing disease progression modeled as a random walk on a directed graph; (iii) how to classify metastatic sites as
Addendum: Inhibition of aldehyde dehydrogenase-2 suppresses cocaine seeking by generating THP, a cocaine use–dependent inhibitor of dopamine synthesis
Authors: Lina Yao, Peidong Fan, Maria Arolfo, Zhang Jiang, M Foster Olive, Jeff Zablocki, Hai-Ling Sun, Nancy Chu, Jeongrim Lee, Hee-Yong Kim, Kwan Leung, John Shryock, Brent Blackburn, Ivan Diamond
Journal: Nature Medicine (2011)
Diabetes, Associated Clinical Spectrum, Long-term Prognosis, and Genotype/Phenotype Correlations in 201 Adult Patients With Hepatocyte Nuclear Factor 1B (<i>HNF1B</i>) Molecular Defects
Authors: Danièle Dubois-Laforgue, Erika Cornu, Cécile Saint-Martin, Joël Coste, Christine Bellanné-Chantelot, José Timsit
Journal: Diabetes Care (2017)

Molecular defects of hepatocyte nuclear factor 1B (HNF1B) are associated with a multiorgan disease, including diabetes (maturity-onset diabetes of the young 5) and kidney abnormalities. The HNF1B syndrome is related to HNF1B mutations or to a 17q12 deletion spanning 15 genes, including HNF1B. Here, we described HNF1B-related diabetes and associated phenotypes and assessed genotype/phenotype correlations at diagnosis and in the long-term.This multicenter retrospective cohort study included 201 patients, aged 18 years or older at follow-up, with HNF1B mutations (n = 101) or deletion (n = 100).Diabetes was present in 159 patients. At diagnosis, clinical symptoms of diabetes were present in 67 of 144 patients and HNF1B renal disease in 64 of 102. Although responsiveness to sulfonylureas/repaglinide was observed in 29 of the 51 tested, 111 of 140 patients (79%) were treated with insulin at follow-up. Diabetic retinopathy and/or neuropathy were present in 46 of 114 patients. Renal cysts were present in 122 of 166 patients, chronic kidney disease stages 3-4 (CKD3-4) in 75 of 169 (44%), and end-stage renal disease (ESRD) in 36 of 169 (21%). Compared with the patients with mutations, those with HNF1B deletion less often had CKD3-4/ESRD at diagnosis (11 of 43 vs. 27 of 35, P < 10-4) and in the long term (40 of 78 vs. 71 of 91, P = 0.0003). They were leaner and more frequently treated with insulin.In patients with HNF1B syndrome, diabetes complications, cardiovascular risk factors, CKD3-4, and ESRD are highly prevalent. At diabetes diagnosis, the presence of morphological and/or functional kidney disease may help etiological diagnosis. Genotype/phenotype correlations may have implications for the care and the prognosis of these patients.
Outcome of unrelated donor stem cell transplantation for hematologic malignancies: Preliminary data from a single academic transplant center
Authors: Muzaffar H. Qazilbash, Joseph P. Lynch, Charles L. Beall, Miklos Auber, Robin Weisenborn, Pam Bunner, Gerald Hobbs, Solveig G. Ericson
Journal: Blood (2000)
Education in Nephrology Fellowship: A Survey-Based Needs Assessment
Authors: Robert W. Rope, Kurtis A. Pivert, Mark G. Parker, Stephen M. Sozio, Sylvia Bereknyei Merell
Journal: Journal of the American Society of Nephrology (2017)

Educational needs assessments for nephrology fellowship training are limited. This study assessed fellows’ perceptions of current educational needs and interest in novel modalities that may improve their educational experience and quantified educational resources used by programs and fellows. We distributed a seven-question electronic survey to all United States–based fellows receiving complimentary American Society of Nephrology (ASN) membership at the end of the 2015–2016 academic year in conjunction with the ASN Nephrology Fellows Survey. One third (320 of 863; 37%) of fellows in Accreditation Council for Graduate Medical Education–accredited positions responded. Most respondents rated overall quality of teaching in fellowship as either “good” (37%) or “excellent” (44%), and most (55%) second-year fellows felt “fully prepared” for independent practice. Common educational resources used by fellows included UpToDate, Journal of the American Society of Nephrology/Clinical Journal of the American Society of Nephrology , and Nephrology Self-Assessment Program ; others—including ASN’s online curricula—were used less often. Fellows indicated interest in additional instruction in several core topics, including home dialysis modalities, ultrasonography, and pathology. Respondents strongly supported interventions to improve pathology instruction and increase time for physiology and clinical review. In conclusion, current nephrology fellows perceive several gaps in training. Innovation in education and training is needed to better prepare future nephrologists for the growing challenges of kidney care.
Multiple Facial Trichoepitheliomas and Vulval Cysts
Authors: Anna Dubois, Angel Alonso-Sanchez, Vrinda Bajaj, Akhtar Husain, Neil Rajan
Journal: JAMA Dermatology (2017)

This case study describes a unique incidence of multiple trichoepitheliomas in combination with epidermoid cysts of the vulva in association with a novel pathogenic mutation in CYLD, extending the phenotypic spectrum.
Analysis of lymphangiogenetic factors in invasive bladder cancer—A tissue microarray analysis
Authors: C. Wulfing, E. Herrmann, T. Kopke, E. Eltze, J. Neumann, S. Bierer, L. Hertle
Journal: Journal of Clinical Oncology (2007)

15530 Introduction: Vascular endothelial growth factors (VEGF) -C, -D and their receptor Flt-4 play an emerging role in lymphangiogenesis of different tumor types. Our aim was to determine the role of VEGF-C, VEGF-D and Flt-4 in invasive transitional cell carcinoma of the bladder. Material and Methods: Archival tumor tissue of 286 patients, who had previously undergone radical cystectomy at our institution, was reviewed and representative tumor blocks were selected for constructing a tissue microarray (TMA). Paraffin sections were assessed immunohistochemically using mono- and polyclonal antibodies against VEGF-C, VEGF-D and Flt-4. Staining results were analysed semiquantitatively and correlated with various clinicopathological factors. Results: Overexpression of VEGF-C, VEGF-D and Flt-4 was found in 24.1%, 37.4% and 46.3% of cases, respectively. While there was no association of VEGF-C to histopathological parameters and clinical outcome, patients with VEGF-D overexpression had higher pathological tumor stages (p=0.021) and regional lymph node metastases (p=0.016). Furthermore, they had significantly worse disease-free survival (p=0.042). Overexpression of Flt-4 was found in the subgroup of G3- and G4-tumors (p=0.001) and correlated with a shorter period of disease- free survival (p=0.033). Conclusion: VEGF-C, VEGF-D and Flt-4 are overexpressed in bladder cancer. VEGF-D predicts higher tumor stages and regional lymph node metastases. It is associated with a worse disease-free survival as well as Flt-4 in the subgroup of high-grade tumors. Further studies should be initiated to evaluate VEGF-D and Flt-4 as potential targets in bladder cancer. No significant financial relationships to disclose.
Renal function in relation to sodium intake: a quantitative review of the literature
Authors: Kyoko Nomura, Kei Asayama, Lotte Jacobs, Lutgarde Thijs, Jan A. Staessen
Journal: Kidney International (2017)

We undertook a quantitative literature review to search for evidence underpinning current guidelines proposing a reduction of sodium intake to less than 2.4 g/d for the management of chronic kidney disease. We searched PubMed for peer-reviewed articles published from January 1980 through May 2016. Two investigators screened 5072 publications and extracted data from 36, including 11 cross-sectional and 5 longitudinal observational studies and 20 intervention trials. Within-study effect sizes were pooled and standardized to a sodium gradient of 100 mmol/d by using inverse-variance weighted random effects models. Among cross-sectional studies, the pooled odds ratio for albuminuria was 1.23 (95% confidence interval [CI], 0.92–1.64, P = 0.16), and the pooled mean difference in glomerular filtration rate amounted to 8.5 ml/min (CI, -2.3 to 19.2 ml/min; P = 0.12). In the cohort studies, the pooled relative risk of a renal endpoint was 1.08 (CI, 0.92–1.29; P = 0.35). In the intervention trials (median duration, 14 days [range, 4–186 days]), the mean differences in estimated glomerular filtration rate and albuminuria (high vs. low sodium intake) averaged 4.6 ml/min (CI, 3.4–5.8 ml/min; P < 0.0001) and 53% (CI, 21–84; P = 0.001), respectively. Cochran's Q statistic indicated significant heterogeneity among cross-sectional studies for both estimated glomerular filtration rate and albuminuria (P < 0.0001) and among intervention trials for albuminuria (P = 0.04). In conclusion, there is no robust evidence suggesting that long-term reduction of salt intake would prevent chronic kidney disease or delay its progression. However, our current findings, which were mainly obtained in people with slight renal impairment, cannot be extrapolated to patients with moderate or severe chronic kidney disease.
Outpatient High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation for Multiple Myeloma Is Associated with a Low Infection Safety Profile.
Authors: Mounzer E. Agha, Andrew M. Yeager, Carol Evans, Nikol Borkowski, Anne Marie Scekeres, Sarah Miller, Cheryl Tompkins, Rowena Schwartz, Albert D. Donnenberg, Jeffrey Shogan
Journal: Blood (2004)