tbuckley/cabot-search huggingface dataset:
A Large Polysaccharide Produced by Helicobacter hepaticus Induces an Anti-inflammatory Gene Signature in Macrophages
Authors: Camille Danne, Grigory Ryzhakov, Maria Martínez-López, Nicholas Edward Ilott, Fanny Franchini, Fiona Cuskin, Elisabeth C. Lowe, Samuel J. Bullers, J. Simon C. Arthur, Fiona Powrie
Journal: Cell Host & Microbe (2017)

Interactions between the host and its microbiota are of mutual benefit and promote health. Complex molecular pathways underlie this dialog, but the identity of microbe-derived molecules that mediate the mutualistic state remains elusive. Helicobacter hepaticus is a member of the mouse intestinal microbiota that is tolerated by the host. In the absence of an intact IL-10 signaling, H. hepaticus induces an IL-23-driven inflammatory response in the intestine. Here we investigate the interactions between H. hepaticus and host immune cells that may promote mutualism, and the microbe-derived molecule(s) involved. Our results show that H. hepaticus triggers early IL-10 induction in intestinal macrophages and produces a large soluble polysaccharide that activates a specific MSK/CREB-dependent anti-inflammatory and repair gene signature via the receptor TLR2. These data identify a host-bacterial interaction that promotes mutualistic mechanisms at the intestinal interface. Further understanding of this pathway may provide novel prevention and treatment strategies for inflammatory bowel disease.
Abstract 13158: Hospitalization for De Novo versus Worsening Chronic Heart Failure: Insights From the ASCEND-HF Trial
Authors: Stephen J Greene, Adrian F Hernandez, Allison Dunning, Andrew P Ambrosy, Paul W Armstrong, Javed Butler, Lukasz Cerbin, Adrian Coles, Justin A Ezekowitz, Marco Metra, Randall C Starling, John R Teerlink, Adriaan A Voors, Christopher M O’Connor, Robert J Mentz
Journal: Circulation (2016)

Introduction: Heart failure (HF) is a heterogeneous syndrome and individual patient survival varies widely. It is unclear how hospitalized acute HF (AHF) patients who are long-term chronic HF survivors differ from those with more recent HF diagnoses. Methods: The ASCEND-HF trial randomized 7,141 hospitalized AHF patients with reduced or preserved ejection fraction (EF) to nesiritide or placebo in addition to standard care. The present analysis compared patients by duration of HF diagnosis prior to index hospitalization using pre-specified cutpoints (0-1 month [i.e. “ de novo ”], &gt;1-12 months, &gt;12-60 months, &gt;60 months). Results: Overall, 5,741 (80.4%) patients had documentation of duration of HF diagnosis ( de novo , N=1536; &gt;1-12 months, N=1020; &gt;12-60 months, N=1653; &gt;60 months, N=1532). Mean age ranged from 64-66 years and mean EF from 29-32% across all HF duration groups. Compared to patients with longer HF duration, de novo patients were more likely to have non-ischemic HF etiology, fewer comorbidities, lower natriuretic peptide levels, and better baseline functional status (all P-value &lt;0.01). After adjustment, compared to de novo patients, longer HF duration was associated with more persistent dyspnea at 24 hours and increased 180-day mortality (Table). The influence of HF duration on mortality did not differ by age, gender, race, etiology of HF, or EF (all P-value for interaction ≥0.05). Conclusion: In this large AHF trial cohort, patient profile differed by duration of the HF diagnosis. De novo HF diagnosis was independently associated with greater early dyspnea relief and improved post-discharge survival compared to those with chronic HF diagnoses.
Post-Transplant Cyclophosphamide Improves Progression Free Survival after Allogeneic Hematopoietic Stem Cell Transplantation in AML/MDS Patients with Prior CTLA-4 or PD-1 Blockade
Authors: Betul Oran, Guillermo Garcia-Manero, Rima M. Saliba, Gheath Alatrash, Elias J. Jabbour, Uday Popat, Farhad Ravandi, Amin M. Alousi, Tapan Kadia, Marina Konopleva, Courtney D. DiNardo, Sherry Pierce, Katy Rezvani, Elizabeth J Shpall, Padmanee Sharma, Richard E. Champlin, Hagop M. Kantarjian, Naval Daver
Journal: Blood (2017)
Perioperative THR-184 and AKI after Cardiac Surgery
Authors: Jonathan Himmelfarb, Glenn M. Chertow, Peter A. McCullough, Thierry Mesana, Andrew D. Shaw, Thoralf M. Sundt, Craig Brown, David Cortville, François Dagenais, Benoit de Varennes, Manuel Fontes, Jerome Rossert, Jean-Claude Tardif
Journal: Journal of the American Society of Nephrology (2017)

Export AKI after cardiac surgery is associated with mortality, prolonged hospital length of stay, use of dialysis, and subsequent CKD. We evaluated the effects of THR-184, a bone morphogenetic protein-7 agonist, in patients at high risk for AKI after cardiac surgery. We conducted a randomized, double-blind, placebo-controlled, multidose comparison of the safety and efficacy of perioperative THR-184 using a two-stage seamless adaptive design in 452 patients between 18 and 85 years of age who were scheduled for nonemergent cardiac surgery requiring cardiopulmonary bypass and had recognized risk factors for AKI. The primary efficacy end point was the proportion of patients who developed AKI according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The proportion of patients who developed AKI within 7 days of surgery was similar in THR-184 treatment groups and placebo groups (range, 74%–79%; P=0.43). Prespecified secondary end point analysis did not show significant differences in the severity of AKI stage (P=0.53) or the total duration of AKI (P=0.44). A composite of death, dialysis, or sustained impaired renal function by day 30 after surgery did not differ between groups (range, 11%–20%; P=0.46). Safety-related outcomes were similar across all treatment groups. In conclusion, compared with placebo, administration of perioperative THR-184 through a range of dose exposures failed to reduce the incidence, severity, or duration of AKI after cardiac surgery in high-risk patients.
Validación clínica del nuevo test EndoFaster® como método diagnóstico en tiempo real de la infección por Helicobacter pylori (HP) durante la realización de una endoscopia
Authors: E Sanchez Rodriguez, R Sánchez Aldehuelo, R Ríos León, Á Flores De Miguel, A Guerrero García, C Teruel Sánchez-Vegazo, S Parejo Carbonell, C Arocena Aranguren, A Albillos Martínez, E Vázquez Sequeiros
Journal: Endoscopy (2017)

Endofaster® es un dispositivo que realiza un diagnóstico en tiempo real de la infección por HP mediante análisis del jugo gástrico sin necesidad de toma biopsias.
Student who died from anorexia was failed by NHS, review finds
Authors: Gareth Iacobucci
Journal: BMJ (2017)

A young woman who died from anorexia was failed by NHS organisations which did not provide her with appropriate care and treatment, a review has concluded.

A report1 from the parliamentary and health service ombudsman said the death of 19 year old Averil Hart on 15 December 2012 was caused by a series of failures involving “every NHS organisation that should have cared for her.”

The review, led by former chief medical officer for England Bill Kirkup, said that the case was symptomatic of widespread problems with adult eating disorder services in the NHS.

The inquiry, conducted after Averil’s family made a complaint to the ombudsman about the treatment she received, found that there had been inadequate coordination and planning of her care …
Self-regulated use of a wearable activity sensor is not associated with improvements in physical activity, cardiometabolic risk or subjective health status
Authors: Saurabh S Thosar, Meike Niederhausen, Jodi Lapidus, Nora F Fino, Joaquin Cigarroa, Jessica Minnier, Sandra Colner, Asha Nayak, Luke J Burchill
Journal: British Journal of Sports Medicine (2017)

Physical activity (PA) trackers are a pervasive feature of modern life. It is expected that by 2020, sales of wearable devices will reach approximately 300 million users1 many with the intention of increasing activity by tracking daily step count and other measures of PA. We assessed whether self-regulated use of a commercial PA tracker without prescribed goals improved (1) PA, (2) cardiometabolic (CM) risk factors or (3) subjective health status (SHS).

We recruited 431 healthy, mostly white (59%) male (61%) volunteers aged 41±9 years (mean±SD), body mass index (BMI) 28±6 kg/m2 (23.6% obese) from a common worksite in North America to wear a commercial PA tracker for 6 months. Behaviour and PA change goals were not prescribed. Participants did not receive any compensation but kept the PA tracker at study completion. The wrist-worn PA tracker (Basis Peak) incorporated standard technology including an optical sensor and 3-axes accelerometer and was synchronised to participants’ mobile devices enabling them to follow their PA. Raw accelerometer data from the PA tracker was collected and compiled by …
Association of Overlapping Surgery With Increased Risk for Complications Following Hip Surgery
Authors: Bheeshma Ravi, Daniel Pincus, David Wasserstein, Anand Govindarajan, Anjie Huang, Peter C. Austin, Richard Jenkinson, Patrick D. G. Henry, J. Michael Paterson, Hans J. Kreder
Journal: JAMA Internal Medicine (2017)

Overlapping surgery, also known as double-booking, refers to a controversial practice in which a single attending surgeon supervises 2 or more operations, in different operating rooms, at the same time.To determine if overlapping surgery is associated with greater risk for complications following surgical treatment for hip fracture and arthritis.This was a retrospective population-based cohort study in Ontario, Canada (population, 13.6 million), for the years 2009 to 2014. There was 1 year of follow-up. This study encompassed 2 large cohorts. The "hip fracture" cohort captured all persons older than 60 years who underwent surgery for a hip fracture during the study period. The "total hip arthroplasty" (THA) cohort captured all primary elective THA recipients for arthritis during the study period. We matched overlapping and nonoverlapping hip fractures by patient age, patient sex, surgical procedure (for the hip fracture cohort), primary surgeon, and hospital.Procedures were identified as overlapping if they overlapped with another surgical procedure performed by the same primary attending surgeon by more than 30 minutes.Complication (infection, revision, dislocation) within 1 year.There were 38 008 hip fractures, and of those, 960 (2.5%) were overlapping (mean age of patients, 66 years [interquartile range, 57-74 years]; 503 [52.4%] were female). There were 52 869 THAs and of those, 1560 (3.0%) overlapping (mean age, 84 years [interquartile range, 77-89 years]; 1293 [82.9%] were female). After matching, overlapping hip fracture procedures had a greater risk for a complication (hazard ratio [HR], 1.85; 95% CI, 1.27-2.71; P = .001), as did overlapping THA procedures (HR, 1.79; 95% CI, 1.02-3.14; P = .04). Among overlapping hip fracture operations, increasing duration of operative overlap was associated with increasing risk for complications (adjusted odds ratio, 1.07 per 10-minute increase in overlap; P = .009).Overlapping surgery was relatively rare but was associated with an increased risk for surgical complications. Furthermore, increasing duration of operative overlap was associated with an increasing risk for complications. These findings support the notion that overlapping provision of surgery should be part of the informed consent process.
Genomic and Epigenomic Signatures in Ovarian Cancer Associated with Resensitization to Platinum Drugs
Authors: Fang Fang, Horacio Cardenas, Hao Huang, Guanglong Jiang, Susan M. Perkins, Chi Zhang, Harold N. Keer, Yunlong Liu, Kenneth P. Nephew, Daniela Matei
Journal: Cancer Research (2017)

DNA methylation aberrations have been implicated in acquired resistance to platinum drugs in ovarian cancer. In this study, we elucidated an epigenetic signature associated with platinum drug resensitization that may offer utility in predicting the outcomes of patients who are coadministered a DNA methyltransferase inhibitor. The ovarian cancer specimens we analyzed were derived from a recent clinical trial that compared the responses of patients with recurrent platinum-resistant ovarian cancer who received carboplatin plus the DNA methyltransferase inhibitor guadecitabine or a standard-of-care chemotherapy regimen selected by the treating physician. Tumor biopsies or malignant ascites were collected from patients before treatment (day 1, cycle 1) or after treatment (after 2 cycles) for epigenomic and transcriptomic profiling using the Infinium HumanMethylation450 BeadChip (HM450). We defined 94 gene promoters that were hypomethylated significantly by guadecitabine, with 1,659 genes differentially expressed in pretreatment versus posttreatment tumors. Pathway analysis revealed that the experimental regimen significantly altered immune reactivation and DNA repair pathways. Progression-free survival correlated with baseline expression levels of 1,155 genes involved in 25 networks. In functional investigations in ovarian cancer cells, engineered upregulation of certain signature genes silenced by promoter methylation (DOK2, miR-193a, and others) restored platinum drug sensitivity. Overall, our findings illuminate how inhibiting DNA methylation can sensitize ovarian cancer cells to platinum drugs, in large part by altering gene expression patterns related to DNA repair and immune activation, with implications for improving the personalized care and survival outcomes of ovarian cancer patients.Significance: Epigenomic targeting may improve therapeutic outcomes in platinum-resistant and recurrent ovarian cancer in part by effects on DNA repair and antitumor immune responses. Cancer Res; 78(3); 631-44. ©2017 AACR.
Genetic diversity and dissemination pathways of highly pathogenic H5N6 avian influenza viruses from birds in Southwestern China along the East Asian–Australian migration flyway
Authors: Jiahao Zhang, Guangjie Lao, Ronghua Zhang, Zhengji Wei, Hexing Wang, Guanming Su, Nan Shan, Bo Li, Huanan Li, Yuandi Yu, Weixin Jia, Ming Liao, Wenbao Qi
Journal: Journal of Infection (2017)
Clinical–pathological characteristics and health care for Tibetan women with breast cancer: a cross-sectional survey
Authors: Yu-Lan Zhao, Han-Huan Luo, Xin-Tian Zhang, Zashi Bianba, Lin Li, Qian Wang, Lei Guo, Dian Wang, Yong-Ge Ze, Shan Zheng
Journal: The Lancet (2017)
Épidémie communautaire de légionellose à Vic-Gurb, Espagne, octobre et novembre 2005
Authors: M R Sala, C Arias, J M Oliva, A Pedrol, P Roura, A Domínguez
Journal: Eurosurveillance (2007)

Cet article rapporte les resultats de l’enquete menee sur une epidemie communautaire de legionellose dans les villes de Vic et Gurb (centre de la Catalogne, Espagne). 55 cas ont ete rapportes en octobre et novembre 2005. Une enquete epidemiologique et environnementale a ete menee.
The first MICCAI challenge on PET tumor segmentation
Authors: Mathieu Hatt, Baptiste Laurent, Anouar Ouahabi, Hadi Fayad, Shan Tan, Laquan Li, Wei Lu, Vincent Jaouen, Clovis Tauber, Jakub Czakon, Filip Drapejkowski, Witold Dyrka, Sorina Camarasu-Pop, Frédéric Cervenansky, Pascal Girard, Tristan Glatard, Michael Kain, Yao Yao, Christian Barillot, Assen Kirov, Dimitris Visvikis
Journal: Medical Image Analysis (2017)
Reply to Jae Hung Jung, Julia L. Han, and Philipp Dahm's Letter to the Editor re: Vasileios I. Sakalis, Markos Karavitakis, Dina Bedretdinova, et al. Medical Treatment of Nocturia in Men with Lower Urinary Tract Symptoms: Systematic Review by the European Association of Urology Guidelines Panel for Male Lower Urinary Tract Symptoms. Eur Urol 2017;72:757–69
Authors: Vasileios I. Sakalis, Stavros Gravas, Marcus J. Drake
Journal: European Urology (2017)
RAL GTPases: Biology and Potential as Therapeutic Targets in Cancer
Authors: Chao Yan, Dan Theodorescu
Journal: Pharmacological Reviews (2017)

More than a hundred proteins comprise the RAS superfamily of small GTPases. This family can be divided into RAS, RHO, RAB, RAN, ARF, and RAD subfamilies, with each shown to play distinct roles in human cells in both health and disease. The RAS subfamily has a well-established role in human cancer with the three genes, <i>HRAS</i>, <i>KRAS</i>, and <i>NRAS</i> being the commonly mutated in tumors. These <i>RAS</i> mutations, most often functionally activating, are especially common in pancreatic, lung, and colorectal cancers. Efforts to inhibit RAS and related GTPases have produced inhibitors targeting the downstream effectors of RAS signaling, including inhibitors of the RAF-mitogen-activated protein kinase/extracellular signal-related kinase (ERK)-ERK kinase pathway and the phosphoinositide-3-kinase-AKT-mTOR kinase pathway. A third effector arm of RAS signaling, mediated by RAL (RAS like) has emerged in recent years as a critical driver of RAS oncogenic signaling and has not been targeted until recently. RAL belongs to the RAS branch of the RAS superfamily and shares a high structural similarity with RAS. In human cells, there are two genes, <i>RALA</i> and <i>RALB</i>, both of which have been shown to play roles in the proliferation, survival, and metastasis of a variety of human cancers, including lung, colon, pancreatic, prostate, skin, and bladder cancers. In this review, we summarize the latest knowledge of RAL in the context of human cancer and the recent advancements in the development of cancer therapeutics targeting RAL small GTPases.
Magnesium phosphate ceramics incorporating a novel indene compound promote osteoblast differentiation in vitro and bone regeneration in vivo
Authors: Ju Ang Kim, Hui-suk Yun, Young-Ae Choi, Jung-Eun Kim, So-Young Choi, Tae-Geon Kwon, Young Kyung Kim, Tae-Yub Kwon, Myung Ae Bae, Nak Jeong Kim, Yong Chul Bae, Hong-In Shin, Eui Kyun Park
Journal: Biomaterials (2017)
Abstract 14917: Single-beat Estimation of Preload Recruitable Stroke Work
Authors: Ryo Inuzuka, Hideaki Senzaki
Journal: Circulation (2016)

Introduction:  The preload recruitable stroke work (PRSW) slope, M w , is a load-insensitive measure of contractility, but its clinical application has been limited by the need to record multiple beats over a wide volume range. In a previous study, we found that M w  is an end-systolic pressure when the end-systolic dimension is equal to the dimension-axis intercept of the PRSW relationship, D w .   Hypothesis:  We hypothesized that the ratio of M w  to mean ejection pressure (Pm, i.e., stroke work/stoke volume), defined as K, is primarily determined by baseline hemodynamic conditions, providing a simple means of estimating single-beat M w  as K*Pm.   Methods:  Pressure-dimension loops were recorded in 14 conscious dogs equipped with sonomicrometers and micromanometers. Multiple-beat left ventricular (LV) M w  was determined during vena caval occlusion under various hemodynamic conditions. Univariate and multivariate linear regression analysis was used to assess the relationship between K and conventional baseline single-beat hemodynamic parameters.   Results:  Various hemodynamic conditions yielded an M w  range from 25 to 147 mmHg and a K range from 0.26 to 1.0. Univariate predictors of K included LV end-systolic dimension, LV end-diastolic dimension, maximum ventricular pressure, fractional shortening (FS), max dP/dt, stroke dimension, and regional stroke work (rSW). On multivariate analysis, FS (p w  almost equaled mean ejection pressure (K = 0.95+-0.04), with FS over 0.3 or max dP/dt over 4,000 mmHg/s. Moreover, K was mathematically identical to Ees/Ea, a marker of ventricular-arterial (VA) coupling; thus, Ees was also accurately estimated from baseline single beats.   Conclusions:  The ratio of M w  to mean ejection pressure reflects VA coupling, which is strongly correlated with conventional hemodynamic parameters. This single-beat method accurately estimates a marker of VA coupling as well as a load-insensitive measure of contractility in the PRSW framework, and thus provides a powerful tool for precisely assessing cardiovascular dynamics.
Abstract 64: Abnormal splicing events in adenoid cystic carcinoma
Authors: Brandon Leonard, Joseph O. Humtsoe, Hyun-Su Kim, Shizhang Ling, Luigi Marchionni, Elana J. Fertig, Michael Considine, Patrick Ha
Journal: Clinical Cancer Research (2017)

Salivary gland adenoid cystic carcinoma (ACC) is a relatively rare and understudied malignancy. While this disease can often be controlled locally by surgery and radiation therapy, distant metastases occur in nearly 50% of cases. Interestingly, these metastases can remain asymptomatic for several years, and there are currently no factors that are known to contribute to their dormancy or aggressiveness. Furthermore, there are no targeted chemotherapeutic agents available to treat any stage of this disease.To identify aberrations that contribute to ACC tumorigenesis, we performed whole genome methylation profiling, RNA sequencing, and exome sequencing on 18 primary ACC tumors and matched normal salivary gland tissue. A novel analysis methodology of Splice Expression Variability Analysis (SEVA) coupled with outlier statistical analyses of mRNA splice junctions revealed the presence of several abnormal splicing events (ASEs) in the studied tumors. Interestingly, the ASEs were significantly overrepresented in tumors as compared to matched normal salivary gland tissue. In vitro analyses found that many of the ASEs are also expressed in the only validated ACC cell line, MDA-ACC01, and multiple patient-derived xenograft (PDX) models of ACC. Overall, these studies have identified an unanticipated aberration in ACC and developed a model in which to study ASEs. Future work will be aimed at determining the functional impact that ASEs have on tumor initiation and growth.Citation Format: Brandon Leonard, Joseph O. Humtsoe, Hyun-Su Kim, Shizhang Ling, Luigi Marchionni, Elana J. Fertig, Michael Considine, Patrick Ha. Abnormal splicing events in adenoid cystic carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 64.
<i>The BMJ</i> charity appeal Christmas 2017: Médecins Sans Frontières’ volunteer doctors need your support
Authors: Jane Feinmann
Journal: BMJ (2017)

The charity has decades of experience in bringing medical aid to the neediest people in emergency situations such as those in war torn Yemen, as <b>Jane Feinmann</b> writes. This is why <i>The BMJ</i> has chosen MSF for its charity appeal this year. Please give generously
STAT4 and T-bet control follicular helper T cell development in viral infections
Authors: Jason S. Weinstein, Brian J. Laidlaw, Yisi Lu, Jessica K. Wang, Vincent P. Schulz, Ningcheng Li, Edward I. Herman, Susan M. Kaech, Patrick G. Gallagher, Joe Craft
Journal: The Journal of Experimental Medicine (2017)

Follicular helper T (Tfh) cells promote germinal center (GC) B cell survival and proliferation and guide their differentiation and immunoglobulin isotype switching by delivering contact-dependent and soluble factors, including IL-21, IL-4, IL-9, and IFN-γ. IL-21 and IFN-γ are coexpressed by Tfh cells during viral infections, but transcriptional regulation of these cytokines is not completely understood. In this study, we show that the T helper type 1 cell (Th1 cell) transcriptional regulators T-bet and STAT4 are coexpressed with Bcl6 in Tfh cells after acute viral infection, with a temporal decline in T-bet in the waning response. T-bet is important for Tfh cell production of IFN-γ, but not IL-21, and for a robust GC reaction. STAT4, phosphorylated in Tfh cells upon infection, is required for expression of T-bet and Bcl6 and for IFN-γ and IL-21. These data indicate that T-bet is expressed with Bcl6 in Tfh cells and is required alongside STAT4 to coordinate Tfh cell IL-21 and IFN-γ production and for promotion of the GC response after acute viral challenge.