tbuckley/cabot-search huggingface dataset:
Gene Therapy-Induced Antigen-Specific Tregs Inhibit Neuro-inflammation and Reverse Disease in a Mouse Model of Multiple Sclerosis
Authors: Geoffrey D. Keeler, Sandeep Kumar, Brett Palaschak, Emily L. Silverberg, David M. Markusic, Noah T. Jones, Brad E. Hoffman
Journal: Molecular Therapy (2017)

The devastating neurodegenerative disease multiple sclerosis (MS) could substantially benefit from an adeno-associated virus (AAV) immunotherapy designed to restore a robust and durable antigen-specific tolerance. However, developing a sufficiently potent and lasting immune-regulatory therapy that can intervene in ongoing disease is a major challenge and has thus been elusive. We addressed this problem by developing a highly effective and robust tolerance-inducing in vivo gene therapy. Using a pre-clinical animal model, we designed a liver-targeting gene transfer vector that expresses full-length myelin oligodendrocyte glycoprotein (MOG) in hepatocytes. We show that by harnessing the tolerogenic nature of the liver, this powerful gene immunotherapy restores immune tolerance by inducing functional MOG-specific regulatory T cells (Tregs) in vivo, independent of major histocompatibility complex (MHC) restrictions. We demonstrate that mice treated prophylactically are protected from developing disease and neurological deficits. More importantly, we demonstrate that when given to mice with preexisting disease, ranging from mild neurological deficits to severe paralysis, the gene immunotherapy abrogated CNS inflammation and significantly reversed clinical symptoms of disease. This specialized approach for inducing antigen-specific immune tolerance has significant therapeutic potential for treating MS and other autoimmune disorders. The devastating neurodegenerative disease multiple sclerosis (MS) could substantially benefit from an adeno-associated virus (AAV) immunotherapy designed to restore a robust and durable antigen-specific tolerance. However, developing a sufficiently potent and lasting immune-regulatory therapy that can intervene in ongoing disease is a major challenge and has thus been elusive. We addressed this problem by developing a highly effective and robust tolerance-inducing in vivo gene therapy. Using a pre-clinical animal model, we designed a liver-targeting gene transfer vector that expresses full-length myelin oligodendrocyte glycoprotein (MOG) in hepatocytes. We show that by harnessing the tolerogenic nature of the liver, this powerful gene immunotherapy restores immune tolerance by inducing functional MOG-specific regulatory T cells (Tregs) in vivo, independent of major histocompatibility complex (MHC) restrictions. We demonstrate that mice treated prophylactically are protected from developing disease and neurological deficits. More importantly, we demonstrate that when given to mice with preexisting disease, ranging from mild neurological deficits to severe paralysis, the gene immunotherapy abrogated CNS inflammation and significantly reversed clinical symptoms of disease. This specialized approach for inducing antigen-specific immune tolerance has significant therapeutic potential for treating MS and other autoimmune disorders.
Abstract 19300: Real-life Evidence of Stroke Prevention in Patients With Atrial Fibrillation: The RELIEF Study
Authors: Craig Coleman, Thomas Evers, Birgit Ehlken
Journal: Circulation (2015)

Introduction: Limited data is available on real-world outcomes in rivaroxaban compared to vitamin K antagonist (VKA) users with non-valvular atrial fibrillation (NVAF). Hypothesis: To assess the effectiveness of newly initiated rivaroxaban or VKA therapy among NVAF patients. Methods: The ‘REal-LIfe Evidence on stroke prevention in patients with atrial Fibrillation’ (RELIEF) study was a retrospective analysis performed in the outpatient setting in Germany using data from the Primary Care Physician panel of a longitudinal electronic medical record database ( IMS Disease Analyzer). Patients had to be ≥18 years of age, newly initiated on rivaroxaban or a VKA (mostly phenprocoumon in Germany) between January 2012 and October 2013, have a diagnosis of NVAF on the day of the first qualifying anticoagulant prescription (index date) or anytime during the 365 days prior, and have follow-up ≥360 days after the index date. Patients were 1:1 propensity score matched. The primary endpoint was the composite of ischemic stroke (International Classification of Disease, Tenth Revision [ICD-10] code I63), transient ischemic attack (TIA) (ICD-10 code G45, except G45.3), intracerebral hemorrhage (ICD-10 code I61), other non-traumatic intracranial hemorrhage (ICD-10 code I62), systemic embolism (ICD-10 code I74) and myocardial infarction (ICD-10 codes I21, I22). Kaplan-Meier survival analysis on the primary endpoint in the matched cohorts was performed, and the time-to-event was reported as a hazard ratio (HR) and 95% confidence interval (CI). Results: A total of 1,039 VKA and 1,039 rivaroxaban users were included and 57 events (20 in rivaroxaban, 37 in VKA) were identified during a one-year follow-up. The incidence of the composite endpoint was significantly lower in rivaroxaban compared to VKA users (1.97 vs. 3.68 events/100 person-years) corresponding to a hazard ratio of 0.536 (95%CI: 0.311-0.923; p=0.0245). Ischemic stroke (0.69 vs. 1.58 events/100 person-years) and TIA (0.59 vs. 1.08 events/100 person-years) were less frequent in the rivaroxaban cohort . Conclusions: The findings indicate that rivaroxaban may be associated with superior effectiveness compared to a VKA when utilized in a real-world setting.
Radiomics Analysis for Evaluation of Pathological Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer
Authors: Zhenyu Liu, Xiao-Yan Zhang, Yan-Jie Shi, Lin Wang, Hai-Tao Zhu, Zhenchao Tang, Shuo Wang, Xiao-Ting Li, Jie Tian, Ying-Shi Sun
Journal: Clinical Cancer Research (2017)

Purpose: To develop and validate a radiomics model for evaluating pathologic complete response (pCR) to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer (LARC).Experimental Design: We enrolled 222 patients (152 in the primary cohort and 70 in the validation cohort) with clinicopathologically confirmed LARC who received chemoradiotherapy before surgery. All patients underwent T2-weighted and diffusion-weighted imaging before and after chemoradiotherapy; 2,252 radiomic features were extracted from each patient before and after treatment imaging. The two-sample t test and the least absolute shrinkage and selection operator regression were used for feature selection, whereupon a radiomics signature was built with support vector machines. Multivariable logistic regression analysis was then used to develop a radiomics model incorporating the radiomics signature and independent clinicopathologic risk factors. The performance of the radiomics model was assessed by its calibration, discrimination, and clinical usefulness with independent validation.Results: The radiomics signature comprised 30 selected features and showed good discrimination performance in both the primary and validation cohorts. The individualized radiomics model, which incorporated the radiomics signature and tumor length, also showed good discrimination, with an area under the receiver operating characteristic curve of 0.9756 (95% confidence interval, 0.9185-0.9711) in the validation cohort, and good calibration. Decision curve analysis confirmed the clinical utility of the radiomics model.Conclusions: Using pre- and posttreatment MRI data, we developed a radiomics model with excellent performance for individualized, noninvasive prediction of pCR. This model may be used to identify LARC patients who can omit surgery after chemoradiotherapy. Clin Cancer Res; 23(23); 7253-62. ©2017 AACR.
Intensive Versus Standard Blood Pressure Control in SPRINT-Eligible Participants of ACCORD-BP
Authors: Leo F. Buckley, Dave L. Dixon, George F. Wohlford, Dayanjan S. Wijesinghe, William L. Baker, Benjamin W. Van Tassell
Journal: Diabetes Care (2017)

OBJECTIVE We sought to determine the effect of intensive blood pressure (BP) control on cardiovascular outcomes in participants with type 2 diabetes mellitus (T2DM) and additional risk factors for cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS This study was a post hoc, multivariate, subgroup analysis of ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure) participants. Participants were eligible for the analysis if they were in the standard glucose control arm of ACCORD-BP and also had the additional CVD risk factors required for SPRINT (Systolic Blood Pressure Intervention Trial) eligibility. We used a Cox proportional hazards regression model to compare the effect of intensive versus standard BP control on CVD outcomes. The “SPRINT-eligible” ACCORD-BP participants were pooled with SPRINT participants to determine whether the effects of intensive BP control interacted with T2DM. RESULTS The mean baseline Framingham 10-year CVD risk scores were 14.5% and 14.8%, respectively, in the intensive and standard BP control groups. The mean achieved systolic BP values were 120 and 134 mmHg in the intensive and standard BP control groups (P &amp;lt; 0.001). Intensive BP control reduced the composite of CVD death, nonfatal myocardial infarction (MI), nonfatal stroke, any revascularization, and heart failure (hazard ratio 0.79; 95% CI 0.65–0.96; P = 0.02). Intensive BP control also reduced CVD death, nonfatal MI, and nonfatal stroke (hazard ratio 0.69; 95% CI 0.51–0.93; P = 0.01). Treatment-related adverse events occurred more frequently in participants receiving intensive BP control (4.1% vs. 2.1%; P = 0.003). The effect of intensive BP control on CVD outcomes did not differ between patients with and without T2DM (P &amp;gt; 0.62). CONCLUSIONS Intensive BP control reduced CVD outcomes in a cohort of participants with T2DM and additional CVD risk factors.
Advances in the physiological assessment and diagnosis of GERD
Authors: Edoardo Savarino, Albert J. Bredenoord, Mark Fox, John E. Pandolfino, Sabine Roman, C. Prakash Gyawali
Journal: Nature Reviews Gastroenterology & Hepatology (2017)

Abstract GERD is a common condition worldwide. Key mechanisms of disease include abnormal oesophagogastric junction structure and function, and impaired oesophageal clearance. A therapeutic trial of acid-suppressive PPI therapy is often the initial management, with endoscopy performed in the setting of alarm symptoms and to exclude other conditions. If symptoms persist and endoscopy does not reveal evidence of GERD, oesophageal function tests are performed, including oesophageal manometry and ambulatory reflux monitoring. However, reflux episodes can be physiological, and some findings on endoscopy and manometry can be encountered in asymptomatic individuals without GERD symptoms. The diagnosis of GERD on the basis of functional oesophageal testing has been previously reported, but no updated expert recommendations on indications and the interpretation of oesophageal function testing in GERD has been made since the Porto consensus over a decade ago. In this Consensus Statement, we aim to describe modern oesophageal physiological tests and their analysis with an emphasis on establishing indications and consensus on interpretation parameters of oesophageal function testing for the evaluation of GERD in clinical practice. This document reflects the collective conclusions of the international GERD working group, incorporating existing data with expert consensus opinion.
Medical Devices for Pediatric Apnea Monitoring and Therapy: Past and New Trends
Authors: Salvatore Andrea Pullano, Ifana Mahbub, Maria Giovanna Bianco, Samira Shamsir, Syed Kamrul Islam, Mark S. Gaylord, Vichien Lorch, Antonino S. Fiorillo
Journal: IEEE Reviews in Biomedical Engineering (2017)

Apnea in the pediatric population is associated with increased morbidity and mortality in a large number of developed as well as developing countries. It is even more prominent in preterm newborn infants and is commonly referred to as apnea of prematurity. Its current diagnosis and therapy involve the use of traditional technologies, which often result in discomfort to the infants due to the use of invasive devices attached to their sensitive skin, especially in overnight clinical sleep analysis (for over a 12- or 24-h period). Emerging trends for the point-of-care diagnosis of this sleep disorder are focused on the design of integrated devices for less complex and noninvasive monitoring. This paper presents a review of the state of the art of clinical technologies and methodologies for sleep apnea detection and their pros and cons, with particular focus on their working principles and relevance to pediatrics. Moreover, an in-depth discussion on emerging future technologies envisioned to be integral parts of the daily home-based applications is included in the paper.
Dissociation in Psychiatric Disorders: A Meta-Analysis of Studies Using the Dissociative Experiences Scale
Authors: Lisa Lyssenko, Christian Schmahl, Laura Bockhacker, Ruben Vonderlin, Martin Bohus, Nikolaus Kleindienst
Journal: American Journal of Psychiatry (2017)

Objective: Dissociation is a complex, ubiquitous construct in psychopathology. Symptoms of dissociation are present in a variety of mental disorders and have been connected to higher burden of illness and poorer treatment response, and not only in disorders with high levels of dissociation. This meta-analysis offers a systematic and evidence-based study of the prevalence and distribution of dissociation, as assessed by the Dissociative Experiences Scale, within different categories of mental disorders, and it updates an earlier meta-analysis. Method: More than 1,900 original publications were screened, and 216 were included in the meta-analysis, comprising 15,219 individuals in 19 diagnostic categories. Results: The largest mean dissociation scores were found in dissociative disorders (mean scores >35), followed by posttraumatic stress disorder, borderline personality disorder, and conversion disorder (mean scores >25). Somatic symptom disorder, substance-related and addictive disorders, feeding and eating disorders, schizophrenia, anxiety disorder, OCD, and most affective disorders also showed mean dissociation scores >15. Bipolar disorders yielded the lowest dissociation scores (mean score, 14.8). Conclusions: The findings underline the importance of careful psychopathological assessment of dissociative symptoms in the entire range of mental disorders.
Abstract 13105: Acute Cardiorenal Syndrome: The Prevalence of Impaired, Improved and Stable Renal Function in Patients With Acute Heart Failure
Authors: Ryan Reid, Sirisha Valupadas, Bilal Quarni, Brian H Rowe, Finlay McAlister, Justin Ezekowitz, Branko Braam
Journal: Circulation (2013)

Introduction:  Acute heart failure (AHF) is frequently accompanied by worsening renal function (WRF) and this has been linked to poor outcomes. However, prior studies have not accounted for the changes in renal function relative to baseline renal function, or the outcomes of patients with improved renal function (RF). We investigated the prevalence of WRF and improved RF in patients admitted with AHF.   Methods:  We included 276 AHF patients enrolled at the University of Alberta Hospital into the AHF-EM study. Definitions from the Kidney Disease Outcomes Quality Initiative (K/DOQI) stages (1-5 stages) were used using eGFR (MDRD) from baseline and discharge. WRF was defined as worsening from stage 1, 2, 3a at admission to 3B or worse, from 3B to worse, or from 4 to 5. Improved RF was defined as improvement of at least one class from 3B, 4 or 5. Stable RF was defined as renal function within the same K/DOQI stage in stages 3A, 3B, 4, or 5.   Results:  Patients were a mean age of 76 years, 50% were male, 34% had diabetes and the mean ejection fraction was 41%. The prevalence of WRF was 13%, Improved RF 10% and stable RF 31%. Improved RF patients were found to have the lowest in-hospital mortality rates (0%), compared to Stable RF (7%) and WRF patients (16%) (p=0.016). Patterns of medication use, medical history or admission parameters such as blood pressure, hydration status, and blood serum electrolytes were not significantly different among groups.   Conclusion:  When patients with an eGFR  2  are considered, the prevalence of WRF is lower than previously estimated, and interestingly a similar number of patients show improvement of RF. Improvement of RF upon treatment of AHF likely indicates ‘genuine’ acute cardiorenal syndrome, while those with WRF may be ‘treatment associated’ acute cardiorenal syndrome. The latter may reflect more severe underlying pathophysiological picture that leads to poor outcomes. (the study was funded by the Canadian Institute for Health Research)
Abstract 18509: The Distribution and Characteristics of Endogenous Cardiac Stem Cells in All Four Chambers of the Adult Human Heart
Authors: Sajiram Sarvananthan, Fiona C Lewis, Giulia Gritti, Beverley J Henning, Najma Latif, Padmini Sarathchandra, Magdi Yacoub, Sian E Harding, Prakash P Punjabi, Georgina M Ellison-Hughes
Journal: Circulation (2016)

Introduction: The adult myocardium, including human, harbours a population of resident (endogenous) multi-potent cardiac stem cells (eCSCs). We evaluated the distribution, stem cell properties, dif...
‘World Rugby Concussion’ by World Rugby Limited: a smartphone application for the general public
Authors: Osman Hassan Ahmed, Adam Arthur, Alastair Bolton, Alex Evens, Philip Slemon
Journal: British Journal of Sports Medicine (2017)

‘World Rugby Concussion’ by World Rugby Limited.

Injury management.

iOS 7.0 or later. Compatible with iPhone, iPad and iPod touch; Android—4.0.3 and up.

Free (no in-app purchases)—V.1.4.2 (18 May 2017).

Concussion is one of the most common injuries in rugby union, with at least one medical attendance per team for a head injury,1 and the World Rugby Concussion app compliments the many existing concussion apps already in circulation.2 Targeted at the general public, this app attempts to both enhance the user’s knowledge and understanding of the basic management of concussion. The app has a focus on concussion symptoms and concussion management guidelines, with a clear layout that hosts the navigational tabs (‘Home’, ‘Pocket CRT’, ‘GRTP’, ‘Video’ and ‘Info’).

The ‘Home’ tab (figure 1) provides training modules in five topics, including a section dedicated …
Regulation of immune-related diseases by multiple factors of chromatin, exosomes, microparticles, vaccines, oxidative stress, dormancy, protein quality control, inflammation and microenvironment: a meeting report of 2017 International Workshop of the Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine on Tumor Immunology
Authors: Bing Cui, Xuetao Cao, Weiping Zou, Yonghong Wan, Ning Wang, Yaohe Wang, Pingping Li, Fang Hua, Yuying Liu, Xiaowei Zhang, Ke Li, Xiaoxi Lv, Bo Huang, Zhuowei Hu
Journal: Acta Pharmaceutica Sinica B (2017)

Immune cells play key roles in cancer and chronic inflammatory disease. A better understanding of the mechanisms and risks will help develop novel target therapies. At the 2017 International Workshop of the Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine on Tumor Immunology held in Beijing, China, on May 12, 2017, a number of speakers reported new findings and ongoing studies on immune-related diseases such as cancer, fibrotic disease, diabetes, and others. A considerably insightful overview was provided on cancer immunity, tumor microenvironments, and new immunotherapy for cancer. In addition, chronic inflammatory diseases were discussed. These findings may offer new insights into targeted immunotherapy.
Phase II study of the safety and efficacy of oral capecitabine in patients with platinum-pretreated advanced or recurrent cervical carcinoma
Authors: S. Lepori, C. Fontanella, G. Maltese, E. Tripodi, F. Martinelli, G. Bogani, A. Ditto, M. Signorelli, C. Scaffa, F. Raspagliesi, D. Lorusso
Journal: Annals of Oncology (2017)
A pleiotropic effect of the<i><scp>APOE</scp></i>gene: association of<i><scp>APOE</scp></i>polymorphisms with multibacillary leprosy in Han Chinese from Southwest China
Authors: D. Wang, D.‐F. Zhang, G.‐D. Li, R. Bi, Y. Fan, Y. Wu, X.‐F. Yu, H. Long, Y.‐Y. Li, Y.‐G. Yao
Journal: British Journal of Dermatology (2017)

BackgroundPatients with leprosy have a very low risk of Alzheimer disease (AD) and β‐amyloid (Aβ) deposition is significantly lower in the brain tissue of elderly patients with leprosy compared with age‐matched controls. Apolipoprotein E (ApoE) plays a critical role in lipid metabolic pathways and in the brain, facilitating the proteolytic clearance of Aβ. We hypothesized that APOE confers risk of leprosy as lipid metabolism is involved in Mycobacterium leprae infection.
Loss of FOXO1 Cooperates with TMPRSS2–ERG Overexpression to Promote Prostate Tumorigenesis and Cell Invasion
Authors: Yinhui Yang, Alexandra M. Blee, Dejie Wang, Jian An, Yunqian Pan, Yuqian Yan, Tao Ma, Yundong He, Joseph Dugdale, Xiaonan Hou, Jun Zhang, S. John Weroha, Wei-Guo Zhu, Y. Alan Wang, Ronald A. DePinho, Wanhai Xu, Haojie Huang
Journal: Cancer Research (2017)

E26 transformation-specific transcription factor ERG is aberrantly overexpressed in approximately 50% of all human prostate cancer due to
A unique event for the francophone respiratory community
Authors: Louis-Philippe Boulet, Elyse Bissonnette, Marc Humbert, Bernard Maître, Bernard Pigearias
Journal: European Respiratory Journal (2017)

In the 17–19th centuries, French was the language of international communication, as English has since become. It is still one of the official languages of many international organisations, is spoken by >250 million individuals worldwide, and is one of the official languages of 41 countries and dependent entities \[1, 2\] (figure 1). French-speaking countries, present on four continents, represent a large variety of cultural and socioeconomic backgrounds, including not only highly developed but also rapidly developing countries. An event that should reinforce the links between French-speaking respiratory medicine communities worldwide <http://ow.ly/iMvk30eQzQi>
PALLAS: PALbociclib CoLlaborative adjuvant study: A randomized phase 3 trial of palbociclib with standard adjuvant endocrine therapy versus standard adjuvant endocrine therapy alone for HR+/HER2- early breast cancer
Authors: E.L. Mayer, A.M. Demichele, G. Pfeiler, W. Barry, O. Metzger, P. Rastogi, F. Symmans, H.J. Burstein, K. Miller, S. Loibl, S. Schmatloch, T. Goulioti, D. Zardavas, C. Fesl, M. Koehler, C. Huang Bartlett, X. Huang, M. Piccart, E. Winer, M. Gnant
Journal: Annals of Oncology (2017)
PGC-1α Promotes Breast Cancer Metastasis and Confers Bioenergetic Flexibility against Metabolic Drugs
Authors: Sylvia Andrzejewski, Eva Klimcakova, Radia M. Johnson, Sébastien Tabariès, Matthew G. Annis, Shawn McGuirk, Jason J. Northey, Valérie Chénard, Urshila Sriram, David J. Papadopoli, Peter M. Siegel, Julie St-Pierre
Journal: Cell Metabolism (2017)
GW28-e0427 MiR-155 in macrophage regulates cardiac function and fibrosis after myocardial infarction possibly through SOCS1-dependent inflammatory response
Authors: Yinfen Zhang, Wangwei He, Yu Huang, Yongquan Lu, Liyuan Zhu, Lin Lin, Jun Li, Qiang Xie
Journal: Journal of the American College of Cardiology (2017)