tbuckley/cabot-search huggingface dataset:
YTH Domain: A Family of <i>N</i> <b>6</b>-Methyladenosine (m<b>6</b>A) Readers
Authors: Shanhui Liao, Hongbin Sun, Chao Xu
Journal: Genomics Proteomics & Bioinformatics (2018)

Abstract Like protein and DNA, different types of RNA molecules undergo various modifications. Accumulating evidence suggests that these RNA modifications serve as sophisticated codes to mediate RNA behaviors and many important biological functions. N6-methyladenosine (m6A) is the most abundant internal RNA modification found in a variety of eukaryotic RNAs, including but not limited to mRNAs, tRNAs, rRNAs, and long non-coding RNAs (lncRNAs). In mammalian cells, m6A can be incorporated by a methyltransferase complex and removed by demethylases, which ensures that the m6A modification is reversible and dynamic. Moreover, m6A is recognized by the YT521-B homology (YTH) domain-containing proteins, which subsequently direct different complexes to regulate RNA signaling pathways, such as RNA metabolism, RNA splicing, RNA folding, and protein translation. Herein, we summarize the recent progresses made in understanding the molecular mechanisms underlying the m6A recognition by YTH domain-containing proteins, which would shed new light on m6A-specific recognition and provide clues to the future identification of reader proteins of many other RNA modifications.
Disease-driving CD4+ T cell clonotypes persist for decades in celiac disease
Authors: Louise F. Risnes, Asbjørn Christophersen, Shiva Dahal-Koirala, Ralf S. Neumann, Geir K. Sandve, Vikas K. Sarna, Knut E.A. Lundin, Shuo-Wang Qiao, Ludvig M. Sollid
Journal: Journal of Clinical Investigation (2018)

Little is known about the repertoire dynamics and persistence of pathogenic T cells in HLA-associated disorders. In celiac disease, a disorder with a strong association with certain HLA-DQ allotypes, presumed pathogenic T cells can be visualized and isolated with HLA-DQ:gluten tetramers, thereby enabling further characterization. Single and bulk populations of HLA-DQ:gluten tetramer-sorted CD4+ T cells were analyzed by high-throughput DNA sequencing of rearranged TCR-α and -β genes. Blood and gut biopsy samples from 21 celiac disease patients, taken at various stages of disease and in intervals of weeks to decades apart, were examined. Persistence of the same clonotypes was seen in both compartments over decades, with up to 53% overlap between samples obtained 16 to 28 years apart. Further, we observed that the recall response following oral gluten challenge was dominated by preexisting CD4+ T cell clonotypes. Public features were frequent among gluten-specific T cells, as 10% of TCR-α, TCR-β, or paired TCR-αβ amino acid sequences of total 1813 TCRs generated from 17 patients were observed in 2 or more patients. In established celiac disease, the T cell clonotypes that recognize gluten are persistent for decades, making up fixed repertoires that prevalently exhibit public features. These T cells represent an attractive therapeutic target.
Elective endoscopic clipping for the treatment of symptomatic diverticular disease: a potential for ‘cure’
Authors: Amyn Haji, Aris Plastiras, Monica Ortenzi, Shraddha Gulati, Andrew Emmanuel, Bu’Hussain Hayee
Journal: Gut (2018)

Symptomatic diverticular disease (DD) is a major worldwide healthcare burden, and diverticular bleeding is one of its most common manifestations. Endoscopic clipping of selected diverticula in the acute or early posthaemorrhage period has been reported as a haemostatic intervention, but the effect of elective clipping is not known.

We present the prospective series of elective endoscopic clipping with the aim of treating all visible diverticula in patients with previous bleeding, resulting in near-complete disappearance of DD.

This may have significant implications for the management of DD worldwide and warrants further prospective research.

This was a prospective, single-centre study enrolling consecutive patients attending a specialist DD clinic at our institution, who had been previously hospitalised for lower GI bleeding due to DD (table 1). The procedures and follow-up colonoscopies were carried out from April 2015 to April 2017 at King’s College Hospital, London, UK. Patients with other GI pathologies were excluded from the study.

View this table:

Table 1 
Episodes of confirmed diverticular bleeding requiring transfusion and hospitalisation before the procedure and in 1 year of follow-up



Patients were enrolled only if the diagnosis had been confirmed by abdominopelvic CT scan and full colonoscopy during an episode of PR bleeding. The results and management plan were discussed in a multidisciplinary team meeting with informed consent from the patients. Any patients requiring previous admissions and transfusion for confirmed severe diverticular bleeding were included in the study.

Patients underwent colonoscopy after full oral bowel preparation (Moviprep, Norgine Pharmaceuticals) under conscious sedation with midazolam and fentanyl. On withdrawal of the colonoscope (Olympus CF-H260DL or CF-H260AZL), all visible diverticula were carefully cleaned of residual stool using water delivered through the working channel …
Identification of a cell-penetrating peptide applicable to a protein-based transcription activator-like effector expression system for cell engineering
Authors: Tomoki Takashina, Takayoshi Koyama, Satoshi Nohara, Masakatsu Hasegawa, Akira Ishiguro, Kenta Iijima, Jun Lu, Mari Shimura, Tadashi Okamura, Tetsushi Sakuma, Takashi Yamamoto, Yukihito Ishizaka
Journal: Biomaterials (2018)
Validation of a quantitative imaging assessment biomarker metric for MRI-estimated proton density fat fraction in a large multi-center clinical trial
Authors: M. Middleton, W. Henderson, J. Cui, A. Mamidipalli, R. Myers, S. Djedjos, C. Yeaton, B. Mccolgan, R. Loomba, C. Sirlin
Journal: Journal of Hepatology (2018)
Prescribable mHealth apps identified from an overview of systematic reviews
Authors: Oyungerel Byambasuren, Sharon Sanders, Elaine Beller, Paul Glasziou
Journal: npj Digital Medicine (2018)

Mobile health apps aimed towards patients are an emerging field of mHealth. Their potential for improving self-management of chronic conditions is significant. Here, we propose a concept of "prescribable" mHealth apps, defined as apps that are currently available, proven effective, and preferably stand-alone, i.e., that do not require dedicated central servers and continuous monitoring by medical professionals. Our objectives were to conduct an overview of systematic reviews to identify such apps, assess the evidence of their effectiveness, and to determine the gaps and limitations in mHealth app research. We searched four databases from 2008 onwards and the Journal of Medical Internet Research for systematic reviews of randomized controlled trials (RCTs) of stand-alone health apps. We identified 6 systematic reviews including 23 RCTs evaluating 22 available apps that mostly addressed diabetes, mental health and obesity. Most trials were pilots with small sample size and of short duration. Risk of bias of the included reviews and trials was high. Eleven of the 23 trials showed a meaningful effect on health or surrogate outcomes attributable to apps. In conclusion, we identified only a small number of currently available stand-alone apps that have been evaluated in RCTs. The overall low quality of the evidence of effectiveness greatly limits the prescribability of health apps. mHealth apps need to be evaluated by more robust RCTs that report between-group differences before becoming prescribable. Systematic reviews should incorporate sensitivity analysis of trials with high risk of bias to better summarize the evidence, and should adhere to the relevant reporting guideline.
Steroidal and non-steroidal FXR agonists elicit clinically-relevant lipoprotein profiles in mice with chimeric humanized livers
Authors: R. Papazyan, K. Rigbolt, R. Lind, M. Feigh, J. Liu, B. Dong, E. Plummer, R.D. Lewis, M. Roth, M. Young
Journal: Journal of Hepatology (2018)
Serological diagnosis of early HCC in NASH: A German multicenter study
Authors: J. Best, L. Bechmann, A. Dechêne, K. Pflanz, S. Bedreli, C. Schotten, T. Berg, J. Fischer, A. Vogel, H. Bantel, A. Weinmann, J. Schattenberg, Y. Huber, H. Wege, K. Schulze, J. von Felden, B. Dominik, R. Thimme, F. Sinner, K. Schuette, K.H. Weiss, S. Berhane, P. Johnson, G. Gerken, A. Canbay
Journal: Journal of Hepatology (2018)
Current Challenges and Opportunities in Treating Glioblastoma
Authors: Andrea Shergalis, Armand Bankhead, Urarika Luesakul, Nongnuj Muangsin, Nouri Neamati
Journal: Pharmacological Reviews (2018)

Glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor, has a high mortality rate despite extensive efforts to develop new treatments. GBM exhibits both intra- and intertumor heterogeneity, lending to resistance and eventual tumor recurrence. Large-scale genomic and proteomic analysis of GBM tumors has uncovered potential drug targets. Effective and "druggable" targets must be validated to embark on a robust medicinal chemistry campaign culminating in the discovery of clinical candidates. Here, we review recent developments in GBM drug discovery and delivery. To identify GBM drug targets, we performed extensive bioinformatics analysis using data from The Cancer Genome Atlas project. We discovered 20 genes, <i>BOC</i>, <i>CLEC4GP1</i>, <i>ELOVL6</i>, <i>EREG</i>, <i>ESR2</i>, <i>FDCSP</i>, <i>FURIN</i>, <i>FUT8-AS1</i>, <i>GZMB</i>, <i>IRX3</i>, <i>LITAF</i>, <i>NDEL1</i>, <i>NKX3-1</i>, <i>PODNL1</i>, <i>PTPRN</i>, <i>QSOX1</i>, <i>SEMA4F</i>, <i>TH</i>, <i>VEGFC</i>, and <i>C20orf166AS1</i> that are overexpressed in a subpopulation of GBM patients and correlate with poor survival outcomes. Importantly, nine of these genes exhibit higher expression in GBM versus low-grade glioma and may be involved in disease progression. In this review, we discuss these proteins in the context of GBM disease progression. We also conducted computational multi-parameter optimization to assess the blood-brain barrier (BBB) permeability of small molecules in clinical trials for GBM treatment. Drug delivery in the context of GBM is particularly challenging because the BBB hinders small molecule transport. Therefore, we discuss novel drug delivery methods, including nanoparticles and prodrugs. Given the aggressive nature of GBM and the complexity of targeting the central nervous system, effective treatment options are a major unmet medical need. Identification and validation of biomarkers and drug targets associated with GBM disease progression present an exciting opportunity to improve treatment of this devastating disease.
Hip and groin time-loss injuries decreased slightly but injury burden remained constant in men’s professional football: the 15-year prospective UEFA Elite Club Injury Study
Authors: Jonas Werner, Martin Hägglund, Jan Ekstrand, Markus Waldén
Journal: British Journal of Sports Medicine (2018)

Hip and groin injuries are common in men's professional football, but the time-trend of these injuries is not known.To investigate hip and groin injury rates, especially time-trends, in men's professional football over 15 consecutive seasons.Prospective cohort study.Men's professional football.47 European teams were followed prospectively for a varying number of seasons between 2001/2002 and 2015/2016, totalling 268 team seasons. Time-loss injuries and individual player exposure during training and matches were recorded. Injury rate was defined as the number of injuries/1000 hours and injury burden as the number of lay-off days/1000 hours. Time-trends for total hip and groin injuries and adductor-related injury rates were analysed using Poisson regression, and injury burden was analysed using a negative binomial regression model.Hip and groin injuries contributed 1812 out of 12 736 injuries (14%), with adductor-related injury as the most common of hip and groin injuries (n=1139, 63%). The rates of hip and groin injury and adductor-related injury were 1.0/1000 hours and 0.6/1000 hours, and these rates decreased significantly with on average 2% (Exp(b)=0.98, 95% CI 0.97 to 0.99, P=0.003) and 3% (Exp(b)=0.97, 95% CI 0.95 to 0.99, P<0.001) per season (year on year), respectively. The seasonal trend of hip and groin injury burden did not improve (Exp(b)=0.99, 95% CI 0.97 to 1.01, P=0.40).Hip and groin injuries constitute a considerable part of all time-loss injuries in men's professional football. Although there was a promising slight decreasing trend in the rates of hip and groin injury (as a category) and adductor-related injury (as a specific diagnosis), the injury burden remained at a consistent level over the study period.
Establishing reliability criteria forLiver ElastPQ Shear-wave Elastography (ElastPQ-SWE): Comparison between 3,5 and 10 measurements
Authors: D. Roccarina, L.I. Prat, M. Guerrero, E. Buzzetti, M. Rosselli, A. Marshall, D. Thorburn, M. Pinzani, E. Tsochatzis
Journal: Journal of Hepatology (2018)
Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Autoantibody Status Predict Outcome of Recurrent Optic Neuritis
Authors: Jiraporn Jitprapaikulsan, John J. Chen, Eoin P. Flanagan, W. Oliver Tobin, Jim P. Fryer, Brian G. Weinshenker, Andrew McKeon, Vanda A. Lennon, Jacqueline A. Leavitt, Jan-Mendelt Tillema, Claudia Lucchinetti, B. Mark Keegan, Orhun Kantarci, Cheryl Khanna, Sarah M. Jenkins, Grant M. Spears, Jessica Sagan, Sean J. Pittock
Journal: Ophthalmology (2018)
Temporal assessment of the non-invasive fibrosis scores FIB-4 and Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS) in a retrospective cohort study among patients with Non-Alcoholic Fatty Liver Disease (NAFLD)
Authors: M. Pérez-Carreras, C. Muñoz Codoceo, M.M. Ortega, M.R. Castro, F.M. Alfonso, A.M. Algibez, Y.R. Gil, G.C. Tortajada
Journal: Journal of Hepatology (2018)
Adalimumab‐Based Treatment Versus Disease‐Modifying Antirheumatic Drugs for Venous Thrombosis in Behçet's Syndrome
Authors: Giacomo Emmi, Antonio Vitale, Elena Silvestri, Maria Boddi, Matteo Becatti, Claudia Fiorillo, Claudia Fabiani, Bruno Frediani, Lorenzo Emmi, Gerardo Di Scala, Matteo Goldoni, Alessandra Bettiol, Augusto Vaglio, Luca Cantarini, Domenico Prisco
Journal: Arthritis & Rheumatology (2018)

Objective Since Behçet's syndrome (BS) is the prototype of inflammation‐induced thrombosis, immunosuppressants are recommended in place of anticoagulants. We undertook this study to assess the clinical efficacy and the corticosteroid‐sparing effect of adalimumab (ADA)–based treatment versus disease‐modifying antirheumatic drug (DMARD) therapy in a large retrospective cohort of patients with BS‐related venous thrombosis. Methods We retrospectively collected data on 70 BS patients treated with DMARDs or ADA‐based regimens (ADA with or without DMARDs) because of venous complications. Clinical and imaging evaluations were performed to define vascular response. We explored differences in outcomes between ADA‐based regimens and DMARDs with respect to efficacy, corticosteroid‐sparing role, and time on treatment. We also evaluated the role of anticoagulants as concomitant treatment. Results After a mean ± SD follow‐up period of 25.7 ± 23.2 months, ADA‐based regimens induced clinical and imaging improvement of venous thrombosis more frequently ( P = 0.001) and rapidly ( P &lt; 0.0001) than did DMARDs. The mean dose of corticosteroids administered at the last follow‐up visit was significantly lower with ADA‐based regimens than with DMARDs ( P &lt; 0.0001). The time on treatment was significantly longer with ADA plus DMARDs than with DMARDs alone ( P = 0.002). No differences were found in terms of efficacy and time on treatment between DMARDs or ADA‐based regimens among patients who received anticoagulants and those who did not. Conclusion In this large retrospective study, we have shown that ADA‐based regimens are more effective and rapid than DMARDs in inducing resolution of venous thrombosis in BS patients, allowing reduction of steroid exposure. Moreover, our findings suggest that anticoagulation does not modify the efficacy of either ADA‐based regimens or DMARDs for venous complications.
Targeting sphingosine-1-phosphate lyase as an anabolic therapy for bone loss
Authors: Sarah Weske, Mithila Vaidya, Alina Reese, Karin von Wnuck Lipinski, Petra Keul, Julia K Bayer, Jens W Fischer, Ulrich Flögel, Jens Nelsen, Matthias Epple, Marta Scatena, Edzard Schwedhelm, Marcus Dörr, Henry Völzke, Eileen Moritz, Anke Hannemann, Bernhard H Rauch, Markus H Gräler, Gerd Heusch, Bodo Levkau
Journal: Nature Medicine (2018)
Notch3 orchestrates epithelial and inflammatory responses to promote acute kidney injury
Authors: Panagiotis Kavvadas, Zela Keuylian, Niki Prakoura, Sandrine Placier, Aude Dorison, Christos E. Chadjichristos, Jean-Claude Dussaule, Christos Chatziantoniou
Journal: Kidney International (2018)
Theacrine protects against nonalcoholic fatty liver disease by regulating acylcarnitine metabolism
Authors: Guo-En Wang, Yi-Fang Li, Yu-Jia Zhai, Lian Gong, Jing-Yu Tian, Mo Hong, Nan Yao, Yan-Ping Wu, Hiroshi Kurihara, Rong-Rong He
Journal: Metabolism (2018)
Medical Nutrition Education, Training, and Competencies to Advance Guideline-Based Diet Counseling by Physicians: A Science Advisory From the American Heart Association
Authors: Karen E. Aspry, Linda Van Horn, Jo Ann S. Carson, Judith Wylie-Rosett, Robert F. Kushner, Alice H. Lichtenstein, Stephen Devries, Andrew M. Freeman, Allison Crawford, Penny Kris-Etherton
Journal: Circulation (2018)

Growing scientific evidence of the benefits of heart-healthy dietary patterns and of the massive public health and economic burdens attributed to obesity and poor diet quality have triggered national calls to increase diet counseling in outpatients with atherosclerotic cardiovascular disease or risk factors. However, despite evidence that physicians are willing to undertake this task and are viewed as credible sources of diet information, they engage patients in diet counseling at less than desirable rates and cite insufficient knowledge and training as barriers. These data align with evidence of large and persistent gaps in medical nutrition education and training in the United States. Now, major reforms in undergraduate and graduate medical education designed to incorporate advances in the science of learning and to better prepare physicians for 21st century healthcare delivery are providing a new impetus and novel ways to expand medical nutrition education and training. This science advisory reviews gaps in undergraduate and graduate medical education in nutrition in the United States, summarizes reforms that support and facilitate more robust nutrition education and training, and outlines new opportunities for accomplishing this goal via multidimensional curricula, pedagogies, technologies, and competency-based assessments. Real-world examples of efforts to improve undergraduate and graduate medical education in nutrition by integrating formal learning with practical, experiential, inquiry-driven, interprofessional, and population health management activities are provided. The authors conclude that enhancing physician education and training in nutrition, as well as increasing collaborative nutrition care delivery by 21st century health systems, will reduce the health and economic burdens from atherosclerotic cardiovascular disease to a degree not previously realized.
Gas‐Stabilizing Gold Nanocones for Acoustically Mediated Drug Delivery
Authors: Christophoros Mannaris, Boon M. Teo, Anjali Seth, Luca Bau, Constantin Coussios, Eleanor Stride
Journal: Advanced Healthcare Materials (2018)

Abstract The efficient penetration of drugs into tumors is a major challenge that remains unmet. Reported herein is a strategy to promote extravasation and enhanced penetration using inertial cavitation initiated by focused ultrasound and cone‐shaped gold nanoparticles that entrap gas nanobubbles. The cones are capable of initiating inertial cavitation under pressures and frequencies achievable with existing clinical ultrasound systems and of promoting extravasation and delivery of a model large therapeutic molecule in an in vitro tissue mimicking flow phantom, achieving penetration depths in excess of 2 mm. Ease of functionalization and intrinsic imaging capabilities provide gold with significant advantages as a material for biomedical applications. The cones show neither cytotoxicity in Michigan Cancer Foundation (MCF)‐7 cells nor hemolytic activity in human blood at clinically relevant concentrations and are found to be colloidally stable for at least 5 d at 37 °C and several months at 4 °C.
Imaging of Metastatic Epithelioid Trophoblastic Tumor With 18F-FDG PET/CT
Authors: Tirth Patel, Jorge Oldan
Journal: Clinical Nuclear Medicine (2018)

Epithelioid trophoblastic tumors are exceptionally rare malignant forms of gestational trophoblastic neoplasia arising from the placenta. We present here a case of a 33-year-old woman with an epithelioid trophoblastic tumor with metastatic disease to the lungs that was initially thought to represent cervical carcinoma. After appropriate diagnosis and treatment, the tumor responded to therapy and was in remission. The cancer recurred 5 years later with new lung metastases. F-FDG PET/CT was used for initial tumor staging, to evaluate treatment response, and to help detect the recurrence.
HLA‐DRB3/4/5 mismatches are associated with increased risk of acute GVHD in 10/10 matched unrelated donor hematopoietic cell transplantation
Authors: Stéphanie Ducreux, Valérie Dubois, Kahina Amokrane, Ibrahim Yakoub‐Agha, Myriam Labalette, Mauricette Michallet, Marie‐Thérèse Rubio, Anne Kennel, Edouard Forcade, Xavier Lafarge, Claude‐Eric Bulabois, Dominique Masson, Etienne Daguindau, Anne Devys, Virginie Moalic, Erwann Quelvennec, Abdelali Boudifa, Christophe Picard, Peter Van Endert, Muriel de Matteis, Florent Delbos, Matthieu Filloux, Béatrice Pedron, Virginie Renac, Françoise Hau, Julie Bonneau, Anne Parissiadis, Marylise Fort, Anne Dormoy, Natacha Maillard, Isabelle Jollet, Patrice Chevallier, Anne Cesbron, Jacques‐Olivier Bay, Fabienne Quainon, Federico Garnier, Gérard Socié, Pascale Loiseau, Raphaël Porcher, Régis Peffault de Latour
Journal: American Journal of Hematology (2018)

Abstract Matching for HLA‐A, ‐B, ‐C, and ‐DRB1 loci (8/8 match) is currently the gold standard for unrelated donor hematopoietic cell transplantation (HCT). In Europe, patients are also matched at the HLA‐DQB1 loci (10/10 match). However, there is increasing evidence that matching at HLA‐DRB3/4/5 loci may help to lower transplant‐related morbidity and mortality. We therefore investigated the impact of HLA‐DRB3/4/5 mismatches on outcomes in 1975 patients who received a first 10/10 matched unrelated donor (MUD) HCT in France from 2000 to 2012 for a hematological malignancy. High‐resolution typing was performed at HLA‐A, ‐B, ‐C, ‐DRB1, ‐DQB1, ‐DPB1, and ‐DRB3/4/5 loci for all donor/recipient pairs. Compared with DRB3/4/5‐matched pairs, patients who received a MUD HCT from a DRB3/4/5 mismatched donor had a significantly increased risk of grade II‐IV acute graft‐versus‐host disease (aGVHD) (Adjusted Hazard Ratio (HR) 1.43 (1.07 to 1.90)) associated with lower graft‐versus‐host disease‐free and relapse‐free survival (GRFS) (Adjusted HR 1.20 (1.02 to 1.42)). Conversely, we observed no differences in terms of chronic GVHD, nonrelapse mortality, relapse and overall survival. However, we believe that patients stand to benefit from DRB3/4/5 loci being considered for unrelated donor selection to improve GRFS and then quality of life after unrelated HCT.
TCTAP A-015 Intracoronary Infusion of Alprostadil and Nitroglycerin with Targeted Perfusion Microcatheter in ST-segment Elevation Myocardial Infarction Patients with Coronary Slow Flow Phenomenon
Authors: Xincheng Sheng, Song Ding, Jun Pu, Ben He
Journal: Journal of the American College of Cardiology (2018)
Ledipasvir/Sofosbuvir for 12 weeks is safe and effective in adolescents with chronic hepatitis C virus infection and hematological malignancies undergoing chemotherapy
Authors: M.H. El-Sayed, F.S.E.S. Ebeid, A.R. Zekri, B. Massetto, K. Kersey, A. Osinusi, F. Zhang, D. Brainard, W. Elsayed, A. El-Haddad
Journal: Journal of Hepatology (2018)