tbuckley/cabot-search huggingface dataset:
MicroRNA-148b Targets the TGF-β Pathway to Regulate Angiogenesis and Endothelial-to-Mesenchymal Transition during Skin Wound Healing
Authors: Vladislav Miscianinov, Andrea Martello, Lorraine Rose, Elisa Parish, Ben Cathcart, Tijana Mitić, Gillian A. Gray, Marco Meloni, Ayman Al Haj Zen, Andrea Caporali
Journal: Molecular Therapy (2018)

Transforming growth factor beta (TGF-β) is crucial for regulation of the endothelial cell (EC) homeostasis. Perturbation of TGF-β signaling leads to pathological conditions in the vasculature, causing cardiovascular disease and fibrotic disorders. The TGF-β pathway is critical in endothelial-to-mesenchymal transition (EndMT), but a gap remains in our understanding of the regulation of TGF-β and related signaling in the endothelium. This study applied a gain- and loss-of function approach and an in vivo model of skin wound healing to demonstrate that miR-148b regulates TGF-β signaling and has a key role in EndMT, targeting TGFB2 and SMAD2. Overexpression of miR-148b increased EC migration, proliferation, and angiogenesis, whereas its inhibition promoted EndMT. Cytokine challenge decreased miR-148b levels in ECs while promoting EndMT through the regulation of SMAD2. Finally, in a mouse model of skin wound healing, delivery of miR-148b mimics promoted wound vascularization and accelerated closure. In contrast, inhibition of miR-148b enhanced EndMT in wounds, resulting in impaired wound closure that was reversed by SMAD2 silencing. Together, these results demonstrate for the first time that miR-148b is a key factor controlling EndMT and vascularization. This opens new avenues for therapeutic application of miR-148b in vascular and tissue repair. Transforming growth factor beta (TGF-β) is crucial for regulation of the endothelial cell (EC) homeostasis. Perturbation of TGF-β signaling leads to pathological conditions in the vasculature, causing cardiovascular disease and fibrotic disorders. The TGF-β pathway is critical in endothelial-to-mesenchymal transition (EndMT), but a gap remains in our understanding of the regulation of TGF-β and related signaling in the endothelium. This study applied a gain- and loss-of function approach and an in vivo model of skin wound healing to demonstrate that miR-148b regulates TGF-β signaling and has a key role in EndMT, targeting TGFB2 and SMAD2. Overexpression of miR-148b increased EC migration, proliferation, and angiogenesis, whereas its inhibition promoted EndMT. Cytokine challenge decreased miR-148b levels in ECs while promoting EndMT through the regulation of SMAD2. Finally, in a mouse model of skin wound healing, delivery of miR-148b mimics promoted wound vascularization and accelerated closure. In contrast, inhibition of miR-148b enhanced EndMT in wounds, resulting in impaired wound closure that was reversed by SMAD2 silencing. Together, these results demonstrate for the first time that miR-148b is a key factor controlling EndMT and vascularization. This opens new avenues for therapeutic application of miR-148b in vascular and tissue repair.
Sub maximally dilated Viatorr CX improves one-year survival compared to conventional covered TIPS: a case-control study
Authors: M. Praktiknjo, S. Fischer, C. Pieper, C. Jansen, A. Pohlmann, J. Lehmann, C.P. Strassburg, D. Thomas, C. Meyer, J. Trebicka
Journal: Journal of Hepatology (2018)
Subset analysis of COMPASS: A randomized 2X2 phase II trial comparing two and four courses of S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) as neoadjuvant chemotherapy for locally advanced gastric cancer.
Authors: Takaki Yoshikawa, Kazuaki Tanabe, Yuichi Ito, Kazuhiro Nishikawa, Kazumasa Fujitani, Takanori Matsui, Tsutomu Hayashi, Toru Aoyama, Haruhiko Cho, Satoshi Morita, Yumi Miyashita, Akira Tsuburaya, Junichi Sakamoto
Journal: Journal of Clinical Oncology (2015)

e15067 Background: The prognosis for stage III gastric cancer is not satisfactory even by S-1 adjuvant chemotherapy. Neoadjuvant chemotherapy is promising approach to improve the survival of locally advanced gastric cancer. Previous single arm phase II studies showed that high response rate and acceptable toxicities were observed by both of S-1/cisplatin (SC) or paclitaxel/cisplatin (PC). However, suitable duration and regimens of preoperative chemotherapy has not been established yet. Methods: Patients received S-1 (80 mg/m2 for 21 days with 1 week rest) / cisplatin (60 mg/m2 at day 8) or paclitaxel / cisplatin (80 mg/m2 and 25 mg/m2, respectively, on days 1, 8, and 15 with 1 week rest) as neoadjuvant chemotherapy in 2X2 randomized phase II trial. The primary endpoint was 3-year overall survival. The planned sample size was 80 eligible patients in total so that the treatment group with the superior observed 3-year OS rate by 10% increase was to be selected with a probability of 88% or higher. Results: Eighty-three patients were assigned to SC (n = 41, two courses in 21 and four courses in 20) and PC (n = 42, two courses in 21 and four courses in 21). Our previous results demonstrated that PC regimen and the four courses could not achieve 10% improvement of 3-year OS rate. The 3-year OS was 67% (95% CI, 43-83%) in two courses of SC, 55% (95%CI, 31-73%) in four courses of SC, 62% (95%CI, 38-79%) in two courses of PC, and 67% (95%CI, 43-83%) in four courses of PC. No treatment interaction was observed between courses and regimen. When stratifying by macroscopic type, esophageal invasion, stage, renal function, age, gender, histology, T, N, minimal peritoneal metastasis, no subset showed tend to be superior survival by four courses. Conclusions: Two courses of neoadjuvant chemotherapy is recommended as most promising neoadjuvant chemotherapy for a test arm of future phase III study for locally advanced gastric cancer. Clinical trial information: UMIN000002595.
Compare HBsAg retention in the endoplasmic reticulum and the ER stress between the cells transfected or infected by the wild type and pre-S HBV mutants using in vitro transfection and in vivo infection of FRG mice
Authors: J.Y.-J. Liang, J.-C. Wu, Y. Chi, C.-P. Sun, C.-W. Su, M.-H. Tao
Journal: Journal of Hepatology (2018)
Influence of geographical origin on access to therapy and therapy outcomes in hepatitis C virus-infected persons: the Swiss Hepatitis C Cohort Study
Authors: M. Brezzi, B. Bertisch, D. Moradpour, A. Cerny, J.-F. Dufour, M. Heim, B. Müllhaupt, D. Semela, F. Negro, O. Keiser
Journal: Journal of Hepatology (2018)
Functional Characterization of the Osteoarthritis Genetic Risk Residing at <i>ALDH1A2</i> Identifies rs12915901 as a Key Target Variant
Authors: Colin Shepherd, Dongxing Zhu, Andrew J. Skelton, Jennifer Combe, Harrison Threadgold, Linyi Zhu, Tonia L. Vincent, Paul Stuart, Louise N. Reynard, John Loughlin
Journal: Arthritis & Rheumatology (2018)

Objective To identify the functional single‐nucleotide polymorphisms (SNPs) and mechanisms conferring increased risk of hand osteoarthritis (OA) at the ALDH1A2 locus, which is a retinoic acid regulatory gene. Methods Tissue samples from 247 patients with knee, hip, or hand OA who had undergone joint surgery were included. RNA‐sequencing analysis was used to investigate differential expression of ALDH1A2 and other retinoic acid signaling pathway genes in cartilage. Expression of ALDH1A2 in joint tissues obtained from multiple sites was quantified using quantitative reverse transcription–polymerase chain reaction. Allelic expression imbalance (AEI) was measured by pyrosequencing. The consequences of ALDH1A2 depletion by RNA interference were assessed in primary human chondrocytes. In silico and in vitro analyses were used to pinpoint which, among 62 highly correlated SNPs, could account for the association at the locus. Results ALDH1A2 expression was observed across multiple joint tissue samples, including osteochondral tissue from the hand. The expression of ALDH1A2 and of several retinoic acid signaling genes was different in diseased cartilage compared to non‐diseased cartilage, with ALDH1A2 showing lower levels in OA cartilage. Experimental depletion of ALDH1A2 resulted in changes in the expression levels of a number of chondrogenic markers, including SOX9 . In addition, reduced expression of the OA risk–conferring allele was witnessed in a number of joint tissues, with the strongest effect in cartilage. The intronic SNP rs12915901 recapitulated the AEI observed in patient tissues, while the Ets transcription factors were identified as potential mediators of this effect. Conclusion The ALDH1A2 locus seems to increase the risk of hand OA through decreased expression of ALDH1A2 in joint tissues, with the effect dependent on rs12915901. These findings indicate a mechanism that may now be targeted to modulate OA risk.
Reducing Body Image–Related Distress in Women With Breast Cancer Using a Structured Online Writing Exercise: Results From the My Changed Body Randomized Controlled Trial
Authors: Kerry A. Sherman, Astrid Przezdziecki, Jessica Alcorso, Christopher Jon Kilby, Elisabeth Elder, John Boyages, Louise Koelmeyer, Helen Mackie
Journal: Journal of Clinical Oncology (2018)

Purpose Breast cancer treatment adverse effects result in one in three survivors experiencing body image–related distress (BID) that negatively impacts on a woman’s ability to recover after cancer and into survivorship. My Changed Body (MyCB) is a Web-based psychological intervention to alleviate BID and improve body appreciation in survivors of breast cancer (BCSs) through a single-session, self-compassion focused writing activity. This randomized controlled trial evaluated the impact of MyCB on BID and body appreciation in BCSs. The moderating effect of lymphedema status (affected or unaffected) and appearance investment (self-importance placed on personal appearance) and the mediating effect of self-compassion were evaluated. Patients and Methods Women (disease-free stage I to III BCSs who had experienced at least one negative event related to bodily changes after breast cancer) were randomly assigned to MyCB (n = 149) or an expressive writing control arm (n = 155). Primary outcomes were reduction in BID and improvement in body appreciation 1 week after intervention. Secondary outcomes included psychological distress (depression and anxiety) and self-compassion. Follow-up assessments occurred 1 week, 1 month, and 3 months after writing. Results Compliance with the MyCB intervention was 88%, and attrition was 9.2%. Intent-to-treat linear mixed models indicated that participants who received MyCB reported significantly less BID ( P = .035) and greater body appreciation ( P = .004) and self-compassion ( P &lt; .001) than expressive writing participants. Intervention effects on BID were moderated by lymphedema status ( P = .007) and appearance investment ( P = .042). Self-compassion mediated effects on both primary outcomes. Therapeutic effects were maintained at 1 month (BID and body appreciation) and 3 months (body appreciation) after intervention. Significant reductions in psychological distress (1-month depression, P = .001; 1-week and 1-month anxiety, P = .007) were evident for MyCB participants with lymphedema. Conclusion This study supports the efficacy of MyCB for reducing BID and enhancing body appreciation among BCSs.
Monofocal HCC: Milan Criteria or BCLC staging system? An analysis of the ITA.LI.CA. Database
Authors: G. Peserico, B. Penzo, F. Pelizzaro, A. Imondi, A. Meneghetti, A. Sartori, M. D’elia, A. Vitale, F. Trevisani, F. Farinati
Journal: Journal of Hepatology (2018)
Protective effect of statins in cirrhosis might be dependent on common genetic risk variants
Authors: M. Reichert, M. Casper, R. Liebe, R. Greinert, E. Vandieken, C. Schneider, F. Grünhage, B. Appenrodt, A. Zipprich, C. Ripoll, F. Lammert
Journal: Journal of Hepatology (2018)
Combined therapy of transarterial chemoembolizatoin and stereotactic body radiotherapy versus transaterial chemoembolizatoin for &lt; 5m hepatocellular carcinoma: A propensity score matching analysis
Authors: B.G. Jun, Y.D. Kim, G.J. Cheon, S.G. Kim, Y.S. Kim, S.W. Jeong, J.Y. Jang, S.H. Lee, H.S. Kim
Journal: Journal of Hepatology (2018)
CX-1158-101: A first-in-human phase 1 study of CB-1158, a small molecule inhibitor of arginase, as monotherapy and in combination with an anti-PD-1 checkpoint inhibitor in patients (pts) with solid tumors.
Authors: Kyriakos P. Papadopoulos, Frank Yung-Chin Tsai, Todd Michael Bauer, Lucas Muigai, Yu Liang, Mark K. Bennett, Keith W. Orford, Siqing Fu
Journal: Journal of Clinical Oncology (2017)

3005 Background: Arginase is secreted by myeloid-derived suppressor cells (MDSCs) and polymorphonuclear cells (PMNs) in the tumor microenvironment, depleting arginine, an amino acid required for T-cell activation and proliferation. CB-1158 is an oral small molecule inhibitor of arginase. CB-1158 reverses PMN- and MDSC-mediated suppression of T-cells in ex vivo human models, and increases plasma and tumor arginine levels in mouse syngeneic tumor models leading to increased pro-inflammatory markers and activated CD8 T-cells in the tumor. CB-1158 has single agent efficacy in mouse tumor models and synergistically enhances the antitumor efficacy of checkpoint inhibitors. Methods: This is an ongoing phase 1 study to evaluate safety and tolerability of CB-1158 as a monotherapy and in combination with anti-PD-1 in pts with solid tumors. Pharmacokinetics (PK), anti-tumor effects, and biomarkers, including plasma arginine, arginase activity, and effects on immune function in blood and in tumors will be evaluated. CB-1158 was administered BID orally in 28-day cycles. Escalating doses were administered to cohorts for safety evaluation. Additional pts were enrolled at dose levels determined to be safe to support biomarker objectives. Results: Nine pts have been enrolled across two monotherapy dose escalation cohorts (50 and 100 mg) and biomarker cohorts. CB-1158 was rapidly absorbed (T max = 4 h) and was cleared with a half-life of 6 h. At doses of 50 and 100 mg, steady-state plasma trough levels were 1.6 and 4.5 µM, sufficient to achieve &gt; 90% arginase inhibition, and plasma arginine levels increased 2.4- and 4-fold, respectively. CB-1158 has been well tolerated with no DLTs or drug-related Grade 3 AEs. Dose escalation is ongoing and updated safety, PK and biomarker data will be presented. Conclusions: CB-1158 is a first-in-class inhibitor of the myeloid-derived immunosuppressive enzyme arginase. CB-1158 has been well tolerated and achieves on-target inhibition resulting in increases in plasma arginine, an amino acid required for T-cell immune responses. Clinical trial information: NCT02903914.
Tobacco smoke exposure in early life and adolescence in relation to lung function
Authors: Jesse D. Thacher, Erica S. Schultz, Jenny Hallberg, Ulrika Hellberg, Inger Kull, Per Thunqvist, Göran Pershagen, Per M. Gustafsson, Erik Melén, Anna Bergström
Journal: European Respiratory Journal (2018)

Maternal smoking during pregnancy is associated with impaired lung function among young children, but less is known about long-term effects and the impact of adolescents' own smoking. We investigated the influence of maternal smoking during pregnancy, secondhand smoke exposure and adolescent smoking on lung function at age 16 years. The BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology) birth cohort collected information on participants' tobacco smoke exposure through repeated questionnaires, and measured saliva cotinine concentrations at age 16 years. Participants performed spirometry and impulse oscillometry (IOS) at age 16 years (n=2295). Exposure to maternal smoking during pregnancy was associated with reduced forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) ratio of −1.1% (95% CI −2.0 to −0.2%). IOS demonstrated greater resistance at 5–20 Hz ( R 5–20 ) in participants exposed to maternal smoking during pregnancy. Adolescents who smoked had reduced FEV 1 /FVC ratios of −0.9% (95% CI −1.8 to −0.1%) and increased resistance of 6.5 Pa·L –1 ·s (95% CI 0.7 to 12.2 Pa·L –1 ·s) in R 5–20 . Comparable associations for FEV 1 /FVC ratio were observed for cotinine concentrations, using ≥12 ng·mL −1 as a cut-off for adolescent smoking. Maternal smoking during pregnancy was associated with lower FEV 1 /FVC ratios and increased airway resistance. In addition, adolescent smoking appears to be associated with reduced FEV 1 /FVC ratios and increased peripheral airway resistance.
The Microglial Innate Immune Receptor TREM2 Is Required for Synapse Elimination and Normal Brain Connectivity
Authors: Fabia Filipello, Raffaella Morini, Irene Corradini, Valerio Zerbi, Alice Canzi, Bernadeta Michalski, Marco Erreni, Marija Markicevic, Chiara Starvaggi-Cucuzza, Karel Otero, Laura Piccio, Francesca Cignarella, Fabio Perrucci, Matteo Tamborini, Marco Genua, Lawrence Rajendran, Elisabetta Menna, Stefania Vetrano, Margaret Fahnestock, Rosa Chiara Paolicelli, Michela Matteoli
Journal: Immunity (2018)
Comparison of magnetic resonance angiography and<sup>18</sup>F-fluorodeoxyglucose positron emission tomography in large-vessel vasculitis
Authors: Kaitlin A Quinn, Mark A Ahlman, Ashkan A Malayeri, Jamie Marko, Ali Cahid Civelek, Joel S Rosenblum, Armin A Bagheri, Peter A Merkel, Elaine Novakovich, Peter C Grayson
Journal: Annals of the Rheumatic Diseases (2018)

Objectives To assess agreement between interpretation of magnetic resonance angiography (MRA) and 18 F-fluorodeoxyglucose positron emission tomography (PET) for disease extent and disease activity in large-vessel vasculitis (LVV) and determine associations between imaging and clinical assessments. Methods Patients with giant cell arteritis (GCA), Takayasu’s arteritis (TAK) and comparators were recruited into a prospective, observational cohort. Imaging and clinical assessments were performed concurrently, blinded to each other. Agreement was assessed by per cent agreement, Cohen’s kappa and McNemar’s test. Multivariable logistic regression identified MRA features associated with PET scan activity. Results Eighty-four patients (GCA=35; TAK=30; comparator=19) contributed 133 paired studies. Agreement for disease extent between MRA and PET was 580 out of 966 (60%) arterial territories with Cohen’s kappa=0.22. Of 386 territories with disagreement, MRA demonstrated disease in more territories than PET (304vs82, p&lt;0.01). Agreement for disease activity between MRA and PET was 90 studies (68%) with Cohen’s kappa=0.30. In studies with disagreement, MRA demonstrated activity in 23 studies and PET in 20 studies (p=0.76). Oedema and wall thickness on MRA were independently associated with PET scan activity. Clinical status was associated with disease activity by PET (p&lt;0.01) but not MRA (p=0.70), yet 35/69 (51%) patients with LVV in clinical remission had active disease by both MRA and PET. Conclusions In assessment of LVV, MRA and PET contribute unique and complementary information. MRA better captures disease extent, and PET scan is better suited to assess vascular activity. Clinical and imaging-based assessments often do not correlate over the disease course in LVV. Trial registration number NCT02257866 .
HCV treatment with DAA in patients listed for liver transplant does not result in an increased risk of HCC recurrence post-liver transplant
Authors: C. Mazzarelli, F. Invernizzi, A. Suddle, M.F. Donato, L.S. Belli, M.D. Cannon, S. Marenco, D. Angrisani, M. Iavarone
Journal: Journal of Hepatology (2018)
TCTAP A-080 Strain Analysis Using Speckle Tracking Echocardiography for Detection of Coronary Artery Disease in Patients of Chronic Stable Angina with No Regional Wall Motion Abnormality at Rest
Authors: Md Saqif Shahriar, Tuhin Haque, Mir Jamal Uddin NICVD Uddin, Mohammad Badiuzzaman, Abdul Momen, Fathima Aaysha Cader, Mahmood Hasan Khan, Md Hasanur Rahman
Journal: Journal of the American College of Cardiology (2018)
Association of Retinal Ganglion Cell Layer Thickness With Future Disease Activity in Patients With Clinically Isolated Syndrome
Authors: Hanna G. Zimmermann, Benjamin Knier, Timm Oberwahrenbrock, Janina Behrens, Catherina Pfuhl, Lilian Aly, Miriam Kaminski, Muna-Miriam Hoshi, Svenja Specovius, René M. Giess, Michael Scheel, Mark Mühlau, Judith Bellmann-Strobl, Klemens Ruprecht, Bernhard Hemmer, Thomas Korn, Friedemann Paul, Alexander U. Brandt
Journal: JAMA Neurology (2018)

Clinically isolated syndrome (CIS) describes a first clinical incident suggestive of multiple sclerosis (MS). Identifying patients with CIS who have a high risk of future disease activity and subsequent MS diagnosis is crucial for patient monitoring and the initiation of disease-modifying therapy.To investigate the association of retinal optical coherence tomography (OCT) results with future disease activity in patients with CIS.This prospective, longitudinal cohort study took place between January 2011 and May 2017 at 2 German tertiary referral centers. A total of 179 patients with CIS were screened (80 in Berlin and 99 in Munich). Patients underwent neurological examination, magnetic resonance imaging (MRI), and OCT. Only eyes with no previous optic neuritis were considered for OCT analysis.The primary outcome was not meeting the no evidence of disease activity (NEDA-3) criteria; secondary outcomes were MS diagnosis (by the 2010 McDonald criteria) and worsening of disability. The primary measure was OCT-derived ganglion cell and inner plexiform layer thickness; the secondary measures included peripapillary retinal nerve fiber layer thickness, inner nuclear layer thickness, and MRI-derived T2-weighted lesions.A total of 97 of the 179 screened patients (54.2%) were enrolled in the study at a median of 93 (interquartile range [IQR], 62-161) days after a first demyelinating event. The median follow-up duration (Kaplan-Meier survival time) was 729 (IQR, 664-903) days. Of 97 patients with CIS (mean age 33.6 [7.9] years; 61 [62.9%] female), 58 (59%) did not meet NEDA-3 criteria during the follow-up period. A Kaplan-Meier analysis showed a significant probability difference in not meeting NEDA-3 criteria by ganglion cell and inner plexiform later thickness (thinnest vs thickest tertile: hazard ratio [HR], 3.33 [95% CI, 1.70-6.55; P < .001; log-rank P = .001). A follow-up diagnosis of MS was more likely for patients with low ganglion cell and inner plexiform layer thickness (thinnest vs thickest tertile: HR, 4.05 [95% CI, 1.93-8.50]; P < .001). Low peripapillary retinal nerve fiber layer thickness likewise indicated risk of not meeting NEDA-3 criteria (thinnest vs thickest tertile: HR, 2.46 [95% CI, 1.29-4.66]; P = .01; log-rank P = .02). Inner nuclear layer thickness and T2-weighted lesion count were not associated with not meeting NEDA-3 criteria.Retinal ganglion cell and inner plexiform layer thickness might prove a valuable imaging marker for anticipating future disease activity and diagnosis of MS in patients with CIS, which can potentially support patient monitoring and initiation of disease-modifying therapy.
Albumin decreases the incidence of paracentesis induced circulatory dysfunction with less than 5 litres of ascitic tap in acute on chronic liver failure (ACLF) patients: Randomized controlled trial (NCT02467348)
Authors: V. Arora, R. Maiwall, S.S. Thomas, V. Rajan, R. Ali, G. Kumar, P. Jain, S.K. Sarin
Journal: Journal of Hepatology (2018)