tbuckley/cabot-search huggingface dataset:
MicroRNA-378 suppresses myocardial fibrosis through a paracrine mechanism at the early stage of cardiac hypertrophy following mechanical stress.
Authors: Jie Yuan, Haibo Liu, Wei Gao, Li Zhang, Yong Ye, Lingyan Yuan, Zhiwen Ding, Jian Wu, Le Kang, Xiaoyi Zhang, Xiaoyan Wang, Guoping Zhang, Hui Gong, Aijun Sun, Xiangdong Yang, Ruizhen Chen, Zhaoqiang Cui, Junbo Ge, Yunzeng Zou
Journal: Theranostics (2018)

Rationale: Excessive myocardial fibrosis is the main pathological process in the development of cardiac remodeling and heart failure; therefore, it is important to prevent excessive myocardial fibrosis. We determined that microRNA-378 (miR-378) is cardiac-enriched and highly repressed during cardiac remodeling. We therefore proposed that miR-378 has a critical role in regulation of cardiac fibrosis, and examined the effects of miR-378 on cardiac fibrosis after mechanical stress. Methods: Mechanical stress was respectively imposed on mice through a transverse aortic constriction (TAC) procedure and on cardiac fibroblasts by stretching silicon dishes. A chemically modified miR-378 mimic (Agomir) or an inhibitor (Antagomir) was administrated to mice by intravenous injection and to cells by direct addition to the culture medium. MiR-378 knockout mouse was constructed. Cardiac fibroblasts were cultured in the conditioned media from the cardiomyocytes with either miR-378 depletion or treatment with sphingomyelinase inhibitor GW4869. Quantitative real-time polymerase chain reaction analysis of gene and miRNA expression, Western blot analysis, immunochemistry and electron microscopy were performed to elucidate the mechanisms. Results: Mechanical stress induced significant increases in fibrotic responses, including myocardial fibrosis, fibroblast hyperplasia, and protein and gene expression of collagen and matrix metalloproteinases (MMPs) both in vivo and in vitro. All these fibrotic responses were attenuated by treatment with a chemically modified miR-378 mimic (Agomir) but were exaggerated by treatment with an inhibitor (Antagomir). MiR-378 knockout mouse models exhibited aggravated cardiac fibrosis after TAC. Media from the cardiomyocytes with either miR-378 depletion or treatment with sphingomyelinase inhibitor GW4869 enhanced the fibrotic responses of stimulated cardiac fibroblasts, confirming that miR-378 inhibits fibrosis in an extracellular vesicles-dependent secretory manner. Mechanistically, the miR-378-induced anti-fibrotic effects manifested partially through the suppression of p38 MAP kinase phosphorylation by targeting MKK6 in cardiac fibroblasts. Conclusions: miR-378 is secreted from cardiomyocytes following mechanical stress and acts as an inhibitor of excessive cardiac fibrosis through a paracrine mechanism.
Contact Lenses for Color Blindness
Authors: Abdel‐Rahman Badawy, Muhammad Umair Hassan, Mohamed Elsherif, Zubair Ahmed, Ali K. Yetisen, Haider Butt
Journal: Advanced Healthcare Materials (2018)

Color vision deficiency (color blindness) is an inherited genetic ocular disorder. While no cure for this disorder currently exists, several methods can be used to increase the color perception of those affected. One such method is the use of color filtering glasses which are based on Bragg filters. While these glasses are effective, they are high cost, bulky, and incompatible with other vision correction eyeglasses. In this work, a rhodamine derivative is incorporated in commercial contact lenses to filter out the specific wavelength bands (≈545-575 nm) to correct color vision blindness. The biocompatibility assessment of the dyed contact lenses in human corneal fibroblasts and human corneal epithelial cells shows no toxicity and cell viability remains at 99% after 72 h. This study demonstrates the potential of the dyed contact lenses in wavelength filtering and color vision deficiency management.
GoldCLIP: Gel-Omitted Ligation-Dependent CLIP
Authors: Jiaqi Gu, Ming Wang, Yang Yang, Ding Qiu, Yiqun Zhang, Jinbiao Ma, Yu Zhou, Gregory J. Hannon, Yang Yu
Journal: Genomics Proteomics & Bioinformatics (2018)

Abstract Protein–RNA interaction networks are essential to understand gene regulation control. Identifying binding sites of RNA-binding proteins (RBPs) by the UV-crosslinking and immunoprecipitation (CLIP) represents one of the most powerful methods to map protein–RNA interactions in vivo. However, the traditional CLIP protocol is technically challenging, which requires radioactive labeling and suffers from material loss during PAGE-membrane transfer procedures. Here we introduce a super-efficient CLIP method (GoldCLIP) that omits all gel purification steps. This nonisotopic method allows us to perform highly reproducible CLIP experiments with polypyrimidine tract-binding protein (PTB), a classical RBP in human cell lines. In principle, our method guarantees sequencing library constructions, providing the protein of interest can be successfully crosslinked to RNAs in living cells. GoldCLIP is readily applicable to diverse proteins to uncover their endogenous RNA targets.
The TNF receptor family member Fn14 is highly expressed in recurrent glioblastoma and in GBM patient-derived xenografts with acquired temozolomide resistance
Authors: David S Hersh, Bryan G Harder, Alison Roos, Sen Peng, Jonathan E Heath, Teklu Legesse, Anthony J Kim, Graeme F Woodworth, Nhan L Tran, Jeffrey A Winkles
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) is a difficult to treat brain cancer that nearly uniformly recurs, and recurrent tumors are largely therapy resistant. Our prior work has demonstrated an important role for the tumor necrosis factor–like weak inducer of apoptosis (TWEAK) receptor fibroblast growth factor–inducible 14 (Fn14) in GBM pathobiology. In this study, we investigated Fn14 expression in recurrent GBM and in the setting of temozolomide (TMZ) resistance. Fn14 mRNA expression levels in nonneoplastic brain, primary (newly diagnosed) GBM, and recurrent GBM (post-chemotherapy and radiation) specimens were obtained from The Cancer Genome Atlas data portal. Immunohistochemistry was performed using nonneoplastic brain, patient-matched primary and recurrent GBM, and gliosarcoma (GSM) specimens to examine Fn14 protein levels. Western blot analysis was used to compare Fn14 expression in parental TMZ-sensitive or matched TMZ-resistant patient-derived xenografts (PDXs) established from primary or recurrent tumor samples. The migratory capacity of control and Fn14-depleted TMZ-resistant GBM cells was assessed using the transwell migration assay. We found that Fn14 is more highly expressed in recurrent GBM tumors than their matched primary GBM counterparts. Fn14 expression is also significantly elevated in GSM tumors. GBM PDX cells with acquired TMZ resistance have higher Fn14 levels and greater migratory capacity than their corresponding parental TMZ-sensitive cells, and the migratory difference is due, at least in part, to Fn14 expression in the TMZ-resistant cells. This study demonstrates that the Fn14 gene is highly expressed in recurrent GBM, GSM, and TMZ-resistant GBM PDX tumors. These findings suggest that Fn14 may be a valuable therapeutic target or drug delivery portal for treatment of recurrent GBM and GSM patients.
Reporting bowel surgeons’ death rates did not lead to “gaming”
Authors: Nigel Hawkes
Journal: BMJ (2018)

Fears that publishing bowel surgeons’ patient death rates would lead to risk averse practices or to exaggerating how ill their patients were to justify poor performance can be set aside, a study in The BMJ suggests.1

It found no evidence of any change in the proportion of patients in England having an elective major resection of the bowel since publication of results began, and death rates have fallen substantially, concluded a team from the Royal College of Surgeons, the London School of Hygiene and Tropical Medicine, and other UK centres.

Publishing surgical data has strong professional backing on transparency grounds, but evidence that it improves outcomes was limited.

Derek Alderson, president of the …
Transforming growth factor-βeta and AXL collaborate to induce CXCL5 and neutrophil infiltration in hepatocellular carcinoma
Authors: C. Haider, H. Julia, W. Roland, H. Heidemarie, L. Zell, G. Timelthaler, M. Grubinger, C. Coulouarn, K. Schlangen, W. Sieghart, M. Peck-Radosavljevic, W. Mikulits
Journal: Journal of Hepatology (2018)
Transcriptome analysis of human and murine cirrhotic livers identifies shared molecular pathways as potential targets to enhance cirrhosis regression
Authors: E. Lafoz, M.V. Barceló, Héctor García-Calderó, M. Vila-Casadesús, D. Tripathi, M. Ruart, J. Lozano, J. Gracia-Sancho, V. Hernandez-Gea, J.-C. Garcia-Pagan
Journal: Journal of Hepatology (2018)
Case 13-2018: A 53-Year-Old Man with Cardiomyopathy and Recurrent Ventricular Tachycardia
Authors: Joshua C. Ziperstein, Timothy W. Churchill, Sandeep S. Hedgire, G. William Dec, James R. Stone
Journal: New England Journal of Medicine (2018)

A 53-year-old man presented with shock and ventricular tachycardia. Cardiac MRI revealed an ejection fraction of 43%, with septal hypokinesis, myocardial edema, and late gadolinium enhancement of the subendocardium. Diagnostic tests were performed.
A combined laser microdissection and proteomic analysis method for identification of liver tumors signatures
Authors: E. Henriet, A.A. Hammoud, J.-W. Dupuy, B. Dartigues, Z. Ezzoukhry, N. Dugot-Senant, T. Leste-Lasserre, M. Nikolski, B.L. Bail, J.-F. Blanc, C. Balabaud, P. Bioulac-Sage, A.-A. Raymond, F. Saltel
Journal: Journal of Hepatology (2018)
Substantial Metabolic Activity of Human Brown Adipose Tissue during Warm Conditions and Cold-Induced Lipolysis of Local Triglycerides
Authors: Graeme Weir, Lynne E. Ramage, Murat Akyol, Jonathan K. Rhodes, Catriona J. Kyle, Alison M. Fletcher, Thomas H. Craven, Sonia J. Wakelin, Amanda J. Drake, Maria-Lena Gregoriades, Ceri Ashton, Nick Weir, Edwin J.R. van Beek, Fredrik Karpe, Brian R. Walker, Roland H. Stimson
Journal: Cell Metabolism (2018)

Current understanding of in vivo human brown adipose tissue (BAT) physiology is limited by a reliance on positron emission tomography (PET)/computed tomography (CT) scanning, which has measured exogenous glucose and fatty acid uptake but not quantified endogenous substrate utilization by BAT. Six lean, healthy men underwent 18fluorodeoxyglucose-PET/CT scanning to localize BAT so microdialysis catheters could be inserted in supraclavicular BAT under CT guidance and in abdominal subcutaneous white adipose tissue (WAT). Arterial and dialysate samples were collected during warm (∼25°C) and cold exposure (∼17°C), and blood flow was measured by 133xenon washout. During warm conditions, there was increased glucose uptake and lactate release and decreased glycerol release by BAT compared with WAT. Cold exposure increased blood flow, glycerol release, and glucose and glutamate uptake only by BAT. This novel use of microdialysis reveals that human BAT is metabolically active during warm conditions. BAT activation substantially increases local lipolysis but also utilization of other substrates such as glutamate.
Total Costs of Chimeric Antigen Receptor T<i>-</i>Cell Immunotherapy
Authors: Inmaculada Hernandez, Vinay Prasad, Walid F. Gellad
Journal: JAMA Oncology (2018)

nivolumab, and pembrolizumab).The 2 terminated studies (both for idelalisib) were stopped owing to significant safety concerns.One product (ponatinib) was temporarily pulled from the market, with the FDA requiring further studies, and a risk evaluation and mitigation strategy; however, the PMR clinical study eventually resumed and was completed.One ongoing trial (for olaparib) was released as a PMR by the FDA.None of the pending or ongoing studies are behind their original schedules as posted in the FDA's PMR database.Discussion | Recently, the FDA has been criticized for its oversight of PMR clinical studies. 2,3The agency has come under fire for failure to penalize sponsors for PMR clinical studies completed late.Our own review of PMR clinical studies for novel oncology drug products granted AA within the last 6 years found that no studies were behind their original schedules.However, PMR studies identified serious safety concerns in 2 incidents that resulted in changes to the labeling for both products (idelalisib and ponatinib).In addition, our analysis identified 3 instances (20%) where confirmatory PMR clinical studies for drugs granted AA failed to meet their primary efficacy end points.To date, none of these 3 drugs have been pulled from the market.These examples underscore the importance of collecting the additional clinical safety and efficacy data outlined in the PMRs and the need for collaborative efforts between the FDA, sponsors, and investigators.
Glucocorticoid receptor dimers control intestinal STAT1 and TNF-induced inflammation in mice
Authors: Marlies Ballegeer, Kelly Van Looveren, Steven Timmermans, Melanie Eggermont, Sofie Vandevyver, Fabien Thery, Karen Dendoncker, Jolien Souffriau, Jolien Vandewalle, Lise Van Wyngene, Riet De Rycke, Nozomi Takahashi, Peter Vandenabeele, Jan Tuckermann, Holger M. Reichardt, Francis Impens, Rudi Beyaert, Karolien De Bosscher, Roosmarijn E. Vandenbroucke, Claude Libert
Journal: Journal of Clinical Investigation (2018)

TNF is an important mediator in numerous inflammatory diseases, e.g., in inflammatory bowel diseases (IBDs). In IBD, acute increases in TNF production can lead to disease flares. Glucocorticoids (GCs), which are steroids that bind and activate the glucocorticoid receptor (GR), are able to protect animals and humans against acute TNF-induced inflammatory symptoms. Mice with a poor transcriptional response of GR dimer–dependent target genes were studied in a model of TNF-induced lethal inflammation. In contrast to the GRWT/WT mice, these GRdim/dim mice displayed a substantial increase in TNF sensitivity and a lack of protection by the GC dexamethasone (DEX). Unchallenged GRdim/dim mice had a strong IFN-stimulated gene (ISG) signature, along with STAT1 upregulation and phosphorylation. This ISG signature was gut specific and, based on our studies with antibiotics, depended on the gut microbiota. GR dimers directly bound to short DNA sequences in the STAT1 promoter known as inverted repeat negative GRE (IR-nGRE) elements. Poor control of STAT1 in GRdim/dim mice led to failure to repress ISG genes, resulting in excessive necroptosis induction by TNF. Our findings support a critical interplay among gut microbiota, IFNs, necroptosis, and GR in both the basal response to acute inflammatory challenges and pharmacological intervention by GCs.
Biochemical response to ursodeoxycholic acid predicts histologic primary biliary cholangitis progression
Authors: T. Namisaki, Y. Fujinaga, K. Moriya, M. Kitade, K. Kaji, H. Kawaratani, K. Seki, H. Takaya, S. Sato, Y. Sawada, T. Akahane, H. Yoshiji
Journal: Journal of Hepatology (2018)
Chloroquine in monotherapy is safe and effective for induction of remission in anti-SLA/LP positive patients with autoimmune hepatitis
Authors: D. Terrabuio, A.S. Evangelista, A.L.V. Guedes, A.R. de Moreto Longo Galvão, F.J. Carrilho, E. Cancado
Journal: Journal of Hepatology (2018)
Precision oncology in pancreatobiliary cancers: A longitudinal study.
Authors: Meena Sadaps, Bassam N. Estfan, Davendra Sohal, Alok A. Khorana
Journal: Journal of Clinical Oncology (2018)

399 Background: Precision oncology – the use of next-generation sequencing (NGS) to identify therapeutic options for advanced cancer patients – is being used widely, but its utility in patients with pancreatobiliary (PB) cancers has not been studied systematically. We evaluated the prevalence of actionable alterations and their impact on therapeutic decision-making in patients with PB cancers. Methods: We conducted a retrospective cohort study of consecutive patients seen at the Cleveland Clinic between 2013 and 2016 with incurable solid tumor malignancies, in whom FoundationOne™ (Cambridge, MA) NGS was ordered. All results were reviewed at a multidisciplinary genomics tumor board (GTB), which determined actionability and made therapeutic recommendations. Treatment decisions (on label, off label, or clinical trials) based on said recommendations were reviewed. Results: The study population was 600 patients, of whom 53 had PB cancers. For these 53, median age was 59.6 years; 62.2% (33/53) were female; 86.8% (46/53) were Caucasian. Eight samples (15.1%) had inadequate tissue; of 45 resulted cases, 21 (46.7%) were recommended treatment, including clinical trials (n = 19) and off-label drugs (n = 2). The most common targets for therapy were FGFR (5/21) and CDKN2 (3/21). Of 21 patients with recommendations, only two (9.5%) received genomics-driven therapy, compared with 31.7% (86/271) of patients with other solid tumor malignancies (p = 0.03). One received an IDH1 inhibitor, and one received dabrafenib and trametinib for a BRAF alteration; both on clinical trials. At time of last follow-up, best responses were unknown and partial response, respectively. Unavailability of clinical trials in the vicinity (9.5%), and clinical trial ineligibility, mainly due to poor performance status (9.5%), were common reasons for lack of actionability. Conclusions: Benefit from precision oncology in the PB population is low, with only 4.4% (2/45) of patients with NGS results eventually receiving genomics-driven therapy. Benefit to patients will not improve until access to clinical trials is enhanced and patients are evaluated for these trials earlier in the course of their disease, when their performance status is likely to be higher.
Lack of reduction of serum alphafetoprotein during treatment with direct antiviral agents predicts hepatocellular carcinoma development in a large cohort of patients with HCV-related cirrhosis
Authors: C. Masetti, R. Lionetti, M. Lupo, M. Siciliano, V. Giannelli, F. Ponziani, E. Teti, C. Dell’unto, S. Francioso, A. Brega, M. Montalbano, U.V. Comandini, C. Taibi, G. Galati, U.V. Gentilucci, A. Picardi, M. Andreoni, M. Pompili, A. Pellicelli, G. D’offizi, A. Gasbarrini, A. De Santis, A. Mario
Journal: Journal of Hepatology (2018)
Alastair John Bellingham
Authors: Tony Pagliuca
Journal: BMJ (2018)

Alastair John Bellingham did his training and research at University College London and the University of Washington, Seattle, before returning to UCL as a senior lecturer in 1971. His research interests were in red cell and genetic blood disorders, and he published seminal findings in Nature and JCI . He was the youngest ever appointed chair of haematology …
99mTechnetium-MebrofeninHepatobiliary Scintigraphy predicts portal hypertension in Child-Pugh Acirrhosis
Authors: T. Chapelle, G. Roeyen, V. Hartman, B. Bracke, H. Ivan, T. Vanwolleghem, D. Ysebaert, S. Francque
Journal: Journal of Hepatology (2018)
Cost-effectiveness of Nusinersen for Spinal Muscular Atrophy—Reply
Authors: Vinay Prasad
Journal: JAMA Pediatrics (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
“FLYING RIBBON” SIGN: A NOVEL CHOLANGIOSCOPY FEATURE OF CHOLANGIOCARCINOMA
Authors: O Urban, E Skanderova, P Fojtik, V Zoundjiekpon, P Falt
Journal: Endoscopy (2018)

A set of cholangioscopic features discriminating cholangiocarcinoma from benign biliary lesions has been described recently. These include ulceration, scarring, papillary projections, mass lesion, abnormal vessels, stricture, coarse granular mucosa and others. We are introducing a new feature named “flying ribbon” sign. It is defined as punctual spiral-like underwater bleeding resembling flying ribbon, occurring either spontaneously or after gentle contact of the tip of cholangioscope with a lesion.
Outcomes and characteristics of patients receiving second-line therapy for advanced pancreatic cancer.
Authors: Erica S Tsang, Hui-Li Wong, Ying Wang, Daniel John Renouf, Winson Y. Cheung, Howard John Lim, Sharlene Gill, Jonathan M. Loree, Hagen F. Kennecke
Journal: Journal of Clinical Oncology (2018)

435 Background: Recent trials have demonstrated improved outcomes in the 1st-line treatment of advanced pancreatic cancer (APC). However, there is limited randomized data to guide 2nd-line chemotherapy (CT) selection. We aimed to characterize predictors and outcomes of 2nd-line CT in patients (pts) with APC. Methods: We identified all pts with APC (locally advanced (LAPC) or metastatic (MPC)) who received ≥1 cycle of 1st-line CT between January 1, 2012 and December 31, 2015 across 6 centers in British Columbia, Canada. Baseline characteristics and survival outcomes were summarized. Results: Of 676 pts with APC (31% LAPC, 69% MPC) who received ≥1 cycle of CT, 164 (24%) received 2nd-line CT. These pts were younger (median 63.7 vs. 67.4 years; p= 0.01), had a lower ECOG (77% ECOG 0-1 vs. 51% ECOG ≥2; p&lt; 0.001), and higher CA19-9 (median 1034 vs. 829; p= 0.01) compared to patients who did not receive 2nd-line CT. There were no differences in rates of 2nd-line CT between LAPC and MPC (28% vs. 23%; p= 0.18). On logistic regression, only 1st-line FOLFIRINOX (OR 5.90, p&lt; 0.001) was associated with 2 nd line CT. CT regimens are summarized by line (Table). Median duration of 2nd-line CT was 3 cycles (range 1-30). Median overall survival (mOS) from diagnosis of patients with 2 nd -line CT was 16 months. mOS from 2nd-line CT was longer with 2nd-line gemcitabine/nab-paclitaxel than fluoropyrimidine or gemcitabine (7.9 vs. 5.1 vs. 4.3 months; p= 0.008). On multivariate analysis, longer OS from 2nd-line CT was associated with gemcitabine/nab-paclitaxel (vs. single agent CT), lower ECOG, LAPC (vs MPC), and lower CA 19-9 (HRs 0.49, 0.67, 0.58, 0.38, respectively). Conclusions: In this population-based cohort, pts treated with 2nd line CT were younger, have better ECOG, similar rates of LAPC vs. MPC, and achieved a median OS of 16 months. 1st-line FOLFIRINOX was the strongest predictor of 2nd-line CT. Gemcitabine/nab-paclitaxel was associated with superior 2nd line OS compared to gemcitabine/fluoropyrimidine. [Table: see text]
Correction to: Role of protein kinases CK1α and CK2 in multiple myeloma: regulation of pivotal survival and stress-managing pathways
Authors: Sabrina Manni, Marilena Carrino, Francesco Piazza
Journal: Journal of Hematology & Oncology (2018)

The original article [1] contains an inadvertent error in the following sentence in the Abstract regarding the erroneous description of Ser/Thr kinases as 'phylogenetically related'.