tbuckley/cabot-search huggingface dataset:
Rogaratinib in patients with advanced cancers selected by FGFR mRNA expression: a phase 1 dose-escalation and dose-expansion study
Authors: Martin Schuler, Byoung Chul Cho, Cyrus Michael Sayehli, Alejandro Navarro, Ross A Soo, Heike Richly, Philippe Alexandre Cassier, David Tai, Nicolas Penel, Lucia Nogova, Se Hoon Park, Martin Schostak, Pablo Gajate, Richard Cathomas, Prabhu Rajagopalan, Joachim Grevel, Sebastian Bender, Oliver Boix, Hendrik Nogai, Matthias Ocker, Peter Ellinghaus, Markus Joerger
Journal: The Lancet Oncology (2019)
ILC2s chew the fat
Authors: Roberto R. Ricardo-Gonzalez, Richard M. Locksley
Journal: The Journal of Experimental Medicine (2019)

In this issue of JEM, Rana et al. (https://doi.org/10.1084/jem.20190689) report that adipose tissue multipotent stromal cells (MSCs) provide multifaceted support for adipose tissue–resident ILC2s through contact-mediated proliferation and IL-33–mediated stress-induced activation.
Correspondence to ‘Time to change the primary outcome of lupus trials’
Authors: Shereen Oon, Molla Huq, Mandana Nikpour
Journal: Annals of the Rheumatic Diseases (2019)

We note with interest and express our principle agreement with the views put forward by Professor Frederic Houssiau in the recent Editorial ‘Time to change the primary outcome of lupus trials’ published in Annals of the Rheumatic Diseases .1 Professor Houssiau advocated using steroid reduction as a primary outcome measure in systemic lupus erythematosus (SLE) clinical trials, or as a minimum, incorporating a steroid reduction target into the primary endpoint. This proposal was prompted by the observation that, like many other recent phase 3 clinical trials conducted with drugs that have a sound biological mechanism for benefit in SLE, the recently published CHABLIS-SC phase 3 clinical trial of subcutaneous blisibimod in SLE2 failed to meet its primary endpoint of a week 52-SLE Responder Index (SRI)-6. However, a significant steroid sparing effect was seen, with a modified endpoint of a week 52-SRI-6 combined with a reduction in steroid dose during weeks 40–52 compared with study entry, showing a trend to benefit for the blisibimod …
Guselkumab versus secukinumab for the treatment of moderate-to-severe psoriasis (ECLIPSE): results from a phase 3, randomised controlled trial
Authors: Kristian Reich, April W Armstrong, Richard G Langley, Susan Flavin, Bruce Randazzo, Shu Li, Ming-Chun Hsu, Patrick Branigan, Andrew Blauvelt
Journal: The Lancet (2019)
Letting the cat out of the bag: athletes, coaches and physiotherapists share their perspectives on injury prevention in elite sports
Authors: Caroline Bolling, Saulo Delfino Barboza, Willem van Mechelen, H Roeline Pasman
Journal: British Journal of Sports Medicine (2019)

To explore how sports injury prevention takes place in elite sport practice and to describe the perspectives of athletes, coaches and physiotherapists regarding the most critical factors that help prevent injury in the elite sports context.Qualitative study. Semistructured interviews with 19 international level athletes, coaches and physiotherapists, from different Olympic sports. Interviews were transcribed verbatim and analysed using comparative data analysis based on Grounded Theory.The participants perceived injury risk as an inherent part of elite sports, because athletes try to enhance performance by pushing their limits. Participants described injury prevention as a learning process that changed over time, based on their sports experience and the injuries that they had sustained along their career. Communication among the athletes, coaches and physiotherapists was described as a key component of the injury prevention process. Study participants emphasised the relevance of teamwork and shared responsibility. Performance was presented as the core of the athlete's daily practice, indicating that injury prevention can be a means to that end but is not a goal in itself for this community.Participants perceive injury prevention as part of elite sports and thus embrace the need for injury prevention. Injury prevention strategies in elite sports were described as a learning process, following the dynamic nature of training for maximal performance. Performance is the participants' main goal.
Abstract 13413: Association Between Obesity Phenotypes and Electrocardiographic Markers of Poor Outcomes
Authors: Muhammad Imtiaz Ahmad, Morgana Mongraw-Chaffin, Kristina H Lewis, Haiying Chen, Jamy D Ard, Elsayed Z Soliman
Journal: Circulation (2018)

Introduction: As accumulating evidence creates doubt about the concept of ‘metabolically healthy obesity’ (MHO), investigating the association of MHO and other obesity phenotypes with ECG markers o...
In vivo vaccination effect in multiple myeloma patients treated with the monoclonal antibody isatuximab
Authors: Djordje Atanackovic, Sara Yousef, Christa Shorter, Srinivas K. Tantravahi, Mary Steinbach, Fiorella Iglesias, Douglas Sborov, Sabarinath Venniyil Radhakrishnan, Marielle Chiron, Rodney Miles, Mohamed Salama, Nicolaus Kröger, Tim Luetkens
Journal: Leukemia (2019)
The proportion of nevus-associated invasive melanoma differs with Breslow thickness: A cross-sectional study of 1087 cutaneous melanomas
Authors: Esperanza Manrique-Silva, Diana Reyes-García, Belen Folgado, Alejandro Martín-Gorgojo, Víctor Traves, Celia Requena, Eduardo Nagore
Journal: Journal of the American Academy of Dermatology (2019)
Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial
Authors: Anthony C Nichols, Julie Theurer, Eitan Prisman, Nancy Read, Eric Berthelet, Eric Tran, Kevin Fung, John R de Almeida, Andrew Bayley, David P Goldstein, Michael Hier, Khalil Sultanem, Keith Richardson, Alex Mlynarek, Suren Krishnan, Hien Le, John Yoo, S Danielle MacNeil, Eric Winquist, J Alex Hammond, Varagur Venkatesan, Sara Kuruvilla, Andrew Warner, Sylvia Mitchell, Jeff Chen, Martin Corsten, Stephanie Johnson-Obaseki, Libni Eapen, Michael Odell, Christina Parker, Bret Wehrli, Keith Kwan, David A Palma
Journal: The Lancet Oncology (2019)
Expression of Idh1R132H in the murine subventricular zone stem cell niche recapitulates early gliomagenesis
Authors: C Bardella, O Al-Dalahmah, D Krell, P Brazauskas, M Tomkova, J Adam, S Serres, H Lockstone, L Freeman-Mills, I Pfeffer, N Sibson, R Goldin, B Schuster-Böeckler, P J Pollard, T Soga, J S McCullagh, C J Schofield, P Mulholland, O Ansorge, S Kriaucionis, P J Ratcliffe, F G Szele, I Tomlinson
Journal: Cancer Cell (2016)
Circular RNA circRNA_000203 aggravates cardiac hypertrophy via suppressing miR-26b-5p and miR-140-3p binding to Gata4
Authors: Hui Li, Jin-Dong Xu, Xian-Hong Fang, Jie-Ning Zhu, Jing Yang, Rong Pan, Shu-Jing Yuan, Ni Zeng, Zhen-Zhen Yang, Hui Yang, Xi-Pei Wang, Jin-Zhu Duan, Sheng Wang, Jian-Fang Luo, Shu-Lin Wu, Zhi-Xin Shan
Journal: Cardiovascular Research (2019)

Abstract Aims Circular RNAs (circRNAs) are involved in gene regulation in a variety of physiological and pathological processes. The present study aimed to investigate the effect of circRNA_000203 on cardiac hypertrophy and the potential mechanisms involved. Methods and results CircRNA_000203 was found to be up-regulated in the myocardium of Ang-II-infused mice and in the cytoplasma of Ang-II-treated neonatal mouse ventricular cardiomyocytes (NMVCs). Enforced expression of circRNA_000203 enhances cell size and expression of atrial natriuretic peptide and β-myosin heavy chain in NMVCs. In vivo, heart function was impaired and cardiac hypertrophy was aggravated in Ang-II-infused myocardium-specific circRNA_000203 transgenic mice (Tg-circ203). Mechanistically, we found that circRNA_000203 could specifically sponge miR-26b-5p, -140-3p in NMVCs. Further, dual-luciferase reporter assay showed that miR-26b-5p, -140-3p could interact with 3′-UTRs of Gata4 gene, and circRNA_000203 could block the above interactions. In addition, Gata4 expression is transcriptionally inhibited by miR-26b-5p, -140-3p mimic in NMVCs but enhanced by over-expression of circRNA_000203 in vitro and in vivo. Functionally, miR-26b-5p, -140-3p, and Gata4 siRNA, could reverse the hypertrophic growth in Ang-II-induced NMVCs, as well as eliminate the pro-hypertrophic effect of circRNA_000203 in NMVCs. Furthermore, we demonstrated that NF-κB signalling mediates the up-regulation of circRNA_000203 in NMVCs exposed to Ang-II treatment. Conclusions Our data demonstrated that circRNA_000203 exacerbates cardiac hypertrophy via suppressing miR-26b-5p and miR-140-3p leading to enhanced Gata4 levels.
Single-cell analysis reveals fibroblast heterogeneity and myofibroblasts in systemic sclerosis-associated interstitial lung disease
Authors: Eleanor Valenzi, Melissa Bulik, Tracy Tabib, Christina Morse, John Sembrat, Humberto Trejo Bittar, Mauricio Rojas, Robert Lafyatis
Journal: Annals of the Rheumatic Diseases (2019)

Objectives Myofibroblasts are key effector cells in the extracellular matrix remodelling of systemic sclerosis-associated interstitial lung disease (SSc-ILD); however, the diversity of fibroblast populations present in the healthy and SSc-ILD lung is unknown and has prevented the specific study of the myofibroblast transcriptome. We sought to identify and define the transcriptomes of myofibroblasts and other mesenchymal cell populations in human healthy and SSc-ILD lungs to understand how alterations in fibroblast phenotypes lead to SSc-ILD fibrosis. Methods We performed droplet-based, single-cell RNA-sequencing with integrated canonical correlation analysis of 13 explanted lung tissue specimens (56 196 cells) from four healthy control and four patients with SSc-ILD, with findings confirmed by cellular indexing of transcriptomes and epitopes by sequencing in additional samples. Results Examination of gene expression in mesenchymal cells identified two major, SPINT2 hi and MFAP5 hi , and one minor, WIF1 hi , fibroblast populations in the healthy control lung. Combined analysis of control and SSc-ILD mesenchymal cells identified SPINT2 hi , MFAP5 hi , few WIF1 hi fibroblasts and a new large myofibroblast population with evidence of actively proliferating myofibroblasts. We compared differential gene expression between all SSc-ILD and control mesenchymal cell populations, as well as among the fibroblast subpopulations, showing that myofibroblasts undergo the greatest phenotypic changes in SSc-ILD and strongly upregulate expression of collagens and other profibrotic genes. Conclusions Our results demonstrate previously unrecognised fibroblast heterogeneity in SSc-ILD and healthy lungs, and define multimodal transcriptome-phenotypes associated with these populations. Our data indicate that myofibroblast differentiation and proliferation are key pathological mechanisms driving fibrosis in SSc-ILD.
Prenatal and Childhood Traffic-Related Air Pollution Exposure and Telomere Length in European Children: The HELIX Project
Authors: Diana B.P. Clemente, Martine Vrijheid, Dries S. Martens, Mariona Bustamante, Leda Chatzi, Asta Danileviciute, Montserrat de Castro, Regina Grazuleviciene, Kristine B. Gutzkow, Johanna Lepeule, Lea Maitre, Rosie R.C. McEachan, Oliver Robinson, Per E. Schwarze, Ibon Tamayo, Marina Vafeiadi, John Wright, Rémy Slama, Mark Nieuwenhuijsen, Tim S. Nawrot
Journal: Environmental Health Perspectives (2019)

Telomere length is a molecular marker of biological aging.Here we investigated whether early-life exposure to residential air pollution was associated with leukocyte telomere length (LTL) at 8 y of age.In a multicenter European birth cohort study, HELIX (Human Early Life Exposome) ([Formula: see text]), we estimated prenatal and 1-y childhood exposure to nitrogen dioxide ([Formula: see text]), particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text]), and proximity to major roads. Average relative LTL was measured using quantitative real-time polymerase chain reaction (qPCR). Effect estimates of the association between LTL and prenatal, 1-y childhood air pollution, and proximity to major roads were calculated using multiple linear mixed models with a random cohort effect and adjusted for relevant covariates.LTL was inversely associated with prenatal and 1-y childhood [Formula: see text] and [Formula: see text] exposures levels. Each standard deviation (SD) increase in prenatal [Formula: see text] was associated with a [Formula: see text] (95% CI: [Formula: see text], [Formula: see text]) change in LTL. Prenatal [Formula: see text] was nonsignificantly associated with LTL ([Formula: see text] per SD increase; 95% CI: [Formula: see text], 0.6). For each SD increment in 1-y childhood [Formula: see text] and [Formula: see text] exposure, LTL shortened by [Formula: see text] (95% CI: [Formula: see text], [Formula: see text]) and [Formula: see text] (95% CI: [Formula: see text], 0.1), respectively. Each doubling in residential distance to nearest major road during childhood was associated with a 1.6% (95% CI: 0.02, 3.1) lengthening in LTL.Lower exposures to air pollution during pregnancy and childhood were associated with longer telomeres in European children at 8 y of age. These results suggest that reductions in traffic-related air pollution may promote molecular longevity, as exemplified by telomere length, from early life onward. https://doi.org/10.1289/EHP4148.
Posttranscriptional regulation of the human reduced folate carrier (RFC) gene by multiple 5′ untranslated regions (UTRs)
Authors: Scott Payton, Christina Haska, Robin Flatley, Larry Matherly
Journal: Cancer Research (2006)

551  RFC is the primary transport route for folates and antifolates (e.g., methotrexate, pemetrexed) into mammalian cells. Folates facilitate transfer of one-carbon units involved in the biosynthesis of dTMP, purine nucleotides, serine, and methionine. Antifolate inhibitors of these pathways are important chemotherapeutic drugs in the treatment of a variety of cancers. The human RFC (hRFC) gene is ubiquitously but differentially expressed in human tissues and tumors. The hRFC gene is regulated by at least five 5′ non-coding exons (A1/A2, A, B, C, and D). These exons are characterized by alternate transcription start sites, multiple splice forms, and selective tissue distributions. Altogether, there are at least 15 unique hRFC transcripts in which different 5′UTRs are fused to a shared splice acceptor region within the first coding exon, with a common hRFC open reading frame. In the classical model of ribosome scanning for translation, ribosomes enter at the 5′ m7G cap of mRNAs, travel in the 3′ direction, and stop to initiate translation at the first AUG codon. Both AUG sequence context and characteristics of the 5′UTR (length, GC context, secondary structure, upstream AUGs) significantly impact overall translation efficiency. Moreover, 5′UTRs can potentially affect transcript stabilities and encode N-terminally modified proteins initiated from upstream in-frame AUGs. 5′UTR sequences may also be involved in an alternate mechanism for translation initiation, in which ribosomes are recruited independently of the 5′ cap to an internal ribosomal entry site (IRES). In this report, we assessed the effects of the various hRFC 5′UTRs on translation efficiencies and mechanism, on steady state levels of hRFC transcripts, protein and function, on transcript stabilities, and on the synthesis of hRFC isoforms initiated from upstream AUGs. We demonstrate by in vitro translation assays with hRFC constructs including various 5′UTRs that synthesis of hRFC protein reflects the characteristics of the individual 5′UTRs. However, within cells, hRFC protein levels are determined not only by differences in translation efficiencies, but also transcript stabilities. For certain hRFC transcripts, a cap-independent translation involving IRESs may occur. For 5′UTRs derived from the hRFC-A1/A2 and -A non-coding exons, translation from upstream initiation sites results in modified hRFC proteins with increased molecular masses (approx. 7 kDa and 2 kDa, respectively) from wild type hRFC. These complex mechanisms for regulating hRFC expression likely provide a means of “fine tuning” carrier levels and function in response to folate requirements and/or to cell- and tissue- specific stimuli. Alterations in these posttranscriptional mechanisms may also be important factors in antifolate resistant tumor cells that have lost hRFC expression.
Publisher Correction: The immune cell landscape in kidneys of patients with lupus nephritis
Authors: Arnon Arazi, Deepak A Rao, Celine C Berthier, Anne Davidson, Yanyan Liu, Paul J Hoover, Adam Chicoine, Thomas M Eisenhaure, A Helena Jonsson, Shuqiang Li, David J Lieb, Fan Zhang, Kamil Slowikowski, Edward P Browne, Akiko Noma, Danielle Sutherby, Scott Steelman, Dawn E Smilek, Patti Tosta, William Apruzzese, Elena Massarotti, Maria Dall'Era, Meyeon Park, Diane L Kamen, Richard A Furie, Fernanda Payan-Schober, William F Pendergraft, Elizabeth A McInnis, Jill P Buyon, Michelle A Petri, Chaim Putterman, Kenneth C Kalunian, E Steve Woodle, James A Lederer, David A Hildeman, Chad Nusbaum, Soumya Raychaudhuri, Matthias Kretzler, Jennifer H Anolik, Michael B Brenner, David Wofsy, Nir Hacohen, Betty Diamond
Journal: Nature Immunology (2019)
Relationship between Altered Gene Expression and DNA Methylation of the DLK1-DIO3 region in Azacitidine-Treated Patients with Myelodysplastic Syndromes and Acute Myeloid Leukemia with Myelodysplasia-Related Changes
Authors: Michaela Dostalova Merkerova, Hana Remesova, Zdenek Krejcik, Nikoleta Loudova, Andrea Hrustincova, Katarina Szikszai, Jitka Vesela, Jaroslav Cermak, Anna Jonasova, Monika Belickova
Journal: Blood (2018)
Stable modifications of aldose reductase-like-1 activity changed cell susceptibility to acrolein, crotonaldehyde, and 4-hydroxynonenal
Authors: Xuyu Zu, Ruilan Yan, Duan-Fang Liao, Deliang Cao
Journal: Cancer Research (2007)

1964  Intracellular carbonyl stress affects cell growth and genetic material stability, posing serious consequences to human health, especially in neoplastic formation. Aldose reductase-like-1 (ARL-1) is a novel protein identified by our laboratory. This study investigated the effect of ARL-1 activity on cytotoxicity and genotoxicity of acrolein, crotonaldehyde, and 4-hydroxynonenal (HNE) using ARL-1 gene targeted cell lines derived from human colon cancer. HCT-8 cells with high endogenous ARL-1 were used for stable ARL-1 knockdown, while RKO cells with no ARL-1 expression were used for stable ARL-1 gene transfer. Totally, three HCT-8 stable clones with ARL-1 knockdown by 50 - 90% and three RKO stable clones with ARL-1 activity increase by 5 - 10 folds were established. Two vector control cell clones for each were also generated for controls. When exposed to acrolein (25 µM), RKO cells with overexpression of ARL-1 showed higher viability by 19.5 - 34.8% than vector control cells (P
AB0084 BehÇet’s disease and budd-chiari syndrome: two cases with diverse progresses
Authors: K Aksu, G Keser, V Inal, F Oksel, H Kocanaogullari, Y Tokat, Y Batur, G Gümüsdis, E Doganavsargil
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Behçet's disease (BD) is a systemic vasculitis of unknown aetiology that can lead to thrombosis of both veins and arteries of various sizes. Thrombosis of hepatic veins, known as Budd-Chiari syndrome (BCS) may be seen in BD, with variable clinical courses as described in 2 patients: Case 1: Thirty-four year-old male patient had oral and genital ulcers and erythema nodosum for 2 years. Within two weeks after presentation, thrombosis of hepatic veins and vena cava inferior was found, while evaluating the patient for abdominal pain and liver function test abnormalities. The patient well responded to the treatment consisting high dose prednisolone, pulse cyclophosphamide and anticoagulant drugs with recanalisation of the veins. At the end of two years, the patient has still been in clinical remission. Case 2: A twenty year-old male patient had oral and genital ulcerations for 4 years and had an episode of uveitis 4 years ago. He was referred to our clinic because of abdominal distension and oedema of lower extremities lasting for 4 months. The laboratory analyses disclosed ascites, grade III varicosity of oesophagus and thrombosis of hepatic veins and vena cava inferior. Mesoatrial shunt operation was performed when the initial treatment with pulse cyclophosphamide and high dose prednisolone failed. Obliteration of the shunt was observed by doppler ultrasonography, performed one week after the operation. He did not respond to the supportive therapy after the shunt operation and was lost with gastrointestinal bleeding. <h3>Objectives</h3> <h3>Methods</h3> <h3>Results</h3> <h3>Conclusion</h3> These two male Behçet's patients with BCS are examples of diverse prognoses, probably depending upon how early the diagnosis is made, and how efficient the treatment is. BCS in BD, may have a better prognosis if the diagnosis is made earlier and the treatment started sooner in the course of the disease.
Abstract 17059: Re-Use of Clinical Trial Data From the NHLBI Data Repository (BioLINCC) for Patient-Level Meta-Analyses of Cardiovascular Outcomes: Challenges and Opportunities
Authors: Helena Sviglin, Gauri Dandi, Eileen Navarro Almario, Tejas Patel, Colin O Wu, Xin Tian, Gyorgy Csako, Md Shamsuzzaman, Bereket Tesfaldet, Jerome Fleg, Anna Kettermann, Charu Gandotra, George Sopko, Lawton Cooper, Sean Coady, Avantika Banerjee, Nashwan Farooque, Laboni Hoque, Carlos Cure, Ruth Kirby, Lijuan Liu, Jue Chen, Ye Yan, Iffat Chowdhury, Keith Burkhart, Karim Calis, Eric Leifer, Ana Szarfman, Michael Domanski, Frank Pucino, Yves Rosenberg, Ahmed A Hasan
Journal: Circulation (2018)

Introduction: An objective of the Meta-AnalyTical Interagency Group (MATIG) is to conduct patient-level meta-analyses of cardiovascular outcomes using data from publicly available repositories. We describe challenges with data re-use from a seminal trial, provide a systematic approach to identify and curate data elements for hypothesis generation, and establish stackable trials to support these analyses. Methods: We used data from the ACCORD trial to assess risk factors and their gender specific differences for the event of hospitalization or death due to heart failure (hdHF), in patients with type 2 diabetes*. We identified the data elements needed to answer the research questions, reviewed the trial protocol to verify definitions, extracted patient-level data, performed quality assessment and statistical analysis. The results showed a gender difference in the effect of intensive vs. standard glucose-lowering therapy on hdHF. To validate the findings, we sought additional trials in BioLINCC to develop a compendium for meta-analysis, and repeated these steps for each trial. Results: Challenges for reusing the ACCORD trial included access to complete patient-level data and metadata. The compendium, developed to evaluate the stackability** of data across trials, identified differences in trial designs, patient populations, study interventions, and data elements that may impact the feasibility and interpretation of meta-analysis. An example of compendium components is shown in Table 1. Conclusion: High-quality metadata facilitate re-use of trial repository data. This compendium standardizes common data elements for gender, racial and age-group specific outcome assessment in major clinical trials. It provides the framework to assess the fitness of trials for patient-level meta-analyses. Efforts are underway by MATIG to expand the compendium to include risk factors and major cardiovascular outcomes across multiple large trials for meta-analysis.
Concerns About Potential Bias in a Randomized Clinical Trial of Integrated Prolonged Exposure Therapy vs Seeking Safety Integrated Coping Skills Therapy—Reply
Authors: Sonya B. Norman
Journal: JAMA Psychiatry (2019)

In Reply Consistent with other research,1 we2 found that Seeking Safety (SS) did not outperform the comparison condition, in this case, prolonged exposure (PE). Najavits, SS's developer who has acknowledged conflict of interest with SS, alleges 3 primary concerns with our study.