tbuckley/cabot-search huggingface dataset:
What Is the Optimal Treatment for Vulnerable Older Women With Ovarian Cancer?
Authors: Kanako Ito, Akihiko Shimomura
Journal: JAMA Oncology (2021)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 Oncology journal
DT04: Pandemic placement: delivering the dermatology undergraduate curriculum at a UK medical school during the COVID‐19 crisis
Journal: British Journal of Dermatology (2021)

fulfilment, driven by opportunities for reflection, supervision and staffing levels, tended to drive identity transitions.Redeployment has a strong impact on dermatology trainee professional identity and may lead to reaffirmation of prior tribal values or disorienting reflection upon future career trajectories.Improved support for community transition, reduction of uncertainty and fostering a sense of purpose among trainees may aid identity enrichment and safeguard the future dermatology consultant workforce.
Dyspnoea upon hospital admission: listen to the bird of ill omen!
Authors: Maxens Decavèle, Thomas Similowski
Journal: European Respiratory Journal (2021)

Dyspnoea, namely a patient's complaint of difficult, disturbing or distressing breathing, is a symptom that prompts physicians to undertake diagnostic and therapeutic procedures in order to identify and correct causative pathophysiological abnormalities. Dyspnoea can become self-perpetuating (a syndrome) when it persists despite mechanistic treatments. It then justifies symptomatic management to alleviate suffering [1, 2]. Above all, dyspnoea is an experience that changes patients' lives and requires holistic approaches [3]. In this issue of the European Respiratory Journal , Stevens et al. [4], from a group that has achieved outstanding progress in the understanding of dyspnoea [5], spotlight yet another aspect of dyspnoea. They highlight its value as a very generic warning sign of impending doom: in unselected patients admitted to hospital, the "mere fact" of reporting dyspnoea is associated with an increased risk of hospital mortality. This risk increases with increasing intensity of dyspnoea. Patients reporting dyspnoea on admission to an hospital ward are at increased risk of death during their hospital stay <https://bit.ly/2Q5pYWR>
CHIR99021 Promotes hiPSC‐Derived Cardiomyocyte Proliferation in Engineered 3D Microtissues
Authors: Ramona Hesselbarth, Tilman U. Esser, Kaveh Roshanbinfar, Stefan Schrüfer, Dirk W. Schubert, Felix B. Engel
Journal: Advanced Healthcare Materials (2021)

Abstract Cardiac tissue engineering is a promising strategy to generate human cardiac tissues for modeling cardiac diseases, screening for therapeutic drugs, and repairing the injured heart. Yet, several issues remain to be resolved including the generation of tissues with high cardiomyocyte density. Here, it is shown that the integration of the glycogen synthase kinase‐3 β inhibitor CHIR99021 in collagen I hydrogels promotes proliferation of human‐induced pluripotent stem cell‐derived (hiPSC) cardiomyocytes post‐fabrication improving contractility of and calcium flow in engineered 3D cardiac microtissues. CHIR99021 has no effect on the gelation kinetics or the mechanical properties of collagen I hydrogels. Analysis of cell density and proliferation based on Ki‐67 staining indicates that integration of CHIR99021 together with external CHIR99021 stimulation increases hiPSC‐cardiomyocyte number by ≈2‐fold within 7 d post‐fabrication. Analysis of the contractility of engineered cardiac tissues after another 3 d in the absence of external CHIR99021 shows that CHIR99021‐induced hiPSC‐cardiomyocyte proliferation results in synchronized calcium flow, rhythmic beating, increased speed of contraction and contraction amplitude, and reduced peak‐to‐peak time. The CHIR99021‐stimulated engineered cardiac microtissues exhibit spontaneous rhythmic contractions for at least 35 d. Collectively, the data demonstrate the potential of induced cardiomyocyte proliferation to enhance engineered cardiac microtissues by increasing cardiomyocyte density.
Health and social care tax to be introduced across UK
Authors: Jacqui Wise
Journal: BMJ (2021)

The prime minister has announced a UK-wide “health and social care levy” to fund NHS backlogs resulting from the covid pandemic and to overhaul social care.

The plan has been criticised for placing a greater burden on young adults and the lowest paid and for failing to tackle the issue of low pay among care workers. Think tanks have also pointed out that the vast majority of the funds raised will go directly to the NHS, with little left over for social care.

From April 2022 national insurance contributions will rise by 1.25 percentage points for employees and employers, and there will be a 1.25 percentage point rise in the tax on share dividends. From April 2023 the rises will stay the same but will be labelled as a health and social care levy and appear as a separate line on payslips. The levy will be extended at this point to cover pensioners who are still in work. The plan is due to be voted on in parliament on Wednesday 8 September.

A 1.25 percentage point increase to national insurance would mean someone on a £30 000 salary would pay an additional £255 a year.

Much of the revenue initially will be devoted to cutting waiting lists in the NHS, with social care receiving only £5.4bn …
Role of prostaglandin E2 in tissue repair and regeneration
Authors: Hui Cheng, Haoyan Huang, Zhikun Guo, Ying Chang, Zongjin Li
Journal: Theranostics (2021)

Tissue regeneration following injury from disease or medical treatment still represents a challenge in regeneration medicine. Prostaglandin E2 (PGE2), which involves diverse physiological processes via E-type prostanoid (EP) receptor family, favors the regeneration of various organ systems following injury for its capabilities such as activation of endogenous stem cells, immune regulation, and angiogenesis. Understanding how PGE2 modulates tissue regeneration and then exploring how to elevate the regenerative efficiency of PGE2 will provide key insights into the tissue repair and regeneration processes by PGE2. In this review, we summarized the application of PGE2 to guide the regeneration of different tissues, including skin, heart, liver, kidney, intestine, bone, skeletal muscle, and hematopoietic stem cell regeneration. Moreover, we introduced PGE2-based therapeutic strategies to accelerate the recovery of impaired tissue or organs, including 15-hydroxyprostaglandin dehydrogenase (15-PGDH) inhibitors boosting endogenous PGE2 levels and biomaterial scaffolds to control PGE2 release.
Call for emergency action to limit global temperature increases, restore biodiversity, and protect health
Authors: Lukoye Atwoli, Abdullah H Baqui, Thomas Benfield, Raffaella Bosurgi, Fiona Godlee, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Carlos Augusto Monteiro, Ian Norman, Kirsten Patrick, Nigel Praities, Marcel G M Olde Rikkert, Eric J Rubin, Peush Sahni, Richard Smith, Nicholas J Talley, Sue Turale, Damián Vázquez
Journal: BMJ (2021)

> Wealthy nations must do much more, much faster.

The United Nations General Assembly in September 2021 will bring countries together at a critical time for marshalling collective action to tackle the global environmental crisis. They will meet again at the biodiversity summit in Kunming, China, and the climate conference (Conference of the Parties (COP)26) in Glasgow, UK. Ahead of these pivotal meetings, we—the editors of health journals worldwide—call for urgent action to keep average global temperature increases below 1.5°C, halt the destruction of nature and protect health.

Health is already being harmed by global temperature increases and the destruction of the natural world, a state of affairs health professionals have been bringing attention to for decades.1 The science is unequivocal; a global increase of 1.5°C above the preindustrial average and the continued loss of biodiversity risk catastrophic harm to health that will be impossible to reverse.2 3 Despite the world’s necessary preoccupation with COVID-19, we cannot wait for the pandemic to pass to rapidly reduce emissions.

Reflecting the severity of the moment, this editorial appears in health journals across the world. We are united in recognising that only fundamental and equitable changes to societies will reverse our current trajectory.

The risks to health of increases above 1.5°C are now well established.2 Indeed, no temperature rise is ‘safe’. In the past 20 years, heat-related mortality among people aged over 65 has increased by more than 50%.4 Higher temperatures have brought increased dehydration and renal function loss, dermatological malignancies, tropical infections, adverse mental health outcomes, pregnancy complications, allergies, and cardiovascular and pulmonary morbidity and mortality.5 6 Harms disproportionately affect the most vulnerable, including children, older populations, ethnic minorities, poorer communities and those with underlying health problems.2 4 

Global heating is also contributing to the decline in …
ALL-Associated p185 and CML-Associated p210 BCR-ABL Induce a Nearly Identical Gene-Expression Profile In Vivo
Authors: S. Gueller, T. Beissert, M. Komor, O. Schneider, R. Henschler, D. Hoelzer, O. G. Ottmann, W. K. Hofmann, M. Ruthardt
Journal: Blood (2002)
Long-term evolution in liver fibrosis and immune profile after direct-acting antivirals therapy in hepatitis C virus-human immunodeficiency virus co-infected patients
Authors: Montserrat Laguno, María Martínez-Rebollar, Martina Casanova, Elisa de Lazzari, Ana González-Cordón, Berta Torres, Alexy Inciarte, Lorena de la Mora, Ainoa Ugarte, Juan Ambrosioni, José Luís Blanco, Esteban Martínez, Josep Mallolas
Journal: Clinical Microbiology and Infection (2021)
Ubiquitination of ATF6 by disease-associated RNF186 promotes the innate receptor-induced unfolded protein response
Authors: Kishu Ranjan, Matija Hedl, Saloni Sinha, Xuchen Zhang, Clara Abraham
Journal: Journal of Clinical Investigation (2021)

Properly balancing microbial responses by the innate immune system through pattern recognition receptors (PRRs) is critical for intestinal immune homeostasis. Ring finger protein 186 (RNF186) genetic variants are associated with inflammatory bowel disease (IBD). However, functions for the E3 ubiquitin ligase RNF186 are incompletely defined. We found that upon stimulation of the PRR nucleotide-binding oligomerization domain containing 2 (NOD2) in human macrophages, RNF186 localized to the ER, formed a complex with ER stress sensors, ubiquitinated the ER stress sensor activating transcription factor 6 (ATF6), and promoted the unfolded protein response (UPR). These events, in turn, led to downstream signaling, cytokine secretion, and antimicrobial pathway induction. Importantly, RNF186-mediated ubiquitination of K152 on ATF6 was required for these outcomes, highlighting a key role for ATF6 ubiquitination in PRR-initiated functions. Human macrophages transfected with the rare RNF186-A64T IBD risk variant and macrophages from common rs6426833 RNF186 IBD risk carriers demonstrated reduced NOD2-induced outcomes, which were restored by rescuing UPR signaling. Mice deficient in RNF186 or ATF6 demonstrated a reduced UPR in colonic tissues, increased weight loss, and less effective clearance of bacteria with dextran sodium sulfate-induced injury and upon oral challenge with Salmonella Typhimurium. Therefore, we identified that RNF186 was required for PRR-induced, UPR-associated signaling leading to key macrophage functions; defined that RNF186-mediated ubiquitination of ATF6 was essential for these functions; and elucidated how RNF186 IBD risk variants modulated these outcomes.
Memorial Meeting.
Journal: JAMA (1884)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Inviting adolescents aged 12-17 for covid-19 vaccination: the need for patience
Authors: Peter A M de Beer, Koenraad Van den Abbeele
Journal: BMJ (2021)

The UK shows restraint in rolling out covid-19 vaccination for adolescents by reserving it for vulnerable children.1 We commend such prudence.2

The European Medicines Agency (EMA) recently accepted the Pfizer-BioNTech and Moderna covid-19 vaccines for use from 12 years old. Expected direct benefits are reductions in multisystem inflammatory syndrome in children and long covid; indirect benefits are less virus circulation and herd immunity because too many adults are refusing. EMA is reviewing vaccine side effects such as myocarditis and pericarditis.

The Dutch Health …
Effect of Heart Rate on the Outcome of Renal Denervation in Patients With Uncontrolled Hypertension
Authors: Michael Böhm, Konstantinos Tsioufis, David E. Kandzari, Kazuomi Kario, Michael A. Weber, Roland E. Schmieder, Raymond R. Townsend, Saarraaken Kulenthiran, Christian Ukena, Stuart Pocock, Sebastian Ewen, Joachim Weil, Martin Fahy, Felix Mahfoud
Journal: Journal of the American College of Cardiology (2021)
M2-逸脱ミクログリアの移植はマウス脊髄損傷後の運動機能回復を促進する【JST・京大機械翻訳】
Authors: Kobashi Shuhei, Terashima Tomoya, Katagi Miwako, Nakae Yuki, Okano Junko, Suzuki Yoshihisa, Urushitani Makoto, Kojima Hideto
Journal: Molecular Therapy (2020)
Phase 2a randomized clinical trial of dupilumab (anti‐IL‐4Rα) for alopecia areata patients
Authors: Emma Guttman‐Yassky, Yael Renert‐Yuval, Jennifer Bares, Margot Chima, Jason E. Hawkes, Patricia Gilleaudeau, Mary Sullivan‐Whalen, Giselle K. Singer, Sandra Garcet, Ana B. Pavel, Mark G. Lebwohl, James G. Krueger
Journal: Allergy (2021)

Treatments for alopecia areata (AA) patients with extensive scalp hair loss are limited, and recent evidence supports a role for type 2 T-cell (Th2)-immune response in AA. Dupilumab, a monoclonal antibody inhibiting Th2 signaling, approved for type 2 diseases including atopic dermatitis, was evaluated in AA patients.Alopecia areata patients with and without concomitant atopic dermatitis were randomized 2:1 to receive weekly subcutaneous dupilumab (300 mg) or placebo for 24 weeks, followed by another 24-week dupilumab open-label phase. The primary outcome was change from baseline in the Severity of Alopecia Tool (SALT) score at week 24; secondary outcomes included a range of measures of hair regrowth.Forty and 20 patients were assigned to the dupilumab and placebo arms, respectively. At week 24, disease worsening was documented in the placebo arm, with a least-squares mean change in the SALT score of -6.5 (95% confidence-interval [CI], -10.4 to -2.6), versus a change of 2.2 (95% CI, -0.6 to 4.94) in the dupilumab arm (p < .05). After 48 weeks of dupilumab treatment, 32.5%, 22.5% and 15% of patients achieved SALT30 /SALT50 /SALT75 improvement, respectively, while in patients with baseline IgE ≥ 200 IU/ml response rates increased to 53.8%, 46.2%, and 38.5%, respectively. Moreover, baseline IgE predicts treatment response with 83% accuracy. No new safety signals were detected.This hypothesis-driven trial is the first to indicate the possible pathogenic role of the Th2 axis and Th2 targeting in AA patients. Patient selection based on baseline serum IgE levels may improve treatment results (Clinicaltrials.gov number, NCT03359356).
PTPN2 mutations cause epithelium-intrinsic barrier loss that synergizes with mucosal immune hyperactivation
Authors: Yan Y. Sweat, Jerrold R. Turner
Journal: Journal of Clinical Investigation (2021)

It is clear that excessive mucosal immune activation and intestinal barrier dysfunction both contribute to inflammatory bowel disease (IBD) pathogenesis. T cell protein tyrosine phosphatase (TCPTP), which extinguishes signaling in immune cells, is linked to IBD and other immune-mediated diseases. In this issue of the JCI, Marchelletta and Krishnan et al. demonstrate that, in intestinal epithelial cells, TCPTP regulates tight junction permeability in vivo. Intestinal epithelial TCPTP loss potentiated cytokine-induced barrier loss, and this synergized with effects of TCPTP loss in immune cells. This work implicates a single mutation as the cause of distinct functional aberrations in diverse cell types and demonstrates how one genetic defect can drive multihit disease pathogenesis.
Amrubicin (AMR) does not reduce LVEF with cumulative doses > 1000 mg/m(2) in 2nd-line treatment of small cell lung cancer (SCLC): A pooled analysis of two phase II trials
Authors: David R. Spigel, Chirag Shah, Paul Lorigan, Richard McNally, Markus Renschler, Jennifer W. Oliver
Journal: Journal of Thoracic Oncology (2009)
A Care Coordination Intervention Improves Symptoms But Not Charges in High-Risk Patients With Inflammatory Bowel Disease
Authors: Jeffrey A Berinstein, Shirley A Cohen-Mekelburg, Gillian M Greenberg, Daniel Wray, Sameer K Berry, Sameer D Saini, A Mark Fendrick, Megan A Adams, Akbar K Waljee, Peter D R Higgins
Journal: Clinical Gastroenterology and Hepatology (2021)
Transcriptome-wide Cas13 guide RNA design for model organisms and viral RNA pathogens
Authors: Xinyi Guo, Jahan A. Rahman, Hans-Hermann Wessels, Alejandro Méndez-Mancilla, Daniel Haro, Xinru Chen, Neville E. Sanjana
Journal: Cell Genomics (2021)

The recent characterization of RNA-targeting CRISPR nucleases has enabled diverse transcriptome engineering and screening applications that depend crucially on prediction and selection of optimized CRISPR guide RNAs (gRNAs). Previously, we developed a computational model to predict RfxCas13d gRNA activity for all human protein-coding genes. Here, we extend this framework to six model organisms (human, mouse, zebrafish, fly, nematode, and flowering plants) for protein-coding genes and noncoding RNAs (ncRNAs) and also to four RNA virus families (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], HIV-1, H1N1 influenza, and Middle East respiratory syndrome [MERS]). We include experimental validation of predictions by testing knockdown of multiple ncRNAs (MALAT1, HOTAIRM1, Gas5, and Pvt1) in human and mouse cells. We developed a freely available web-based platform (cas13design) with pre-scored gRNAs for transcriptome-wide targeting in several organisms and an interactive design tool to predict optimal gRNAs for custom RNA targets entered by the user. This resource will facilitate CRISPR-Cas13 RNA targeting in model organisms, emerging viral threats to human health.
Identification of direct transcriptional targets of NFATC2 that promote β cell proliferation
Authors: Shane P. Simonett, Sunyoung Shin, Jacob A. Herring, Rhonda Bacher, Linsin A. Smith, Chenyang Dong, Mary E. Rabaglia, Donnie S. Stapleton, Kathryn L. Schueler, Jeea Choi, Matthew N. Bernstein, Daniel R. Turkewitz, Carlos Perez-Cervantes, Jason Spaeth, Roland Stein, Jeffery S. Tessem, Christina Kendziorski, Sündüz Keleş, Ivan P. Moskowitz, Mark P. Keller, Alan D. Attie
Journal: Journal of Clinical Investigation (2021)

The transcription factor NFATC2 induces β cell proliferation in mouse and human islets. However, the genomic targets that mediate these effects have not been identified. We expressed active forms of Nfatc2 and Nfatc1 in human islets. By integrating changes in gene expression with genomic binding sites for NFATC2, we identified approximately 2200 transcriptional targets of NFATC2. Genes induced by NFATC2 were enriched for transcripts that regulate the cell cycle and for DNA motifs associated with the transcription factor FOXP. Islets from an endocrine-specific Foxp1, Foxp2, and Foxp4 triple-knockout mouse were less responsive to NFATC2-induced β cell proliferation, suggesting the FOXP family works to regulate β cell proliferation in concert with NFATC2. NFATC2 induced β cell proliferation in both mouse and human islets, whereas NFATC1 did so only in human islets. Exploiting this species difference, we identified approximately 250 direct transcriptional targets of NFAT in human islets. This gene set enriches for cell cycle–associated transcripts and includes Nr4a1. Deletion of Nr4a1 reduced the capacity of NFATC2 to induce β cell proliferation, suggesting that much of the effect of NFATC2 occurs through its induction of Nr4a1. Integration of noncoding RNA expression, chromatin accessibility, and NFATC2 binding sites enabled us to identify NFATC2-dependent enhancer loci that mediate β cell proliferation.
Non-P450 Drug-Metabolizing Enzymes: Contribution to Drug Disposition, Toxicity, and Development
Authors: Tatsuki Fukami, Tsuyoshi Yokoi, Miki Nakajima
Journal: The Annual Review of Pharmacology and Toxicology (2021)

Most clinically used drugs are metabolized in the body via oxidation, reduction, or hydrolysis reactions, which are considered phase I reactions. Cytochrome P450 (P450) enzymes, which primarily catalyze oxidation reactions, contribute to the metabolism of over 50% of clinically used drugs. In the last few decades, the function and regulation of P450s have been extensively studied, whereas the characterization of non-P450 phase I enzymes is still incomplete. Recent studies suggest that approximately 30% of drug metabolism is carried out by non-P450 enzymes. This review summarizes current knowledge of non-P450 phase I enzymes, focusing on their roles in controlling drug efficacy and adverse reactions as an important aspect of drug development.