tbuckley/cabot-search huggingface dataset:
Long-term Survival After Out-of-Hospital Cardiac Arrest
Authors: Simon A. Amacher, Chantal Bohren, René Blatter, Christoph Becker, Katharina Beck, Jonas Mueller, Nina Loretz, Sebastian Gross, Kai Tisljar, Raoul Sutter, Christian Appenzeller-Herzog, Stephan Marsch, Sabina Hunziker
Journal: JAMA Cardiology (2022)

<h3>Importance</h3> Data on long-term survival beyond 12 months after out-of-hospital cardiac arrest (OHCA) of a presumed cardiac cause are scarce. <h3>Objective</h3> To investigate the long-term survival of adult patients after surviving the initial hospital stay for an OHCA. <h3>Data Sources</h3> A systematic search of the EMBASE and MEDLINE databases was performed from database inception to March 25, 2021. <h3>Study Selection</h3> Clinical studies reporting long-term survival after OHCA were selected based on predefined inclusion and exclusion criteria according to a preregistered study protocol. <h3>Data Extraction and Synthesis</h3> Patient data were reconstructed from Kaplan-Meier curves using an iterative algorithm and then pooled to generate survival curves. As a separate analysis, an aggregate data meta-analysis was performed. <h3>Main Outcomes and Measures</h3> The primary outcome was long-term survival (&gt;12 months) after OHCA for patients surviving to hospital discharge or 30 days after OHCA. <h3>Results</h3> The search identified 15 347 reports, of which 21 studies (11 800 patients) were included in the Kaplan-Meier–based meta-analysis and 33 studies (16 933 patients) in an aggregate data meta-analysis. In the Kaplan-Meier–based analysis, the median survival time for patients surviving to hospital discharge was 5.0 years (IQR, 2.3-7.9 years). The estimated survival rates were 82.8% (95% CI, 81.9%-83.7%) at 3 years, 77.0% (95% CI, 75.9%-78.0%) at 5 years, 63.9% (95% CI, 62.3%-65.4%) at 10 years, and 57.5% (95% CI, 54.8%-60.1%) at 15 years. Compared with patients with a nonshockable initial rhythm, patients with a shockable rhythm had a lower risk of long-term mortality (hazard ratio, 0.30; 95% CI, 0.23-0.39;<i>P</i> &lt; .001). Different analyses, including an aggregate data meta-analysis, confirmed these results. <h3>Conclusions and Relevance</h3> In this comprehensive systematic review and meta-analysis, long-term survival after 10 years in patients surviving the initial hospital stay after OHCA was between 62% and 64%. Additional research is needed to understand and improve the long-term survival in this vulnerable patient population.
改善皮肤中的脂质分布可以预防干燥和刺激
Journal: British Journal of Dermatology (2022)

British Journal of DermatologyVolume 186, Issue 5 p. e215-e215 Plain Language Summary 改善皮肤中的脂质分布可以预防干燥和刺激 First published: 02 May 2022 https://doi.org/10.1111/bjd.21268AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Linked Article: Danby et al. Br J Dermatol 2022; 186:875–886. 皮肤中的脂质类型和分布会影响其抵御外部环境的屏障作用。特应性湿疹(特应性皮炎)患者皮肤中的关键脂质较少，比如神经酰胺。这改变了脂质自身的分布方式，因此排列不够紧密，导致皮肤屏障受损。受损的皮肤容易干燥(水分缺失)，对皮肤刺激的反应更强，出现发痒。随着年龄的增长，皮肤脂质也会发生改变，导致皮肤干燥。 在英国进行的一项研究中，我们希望了解用含有特定组合的脂质进行治疗，是否能够改善脂质分布，是否能够更好地保护皮肤。这项研究纳入了34位皮肤干燥、易发湿疹的成年受试者，持续4周在一小块皮肤上涂抹脂质乳霜。作为对照，我们还要求受试者在另外一小块皮肤上以相同方式涂抹一种普通润肤霜(保湿，不含皮肤脂质)。 与使用普通润肤霜相比，使用脂质乳霜后脂质分布更为紧密。皮肤屏障也更强。屏障作用最强的受试者，其皮肤中的脂质最紧密。脂质乳霜还缓解了皮肤干燥情况，保护皮肤免于发炎刺痛。 这项研究显示，我们试验的这种脂质乳霜能够帮助有湿疹等皮肤问题的人改善皮肤的健康状况。与常用的润肤霜相比，它能够起到更好的保护作用，减少皮肤刺激和干燥。 Volume186, Issue5May 2022Pages e215-e215 RelatedInformation
The E-Cigarette Flavor Debate — Promoting Adolescent and Adult Welfare
Authors: Abigail S. Friedman, Kenneth E. Warner
Journal: New England Journal of Medicine (2022)

Interview with Dr. Abigail Friedman on policy approaches to combating adolescent vaping and helping adult smokers quit. (10:08)Download Although restricting access to nontobacco flavors of e-cigarettes may reduce vaping among adolescents and mitigate associated risks, it could also impede smoking cessation among adults, thereby increasing smoking-attributable mortality. But policy solutions could exist.
Induction of Synthetic Lethality by Activation of Mitochondrial ClpP and Inhibition of HDAC1/2 in Glioblastoma
Authors: Trang T.T. Nguyen, Enyuan Shang, Salveena Schiffgens, Consuelo Torrini, Chang Shu, Hasan Orhan Akman, Varun V. Prabhu, Joshua E. Allen, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin
Journal: Clinical Cancer Research (2022)

Novel therapeutic targets are critical to unravel for the most common primary brain tumor in adults, glioblastoma (GBM). We have identified a novel synthetic lethal interaction between ClpP activation and HDAC1/2 inhibition that converges on GBM energy metabolism.Transcriptome, metabolite, and U-13C-glucose tracing analyses were utilized in patient-derived xenograft (PDX) models of GBM. Orthotopic GBM models were used for in vivo studies.We showed that activation of the mitochondrial ClpP protease by mutant ClpP (Y118A) or through utilization of second-generation imipridone compounds (ONC206 and ONC212) in combination with genetic interference of HDAC1 and HDAC2 as well as with global (panobinostat) or selective (romidepsin) HDAC inhibitors caused synergistic reduction of viability in GBM model systems, which was mediated by interference with tricarboxylic acid cycle activity and GBM cell respiration. This effect was partially mediated by activation of apoptosis along with activation of caspases regulated chiefly by Bcl-xL and Mcl-1. Knockdown of the ClpP protease or ectopic expression of a ClpP D190A mutant substantially rescued from the inhibition of oxidative energy metabolism as well as from the reduction of cellular viability by ClpP activators and the combination treatment, respectively. Finally, utilizing GBM PDX models, we demonstrated that the combination treatment of HDAC inhibitors and imipridones prolonged host survival more potently than single treatments or vehicle in vivo.Collectively, these observations suggest that the efficacy of HDAC inhibitors might be significantly enhanced through ClpP activators in model systems of human GBM.
Physician-Assisted Death for Patients With Dementia
Authors: Sisco M. P. van Veen, Guy A. M. Widdershoven, Aartjan T. F. Beekman
Journal: JAMA Psychiatry (2022)

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 Psychiatry 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 Psychiatry journal
The microbiome restrains melanoma bone growth by promoting intestinal NK and Th1 cell homing to bone
Authors: Subhashis Pal, Daniel S. Perrien, Tetsuya Yumoto, Roberta Faccio, Andreea Stoica, Jonathan Adams, Craig M. Coopersmith, Rheinallt M. Jones, M. Neale Weitzmann, Roberto Pacifici
Journal: Journal of Clinical Investigation (2022)

Bone metastases are frequent complications of malignant melanoma leading to reduced quality of life and significant morbidity. Regulation of immune cells by the gut microbiome influences cancer progression, but the role of the microbiome in tumor growth in bone is unknown. Using intracardiac or intratibial injections of B16-F10 melanoma cells into mice, we showed that gut microbiome depletion by broad-spectrum antibiotics accelerated intraosseous tumor growth and osteolysis. Microbiome depletion blunted melanoma-induced expansion of intestinal NK cells and Th1 cells and their migration from the gut to tumor-bearing bones. Demonstrating the functional relevance of immune cell trafficking from the gut to the bone marrow (BM) in bone metastasis, blockade of S1P-mediated intestinal egress of NK and Th1 cells, or inhibition of their CXCR3/CXCL9-mediated influx into the BM, prevented the expansion of BM NK and Th1 cells and accelerated tumor growth and osteolysis. Using a mouse model, this study revealed mechanisms of microbiota-mediated gut-bone crosstalk that are relevant to the immunological restraint of melanoma metastasis and tumor growth in bone. Microbiome modifications induced by antibiotics might have negative clinical consequences in patients with melanoma.
What’s in a Number? Breaking Down the Residency Match Rate
Authors: Nicole M. Mott, J. Bryan Carmody, David A. Marzano, Maya M. Hammoud
Journal: New England Journal of Medicine (2022)

Focusing on the high residency match rate for certain applicants may obscure data that could better capture the current state of the residency-selection process, set realistic expectations for applicants, and highlight areas for reform.
Odronextamab, a human CD20×CD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial
Authors: Rajat Bannerji, Jon E Arnason, Ranjana H Advani, Jennifer R Brown, John N Allan, Stephen M Ansell, Jeffrey A Barnes, Susan M O'Brien, Julio C Chávez, Johannes Duell, Andreas Rosenwald, Jennifer L Crombie, Melanie Ufkin, Jingjin Li, Min Zhu, Srikanth R Ambati, Aafia Chaudhry, Israel Lowy, Max S Topp
Journal: The Lancet Haematology (2022)
Photodistributed Toxic Epidermal Necrolysis
Authors: Lindsey J. Gaghan, Margaret M. Coates, Lauren N. Crouse, Jayson Miedema, Julie E. Mervak, Carolyn M. Ziemer
Journal: JAMA Dermatology (2022)

Cases of photodistributed Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been infrequently reported since the first documented case in 1989. This emerging clinical entity and its underlying mechanism have yet to be fully characterized.To report a case of photodistributed SJS/TEN and highlight similarities to other cases reported in the literature.Case report and literature review of published cases of photodistributed SJS/TEN. The case report describes a 29-year-old woman with recent lamotrigine and trimethoprim-sulfamethoxazole exposure who developed TEN in a photodistributed pattern 1 day after prolonged sun exposure. A search of PubMed using the keywords toxic epidermal necrolysis, Stevens-Johnson syndrome, photo-distributed, photo-induced, and sun-exposed was performed to identify other cases reported in the literature.Literature review revealed 8 previously reported cases of healthy individuals with known drug and UV radiation (UVR) exposures who subsequently developed SJS or TEN with photodistribution. Cases reviewed were skewed demographically to young women aged 19 to 48 years (8 of 9 patients) with all cases reporting UVR exposure 24 to 72 hours prior to the onset of symptoms.Photodistributed TEN has been increasingly described in the literature and may represent a distinct variant of SJS/TEN. While the pathogenesis remains unclear, the role of UVR as a "second hit" is suggested by the data presented in the cases documented thus far.
Evaluation of Nomacopan for Treatment of Bullous Pemphigoid
Authors: Christian D. Sadik, Hanan Rashid, Christoph M. Hammers, Gilles F.H. Diercks, Anke Weidinger, Stefan Beissert, Franziska Schauer, James Fettiplace, Diamant Thaçi, Yenting Ngai, Miles A. Nunn, Detlef Zillikens, Barbara Horváth
Journal: JAMA Dermatology (2022)

Bullous pemphigoid is a difficult-to-treat autoimmune blistering skin disease that predominantly affects older adults and is associated with an increased mortality rate.To examine the safety and therapeutic potential of nomacopan, an inhibitor of leukotriene B4 and complement C5, in patients with bullous pemphigoid.This multicenter, single-group, phase 2a nonrandomized controlled trial was conducted in the dermatology departments of universities in the Netherlands and Germany. Participants were enrolled between September 2018 and April 2020. Older adult patients (aged ≥55 years) with mild to moderate, new-onset or relapsing bullous pemphigoid were recruited into the study.Patients received nomacopan, 90 mg, subcutaneously on day 1 and 30 mg subcutaneously daily until day 42.The primary end point was the proportion of patients with grade 3 to 5 (severe) adverse events associated or possibly associated with nomacopan. Secondary end points included mean absolute and percentage changes in the Bullous Pemphigoid Disease Area Index (BPDAI) activity score, the BPDAI pruritus score, and the patient-reported outcome measures Dermatology Life Quality Index (DLQI) and Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL).A total of 9 patients (median [range] age, 75 [55-85] years) with bullous pemphigoid were included in the trial, of whom 5 were women (55.6%). No serious adverse events associated with nomacopan were found. The mean (90% CI) BPDAI activity score decreased from 32.0 (8.7) points on day 1 to 19.6 (9.0) points on day 42. Seven of 9 patients (77.8%) responded to nomacopan with a reduction in the BPDAI activity score of at least 8 points between days 1 and 42; in 3 responders, the reduction was 80% or greater. On day 42, the mean (90% CI) BPDAI pruritus score had decreased by 6.8 (4.6) points from 17.6 (4.0) points on day 1. The mean (90% CI) DLQI score decreased from 11.3 (4.2) points at baseline to 6.4 (3.8) points by day 42, and the mean (90% CI) TABQOL score decreased from 14.6 (5.4) points at baseline to 10.3 (5.0) points on day 42.Results of this nonrandomized controlled trial suggest that nomacopan can be well tolerated in older patients with bullous pemphigoid and may have therapeutic benefits for suppressing acute flares of this disease. A larger, placebo-controlled randomized clinical trial is warranted to confirm this safety profile and to establish nomacopan as a new therapeutic option for bullous pemphigoid.ClinicalTrials.gov Identifier: NCT04035733.
Establishment of the LNCaP Cell Line – The Dawn of an Era for Prostate Cancer Research
Authors: Cory Abate-Shen, Francisca Nunes de Almeida
Journal: Cancer Research (2022)

Abstract Among the relatively few established human prostate cancer cell lines, LNCaP cells are unique in their ability to model key stages of prostate cancer progression. Analyses of LNCaP cells and their derivatives have been invaluable for elucidating important translational aspects of prostate tumorigenesis, metastasis, and drug response, particularly in the context of androgen receptor signaling. Here, we present major highlights from a wealth of literature that has exploited LNCaP cells and their derivatives to inform on prostate cancer progression and androgen response for improving the treatment of patients with prostate cancer. See related article by Horoszewicz and colleagues, Cancer Res 1983;43:1809–18
2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines
Authors: Paul A. Heidenreich, Biykem Bozkurt, David Aguilar, Larry A. Allen, Joni J. Byun, Monica M. Colvin, Anita Deswal, Mark H. Drazner, Shannon M. Dunlay, Linda R. Evers, James C. Fang, Savitri E. Fedson, Gregg C. Fonarow, Salim S. Hayek, Adrian F. Hernandez, Prateeti Khazanie, Michelle M. Kittleson, Christopher S. Lee, Mark S. Link, Carmelo A. Milano, Lorraine C. Nnacheta, Alexander T. Sandhu, Lynne Warner Stevenson, Orly Vardeny, Amanda R. Vest, Clyde W. Yancy
Journal: Circulation (2022)

The "2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure" replaces the "2013 ACCF/AHA Guideline for the Management of Heart Failure" and the "2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure." The 2022 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with heart failure.A comprehensive literature search was conducted from May 2020 to December 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from MEDLINE (PubMed), EMBASE, the Cochrane Collaboration, the Agency for Healthcare Research and Quality, and other relevant databases. Additional relevant clinical trials and research studies, published through September 2021, were also considered. This guideline was harmonized with other American Heart Association/American College of Cardiology guidelines published through December 2021. Structure: Heart failure remains a leading cause of morbidity and mortality globally. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve quality of care and align with patients' interests. Many recommendations from the earlier heart failure guidelines have been updated with new evidence, and new recommendations have been created when supported by published data. Value statements are provided for certain treatments with high-quality published economic analyses.
An <i>in vitro</i> intestinal model captures immunomodulatory properties of the microbiota in inflammation
Authors: Jaclyn Y. Lock, Mariaelena Caboni, Philip Strandwitz, Madeleine Morrissette, Kevin DiBona, Brian A. Joughin, Kim Lewis, Rebecca L. Carrier
Journal: Gut Microbes (2022)

Considerable effort has been put forth to understand mechanisms by which the microbiota modulates and responds to inflammation. Here, we explored whether oxidation metabolites produced by the host during inflammation, sodium nitrate and trimethylamine oxide, impact the composition of a human stool bacterial population in a gut simulator. We then assessed whether an immune-competent in vitro intestinal model responded differently to spent medium from bacteria exposed to these cues compared to spent medium from a control bacterial population. The host-derived oxidation products were found to decrease levels of Bacteroidaceae and overall microbiota metabolic potential, while increasing levels of proinflammatory Enterobacteriaceae and lipopolysaccharide in bacterial cultures, reflecting shifts that occur in vivo in inflammation. Spent microbiota media induced elevated intracellular mucin levels and reduced intestinal monolayer integrity as reflected in transepithelial electrical resistance relative to fresh medium controls. However, multiplexed cytokine analysis revealed markedly different cytokine signatures from intestinal cultures exposed to spent medium with added oxidation products relative to spent control medium, while cytokine signatures of cultures exposed to fresh media were similar regardless of addition of host-derived cues. Further, the presence of immune cells in the intestinal model was required for this differentiation of cytokine signatures. This study indicates that simple in vitro immune-competent intestinal models can capture bacterial-mammalian cross-talk in response to host-derived oxidation products and supports utility of these systems for mechanistic studies of interactions between the gut microbiome and host in inflammation.
Investigating Nontuberculous Mycobacteria Transmission at the Colorado Adult Cystic Fibrosis Program
Authors: Jane E. Gross, Silvia Caceres, Katie Poch, Nabeeh A. Hasan, Fan Jia, L. Elaine Epperson, Ettie Lipner, Charmie Vang, Jennifer R. Honda, Matthew Strand, Vinicius Calado Nogueira de Moura, Charles L. Daley, Michael Strong, Rebecca M. Davidson, Jerry A. Nick
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Healthcare-associated transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been investigated at CF centers worldwide, with conflicting conclusions. We investigated transmission at the Colorado Adult CF Program. Objectives: To systematically investigate healthcare-associated transmission and/or acquisition of NTM to determine similarity among respiratory and environmental isolates, and to compare home residence watershed mapping among pwCF having genetically similar NTM isolates. Methods: Whole-genome sequencing of NTM isolates from 80 pwCF was conducted to identify genetically similar isolate clusters (⩽30 SNP differences). Epidemiology, comparison of respiratory and environmental isolates, and home residence watershed mapping were analyzed. Measurements and Main Results: Whole-genome sequencing analysis revealed 11 clusters of NTM [6 Mycobacterium abscessus subspecies (ssp.) abscessus, 1 M. abscessus ssp. massiliense, 2 Mycobacterium avium, and 2 Mycobacterium intracellulare] among pwCF. Epidemiologic investigation demonstrated opportunities for healthcare-associated transmission in two M. abscessus and two M. avium clusters. Respiratory and healthcare environmental isolate comparisons revealed no genetic similarity. Individuals comprising one M. abscessus cluster, with no plausible healthcare-associated transmission, resided in the same watershed. Conclusions: This study suggests healthcare-associated transmission of M. abscessus is rare and includes a report of potential healthcare-associated transmission of M. avium among pwCF. One M. abscessus cluster possibly had common acquisition arising from residing in the same watershed. The presence of genetically similar isolates is insufficient to demonstrate healthcare-associated NTM transmission. Standardizing epidemiologic investigation, combined with environmental sampling and watershed analysis, will improve understanding of the frequency and nature of healthcare-associated NTM transmission among pwCF.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2022)

Targeting Androgen Receptor in T CellsPatients with prostate cancer respond poorly to checkpoint blockade immunotherapy (CBI).Guan and colleagues found that this resulted from androgen receptor (AR) activity impacting T-cell responses.Single-cell RNA sequencing was done on patients with metastatic castration-resistant prostate cancer that progressed on enzalutamide (AR antagonist) and subsequently received anti-PD1 CBI.Comparing differences in CD8 þ T-cell gene expression in CBI responders versus nonresponders identified AR as a key transcription factor active in nonresponders.Using mouse models of prostate cancer, the authors showed that anti-PDL1 CBI was effective only when combined with androgen deprivation and AR antagonists.The therapy was independent of AR activity in tumors but required CD8 þ T cells that exhibited enhanced activity with AR inhibition or genetic AR deficiency.Mechanistically, AR was found to bind regulatory elements in T-cell effector genes (e.g., IFNG and GZMB), reducing their expression.Expert Commentary: Androgen deprivation and androgen receptor antagonism acts directly within T cells to enhance their responsiveness to checkpoint blockade immunotherapy.