tbuckley/cabot-search huggingface dataset:
Skeletal Muscle Capillaries in Nondiabetics
Authors: RUDOLF VRACKO
Journal: Circulation (1970)

To evaluate the variations of capillary calibers and those of basal lamina (BL), pericytes, endothelium, and lumen within a sample of skeletal muscle and among samples from different anatomic sites, areas occupied by total capillary cross sections, by the lumen, endothelium, pericytes, and BL were measured on electron micrographs. Twenty capillary cross sections from each of the 41 specimens of skeletal muscle from 23 nondiabetic males were used. For all parameters, a marked variation was noted within each specimen, between specimens from identical sites of different individuals, and between different anatomic sites of the same individuals. In general, the capillaries are largest in the lower leg and foot muscles; the lumen is smallest at the levels of mid-thigh and lower leg; the capillaries of the lower extremity have a greater investment of BL, endothelium, and pericytes than the capillaries of the trunk and hand muscles. The areas occupied by endothelial cytoplasm, pericyte cytoplasm, and by BL are larger in bigger capillaries apparently owing to greater circumference. In addition, the capillaries of the leg, particularly those of the lower leg, have an absolutely greater investment of BL than capillaries from proximal sites. Reasons for these regional differences in the overall size of capillaries and in the investment of BL are not known.
Abstract 13750: Acetaldehyde-Induced Relaxation of Superior Mesenteric Artery: Potential Role in Postprandial Hyperemia
Authors: Lexiao Jin, Pawel Lorkiewicz, Marina Malovichko, Aruni Bhatnagar, sanjay srivastava, Daniel J Conklin
Journal: Circulation (2019)

Introduction: Acetaldehyde (AA) is the second smallest aldehyde, is generated endogenously, and is ubiquitous in foods, beverages, as a gas phase combustion product, and as product of ethanol (EtOH...
Chronic air pollution and health burden in Dhaka city
Authors: Shafayet Ahmed Siddiqui, Md Jakaria, Mohammad Nurul Amin, Abdullah Al Mahmud, David Gozal
Journal: European Respiratory Journal (2020)

<b>Air pollution levels in developing countries such as Bangladesh with a relatively young population pose an inordinate health risk for many years to come unless significant environmental control measures are effectively undertaken</b>https://bit.ly/3bvzesx
Covid-19: Africa records over 10 000 cases as lockdowns take hold
Authors: Owen Dyer
Journal: BMJ (2020)

Covid-19: Africa records over 10 000 cases as lockdowns take hold Owen Dyer Montreal Africa, so far the continent least affected by covid-19, registered 10 268 confirmed cases and 491 deaths on 7 April, passing a worrying landmark for public health experts who are still hopeful that mass spread can be averted.
Opioid agonist treatment and risk of mortality during opioid overdose public health emergency: population based retrospective cohort study
Authors: Lindsay A Pearce, Jeong Eun Min, Micah Piske, Haoxuan Zhou, Fahmida Homayra, Amanda Slaunwhite, Mike Irvine, Gina McGowan, Bohdan Nosyk
Journal: BMJ (2020)

Abstract Objective To compare the risk of mortality among people with opioid use disorder on and off opioid agonist treatment (OAT) in a setting with a high prevalence of illicitly manufactured fentanyl and other potent synthetic opioids in the illicit drug supply. Design Population based retrospective cohort study. Setting Individual level linkage of five health administrative datasets capturing drug dispensations, hospital admissions, physician billing records, ambulatory care reports, and deaths in British Columbia, Canada. Participants 55 347 people with opioid use disorder who received OAT between 1 January 1996 and 30 September 2018. Main outcome measures All cause and cause specific crude mortality rates (per 1000 person years) to determine absolute risk of mortality and all cause age and sex standardised mortality ratios to determine relative risk of mortality compared with the general population. Mortality risk was calculated according to treatment status (on OAT, off OAT), time since starting and stopping treatment (1, 2, 3-4, 5-12, &gt;12 weeks), and medication type (methadone, buprenorphine/naloxone). Adjusted risk ratios compared the relative risk of mortality on and off OAT over time as fentanyl became more prevalent in the illicit drug supply. Results 7030 (12.7%) of 55 347 OAT recipients died during follow-up. The all cause standardised mortality ratio was substantially lower on OAT (4.6, 95% confidence interval 4.4 to 4.8) than off OAT (9.7, 9.5 to 10.0). In a period of increasing prevalence of fentanyl, the relative risk of mortality off OAT was 2.1 (95% confidence interval 1.8 to 2.4) times higher than on OAT before the introduction of fentanyl, increasing to 3.4 (2.8 to 4.3) at the end of the study period (65% increase in relative risk). Conclusions Retention on OAT is associated with substantial reductions in the risk of mortality for people with opioid use disorder. The protective effect of OAT on mortality increased as fentanyl and other synthetic opioids became common in the illicit drug supply, whereas the risk of mortality remained high off OAT. As fentanyl becomes more widespread globally, these findings highlight the importance of interventions that improve retention on opioid agonist treatment and prevent recipients from stopping treatment.
Barrier Enclosure during Endotracheal Intubation
Authors: Robert Canelli, Christopher W Connor, Mauricio Gonzalez, Ala Nozari, Rafael Ortega
Journal: New England Journal of Medicine (2020)

Protective Shield for Intubation A four-sided plexiglass box with access holes for an operator was used to provide additional protection for an operator performing intubation. The box reduced the a...
Covid-19: government promises 100 000 tests per day in England by end of April
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The government has pledged to carry out 100 000 tests for covid-19 per day in England by the end of April, ramping up its current capacity.

The promise by the health secretary Matt Hancock follows mounting backlash against the government over its failure to boost testing capacity—a matter which has dominated the national news agenda in the UK over the past few days.

In particular, the government’s failure to fulfil promises to roll out testing for NHS staff has left medical leaders frustrated,1 with large numbers of doctors having to self-isolate because they are unsure if they have the virus.

Currently, there are only around 10 000 tests being carried out a day in England, which lags way behind many other developed countries. The government had previously set a target to test 25 000 per day by …
Community Transmission of SARS-CoV-2 at Two Family Gatherings — Chicago, Illinois, February–March 2020
Authors: Isaac Ghinai, Susan Woods, Kathleen A. Ritger, Tristan D. McPherson, Stephanie R. Black, Laura Sparrow, Marielle J. Fricchione, Janna L. Kerins, Massimo Pacilli, Peter S. Ruestow, M. Allison Arwady, Suzanne F. Beavers, Daniel C. Payne, Hannah L. Kirking, Jennifer E. Layden
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Evaluating and testing persons for
Catecholamines Induce Trained Immunity in Monocytes In Vitro and In Vivo
Authors: Charlotte D.C.C. van der Heijden, Laszlo Groh, Samuel T. Keating, Charlotte Kaffa, Marlies P. Noz, Simone Kersten, Antonius E. van Herwaarden, Alexander Hoischen, Leo A.B. Joosten, Henri J.L.M. Timmers, Mihai G. Netea, Niels P. Riksen
Journal: Circulation Research (2020)

Rationale: Exposure to high catecholamine levels is associated with inflammatory changes of myeloid cells and atherosclerosis, but the underlying mechanisms are only partly understood. Objective: To investigate whether the proinflammatory effects of noradrenaline and adrenaline can, in part, be explained by the induction of an immunologic memory in innate immune cells, termed trained immunity. Methods and Results: In vitro, we exposed human primary monocytes to (nor)adrenaline for 24 hours, after which cells were rested and differentiated to macrophages over 5 days. After restimulation with lipopolysaccharide on day 6, (nor)adrenaline-exposed cells showed increased TNF-α (tumor necrosis factor-α) production. This coincided with an increase in glycolysis and oxidative phosphorylation measured with Seahorse technology on day 6 before restimulation. Inhibition of the β-adrenoreceptor–cAMP signaling pathway prevented the induction of training. In vivo, we studied the functional, transcriptional, and epigenetic impact of peak-wise exposure to high catecholamine levels on monocytes isolated from pheochromocytoma/paraganglioma (PHEO) patients. In PHEO patients (n=10), the peripheral blood cell composition showed a myeloid bias and an increase of the inflammatory CD14++CD16+ (cluster of differentiation) intermediate monocyte subset compared with controls with essential hypertension (n=14). Ex vivo production of proinflammatory cytokines was higher in PHEO patients. These inflammatory changes persisted for 4 weeks after surgical removal of PHEO. Transcriptome analysis of circulating monocytes at baseline showed various differentially expressed genes in inflammatory pathways in PHEO patients; epigenetic profiling of the promoters of these genes suggests enrichment of the transcriptionally permissive chromatin mark H3K4me3 (trimethylation of lysine 4 on histone H3), indicative of in vivo training. Conclusions: Catecholamines induce long-lasting proinflammatory changes in monocytes in vitro and in vivo, indicating trained immunity. Our data contribute to the understanding of pathways driving inflammatory changes in conditions characterized by high catecholamine levels and propose that trained immunity underlies the increased cardiovascular event rate in PHEO patients.
Helicobacter pylori: preying on SIVA for survival in the stomach
Authors: José B. Sáenz, Jason C. Mills
Journal: Journal of Clinical Investigation (2020)

Infection with the Gram-negative bacterium Helicobacter pylori remains the most important modifiable risk factor for the development of gastric cancer, a leading cause of cancer-related deaths worldwide. How the interactions between H. pylori and its host shape the gastric environment during chronic infection warrants further investigation. In this issue of the JCI, Palrasu et al. used human cell lines and mouse models to provide mechanistic insight into H. pylori’s ability to delay apoptosis in gastric epithelial cells by actively driving the degradation of a proapoptotic factor, SIVA1. Their findings suggest that promoting the survival of gastric epithelial cells has implications not only for H. pylori pathogenesis but for host tumorigenesis.
Risk of heart failure in type 2 diabetes complicated by incident ischaemic heart disease and end‐stage renal disease
Authors: Mariam E. Malik, Christian Madelaire, Maria D'Souza, Paul Blanche, Søren L. Kristensen, Caroline Kistorp, Finn Gustafsson, Lars Køber, Rasmus Rørth, John McMurray, Naveed Sattar, Gunnar Gislason, Christian Torp‐Pedersen, Morten Schou
Journal: European Journal of Heart Failure (2020)
Integrated mRNA and microRNA transcriptome profiling during differentiation of human nasal polyp epithelium reveals an altered ciliogenesis
Authors: Borja Callejas‐Díaz, Guerau Fernandez, Mireya Fuentes, Asunción Martínez‐Antón, Isam Alobid, Jordi Roca‐Ferrer, César Picado, Valeria Tubita, Joaquim Mullol
Journal: Allergy (2020)

Human adult basal stem/progenitor cells (BSCs) obtained from chronic rhinosinusitis with nasal polyps (CRSwNP) when differentiated in an air-liquid interface (ALI) usually provide a pseudostratified airway epithelium with similar abnormalities than original in vivo phenotype. However, the intrinsic mechanisms regulating this complex process are not well defined and their understanding could offer potential new therapies for CRSwNP (incurable disease).We performed a transcriptome-wide analysis during in vitro mucociliary differentiation of human adult BSCs from CRSwNP, compared to those isolated from control nasal mucosa (control-NM), in order to identify which key mRNA and microRNAs are regulating this complex process in pathological and healthy conditions.A number of genes, miRs, biological processes, and pathways were identified during mucociliary differentiation of both CRSwNP and control-NM epithelia, and notably, we have demonstrated for the first time that genetic transcriptional program responsible of ciliogenesis and cilia function is significantly impaired in CRSwNP epithelium, presumably produced by an altered expression of microRNAs, particularly of those miRs belonging to mir-34 and mi-449 families.This study provides for the first time a novel insight into the molecular basis of sinonasal mucociliary differentiation, demonstrating that transcriptome related to ciliogenesis and cilia function is significantly impaired during differentiation of CRSwNP epithelium due to an altered expression of microRNAs.
Association of Long Noncoding RNA Biomarkers With Clinical Immune Subtype and Prediction of Immunotherapy Response in Patients With Cancer
Authors: Yunfang Yu, Wenda Zhang, Anlin Li, Yongjian Chen, Qiyun Ou, Zifan He, Yiwen Zhang, Ruixin Liu, Herui Yao, Erwei Song
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Long noncoding RNAs (lncRNAs) are involved in innate and adaptive immunity in cancer by mediating the functional state of immunologic cells, pathways, and genes. However, whether lncRNAs are associated with immune molecular classification and clinical outcomes of cancer immunotherapy is largely unknown. <h3>Objectives</h3> To explore lncRNA-based immune subtypes associated with survival and response to cancer immunotherapy and to present a novel lncRNA score for immunotherapy prediction using computational algorithms. <h3>Design, Setting, and Participants</h3> In this cohort study, an individual patient analysis based on a phase 2, single-arm clinical trial and multicohort was performed from June 25 through September 30, 2019. Data are from the phase 2 IMvigor210 trial and from The Cancer Genome Atlas (TCGA). The study analyzed lncRNA and genomic data of 348 patients with bladder cancer from the IMvigor210 trial and 71 patients with melanoma from TCGA who were treated with immunotherapy. In addition, a pancancer multicohort that included 2951 patients was obtained from TCGA. <h3>Main Outcomes and Measures</h3> The primary end point was overall survival (OS). <h3>Results</h3> Among 348 patients from the IMvigor210 trial (272 [78.2%] male) and 71 patients with melanoma from TCGA (mean [SD] age, 58.3 [13.4] years; 37 [52.1%] female), 4 distinct classes with statistically significant differences in OS (median months, not reached vs 9.6 vs 8.1 vs 6.7 months;<i>P</i> = .002) were identified. The greatest OS benefit was obtained in the immune-active class, as characterized by the immune-functional lncRNA signature and high CTL infiltration. Patients with low vs high lncRNA scores had statistically significantly longer OS (hazard ratio, 0.32; 95% CI, 0.24-0.42;<i>P</i> &lt; .001) in the IMvigor210 trial and across various cancer types. The lncRNA score was associated with immunotherapeutic OS benefit in the IMvigor210 trial cohort (area under the curve [AUC], 0.79 at 12 months and 0.77 at 20 months) and in TCGA melanoma cohort (AUC, 0.87 at 24 months), superior tumor alteration burden, programmed cell death ligand 1 (PD-L1) expression, and cytotoxic T-lymphocyte (CTL) infiltration. Addition of the lncRNA score to the combination of tumor alteration burden, PD-L1 expression, and CTL infiltration to build a novel multiomics algorithm correlated more strongly with OS in the IMvigor210 trial cohort (AUC, 0.81 at 12 months and 0.80 at 20 months). <h3>Conclusions and Relevance</h3> This study identifies novel lncRNA-based immune classes in cancer immunotherapy and recommends immunotherapy for patients in the immune-active class. In addition, the study recommends that the lncRNA score should be integrated into multiomic panels for precision immunotherapy.
Evaluation of cell surface reactive immuno-adjuvant in combination with immunogenic cell death inducing drug for in situ chemo-immunotherapy
Authors: Adam A. Walters, Julie Tzu-Wen Wang, Khuloud T. Al-Jamal
Journal: Journal of Controlled Release (2020)

Apoptotic cells and cell fragments, especially those produced as a result of immunogenic cell death (ICD), are known to be a potential source of cancer vaccine immunogen. However, due to variation between tumours and between individuals, methods to generate such preparations may require extensive ex vivo personalisation. To address this, we have utilised the concept of in situ vaccination whereby an ICD inducing drug is injected locally to generate immunogenic apoptotic fragments/cells. These fragments are then adjuvanted by a co-administered cell reactive CpG adjuvant. We first evaluate means of labelling tumour cells with CpG adjuvant, we then go on to demonstrate in vitro that labelling is preserved following apoptosis and, furthermore, that the apoptotic body-adjuvant complexes are readily transferred to macrophages. In in vivo studies we observe synergistic tumour growth delays and elevated levels of CD4+ and CD8+ cells in tumours receiving adjuvant drug combination. CD4+/CD8+ cells are likewise elevated in the tumour draining lymph node and activated to a greater extent than individual treatments. This study represents the first steps toward the evaluation of rationally formulated drug-adjuvant combinations for in situ chemo-immunotherapy.
PRDM16 suppresses HIF-targeted gene expression in kidney cancer
Authors: Anirban Kundu, Hyeyoung Nam, Sandeep Shelar, Darshan S. Chandrashekar, Garrett Brinkley, Suman Karki, Tanecia Mitchell, Carolina B. Livi, Phillip Buckhaults, Richard Kirkman, Yawen Tang, Glenn C. Rowe, Shi Wei, Sooryanarayana Varambally, Sunil Sudarshan
Journal: The Journal of Experimental Medicine (2020)

Analysis of transcriptomic data demonstrates extensive epigenetic gene silencing of the transcription factor PRDM16 in renal cancer. We show that restoration of PRDM16 in RCC cells suppresses in vivo tumor growth. RNaseq analysis reveals that PRDM16 imparts a predominantly repressive effect on the RCC transcriptome including suppression of the gene encoding semaphorin 5B (SEMA5B). SEMA5B is a HIF target gene highly expressed in RCC that promotes in vivo tumor growth. Functional studies demonstrate that PRDM16's repressive properties, mediated by physical interaction with the transcriptional corepressors C-terminal binding proteins (CtBP1/2), are required for suppression of both SEMA5B expression and in vivo tumor growth. Finally, we show that reconstitution of RCC cells with a PRDM16 mutant unable to bind CtBPs nullifies PRDM16's effects on both SEMA5B repression and tumor growth suppression. Collectively, our data uncover a novel epigenetic basis by which HIF target gene expression is amplified in kidney cancer and a new mechanism by which PRDM16 exerts its tumor suppressive effects.
Abstract 15285: Adolescents and Adults With a Fontan Circulation Have Worse Cognitive Outcomes Than Individuals With Repaired Transposition of the Great Arteries and Healthy Matched Controls
Authors: Charlotte E Verrall, Diana Zannino, Yufei Jiang, Karin Du Plessis, David Celermajer, Yves d’Udekem, David S Winlaw, Rachael L Cordina
Journal: Circulation (2019)

Introduction: Neurocognitive impairment is common in children with congenital heart disease (CHD), however outcomes in adolescents and young adults (AYAs) are underreported. This study investigates...
<i>Retracted:</i> Increasing Prevalence of Antinuclear Antibodies in the <scp>United States</scp>
Authors: Gregg E Dinse, Christine G Parks, Clarice R Weinberg, Caroll A Co, Jesse Wilkerson, Darryl C Zeldin, Edward K L Chan, Frederick W Miller
Journal: Arthritis & Rheumatology (2020)

Growing evidence suggests increasing frequencies of autoimmunity and certain autoimmune diseases, but findings are limited by the lack of systematic data and evolving approaches and definitions. This study was undertaken to investigate whether the prevalence of antinuclear antibodies (ANA), the most common biomarker of autoimmunity, changed over a recent 25-year span in the US.Serum ANA were measured by standard indirect immunofluorescence assays on HEp-2 cells in 14,211 participants age ≥12 years from the National Health and Nutrition Examination Survey, with approximately one-third from each of 3 time periods: 1988-1991, 1999-2004, and 2011-2012. We used logistic regression adjusted for sex, age, race/ethnicity, and survey design variables to estimate changes in ANA prevalence across the time periods.The prevalence of ANA was 11.0% (95% confidence interval [95% CI] 9.7-12.6%) in 1988-1991, 11.5% (95% CI 10.3-12.8%) in 1999-2004, and 15.9% (95% CI 14.3-17.6%) in 2011-2012 (P for trend < 0.0001), which corresponds to ~22 million, ~27 million, and ~41 million affected individuals, respectively. Among adolescents age 12-19 years, ANA prevalence increased substantially, with odds ratios (ORs) of 2.02 (95% CI 1.16-3.53) and 2.88 (95% CI 1.64-5.04) in the second and third time periods relative to the first (P for trend < 0.0001). ANA prevalence increased in both sexes (especially in men), older adults (age ≥50 years), and non-Hispanic whites. These increases in ANA prevalence were not explained by concurrent trends in weight (obesity/overweight), smoking exposure, or alcohol consumption.The prevalence of ANA in the US has increased considerably in recent years. Additional studies to determine factors underlying these increases in ANA prevalence could elucidate causes of autoimmunity and enable the development of preventative measures.
A review of physician preparedness in response to a systemic crisis: The case of Eastern Regional Health Authority, Newfoundland, Canada, estrogen receptor (ER) breast cancer (BC) errors
Authors: C. Popadiuk
Journal: Journal of Clinical Oncology (2009)

e17551 Background: From March until October 2008, a Commission of Inquiry was held in St. John's, Canada, investigating systemic errors leading to incorrect ER results in BC patients. 386 ER negative BC samples tested between 1997 and 2005 were incorrect. Of 91 witnesses, 26 physicians testified about their roles in this “crisis.” Physicians have traditionally been trained to respond to individual clinical crises and acute traumatic situations. This study summarizes the physicians’ training and preparedness in response to a systemic organizational crisis. Methods: Inquiry exhibits, submissions, and transcripts of physician testimony were reviewed for evidence of education and experience in crisis management (CM) as applied to a complex organization. Education and experience with organizational health care crisis were tabulated and prevalent themes relevant for physicians summarized. Results: Evidence was reviewed from 5 oncologists, 17 pathologists, 1 health information analyst, and 3 senior physician leaders. 20 physicians held departmental or divisional leadership roles, one had an advanced degree in Public Health and one had direct experience in a complex private organization. 5 out of province expert consultants had direct experience with continuous quality control applied to large organizations. No physicians were formally trained in CM in terms of acute crisis response. Two prevailing concerns were expressed: 1) delayed and incomplete disclosure of information to patients and public, and 2) numerous preceding systems problems identified by physicians that did not translate into necessary systemic changes to prevent the crisis. Conclusions: The practice of CM recognizes the need to eliminate technological and human systems failure and to develop formal communication systems to avoid or to manage crisis situations. Large-scale organizational crisis management is an important concept for physicians to understand and actively participate in their professional roles. At present most physicians do not receive formal training in CM. No significant financial relationships to disclose.