tbuckley/cabot-search huggingface dataset:
Titrating Oxygen Therapy in Critically Ill Patients
Authors: Martin Urner, Carolyn S. Calfee, Eddy Fan
Journal: JAMA (2021)

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IL-17 priming increases the engraftment potential of highly purified cd34+ hematopoietic stem cells on individual mesenchymal / stromal progenitor derived stromal cell colonies
Authors: Vincent F. La Russa, Paul Schwartzenberger, Alan Miller, Jay Kohls, Charles Scher, Raj P. Warrier, Weimer Roy Weimer, Azzarn Alzobie
Journal: Blood (2000)
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, Nick Talley, Sue Turale, Damián Vázquez
Journal: Cardiovascular Research (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 …
Activation of Hippo signaling pathway mediates mitochondria dysfunction and dilated cardiomyopathy in mice
Authors: Wei Wu, Mark Ziemann, Kevin Huynh, Gang She, Zheng-Da Pang, Yi Zhang, Thy Duong, Helen Kiriazis, Tian-Tian Pu, Ru-Yue Bai, Jing-Jing Li, Yu Zhang, Ming-Xia Chen, Junichi Sadoshima, Xiu-Ling Deng, Peter J. Meikle, Xiao-Jun Du
Journal: Theranostics (2021)

Rationale: Mitochondrial dysfunction facilitates heart failure development forming a therapeutic target, but the mechanism involved remains unclear. We studied whether the Hippo signaling pathway mediates mitochondrial abnormalities that results in onset of dilated cardiomyopathy (DCM). Methods: Mice with DCM due to overexpression of Hippo pathway kinase Mst1 were studied. DCM phenotype was evident in adult animals but contractile dysfunction was identified as an early sign of DCM at 3 weeks postnatal. Electron microscopy, multi-omics and biochemical assays were employed. Results: In 3-week and adult DCM mouse hearts, cardiomyocyte mitochondria exhibited overt structural abnormalities, smaller size and greater number. RNA sequencing revealed comprehensive suppression of nuclear-DNA (nDNA) encoded gene-sets involved in mitochondria turnover and all aspects of metabolism. Changes in cardiotranscriptome were confirmed by lower protein levels of multiple mitochondrial proteins in DCM heart of both ages. Mitochondrial DNA-encoded genes were also downregulated; due apparently to repression of nDNA-encoded transcriptional factors. Lipidomics identified remodeling in cardiolipin acyl-chains, increased acylcarnitine content but lower coenzyme Q10 level. Mitochondrial dysfunction was featured by lower ATP content and elevated levels of lactate, branched-chain amino acids and reactive oxidative species. Mechanistically, inhibitory YAP-phosphorylation was enhanced, which was associated with attenuated binding of transcription factor TEAD1. Numerous suppressed mitochondrial genes were identified as YAP-targets. Conclusion: Hippo signaling activation mediates mitochondrial damage by repressing mitochondrial genes, which causally promotes the development of DCM. The Hippo pathway therefore represents a therapeutic target against mitochondrial dysfunction in cardiomyopathy.
Analytic Pearson residuals for normalization of single-cell RNA-seq UMI data
Authors: Jan Lause, Philipp Berens, Dmitry Kobak
Journal: Genome biology (2021)

Standard preprocessing of single-cell RNA-seq UMI data includes normalization by sequencing depth to remove this technical variability, and nonlinear transformation to stabilize the variance across genes with different expression levels. Instead, two recent papers propose to use statistical count models for these tasks: Hafemeister and Satija (Genome Biol 20:296, 2019) recommend using Pearson residuals from negative binomial regression, while Townes et al. (Genome Biol 20:295, 2019) recommend fitting a generalized PCA model. Here, we investigate the connection between these approaches theoretically and empirically, and compare their effects on downstream processing.We show that the model of Hafemeister and Satija produces noisy parameter estimates because it is overspecified, which is why the original paper employs post hoc smoothing. When specified more parsimoniously, it has a simple analytic solution equivalent to the rank-one Poisson GLM-PCA of Townes et al. Further, our analysis indicates that per-gene overdispersion estimates in Hafemeister and Satija are biased, and that the data are in fact consistent with the overdispersion parameter being independent of gene expression. We then use negative control data without biological variability to estimate the technical overdispersion of UMI counts, and find that across several different experimental protocols, the data are close to Poisson and suggest very moderate overdispersion. Finally, we perform a benchmark to compare the performance of Pearson residuals, variance-stabilizing transformations, and GLM-PCA on scRNA-seq datasets with known ground truth.We demonstrate that analytic Pearson residuals strongly outperform other methods for identifying biologically variable genes, and capture more of the biologically meaningful variation when used for dimensionality reduction.
Oral microbiome shifts during pregnancy and adverse pregnancy outcomes: Hormonal and Immunologic changes at play
Authors: Changchang Ye, Yvonne Kapila
Journal: Periodontology 2000 (2021)

Abstract Because of hormonal and immunologic changes, there are significant changes in the oral microbiome that emerge during pregnancy. Recent evidence further suggests that there is an association between the presence of periodontal disease and a pregnancy‐associated oral dysbiosis. Although this oral dysbiosis and pathogenic periodontal bacteria are considered to be associated with adverse pregnancy outcomes, it is still not clear how an oral dysbiosis during pregnancy can modulate oral diseases and birth outcomes. To develop preventive or therapeutic interventions, it is critical to understand the oral microbiome changes that emerge during pregnancy and their association with adverse pregnancy outcomes. In the present review, we summarize the current literature on normal changes in the oral microbiome that occur during pregnancy; the pathogenic changes in the oral microbiome believed to occur in association with adverse pregnancy outcomes; and the association between the placental microbiome and the oral microbiome.
Results of the CAPSID randomized trial for high-dose convalescent plasma in patients with severe COVID-19
Authors: Sixten Körper, Manfred Weiss, Daniel Zickler, Thomas Wiesmann, Kai Zacharowski, Victor M. Corman, Beate Grüner, Lucas Ernst, Peter Spieth, Philipp M. Lepper, Martin Bentz, Sebastian Zinn, Gregor Paul, Johannes Kalbhenn, Matthias M. Dollinger, Peter Rosenberger, Thomas Kirschning, Thomas Thiele, Thomas Appl, Benjamin Mayer, Michael Schmidt, Christian Drosten, Hinnerk Wulf, Jan Matthias Kruse, Bettina Jungwirth, Erhard Seifried, Hubert Schrezenmeier
Journal: Journal of Clinical Investigation (2021)

BACKGROUNDCOVID-19 convalescent plasma (CCP) has been considered a treatment option for COVID-19. This trial assessed the efficacy of a neutralizing antibody containing high-dose CCP in hospitalized adults with COVID-19 requiring respiratory support or intensive care treatment.METHODSPatients (n = 105) were randomized 1:1 to either receive standard treatment and 3 units of CCP or standard treatment alone. Control group patients with progress on day 14 could cross over to the CCP group. The primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria for severe COVID-19 on day 21.ResultsThe primary outcome occurred in 43.4% of patients in the CCP group and 32.7% in the control group (P = 0.32). The median time to clinical improvement was 26 days in the CCP group and 66 days in the control group (P = 0.27). The median time to discharge from the hospital was 31 days in the CCP group and 51 days in the control group (P = 0.24). In the subgroup that received a higher cumulative amount of neutralizing antibodies, the primary outcome occurred in 56.0% of the patients (vs. 32.1%), with significantly shorter intervals to clinical improvement (20 vs. 66 days, P < 0.05) and to hospital discharge (21 vs. 51 days, P = 0.03) and better survival (day-60 probability of survival 91.6% vs. 68.1%, P = 0.02) in comparison with the control group.ConclusionCCP added to standard treatment was not associated with a significant improvement in the primary and secondary outcomes. A predefined subgroup analysis showed a significant benefit of CCP among patients who received a larger amount of neutralizing antibodies.Trial registrationClinicalTrials.gov NCT04433910.FundingBundesministerium für Gesundheit (German Federal Ministry of Health): ZMVI1-2520COR802.
Primary Cutaneous Natural Killer/T-Cell Lymphoma
Authors: Xia Lu, Ying Kan, Wei Wang, Jigang Yang
Journal: Clinical Nuclear Medicine (2021)

A 24-year-old man with a history of hemophagocytic lymphohistiocytosis (HLH) presented with swelling of the left foot and skin ulcer. The patient received bone marrow transplantation for HLH 3 years ago for his HLH. Biopsy of left foot skin demonstrated primary cutaneous natural killer/T-cell lymphoma: a posttransplant lymphoproliferative disorder. FDG PET/CT images demonstrated multiple foci of abnormal accumulation in the body, especially in the skin. Follow-up PET/CT after chemotherapy demonstrated that most abnormal activities disappeared except for the lesion in the left foot.
Projected Association of Human Papillomavirus Vaccination With Oropharynx Cancer Incidence in the US, 2020-2045
Authors: Yuehan Zhang, Carole Fakhry, Gypsyamber D’Souza
Journal: JAMA Oncology (2021)

Oropharynx cancer (OPC) incidence has increased for several decades in the US. It is unclear when and how this trend will be affected by current HPV vaccination trends.To assess the association of HPV vaccination with future OPC incidence in the US.This population-based age-period-cohort analysis obtained OPC incidence data from the Surveillance, Epidemiology, and End Results program from 69 562 patients 34 to 83 years of age diagnosed with OPC. The HPV vaccination data were obtained from the National Immunization Survey-Teen (60 124 participants) and National Health Interview Survey (16 904 participants). Data were collected from January 1, 1992, to December 31, 2017. Age-period-cohort forecasting models projected expected 2018 to 2045 OPC incidence under a counterfactual scenario of no HPV vaccination and current levels of HPV vaccination, stratifying by sex. Data analyses were completed by December 2020.Age- and sex-specific cumulative prevalence of HPV vaccination in 2016 to 2017 projected forward.Projected OPC incidence and number of OPC cases expected to be prevented by HPV vaccination.Under current HPV vaccination rates, between 2018 and 2045, OPC incidence is projected to decrease in younger individuals (36-45 years of age: from 1.4 to 0.8 per 100 000 population; 46-55 years of age: from 8.7 to 7.2 per 100 000 population) but continue to increase among older individuals (70-83 years of age: from 16.8 to 29.0 per 100 000 population). The association of HPV vaccination with overall OPC incidence through 2045 will remain modest (no vaccination vs vaccination: 14.3 vs 13.8 per 100 000 population in 2045). By 2045 HPV vaccination is projected to reduce OPC incidence among individuals 36 to 45 years of age (men: 48.1%; women: 42.5%) and 46 to 55 years of age (men: 9.0%; women: 22.6%), but among those 56 years or older, rates are not meaningfully reduced. Between 2018 and 2045, a total of 6334 OPC cases will be prevented by HPV vaccination, of which 88.8% of such cases occur in younger age (≤55 years) groups.According to the projections of this population-based age-period-cohort study, current HPV vaccination rates will have a limited association with overall OPC incidence through 2045 because older individuals who have not yet been vaccinated remain at high risk for OPC. However, reductions in OPC incidence should occur among young and middle-aged adults, the group at lowest risk of diagnosis. These findings forecast a continued shift in the landscape of OPC to an older population.
POS0885 HIGH INCIDENCE AND MORTALITY OF PNEUMOCYSTIS JIROVECI INFECTION IN ANTI-MDA5-ANTIBODY POSITIVE DERMATOMYOSITIS: EXPERIENCE FROM A SINGLE CENTER
Authors: Q. Yan, S. Chen, L. Huang, Q. Fu, Y. Ye
Journal: Annals of the Rheumatic Diseases (2021)

Background: Idiopathic inflammatory myopathies (IIM) was associated with a significantly higher risk of opportunistic infections that including Pneumocystis jiroveci pneumonia(PJP) which is potentially fatal opportunistic infection. However, no prior studies have evaluated the PJP infection in subtypes of IIM. Objectives: To investigate the incidence rate and mortality rate of PJP infection in subgroups of IIM patients according to myopathy specific antibodies. Methods: In the first part, we reviewed 463 consecutive patients with IIM retrospectively to analyze incidence of PJP infection. In the next part, we enrolled 30 consecutive PJP infection patients with any rheumatic disease was to identify the mortality rate and risk factors. Kaplan-Meier curve with log rank test was used to access differences in survival. Univariate and multivariate analyses were performed to identify prognostic factors using Cox regression. Results: We found that 12(7.5%) PJP cases occurred in 160 anti-MDA5-ab-positive DM patients, while only two (0.7%) PJP cases were found in 303 anti-MDA5-ab-negtive DM/PM patients(P &lt; 0.05). PJP infection typically happened in the first two months of the treatment for anti-MDA5-ab-positive DM patients who have a significant decrease in the CD4+ T cell counts and Lymphocyte counts (P &lt; 0.05). Only two (16.7%) anti-MDA5-ab-positive DM patients recover from PJP, with lethally higher mortality than those PJP infection with other rheumatic diseases (83.3% vs. 38.9%, P &lt; 0.05). We found no association between the time to anti-PJP treatment and treatment outcomes in anti-MDA5-ab-positive DM; yet we confirmed in PJP infection with other rheumatic diseases that anti-PJP treatment within 6 days crucially increased the survival (P &lt; 0.05). Conclusion: PJP infection has alarming high incidence and mortality in anti-MDA5-ab-positive DM patients. Unlike PJP infection with other rheumatic diseases, timely treatment for PJP doesn’t improve the prognosis of this particular subtype. Therefore, the necessity of further study of PJP prophylaxis treatment in anti-MDA5-ab-positive DM patients is verified. References: [1]Hsu CY, et al. Comparing the burdens of opportunistic infections among patients with systemic rheumatic diseases: a nationally representative cohort study. ARTHRITIS RES THER 2019, 21(1):211. Acknowledgements: The authors thank Dr. An Sun, Disclosure of Interests: None declared
Screening and Interventions for Social Risk Factors
Authors: Michelle Eder, Michelle Henninger, Shauna Durbin, Megan O. Iacocca, Allea Martin, Laura M. Gottlieb, Jennifer S. Lin
Journal: JAMA (2021)

Evidence-based guidance is limited on how clinicians should screen for social risk factors and which interventions related to these risk factors improve health outcomes.To describe research on screening and interventions for social risk factors to inform US Preventive Services Task Force considerations of the implications for its portfolio of recommendations.Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Sociological Abstracts, and Social Services Abstracts (through 2018); Social Interventions Research and Evaluation Network evidence library (January 2019 through May 2021); surveillance through May 21, 2021; interviews with 17 key informants.Individual-level and health care system-level interventions with a link to the health care system that addressed at least 1 of 7 social risk domains: housing instability, food insecurity, transportation difficulties, utility needs, interpersonal safety, education, and financial strain.One investigator abstracted data from studies and a second investigator evaluated data abstractions for completeness and accuracy; key informant interviews were recorded, transcribed, summarized, and integrated with evidence from the literature; narrative synthesis with supporting tables and figures.Validity of multidomain social risk screening tools; all outcomes reported for social risk-related interventions; challenges or unintended consequences of screening and interventions.Many multidomain social risk screening tools have been developed, but they vary widely in their assessment of social risk and few have been validated. This technical brief identified 106 social risk intervention studies (N = 5 978 596). Of the interventions studied, 73 (69%; n = 127 598) addressed multiple social risk domains. The most frequently addressed domains were food insecurity (67/106 studies [63%], n = 141 797), financial strain (52/106 studies [49%], n = 111 962), and housing instability (63/106 studies [59%], n = 5 881 222). Food insecurity, housing instability, and transportation difficulties were identified by key informants as the most important social risk factors to identify in health care. Thirty-eight studies (36%, n = 5 850 669) used an observational design with no comparator, and 19 studies (18%, n = 15 205) were randomized clinical trials. Health care utilization measures were the most commonly reported outcomes in the 68 studies with a comparator (38 studies [56%], n = 111 102). The literature and key informants described many perceived or potential challenges to implementation of social risk screening and interventions in health care.Many interventions to address food insecurity, financial strain, and housing instability have been studied, but more randomized clinical trials that report health outcomes from social risk screening and intervention are needed to guide widespread implementation in health care.
Tackling the climate of fear faced by ethnic minority groups in medical education and regulation
Authors: Daniel J Warrington, Anish Verma, Gavin H T Ball, James G S Whiteway
Journal: BMJ (2021)

As final year UK medical students entering the foundation training programme next year, we welcome the call by Esmail and Everington to eradicate ethnic disadvantage in medical education and regulation.1

Doctors, particularly those from ethnic minorities, have been working in a climate of fear since the high profile prosecutions of Hadiza Bawa-Garba, David Sellu, and Omer Karim. The Bawa-Garba case resonated …
Decreased neuronal synaptosome associated protein 29 contributes to poststroke cognitive impairment by disrupting presynaptic maintenance
Authors: Weijie Yan, Jiahui Fan, Xia Zhang, Huimeng Song, Rongqi Wan, Wei Wang, Yanling Yin
Journal: Theranostics (2021)

Background: Poststroke cognitive impairments are common in stroke survivors, and pose a high risk of incident dementia. However, the cause of these cognitive impairments is obscure and required an investigation. Methods: Oxygen-glucose deprivation (OGD) model and middle cerebral artery occlusion (MCAO) model were used to imitate in vitro or in vivo acute cerebral ischemia, respectively. The differentially expressed synaptosome associated protein 29 (SNAP29)-interacting proteins upon ischemia and reperfusion were analyzed with bioinformatics analysis and the results indicated that the changes of SNAP29 after acute ischemia were mainly involved in the synaptic functions. The outcomes of SNAP29 reduction were assessed with SNAP29 knockdown, which mimicked the distribution of SNAP29 along neuronal processes after acute ischemia. Using the whole-cell patch clamp recording method and transmission electron microscope, the pre-synaptic function and readily releasable pool (RRP) were observed after SNAP29 knock down. Using photogenetic manipulations and behavioral tests, the neuronal projection and cognitive functions of mice with SNAP29 knock down in hippocampus CA1 region were evaluated. Results: It was found that SNAP29 protein levels decreased in both in vitro and in vivo ischemic models. Further, the SNAP29 reduction wasn't associated with impaired autophagy flux and neuronal survival. When SNAP29 was knocked down in primary cortical neurons, the frequency of AMPARs-mediated mEPSCs, but not the amplitude, significantly decreased. Meanwhile, the mice with SNAP29 knockdown at CA1 region of hippocampus developed an impairment in hippocampus-mPFC (middle prefrontal cortex) circuit and behavioral dysfunctions. Moreover, the size of RRP at presynaptic sites was diminished. Conclusion: Since SNAP29 protein levels didn't significantly influence the neuronal survival and its decrease was sufficient to disturb the neural circuit via a presynaptic manner, the SNAP29-associated strategies may be an efficient target against poststroke synaptic dysfunction and cognitive deficits.