tbuckley/cabot-search huggingface dataset:
Sex- and age-related trajectories of the adult human gut microbiota shared across populations of different ethnicities
Authors: Xiuying Zhang, Huanzi Zhong, Yufeng Li, Zhun Shi, Huahui Ren, Zhe Zhang, Xianghai Zhou, Shanmei Tang, Xueyao Han, Yuxiang Lin, Fangming Yang, Dan Wang, Chao Fang, Zuodi Fu, Lianying Wang, Shida Zhu, Yong Hou, Xun Xu, Huanming Yang, Jian Wang, Karsten Kristiansen, Junhua Li, Linong Ji
Journal: Nature Aging (2021)
Breathomics for the clinician: the use of volatile organic compounds in respiratory diseases
Authors: Wadah Ibrahim, Liesl Carr, Rebecca Cordell, Michael J Wilde, Dahlia Salman, Paul S Monks, Paul Thomas, Chris E Brightling, Salman Siddiqui, Neil J Greening
Journal: Thorax (2021)

Exhaled breath analysis has the potential to provide valuable insight on the status of various metabolic pathways taking place in the lungs locally and other vital organs, via systemic circulation. For years, volatile organic compounds (VOCs) have been proposed as feasible alternative diagnostic and prognostic biomarkers for different respiratory pathologies.We reviewed the currently published literature on the discovery of exhaled breath VOCs and their utilisation in various respiratory diseasesKey barriers in the development of clinical breath tests include the lack of unified consensus for breath collection and analysis and the complexity of understanding the relationship between the exhaled VOCs and the underlying metabolic pathways. We present a comprehensive overview, in light of published literature and our experience from coordinating a national breathomics centre, of the progress made to date and some of the key challenges in the field and ways to overcome them. We particularly focus on the relevance of breathomics to clinicians and the valuable insights it adds to diagnostics and disease monitoring.Breathomics holds great promise and our findings merit further large-scale multicentre diagnostic studies using standardised protocols to help position this novel technology at the centre of respiratory disease diagnostics.
Delaying Electrocardiography in Cardiac Arrest: A Pause for the Cause
Authors: Rajat Kalra, Demetris Yannopoulos
Journal: JAMA Network Open (2021)

Enrico Baldi, MD; Sebastian Schnaubelt, MD; Maria Luce Caputo, MD; Catherine Klersy, MD, MScEpid; Christian Clodi, MD; Jolie Bruno, MD; Sara Compagnoni, MD; Claudio Benvenuti, RN; Hans Domanovits, MD; Roman Burkart, RN; Rosa Fracchia, MD; Roberto Primi, MSc; Gerhard Ruzicka, MD; Michael Holzer, MD; Angelo Auricchio, MD, PhD; Simone Savastano, MD
Type I interferon signaling and macrophages: a double-edged sword?
Authors: Barbara Adler, Heiko Adler
Journal: Cellular and Molecular Immunology (2021)

In a recent issue of the Journal of Experimental Medicine, Zhang et al. reported that type I interferon (type I IFN) signaling mediates Mycobacterium tuberculosis (Mtb)-induced macrophage (MΦ) death, most likely by a new, currently unknown cell death pathway. 1 Type I IFNs are a major host defense against viral and bacterial infections.They are produced by a variety of cell types, including MΦs.After recognition of pathogen-associated molecular patterns by, for example, Toll-like receptors, host cells produce type I IFNs that can act in both autocrine and paracrine ways to activate or repress IFN-stimulated genes. 2,3In addition to interfering with multiple stages in the life cycle of pathogens, type I IFNs have additional functions influencing both innate and adaptive immune responses, which can result in beneficial but also detrimental effects in the host (Fig. 1).It seems that the outcome of the type I IFN response is highly context-dependent. 3For example, type I IFN signaling during bacterial infections is dependent on many factors, e.g., whether the bacteria are intraor extracellular, thereby activating different signaling pathways.While type I IFN signaling is crucial for host defense against some bacteria, e.g., pneumococci, it may promote infection by others, including Mtb. 3,4 Mtb infects MΦs, and once inside the cell, it inhibits the development of phagosomes to phagolysosomes, enabling Mtb not only to survive but also to replicate.Infected MΦs will eventually die, releasing bacteria that spread to more cells.Thus, Mtb-induced MΦ death is a crucial factor in the pathogenesis of tuberculosis.Despite the importance of Mtbinduced MΦ death, the underlying mechanism remains elusive.Therefore, Zhang et al. 1 investigated which type of cell death Mtb-infected MΦs undergo.Surprisingly, they discovered that the hitherto known types of cell death are obviously not involved.Specifically, by using a variety of approaches, e.g., the application of inhibitors of specific cell death pathways and knockout cells, they excluded apoptosis, pyroptosis, necroptosis, parthanatos, ferroptosis, and autophagy-dependent cell death.From these data, the authors concluded that Mtb-induced MΦ death might involve a novel mechanism.To identify this mechanism, the authors performed a genome-wide CRISPR-Cas9 screen in an Mtbinfected MΦ cell line.This screen identified type I IFN signaling as important for the death of Mtb-infected MΦs.Subsequent genetic and immunological studies confirmed that autocrine and paracrine type I IFN signaling play an important role in the death of Mtb-infected MΦs.Crucially, the authors went on to demonstrate that blocking type I IFN signaling protects Mtb-infected mice and,
Ten reasons why corticosteroid therapy reduces mortality in severe COVID-19
Authors: José M. Añón, Jesús Villar
Journal: Intensive Care Medicine (2021)

We have read with interest the recent article by Arabi et al. [1] published in Intensive Care Medicine where the authors provided 10 reasons why corticosteroid therapy reduces mortality in severe coronavirus disease 2019 .The authors stated that the best available evidence to support the use of corticosteroids in COVID-19 is based on the results of the RECOVERY trial [2] and the WHO REACT prospective meta-analysis [3].They mentioned the DEXA-ARDS trial [4] where dexamethasone, (20 mg and 10 mg for 5 days each) markedly decreased 60-day mortality in mechanically ventilated patients with persistent moderate-to-severe acute respiratory distress syndrome (ARDS).Several comments can be made regarding these statements.In the RECOVERY trial [2], patients allocated to dexamethasone received 6 mg/day for 10 days.It is unclear why a dose of 6 mg was selected.RECOVERY [2] investigators postulated that higher doses could be harmful.A subgroup analysis of the DEXA-ARDS trial [4] revealed (data unpublished) that 62 patients had H1N1-ARDS and the number of deaths at 60-days was lower in the dexamethasone arm [3/31 (9.7%) vs 8/31 (25.8%)].Although this difference was not statistically significant (p = 0.182) probably due to reduced statistical power, it suggests that higher doses of dexamethasone could be more beneficial in COVID-19-related acute respiratory distress syndrome (ARDS).In the WHO REACT meta-analysis [3], data from 7 trials were pooled.Five trials reported mortality at 28 days, one trial at 21 days, and one trial at 30 days.The
Polygenic risk scores in cardiovascular risk prediction: A cohort study and modelling analyses
Authors: Luanluan Sun, Lisa Pennells, Stephen Kaptoge, Christopher P. Nelson, Scott C. Ritchie, Gad Abraham, Matthew Arnold, Steven Bell, Thomas Bolton, Stephen Burgess, Frank Dudbridge, Qi Guo, Eleni Sofianopoulou, David Stevens, John R. Thompson, Adam S. Butterworth, Angela Wood, John Danesh, Nilesh J. Samani, Michael Inouye, Emanuele Di Angelantonio
Journal: PLoS Medicine (2021)

Background Polygenic risk scores (PRSs) can stratify populations into cardiovascular disease (CVD) risk groups. We aimed to quantify the potential advantage of adding information on PRSs to conventional risk factors in the primary prevention of CVD. Methods and findings Using data from UK Biobank on 306,654 individuals without a history of CVD and not on lipid-lowering treatments (mean age [SD]: 56.0 [8.0] years; females: 57%; median follow-up: 8.1 years), we calculated measures of risk discrimination and reclassification upon addition of PRSs to risk factors in a conventional risk prediction model (i.e., age, sex, systolic blood pressure, smoking status, history of diabetes, and total and high-density lipoprotein cholesterol). We then modelled the implications of initiating guideline-recommended statin therapy in a primary care setting using incidence rates from 2.1 million individuals from the Clinical Practice Research Datalink. The C-index, a measure of risk discrimination, was 0.710 (95% CI 0.703–0.717) for a CVD prediction model containing conventional risk predictors alone. Addition of information on PRSs increased the C-index by 0.012 (95% CI 0.009–0.015), and resulted in continuous net reclassification improvements of about 10% and 12% in cases and non-cases, respectively. If a PRS were assessed in the entire UK primary care population aged 40–75 years, assuming that statin therapy would be initiated in accordance with the UK National Institute for Health and Care Excellence guidelines (i.e., for persons with a predicted risk of ≥10% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), then it could help prevent 1 additional CVD event for approximately every 5,750 individuals screened. By contrast, targeted assessment only among people at intermediate (i.e., 5% to &lt;10%) 10-year CVD risk could help prevent 1 additional CVD event for approximately every 340 individuals screened. Such a targeted strategy could help prevent 7% more CVD events than conventional risk prediction alone. Potential gains afforded by assessment of PRSs on top of conventional risk factors would be about 1.5-fold greater than those provided by assessment of C-reactive protein, a plasma biomarker included in some risk prediction guidelines. Potential limitations of this study include its restriction to European ancestry participants and a lack of health economic evaluation. Conclusions Our results suggest that addition of PRSs to conventional risk factors can modestly enhance prediction of first-onset CVD and could translate into population health benefits if used at scale.
Abstract 13582: The Effect of Time-restricted Feeding on Weight: A Randomized Feeding Trial
Authors: Nisa Maruthur, Scott Pilla, May T Maw, Daisy Duan, Di Zhao, Eliseo Guallar, Ruth Alma Turkson Ocran, Karen White, Beiwen Wu, Jeanne Charleston, Lawrence J Appel, Jeanne M Clark
Journal: Circulation (2020)

Introduction: Time-restricted feeding (TRF) may improve cardiometabolic outcomes. Prior studies of TRF in humans were limited by lack of randomization and controlled feeding, inadequate sample size and short duration. Hypothesis: Participants following a TRF pattern will lose more weight at 12 weeks than those following a Usual Feeding Pattern (UFP). Methods: We randomized 41 adults with BMI 30-49.9 kg/m 2 and HbA1c 5.7-6.9% to either TRF (80% of total calories before 1 pm) or a UFP (50% of calories after 5 pm) for 12 weeks. Dietary caloric requirement for weight maintenance was determined at baseline for each participant and held constant during the intervention. Participants in both arms consumed the same diet with the same nutrient and food content and only consumed food prepared by the study metabolic kitchen. The primary outcome was weight. Weight and office blood pressure were measured at baseline and 4, 8, and 12 weeks and were analyzed using a linear mixed effects model with an unstructured covariance with indicators for visit and intervention interacted with visit. Results: All participants completed the study (TRF, n=21; UFP, n=20). Demographics were similar across arms; mean age was 59 years, and over 90% of participants were female and were black. Baseline weight and systolic BP were higher in the UFP than TRF arm (Table). Weight and blood pressure decreased in both arms during the study, but these decreases did not differ by arm. Conclusions: In this controlled feeding study, TRF did not reduce weight and blood pressure compared to UFP.
MO01.19 An Indirect Comparison of Pembrolizumab Monotherapy Versus Ipilimumab+Nivolumab for First-Line Metastatic NSCLC with PD-L1 TPS≥1%
Authors: B. Halmos, T. Burke, C. Kalyvas, R. Insinga, K. Vandormael, A. Frederickson, B. Piperdi
Journal: Journal of Thoracic Oncology (2021)
A Method to Quantify Mean Hypertension Treatment Daily Dose Intensity Using Health Care System Data
Authors: Lillian Min, Jin-Kyung Ha, Carole E. Aubert, Timothy P. Hofer, Jeremy B. Sussman, Kenneth M. Langa, Mary Tinetti, Hyungjin Myra Kim, Matthew L. Maciejewski, Leah Gillon, Angela Larkin, Chiao-Li Chan, Eve A. Kerr, Dawn Bravata, William C. Cushman
Journal: JAMA Network Open (2021)

Simple measures of hypertension treatment, such as achievement of blood pressure (BP) targets, ignore the intensity of treatment once the BP target is met. High-intensity treatment involves increased treatment burden and can be associated with potential adverse effects in older adults. A method was previously developed to identify older patients receiving intense hypertension treatment by low BP and number of BP medications using national Veterans Health Administration and Medicare Part D administrative pharmacy data to evaluate which BP medications a patient is likely taking on any given day.To further develop and validate a method to more precisely quantify dose intensity of hypertension treatment using only health system administrative pharmacy fill data.Observational, cross-sectional study of 319 randomly selected older veterans in the national Veterans Health Administration health care system who were taking multiple BP-lowering medications and had a total of 3625 ambulatory care visits from July 1, 2011, to June 30, 2013. Measure development and medical record review occurred January 1, 2017, through November 30, 2018, and data analysis was conducted from December 1, 2019, to August 31, 2020.For each BP-lowering medication, a moderate hypertension daily dose (HDD) was defined as half the maximum dose above which no further clinical benefit has been demonstrated by that medication in hypertension trials. Patients' total HDD was calculated using pharmacy data (pharmacy HDDs), accounting for substantial delays in refills (>30 days) when a patient's pill supply was stretched (eg, cutting existing pills in half). As an external comparison, the pharmacy HDDs were correlated with doses manually extracted from clinicians' visit notes (clinically noted HDDs). How well the pharmacy HDDs correlated with clinically noted HDDs was calculated (using C statistics). To facilitate interpretation, HDDs were described in association with the number of medications.A total of 316 patients (99.1%) were male; the mean (SD) age was 75.6 (7.2) years. Pharmacy HDDs were highly correlated (r = 0.92) with clinically noted HDDs, with a mean (SD) of 2.7 (1.8) for pharmacy HDDs and 2.8 (1.8) for clinically noted HDDs. Pharmacy HDDs correlated with high-intensity, clinically noted HDDs ranging from a C statistic of 92.8% (95% CI, 92.0%-93.7%) for 2 or more clinically noted HDDs to 88.1% (95% CI, 85.5%-90.6%) for 6 or more clinically noted HDDs.This study suggests that health system pharmacy data may be used to accurately quantify hypertension regimen dose intensity. Together with clinic-measured BP, this tool can be used in future health system-based research or quality improvement efforts to fine-tune, manage, and optimize hypertension treatment in older adults.
Abstract 16278: Prediction of Contrast-Induced Nephropathy by Tissue-Inhibitor of Metalloproteinase-2 (TIMP-2) and Insulin-Like Growth Factor Binding-Protein-7 (IGFBP7) After Coronary or Peripheral Angiography
Authors: Avinash Toomu, Paula Anzenberg, Emily Liu, Taelor Getz, Sandeep Toomu, Jessica Gonzales, Romteen Sedighi, Lori B Daniels
Journal: Circulation (2018)

Introduction: Contrast-induced nephropathy (CIN) occurs in 10-30% of patients undergoing angiography, and is associated with morbidity and mortality. Although the onset of kidney stress occurs with...
Effectiveness of red dichromatic imaging for dissection of the submucosal layer when hematoma is encountered
Authors: Shuichi Miyamoto, Tomohiko R. Ohya, Kaori Nishi, Satoshi Abiko, Ryo Sugiura, Yoshiya Yamamoto, Naoya Sakamoto
Journal: Endoscopy (2021)

Endoscopic submucosal dissection (ESD) for gastric tumors is performed worldwide. When vascularized lesions are treated, hematoma in the submucosal layer is sometimes encountered during dissection. The presence of submucosal fibrosis and hematoma often makes dissection very difficult because identifying the correct submucosal tissue plane is almost impossible despite attempts at washing using the scope’s water jet function. Red dichromatic imaging (RDI; Dual Red Imaging) is a recently released novel image-enhanced endoscopic technology (Olympus Medical Systems, Tokyo, Japan) [1] [2] [3] [4]. We report a case in which RDI helped identify submucosal fibrous tissue in the submucosal layer with hematoma during gastric ESD.
Top-down coordination of local cortical state during selective attention
Authors: Jochem van Kempen, Marc A. Gieselmann, Michael Boyd, Nicholas A. Steinmetz, Tirin Moore, Tatiana A. Engel, Alexander Thiele
Journal: Neuron (2021)

Spontaneous fluctuations in cortical excitability influence sensory processing and behavior. These fluctuations, long thought to reflect global changes in cortical state, were recently found to be modulated locally within a retinotopic map during spatially selective attention. We report that periods of vigorous (On) and faint (Off) spiking activity, the signature of cortical state fluctuations, are coordinated across brain areas with retinotopic precision. Top-down attention enhanced interareal local state coordination, traversing along the reverse cortical hierarchy. The extent of local state coordination between areas was predictive of behavioral performance. Our results show that cortical state dynamics are shared across brain regions, modulated by cognitive demands and relevant for behavior.
Abstract 7: Chromatin Organization in Diseased and Healthy Mouse Heart
Authors: Chukwuemeka George Anene Nzelu, Dominic Lee, Wilson Tan, Zenia Tiang, Matias A Ilmaris, Peter Li, Melissa Fullwood, Roger Foo
Journal: Circulation Research (2017)

Background: The three-dimensional chromatin structure regulates transcription by bringing regulatory elements such as enhancers in close spatial proximity with target genes. This arrangement helps to ensure cell type-specific gene expression profiles. We employed Hi-C, Chip-seq and CRISPR knock out to provide a detailed genome-wide view of the 3D chromatin structure in healthy and diseased mouse heart tissue and also to link regulatory elements with their target genes. Results: The 3D chromatin organization of Sham and TAC adult ventricular cardiomyocytes (CMs) as well as atrial-origin HL1 cardiomyocytes showed high degree of similarity. While topological associated domains are stable across all cell types, the A and B genomic compartments showed important variations, which correlated well with differential gene expression profiles. Analysis of the interactions in regions enriched with the histone enhancer mark H3K27ac identified putative regulatory elements responsible for cell-type specific gene expression. In addition, CRISPR deletion of a regulatory region upstream of Nppb and Nppa loci led to a downregulation of these genes in HL1 cells, confirming results obtained via Hi-C and 4C Conclusion: We show evidence of the relationship between genome organization and gene expression by comparing atrial and Sham and TAC ventricular cardiac cells. Importantly, this is the first detailed report of genome-wide 3D chromatin interactions in cardiac cells, revealing cardiac-relevant genomic compartments that associate with cardiac-specific gene expression.
Daily aspirin for primary prevention increased risk for major GI bleeding in healthy older adults
Authors: Calvin Hirsch
Journal: Annals of Internal Medicine (2021)

Source Citation Mahady SE, Margolis KL, Chan A, et al. Major GI bleeding in older persons using aspirin: incidence and risk factors in the ASPREE randomised controlled trial. Gut. 2020. [Epub ahead of print.] 32747412
Aortic Valve Replacement in Low-Risk Patients With Severe Aortic Stenosis Outside Randomized Trials
Authors: Alberto Alperi, Pierre Voisine, Dimitri Kalavrouziotis, Eric Dumont, François Dagenais, Jean Perron, Iria Silva, Fernando Bernardi, Siamak Mohammadi, Josep Rodés-Cabau
Journal: Journal of the American College of Cardiology (2021)
Pathogen-specific antimicrobials engineered de novo through membrane-protein biomimicry
Authors: Andrew W. Simonson, Agustey S. Mongia, Matthew R. Aronson, John N. Alumasa, Dennis C. Chan, Atip Lawanprasert, Michael D. Howe, Adam Bolotsky, Tapas K. Mal, Christy George, Aida Ebrahimi, Anthony D. Baughn, Elizabeth A. Proctor, Kenneth C. Keiler, Scott H. Medina
Journal: Nature Biomedical Engineering (2021)
MO01.33 CRESTONE – Clinical Study of REsponse to Seribantumab in Tumors with NEuregulin-1 (NRG1) Fusions – A Phase 2 Study of the anti-HER3 mAb for Advanced or Metastatic Solid Tumors (NCT04383210)
Authors: D. Spigel, S.N. Waqar, M.E. Burkard, J.J. Lin, Y.K. Chae, M.A. Socinski, S. Gadgeel, K.L. Reckamp, S.M. Leland, D. Plessinger, L. Kunkel, J.R. Bauman, G. Otterson, B. Halmos, S.-H. Ignatius Ou, T. Patil, Y.Y. Elamin, E.S. Kim
Journal: Journal of Thoracic Oncology (2021)
Neuronal delivery of antibodies has therapeutic effects in animal models of botulism
Authors: Patrick M. McNutt, Edwin J. Vazquez-Cintron, Luis Tenezaca, Celinia A. Ondeck, Kyle E. Kelly, Mark Mangkhalakhili, James B. Machamer, Christopher A. Angeles, Elliot J. Glotfelty, Jaclyn Cika, Cesar H. Benjumea, Justin T. Whitfield, Philip A. Band, Charles B. Shoemaker, Konstantin Ichtchenko
Journal: Science Translational Medicine (2021)

Intraneuronal delivery of a therapeutic, single-domain antibody reverses botulism symptoms and increases survival of mice, guinea pigs, and monkeys.
Mouse Lung Structure and Function after Long-Term Exposure to an Atmospheric Carbon Dioxide Level Predicted by Climate Change Modeling
Authors: Alexander N. Larcombe, Melissa G. Papini, Emily K. Chivers, Luke J. Berry, Robyn M. Lucas, Caitlin S. Wyrwoll
Journal: Environmental Health Perspectives (2021)

Climate change models predict that atmospheric carbon dioxide [CO2] levels will be between 700 and 900 ppm within the next 80 y. Despite this, the direct physiological effects of exposure to slightly elevated atmospheric CO2 (as compared with ∼410 ppm experienced today), especially when exposures extend from preconception to adulthood, have not been thoroughly studied.In this study we aimed to assess the respiratory structure and function effects of long-term exposure to 890 ppmCO2 from preconception to adulthood using a mouse model.We exposed mice to CO2 (∼890 ppm) from prepregnancy, through the in utero and early life periods, until 3 months of age, at which point we assessed respiratory function using the forced oscillation technique, and lung structure.CO2 exposure resulted in a range of respiratory impairments, particularly in female mice, including higher tissue elastance, longer chord length, and lower lung compliance. Importantly, we also assessed the lung function of the dams that gave birth to our experimental subjects. Even though these mice had been exposed to the same level of increased CO2 for a similar amount of time (∼8wk), we measured no impairments in lung function. This suggests that the early life period, when lungs are undergoing rapid growth and development, is particularly sensitive to CO2.To the best of our knowledge, this study, for the first time, shows that long-term exposure to environmentally relevant levels of CO2 can impact respiratory function in the mouse. https://doi.org/10.1289/EHP7305.