tbuckley/cabot-search huggingface dataset:
Non-occupational and occupational factors associated with specific SARS-CoV-2 antibodies among hospital workers – A multicentre cross-sectional study
Authors: Christian R. Kahlert, Raphael Persi, Sabine Güsewell, Thomas Egger, Onicio B. Leal-Neto, Johannes Sumer, Domenica Flury, Angela Brucher, Eva Lemmenmeier, J. Carsten Möller, Philip Rieder, Reto Stocker, Danielle Vuichard-Gysin, Benedikt Wiggli, Werner C. Albrich, Baharak Babouee Flury, Ulrike Besold, Jan Fehr, Stefan P. Kuster, Allison McGeer, Lorenz Risch, Matthias Schlegel, Andrée Friedl, Pietro Vernazza, Philipp Kohler
Journal: Clinical Microbiology and Infection (2021)

Protecting healthcare workers (HCWs) from coronavirus disease-19 (COVID-19) is critical to preserve the functioning of healthcare systems. We therefore assessed seroprevalence and identified risk factors for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) seropositivity in this population.Between 22 June 22 and 15 August 2020, HCWs from institutions in northern/eastern Switzerland were screened for SARS-CoV-2 antibodies. We recorded baseline characteristics, non-occupational and occupational risk factors. We used pairwise tests of associations and multivariable logistic regression to identify factors associated with seropositivity.Among 4664 HCWs from 23 healthcare facilities, 139 (3%) were seropositive. Non-occupational exposures independently associated with seropositivity were contact with a COVID-19-positive household (adjusted OR 59, 95% CI 33-106), stay in a COVID-19 hotspot (aOR 2.3, 95% CI 1.2-4.2) and male sex (aOR 1.9, 95% CI 1.1-3.1). Blood group 0 vs. non-0 (aOR 0.5, 95% CI 0.3-0.8), active smoking (aOR 0.4, 95% CI 0.2-0.7), living with children <12 years (aOR 0.3, 95% CI 0.2-0.6) and being a physician (aOR 0.2, 95% CI 0.1-0.5) were associated with decreased risk. Other occupational risk factors were close contact to COVID-19 patients (aOR 2.7, 95% CI 1.4-5.4), exposure to COVID-19-positive co-workers (aOR 1.9, 95% CI 1.1-2.9), poor knowledge of standard hygiene precautions (aOR 1.9, 95% CI 1.2-2.9) and frequent visits to the hospital canteen (aOR 2.3, 95% CI 1.4-3.8).Living with COVID-19-positive households showed the strongest association with SARS-CoV-2 seropositivity. We identified several potentially modifiable work-related risk factors, which might allow mitigation of the COVID-19 risk among HCWs. The lower risk among those living with children, even after correction for multiple confounders, is remarkable and merits further study.
Resource Uptake and the Evolution of Moderately Efficient Enzymes
Authors: Florian Labourel, Etienne Rajon
Journal: Molecular Biology and Evolution (2021)

Enzymes speed up reactions that would otherwise be too slow to sustain the metabolism of selfreplicators. Yet, most enzymes seem only moderately efficient, exhibiting kinetic parameters orders of magnitude lower than their expected physically achievable maxima and spanning over surprisingly large ranges of values. Here, we question how these parameters evolve using a mechanistic model where enzyme efficiency is a key component of individual competition for resources. We show that kinetic parameters are under strong directional selection only up to a point, above which enzymes appear to evolve under near-neutrality, thereby confirming the qualitative observation of other modeling approaches. While the existence of a large fitness plateau could potentially explain the extensive variation in enzyme features reported, we show using a population genetics model that such a widespread distribution is an unlikely outcome of evolution on a common landscape, as mutation-selection-drift balance occupy a narrow area even when very moderate biases towards lower efficiency are considered. Instead, differences in the evolutionary context encountered by each enzyme should be involved, such that each evolves on an individual, unique landscape. Our results point to drift and effective population size playing an important role, along with the kinetics of nutrient transporters, the tolerance to high concentrations of intermediate metabolites, and the reversibility of reactions. Enzyme concentration also shapes selection on kinetic parameters, but we show that the joint evolution of concentration and efficiency does not yield extensive variance in evolutionary outcomes when documented costs to protein expression are applied.
Abstract 13382: Increased Adiposity is Associated With Risk of Adverse Clinical Events in Fontan Patients
Authors: Jacob Y Cao, Derek Tran, Julie Briody, Chantal Attard, Ebrahim B Hassan, Peter Simm, Luke Burchill, Stephen Twigg, Maria A Fiatarone-Singh, Julian Ayer, David Celermajer, Yves d’Udekem, Rachael L Cordina
Journal: Circulation (2020)

Introduction: Increased adiposity and reduced lean mass are prevalent in Fontan patients and could be impactful because of the reliance on the peripheral muscle pump and the importance of favourable pulmonary physiology in univentricular physiology. The current study aimed to determine the impact of body fat and lean mass on the risk of adverse outcomes in Fontan patients. Methods: Patients with dual-energy X-ray absorptiometry (DXA) scans from the Australian and New Zealand Fontan Registry were included; they had been consecutively recruited for 2 previous cohort studies. Regression analysis was used to characterize the association between body composition and the composite endpoint of Fontan failure (which included death, transplantation, New York Heart Association (NYHA) functional class III/IV, protein-losing enteropathy, and plastic bronchitis) and development of moderate or worse ventricular dysfunction. Results: 131 DXA scans were analyzed, with mean follow-up of 2.5 (SD 2.2) years after DXA. Mean body fat percentage (%BF) was 29% (SD 10) with 48% having increased adiposity compared with local reference data. Mean appendicular lean mass index (ALMI) z-score was -1.5 (SD 1.1); one third of patients had skeletal muscle deficiency (defined as ALMI z-score between -1 and -2) and another third had Fontan-associated myopenia (defined as ALMI z-score &amp;lt -2). Nine patients reached the composite endpoint during the follow-up period. Age and %BF were predictors of the endpoint in univariable regression (age: HR 1.09 per year, 95% CI 1.02-1.17, p = 0.01; %BF: HR 1.08, 95% CI 1.01-1.17, p = 0.03). On multivariable regression, %BF remained a significant predictor with every 1% increase conferring an 9% increased risk (HR 1.09, 95% CI 1.00-1.19; p = 0.045). ALMI was not a predictor of the endpoint (HR 1.40, 95% CI 0.71-2.76, p = 0.33). However, all patients who experienced a Fontan failure event (n=4) concurrently had increased adiposity and skeletal muscle deficiency. Conclusions: Increased adiposity is associated with increased risk for adverse clinical outcomes. Appropriate lifestyle interventions to optimise body composition should be an important aspect of routine care in this population.
Abstract 14883: The Role of Obstructive Sleep Apnea in Hospitalization in Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus
Authors: Zeba Hashmath, Abhishek Bose, Parag A Chevli, Akil Sherif, Fnu Avinashsingheswarsingh, Shubhi Pandey, Tanvi Shah, Joseph Kirkpatrick
Journal: Circulation (2020)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disease with diverse etiologies. Obstructive sleep apnea (OSA) is known to increase the risk of diastolic dysfunction and heart failure. OSA also increases the risk and severity of type 2 diabetes (DM2) independent of age and obesity. However, its role in patients with HFpEF and concomitant DM2 is unclear. Hypothesis: Our aim was to study the role of OSA in hospitalizations in patients with HFpEF and concomitant DM2. Methods: We did a retrospective chart analysis of 142 patients age (72 ± 11, 54.9% women) with HFpEF and known DM2 for five years after the initial diagnosis of HFpEF. Presence of OSA at the time of initial HFpEF diagnosis was noted based on the results of a documented sleep study. A multivariable cox-proportional hazard model was used to assess whether the presence of OSA had any significant impact on the risk of future HFpEF hospitalization. Kaplan-Meier analysis was used to calculate if OSA predicted time to future HFpEF hospitalization. Results: After a five year follow up, 63 (44.3%) participants developed HFpEF exacerbation. Patients were dichotomized based on presence (n=40, 28.1%) or absence (n=102, 71.8%) of OSA. In a multivariable model adjusted for baseline demographics, risk factors and medications, presence of OSA did not predict risk for a future HFpEF hospitalization (p=0.57, Table). Additionally, on Kaplan-Meier analysis, presence of OSA was not a significant predictor for HFpEF hospitalization (p=0.77, Figure). Conclusion: In patients with HFpEF and concomitant DM2, presence of OSA was not a predictor for future heart failure hospitalizations.
Trends in Home Birth Information Seeking in the United States and United Kingdom During the COVID-19 Pandemic
Authors: Christina N. Schmidt, Laeesha N. Cornejo, Nicholas A. Rubashkin
Journal: JAMA Network Open (2021)

ResultsMean (SD) RSV scores during the COVID-19 era were 53.5 (12.4) in the United States and 39.0 (10.9) in the United Kingdom, compared with pre-COVID-19 scores of 40.6 (14.3) and 31.2 (10.9), respectively.We found a 239% increase in home birth-related RSVs in the United States (relative risk [RR], 3.39; 95% CI, 2.48-2.64;P < .001)and a 53% increase in the United Kingdom (RR, 1.53; 95% CI, 1.06-2.21;P = .02)(Figure).Higher RSVs were noted in the earlier months of the pandemic, and 8 of 9 (89%) and 6 of 9 (67%) of the weeks with the highest volume of searches (ie, >90th percentile RSV score) in the United States and the United Kingdom, respectively, occurred between March and May 2020. DiscussionIn this study, we identified increased public interest in home birth during the COVID-19 pandemic in the United States and the United Kingdom, most prominently during the early months of the outbreak.This increased information-seeking parallels media coverage and anecdotal reports from home birth practitioners, who have noted heightened demand for home birth services.While the largest spike in searches for home birth information occurred early in the pandemic, RSVs have persisted at levels greater than prepandemic trends.The association was more prominent in the Figure.
George F. Vande Woude: In Memoriam (1935–2021)
Authors: Peter A. Jones
Journal: Cancer Research (2021)

</br>![][1]</img> The American Association for Cancer Research (AACR), and indeed the entire cancer research community, lost a truly exceptional and well-loved scientist on April 13, 2021. George Vande Woude passed away in the company of his four children in Grand Rapids, MI, after a lengthy
Simulated aeromedical evacuation exacerbates burn induced lung injury: targeting mitochondrial DNA for reversal
Authors: Meng-Jing Xiao, Xiao-Fang Zou, Bin Li, Bao-Long Li, Shi-Jian Wu, Bo Zhang
Journal: Military Medical Research (2021)

Aeromedical evacuation of patients with burn trauma is an important transport method in times of peace and war, during which patients are exposed to prolonged periods of hypobaric hypoxia; however, the effects of such exposure on burn injuries, particularly on burn-induced lung injuries, are largely unexplored. This study aimed to determine the effects of hypobaric hypoxia on burn-induced lung injuries and to investigate the underlying mechanism using a rat burn model.A total of 40 male Wistar rats were randomly divided into four groups (10 in each group): sham burn (SB) group, burn in normoxia condition (BN) group, burn in hypoxia condition (BH) group, and burn in hypoxia condition with treatment intervention (BHD) group. Rats with 30% total body surface area burns were exposed to hypobaric hypoxia (2000 m altitude simulation) or normoxia conditions for 4 h. Deoxyribonuclease I (DNase I) was administered systemically as a treatment intervention. Systemic inflammatory mediator and mitochondrial deoxyribonucleic acid (mtDNA) levels were determined. A histopathological evaluation was performed and the acute lung injury (ALI) score was determined. Malonaldehyde (MDA) content, myeloperoxidase (MPO) activity, and the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome level were determined in lung tissues. Data among groups were compared using analysis of variance followed by Tukey's test post hoc analysis.Burns resulted in a remarkably higher level of systemic inflammatory cytokines and mtDNA release, which was further heightened by hypobaric hypoxia exposure (P < 0.01). Moreover, hypobaric hypoxia exposure gave rise to increased NLRP3 inflammasome expression, MDA content, and MPO activity in the lung (P < 0.05 or P < 0.01). Burn-induced lung injuries were exacerbated, as shown by the histopathological evaluation and ALI score (P < 0.01). Administration of DNase I markedly reduced mtDNA release and systemic inflammatory cytokine production. Furthermore, the NLRP3 inflammasome level in lung tissues was decreased and burn-induced lung injury was ameliorated (P < 0.01).Our results suggested that simulated aeromedical evacuation further increased burn-induced mtDNA release and exacerbated burn-induced inflammation and lung injury. DNase I reduced the release of mtDNA, limited mtDNA-induced systemic inflammation, and ameliorated burn-induced ALI. The intervening mtDNA level is thus a potential target to protect from burn-induced lung injury during aeromedical conditions and provides safer air evacuations for severely burned patients.
Gene therapy restores dopamine transporter expression and ameliorates pathology in iPSC and mouse models of infantile parkinsonism
Authors: Joanne Ng, Serena Barral, Carmen De La Fuente Barrigon, Gabriele Lignani, Fatma A. Erdem, Rebecca Wallings, Riccardo Privolizzi, Giada Rossignoli, Haya Alrashidi, Sonja Heasman, Esther Meyer, Adeline Ngoh, Simon Pope, Rajvinder Karda, Dany Perocheau, Julien Baruteau, Natalie Suff, Juan Antinao Diaz, Stephanie Schorge, Jane Vowles, Lucy R. Marshall, Sally A. Cowley, Sonja Sucic, Michael Freissmuth, John R. Counsell, Richard Wade-Martins, Simon J. R. Heales, Ahad A. Rahim, Maximilien Bencze, Simon N. Waddington, Manju A. Kurian
Journal: Science Translational Medicine (2021)

Viral vectors restore dopamine transporter function and ameliorate neuropathology in iPSC-derived neurons and a mouse model of infantile parkinsonism.
Acknowledging breathlessness post-covid
Authors: Nicholas Hopkinson
Journal: BMJ (2021)

Covid-19 is a respiratory infection, although it can be associated with both acute and long term systemic complications. Breathlessness is among the most common symptoms reported in people followed up after hospital admission,1 following infection identified in the community,2 and in those reporting that they have long-covid.3 Consistent with this, Ayoubkhani and colleagues report rates of respiratory disease, …
Abstract 16194: Prior Atrial Fibrillation and WCD-detected Arrhythmic Outcomes - Data From the WEARIT-II Prospective Registry
Authors: Ido Goldenberg, Arwa Younis, Scott McNitt, Helmut U Klein, Ilan Goldenberg, Valentina Kutyifa
Journal: Circulation (2020)

Introduction: The Wearable Cardioverter Defibrillator (WCD) is utilized in patients with assumed but not yet confirmed risk for sudden cardiac death (SCD). Many of these patients also present with a history of atrial fibrillation (AF). However, the rate of WCD-detected ventricular or atrial arrhythmia events in this specific high-risk cohort is not well understood. Methods: In WEARIT-II, the cumulative probability of any sustained or non-sustained VT/VF (WCD-treated and non-treated), and atrial/supraventricular arrhythmias during WCD use was assessed using the Kaplan-Meier method, with comparisons by the log-rank test. The incidence of ventricular and atrial arrhythmia events were expressed as events per 100 patient-years, and were analyzed by negative binomial regression. Results: The WEARIT-II trial enrolled 2000 patients, 557 (28%) of whom had AF prior to enrollment. The cumulative probability of any sustained or non-sustained WCD-detected VT/VF during WCD use was significantly higher among patients with a history of AF than in patients without AF (6% vs. 3%, p=0.001, Figure). Similarly, the recurrent rate of any sustained or non-sustained VT/VF was significantly higher in patients with prior AF vs. no prior AF (131.5 events per 100 patient-years vs. 22.7 events per 100 patient-years, p=0.001). Patients with prior AF also had a significantly higher burden of WCD-detected atrial arrhythmias/SVT (64 events per 100 patient-years vs 13.7 events per 100 patient-years, p&lt;0.001). Conclusions: Our results demonstrate that patients with a history of AF wearing the WCD for risk assessment have a higher incidence of ventricular arrhythmias that may facilitate the decision making for ICD implantation.
Does the evidence support brief (≤30-mins), moderate (31–60-mins), or long duration naps (61+ mins) on the night shift? A systematic review
Authors: P. Daniel Patterson, Mary K. Liszka, Quentin S. Mcilvaine, Lily Nong, Matthew D. Weaver, Rose L. Turner, Thomas E. Platt, Samantha E. Opitz, Francis X. Guyette, Christian Martin-Gill, Leonard S. Weiss, Daniel J. Buysse, Clifton W. Callaway
Journal: Sleep Medicine Reviews (2021)
Abstract P146: Comparative Effectiveness Of Direct Oral Anticoagulants Versus Warfarin Among Medicare Beneficiaries With Atrial Fibrillation
Authors: Shirin Ardeshirrouhanifard, Huijun An, Ravi Goyal, Mukaila Raji, Caleb Alexander, Hemalkumar Mehta
Journal: Circulation (2021)

Objective: Post-hoc analysis of three pivotal clinical trials suggests no difference in risk of ischemic stroke or systemic embolism among cancer patients with atrial fibrillation treated with direct oral anticoagulants (DOACs) vs. warfarin. However, these studies were underpowered and also do not reflect the context of real-world use. We compared the effectiveness of DOACs versus warfarin for the risk of stroke or systemic embolism and all-cause death in patients with NVAF. Methods: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2009 to 2016 and included patients aged ≥66 years diagnosed with cancer (breast, bladder, colorectal, esophagus, lung, ovary, kidney, pancreas, prostate, stomach or uterus) and NVAF. We limited the cohort to patients who newly initiated warfarin or DOACs (from 2010 to 2016) with no history of ischemic stroke or systemic embolism. The primary outcome was hospitalization due to ischemic stroke or systemic embolism and the secondary outcome was all-cause death. We used Fine and Gray’s competing risk model, while treating death as a competing risk, to determine the association of oral anticoagulants with the incidence of stroke or systemic embolism. We also adjusted the analysis using inverse probability of treatment weighted (IPTW). Additionally, an IPTW-adjusted Cox proportional hazards regression model was constructed for all-cause death. Results: Of 1,028,784 patients with cancer, 158,744 (15.4%) were diagnosed with atrial fibrillation. After applying all inclusion criteria, the final study cohort included 7,334 cancer patients diagnosed with incident NVAF who newly initiated warfarin or DOACs, of which 3,194 (43.6%) used warfarin and 4,140 (56.4%) used DOACs. The unadjusted rate of stroke or systemic embolism was similar among warfarin and DOACs users (1.20 vs. 1.32 cases per 100 person-years, p=0.27). In the IPTW weighted competing risk model, the use of DOACs was not associated with an increased risk of stroke or systemic embolism compared with warfarin users (Hazard Ratio [HR] 1.41, 95% confidence intervals [CI] 0.90-2.20). However, DOACs users had a significantly lower risk of all-cause death compared with warfarin users (HR 0.82, CI 0.74-0.91). Conclusion: Among cancer patients diagnosed with NVAF, DOACs had a similar risk for stroke or systemic embolism compared to warfarin, although DOAC use was associated with reduced risk of all-cause mortality.
Culture media for clinical bacteriology in low- and middle-income countries: challenges, best practices for preparation and recommendations for improved access
Authors: Jeanne Orekan, Barbara Barbé, Sopheap Oeng, Jean-Baptiste Ronat, Joanne Letchford, Jan Jacobs, Dissou Affolabi, Liselotte Hardy
Journal: Clinical Microbiology and Infection (2021)

Culture media are fundamental in clinical microbiology. In laboratories in low- and middle-income countries (LMICs), they are mostly prepared in-house, which is challenging.This narrative review describes challenges related to culture media in LMICs, compiles best practices for in-house media preparation, gives recommendations to improve access to quality-assured culture media products in LMICs and formulates outstanding questions for further research.Scientific literature was searched using PubMed and predefined MeSH terms. In addition, grey literature was screened, including manufacturer's websites and manuals as well as microbiology textbooks.Bacteriology laboratories in LMICs often face challenges at multiple levels: lack of clean water and uninterrupted power supply, high environmental temperatures and humidity, dust, inexperienced and poorly trained staff, and a variable supply of consumables (often of poor quality). To deal with this at a base level, one should be very careful in selecting culture media. It is recommended to look for products supported by the national reference laboratory that are being distributed by an in-country supplier. Correct storage is key, as is appropriate preparation and waste management. Centralized media acquisition has been advocated for LMICs, a role that can be taken up by the national reference laboratories, next to guidance and support of the local laboratories. In addition, there is an important role in tropicalization and customization of culture media formulations for private in vitro diagnostic manufacturers, who are often still unfamiliar with the LMIC market and the plethora of bacteriology products.The present narrative review will assist clinical microbiology laboratories in LMICs to establish best practices for handling culture media by defining quality, regulatory and research paths.
American Medical Association confronts its racist past with plan for a more equal future
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

The American Medical Association (AMA) has set out a plan to dismantle structural racism, starting within the organisation, and to work towards a future of health equity.1

The AMA, which has among its members 240 000 doctors and more than 190 state and specialty medical societies, said that race is social, not biological. “Race is a socially constructed way of grouping people, based on skin colour and other apparent physical differences. It has been defined by an arbitrarily organised combination of physical traits, geographic ancestry, language, religion, and a variety of other cultural features.”

The plan began three years ago when the AMA’s annual House of Delegates meeting considered a report defining “health equity” and outlining the association’s role in tackling inequities in healthcare. It recommended that the organisation set up a centre to initiate, coordinate, and track its health equity activities.

The plan presents what the AMA …