bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid antiretroviral therapy initiation and its effect on treatment response in MSM in West Africa
Authors: Dah Ter Tiero Elias , Yaya Issifou , Mensah Ephrem , Coulibaly Alou , Kouamé Jean-Baptiste Malan , Traoré Issa , Mora Marion , Palvadeau Paméla , Anoma Camille , Keita Bintou Dembélé , Spire Bruno , Laurent Christian 
Published: August 2021

Objective:
To assess the time from HIV diagnosis to ART initiation and the effect of rapid ART initiation (i.e. within 7 days of HIV diagnosis) on attrition and virologic and immunologic responses among MSM in Burkina Faso, Côte d’Ivoire, Mali, and Togo.

Design:
Prospective cohort study between 2015 and 2019.

Methods:
MSM aged 18 years or older newly diagnosed with HIV infection were eligible to participate. ART was proposed to participants upon HIV diagnosis, irrespective of clinical stage and CD4+ cell count, and was initiated as soon as possible, with no specific time frame. Determinants of rapid ART initiation and its effect on treatment outcomes were assessed using multivariate analyses.

Results:
Of 350 MSM, 335 (95.7%) initiated ART after a median time of 5 days. Of the latter, 216 (64.5%) had rapid ART initiation. The 335 participants were followed up for a median time of 24.1 months. One hundred and eleven (33.1%) were not retained in care. Rapid ART initiation was less likely in participants with a CD4+ cell count at least 200 cells/μl [adjusted odds ratio (aOR) 0.37, 95% confidence interval (CI) 0.15–0.88]. It improved viral load suppression (aOR 6.96, 95% CI 1.98–24.46) but had no effect on attrition (aOR 0.87, 95% CI 0.57–1.33) or CD4+ cell count increase (adjusted coefficient 28.23, 95% CI −17.00 to 73.45).

Conclusion:
These results in MSM in West Africa support the WHO recommendation for rapid ART initiation. Clinics need to develop context-specific strategies for rapid ART initiation and for retaining MSM in HIV care.
ClinicalTrials.gov, number NCT02626286.
Artificial Intelligence in Chest Radiography Reporting Accuracy
Authors: Rudolph Jan , Huemmer Christian , Ghesu Florin-Cristian , Mansoor Awais , Preuhs Alexander , Fieselmann Andreas , Fink Nicola , Dinkel Julien , Koliogiannis Vanessa , Schwarze Vincent , Goller Sophia , Fischer Maximilian , Jörgens Maximilian , Ben Khaled Najib , Vishwanath Reddappagari Suryanarayana , Balachandran Abishek , Ingrisch Michael , Ricke Jens , Sabel Bastian Oliver , Rueckel Johannes 
Published: August 2021

Objectives
Chest radiographs (CXRs) are commonly performed in emergency units (EUs), but the interpretation requires radiology experience. We developed an artificial intelligence (AI) system (precommercial) that aims to mimic board-certified radiologists' (BCRs') performance and can therefore support non–radiology residents (NRRs) in clinical settings lacking 24/7 radiology coverage. We validated by quantifying the clinical value of our AI system for radiology residents (RRs) and EU-experienced NRRs in a clinically representative EU setting.

Materials and Methods
A total of 563 EU CXRs were retrospectively assessed by 3 BCRs, 3 RRs, and 3 EU-experienced NRRs. Suspected pathologies (pleural effusion, pneumothorax, consolidations suspicious for pneumonia, lung lesions) were reported on a 5-step confidence scale (sum of 20,268 reported pathology suspicions [563 images × 9 readers × 4 pathologies]) separately by every involved reader. Board-certified radiologists' confidence scores were converted into 4 binary reference standards (RFSs) of different sensitivities. The RRs' and NRRs' performances were statistically compared with our AI system (trained on nonpublic data from different clinical sites) based on receiver operating characteristics (ROCs) and operating point metrics approximated to the maximum sum of sensitivity and specificity (Youden statistics).

Results
The NRRs lose diagnostic accuracy to RRs with increasingly sensitive BCRs' RFSs for all considered pathologies. Based on our external validation data set, the AI system/NRRs' consensus mimicked the most sensitive BCRs' RFSs with areas under ROC of 0.940/0.837 (pneumothorax), 0.953/0.823 (pleural effusion), and 0.883/0.747 (lung lesions), which were comparable to experienced RRs and significantly overcomes EU-experienced NRRs' diagnostic performance. For consolidation detection, the AI system performed on the NRRs' consensus level (and overcomes each individual NRR) with an area under ROC of 0.847 referenced to the BCRs' most sensitive RFS.

Conclusions
Our AI system matched RRs' performance, meanwhile significantly outperformed NRRs' diagnostic accuracy for most of considered CXR pathologies (pneumothorax, pleural effusion, and lung lesions) and therefore might serve as clinical decision support for NRRs.
An adaptive randomized controlled trial of non-invasive respiratory strategies in acute respiratory failure patients with COVID-19
Authors: Perkins Gavin D , Ji Chen , Connolly Bronwen A , Couper Keith , Lall Ranjit , Baillie J Kenneth , Bradley Judy M , Dark Paul , Dave Chirag , De Soyza Anthony , Dennis Anna V , Devrell Anne , Fairbairn Sara , Ghani Hakim , Gorman Ellen A , Green Christopher A , Hart Nicholas , Hee Siew Wan , Kimbley Zoe , Madathil Shyam , McGowan Nicola , Messer Benjamin , Naisbitt Jay , Norman Chloe , Parekh Dhruv , Parkin Emma M , Patel Jaimin , Regan Scott E , Ross Clare , Rostron Anthony J , Saim Mohammad , Simonds Anita K , Skilton Emma , Stallard Nigel , Steiner Michael , Vancheeswaran Rama , Yeung Joyce , McAuley Daniel F 
Published: August 2021

ABSTRACTBackgroundBoth continuous positive airway pressure (CPAP) and high-flow nasal oxygenation (HFNO) have been recommended for acute respiratory failure in COVID-19. However, uncertainty exists regarding effectiveness and safety.MethodsIn the Recovery-Respiratory Support multi-center, three-arm, open-label, adaptive, randomized controlled trial, adult hospitalized patients with acute respiratory failure due to COVID-19, deemed suitable for treatment escalation, were randomly assigned to receive CPAP, HFNO, or conventional oxygen therapy. Comparisons were made between each intervention and conventional oxygen therapy. The primary outcome was a composite of tracheal intubation or mortality within 30-days.ResultsOver 13-months, 1272 participants were randomized and included in the analysis (380 (29.9%) CPAP; 417 (32.8%) HFNO; 475 (37.3%) conventional oxygen therapy). The need for tracheal intubation or mortality within 30-days was lower in the CPAP group (CPAP 137 of 377 participants (36.3%) vs conventional oxygen therapy 158 of 356 participants (44.4%); unadjusted odds ratio 0.72; 95% CI 0.53 to 0.96, P=0.03). There was no difference between HFNO and conventional oxygen therapy (HFNO 184 of 414 participants (44.4%) vs conventional oxygen therapy 166 of 368 participants (45.1%); unadjusted odds ratio 0.97; 95% CI 0.73 to 1.29, P=0.85).ConclusionsCPAP, compared with conventional oxygen therapy, reduced the composite outcome of intubation or death within 30 days of randomisation in hospitalized adults with acute respiratory failure due to COVID-19. There was no effect observed, compared with conventional oxygen therapy, with the use of HFNO.(Funded by the UK National Institute for Health Research;ISRCTN 16912075).
Evolutionary origin of sex differentiation system in insects
Authors: Chikami Yasuhiko , Okuno Miki , Toyoda Atsushi , Itoh Takehiko , Niimi Teruyuki 
Published: August 2021

AbstractThe evolution of the functionality of genes and genetic systems is a major source of animal diversity. Its best example is insect sex differentiation systems: promoting male and female differentiation (dual-functionality) or only male differentiation (single-functionality). However, the evolutionary origin of such functional diversity is largely unknown. Here, we investigate the ancestral functions ofdoublesex, a key factor of insect sex differentiation system, using the apterygote insect,Thermobia domestica, and reveal that itsdoublesexis essential for only males at the phenotypic level, but contributes to promoting female-specificvitellogeninexpression in females. This functional discordance between the phenotypic and transcription-regulatory levels inT. domesticashows a new type of functionality of animal sex differentiation systems. Then, we examine how the sex differentiation system transited from the single-functionality to the dual-functionality in phenotypes and uncover that a conserved female-specific motif ofdoublesexis detected in taxa with the dual-functionaldoublesex. It is estimated that the role of the sex differentiation system for female phenotypes may have evolved through accumulating mutations in the protein motif structures that led to the enhancement of its transcription-regulatory function.
Effect of electrical hybrid-frequency waterbath stunning on the spontaneous electroencephalogram (EEG) and electrocardiogram (ECG) of broilers
Authors: La Vega L.T , Sato D , Piza L. V , Costa E. J. X 
Published: August 2021

ABSTRACTConcerns about animal welfare and meat quality have encouraged research on new methods for the stunning of broilers during animal slaughter. In this study, the electroencephalogram (EEG) and electrocardiogram (ECG) of broilers were acquired during stunning using an electrical hybrid instead of a single frequency. Considering a square-wave with a current of 220 mA and a frequency of 1100 Hz (duty-cycle 50%), the hybrid-frequency waveform is obtained generating pulses at 6600 Hertz in the pulse-width phase. Sixty broilers aged 42 days were randomly sampled; thirty were used for EEG measurement and thirty for ECG measurement. For EEG measurements, the birds’ scalps were anaesthetized, and EEG electrode needles were inserted on the subcutaneous part of the occipital scalp. For ECG, the non-invasive surface electrode was used. The electrodes were connected to a digital EEG/ECG system. The results showed that the hybrid-frequency waveform system generated epileptic forms in the birds’ EEGs. Therefore, a hybrid-frequency system may present better carcass quality results, while preserving the birds’ welfare, when compared with a single frequency system use.
Estimating the number of symptomatic SARS-CoV-2 infections among vaccinated individuals in the United States—January–April, 2021
Authors: Kugeler Kiersten J. , Williamson John , Curns Aaron T. , Healy Jessica M. , Nolen Leisha D. , Clark Thomas A. , Martin Stacey W. , Fischer Marc 
Published: August 2021

AbstractAs of March 2021, three COVID-19 vaccines have been authorized by the U.S. Food and Drug Administration (FDA) for use in the United States. Each has substantial efficacy in preventing COVID-19. However, as efficacy from trials was <100% for all three vaccines, disease in vaccinated people is expected to occur. We created a spreadsheet-based tool to estimate the number of symptomatic vaccine breakthrough infections based on published vaccine efficacy (VE) data, percent of the population that has been fully vaccinated, and average number of COVID-19 cases reported per day. We estimate that approximately 51,000 symptomatic vaccine breakthrough infections (95% CI: ∼48,000–55,000 cases) occurred in the United States during January–April 2021 among >77 million fully vaccinated people, reflecting <0.5% of COVID-19 cases that occurred during that time. With ongoing SARS-CoV-2 transmission and increasing numbers of people vaccinated in the United States, vaccine breakthrough infections will continue to accumulate before population immunity is sufficient to interrupt transmission. Understanding expectations regarding number of vaccine breakthrough infections enables accurate public health messaging to help ensure that the occurrence of such cases does not negatively affect vaccine perceptions, confidence, and uptake.
High-risk alcohol consumption may increase the risk of SARS-CoV-2 seroconversion: a prospective seroepidemiologic cohort study among American college students
Authors: Kianersi Sina , Ludema Christina , Macy Jonathan T. , Chen Chen , Rosenberg Molly 
Published: August 2021

AbstractAimsTo estimate the associations between high-risk alcohol consumption and (1) SARS-CoV-2 seroconversion, (2) self-reported new SARS-CoV-2 infection, and (3) symptomatic COVID-19.DesignProspective cohortSettingIndiana University Bloomington (IUB), a public university of 34,660 students in southern Indiana.ParticipantsAt the beginning of the fall 2020 semester, we randomly sampled N=1,267 IU undergraduate students, aged 18 years or older and residing in Monroe County, IN.MeasurementsPrimary exposure was high-risk alcohol consumption measured with the AUDIT questionnaire. We used an AUDIT score of 8 or more as the cut-off score when detecting high-risk alcohol consumption. Primary outcome was SARS-CoV-2 seroconversion, assessed with two SARS-CoV-2 antibody tests, at baseline and endline. Secondary outcomes were a) self-reported new SARS-CoV-2 infection at the study endline, and b) self-reported symptomatic COVID-19 at baseline.FindingsPrevalence of high-risk alcohol consumption was 34%. We found that students with high-risk alcohol consumption status had 2.34 [95% CI: (1.29, 4.24)] times the risk of SARS-CoV-2 seroconversion and 1.89 [95% CI: (1.08, 3.32)] times the risk of self-reporting a positive SARS-CoV-2 infection, compared to students with no such risk. Moreover, students with high-risk alcohol consumption were 18% more likely to develop symptomatic COVID-19, though this association was not statistically significant. Similar results were found after adjusting for sex at birth, race, and year in school. Findings from sensitivity analyses corroborated these results and suggested potential for a dose-response relationship.ConclusionsIn this sample of American college students, high-risk alcohol consumption was associated with higher risk for SARS-CoV-2 seroconversion/infection. These findings could have implications for colleges’ reopening planning in fall 2021.
The symptomatology of fever: a step towards qualitative definition of fever
Authors: Kapoor Mayank , Kumar Nitin , Panda Prasan Kumar 
Published: August 2021

AbstractBackgroundThe old definitions of fever are based on cross-sectional surveys of the population without analyzing the associated symptomatology.ObjectivesTo analyze associated symptoms with fever in a longitudinal follow-up study.MethodsIn a longitudinal study over one year, 196 participants recorded three temperature readings daily, one after waking up, one between 12-3 PM, one before sleeping, and filled the symptomatology questionnaire in a thermometry diary.ResultsPer protocol analysis was done for febrile participants (n=144). Fatigue (50.3%), warmth (47.3%), headache/head heaviness (47.0%), feeling malaise/general weakness (46.7%), loss of appetite (46.5%), muscle cramps/muscle aches (45.6%), chills/shivering (44.6%), increased sweating (43.0%), nausea (42.5%), irritability (38.9%), increased breathing rate (37.1%), and restlessness/anxiety/palpitations (36.5%) were the symptoms maximally seen during the febrile phase. A higher number of associated symptoms are associated with higher temperature readings. Dehydration suggested the numerically highest temperature values (100.86 ± 1.70°F) but seen in few febrile patients.ConclusionsIncorporation of symptom analysis in febrile patients is the need of the hour. Fatigue and warmth are found to be most prevelent symptoms during febrile phase. Associated symptoms can help in predicting the intensity of fever also.
Increasing Numbers of Non-communicable Disease Co-morbidities: Major Risk Factors for Hospitalization among a Cohort of People with HIV and COVID-19 Coinfection
Authors: Virata Michael D. , Shenoi Sheela V. , Ladines-Lim Joseph , Villanueva Merceditas S. , Barakat Lydia A. 
Published: August 2021

AbstractData regarding coronavirus disease (COVID-19) infection complications among people with HIV (PWH) are expanding but sometimes conflicting. This report presents the results of a retrospective review of 103 patients at a single urban academic health center with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The study showed that hospitalization is related to host factors such as age 65 years or older with an increasing number of specific non-communicable disease comorbidities, and not to HIV-attributable factors.
Identifying robust functional modules using three-body correlations in Escherichia coli
Authors: Chen Tianlong , Singh Pramesh , Bassler Kevin E. 
Published: August 2021

AbstractUnderstanding the underlying structure of a gene regulatory network is crucial to understand the biological functions of genes or groups of genes. A common strategy to investigate it is to find community structure of these networks. However, methods of finding these communities are often sensitive to noise in the gene expression data and the inherent stochasticity of the community detection algorithms. Here we introduce an approach for identifying functional groups and their hierarchical organization in gene co-expression networks from expression data. A network describing the relatedness in the expression profiles of genes is first inferred using an information theoretic approach. Community structure within the inferred network is found by using modularity maximization. This community structure is further refined using three-body structural correlations to robustly identify important functional gene communities. We apply this approach to the expression data of Escherichia coli genes and identify 25 robust groups, many of which show key associations with important biological functions as demonstrated by Gene Ontology (GO) term enrichment analysis. Thus, our approach makes specific and novel predictions about the function of these genes.
Using single-cell models to predict the functionality of synthetic circuits at the population scale
Authors: Aditya Chetan , Bertaux François , Batt Gregory , Ruess Jakob 
Published: August 2021

AbstractMathematical modeling has become a major tool to guide the characterization and synthetic construction of cellular processes. However, models typically lose their capacity to explain or predict experimental outcomes as soon as any, even minor, modification of the studied system or its operating conditions is implemented. This limits our capacity to fully comprehend the functioning of natural biological processes and is a major roadblock for the de novo design of complex synthetic circuits. Here, using a specifically constructed yeast optogenetic differentiation system as an example, we show that a simple deterministic model can explain system dynamics in given conditions but loses validity when modifications to the system are made. On the other hand, deploying theory from stochastic chemical kinetics and developing models of the system’s components that simultaneously track single-cell and population processes allows us to quantitatively predict emerging dynamics of the system without any adjustment of model parameters. We conclude that carefully characterizing the dynamics of cell-to-cell variability using appropriate modeling theory may allow one to unravel the complex interplay of stochastic single-cell and population processes and to predict the functionality of composed synthetic circuits in growing populations before the circuit is constructed.
Evolutionary flexibility in routes to mat formation by Pseudomonas
Authors: Mukherjee Anuradha , Gallie Jenna 
Published: August 2021

ABSTRACTMany bacteria form mats at the air-liquid interface of static microcosms. These structures typically involve the secretion of exopolysaccharide(s), the production of which is often controlled by the secondary messenger c-di-GMP. Mechanisms of mat formation have been particularly well characterized in Pseudomonas fluorescens SBW25; mutations that lead to an increase in c-di-GMP production by diguanylate cyclases (WspR, AwsR, or MwsR) result in the secretion of cellulose, and mat formation. Here, we characterize and compare mat formation in two close relatives of SBW25: Pseudomonas simiae PICF7 and Pseudomonas fluorescens A506. We find that PICF7 – the strain more closely related to SBW25 – can form mats through mutations affecting the activity of the same three diguanylate cyclases as SBW25. However, instead of cellulose, these mutations activate the production of the Pel exopolysaccharide. We also provide evidence for at least two further – as yet uncharacterized – routes to PICF7 mat formation. P. fluorescens A506, while retaining the same mutational routes to mat formation as SBW25 and PICF7, forms mats by a semi-heritable mechanism that likely culminates in Pga and/or Psl production. Overall, our results demonstrate a high level of evolutionary flexibility in the molecular and structural routes to mat formation, even among close relatives.
Evolution of functional diversity in the holozoan tyrosine kinome
Authors: Yeung Wayland , Kwon Annie , Taujale Rahil , Bunn Claire , Venkat Aarya , Kannan Natarajan 
Published: August 2021

AbstractThe emergence of multicellularity is strongly correlated with the expansion of tyrosine kinases, a conserved family of signaling enzymes that regulates pathways essential for cell-to-cell communication. Although tyrosine kinases have been classified from several model organisms, a molecular-level understanding of tyrosine kinase evolution across all holozoans is currently lacking. Using a hierarchical sequence constraint-based classification of diverse holozoan tyrosine kinases, we construct a new phylogenetic tree that identifies two ancient clades of cytoplasmic and receptor tyrosine kinases separated by the presence of an extended insert segment in the kinase domain connecting the D and E helices. Present in nearly all receptor tyrosine kinases, this fast-evolving insertion imparts diverse functionalities such as post-translational modification sites and regulatory interactions. Eph and EGFR receptor tyrosine kinases are two exceptions which lack this insert, each forming an independent lineage characterized by unique functional features. We also identify common constraints shared across multiple tyrosine kinase families which warrant the designation of three new subgroups: Src Module (SrcM), Insulin Receptor Kinase-Like (IRKL), and Fibroblast, Platelet-derived, Vascular, and growth factor Receptors (FPVR). Subgroup-specific constraints reflect shared autoinhibitory interactions involved in kinase conformational regulation. Conservation analyses describe how diverse tyrosine kinase signaling functions arose through the addition of family-specific motifs upon subgroup-specific features and co-evolving protein domains. We propose the oldest tyrosine kinases, IRKL, SrcM, and Csk, originated from unicellular pre-metazoans and were co-opted for complex multicellular functions. The increased frequency of oncogenic variants in more recent tyrosine kinases suggests that lineage-specific functionalities are selectively altered in human cancers.