bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Objective Search for Unrecognized Bias in Validated COVID-19 Prediction Models
Authors: Estiri Hossein , Strasser Zachary H , Rashidian Sina , Klann Jeffery G , Wagholikar Kavishwar B , McCoy Thomas H , Murphy Shawn N 
Published: October 2021

ABSTRACTThe growing recognition of algorithmic bias has spurred discussions about fairness in artificial intelligence (AI) / machine learning (ML) algorithms. The increasing translation of predictive models into clinical practice brings an increased risk of direct harm from algorithmic bias; however, bias remains incompletely measured in many medical AI applications. Using data from over 56 thousand Mass General Brigham (MGB) patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we evaluate unrecognized bias in four AI models developed during the early months of the pandemic in Boston, Massachusetts that predict risks of hospital admission, ICU admission, mechanical ventilation, and death after a SARS-CoV-2 infection purely based on their pre-infection longitudinal medical records.We discuss that while a model can be biased against certain protected groups (i.e., perform worse) in certain tasks, it can be at the same time biased towards another protected group (i.e., perform better). As such, current bias evaluation studies may lack a full depiction of the variable effects of a model on its subpopulations.If the goal is to make a change in a positive way, the underlying roots of bias need to be fully explored in medical AI. Only a holistic evaluation, a diligent search for unrecognized bias, can provide enough information for an unbiased judgment of AI bias that can invigorate follow-up investigations on identifying the underlying roots of bias and ultimately make a change.
Application of Cas12j for Streptomyces editing and cluster activation
Authors: Tan Lee Ling , Heng Elena , Zulkarnain Nadiah , Leong Chung Yan , Ng Veronica , Yang Lay Kien , San Seow Deborah Chwee , Peh Guangrong , Lim Yee Hwee , Lokanand Koduru , Kanagasundaram Yoganathan , Ng Siew Bee , Wong Fong Tian 
Published: October 2021

AbstractIn recent years, CRISPR-Cas toolboxes for Streptomyces editing have rapidly accelerated natural product discovery and engineering. However, Cas efficiencies are also oftentimes strain dependent, subsequently a variety of Cas proteins would allow for flexibility and enable genetic manipulation within a wider range of Streptomyces strains. In this work, we have further expanded the Cas toolbox by presenting the first example of Cas12j mediated editing in Streptomyces sp. A34053. In our study, we have also observed significantly improved editing efficiencies with Acidaminococcus sp. Cas12j compared to Cas12a, Francisella tularensis subsp. novicida U112’s type V-A Cas (FnCpf1).
Double-layered two-directional somatopleural cell migration during chicken body wall development revealed with local fluorescent tissue labeling
Authors: Sakamoto Nobuyuki , Aoyama Hirohiko , Ikegami Koji 
Published: October 2021

AbstractThe ventral body wall is derived from the somatic layer of the lateral plate mesoderm, somatopleure, and somite. The primary ventral body wall is formed as a result of the lateral growth of the somatopleure. The secondary body wall is generated through the migration of somitic cells into the somatopleure. While it is reported that the cervical somatopleural cells migrate caudally to the thoracic region during body wall development, the migration of the thoracic somatopleural cells has not been elucidated. To investigate the migration behavior of the somatopleural cells in the thorax during chicken ventral body wall development, we labeled the thoracic somatopleural cells of one somite wide by DiI labeling or gene transfection of enhanced green fluorescent protein and observed the three-dimensional distribution of the labeled cells with the tissue-clearing technique FRUIT. Our labeling experiments revealed the rostral migration of the somatopleural cells into a deep part of the thoracic body wall in embryonic day 6.5 chickens. For embryonic day 8.5 chickens, these deep migrating somatopleural cells were found around the sternal ribs. Thus, we identified the double-layered two-directional migrating pathways of the somatopleural cells: the rostral migration of the deep somatopleural cells and the lateral migration of the superficial somatopleural cells. Our findings imply that the rostral migration of deep somatopleural cells and the lateral migration of superficial ones might be associated with the developing sternal ribs and the innervation of the thoracic cutaneous nerves, respectively.Mini-abstractDouble-layered two-directional migrations of the somatopleural cells in the thoracic body wall during chicken development were revealed by one-somite-wide labeling of the somatopleure.
Genetic features of antimicrobial drug-susceptible extraintestinal pathogenicEscherichia colipandemic sequence type 95
Authors: Allegretti Yuan Hu , Yamaji Reina , Adams-Sapper Sheila , Riley Lee W 
Published: October 2021

AbstractExtraintestinal pathogenicEscherichia coli(ExPEC) belonging to multilocus sequence type 95 (ST95) is one of the most geographically widespread ExPEC lineages causing bloodstream (BSI) and urinary tract infections (UTI). In contrast to other widespread ExPEC sequence types, a large proportion ST95 strains remains susceptible to all antimicrobial agents used to treat BSI or UTI. We aimed to identify genomic features of ST95 associated with its relatively high drug-susceptible frequency. We analyzed whole genomes of 1749 ST95 isolates, 80 from patients with BSI or UTI in Northern California, and 1669 isolates from the Enterobase database. We first compared whole-genome sequences (WGS) of 887 drug-susceptible strains and 862 strains resistant to one or more drugs (defined genotypically as strains harboring drug-resistance genes annotated in the ResFinder database) to identify genetic features associated with strains devoid of drug-resistance genes. We then conducted a pan-genome-wide association study on human clinical isolates of ST95, which included 553 UTI and BSI ST95 isolates. We found 44 accessory genes to be significantly associated with ST95 strains lacking drug resistance genes. Fifteen of these were not found in any of the WGSs of ST131 ExPEC strains, which are frequently multidrug-resistant. These genes were annotated to encode transporter or transfer systems and DNA repair polymerases. A large proportion of ST95 strains may have evolved to adapt to antibiotic-imposed stresses without acquiring drug-resistance genes.ImportanceDespite the increasing prevalence of antibiotic-resistantEscherichia colistrains that cause urinary tract and bloodstream infections, a major pandemic lineage of extraintestinal pathogenicE. coli(ExPEC) ST95 has a comparatively low frequency of drug resistance. We compared genomes of 1749 ST95 isolates to identify genetic features that may explain why most strains of ST95 resist becoming drug-resistant. Identification of such genomic features could contribute to the development of novel strategies to prevent the spread of antibiotic-resistant genes and devise new measures to control antibiotic-resistant infections.
Evolution of maternal and early zygotic transcript regulation across Drosophila
Authors: Omura Charles S. , Lott Susan E. 
Published: October 2021

AbstractThe complements of mRNAs in early embryonic development are crucial for setting up developmental trajectories across all animals. The earliest stages of development are regulated by mRNAs deposited into the egg by the mother, until the zygote can become competent to transcribe its own genome. Previously, we showed that the set of maternally deposited and early transcribed zygotic mRNAs inDrosophilaare generally conserved across species, but with some notable variation. We also showed that a majority of regulators of these two types of transcripts are shared. In this study, we examine the differences in regulatory motifs associated with maternal deposition and early zygotic transcription across species ofDrosophila. For maternal transcripts, while the regulators are mostly conserved, we find theDrosophila pseudoobscuraspecies subgroup appears to contain numerous novel regulatory motifs unique to these species. These novel motifs are enriched in transposable elements exclusive to this group. As this species group had been previously identified as having an exceptional amount of divergence in early embryonic transcripts, this change in regulation may be responsible. However, transcripts that are present at the maternal stage only in these species are equally enriched in novel (group-specific) and conserved binding sites, so the novel regulation is not the sole cause of regulatory divergence in these species. At the zygotic stage, we observe a wide variety of species-specific motifs. Additionally, at both stages we observe motifs conserved across species having different effects on gene expression in different species, and regulating different sets of genes in different species. By examining changes in motif content across species, we find that changes in motif content alone is generally insufficient to drive gene expression changes across species.
The indoor mycobiome of daycare centers is affected by occupancy and climate
Authors: Estensmo Eva Lena F. , Botnen Synnøve Smebye , Maurice Sundy , Martin-Sanchez Pedro M. , Morgado Luis , Engh Ingeborg Bjorvand , Høiland Klaus , Skrede Inger , Kauserud Håvard 
Published: October 2021

AbstractMany children spend considerable time in daycare centers and may here be influenced by indoor microorganisms, including fungi. In this study, we investigate the indoor mycobiome of 125 daycare centers distributed along strong environmental gradients throughout Norway. Dust samples were collected from doorframes outside and inside buildings using a citizen science sampling approach. Fungal communities in the dust samples were analyzed using DNA metabarcoding of the ITS2 region. We observed a marked difference between the outdoor and indoor mycobiomes. The indoor mycobiome included considerably more yeasts and molds compared to the outdoor samples, with Saccharomyces, Mucor, Malassezia and Penicillium among the most dominant fungal genera. Changes in the indoor fungal richness and composition correlated to numerous variables related to both outdoor and indoor conditions; there was a clear geographic structure in the indoor mycobiome composition that mirrored the outdoor climate, ranging from humid areas in western Norway to drier and colder areas in eastern Norway. Moreover, the number of children in the daycare centers, as well as various building features, influenced the indoor mycobiome composition. We conclude that the indoor mycobiome in Norwegian daycare centers is structured by multiple factors and is dominated by yeasts and molds. This study exemplifies how citizen science sampling enables DNA-based analyses of a high number of samples covering wide geographic areas.ImportanceWith an alarming increase in chronic diseases like childhood asthma and allergies, there is an increased focus on the exposure of young children to indoor biological and chemical air pollutants. Our study of 125 daycares throughout Norway demonstrates that the indoor mycobiome not only reflects co-occurring outdoor fungi but includes a high abundance of yeast and mold fungi with an affinity for indoor environments. A multitude of factors influence the indoor mycobiome in daycares, including building type, inhabitants, as well as the outdoor environment. Many of the detected yeasts and molds are likely associated with the human body, where some have been coupled to allergies and respiratory problems. Our results call for further studies investigating the potential impact of the identified daycare-associated mycobiomes on children health.
Combinatorial viral vector-based and live-attenuated vaccines without an adjuvant to generate broader immune responses to effectively combat pneumonic plague
Authors: Kilgore Paul B. , Sha Jian , Hendrix Emily K. , Motin Vladimir L. , Chopra Ashok K. 
Published: October 2021

AbstractMice immunized with a combination of an adenovirus vector (Ad5-YFV) and live-attenuated (LMA)-based vaccines were evaluated for protective efficacy against pneumonic plague. While the Ad5-YFV vaccine harbors a fusion cassette of three genes encodingYscF,F1, andLcrV, LMA represents a mutant of parentalYersinia pestisCO92 deleted for genes encodingLpp,MsbB, andAil. Ad5-YFV and LMA were either administered simultaneously (1-dose regimen) or 21 days apart in various order and route of administration combinations (2-dose regimen). The 2-dose regimen induced robust immune responses to provide full protection to animals against parental CO92 and its isogenic F1 (CAF-)-deletion mutant challenges during both short- and long-term studies. Mice intranasally (i.n.) immunized with Ad5-YFV first followed by LMA (i.n. or intramuscularly [i.m.]) had higher T- and B-cell proliferative responses and LcrV antibody titers than those in mice vaccinated with LMA (i.n. or i.m.) first ahead of Ad5-YFV (i.n.) during the long-term study. Specifically, the needle- and adjuvant-free vaccine combination (i.n.) is ideal for use in plague endemic regions. Conversely, with a 1-dose regimen, mice vaccinated with Ad5-YFV i.n. and LMA by the i.m. route provided complete protection to animals against CO92 and its CAF-mutant challenges, and elicited Th1/Th2, as well as Th17 responses, thus suitable for emergency vaccination during a plague outbreak or bioterrorist attack. This is a first study in which a viral vector-based and live-attenuated vaccines were effectively used in combination representing adjuvant- and/or needle- free immunization, with each vaccine triggering a distinct cellular immune response.ImportanceYersinia pestis, the causative agent of plague, is a Tier-1 select agent and a re-emerging human pathogen. A 2017 outbreak in Madagascar with >75% of cases being pneumonic and 8.6% causalities emphasized the importance of the disease. The World Health Organization has indicated an urgent need to develop new generation subunit and live-attenuated plague vaccines. We have developed a subunit vaccine including three components (YscF,F1, and LcrV) using an adenovirus platform (Ad5-YFV). In addition, we have deleted virulence genes ofY. pestis(e.g., lpp,msbB, andail) to develop a live-attenuated vaccine (LMA). Both of these vaccines generated robust humoral and cellular immunity and were highly efficacious in several animal models. We hypothesized the use of a heterologous prime-boost strategy or administrating both vaccines simultaneously could provide an adjuvant- and/or a needle- free vaccine(s) which have attributes of both vaccines for use in endemic regions and during an emergency situation.
Estimating dengue transmission intensity from serological data: a comparative analysis using mixture and catalytic models
Authors: Cox Victoria , O’Driscoll Megan , Imai Natsuko , Prayitno Ari , Hadinegoro Sri Rezeki , Taurel Anne-Frieda , Coudeville Laurent , Dorigatti Ilaria 
Published: October 2021

AbstractBackgroundDengue virus (DENV) infection is a global health concern of increasing magnitude. To target intervention strategies, accurate estimates of the force of infection (FOI) are necessary. Catalytic models have been widely used to estimate DENV FOI and rely on a binary classification of serostatus as seropositive or seronegative, according to pre-defined antibody thresholds. Previous work has demonstrated the use of thresholds can cause serostatus misclassification and biased estimates. In contrast, mixture models do not rely on thresholds and use the full distribution of antibody titres. To date, there has been limited application of mixture models to estimate DENV FOI.MethodsWe compare the application of mixture models and time-constant and time-varying catalytic models to simulated data and to serological data collected in Vietnam from 2004 to 2009 (N ≥ 2178) and Indonesia in 2014 (N = 3194).ResultsThe simulation study showed greater estimate bias from the time-constant and time-varying catalytic models (FOI bias = 1.3% (0.05%, 4.6%) and 2.3% (0.06%, 7.8%), seroprevalence bias = 3.1% (0.25%, 9.4%) and 2.9% (0.26%, 8.7%), respectively) than from the mixture model (FOI bias = 0.41% (95% CI 0.02%, 2.7%), seroprevalence bias = 0.11% (0.01%, 3.6%)). When applied to real data from Vietnam, the mixture model frequently produced higher FOI and seroprevalence estimates than the catalytic models.ConclusionsOur results suggest mixture models represent valid, potentially less biased, alternatives to catalytic models, which could be particularly useful when estimating FOI and seroprevalence in low transmission settings, where serostatus misclassification tends to be higher.Author summaryCharacterising the transmission intensity of dengue virus in different geographic areas over time is essential to understand who is at greatest risk of infection, and to inform the implementation of interventions, such as vector control and vaccination. It is therefore important to understand how methodological differences and model choice may influence estimates of transmission intensity. We compared the application of catalytic and mixture models to calculate the force of infection (FOI) of dengue virus from antibody titre data. We observed greater bias in FOI estimates obtained from catalytic models than from mixture models in areas where the transmission intensity was low. In high transmission intensity areas, catalytic and mixture models produced consistent estimates. Our results indicate that in low transmission settings, when antibody titre data are available, mixture models could be preferential to estimate dengue virus FOI.
100,000 lumens to treat seasonal affective disorder: A proof of concept RCT of bright, whole-room, all-day (BROAD) light therapy
Authors: Sandkühler Julia Fabienne , Brochhagen Sarah , Rohde Paul , Muscheidt Rosa Clara , Grömer Teja Wolfgang , Müller Helge , Brauner Jan Markus 
Published: October 2021

AbstractBackgroundSeasonal affective disorder (SAD) is common and debilitating. The standard of care includes light therapy provided by a light box; however, this treatment is restrictive and only moderately effective. Advances in LED technology enable lighting solutions that emit vastly more light than traditional light boxes. Here, we assess the feasibility of BROAD (Bright, whole-ROom, All-Day) light therapy and get a first estimate for its potential effectiveness.MethodsPatients were randomly assigned to a treatment for four weeks; either a very brightly illuminated room in their home for at least six hours per day (BROAD light therapy) or 30 minutes in front of a standard 10,000 lux SAD light box. Feasibility was assessed by monitoring recruitment, adherence, and side effects. SAD symptoms were measured at baseline and after two and four weeks, with the Hamilton Depression Rating Scale-Seasonal Affective Disorders 29-items, self-report version.ResultsAll 62 patients who started treatment were available at four-week follow-up and no significant adverse effects were reported. SAD symptoms of both groups improved similarly and considerably, in line with previous results. Exploratory analyses indicate that a higher illuminance (lux) is associated with a larger symptom improvement in the BROAD light therapy group.ConclusionsBROAD light therapy is feasible and seems similarly effective as the standard of care while not confining the participants to 30 minutes in front of a light box. In follow-up trials, BROAD light therapy could be modified for increased illuminance, which would likely improve its effectiveness.
Prevalence and Clinical Profiling of Dysglycemia and HIV infection in Persons with Pulmonary Tuberculosis in Brazil
Authors: Arriaga María B. , Araújo-Pereira Mariana , Barreto-Duarte Beatriz , Sales Caio , Miguez-Pinto João Pedro , Nogueira Evelyn B. , Nogueira Betânia M. F. , Rocha Michael S. , Souza Alexandra B. , Benjamin Aline , de Oliveira Jamile G. , Moreira Adriana S. R. , Queiroz Artur T. L. , Rodrigues Moreno M. S. , Spener-Gomes Renata , Figueiredo Marina C. , Durovni Betina , Cavalcante Solange , Lapa-e-Silva José R. , Kristki Afrânio L. , Cordeiro-Santos Marcelo , Sterling Timothy R. , Rolla Valeria C. , Andrade Bruno B. ,   the RePORT-Brazil consortium
Published: October 2021

AbstractBackgroundThere are scarce data on the prevalence and disease presentation of HIV in patients with tuberculosis (TB) and dysglycemia (diabetes [DM] and prediabetes [PDM]), especially in TB-endemic countries.MethodsWe assessed the baseline epidemiological and clinical characteristics of patients with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort in Brazil (RePORT-Brazil) during 2015-2019. Dysglycemia was defined by elevated glycated hemoglobin and stratified as PDM or DM. Additionally, we used data from TB cases obtained through the Brazilian National Notifiable Diseases Information System (SINAN), during 2015-2019. In SINAN, diagnosis of diabetes was based on self-report. Logistic regression models were performed to test independent associations between HIV, dysglycemia status, and other baseline characteristics in both cohorts.ResultsIn the RePORT-Brazil cohort, the prevalence of DM and of PDM was 23.7% and 37.8%, respectively. Furthermore, the prevalence of HIV was 21.4% in the group of persons with TB-dysglycemia and 20.5% in that of patients with TBDM. In the SINAN cohort, the prevalence of DM was 9.2%, and among the TBDM group the prevalence of HIV was 4.1%. Logistic regressions demonstrated that aging was independently associated with PDM or DM in both the RePORT-Brazil and SINAN cohorts. In RePORT-Brazil, illicit drug use was associated with PDM, whereas a higher body mass index (BMI) was associated with DM occurrence. Of note, HIV was not associated with an increased risk of PDM or DM in patients with pulmonary TB in both cohorts. Moreover, in both cohorts, the TBDM-HIV group presented with a lower proportion of positive sputum smear and a higher frequency of tobacco and alcohol users.ConclusionThere is a high prevalence of dysglycemia in patients with pulmonary TB in Brazil, regardless of the HIV status. This reinforces the idea that DM should be systematically screened in persons with TB. Presence of HIV does not substantially impact clinical presentation in persons with TBDM, although it is associated with more frequent use of recreational drugs and smear negative sputum samples during TB screening.