bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution
Authors: Wagner Cassia , Kistler Kathryn E. , Perchetti Garrett A. , Baker Noah , Frisbie Lauren A. , Torres Laura Marcela , Aragona Frank , Yun Cory , Figgins Marlin , Greninger Alexander L. , Cox Alex , Oltean Hanna N. , Roychoudhury Pavitra , Bedford Trevor 
Published: September 2023

AbstractKnockout of the ORF8 protein has repeatedly spread through the global viral population during SARS-CoV-2 evolution. Here we use both regional and global pathogen sequencing to explore the selection pressures underlying its loss. In Washington State, we identified transmission clusters with ORF8 knockout throughout SARS-CoV-2 evolution, not just on novel, high fitness viral backbones. Indeed, ORF8 is truncated more frequently and knockouts circulate for longer than for any other gene. Using a global phylogeny, we find evidence of positive selection to explain this phenomenon: nonsense mutations resulting in shortened protein products occur more frequently and are associated with faster clade growth rates than synonymous mutations in ORF8. Loss of ORF8 is also associated with reduced clinical severity, highlighting the diverse clinical impacts of SARS-CoV-2 evolution.
The High Price of Equity in Pulse Oximetry: A cost evaluation and need for interim solutions
Authors: Dempsey Katelyn , Lindsay Mary , Tcheng James E. , Wong An-Kwok Ian 
Published: September 2023

AbstractImportanceDisparities in pulse oximetry accuracy, disproportionately affecting patients of color, have been associated with serious clinical outcomes. Although many have called for pulse oximetry hardware replacement, the cost associated with this replacement is not known.ObjectiveTo estimate the cost of replacing all pulse oximetry hardware throughout a hospital system.DesignSingle-center survey, 2023SettingSingle center.ParticipantOne academic medical center with three hospitals.Main Outcomes and MeasuresCost of fleet replacement as identified by current day prices for hardware.ResultsNew and used prices for 5,079/5,678 (89.5%) across three hospitals for pulse oximetry devices were found. The average equipment cost to replace pulse oximetry hardware is $15,704.12 per bed. Replacement and integration costs are estimated at $28.5-31.8 million for the entire medical system. Extrapolating these costs to 5,564 hospitals in the United States results in an estimated cost of $14.1 billion.Conclusions and Relevance“Simply replacing” pulse oximetry hardware to address disparities may be neither simple, cheap, or timely. Solutions for addressing pulse oximetry accuracy disparities leveraging current technology may be necessary.Trial RegistrationPro00113724, exemptKey pointsQuestionWhat is the cost and complexity of replacing pulse oximetry technology to improve disparities, both at a single institution and across the US?FindingsIn this observational study of pulse oximetry devices in an academic medical system with three hospitals, new and used prices were found for 5,079/5,678 devices (89.5%), with fleet replacement and integration cost of $28.5-31.8 million and some life cycles extending beyond 18 years. When extrapolated to 5,564 hospitals in the United States, estimated replacement costs are $9.7-$20.1 billion.MeaningThe monetary and time cost of pulse oximetry hardware replacement is substantial, and solutions utilizing current pulse oximetry technology are essential to delivering equitable care to all patients.
Real-time pooled optical screening with single-cell isolation capability
Authors: Karempudi Praneeth , Amselem Elias , Jones Daniel , Khaji Zahra , Tenje Maria , Elf Johan 
Published: September 2023

AbstractIn a pooled optical screen, a genetically diverse library of living cells is imaged and characterised for phenotypic variations without knowing the genotype of the cells. The genotypes are identified in situ after the cells have been fixed or by physical extraction of interesting phenotypes followed by sequencing. Mother-machine microfluidics devices are efficient tools in pooled optical screens since many strains can be imaged in the same field of view, but the throughput is often limited. In this work, we show a method to extract single bacterial cells from a compact 100,000-trap mother-machine-based fluidic device using an optical tweezer. Unlike previous devices, the fluids in our design are routed in 3D to enable fast loading of cells, increased trap density, and faster imaging. We have also developed software that allows real-time analysis of the phenotyping data.
Validity and reliability of a new whole room indirect calorimeter to assess metabolic response to small-calorie loads
Authors: Baugh Mary Elizabeth , Ahrens Monica L. , Hutelin Zach , Stylianos Charlie , Wohlers-Kariesch Erica , Oster Mary E. , Dotson Jon , Moon Jon , Hanlon Alexandra L. , DiFeliceantonio Alexandra G. 
Published: September 2023

AbstractObjectiveTo provide an overview of our whole room indirect calorimeter (WRIC), demonstrate validity and reliability of our WRIC, and explore a novel application of Bayesian hierarchical modeling to assess responses to small carbohydrate loads.MethodsSeven gas infusion studies were performed using a gas blender and profiles designed to mimic resting and postprandial metabolic events to assess WRIC validity. In a crossover design, 16 participants underwent fasting and postprandial measurements, during which they consumed a 75-kcal drink containing sucrose, dextrose, or fructose. Linear mixed effects models were used to compare resting and postprandial metabolic rate (MR) and CO (CO). Bayesian Hierarchical Modeling was also used to model postprandial CO trajectories for each participant and condition.ResultsMean total error in infusions were 1.27 ± 1.16% and 0.42 ± 1.21% for VO2and VCO2respectively, indicating a high level of validity. Mean resting MR was similar across conditions (=1.05 ± 0.03 kcal/min,p=0.82, ICC: 0.91). While MR increased similarly among all conditions (∼13%,p=0.29), postprandial CO parameters were significantly lower for dextrose compared with sucrose or fructose.ConclusionsOur WRIC validation and novel application of statistical methods presented here provide important foundations for new research directions using WRIC.
An Integrated Comparative Genomics, Subtractive Proteomics and Immunoinformatics Framework for the Rational Design of a Pan-SalmonellaMulti-Epitope Vaccine
Authors: Bhattacharjee Arittra , Hosen Md. Rakib , Lamisa Anika Bushra , Ahammad Ishtiaque , Chowdhury Zeshan Mahmud , Jamal Tabassum Binte , Sohag Md. Mehadi Hasan , Hossain Mohammad Uzzal , Das Keshob Chandra , Keya Chaman Ara , Salimullah Md 
Published: September 2023

AbstractSalmonellainfections are a global public health issue due to the high cost of illness surveillance, prevention, and treatment. In this study, we explored the core proteome inSalmonellato design a multi-epitope vaccine through Subtractive Proteomics and immunoinformatics approaches. A total of 2395 core proteins presents in 30 different strains ofSalmonella(reference strain-NZ CP014051) were curated. Utilizing the subtractive proteomics approach on theSalmonellacore proteome, Curlin major subunit A (CsgA) was selected as the vaccine candidate.csgAis a conserved gene that is related with biofilm formation. Immunodominant B and T cell epitopes from CsgA were predicted using numerous immunoinformatics tools. T lymphocyte epitopes had adequate population coverage and their corresponding MHC alleles showed significant binding scores after peptide-protein based molecular docking. Afterward, a multiepitope vaccine was constructed with peptide linkers and Human Beta Defensin-2 (as an adjuvant). The vaccine was found to be highly antigenic, non-toxic, non-allergic, and had physicochemical properties. Additionally, Molecular Dynamics Simulation and Immune Simulation demonstrated that the vaccine can bind with Toll Like Receptor 4 and elicit robust immune response. Usingin vitro,in vivo, and clinical trials, our results would yield a Pan-Salmonellavaccine that will provide protection against variousSalmonellaspecies.
Brain-to-brain coupling forecasts future joint action outcomes
Authors: Markiewicz Roksana , Segaert Katrien , Mazaheri Ali 
Published: September 2023

AbstractIn this study, we investigated whether brain-to-brain coupling patterns could predict performance in a time-estimation task which requires two players to cooperate. The participant pairs, were tasked with synchronising button presses after converging on a shared representation of ’short’, ’medium’, and ’long’ time intervals while utilizing feedback to adjust responses. We employed EEG-hyperscanning and focused on post-feedback brain activity. We found that negative feedback led to increased frontal mid-line theta activity across individuals. Moreover, a correlation in post-feedback theta power between players forecasted failed joint action, while an anti-correlation forecasted success. These findings suggest that temporally coupled feedback related brain activity between two individuals serves as an indicator of redundancy in adjustment of a common goal representation. Additionally, the anti-correlation of this activity reflects cognitive strategic mechanisms that ensure optimal joint action outcomes. Rather than apaired overcompensation, successful cooperation requiresflexible strategic agilityfrom both partners.
Assessing the hydromechanical control of plant growth
Authors: Laplaud Valentin , Muller Elise , Demidova Natalia , Drevensek Stéphanie , Boudaoud Arezki 
Published: September 2023

AbstractMulticellular organisms grow and acquire their shapes through the differential expansion and deformation of their cells. Recent research has addressed the role of cell and tissue mechanical properties in these processes. In plants, it is believed that growth rate is a function of the mechanical stress exerted on the cell wall, the thin polymeric layer surrounding cells, involving an effective viscosity. Nevertheless, recent studies have questioned this view, suggesting that cell wall elasticity sets growth rate or that uptake of water is limiting for plant growth. To assess these issues, we developed a microfluidic device to quantify growth rates, elastic properties, and hydraulic conductivity of individualMarchantia polymorphaplants in a controlled environment with a high throughput. We characterized the effect of osmotic treatment and of abscisic acid on growth and hydromechanical properties. Overall, the instantaneous growth rate of individuals is correlated to both bulk elastic modulus and hydraulic conductivity. Our results are consistent with a framework in which growth rate is determined primarily by elasticity of the wall and its remodelling, and secondarily by hydraulic conductivity. Accordingly, the coupling between chemistry of the cell wall and hydromechanics of the cell appears as key to set growth patterns during morphogenesis.
Mosquito aging modulates the development, virulence and transmission potential of pathogens
Authors: Somé Bernard , Guissou Edwige , Da Dari F. , Richard Quentin , Choisy Marc , Yameogo Koudraogo Bienvenue , Hien Domombabele FdS , Yerbanga Rakiswende S , Ouedraogo Georges Anicet , Dabiré Kounbobr R , Djidjou-Demasse Ramsès , Cohuet Anna , Lefèvre Thierry 
Published: September 2023

AbstractHost age variation is a striking source of heterogeneity that can shape the evolution and transmission dynamic of pathogens. Compared to vertebrate systems, our understanding of the impact of host age on invertebrate-pathogen interactions remains limited. We examined the influence of mosquito age on key life-history traits driving human malaria transmission. Females ofAnopheles coluzzii, a major malaria vector, belonging to three age classes (4, 8, and 12 day-old), were experimentally infected withPlasmodium falciparumfield isolates. Our findings revealed reduced competence in 12-day-old mosquitoes, characterized by lower oocyst/sporozoite rates and intensities compared to younger mosquitoes. Despite shorter median longevities in older age classes, infected 12-day-old mosquitoes exhibited improved survival, suggesting that the infection might act as a fountain of youth for older mosquitoes specifically. The timing of sporozoite appearance in the salivary glands remained consistent across mosquito age classes, with an extrinsic incubation period of approximately 13 days. Integrating these results into an epidemiological model revealed a lower vectorial capacity for older mosquitoes compared to younger ones, albeit still substantial due to extended longevity in the presence of infection. Considering age heterogeneity provides valuable insights for ecological and epidemiological studies, informing targeted control strategies to mitigate pathogen transmission.
Evaluating functional brain organization in individuals and identifying contributions to network overlap
Authors: Bijsterbosch Janine D. , Farahibozorg Seyedeh-Rezvan , Glasser Matthew F. , Van Essen David , Snyder Lawrence H. , Woolrich Mark W. , Smith Stephen M. 
Published: September 2023

AbstractIndividual differences in the spatial organization of resting state networks have received increased attention in recent years. Measures of individual-specific spatial organization of brain networks and overlapping network organization have been linked to important behavioral and clinical traits and are therefore potential biomarker targets for personalized psychiatry approaches. To better understand individual-specific spatial brain organization, this paper addressed three key goals. First, we determined whether it is possible to reliably estimate weighted (non-binarized) resting state network maps using data from only a single individual, while also maintaining maximum spatial correspondence across individuals. Second, we determined the degree of spatial overlap between distinct networks, using test-retest and twin data. Third, we systematically tested multiple hypotheses (spatial mixing, temporal switching, and coupling) as candidate explanations for why networks overlap spatially. To estimate weighted network organization, we adopt the Probabilistic Functional Modes (PROFUMO) algorithm, which implements a Bayesian framework with hemodynamic and connectivity priors to supplement optimization for spatial sparsity/independence. Our findings showed that replicable individual-specific estimates of weighted resting state networks can be derived using high quality fMRI data within individual subjects. Network organization estimates using only data from each individual subject closely resembled group-informed network estimates (which was not explicitly modeled in our individual-specific analyses), suggesting that cross-subject correspondence was largely maintained. Furthermore, our results confirmed the presence of spatial overlap in network organization, which was replicable across sessions within individuals and in monozygotic twin pairs. Intriguingly, our findings provide evidence that network overlap is indicative of linear additive coupling. These results suggest that regions of network overlap concurrently process information from all contributing networks, potentially pointing to the role of overlapping network organization in the integration of information across multiple brain systems.
BaRDIC: robust peak calling for RNA-DNA interaction data
Authors: Mylarshchikov Dmitry E. , Nikolskaya Arina I. , Bogomaz Olesja D. , Zharikova Anastasia A. , Mironov Andrey A. 
Published: September 2023

ABSTRACTChromatin-associated non-coding RNAs play important roles in various cellular processes by targeting genomic loci. Two types of genome-wide NGS experiments exist to detect such targets: “one-to-all”, which focuses on targets of a single RNA, and “all-to-all”, which captures targets of all RNAs in a sample. As with many NGS experiments, they are prone to biases and noise, so it becomes essential to detect “peaks” – specific interactions of an RNA with genomic targets. Here we present BaRDIC – Binomial RNA-DNA Interaction Caller – a tailored method to detect peaks in both types of RNA-DNA interaction data. BaRDIC is the first tool to simultaneously take into account the two most prominent biases in the data: chromatin heterogeneity and distance-dependent decay of interaction frequency. Since RNAs differ in their interaction preferences, BaRDIC adapts peak sizes according to the abundances and contact patterns of individual RNAs. These features enable BaRDIC to make more robust predictions than currently applied peak-calling algorithms and better handle the characteristic sparsity of all-to-all data. BaRDIC package is freely available athttps://github.com/dmitrymyl/BaRDIC.
Falling shoulders ahead: adaptive alien genes are maintained amid vanishing introgression footprint in sea squirts
Authors: Touchard Fanny , Cerqueira Frédérique , Bierne Nicolas , Viard Frédérique 
Published: September 2023

AbstractHuman transport of species across oceans disrupts natural dispersal barriers and facilitates hybridisation between previously allopatric species. The recent introduction of the North Pacific sea squirt,Ciona robusta, into the native range of the North Atlantic sea squirt,C. intestinalis, is a good example of this outcome. Recent studies have revealed an adaptive introgression, in a single chromosomal region, from the introduced into the native species. Here, we monitored this adaptive introgression over time, examining both the frequency of adaptive alien genes at the core and the hitchhiking footprint in the shoulders of the introgression island, by studying a thousandCiona spp.individuals collected in 22 ports of the contact zone, 14 of which were sampled 20 generations apart. For that purpose, we developed a KASP multiplex genotyping approach, which proved effective in identifying native, non-indigenous and hybrid individuals and in detecting introgressed haplotypes. Adaptive alien genes were detected where they had been found 20 generations ago, as well as in some newly sampled ports. The core region of the introgression, where the frequency ofC. robustaalleles is the highest and locally adaptive genes must be, remains stable in both space and time. In contrast, we observed an erosion ofC. robustaancestry tracts in flanking chromosomal shoulders on the edges of the core, consistent with the second phase of a local sweep and a purge of incompatible introgressed alleles. Our study reveals how the shoulders of an adaptive introgression island fall over time after the initial sweep.
A hepatocyte-specific transcriptional program driven by Rela and Stat3 exacerbates experimental colitis in mice by modulating bile synthesis
Authors: Jyotsna  , Sarkar Binayak , Yadav Mohit , Deka Alvina , Markandey Manasvini , Sanyal Priyadarshini , Nagarajan Perumal , Gaikward Nilesh , Ahuja Vineet , Mohanty Debasisa , Basak Soumen , Gokhale Rajesh S 
Published: September 2023

AbstractHepatic factors secreted by the liver promote homeostasis and are pivotal for maintaining the liver-gut axis. Bile acid metabolism is one such example wherein, bile acid synthesis occurs in the liver and its biotransformation happens in the intestine. Dysfunctional interactions between the liver and the intestine stimulate varied pathological outcomes through its bidirectional portal communication. Indeed, aberrant bile acid metabolism has been reported in inflammatory bowel disease (IBD). However, the molecular mechanisms underlying these crosstalks that perpetuate intestinal permeability and inflammation remain obscure. Here, we identify a novel hepatic gene program regulated by Rela and Stat3 that accentuates the inflammation in an acute experimental colitis model. Hepatocyte-specific ablation of Rela and Stat3 reduces the levels of primary bile acids in both the liver and the gut and shows a restricted colitogenic phenotype. On supplementation of chenodeoxycholic acid (CDCA), knock-out mice exhibit enhanced colitis-induced alterations. This study provides persuasive evidence for the development of multi-organ strategies for treating IBD and identifies a hepatocyte-specificrela-stat3network as a promising therapeutic target.
NEUROMETABOLOMIC IMPACTS OF MODELED WILDFIRE SMOKE AND PROTECTIVE BENEFITS OF ANTI-AGING THERAPEUTICS IN AGED FEMALE C57BL/6J MICE
Authors: Scieszka David , Gu Haiwei , Barkley-Levenson Amanda , Barr Ed , Garcia Marcus , Begay Jessica G , Herbert Guy , Bhaskar Kiran , McCormick Mark , Brigman Jonathan , Ottens Andrew , Bleske Barry , Campen Matthew J 
Published: September 2023

ABSTRACTWildland fires have become progressively more extensive over the past 30 years in the US, and now routinely generate smoke that deteriorates air quality for most of the country. We explored the neurometabolomic impact that smoke derived from biomass has on older (18 months) female C57BL/6J mice, both acutely and after 10 weeks of recovery from exposures. Mice (N=6/group) were exposed to wood smoke (WS) 4 hours/day, every other day, for 2 weeks (7 exposures total) to an average concentration of 0.448mg/m3per exposure. One group was euthanized 24 hours after the last exposure. Other groups were then placed on 1 of 4 treatment regimens for 10 weeks after wood smoke exposures: vehicle; resveratrol in chow plus nicotinamide mononucleotide in water (RNMN); senolytics via gavage (dasatanib+quercetin; DQ); or both RNMN with DQ (RNDQ). Among the findings, the aging from 18 months to 21 months was associated with the greatest metabolic shift, including changes in nicotinamide metabolism, with WS exposure effects that were relatively modest. WS caused a reduction in NAD+ within the prefrontal cortex immediately after exposure and a long-term reduction in serotonin that persisted for 10 weeks. The serotonin reductions were corroborated by forced swim tests, which revealed an increased immobility (reduction in motivation) immediately post-exposure and persisted for 10 weeks. RNMN had the most beneficial effects after WS exposure, while RNDQ caused markers of brain aging to be upregulated within WS-exposed mice. Findings highlight the persistent neurometabolomic and behavioral effects of woodsmoke exposure in an aged mouse model.Significance StatementNeurological impacts of wildfire smoke are largely underexplored but include neuroinflammation and metabolic changes. The present study highlights modulation of major metabolites in the prefrontal cortex and behavioral consequences in aged (18 month) female mice that persists 10 weeks after wood smoke exposure ended. Supplements derived from the anti-aging field were able to mitigate much of the woodsmoke effect, especially a combination of resveratrol and nicotinamide mononucleotide.