bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychological distress and work and social adjustment in the COVID-19 pandemic: a cross-Country analysis
Authors: Distaso Walter , Nikčević Ana V. , Spada Marcantonio M. 
Published: February 2022

AbstractWe investigate the determinants of several measures of psychological distress and work and social adjustment, using data from a large survey covering six countries and three continents over the COVID-19 pandemic. Our analysis reveals substantial cross-country heterogeneity and identifies a strong effect of COVID-19 specific measures of distress onto generic ones, but not the other way around. The results confirm the importance of controlling for individual characteristics, which help explain some of the cross-country differences. Finally, they also highlight specific categories of individuals who have recorded extremely high levels of psychological distress.
Non-self RNA rewires IFNβ signaling: A mathematical model of the innate immune response
Authors: Korwek Zbigniew , Czerkies Maciej , Jaruszewicz-Błońska Joanna , Prus Wiktor , Kosiuk Ilona , Kochańczyk Marek , Lipniacki Tomasz 
Published: February 2022

AbstractType I interferons (IFNs) are key coordinators of the innate immune response to viral infection, which through activation of STAT1/2 in bystander cells induce the expression of IFN-stimulated genes (ISGs). The complex system-level mechanisms of IFN signaling are however not well understood. Here, we show that in cells transfected with an analog of viral RNA, poly(I:C), transcriptional activity of STAT1/2 is terminated due to depletion of the interferon β (IFNβ) receptor, IFNAR. Two ISGs, RNase L and PKR, not only hinder replenishment of IFNAR, but also suppress negative regulators of IRF3 and NF-κB, consequently promoting IFNβ transcription. We incorporated these findings into a comprehensive mathematical model of innate immunity. By coupling signaling through the IRF3/NF-κB and STAT1/2 pathways with the activity of RNase L and PKR, the model explains how poly(I:C) switches the transcriptional program from STAT1/2-induced to IRF3/NF-κB-induced, turning IFNβ-responding cells to IFNβ-secreting cells.One-sentence summaryA computational model explains how non-self RNA turns cells from IFNβ- responders to IFNβ-producers.
Determining the Origins of Repeat Trichomonas vaginalis Infections Using Clinical Versus Genotype-Informed Criteria
Authors: Larkin Heather , Bradic Martina , Schmidt Norine , Martin David H. , Carlton Jane M. , Kissinger Patricia J. 
Published: February 2022

AbstractBackgroundHigh rates of repeat infections post-treatment are reported in women infected with Trichomonas vaginalis (TV). Determining the origin of repeat infections is generally limited to clinical queries of adherence to treatment and sexual exposure. The purpose of this study was to add micro-satellite (MS) genotype data to classification criteria for origin of repeat TV infection, and examine if the addition of TV genotype changes classification as treatment failure, re-infection, or new infectionMethodsWomen were enrolled at clinics in Birmingham, AL; Jackson, MS; and New Orleans, LA as part of a randomized clinical trial comparing single-dose (2 g) and multi-dose (500 mg twice daily x 7 days) metronidazole (MTZ) treatment regimens. Participants provided vaginal swabs and completed a behavioral audio-computer assisted self-interview (ACASI). TV specimens were genotyped at 11 microsatellite (MS) loci. Women with repeat TV infections at TOC, were classified as treatment failure, re-infection or new infections using behavioral and genotype data; classifications were compared.ResultsData were available for 45 women. Genotype concordance was defined as <4 MS loci different and genotype discordance was defined as ≥ 4 MS loci different. Clinical criteria vs. genotype-informed criteria classifications were treatment failure (66.7% vs 64.4%) re-infection (26.7% vs. 17.8%) and new infections (6.7% vs. 17.8%) respectively; Bowker’s test of symmetry had Χ2=16.00 p=0.0011, indicating differences in results.ConclusionsThe majority of women, using either criteria, were classified as treatment failure. Clinical assessment may overestimate reinfections and underestimate new infections. Patient counseling should be adapted accordingly.SummaryTo more precisely determine the origin of repeat Trichomonas vaginalis infection, we compared genotype microsatellite size polymorphism data to clinical criteria and found that clinical data overestimated reinfection and underestimated new infections. Patient counselling should consider new partners.
Project Prevent: Assessing the Value of Education-Focused Laws in Reducing Child Sexual Abuse
Authors: Thompson Bradley Merrill , Srivastava Kunal 
Published: February 2022

I.AbstractWe investigated the impact of new state laws requiring or encouraging education on Child Sexual Abuse (“CSA”) in schools. From 2005 through June, 2019, 31 states enacted such laws. By comparing the states with and without those laws using a difference-in-differences calculation, and controlling for changes in population, wages, employment and other relevant CSA laws, we conclude that most likely such laws:
Increased the number of CSA reports made to state departments of child services each year, andDecreased the number of CSA cases that those departments were able to substantiate from the reported cases.
We had hypothesized, however, that effective educational content would cause more reported cases to be substantiated as people learn what to report, but implementation of the new laws apparently instead increased the proportion of unsubstantiated reports of CSA.Our research does not tell us whether that is good or bad. In the best scenario, children are helped, but at the expense of potentially hurting those who are wrongly accused. In another scenario, children and the wrongly accused are hurt. In arguably the worst scenario, child are hurt and perpetrators are helped.We recommend that policymakers support research to learn why the laws are shifting more cases to unsubstantiated. Depending on the answer, the laws may be worthwhile to continue but with a modification to how the reporting is done, creating a new path for reporting troublesome but lawful activity. Such a modification would preserve the benefit to children while avoiding the harm to adults.
Moment-to-moment fluctuations of hemodynamic responses in posterior default mode networks differentially predict level of attentional lapses in adolescents with Attention-Deficit/Hyperactivity Disorder
Authors: Sørensen Lin , Chung Yu Sun , Khadka Sabin , Stevens Michael C. 
Published: February 2022

AbstractBackgroundThe neurobiological underpinnings of the characteristically higher intra-individual variability of reaction times (IIVRT) in patients with ADHD remain poorly understood. The aim of the current study was to characterize the role of the default mode and other canonical brain networks measured by functional magnetic resonance imaging (fMRI) to task performance fluctuations measured by IIVRT. To our knowledge, no prior fMRI study has shown the involvement of posterior default mode network (DMN) in ADHD IIVRT. We expected that moment-to-moment fluctuations in hemodynamic responses in posterior DMN would predict higher IIVRT in ADHD.MethodsAdolescents (12 to 19 years old) with ADHD (n= 55) and healthy controls (n= 55) performed a fMRI Go/NoGo task. Whole-brain independent component analysis (ICA) segregated hemodynamic responses into functional brain networks, then further decomposed into individual trial-specific estimates of hemodynamic response amplitude. Mean and variability metrics of these amplitudes were tested in stepwise linear regression analyses to identify which functional brain networks predicted high IIVRT.ResultsAs hypothesized, variability in hemodynamic responses in posterior DMN regions predicted level of IIVRT. In posterior cingulate cortex this variability predicted higher IIVRT only in ADHD, whereas in precuneus variability in hemodynamic responses predicted lower IIVRT. Average hemodynamic responses in a bilateral superior temporal cortex network predicted higher IIVRT only in ADHD.ConclusionOur findings suggest that estimating variability in hemodynamic responses is crucial to understand the involvement of the intrinsic default mode in attentional lapses in ADHD. The parcellation into subnetworks showed the differentiating role of default mode in attentional lapses in ADHD.
Designing a Multi-Epitope Vaccine Candidate against Salmonella Typhi Using Immunoinformatics Approach
Authors: Sirajee Ahmad Salman , Ahsan Sunjukta 
Published: February 2022

AbstractSalmonella enterica subsp. enterica serovar Typhi (Salmonella Typhi) is the causative agent of typhoid. A large population living in developing and under-developed countries are mainly susceptible to the infection of this pathogen. The use of an effective vaccine targeting the highest-risk populations could be an extremely useful approach in the prevention of typhoid. The currently licenced and widely used typhoid conjugate vaccine (Vi-TCV) can promote emergence of Vi antigen negative strains, necessitating the design of alternative vaccine candidates. Vaccine consisting of multiple epitopes from different surface proteins can serve as a solution to this problem. In this study, 10 Salmonella Typhi whole genome sequences were retrieved from NCBI database. From the proteomes of these organisms, epitopes from four surface proteins such as peptidoglycan-associated lipoprotein (Accession No. AYU85048.1), outer membrane protein S1 (Accession No. AYU86170.1), outer membrane protein F (Accession No. AYU85220.1 and outer membrane porin L (Accession No. AYU87629.1) returned better results than some other surface proteins in terms of antigenicity, promiscuity to interact with MHC alleles, non-allergenicity, non-similarity with human proteins, conservation and population coverage. These epitopes were joined together using suitable adjuvant and linkers, resulting in a vaccine candidate comprising 201 amino acids. This multi epitope vaccine candidate exhibited promising results in molecular docking, molecular dynamics simulation and immune simulation. BLAST search revealed that the chosen epitopes for vaccine development against Salmonella Typhi are 100% identical with corresponding epitopes of Salmonella Paratyphi A, Salmonella Typhimurium and Salmonella Enteritidis, indicating that the proposed vaccine might give cross protection against major Salmonella pathogenic serovars. The prospective results in this dry laboratory work demonstrates potential positive outcomes in the future for in vivo animal model testing and clinical analyses.
Nanoparticle-delivered TLR4 and RIG-I agonists enhance immune response to SARS-CoV-2 subunit vaccine
Authors: Atalis Alexandra , Keenum Mark C , Pandey Bhawana , Beach Alexander , Pradhan Pallab , Vantucci Casey , Jain Ritika , Hosten Justin , Smith Clinton , Kramer Liana , Jimenez Angela , Ochoa Miguel Armenta , Frey David , Roy Krishnendu 
Published: February 2022

ABSTRACTDespite recent success in vaccinating populations against SARS-CoV-2, concerns about immunity duration, continued efficacy against emerging variants, protection from infection and transmission, and worldwide vaccine availability, remain. Although mRNA, pDNA, and viral-vector based vaccines are being administered, no protein subunit-based SARS-CoV-2 vaccine is approved. Molecular adjuvants targeting pathogen-recognition receptors (PRRs) on antigen-presenting cells (APCs) could improve and broaden the efficacy and durability of vaccine responses. Native SARS-CoV-2 infection stimulate various PRRs, including toll-like receptors (TLRs) and retinoic-acid-inducible gene I-like receptors (RIG-I). We hypothesized that targeting the same PRRs using adjuvants on nanoparticles along with a stabilized spike (S) protein antigen could provide broad and efficient immune responses. Formulations targeting TLR4 (MPLA), TLR7/8 (R848), TLR9 (CpG), and RIG-I (PUUC) delivered on degradable polymer-nanoparticles (NPs) were combined with the S1 subunit of S protein and assessed in vitro with isogeneic mixed lymphocyte reactions (iso-MLRs). For in vivo studies, the adjuvanted nanoparticles were combined with stabilized S protein and assessed using intranasal and intramuscular prime-boost vaccination models in mice. Combination NP-adjuvants targeting both TLR and RIG-I (MPLA+PUUC, CpG+PUUC, or R848+PUUC) differentially increased proinflammatory cytokine secretion (IL-1β, IL-12p70, IL-27, IFN-β) by APCs cultured in vitro, and induced differential T cell proliferation. When delivered intranasally, MPLA+PUUC NPs enhanced local CD4+CD44+ activated memory T cell responses while MPLA NPs increased anti-S-protein-specific IgG and IgA in the lung. Following intramuscular delivery, PUUC-carrying NPs induced strong humoral immune responses, characterized by increases in anti-S-protein IgG and neutralizing antibody titers and germinal center B cell populations (GL7+ and BCL6+ B cells). MPLA+PUUC NPs further boosted S-protein-neutralizing antibody titers and T follicular helper cell populations in draining lymph nodes. These results suggest that SARS-CoV-2-mimicking adjuvants and subunit vaccines could lead to robust and unique route-specific adaptive immune responses and may provide additional tools against the pandemic.GRAPHICAL ABSTRACT
Physiological stress responses to non-mimetic model brood parasite eggs: leukocyte profiles and heat-shock protein Hsp70 levels
Authors: Ruiz-Raya Francisco , Abaurrea Teresa , Vigo Ramón , Soler Manuel 
Published: February 2022

AbstractObligate avian brood parasites lay their eggs in the nest of other bird species (hosts). Brood parasitism often imposes severe fitness costs on hosts, which selects for the evolution of effective anti-parasitic defences, such as recognition and rejection of brood parasite eggs. Glucocorticoids have been recently found to mediate host physiological and behavioural adjustments in response to brood parasite eggs; however, it remains unclear whether brood parasitism triggers a general response involving multiple physiological elements. In this study, we experimentally investigated whether a salient brood parasitic stimulus (the presence of a non-mimetic model egg in the nest) causes physiological adjustments in adult Eurasian blackbirds (Turdus merula) at immune (leukocyte profiles) and cellular (heat-shock protein Hsp70 synthesis) level. Also, we explored whether these physiological changes are mediated by variations in corticosterone levels. We found that experimental brood parasitism caused an increase in heterophils and a decrease in lymphocytes, leading to higher H/L ratios in parasitized birds. Nevertheless, we did not find trade-offs between immune function and corticosterone levels. Hsp70 synthesis was not affected by our experimental manipulation. Our findings provide evidence that brood parasite eggs trigger a general stress response in egg-rejecter hosts, including changes in cellular immune profiles.
Stress-Mediated Attenuation of Translation Undermines T Cell Tumor Control
Authors: Riesenberg Brian P. , Hunt Elizabeth G. , Tennant Megan D. , Hurst Katie E. , Andrews Alex M. , Leddy Lee R. , Neskey David M. , Hill Elizabeth G. , Rangel Rivera Guillermo O. , Paulos Chrystal M. , Gao Peng , Thaxton Jessica E. 
Published: February 2022

AbstractProtein synthesis enables cell growth and survival, but the molecular mechanisms through which T cells suppress or maintain protein translation in the stress of solid tumors are unknown. Using mouse models and human tumors we demonstrate that protein translation in T cells is repressed by the solid tumor microenvironment (TME) due to activation of the unfolded protein response (UPR) via phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (p-eIF2α). Given that acute glucose deprivation in T cells exacerbated p-eIF2α, we show that metabolic reprogramming toward glycolytic independence allays the UPR and p-eIF2α, enabling sustained protein translation in T cells in TME stress. UPR mitigation was associated with enhanced degradation of proteins in antitumor T cells, as proteasome inhibition resulted in eIF2α phosphorylation, attenuation of translation, and loss of antitumor efficacy. In contrast, proteasome stimulation relieved translation inhibition, inducing robust T cell tumor control, offering a new therapeutic avenue to fuel the efficacy of tumor immunotherapy.
Fundamental limits of amplification-free CRISPR-Cas12 and Cas13 diagnostics
Authors: Huyke Diego A. , Ramachandran Ashwin , Bashkirov Vladimir I. , Kotseroglou Efthalia K. , Kotseroglou Theofilos , Santiago Juan G. 
Published: February 2022

ABSTRACTInterest in CRISPR diagnostics continues to increase. CRISPR-Cas12 and -Cas13 based detection are particularly interesting as they enable highly specific detection of nucleic acids. The fundamental sensitivity limits of Cas12 and Cas13 enzymes are governed by their kinetic rates and are critical to develop amplification-free assays. However, these kinetic rates remain poorly understood and their reporting has been inconsistent. We here measure kinetic parameters for several enzymes (LbCas12a, AsCas12a, AapCas12b, LwaCas13a and LbuCas13a) and evaluate their limits of detection (LoD) for amplification-free target detection. Collectively, we here present quantitation of enzyme kinetics for 14 gRNAs and nucleic acid targets for a total of 50 sets of kinetic rate parameters and 25 LoDs. Importantly, we also validate the self-consistency our measurements by comparing trends and limiting behaviors with a Michaelis-Menten, trans-cleavage reaction kinetics model. Our measurements reveal that activated Cas12 and Cas13 enzymes exhibit typical trans-cleavage catalytic efficiencies between order 105 and 106 M-1 s-1. Moreover, for assays that use fluorescent reporter molecules (ssDNA and ssRNA) for target detection, we find most CRISPR enzymes have an amplification-free LoD in the picomolar range. We find also that successful detection of target requires cleavage (by activated CRISPR enzyme) of at least ~0.1% of the fluorescent reporter molecules. This fraction of cleaved reporters is required to differentiate signal from background, and we hypothesize that this fraction is largely independent of the detection method (i.e., endpoint vs reaction velocity). Our results provide a map of the feasible application range and highlight areas of improvement for the emerging field of CRISPR diagnostics.
ClustAssess: tools for assessing the robustness of single-cell clustering
Authors: Shahsavari Arash , Munteanu Andi , Mohorianu Irina 
Published: February 2022

AbstractThe transition from bulk to single-cell analyses refocused the computational challenges for high-throughput sequencing data-processing. The core of single-cell pipelines is partitioning cells and assigning cell-identities; extensive consequences derive from this step; generating robust and reproducible outputs is essential. From benchmarking established single-cell pipelines, we observed that clustering results critically depend on algorithmic choices (e.g. method, parameters) and technical details (e.g. random seeds).We presentClustAssess, a suite of tools for quantifying clustering robustness both within and across methods. The tools provide fine-grained information enabling (a) the detection of optimal number of clusters, (b) identification of regions of similarity (and divergence) across methods, (c) a data driven assessment of optimal parameter ranges. The aim is to assist practitioners in evaluating the robustness of cell-identity inference based on the partitioning, and provide information for choosing robust clustering methods and parameters.We illustrate its use on three case studies: a single-cell dataset of in-vivo hematopoietic stem and progenitors (10x Genomics scRNA-seq), in-vitro endoderm differentiation (SMART-seq), and multimodal in-vivo peripheral blood (10x RNA+ATAC). The additional checks offer novel viewpoints on clustering stability, and provide a framework for consistent decision-making on preprocessing, method choice, and parameters for clustering.
The gut bacterial community potentiates Clostridioides difficile infection severity
Authors: Lesniak Nicholas A. , Schubert Alyxandria M. , Flynn Kaitlyn J. , Leslie Jhansi L. , Sinani Hamide , Bergin Ingrid L. , Young Vincent B. , Schloss Patrick D. 
Published: February 2022

AbstractThe severity of Clostridioides difficile infections (CDI) has increased over the last few decades. Patient age, white blood cell count, creatinine levels as well as C. difficile ribotype and toxin genes have been associated with disease severity. However, it is unclear whether there is an association between members of the gut microbiota and disease severity. The gut microbiota is known to interact with C. difficile during infection. Perturbations to the gut microbiota are necessary for C. difficile to colonize the gut. The gut microbiota can inhibit C. difficile colonization through bile acid metabolism, nutrient consumption and bacteriocin production. Here we sought to demonstrate that members of the gut bacterial communities can also contribute to disease severity. We derived diverse gut communities by colonizing germ-free mice with different human fecal communities. The mice were then infected with a single C. difficile ribotype 027 clinical isolate which resulted in moribundity and histopathologic differences. The variation in severity was associated with the human fecal community that the mice received. Generally, bacterial populations with pathogenic potential, such as Escherichia, Helicobacter, and Klebsiella, were associated with more severe outcomes. Bacterial groups associated with fiber degradation, bile acid metabolism and lantibiotic production, such as Anaerostipes and Coprobacillus, were associated with less severe outcomes. These data indicate that, in addition to the host and C. difficile, populations of gut bacteria can influence CDI disease severity.ImportanceClostridioides difficile colonization can be asymptomatic or develop into an infection, ranging in severity from mild diarrhea to toxic megacolon, sepsis, and death. Models that predict severity and guide treatment decisions are based on clinical factors and C. difficile characteristics. Although the gut microbiome plays a role in protecting against CDI, its effect on CDI disease severity is unclear and has not been incorporated into disease severity models. We demonstrated that variation in the microbiome of mice colonized with human feces yielded a range of disease outcomes. These results revealed groups of bacteria associated with both severe and mild C. difficile infection outcomes. Gut bacterial community data from patients with CDI could improve our ability to identify patients at risk of developing more severe disease and improve interventions which target C. difficile and the gut bacteria to reduce host damage.