bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV Linkage to Care and Pre-Exposure Prophylaxis Among Persons in Non–Health Care Sites Who Are Tested for HIV for the First Time, United States, 2019
Authors: Beltrami John , Rao Shubha , Wang Guoshen , Minor Patrick , Dunbar Erica 
Published: September 2022

Context:
The Centers for Disease Control and Prevention recommends that all persons aged 13 to 64 years are tested for human immunodeficiency virus (HIV). However, results from US surveys show that 50% of persons and less had ever tested for HIV.

Program:
The Centers for Disease Control and Prevention annually funds 60 health departments to conduct comprehensive HIV prevention and surveillance activities that include HIV testing.

Implementation:
We selected the 31 health departments with quality data (ie, ≤20% missing or invalid values for variables to verify linkage to HIV medical care and new HIV diagnoses) in 2019. Main outcomes were new HIV diagnoses, linkage, and pre-exposure prophylaxis (PrEP) awareness and referrals. We used SAS 9.4 to conduct descriptive, chi-square, and multivariate regression analyses. Our objectives were to determine outcomes and characteristics of persons in non–health care settings who tested for HIV for the first time.

Evaluation:
Compared with persons who previously tested for HIV, persons who tested for the first time were more likely to be aged 13 to 29 years than aged 30 years and older (62.0% [24 295/39 192] vs 42.1% [61 911/147 087], P < .001) and have a higher percentage of new HIV diagnoses (0.6% [242/39 320] vs 0.5% [667/147 475], P < .001). Among persons who tested for the first time, overall percentages of linkage, PrEP awareness, and PrEP referral were 73.4%, 33.3%, and 30.8%, respectively. Compared with referent groups, persons who tested for the first time in the South and had a new HIV diagnosis were less likely to be linked (adjusted prevalence ratio [aPR] = 0.72, 95% confidence interval [CI]: 0.59-0.89); persons who inject drugs were less likely to be aware of PrEP (aPR = 0.84, 95% CI: 0.77-0.91); and persons in the Northeast were less likely to receive PrEP referrals (aPR = 0.28, 95% CI: 0.26-0.31).

Discussion:
Non–health care sites should consider increasing HIV testing, PrEP awareness, and prompt referrals to PrEP and HIV treatment services for persons who have never previously tested.
Comprehensive Improvement of Cardiology Inpatient Transfers: A Bed-availability Triggered Approach
Authors: Moore Judson A. , Eilers Lindsay F. , Willis Amanda J. , Chance Michael D. , La Salle Julie A. , Delgado Ellen H. , Bien Katie M. , Goldman Jordana R. , Sheth Shreya S. 
Published: September 2022

Introduction:
Patient transfers pose a potential risk during hospitalizations. Structured communication practices are necessary to ensure effective handoffs, but occur amidst competing priorities and constraints. We sought to design and implement a multidisciplinary process to enhance communication between pediatric cardiovascular intensive care unit and cardiology floor teams with a comprehensive approach evaluating efficiency, safety, and culture.

Methods:
We conducted a prospective quality improvement study to enact a bed-availability triggered bedside handoff process. The primary aim was to reduce the time between handoff and unit transfer. Secondary metrics captured the impact on safety (reported safety events, overnight transfers, bounce backs, and I-PASS utilization), efficiency (transfer latency, unnecessary patient handoffs, and cumulative time providers were engaged in handoffs), and culture (team members perceptions of satisfaction, collaboration, and handoff efficiency via survey data).

Results:
Eighty-two preimplementation surveys, 26 stakeholder interviews, and 95 transfers were completed during the preintervention period. During the postintervention period, 145 handoffs were audited. We observed significant reductions in transfer latency, unnecessary handoffs, and cumulative provider handoff time. Overnight transfers decreased, and no negative impact was observed in reported safety events or bouncebacks. Survey results showed a positive impact on collaboration, efficiency, and satisfaction among team members.

Conclusions:
Developing safer handoff practices require a collaborative, structured, and stepwise approach. Advances are attainable in high-volume centers, and comprehensive measurement of change is necessary to ensure a positive impact on the overall patient and provider environment.
Atomistic Simulations and Network-Based Energetic Profiling of Binding and Allostery in the SARS-CoV-2 Spike Omicron BA.1, BA.1.1, BA.2 and BA.3 Subvariant Complexes with the Host Receptor: Revealing Hidden Functional Roles of the Binding Hotspots in Mediating Epistatic Effects and Long-Range Communication with Allosteric Pockets
Authors: Verkhivker Gennady , Agajanian Steve , Kassab Ryan , Krishnan Keerthi 
Published: September 2022

AbstractIn this study, we performed all-atom MD simulations of the RBD-ACE2 complexes for BA.1, BA.1.1, BA.2, an BA.3 Omicron subvariants, conducted a systematic mutational scanning of the RBD-ACE2 binding interfaces and analysis of electrostatic effects. The binding free energy computations of the Omicron RBD-ACE2 complexes and comprehensive examination of the electrostatic interactions quantify the driving forces of binding and provide new insights into energetic mechanisms underlying evolutionary differences between Omicron variants. A systematic mutational scanning of the RBD residues determines the protein stability centers and binding energy hotpots in the Omicron RBD-ACE2 complexes. By employing the ensemble-based global network analysis, we proposed a community-based topological model of the Omicron RBD interactions that characterized functional roles of the Omicron mutational sites in mediating non-additive epistatic effects of mutations. Our findings suggested that non-additive contributions to the binding affinity may be mediated by R493, Y498, and Y501 sites and are greater for the Omicron BA.1.1 and BA.2 complexes that display the strongest ACE2 binding affinity among the Omicron subvariants. A network-centric adaptation model of the reversed allosteric communication is unveiled in this study that established a robust connection between allosteric network hotspots and potential allosteric binding pockets. Using this approach, we demonstrated that mediating centers of long-range interactions could anchor the experimentally validated allosteric binding pockets. Through an array of complementary approaches and proposed models, this comprehensive and multi-faceted computational study revealed and quantified multiple functional roles of the key Omicron mutational site R493, R498 and Y501 acting as binding energy hotspots, drivers of electrostatic interactions as well as mediators of epistatic effects and long-range communications with the allosteric pockets.
DeepVariant calling provides insights into race diversity and its implication for sorghum breeding
Authors: Ruperao Pradeep , Gandham Prasad , Odeny Damaris A , Selvanayagam Sivasubramani , Thirunavukkarasu Nepolean , Das Roma R , Srikanda Manasa , Gandhi Harish , Habyarimana Ephrem , Manyasa Eric , Nebie Baloua , Deshpande Santosh P , Rathore Abhishek 
Published: September 2022

AbstractDue to evolutionary divergence, sorghum race populations exhibit vast genetic and morphological variations. A k-mer-based sorghum race sequence comparison identified the conserved k-mers of all sorghum race accessions and the race-specific genetic signatures identified the gene variability in 10,321 genes (PAVs). To understand the sorghum race structure, diversity and domestication, deep learning-based variant calling approach was employed in a set of genotypic data derived from a diverse panel of 272 sorghum accessions. The data resulted in 1.7 million high-quality genome-wide SNPs and identified selective signature (both positive and negative) regions through a genome-wide scan with different (iHS and XP-EHH) statistical methods. We discovered 2,370 genes associated with selection signatures including 179 selective sweep regions distributed over 10 chromosomes. Localization of these regions undergoing selective pressure with previously reported QTLs and genes revealed that the signatures of selection could be related to the domestication of important agronomic traits such as biomass and plant height. The developed k-mer signatures will be useful in the future to identify the sorghum race and SNP markers assist in plant breeding programs.
Defining antigen targets to dissect vaccinia virus (VACV) and Monkeypox virus (MPXV)-specific T cell responses in humans
Authors: Grifoni Alba , Zhang Yun , Tarke Alison , Sidney John , Rubiro Paul , Reina-Campos Maria , Filaci Gilberto , Dan Jennifer , Scheuermann Richard H. , Sette Alessandro 
Published: September 2022

AbstractThe current Monkeypox virus (MPXV) outbreak in non-endemic countries is raising concern about the pandemic potential of novel orthopoxviruses. Little is known regarding MPXV immunity in the context of MPXV infection or vaccination with Vaccinia-based vaccines (VACV). As with vaccinia, T cells are likely to provide an important contribution to overall immunity to MPXV. Here we leveraged the epitope information available in Immune Epitope Database (IEDB) on VACV to predict potential MPXV targets recognized by CD4+ and CD8+ T cell responses. We found a high degree of conservation between VACV epitopes and MPXV, and defined T cell immunodominant targets. These analyses enabled the design of peptide pools able to experimentally detect VACV-specific T cell responses and MPXV cross-reactive T cells in a cohort of vaccinated individuals. Our findings will facilitate the monitoring of cellular immunity following MPXV infection and vaccination.
A dual function for the chromatin organizer Special A-T rich Binding Protein 1 in B-lineage cells
Authors: Thomas Morgane , Martin Ophélie Alyssa , Bruzeau Charlotte , Pollet Justine , Bender Sébastien , Carrion Claire , Le Noir Sandrine , Pinaud Eric 
Published: September 2022

AbstractSATB1 (Special A-T rich Binding protein 1) is a cell type specific factor involved in chromatin remodelling events that participate in the regulation of the genetic network in developing T cells and neurons. In T cells, SATB1 is a key factor required for lineage commitment, VDJ recombination, development and maturation. In B cells, SATB1 is described as binding to the MARs-Eµ regions of the IgH locus. Considering that its expression varies during differentiation, the involvement of this factor needed to be clarified in B cells. Using a KO mouse model deleting SATB1 from the pro-B cell stage, we were able to examine the consequences of SATB1 deletion in naive and activated B cell subsets. Our model indicates firstly that SATB1 is not essential for B cell development and the establishment of a broad IgH repertoire. Second, we show that this factor exhibits an ambivalent function in mature B cells, acting sequentially as a positive and negative regulator of Ig gene transcription in naive and activated cells, respectively. Third, our study indicates that the negative regulatory function of SATB1 in B cells extends to the germinal center response in which this factor limits somatic hypermutation of Ig genes. This finding suggests that SATB1 may limit the introduction of unwanted mutations into B cells.
Phase separation-based visualization of protein-protein interactions and kinase activities in plants
Authors: Safi Alaeddine , Smagghe Wouter , Gonçalves Amanda , Xu Ke , Fernandez Ana Ibis , Cappe Benjamin , Riquet Franck B. , Mylle Evelien , Van Damme Daniël , Geelen Danny , Jaeger Geert De , Beeckman Tom , Leene Jelle Van , Vanneste Steffen 
Published: September 2022

AbstractProtein activities depend heavily on protein complex formation and dynamic post-translational modifications, such as phosphorylation. Their dynamic nature is notoriously difficult to monitor in planta at cellular resolution, often requiring extensive optimization and high-end microscopy. Here, we generated and exploited the SYnthetic Multivalency in PLants (SYMPL)-vector set to study protein-protein interactions (PPIs) and kinase activities in planta based on phase separation. This technology enabled easy detection of inducible, binary and ternary protein-protein interactions among cytoplasmic, nuclear and plasma membrane proteins in plant cells via a robust image-based readout. Moreover, we applied the SYMPL toolbox to develop an in vivo reporter for SnRK1 kinase activity, allowing us to visualize tissue-specific, dynamic SnRK1 activation upon energy deprivation in stable transgenic Arabidopsis plants. The applications of the SYMPL cloning toolbox lay the foundation for the exploration of PPIs, phosphorylation and other post-translational modifications with unprecedented ease and sensitivity.
Predicting cell population-specific gene expression from genomic sequence
Authors: Michielsen Lieke , Reinders Marcel J.T. , Mahfouz Ahmed 
Published: September 2022

ABSTRACTMost regulatory elements, especially enhancer sequences, are cell population-specific. One could even argue that a distinct set of regulatory elements is what defines a cell population. However, discovering which non-coding regions of the DNA are essential in which context, and as a result, which genes are expressed, is a difficult task. Some computational models tackle this problem by predicting gene expression directly from the genomic sequence. These models are currently limited to predicting bulk measurements and mainly make tissue-specific predictions. Here, we present a model that leverages single-cell RNA-sequencing data to predict gene expression. We show that cell population-specific models outperform tissue-specific models, especially when the expression profile of a cell population and the corresponding tissue are dissimilar. Further, we show that our model can prioritize GWAS variants and learn motifs of transcription factor binding sites. We envision that our model can be useful for delineating cell population-specific regulatory elements.
Proteomic signatures of the serological response to flu vaccination in a large human cohort study
Authors: Wu Shaohuan , Pushalkar Smruti , Maity Shuvadeep , Pressler Matthew , Rendleman Justin , Vitrinel Burcu , Carlock Michael , Ross Ted , Choi Hyungwon , Vogel Christine 
Published: September 2022

AbstractThe serological response to the influenza virus vaccine is highly heterogeneous for reasons that are not entirely clear. While the impact of demographic factors such as age, body mass index (BMI), sex, prior vaccination and titer levels are known to impact seroconversion, they only explain a fraction of the response. To identify signatures of the vaccine response, we quantified 273 proteins from serum samples of 160 flu vaccine recipients (2019-2020 season). We found that levels of proteins functioning in cholesterol transport were positively associated with seroconversion, likely linking to the known impact of BMI. When adjusting seroconversion for the demographic factors, we identified additional, unexpected signatures: proteins regulating actin cytoskeleton dynamics were significantly elevated in participants with high adjusted seroconversion. Viral strain specific analysis showed that this trend was largely driven by the H3N2 strain. Further, we identified complex associations between adjusted seroconversion and other factors: levels of proteins of the complement system associated positively with adjusted seroconversion in younger participants, while they were associated negatively in the older population. We observed the opposite trends for proteins of high density lipoprotein remodeling, transcription, and hemostasis. In sum, careful integrative modeling can extract new signatures of seroconversion from highly variable data that suggest links between the humoral response as well as immune cell communication and migration.
Functional MRS studies of GABA and Glutamate/Glx – a systematic review and meta-analysis
Authors: Pasanta Duanghathai , He Jason L. , Ford Talitha , Oeltzschner Georg , Lythgoe David J. , Puts Nicolaas A. 
Published: September 2022

AbstractFunctional magnetic resonance spectroscopy (fMRS) can be used to investigate neurometabolic responses to external stimuli in-vivo, but findings are inconsistent. We performed a systematic review and meta-analysis on fMRS studies of the primary neurotransmitters Glutamate (Glu), Glx (Glutamate + Glutamine), and GABA. Data were extracted, grouped by metabolite, stimulus domain, and brain region, and analysed by determining standardized effect sizes. The quality of individual studies was rated. When results were analysed by metabolite type small to moderate effect sizes of 0.29-0.47 (p < 0.05) were observed for changes in Glu and Glx regardless of stimulus domain and brain region, but no significant effects were observed for GABA. Further analysis suggests that Glu, Glx and GABA responses differ by stimulus domain or task and vary depending on the time course of stimulation and data acquisition. Here, we establish effect sizes and directionality of GABA, Glu and Glx response in fMRS. This work highlights the importance of standardised reporting and minimal best practice for fMRS research.
Synaptic status differentially regulates neurofilaments in dendritic spines
Authors: Gürth Clara-Marie , do Rego Barros Fernandes Lima Maria Augusta , Cereceda Delgado Angel Rafael , Palacios Victor Macarrón , Hubrich Jasmine , D’Este Elisa 
Published: September 2022

AbstractNeurofilaments are one of the main cytoskeletal components in neurons and they can be found in the form of oligomers at pre- and postsynapses. How their presence is regulated at the postsynapse remains widely unclear. Here we systematically quantified by immunolabeling the occurrence of the neurofilament isoform triplet neurofilament light (NFL), medium (NFM), and heavy (NFH) at the postsynapse with STED nanoscopy together with markers of synaptic strength and activity. Our data shows that within dendritic spines neurofilament isoforms rarely colocalize with each other and that they are present to different extents, with NFL being the most abundant isoform. The amount of the three isoforms correlates with markers of postsynaptic strength and presynaptic activity to varying degrees: while NFL shows moderate correlation to both synaptic traits suggesting its involvement in synaptic response, NFM and NFH were only correlated on a low level. By quantifying the presence of neurofilaments at the postsynapse within the context of the synaptic status, this work sheds new light on the regulation of synaptic neurofilaments and their possible contribution to psychiatric disorders.
What does heritability of Alzheimer’s disease represent?
Authors: Baker Emily , Leonenko Ganna , Schmidt Karl Michael , Hill Matthew , Myers Amanda J. , Shoai Maryam , de Rojas Itziar , Tesi Niccoló , Holstege Henne , van der Flier Wiesje M. , Pijnenburg Yolande A.L. , Ruiz Agustin , Hardy John , van der Lee Sven , Escott-Price Valentina 
Published: September 2022

AbstractINTRODUCTIONBoth Alzheimer’s disease (AD) and ageing have a strong genetic component. In each case, many associated variants have been discovered, but how much missing heritability remains to be discovered is debated. Variability in the estimation of SNP-based heritability could explain the differences in reported heritability.METHODSWe compute heritability in five large independent cohorts (N=7,396, 1,566, 803, 12,528 and 3,963) to determine whether a consensus for the AD heritability estimate can be reached. These cohorts vary by sample size, age of cases and controls and phenotype definition. We compute heritability a) for all SNPs, b) excluding APOE region, c) excluding both APOE and genome-wide association study hit regions, and d) SNPs overlapping a microglia gene-set.RESULTSSNP-based heritability of Alzheimer’s disease is between 38 and 66% when age and genetic disease architecture are correctly accounted for. The heritability estimates decrease by 12% [SD=8%] on average when the APOE region is excluded and an additional 1% [SD=3%] when genome-wide significant regions were removed. A microglia gene-set explains 69-84% of our estimates of SNP-based heritability using only 3% of total SNPs in all cohorts.CONCLUSIONThe heritability of neurodegenerative disorders cannot be represented as a single number, because it is dependent on the ages of cases and controls. Genome-wide association studies pick up a large proportion of total AD heritability when age and genetic architecture are correctly accounted for. Around 13% of SNP-based heritability can be explained by known genetic loci and the remaining heritability likely resides around microglial related genes.Author SummaryEstimates of heritability in Alzheimer’s disease, the proportion of phenotypic variance explained by genetics, are very varied across different studies, therefore, the amount of ‘missing’ heritability not yet captured by current genome-wide association studies is debated. We investigate this in five independent cohorts, provide estimates based on these cohorts and detail necessary suggestions to accurately calculate heritability in age-related disorders. We also confirm the importance of microglia relevant genetic markers in Alzheimer’s disease. This manuscript provides suggestions for other researchers computing heritability in late-onset disorders and the microglia gene-set used in this study will be published alongside this manuscript and made available to other researchers. The correct assessment of disease heritability will aid in better understanding the amount of ‘missing heritability’ in Alzheimer’s disease.