bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Determinants of Elevated Pathobiological Determination of Atherosclerosis in Youth Risk Score in Perinatally HIV-Infected Adolescents in South Africa
Authors: Mahtab Sana , Frigati Lisa J. , Ntusi Ntobeko A. B. , Nyathi Mothabisi , Asafu-Agyei Nana Akua , Myer Landon , Zar Heather J. , Jao Jennifer 
Published: October 2023

Background:
Youth living with perinatally acquired HIV infection (YLPHIV) are at risk of developing atherosclerotic cardiovascular disease.

Methods:
We determined the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary arteries (CA) and abdominal aorta (AA) risk scores among YLPHIV who are ≥15 years old in Cape Town Adolescent and Antiretroviral Cohort. PDAY score was calculated using non–high-density lipoprotein, high-density lipoprotein cholesterol, hyperglycemia, hypertension, obesity, and smoking; a score ≥1 was considered elevated. HIV viremia was categorized as sustained (SV) = viral load (VL) >50 copies/mL, transient (TV) = mix of VL >50 and ≤50 copies/mL, or sustained-virologic suppression = VL <50 copies/mL throughout the study. Among YLPHIV, logistic models were fit to assess factors associated with elevated PDAY.

Results:
Overall, 218 YLPHIV [median age 16.8 (interquartile range: 15.9–17.8) years, male 47%] were included. Among YLPHIV, 8% (n = 17) had SV, and 54% (n = 118) had TV. Median antiretroviral therapy (ART) duration was 12 (interquartile range: 8–14) years. Among YLPHIV, 30.3% and 18.4% had elevated PDAY for CA and AA, respectively.
Among YLPHIV, SV [adjusted odds ratio (aOR) = 18.4, P < 0.01] and TV (aOR = 2.10, P = 0.04) compared with virologic suppression and ART duration in years (aOR = 1.12, P = 0.03) were associated with elevated CA. Male sex was associated with both elevated CA and AA (aOR = 2.14, P = 0.02, and aOR = 3.43, P = 0.01, respectively) and association of SV with elevated AA (aOR = 3.24, P = 0.09).

Conclusions:
A substantial proportion of YLPHIV have PDAY scores reflecting increased aggregate atherosclerotic risk. Among YLPHIV, viremia, lifetime ART duration, and male sex contribute to this risk, highlighting the importance of HIV control and the need to monitor cardiometabolic health.
The relationship between the number of COVID-19 vaccines and infection with Omicron ACE2 inhibition at 18-months post initial vaccination in an adult cohort of Canadian paramedics
Authors: Yap Justin , Kayda Iryna , Asamoah-Boaheng Michael , Haig Scott , Kirkham Tracy , Cheskes Sheldon , Demers Paul , Goldfarb David , Grunau Brian 
Published: October 2023

The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has rapidly evolved since late 2019, due to highly transmissible Omicron variants. While most Canadian paramedics have received COVID-19 vaccination, the optimal ongoing vaccination strategy is unclear. We investigated neutralizing antibody (NtAb) response against wild-type (WT) Wuhan Hu-1 and Omicron BA.4/5 lineages based on the number of doses and past SARS-CoV-2 infection, at 18 months post initial vaccination (with a Wuhan Hu-1 platform mRNA vaccine [BNT162b2 or mRNA-1273}). Demographic information, previous COVID-19 vaccination, infection history, and blood samples were collected from paramedics 18 months post initial mRNA COVID-19 vaccine dose. Outcome measures were ACE2 percent inhibition against Omicron BA.4/5 and WT antigens. We compared outcomes based on number of vaccine doses (two vs. three) and previous SARS-CoV-2 infection status, using the Mann-Whitney U test. Of 657 participants, the median age was 40 years (IQR 33-50) and 251 (42%) were females. Overall, median percent inhibition to BA.4/5 and WT was 71.61% (IQR 39.44-92.82) and 98.60% (IQR 83.07-99.73), respectively. Those with a past SARS-CoV-2 infection had a higher median percent inhibition to BA.4/5 and WT, when compared to uninfected individuals overall and when stratified by two or three vaccine doses. When comparing two vs. three WT vaccine doses among SARS-CoV-2 negative participants, we did not detect a difference in BA.4/5 percent inhibition, but there was a difference in WT percent inhibition. Among those with previous SARS-CoV-2 infection(s), when comparing two vs. three WT vaccine doses, there was no observed difference between groups. These findings demonstrate that additional Wuhan Hu-1 platform mRNA vaccines did not improve NtAb response to BA.4/5, but prior SARS-CoV-2 infection enhances NtAb response.
Microbial Infection among SARS-COV-2 Infected Patients in a COVID-19 dedicated tertiary care hospital of Bangladesh: a Cross Sectional Study
Authors: Islam A N M Shamsul , Khanam Fahmida , Farhana Nasreen , Choudhury Rafaat , Jahan Naznin Akter , Uddin Mohammad Jamal , Refat Md. Nazmul Hassan , Nasreen Fatima 
Published: October 2023

Objectives: This study aimed to determine patterns of respiratory, blood-borne, and uropathogenic microbial pathogens among SARS-CoV-2 infected patients in a COVID-19 dedicated hospital in Bangladesh.

Design: Cross-sectional study
Setting: In a COVID-19 dedicated tertiary care Hospital, Dhaka, Bangladesh conducted from March to June 2021
Participants: Hospitalized COVID 19 infected patients irrespective of age and sex
Primary and secondary outcome measures: Primary outcome measures were proportion of co-infection in COVID-19 patients and characterization of microbes causing co-infection. Secondary outcome measures were to find out if there is any relation between co-infection and age, co-infection and sex, co-infection and comorbidity.
Interventions: not applicable
Results:
Out of 79 patients, 61% were male, mean age was 49.53 years. Co-infection was seen in 7.7% patients and out of which 5.1% of isolates were from urine sample, followed by 2.6% from blood. Bacteria isolated from urine were Enterococci (2.6%), coagulase negative Staphylococcus CONS (1.3%), and Enterobacter spp. (1.3%). Pseudomonas spp. was found in blood sample. Mixed growth was found in NS and TS with predominant species being Staphylococcus aureus, Streptococcus spp. At the time the data was collected, 55.7% of patients had been given antimicrobials, and 30.4% of patients had been given a single antimicrobial. HBsAg was positive in 1.3% patients. None were anti HCV or Dengue NS1Ag positive.
Conclusion: Microbial infection has been seen to be associated with SARS-CoV-2 infections and is of great value in prescribing antimicrobial and reducing fatal outcomes of hospitalized patients.
NetTCR 2.2 - Improved TCR specificity predictions by combining pan- and peptide-specific training strategies, loss-scaling and integration of sequence similarity
Authors: Jensen Mathias Fynbo , Nielsen Morten 
Published: October 2023

AbstractThe ability to predict binding between peptides presented by the Major Histocompatibility Complex (MHC) class I molecules and T-cell receptors (TCR) is of great interest in areas of vaccine development, cancer treatment and treatment of autoimmune diseases. However, the scarcity of paired-chain data, combined with the bias towards a few well-studied epitopes, has challenged the development of pan-specific machine-learning (ML) models with accurate predictive power towards peptides characterized by little or no TCR data. To deal with this, we here benefit from a larger paired-chain peptide-TCR dataset and explore different ML model architectures and training strategies to better deal with imbalanced data. We show that while simple changes to the architecture and training strategies results in greatly improved performance, particularly for peptides with little available data, predictions on unseen peptides remain challenging, especially for peptides distant to the training peptides. We also demonstrate that ML models can be used to detect potential outliers, and that the removal of such outliers from training further improves the overall performance. Furthermore, we show that a model combining the properties of pan-specific and peptide-specific models achieves improved performance, and that performance can be further improved by integrating similarity-based predictions, especially when a low false positive rate is desirable. Moreover, in the context of the IMMREP 2022 benchmark, this updated modeling framework archived state-of-the-art performance. Finally, we show that combining all these approaches results in acceptable predictive accuracy for peptides characterized with as little as 15 positive TCRs. This observation thus places great promise on rapidly expanding the peptide covering of the current models for predicting TCR specificity. The final NetTCR 2.2 models are available athttps://github.com/mnielLab/NetTCR-2.2, and as a web server athttps://services.healthtech.dtu.dk/services/NetTCR-2.2/.
The NFκBDifis required for behavioral and molecular correlates of sleep homeostasis inDrosophila
Authors: O’Hara Michael K. , Saul Christopher , Handa Arun , Sehgal Amita , Williams Julie A. 
Published: October 2023

AbstractThe nuclear factor binding the κ light chain in B-cells (NFκB) is involved in a wide range of cellular processes including development, growth, innate immunity, and sleep. However, efforts have been limited toward understanding how specific NFκB transcription factors function in sleep.Drosophilafruit flies carry three genes encoding NFκB transcription factors,Dorsal,Dorsal Immunity Factor(Dif), andRelish. We previously found that loss of theRelishgene from fat body suppressed daily nighttime sleep, and abolished infection-induced sleep. Here we show thatDifregulates daily sleep and recovery sleep following prolonged wakefulness. Mutants ofDifshowed reduced daily sleep and suppressed recovery in response to sleep deprivation. Pan-neuronal knockdown ofDifstrongly suppressed daily sleep, indicating that in contrast toRelish,Diffunctions from the central nervous system to regulate sleep.Based on the distribution of aDif-associated GAL4 driver, we hypothesized that its effects on sleep were mediated by the pars intercerebralis (PI). While RNAi knock-down ofDifin the PI reduced daily sleep, it had no effect on the recovery response to sleep deprivation. However, recovery sleep was suppressed when RNAi knock-down ofDifwas distributed across a wider range of neurons. Induction of thenemuri(nur) antimicrobial peptide by sleep deprivation was suppressed inDifmutants and pan-neuronal over-expression ofnuralso suppressed theDifmutant phenotype. Together, these findings indicate thatDiffunctions from brain to targetnemuriand to promote sleep.Statement of SignificanceNFκB transcription factors drive inflammatory processes that underly a multitude of human diseases that are accompanied by sleep disturbance. However, genetic studies in mammals that investigate a function of NFκB in sleep have been limited. Using genetic approaches in theDrosophilafruit fly, we show that theDifNFκB, homologous to theRelfamily of NFκBs in humans, functions from neuronal tissue to regulate daily sleep and to mediate responses to sleep loss. These findings enhance our understanding of the role of a specific NFκB gene in sleep regulation.
Animal Emotions and Consciousness: Researchers’ Perceptions, Biases, and Prospects for Future Progress
Authors: Zipple Matthew N , Hazelwood Caleb , Webster Mackenzie F , Benítez Marcela E 
Published: October 2023

AbstractDo animals have emotions? Scientists and philosophers have long struggled with this question, with debates ranging from whether animals experience an “internal world” to whether we are capable of studying it. Recently, theoretical, and methodological advances have rekindled this debate, yet, it is unclear where the scientific consensus on these topics lies today. To address this gap, we administered a survey of professional animal behavior researchers to assess perceptions regarding (1) the taxonomic distribution of emotions and consciousness in non-human animals, (2) respondents’ confidence in this assessment, and (3) attitudes towards potential for progress and possible pitfalls when addressing these questions. In general, animal behavior researchers (n=100) ascribed emotionality and consciousness to a broad swath of the animal taxa, including non-human primates, other mammals, birds, and cephalopods, with varying degrees of confidence. There was a strong positive relationship between how likely a respondent was to attribute emotions to a given taxa and their confidence in that assessment, with respondents assuming an absence of emotions and consciousness when they were unsure. In addition, respondents’ assessments were shaped by several traits (e.g., advanced cognitive abilities, consciousness) that they also admitted were not necessary for an animal to experience emotions. Ultimately, a large majority of researchers were optimistic that tools either currently exist or will exist in the future to rigorously address these questions (>85%) and that animal behavior, as a field, should do more to encourage emotions research (71%). We discuss implications of our findings for publication bias, ethical considerations, and identify an emergent consensus for the need of a functional definition of emotions to facilitate future work.Significance StatementEmotions and consciousness are fundamental components of human experience—these phenomena are central to our behavior, relationships, and sense of meaning. Whether these experiences are shared by non-human animals has long been a subject of philosophical and scientific debate. In this paper we describe, for the first time, results from a survey of animal behavior researchers regarding their perceptions of these questions and the ability of science to answer them. Researchers ascribe emotions and consciousness to many taxa, and their likelihood of doing was strongly predicted by phylogeny and researchers’ confidence in their answers. We hope these results spur additional interdisciplinary collaboration to rigorously pursue these questions and create a baseline for future comparisons to track scientific attitudes over time.“I have chosen bats instead of wasps or flounders because if one travels too far down the phylogenetic tree, people gradually shed their faith that there is experience there at all”--Thomas Nagel
The Interferon-inducible NAMPT acts as a protein phosphoribosylase to restrict viral infection
Authors: Zhang Shu , Xie Na , Liu Yongzhen , Qin Chao , Savas Ali Can , Wang Ting-Yu , Li Shutong , Rao Youliang , Shambayate Alexandra , Chou Tsui-Fen , Brenner Charles , Huang Canhua , Feng Pinghui 
Published: October 2023

SummaryAs obligate intracellular pathogens, viruses often activate host metabolic enzymes to supply intermediates that support progeny production. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of the salvage NAD+synthesis, is an interferon-inducible protein that inhibits the replication of several RNA and DNA viruses with unknown mechanism. Here we report that NAMPT restricts herpes simplex virus 1 (HSV-1) replication via phosphoribosyl-hydrolase activity toward key viral structural proteins, independent of NAD+synthesis. Deep mining of enriched phosphopeptides of HSV-1-infected cells identified phosphoribosylated viral structural proteins, particularly glycoproteins and tegument proteins. Indeed, NAMPT de-phosphoribosylates viral proteinsin vitroand in cells. Chimeric and recombinant HSV-1 carrying phosphoribosylation-resistant mutations show that phosphoribosylation promotes the incorporation of structural proteins into HSV-1 virions and subsequent virus entry. Moreover, loss of NAMPT renders mice highly susceptible to HSV-1 infection. The work describes a hidden enzyme activity of a metabolic enzyme in viral infection and host defense, offering a system to interrogate roles of phosphoribosylation in metazoans.
Using data-dependent and independent hybrid acquisitions for fast liquid chromatography-based untargeted lipidomics
Authors: Tokiyoshi Kanako , Matsuzawa Yuki , Takahashi Mikiko , Takeda Hiroaki , Hasegawa Mayu , Miyamoto Junki , Tsugawa Hiroshi 
Published: October 2023

ABSTRACTUntargeted lipidomics using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has become an essential technique for large cohort studies. When a fast LC gradient of less than 10 min is used for the rapid screening of lipids, the annotation rate decreases because of the lower coverage of the MS/MS spectra caused by the narrow peak width. We propose a systematic procedure to achieve a high annotation rate in fast LC-based untargeted lipidomics by integrating data-dependent acquisition (DDA), and sequential window acquisition of all theoretical mass spectra data-independent acquisition (SWATH-DIA) techniques with the updated MS-DIAL program. Our strategy uses variable SWATH-DIA methods for quality control (QC) samples, which are a mixture of biological samples analyzed multiple times to correct MS signal drifts. In contrast, biological samples are analyzed using DDA to facilitate the structural elucidation of lipids using the pure spectrum to the maximum extent. We demonstrate our workflow using an 8.6 min LC gradient, where QCs are analyzed using five different SWATH-DIA methods. The results indicated that using both DDA and SWATH-DIA achieves 2.0-fold annotation coverage from publicly available benchmark data obtained by a fast LC-DDA-MS technique and offers 94.5% lipid coverage compared with the benchmark dataset from a 25 min LC gradient. Our study demonstrated that harmonized improvements in the analytical conditions and informatics tools provide a comprehensive lipidome in fast LC-based untargeted lipidomics, not only for large-scale studies but also for small-scale experiments, contributing to both clinical applications and basic biology.
The Distal-Proximal Relationships Among the Human Moonlighting Proteins: Evolutionary hotspots and Darwinian checkpoints
Authors: Nawn Debaleena , Hassan Sk. Sarif , Sil Moumita , Ghosh Ankita , Goswami Arunava , Basu Pallab , Dayhoff Guy W. , Lundstrom Kenneth , Uversky Vladimir N. 
Published: October 2023

AbstractMoonlighting proteins, known for their ability to perform multiple, often unrelated functions within a single polypeptide chain, challenge the traditional “one gene, one protein, one function” paradigm. As organisms evolved, their genomes remained relatively stable in size, but the introduction of post-translational modifications and sub-strategies like protein promiscuity and intrinsic disorder enabled multifunctionality. Enzymes, in particular, exemplify this phenomenon, engaging in unrelated processes alongside their primary catalytic roles. This study employs a systematic, quantitative informatics approach to shed light on human moonlighting protein sequences. Phylogenetic analyses of human moonlighting proteins are presented, elucidating the distal-proximal relationships among these proteins based on sequence-derived quantitative features. The findings unveil the captivating world of human moonlighting proteins, urging further investigations in the emerging field of moonlighting proteomics, with the potential for significant contributions to our understanding of multifunctional proteins and their roles in diverse cellular processes and diseases.
E. coliRecBCD Nuclease Domain Regulates Helicase Activity but not Single Stranded DNA Translocase Activity
Authors: Fazio Nicole , Mersch Kacey N. , Hao Linxuan , Lohman Timothy M. 
Published: October 2023

AbstractMuch is still unknown about the mechanisms by which helicases unwind duplex DNA. Whereas structure-based models describe DNA unwinding as a consequence of mechanically pulling the DNA duplex across a wedge domain in the helicase by the single stranded (ss)DNA translocase activity of the ATPase motors, biochemical data indicate that processive DNA unwinding by theE. coliRecBCD helicase can occur in the absence of ssDNA translocation of the canonical RecB and RecD motors. Here, we present evidence that dsDNA unwinding is not a simple consequence of ssDNA translocation by the RecBCD motors. Using stopped-flow fluorescence approaches, we show that a RecB nuclease domain deletion variant (RecBΔNucCD) unwinds dsDNA at significantly slower rates than RecBCD, while the rate of ssDNA translocation is unaffected. This effect is primarily due to the absence of the nuclease domain and not the absence of the nuclease activity, since a nuclease-dead mutant (RecBD1080ACD), which retains the nuclease domain, showed no significant change in rates of ssDNA translocation or dsDNA unwinding relative to RecBCD on short DNA substrates (≤ 60 base pairs). This indicates that ssDNA translocation is not rate-limiting for DNA unwinding. RecBΔNucCD also initiates unwinding much slower than RecBCD from a blunt-ended DNA, although it binds with higher affinity than RecBCD. RecBΔNucCD also unwinds DNA ∼two-fold slower than RecBCD on long DNA (∼20 kilo base pair) in single molecule optical tweezer experiments, although the rates for RecBD1080ACD unwinding are intermediate between RecBCD and RecBΔNucCD. Surprisingly, significant pauses occur even in the absence ofchi(crossover hotspot instigator) sites. We hypothesize that the nuclease domain influences the rate of DNA base pair melting, rather than DNA translocation, possibly allosterically. Since the rate of DNA unwinding by RecBCD also slows after it recognizes achisequence, RecBΔNucCD may mimic a post-chistate of RecBCD.
Active regulatory elements recruit cohesin to establish cell-specific chromatin domains
Authors: Georgiades Emily , Harrold Caroline L. , Roberts Nigel , Kassouf Mira , Riva Simone G. , Sanders Edward , Francis Helena S. , Blayney Joseph , Oudelaar A. Marieke , Milne Thomas A. , Higgs Douglas R. , Hughes Jim 
Published: October 2023

AbstractAs the structure of the genome is analysed at ever increasing resolution it is becoming clear that there is considerable variation in the 3D chromatin architecture across different cell types. It has been proposed that this may, in part, be due to increased recruitment of cohesin to activated cis-elements (enhancers and promoters) leading to cell-type specific loop extrusion underlying the formation of new subTADs. Here we show that cohesin correlates well with the presence of active enhancers and this varies in an allele-specific manner with the presence or absence of polymorphic enhancers which vary from one individual to another. Using the alpha globin cluster as a model, we show that when all enhancers are removed, peaks of cohesin disappear from these regions and the erythroid specific subTAD is no longer formed. Re-insertion of the major alpha globin enhancer (R2) is associated with the appearance of a new peak of cohesin at the site of insertion. In complementary experiments insertion of R2 into a “neutral” region of the genome recruits cohesin, induces transcription and creates a new large (75kb) erythroid specific domain. Together these findings support the proposal that active enhancers recruit cohesin, stimulate loop extrusion and promote the formation of cell specific subTADs.
On multiple infections by parasites with complex life cycles
Authors: Nguyen Phuong L. , Gokhale Chaitanya S. 
Published: October 2023

AbstractHost manipulation is a common strategy of parasites with complex life cycles. It directly affects predator-prey dynamics in trophically transmitted parasites. Theoretical studies suggest that predation-enhancing manipulation of-ten decimates the prey population, making parasites prone to extinction. Host manipulation, however, can also reduce predation due to conflicting interests when multiple parasites infect a host, which is often neglected in theoretical studies. Misaligned interests of coinfecting parasites can occur due to limited carrying capacity or parasitoid developmental stage. Including this realistic complexity in a mathematical model, the results depart from previous studies substantially. We show that coinfecting multi-trophic parasites can preserve the predator-prey system and themselves through manipulation and reproduction parameters. Our study highlights the necessity of and provides the means for incorporating the reality of multiple parasites and their multi-trophic life cycles into the theory of parasite ecology.