bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single blinded, phase IV, adaptive randomised control trial to evaluate the safety of coadministration of seasonal influenza and COVID-19 vaccines (The FluVID study)
Authors: Ramsay JA , Jones M , Vande More AM , Hunt SL , Williams PCM , Messer M , Wood N , Macartney K , Lee FJ , Britton WJ , Snelling TL , Caterson ID 
Published: June 2023

AbstractObjectivesWe evaluated the frequency of moderate and severe adverse events following coadministration of seasonal influenza vaccine (SIV) versus placebo with COVID-19 vaccines among adults to support practice guidelines.MethodsFluVID is a participant-blinded, phase IV, randomised control trial. On the same day as the participant’s scheduled COVID-19 vaccine, participants were randomised to receive SIV or saline placebo; those assigned placebo at visit one then received SIV a week later, and vice versa. Self-reported adverse events were collected for daily seven days following each visit.The primary endpoint was any solicited adverse event of at least moderate severity occurring up to seven days following receipt of SIV or placebo. This was modelled using a Bayesian logistic regression model. Analyses were performed by COVID-19 vaccine type and dose number.ResultsOverall, 248 participants were enrolled; of these, 195 had received BNT162b2 and 53 had received mRNA1273 COVID-19 vaccines according to national guidelines. After randomisation, 119 were assigned to receive SIV and 129 were assigned to receive placebo at visit one.Adverse events were most frequently reported as mild (grade 1) in nature. Among 142 BNT162b2 booster dose one and 43 BNT162b2 booster dose two recipients, the posterior median risk difference for moderate/severe adverse events following SIV versus placebo was 13% (95% credible interval [CrI] -0.03 to 0.27) and 13% (95%CrI -0.37 to 0.12), respectively. Among 18 mRNA1273 booster dose one and 35 mRNA1273 booster dose two recipients, the posterior median risk difference of moderate/severe adverse events following influenza vaccine versus placebo was 6% (95%CrI -0.29 to 0.41) and -4% (95%CrI -0.30 to 0.23), respectively.ConclusionAdverse events following SIV and COVID-19 co-administration were generally mild and occurred with similar frequency to events following COVID-19 vaccine alone. We found no evidence to justify routine separation of SIV and COVID-19 vaccine doses.Clinical trial registrationACTRN12621001063808HighlightsThe coadministration of mRNA COVID-19 and influenza vaccines typically resulted in mild events that were limited to 4 days.Frequency and nature of adverse events were similar to those in other randomised trials.This trial demonstrates a suitable design for evaluating vaccine schedules and coadministration.
Chronotype changes after sex hormone use: a prospective cohort study in transgender users of gender-affirming hormones
Authors: Morssinkhof Margot W. L. , Zwager Annefleur , Tuuk Karin van der , Heijer Martin den , van der Werf Ysbrand D. , Stenvers Dirk Jan , Broekman Birit F. P. 
Published: June 2023

BackgroundChronotype, an individual’s preferred sleep-wake timing, is influenced by sex and age. Men report a later chronotype than women and age is associated with earlier chronotype. The sex-related changes in chronotype coincide with puberty and menopause. However, the effects of sex hormones on human chronotype remain unclear.AimTo examine the impact of 3 months of gender-affirming hormone therapy (GAHT) on chronotype in transgender persons.MethodsThis study used data from 93 participants from the prospective RESTED cohort, including 49 transmasculine (TM) participants starting testosterone and 44 transfeminine (TF) participants starting estrogens and antiandrogens. Midpoint of sleep and sleep duration were measured using the ultra-short Munich ChronoType Questionnaire (µMCTQ).ResultsAfter 3 months of GAHT, TM participants’ midpoint of sleep increased by 24 minutes (95%CI: 3 to 45), whereas TF participants’ midpoint of sleep decreased by 21 minutes (95%CI: −38 to −4). Total sleep duration did not change significantly in either group.ConclusionThis study provides the first prospective assessment of sex hormone use and chronotype in transgender persons, showing that GAHT can change chronotype in line with cisgender sex differences. These findings provide a basis for future studies on biological mechanisms and clinical consequences of chronotype changes.
Anti-SARS-CoV-2 Antibody Kinetics up to 6 months of follow-up: Result from a Nation-wide Population-based, Age Stratified Sero-Epidemiological Prospective Cohort Study in India
Authors: Misra Puneet , Singh Arvind Kumar , Mishra Baijayantimala , Behera Bijayini , Patro Binod Kumar , Medigeshi Guruprasad R , Joshi Hari Shanker , Ahmad Mohammad , Chaturvedi P K , Chinnakali Palanivel , Haldar Partha , Bairwa Mohan , Kharya Pradeep , Dhodapkar Rahul , Rath Ramashankar , Guleria Randeep , Rai Sanjay K , Kar Sitanshu Sekhar , Kant Shashi , Sarkar Sonali , Baidya Subrata , Meena Suneeta , Mandal Suprakash , Kishore Surekha , Majumder Tapan , Hada Vivek 
Published: June 2023

AbstractRepeated serological testing tells about the change in the overall infection in a community. This study aimed to evaluate changes in antibody prevalence and kinetics in a closed cohort over six months in different sub-populations in India. The study included 10,000 participants from rural and urban areas in five states and measured SARS-CoV-2 antibodies in serum in three follow-up rounds. The overall seroprevalence increased from 73.9% in round one to 90.7% in round two and 92.9% in round three. Among seropositive rural participants in round one, 98.2% remained positive in round two, and this percentage remained stable in urban and tribal areas in round three. The results showed high antibody prevalence that increased over time and was not different based on area, age group, or sex. Vaccinated individuals had higher antibody prevalence, and nearly all participants had antibody positivity for up to six months.
Genomic Sequencing Surveillance and Antigenic Site Mutations of Respiratory Syncytial Virus in Arizona, USA
Authors: Holland LaRinda A. , Holland Steven C. , Smith Matthew F. , Leonard Victoria R. , Murugan Vel , Nordstrom Lora , Mulrow Mary , Salgado Raquel , White Michael , Lim Efrem S. 
Published: June 2023

AbstractWe conducted Respiratory Syncytial Virus (RSV) genomic sequencing surveillance of 100 RSV-A and 27 RSV-B specimens collected between November 2022 and April 2023 in Arizona, USA. We identified mutations in the pre-fusion F protein antigenic sites in both RSV-A and RSV-B. Continued genomic surveillance will be important to ensure RSV vaccine effectiveness.
Multiple imputation strategies for missing event times in a multi-state model analysis
Authors: Curnow E. , Hughes R. A. , Birnie K. , Tilling K. , Crowther M. J. 
Published: June 2023

AbstractIn clinical studies, multi-state model (MSM) analysis is often used to describe the sequence of events that patients experience, enabling better understanding of disease progression. A complicating factor in many MSM studies is that the exact event times may not be known. Motivated by a real dataset of patients who received stem cell transplants, we considered the setting in which some event times were exactly observed and some were missing. In our setting, there was little information about the time intervals in which the missing event times occurred and missingness depended on the event type, given the analysis model covariates. These additional challenges limited the usefulness of some missing data methods (maximum likelihood, complete case analysis, and inverse probability weighting). We show, for the first time in the MSM context, that multiple imputation (MI) of event times can perform well in this setting. MI is a flexible method that can be used with any complete data analysis model. Through an extensive simulation study, we show that MI by predictive mean matching (PMM), in which sampling is from a set of observed times without reliance on a specific parametric distribution, has little bias when event times are missing at random, conditional on the observed data. Applying PMM separately for each sub-group of patients with a different pathway through the MSM tends to further reduce bias and improve precision. We recommend MI using PMM methods when performing MSM analysis with Markov models and partially observed event times.
Health Care Workers Knowledge, Attitudes, and Practice Towards Childhood Tuberculosis in Primary Health Facilities in Lusaka, Zambia
Authors: Kaumba Paul Chabala , Kagujje Mary , Chungu Chalilwe , Nyangu Sarah , Sanjase Nsala , Maimbolwa Minyoi Mubita , Shuma Brian , Chilukutu Lophina , Muyoyeta Monde 
Published: June 2023

AbstractBACKGROUNDZambia is among the countries with high tuberculosis (TB) and Tuberculosis/Human Immunodeficiency Virus (TB/HIV) burdens, with a significant number of cases affecting children. However, a considerable portion of TB cases, especially in children, remains undiagnosed. This study aimed to assess and understand the factors influencing the knowledge, attitudes, and practices of health care workers (HCWs) regarding childhood TB in Zambia.METHODUsing a cross-sectional survey design, a self-administered anonymous questionnaire was employed to evaluate HCWs’ knowledge, attitudes, and practices related to TB. The study was conducted at two primary health facilities in Lusaka, Zambia, between July and August 2020. The questionnaire data collected was later transcribed to an electronic system called DHIS 2.RESULTSOut of 238 participants, the majority (72.3%) were female HCWs. Most staff members across various departments demonstrated awareness of the primary TB symptom, which is coughing. However, approximately half of the participants had limited knowledge regarding the transmission of TB through oral activities such as singing and laughing. Furthermore, the study found that 21.4% of HCWs reported regular interaction with children in their daily work, while 17.2% did not.Among the HCWs, 73.1% referred children to the TB clinic to submit a sputum sample, 55.5% requested a sample from the patient, 55.9% expedited the process for children, 58.4% provided education on cough etiquette, and 42.4% recorded the child in the presumptive TB register. Only a negligible 0.8% of HCWs did not take any action for children exhibiting TB symptoms.CONCLUSIONThe study highlighted variations in knowledge levels based on gender, department, and training history among the HCWs. Those working in the TB department generally exhibited better knowledge and attitudes regarding TB, with a 50/50% variation. Therefore, it is crucial to enhance the TB knowledge, attitudes, and practices of female HCWs, who constitute most staff involved in TB diagnosis and treatment.This study emphasizes the importance of improving the understanding of childhood TB among HCWs, particularly among female staff. Enhancing their knowledge and attitudes towards TB will contribute to early diagnosis and improved management of TB cases, ultimately reducing the burden of childhood TB in Zambia.
Maternal, placental and fetal response to a non-viral, polymeric nanoparticle gene therapy in nonhuman primates
Authors: Wilson Rebecca L. , Kropp Schmidt Jenna , Davenport Baylea N. , Ren Emily , Keding Logan T. , Shaw Sarah A. , Schotzko Michele L. , Antony Kathleen M. , Simmons Heather A. , Golos Thaddeus G. , Jones Helen N. 
Published: June 2023

BackgroundCurrently, there are no placenta-targeted treatments to alter thein uteroenvironment. Water-soluble polymers have a distinguished record of clinical relevance outside of pregnancy. We have demonstrated the effective delivery of polymer-based nanoparticles containing a non-viral humaninsulin-like 1 growth factor(IGF1) transgene to correct placental insufficiency in small animal models of fetal growth restriction (FGR). Our goal was to extend these studies to the pregnant nonhuman primate (NHP) and assess maternal, placental and fetal responses to nanoparticle-mediatedIGF1treatment.MethodsPregnant macaques underwent ultrasound-guided intraplacental injections of nanoparticles (GFP-orIGF1-expressing plasmid under the control of the trophoblast-specificPLAC1promoter complexed with a HPMA-DMEAMA co-polymer) at approximately gestational day 100 (term = 165 days). Fetectomy was performed 24 h (GFP; n =1), 48 h (IGF1; n = 3) or 10 days (IGF1; n = 3) after nanoparticle delivery. Routine pathological assessment was performed on biopsied maternal tissues, and placental and fetal tissues. Maternal blood was analyzed for complete blood count (CBC), immunomodulatory proteins and growth factors, progesterone (P4) and estradiol (E2). Placental ERK/AKT/mTOR signaling was assessed using western blot and qPCR.FindingsFluorescent microscopy and in situ hybridization confirmed placental uptake and transgene expression in villous syncytiotrophoblast. No off-target expression was observed in maternal and fetal tissues. Histopathological assessment of the placenta recorded observations not necessarily related to theIGF1nanoparticle treatment. In maternal blood, CBCs, P4 and E2 remained within the normal range for pregnant macaques across the treatment period. Changes to placental ERK and AKT signaling at 48 h and 10 d afterIGF1nanoparticle treatment indicated an upregulation in placental homeostatic mechanisms to prevent over activity in the normal pregnancy environment.InterpretationMaternal toxicity profile analysis and lack of adverse reaction to nanoparticle-mediatedIGF1treatment, combined with changes in placental signaling to maintain homeostasis indicates no deleterious impact of treatment.FundingNational Institutes of Health, and Wisconsin National Primate Research Center.
Listeria monocytogenesinfection in pregnant macaques alters the maternal gut microbiome
Authors: Hugon Anna Marie , Deblois Courtney L. , Simmons Heather A. , Mejia Andres , Schotzo Michele L. , Czuprynski Charles J. , Suen Garret , Golos Thaddeus G. 
Published: June 2023

AbstractObjectivesThe bacteriumListeria monocytogenes(Lm) is associated with adverse pregnancy outcomes. Infection occurs through consumption of contaminated food that is disseminated to the maternal-fetal interface. The influence on the gastrointestinal microbiome during Lm infection remains unexplored in pregnancy. The objective of this study was to determine the impact of listeriosis on the gut microbiota of pregnant macaques.MethodsA nonhuman primate model of listeriosis in pregnancy has been previously described [1, 2]. Both pregnant and nonpregnant cynomolgus macaques were inoculated with L. monocytogenes and bacteremia and fecal shedding were monitored for 14 days. Nonpregnant animal tissues were collected at necropsy to determine bacterial burden, and fecal samples from both pregnant and nonpregnant animals were evaluated by 16S rRNA next-generation sequencing.ResultsUnlike pregnant macaques, nonpregnant macaques did not exhibit bacteremia, fecal shedding, or tissue colonization by Lm. Dispersion of Lm during pregnancy was associated with a significant decrease in alpha-diversity of the host gut microbiome, compared to nonpregnant counterparts. The combined effects of pregnancy and listeriosis were associated with a significant loss in microbial richness, although there were increases in some genera and decreases in others.ConclusionsAlthough pregnancy alone is not associated with gut microbiome disruption, we observed dysbiosis with listeriosis during pregnancy. The macaque model may provide an understanding of the roles that pregnancy and the gut microbiota play in the ability of Lm to establish intestinal infection and disseminate throughout the host, thereby contributing to adverse pregnancy outcomes and risk to the developing fetus.Summary sentenceIntestinal microbial composition in macaques is influenced by significant interaction between the pregnant state and exposure toListeria monocytogenes, associated in particular with significant changes toAkkermansia, Eubacteria ruminantum, Methanobrevibacter, Prevotella,andTreponema.
APOGEE 2: multi-layer machine-learning model for the interpretable prediction of mitochondrial missense variants
Authors: Bianco Salvatore Daniele , Parca Luca , Petrizzelli Francesco , Biagini Tommaso , Giovannetti Agnese , Liorni Niccolò , Napoli Alessandro , Carella Massimo , Procaccio Vincent , Lott Marie , Zhang Shiping , Vescovi Angelo Luigi , Wallace Douglas C. , Caputo Viviana , Mazza Tommaso 
Published: June 2023

ABSTRACTAPOGEE 2 is a mitochondrially-centered ensemble method designed to improve the accuracy of pathogenicity predictions for interpreting missense mitochondrial variants. Built on the joint consensus recommendations by the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP), APOGEE 2 features an improved machine learning method and a curated training set for enhanced performance metrics. It offers region-wise assessments of genome fragility and mechanistic analyses of specific amino acids that cause perceptible long-range effects on protein structure. With clinical and research use in mind, APOGEE 2 scores and pathogenicity probabilities are precompiled and available in MitImpact. APOGEE 2’s ability to address challenges in interpreting mitochondrial missense variants makes it an essential tool in the field of mitochondrial genetics.
dingo: a Python package for metabolic flux sampling
Authors: Chalkis Apostolos , Fisikopoulos Vissarion , Tsigaridas Elias , Zafeiropoulos Haris 
Published: June 2023

AbstractSummaryWe presentdingo, a Python package that supports a variety of methods to sample from the flux space of metabolic models, based on state-of-the-art random walks and rounding methods. For uniform samplingdingo’s implementation of the Multiphase Monte Carlo Sampling algorithm, provides a significant speed-up and outperforms existing software. Indicatively,dingocan sample from the flux space of the largest metabolic model up to now (Recon3D) in less than 30 hours using a personal computer, under several statistical guarantees; this computation is out of reach for other similar software. In addition, supports common analysis methods, such as Flux Balance Analysis (FBA) and Flux Variability Analysis (FVA), and visualization components.dingocontributes to the arsenal of tools in metabolic modeling by enabling flux sampling in high dimensions (in the order of thousands).Availability and implementationhttps://github.com/GeomScale/dingoContacttolis.chal@gmail.gr,haris.zafeiropoulos@kuleuven.be
High-accuracy meets high-throughput for microbiome profiling with near full-length 16S rRNA amplicon sequencing on the Nanopore platform
Authors: Lin Xuan , Waring Katherine , Tyson John , Ziels Ryan M. 
Published: June 2023

AbstractAmplicon sequencing of small subunit (SSU) rRNA genes is a foundational method for studying microbial communities within various environmental, human, and engineered ecosystems. Currently, short-read platforms are commonly employed for high-throughput applications of SSU rRNA amplicon sequencing, but at the cost of poor taxonomic classification. The low-cost Oxford Nanopore Technologies (ONT) platform is capable of sequencing full-length SSU rRNA genes, but the lower raw-read accuracies of previous ONT sequencing chemistries have limited accurate taxonomic classification and de novo generation of operational taxonomic units (OTUs) and amplicon sequence variants (ASVs). Here, we examine the potential for Nanopore sequencing with newer (R10.4+) chemistry to provide high-throughput and high-accuracy full-length 16S rRNA gene amplicon sequencing. We present a sequencing workflow utilizing unique molecular identifiers (UMIs) for error-correction of SSU rRNA (e.g. 16S rRNA) gene amplicons, termed ssUMI. Using two synthetic microbial community standards, the ssUMI workflow generated consensus sequences with 99.99% mean accuracy using a minimum UMI subread coverage threshold of 3x, and was capable of generating error-free ASVs and 97% OTUs with no false-positives. Non-corrected Nanopore reads generated error-free 97% OTUs but with reduced detection sensitivity, and also generated false-positive ASVs. We showcase the cost-competitive and high-throughput scalability of the ssUMI workflow by sequencing 90 time-series samples from seven different wastewater matrices, generating ASVs that were tightly clustered based on sample matrix type. This work demonstrates that highly accurate full-length 16S rRNA gene amplicon sequencing on Nanopore is possible, paving the way to more accessible microbiome science.
Controlling target brain regions by optimal selection of input nodes
Authors: Manjunatha Karan Kabbur Hanumanthappa , Baron Giorgia , Benozzo Danilo , Silvestri Erica , Corbetta Maurizio , Chiuso Alessandro , Bertoldo Alessandra , Suweis Samir , Allegra Michele 
Published: June 2023

AbstractThe network control theory framework holds great potential to inform neurostimulation experiments aimed at inducing desired activity states in the brain. However, the current applicability of the framework is limited by inaccurate modeling of brain dynamics, and an overly ambitious focus on whole-brain activity control. In this work, we leverage recent progress in linear modeling of brain dynamics (effective connectivity) and we exploit the concept of target controllability to focus on the control of a single region or a small subnetwork of nodes. We discuss when control may be possible with a reasonably low energy cost and few stimulation loci, and give general predictions on where to stimulate depending on the subset of regions one wishes to control. Importantly, using the robustly asymmetric effective connectome instead of the symmetric structural connectome (as in previous research), we highlight the fundamentally different roles in- and out-hubs have in the control problem, and the relevance of inhibitory connections. The large degree of inter-individual variation in the effective connectome implies that the control problem is best formulated at the individual level, but we discuss to what extent group results may still prove useful.
DnaK duplicates and regionally evolves for the increase of proteomic complexity in bacteria
Authors: Pan Zhuo , Zhuo Li , Wan Tian-yu , Chen Rui-yun , Li Yue-zhong 
Published: June 2023

AbstractHsp70 is important for organismic cells to maintain proteostasis and the chaperone protein is duplicated in all eukaryotes and many prokaryotes. Although the functioning mechanism of Hsp70 has been clearly illuminated, the chaperone duplication and functional evolution has been less investigated. DnaK is a highly conserved bacterial Hsp70 family. Here we showed that thednaKgene is present in 98.9% bacteria and 6.4% bacteria possess duplicateddnaKs; the occurrence and duplication is positively corelated to the increase of proteomic complexity. We identified the interactomes of the two DnaK paralogs inMyxococcus xanthusDK1622, which are mostly nonoverlapped, but both preferring the α&β domain proteins. Consistent with the proteomes, the MxDnaK substrates are both significantly size-larger and pI-higher than that of the singleE. coliDnaK. MxDnaK1 is heat-shock inducible, prefers to bind cytosolic proteins, while MxDnaK2 is decreased by heat shock, and is more associated with membrane proteins. The nucleotide binding domain and the substrate binding beta domain are responsible for the significant changes of DnaK substrates, and the former also determines the dimerization of MxDnaK2, but not MxDnaK1. Our work highlights that DnaK is duplicated and regionally evolved for the increase of proteomic complexity in bacteria.