bluuebunny/crossref_metadata_2025_split huggingface dataset:
Men’s perceptions and perceived acceptability of their female partner’s use of self-administered intravaginal therapies for treatment of cervical precancer in Kenya
Authors: Mungo Chemtai , Adewumi Konyin , Ellis Grace , Rop Mercy , Adoyo Everlyn , Zou Yating , Rahangdale Lisa 
Published: February 2024

AbstractBackgroundCervical cancer continues to be a major health issue in low- and middle-income countries (LMICs). Despite increasing access to screening, access to precancer treatment remains a significant challenge in LMICs, highlighting a need for innovative, accessible, and resource-appropriate treatment approaches, including self-administered therapies.MethodsA cross-sectional mixed-methods study was conducted among men aged 25-65 with a current female partner in Kisumu County, Kenya. Participants were sequentially recruited and surveyed to evaluate their understanding of HPV and cervical cancer, their views on screening and treatment, and their attitudes toward self-administered therapies. Focus group discussions with a subset of the survey participants further explored their treatment preferences and perceptions.ResultsTwo hundred fourteen men participated in the survey, and 39 men participated in focus group discussions. The median age was 39 years, and 51% had a primary school education or less. Most (96%) were in a committed relationship, and 74% earned $10 or less daily. There was strong support for self-administered topical therapies, with 98% willing to support their partners using such treatments if available. Additionally, most participants were open to supporting necessary abstinence or condom use, though 76% believed their partners might hesitate to request condom use. When given an option, most preferred their partner to self-administer such therapies at home compared to provider administration at a health facility, citing convenience, cost-effectiveness, and privacy. Preferences varied between two potential therapies, 5-Fluorouracil (5FU) and Artesunate, based on their administration frequency, duration, and abstinence requirements. Qualitative findings largely supported the quantitative analysis.ConclusionsThe study demonstrates strong support for self-administered topical therapies for cervical precancer among Kenyan men. Additional research on acceptability, feasibility, and efficacy in different LMICs could pave the way for these therapies to help bridge current cervical precancer treatment gaps in these settings.
Preconception health in adolescence and adulthood across generations in the UK: findings from three British birth cohort studies
Authors: Righton Olivia , Flynn Angela , Alwan Nisreen A. , Schoenaker Danielle 
Published: February 2024

AbstractOptimising preconception health in women and men holds significant potential for improving pregnancy and offspring health outcomes. To create a picture of the state of preconception health in the UK, this study aimed to describe the prevalence of and changes in preconception health indicators reported in three British birth cohort studies: the 1970 British Birth Cohort Study (BCS70; born in 1970; N=17,198), Next Steps (1989-1990; N=15,770), and Millennium Cohort Study (MCS; 2000-2002; N=19,517). The analysis focused on data obtained during participants’ adolescence (16-17 years) and subsequent follow-ups at 25-26 years for BCS70 and Next Steps. Self-reported preconception indicators were defined in line with a previously published review and reported as proportions.Across cohorts, data were available for 14 preconception indicators across four domains: health behaviours and weight, reproductive health and family planning, physical health conditions, and wider determinants of health. Findings revealed persistent suboptimal health behaviours in both genders and across generations, including low intakes of fruit. While alcohol, tobacco, and soft drink intake decreased across generations, obesity prevalence surged. This study underscores the need for public health interventions targeting the root causes of adverse health behaviours towards improvement of fruit consumption, further reduction in alcohol, tobacco, and soft drink consumption, and addressing the escalating obesity rates among individuals of reproductive age. Ongoing monitoring is needed to continue tracking these existing indicators over time, while improved data quality and availability of a wider range of preconception indicators are crucial to comprehensively understanding the complexities of preconception health, enabling the development of more targeted and effective interventions.
A familial modeling framework for advancing precision medicine in neuropsychiatric disorders: A study in children with RASopathies
Authors: Bruno Jennifer L. , Merrin Jacob Joseph , Hosseini Hadi , Green Tamar 
Published: February 2024

AbstractObjectiveDespite the significant and growing burden of childhood psychiatric disorders, treatment is hindered by lack of evidence-based precision approaches. We utilized parent cognitive and behavioral traits in a predictive framework to provide a more individualized estimate of expected child neuropsychiatric and neuroanatomical outcomes relative to traditional case-control studies. We examined children with Noonan Syndrome, a neurogenetic syndrome affecting the Ras/mitogen-activated protein kinase (Ras/MAPK), as a model for developing precision medicine approaches in childhood neuropsychiatric disorders.MethodsParticipants included 53 families of children with Noonan syndrome (age 4-12.9 years, mean = 8.48, SD = 2.12, 34 female). This cross-sectional study utilized univariate regression to examine the association between non carrier parent traits (cognition and behavior) and corresponding child traits. We also used multivariate machine learning to examine the correspondence between parent cognition and child multivariate neuroanatomical outcomes. Main outcome measures included child and parent cognition, anxiety, depression, attention-deficit hyperactivity (ADHD) and somatic symptoms. We also included child neuroanatomy measured via structural MRI.ResultsParent cognition (especially visuospatial/motor abilities), depression, anxiety and ADHD symptoms were significantly associated with child outcomes in these domains. Parent cognition was also significantly associated with child neuroanatomical variability. Several temporal, parietal and subcortical regions that were weighted most strongly in the multivariate model were previously identified as morphologically different when children with NS were compared to typically developing children. In contrast, temporal regions, and the amygdala, which were also weighted strongly in the model, were not identified in previous work but were correlated with parent cognition in post-hoc analysis suggesting a larger familial effect on these regions.ConclusionsUtilizing parent traits in a predictive framework affords control for familial factors and thus provides a more individualized estimate of expected child cognitive, behavioral, and neuroanatomical outcomes. Understanding how parent traits influence neuroanatomical outcomes helps to further a mechanistic understanding of Ras/MAPK’s impact on neurodevelopmental outcomes. Further refinement of predictive modeling to estimate individualized child outcomes will advance a precision medicine approach to treating NS, other neurogenetic syndromes, and neuropsychiatric disorders more broadly.
Genetic dissection of the tissue-specific roles of type III effectors and phytotoxins in the pathogenicity ofPseudomonas syringaepv.syringaeto cherry
Authors: Vadillo-Dieguez Andrea , Zeng Ziyue , Mansfield John W. , Grinberg Nastasiya F. , Lynn Samantha C. , Gregg Adam , Connell John , Harrison Richard J. , Jackson Robert W. , Hulin Michelle T. 
Published: February 2024

AbstractWhen compared with other phylogroups (PGs) of thePseudomonas syringae (Ps)species complex,Pspv. syringaestrains within PG2 have a reduced repertoire of type III effectors (T3Es) but produce several phytotoxins. Effectors within the cherry pathogenPss9644 were grouped based on their frequency in strains fromPrunusas: the conserved effector locus (CEL) common to mostPspathogens; a CORE of effectors common to PG2; a set of PRUNUS effectors common to cherry pathogens; and a FLEXIBLE set of T3Es.Pss9644 also contains gene clusters for biosynthesis of toxins syringomycin/syringopeptin and syringolin A. After confirmation of virulence gene expression, mutants with a sequential series of T3E and toxin deletions were pathogenicity tested on wood, leaves and fruits of sweet cherry (Prunus avium) and leaves of ornamental cherry (Prunus incisa). The toxins had a key role in disease development in fruits but were less important in leaves and wood. An effectorless mutant retained some pathogenicity to fruit but not wood or leaves. Striking redundancy was observed amongst effector groups. The CEL effectors have important roles during the early-stages of leaf infection and acted synergistically with toxins in all tissues. Deletion of separate groups of T3Es had much more effect inPrunus incisathan in sweet cherry. Mixed inocula were used to complement the toxin mutationsin transand indicated that strain mixtures may be important in the field. Our results highlight the niche-specific role of toxins in cherry tissues and the complexity of effector redundancy in the pathogenPss9644.
Visually Induced Involuntary Movements
Authors: Martin Alexandra , Ventura Joel , Bakshi Avijit , Panic Sacha , Lackner James R. 
Published: February 2024

ABSTRACTLooking at a virtual 3D environment with structural features rotating at 60°/s in a head-mounted display soon elicits an illusion of self-rotation and displacement in the opposite direction. We explored in 75 s long trials the effects of visually induced self-rotation on the head, torso, and horizontally extended right arm of standing subjects. The degree of body and limb movement was contingent on whether the arm was extended out freely or pointing at a briefly proprioceptively specified target position, but did not depend on whether the hand held a rod or not. Most subjects in the Free condition showed significant unintentional arm deviations, which averaged approximately 55° in the direction opposite the induced illusory self-motion, and were more than 150° in some cases. In contrast, on average, the deviations in the Pointing condition were a quarter of those in the Free condition. Deviations of head and torso positions also occurred in all conditions. Total arm and head deviations were the sum of deviations of the arm and head with respect to the torso plus deviations of the torso with respect to space. When given a pointing target, subjects were largely able to detect and correct for arm and head deviations with respect to the torso but not for the parts of arm and head deviation that were due to deviations of the torso with respect to space. In all conditions, the arm, head, and torso deviations occurred before subjects began to experience compelling self-rotation and displacement. This is contrasted with the compensations for expected but absent Coriolis forces that are made when stationary subjects make reaching movements to targets during exposure to structured moving visual scenes. These compensations do not occur until subjects experience self-rotation and spatial displacement. These results have implications for vehicle control and maneuvering in environments that induce illusory motion and displacement, and in situations where there is motion in a large area of the visual field. The impact of these effects on joystick control is described and discussed. We also describe the subjective sense of ownership attributed to hand-held objects when experiencing illusory self-motion and displacement.
hoxbgenes determine the timing of cell ingression by regulating cell surface fluctuations during zebrafish gastrulation
Authors: Moriyama Yuuta , Mitsui Toshiyuki , Heisenberg Carl-Philipp 
Published: February 2024

SUMMARYDuring embryonic development, cell behaviors need to be tightly regulated in time and space. Yet, how the temporal and spatial regulations of cell behaviors are interconnected during embryonic development remains elusive. To address this, we turned to zebrafish gastrulation, the process where dynamic cell behaviors generate the three principal germ layers of the early embryo. Here, we show thathoxbcluster genes are expressed in a temporally collinear manner at the blastoderm margin of the embryo to regulate the timing of mesoderm and endoderm (mesendoderm) cell ingression. Under- or over-expression ofhoxbgenes perturb the timing of mesendoderm cell ingression and, consequently, the positioning of these cells along the forming anterior-posterior body axis. Finally, we found thathoxbgenes control the timing of mesendoderm ingression by regulating cell surface fluctuations. Thus,hoxbgenes interconnect the temporal and spatial pattern of cell behavior in the early embryo by controlling cell surface fluctuations.Highlightshoxbgene expression shows temporal collinearity at the blastoderm margin during zebrafish gastrulation.Temporal collinear expression ofhoxbgenes at the blastoderm margin regulates the timing of cell ingression and delineates spatial collinearity after gastrulation.hoxbgenes regulate cell surface fluctuations and bleb formation at the blastoderm margin during cell ingressionGraphical abstracthoxbgenes are expressed at the blastoderm margin in a temporally collinear manner and determine the timing of mesendoderm ingression by triggering dynamic cell surface fluctuations and cell blebbing. This results in a spatial collinearity of mesendoderm cell positioning along the anterior-posterior extent of the forming body axis with early ingressing cells being positioned more anteriorly than late ingressing cells.
Cortico-spinal Mechanisms of Periphery Neuromodulation induced Analgesia
Authors: Wei Zhaoxing , Duan Yunyun , Zhu Yupu , Lin Xiaomin , Zhang Ming , Brooks Jonathan C.W. , Liu Yaou , Hu Li , Kong Yazhuo 
Published: February 2024

AbstractNociceptive acute and chronic pain significantly impact the quality of life and create tremendous societal burdens. Given the side effects associated with pharmacological analgesia, noninvasive periphery neuromodulation techniques, like Transcutaneous Electrical Nerve Stimulation (TENS), have emerged as promising approaches for pain relief. Current human research, focusing partly on cerebral, brainstem, or peripheral mechanisms of neuromodulation, lacks comprehensive understanding from the perspective of the entire central nervous system. This study utilized a three-way mixed experimental design, combining cutting-edge cortico-spinal fMRI with thermal stimuli, to systematically explore the central analgesic mechanisms of two typical TENS modes: Conventional (high frequency, low intensity) and Acupuncture-Like (low frequency, high intensity). Behavioral and fMRI analysis revealed that, the direct spinal inhibition (PAG-spinal connectivity) partially mediated by PAG-vmPFC connectivity leads to local analgesic effects in Conventional TENS; a top-down diffuse noxious inhibition (PAG-S1 connectivity) fully mediated through PAG-spinal connectivity leads to diffuse analgesic effects in Acupuncture-Like TENS. Employing advanced cortico-spinal fMRI technique, our findings provide systematic neural evidence of the analgesic mechanisms induced by TENS and shed new light on future neuromodulation approaches.
Comparative Metagenomics Provide Mechanistic Insights into the Biodegradation of the Non-hydrolysable Plastic Polyvinyl Chloride in Gut Microbiota of Insect Larvae
Authors: Peng Haoran , Zhang Zhe , Kang Xiaoxi , Zhang Yunhua , Zhang Huilin , Wang Yuxuan , Yang Dongchen , Zhang Jinlin , Wang Yajie , Zhu Yong-Guan , Ju Feng 
Published: February 2024

AbstractUsing microbiomes to mitigate global plastic pollution is of paramount importance. Insect microbiomes have garnered emerging interest for their ability to biodegrade non-hydrolysable plastic polymers. The larvae ofSpodoptera frugiperda, a globally prevalent migratory crop pest, are accidentally discovered to consume polyvinyl chloride (PVC) plastic films, highlighting the role of their gut microbiome. Following the migration ofS. frugiperdin China, this study displays a comprehensive geographical profile of its larval gut microbiota and a significant shift after PVC feeding. Using comparative metagenomics we revealed the functional redundancy within the larval gut microbiomes of two distinct insects after PVC ingestion, we discovered a surprisingly potent PVC-dechlorinating activity of an NADH peroxidase (6.48 mg/L chlorine produced in 96 hours with NADH as a cofactor) encoded byEnterococcus casseliflavusEMBL-3. These findings open a new avenue for understanding plastic biodegradation mechanism and enable the development of biotechnologies to mitigate global plastic pollution.
Natural selection exerted by historical coronavirus epidemic(s): comparative genetic analysis in China Kadoorie Biobank and UK Biobank
Authors: Morris Sam. C. , Lin Kuang , Millwood Iona Y. , Yu Canqing , Lv Jun , Pei Pei , Li Liming , Sun Dianjianyi , Smith George Davey , Chen Zhengming , Walters Robin 
Published: February 2024

AbstractBackgroundPathogens have been one of the primary sources of natural selection affecting modern humans. The footprints of historical selection events – “selective sweeps” – can be detected in the genomes of present-day individuals. Previous analyses of 629 samples from the 1000 Genomes Project suggested that an ancient coronavirus epidemic ∼20,000 years ago drove multiple selective sweeps in the ancestors of present-day East Asians, but not in other worldwide populations.ResultsUsing a much larger genetic dataset of 76,719 unrelated individuals from each of the China Kadoorie Biobank (CKB) and UK Biobank (UKB) to identify regions of long-range linkage disequilibrium, we further investigated signatures of past selective sweeps and how they reflect previous viral epidemics. Using independently-curated lists of human host proteins which interact physically or functionally with viruses (virus-interacting proteins; VIPs), we found enrichment in CKB for regions of long-range linkage disequilibrium at genes encoding VIPs for coronaviruses, but not DNA viruses. By contrast, we found no clear evidence for any VIP enrichment in UKB. These findings were supported by additional analyses using saltiLASSi, a selection-scan method robust to false positives caused by demographic events. By contrast, for GWAS signals for SARS-Cov2 susceptibility (critical illness, hospitalisation, and reported infection), there was no difference between UKB and CKB in the number located at or near signals of selection, as expected for a novel virus which has had no opportunity to impact the CKB/UKB study populations.ConclusionsTogether, these results provide evidence of selection events consistent with historical coronavirus epidemic(s) originating in East Asia. These results show how biobank-scale datasets and evolutionary genomics theory can provide insight into the study of past epidemics. The results also highlights how historic infectious diseases epidemics can shape the genetic architecture of present-day human populations.
Introducing synthetic thermostable RNase inhibitors to single-cell RNA-seq
Authors: Noble J.C. , Lentini Antonio , Hageman-Jensen Michael , Sandberg Rickard , Reinius Björn 
Published: February 2024

AbstractSingle-cell RNA-sequencing (scRNAseq) is revolutionizing biomedicine, propelled by advances in methodology, ease of use, and cost reduction of library preparation. Over the past decade, there have been remarkable technical improvements in most aspects of single-cell transcriptomics. Yet, there has been little to no progress in advancing RNase inhibition despite maintained RNA integrity being critical during cell collection, storage, and cDNA library generation. Here, we demonstrate that a synthetic thermostable RNase inhibitor yields single-cell libraries of equal or superior quality compared to ubiquitously used protein-based recombinant RNase inhibitors (RRIs). Importantly, the synthetic RNase inhibitor provides additional unique improvements in reproducibility and throughput, enables new experimental workflows including retained RNase inhibition throughout heat cycles, and can reduce the need for dry-ice transports.In summary, replacing RRIs represents a substantial advancement in the field of single-cell transcriptomics.
AMycobacterium tuberculosissecreted virulence factor disrupts host snRNP biogenesis
Authors: Chauhan Komal , Passricha Nishat , Kapoor Yogita , Datta Dipanwita , Arora Naresh , Das Mrinmoy , Rao Kavya , Singh Lakshyaveer , Dutt Ravi , Sharma Raman Deep , Sarkar Binayak , Malakkar Basanti , Kalam Haroon , Saini Prince , Mehra Lalita , Das Prasenjit , Ahuja Vineet , Singhal Amit , Nandicoori Vinay , Kumar Dhiraj 
Published: February 2024

AbstractWe earlier reported thatMycobacterium tuberculosis(Mtb) alters host RNA splicing to help its intracellular growth. Here, we report an unprecedented mechanism whereby a secreted virulence factor fromMtbinterferes with the biogenesis of key spliceosomal components, causing an altered RNA splicing pattern. A high-throughput yeast-2-hybrid screen identified severalMtb-secreted proteins that can interact with the host RNA splicing factors (SFs). Through custom-designed in-cell assays, we show that one of those proteins, Rv1435c, targets specific exon-skipping events to alter RNA splicing. We show that Rv14345c orhostsplicingregulator 1 (hsr1) facilitates direct interaction betweenMtbphagosomes and U5 snRNA and SNRPF, key components of the snRNPs. Genetic deletion ofhsr1reverses the specific exon-skipping events caused by WTMtbinfection. TheΔhsr1strain shows compromised growth duringex vivoinfection in the macrophages andin vivoinfection in the mice. Tissue sections from the WTMtborΔhsr1-infected mice showed significant hsr1-dependent SNRPF staining, a phenomenon also noted in the human intestinal tuberculosis (ITB) biopsies. We infer that hsr1 is a virulence factor which alters RNA splicing by interacting with U5snRNA and SNRPF. The splicing regulators from the host and pathogen are novel targets for anti-tuberculosis therapy.
The epigenetic landscape of oligodendrocyte progenitors changes with time
Authors: Dansu David K. , Sauma Sami , Huang Dennis , Li Meng , Moyon Sarah , Casaccia Patrizia 
Published: February 2024

ABSTRACTSUMMARYDansu et al. identify distinct histone H4 modifications as potential mechanism underlying the functional differences between adult and neonatal progenitors. While H4K8ac favors the expression of differentiation genes, their expression is halted by H4K20me3.Adult oligodendrocyte progenitors (aOPCs) generate myelinating oligodendrocytes, like neonatal progenitors (nOPCs), but they also display unique functional features. Here, using RNA-sequencing, unbiased histone proteomics analysis and ChIP-sequencing, we define the transcripts and histone marks underlying the unique properties of aOPCs. We describe the lower proliferative capacity and higher levels of expression of oligodendrocyte specific genes in aOPCs compared to nOPCs, as well as the greater levels of H4 histone marks. We also report increased occupancy of the H4K8ac mark at chromatin locations corresponding to oligodendrocyte-specific transcription factors and lipid metabolism genes. Pharmacological inhibition of H4K8ac deposition reduces the levels of these transcripts in aOPCs, rendering their transcriptome more similar to nOPCs. The repressive H4K20me3 mark is also higher in aOPCs compared to nOPCs and pharmacological inhibition of its deposition results in increased levels of genes related to the mature oligodendrocyte state. Overall, this study identifies two histone marks which are important for the unique transcriptional and functional identity of aOPCs.