bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIV burden and the global fast-track targets progress among pregnant women in Tanzania calls for intensified case finding: Analysis of 2020 antenatal clinics HIV sentinel site surveillance
Authors: Mboya Erick , Mizinduko Mucho , Balandya Belinda , Mushi Jeremiah , Sabasaba Amon , Amani Davis Elias , Kamori Doreen , Ruhago George , Faustine Prosper , Maokola Werner , Sambu Veryeh , Nyamuhagata Mukome , Jullu Boniphace S. , Juya Amiri , Rugemalila Joan , Mgomella George , Asiimwe Sarah , Pembe Andrea B. , Sunguya Bruno 
Published: May 2023

AbstractBackgroundFor successful HIV response, updated information on the burden and progress towards elimination targets are required to guide programmatic interventions. We used data from the 2020 HIV sentinel surveillance to update on the burden, HIV status awareness, ART coverage, and factors associated with HIV infection among pregnant women in Tanzania mainland.MethodologyWe conducted the ANC surveillance in 159 ANC sites from all 26 regions of Tanzania’s mainland from September to December 2020. This cross-sectional study included all pregnant women (≥15 years) on their first ANC visit in the current pregnancy during the survey period. Routine HIV counseling and testing were done at the facility. Multivariable logistic regression model was used to examine factors associated with HIV infections.ResultsA total of 38,783 pregnant women were enrolled (median age (IQR) =25 (21–30) years). HIV prevalence was 5.9% (95%CI: 5.3% - 6.6%), ranging from 1.9% in Manyara region to 16.4% in Njombe region. Older age, lower and no education, not being in marital union, and living in urban or semi-urban areas was associated with higher odds of HIV infection. HIV status awareness among women who tested positive was 70.9% (95% CI: 67.5%- 74.0%). ART coverage among those aware of their status was 91.6% (86.5%- 94.9%). Overall, 66.6% (95% CI: 62.4%- 70.6%) of all pregnant women tested positive for HIV knew their HIV status and were on ART.ConclusionHIV is increasingly prevalent among pregnant women in Tanzania especially among older, those with lower or no formal education, those outside marital union and pregnant women living in urban and semi-urban areas. Behind the global fast-target to end HIV/ AIDS, about a third of pregnant women living with HIV initiating ANC were not on ART. Interventions to increase HIV testing and linkage to care among women of reproductive age should be intensified.
Relationship between prokaryotic GC content and environmental salinity
Authors: Hu En-Ze , Sun Shen , Niu Deng-Ke 
Published: May 2023

AbstractBackgroundThe correlation between GC content and halophilicity has received limited attention, despite the numerous environmental factors associated with GC content evolution. While higher GC content has been linked to halophiles in some archaeal cases, it is widely believed that selective pressure from high-intensity ultraviolet radiation in halophilic archaea drives GC content increase, as it prevents DNA photoproduct formation. However, this assumption has not been statistically analyzed in a phylogenetically independent manner prior to our study.ResultsUsing phylogenetic generalized least squares, we investigated the relationship between GC content and halophilicity in 1226 bacteria and 181 archaea. Our analysis found significant positive correlations in bacteria but not in archaea. Resampling analysis indicates that the absence of significant correlation in archaea may be due to the relatively small sample size. We also observed that the strength of the correlation is negatively influenced by the functional constraint of genomic components. Additionally, we found that halophilic bacteria and archaea do not have lower photoreactivity (a measure of DNA vulnerability to ultraviolet radiation) than the photoreactivity expected from their GC contents.ConclusionsIn contrast to previous assumptions, we did not find evidence to support the widespread photoprotection hypothesis or another hypothesis that high GC content in halophiles stabilizes nucleic acid structures. Instead, our findings align with a nonadaptive hypothesis. Halophilic prokaryotes likely evolved high GC content due to frequent GC-biased gene conversion in response to DNA double-strand breaks induced directly or indirectly by high salt concentrations.
Redefining Pleiotropic Drug Resistance in a Pathogenic Yeast: Pdr1 Functions as a Sensor of Cellular Stresses inCandida glabrata
Authors: Gale Andrew N. , Pavesic Matthew W. , Nickels Timothy J. , Xu Zhuwei , Cormack Brendan P. , Cunningham Kyle W. 
Published: May 2023

AbstractCandida glabratais a prominent opportunistic fungal pathogen of humans. The increasing incidence ofC. glabratainfections is attributed to both innate and acquired resistance to antifungals. Previous studies suggest the transcription factor Pdr1 and several target genes encoding ABC transporters are critical elements of pleiotropic defense against azoles and other antifungals. This study utilizesHermestransposon insertion profiling to investigate Pdr1-independent and Pdr1-dependent mechanisms that alter susceptibility to the frontline antifungal fluconazole. Several new genes were found to alter fluconazole susceptibility independent of Pdr1 (CYB5,SSK1,SSK2,HOG1,TRP1). A bZIP transcription repressor of mitochondrial function (CIN5) positively regulated Pdr1 while hundreds of genes encoding mitochondrial proteins were confirmed as negative regulators of Pdr1. The antibiotic oligomycin activated Pdr1 and antagonized fluconazole efficacy likely by interfering with mitochondrial processes inC. glabrata. Unexpectedly, disruption of many 60S ribosomal proteins also activated Pdr1, thus mimicking the effects of the mRNA translation inhibitors. Cycloheximide failed to fully activate Pdr1 in a cycloheximide-resistant Rpl28-Q38E mutant. Similarly, fluconazole failed to fully activate Pdr1 in a strain expressing a low-affinity variant of Erg11. Fluconazole activated Pdr1 with very slow kinetics that correlated with the delayed onset of cellular stress. These findings are inconsistent with the idea that Pdr1 directly senses xenobiotics and support an alternative hypothesis where Pdr1 senses cellular stresses that arise only after engagement of xenobiotics with their targets.ImportanceCandida glabratais an opportunistic pathogenic yeast that causes discomfort and death. Its incidence has been increasing because of natural defenses to our common antifungal medications. This study explores the entire genome for impacts on resistance to fluconazole. We find several new and unexpected genes can impact susceptibility to fluconazole. Several antibiotics can also alter the efficacy of fluconazole. Most importantly, we find that Pdr1 – a key determinant of fluconazole resistance – is not regulated directly through binding of fluconazole and instead is regulated indirectly by sensing the cellular stresses caused by fluconazole blockage of sterol biosynthesis. This new understanding of drug resistance mechanisms could improve the outcomes of current antifungals and accelerate the development of novel therapeutics.
CrOssing fiber Modeling in the Peritumoral Area using dMRI (COMPARI)
Authors: Golkar Ehsan , Parker Drew , Brem Steven , Almairac Fabien , Verma Ragini 
Published: May 2023

AbstractVisualization of fiber tracts around the tumor is critical for neurosurgical planning and preservation of crucial structural connectivity during tumor resection. Biophysical modeling approaches estimate fiber tract orientations from differential water diffusivity information of diffusion MRI. However, the presence of edema and tumor infiltration presents a challenge to visualize crossing fiber tracts in the peritumoral region. Previous approaches proposed free water modeling to compensate for the effect of water diffusivity in edema, but those methods were limited in estimating complex crossing fiber tracts. We propose a new cascaded multi-compartment model to estimate tissue microstructure in the presence of edema and pathological contaminants in the area surrounding brain tumors. In our model (COMPARI), the isotropic components of diffusion signal, including free water and hindered water, were eliminated, and the fiber orientation distribution (FOD) of the remaining signal was estimated. In simulated data, COMPARI accurately recovered fiber orientations in the presence of extracellular water. In a dataset of 23 patients with highly edematous brain tumors, the amplitudes of FOD and anisotropic index distribution within the peritumoral region were higher with COMPARI than with a recently proposed multi-compartment constrained deconvolution model. In a selected patient with metastatic brain tumor, we demonstrated COMPARI’s ability to effectively model and eliminate water from the peritumoral region. The white matter bundles reconstructed with our model were qualitatively improved compared to those of other models, and allowed the identification of crossing fibers. In conclusion, the removal of isotropic components as proposed with COMPARI improved the bio-physical modeling of dMRI in edema, thus providing information on crossing fibers, thereby enabling improved tractography in a highly edematous brain tumor. This model may improve surgical planning tools to help achieve maximal safe resection of brain tumors.
Preparing correctional settings for the next pandemic: a modelling study of COVID-19 outbreaks in two high-income countries
Authors: Kwon Jisoo A. , Bretaña Neil A. , Kronfli Nadine , Dussault Camille , Grant Luke , Galouzis Jennifer , Hoey Wendy , Blogg James , Lloyd Andrew R. , Gray Richard T. 
Published: May 2023

AbstractCorrectional facilities are high-priority settings for coordinated public health responses to the COVID-19 pandemic. These facilities are at high risk of disease transmission due to close contacts between people in prison and with the wider community. People in prison are also vulnerable to severe disease given their high burden of co-morbidities. We developed a mathematical model to evaluate the effect of various public health interventions, including vaccination, on the mitigation of COVID-19 outbreaks, applying it to prisons in Australia and Canada. We found that, in the absence of any intervention, an outbreak would occur and infect almost 100% of people in prison within 20 days of the index case. However, the rapid rollout of vaccines with other non-pharmaceutical interventions would almost eliminate the risk of an outbreak. Our study highlights that high vaccination coverage is required for variants with high transmission probability to completely mitigate the outbreak risk in prisons.Article Summary LineHigh vaccination coverage is required to eliminate the risk of an outbreak in prisons
C-type natriuretic peptide improves maternally aged oocytes quality by inhibiting excessive PINK1/Parkin-mediated mitophagy
Authors: Zhang Hui , Li Chan , Liu Qingyang , Li Jingmei , Wu Hao , Xu Rui , Sun Yidan , Cheng Ming , Zhao Xiaoe , Pan Menghao , Wei Qiang , Ma Baohua 
Published: May 2023

AbstractThe overall oocyte quality declines with ageing, and this effect is strongly associated with a higher reactive oxygen species (ROS) level and the resultant oxidative damage. C-type natriuretic peptide (CNP) is a well-characterized physiological meiotic inhibitor that has been successfully used to improve immature oocyte quality during in vitro maturation (IVM). However, the underlying roles of CNP in maternally aged oocytes have not been reported. Here, we found that the age-related reduction in the serum CNP concentration was highly correlated with decreased oocyte quality. Treatment with exogenous CNP promoted follicle growth and ovulation in aged mice and enhanced meiotic competency and fertilization ability. Interestingly, the cytoplasmic maturation of aged oocytes was thoroughly improved by CNP treatment, as assessed by spindle/chromosome morphology and redistribution of organelles (mitochondria, the endoplasmic reticulum [ER], cortical granules [CGs], and the Golgi apparatus). CNP treatment also ameliorated DNA damage and apoptosis caused by ROS accumulation in aged oocytes. Importantly, oocyte RNA-seq revealed that the beneficial effect of CNP on aged oocytes was mediated by restoration of mitochondrial oxidative phosphorylation, eliminating excessive mitophagy. CNP reversed the defective phenotypes in aged oocytes by alleviating oxidative damage and suppressing excessive PINK1/Parkin-mediated mitophagy. Mechanistically, CNP functioned as a cAMP/PKA pathway modulator to decrease PINK1 stability and inhibit Parkin recruitment. In summary, our results demonstrated that CNP supplementation constitutes an alternative therapeutic approach for advanced maternal age-related oocyte deterioration and may improve the overall success rates of clinically assisted reproduction in older women.
Mathematical modeling of clonal interference by density-dependent selection in heterogeneous cancer cell lines
Authors: Veith Thomas , Alahmari Saeed , Schultz Andrew , Johnson Joseph , Maksin Konstantin , Andor Noemi 
Published: May 2023

AbstractMany cancer cell lines are aneuploid and heterogeneous, with multiple karyotypes co-existing within the same cell line. Karyotype heterogeneity has been shown to manifest phenotypically, affecting how cells respond to drugs or to minor differences in culture media. Knowing how to interpret karyotype heterogeneity phenotypically, would give insights into cellular phenotypes before they unfold temporally. Here we reanalyze single cell RNA (scRNA)- and scDNA sequencing data from eight stomach cancer cell lines by placing gene expression programs into a phenotypic context. We quantify differences in growth rate and contact inhibition between the eight cell lines using live-cell imaging, and use these differences to prioritize transcriptomic biomarkers of growth rate and carrying capacity. Using these biomarkers, we find significant differences in the predicted growth rate or carrying capacity between multiple karyotypes detected within the same cell line. We use these predictions to simulate how the clonal composition of a cell line will change depending on the timing of splitting cells. Once validated, these models can aid the design of experiments that steer evolution with density dependent selection.
The spatiotemporal richness of hummingbird wing deformations
Authors: Skandalis Dimitri A. , Baliga Vikram B. , Goller Benjamin , Altshuler Douglas A. 
Published: May 2023

ABSTRACTAnimals exhibit an abundant diversity of forms, and this diversity is even more evident when considering animals that can change shape on demand. The evolution of flexibility contributes to aspects of performance from propulsive efficiency to environmental navigation. It is, however, challenging to quantify and compare body parts that, by their nature, dynamically vary in shape over many time scales. Commonly, body configurations are tracked by labelled markers and quantified parametrically through conventional measures of size and shape (descriptor approach) or non-parametrically through data-driven analyses that broadly capture spatiotemporal deformation patterns (shape variable approach). We developed a weightless marker tracking technique and combined these analytic approaches to study wing morphological flexibility in hoverfeeding Anna’s hummingbirds (Calypte anna). Four shape variables explained >95% of typical stroke cycle wing shape variation and were broadly correlated with specific conventional descriptors like wing twist and area. Moreover, shape variables decomposed wing deformations into pairs of in- and out-of-plane components at integer multiples of the stroke frequency. This property allowed us to identify spatiotemporal deformation profiles characteristic of hoverfeeding with experimentally imposed kinematic constraints, including through shape variables explaining <10% of typical shape variation. Hoverfeeding in front of a visual barrier restricted stroke amplitude and elicited increased stroke frequencies together with in- and out-of-plane deformations throughout the stroke cycle. Lifting submaximal loads increased stroke amplitudes at similar stroke frequencies together with prominent in-plane deformations during the upstroke and pronation. Our study highlights how spatially and temporally distinct changes in wing shape can contribute to agile fluidic locomotion.SummaryHummingbirds exhibit complex wing deformations throughout the stroke cycle, and the timing and origin of these deformations differs between hoverfeeding behaviours.
Sex and dominance status affect allogrooming in free-ranging feral cattle
Authors: Hodgson George M. W. , Flay Kate J. , Perroux Tania A. , Chan Wai Yan , McElligott Alan G. 
Published: May 2023

ABSTRACTSocial interactions are fundamental properties of gregarious species, helping to establish dominance hierarchies and maintain social bonds within groups, thus having significant effects on fitness. Cattle (Bos taurus) are social ungulates which engage in affiliative and agonistic relationships with other individuals. Although there are approximately 1.5 billion cattle on the planet, the opportunity to research cattle behaviour in free-ranging groups is rare, as there are few feral populations worldwide. Cattle engage in positive social behaviours such as allogrooming, where one individual licks the body of another. The relationship between affiliative behaviours and other individual characteristics (such as sex and dominance status) are frequently studied in other gregarious species, but are largely undetermined in cattle. To investigate the relationships between sex, dominance status and allogrooming, we observed a mixed-sex feral cattle herd in Hong Kong, recording dominance interactions and allogrooming events. We found that dominant females received more allogrooming than subordinate females, but subordinate females did not perform more than dominant ones. Males performed allogrooming more towards females than other males, but females groomed both sexes equally. Sex affected dominance position, with males obtaining higher status than females, but not all females were subordinate to males. These preferential allogrooming patterns improve our knowledge of sex-specific interactions, and help us to understand the dynamics of agonistic and affiliative behaviours in multi-male, multi-female ungulate groups. Studying a free-ranging feral population provides us with a unique insight into ungulate behavioural patterns and the evolution of cattle social behaviours.
Pseudoirreversible inhibition elicits persistent efficacy of a sphigosine-1-phosphate receptor-1 antagonist
Authors: Maruyama Yuya , Ohsawa Yusuke , Suzuki Takayuki , Yamauchi Yuko , Ohno Kohsuke , Inoue Hitoshi , Yamamoto Akitoshi , Hayashi Morimichi , Okuhara Yuji , Muramatsu Wataru , Namiki Kano , Hagiwara Naho , Miyauchi Maki , Miyao Takahisa , Ishikawa Tatsuya , Horie Kenta , Hayama Mio , Akiyama Nobuko , Hirokawa Takatsugu , Akiyama Taishin 
Published: May 2023

ABSTRACTSphingosine 1-phosphate receptor 1 (S1PR1), a G protein-coupled receptor, is required for lymphocyte trafficking, and is a promising therapeutic target in inflammatory diseases. We synthesized a competitive antagonist, KSI-6666, that persistently inhibits S1PR1 activity and effectively suppresses pathogenic inflammation. Metadynamics simulation proposed that the interaction of KSI-6666 with a methionine residue in the ligand-binding pocket of S1PR1 may inhibit the dissociation of KSI-6666 from S1PR1. Consistently, in vitro functional and mutational analyses revealed that KSI-6666 causes pseudoirreversible inhibition of S1PR1, dependent on the methionine residue of the protein and substituents on the distal benzene ring of KSI-6666. Moreover, in vivo study suggested that this pseudoirreversible inhibition is responsible for the persistent activity of KSI-6666. In this study, we discover that KSI-6666 is a potent S1PR1 antagonist, achieving pseudoirreversible inhibition of S1PR1 activity through interacting with a specific methionine residue.
Adopting Duplex Sequencing™ Technology for Genetic Toxicity Testing: A Proof-of-Concept Mutagenesis Experiment with N-Ethyl-N-Nitrosourea (ENU)-Exposed Rats
Authors: Smith-Roe Stephanie L. , Hobbs Cheryl A. , Hull Victoria , Auman J. Todd , Recio Leslie , Streicker Michael A. , Rivas Miriam V. , Pratt Gabriel A. , Lo Fang Yin , Higgins Jacob E. , Schmidt Elizabeth K. , Williams Lindsey N. , Nachmanson Daniela , Valentine Charles C. , Salk Jesse J. , Witt Kristine L. 
Published: May 2023

ABSTRACTDuplex sequencing (DuplexSeq) is an error-corrected next-generation sequencing (ecNGS) method in which molecular barcodes informatically link PCR-copies back to their source DNA strands, enabling computational removal of errors by comparing grouped strand sequencing reads. The resulting background of less than one artifactual mutation per 107nucleotides allows for direct detection of somatic mutations. TwinStrand Biosciences, Inc. has developed a DuplexSeq-based mutagenesis assay to sample the rat genome, which can be applied to genetic toxicity testing. To evaluate this assay for early detection of mutagenesis, a time-course study was conducted using male Hsd:Sprague Dawley SD rats (3 per group) administered a single dose of 40 mg/kg N-ethyl-N-nitrosourea (ENU) via gavage, with mutation frequency (MF) and spectrum analyzed in stomach, bone marrow, blood, and liver tissues at 3 h, 24 h, 7 d, and 28 d post-exposure. Significant increases in MF were observed in ENU-exposed rats as early as 24 h for stomach (site of contact) and bone marrow (a highly proliferative tissue) and at 7 d for liver and blood. The canonical, mutational signature of ENU was established by 7 d post-exposure in all four tissues. Interlaboratory analysis of a subset of samples from different tissues and time points demonstrated remarkable reproducibility for both MF and spectrum. These results demonstrate that MF and spectrum can be evaluated successfully by directly sequencing targeted regions of DNA obtained from various tissues, a considerable advancement compared to currently usedin vivogene mutation assays.HIGHLIGHTSDuplexSeq is an ultra-accurate NGS technology that directly quantifies mutationsENU-dependent mutagenesis was detected 24 h post-exposure in proliferative tissuesMultiple tissues exhibited the canonical ENU mutation spectrum 7 d after exposureResults obtained with DuplexSeq were highly concordant between laboratoriesThe Rat-50 Mutagenesis Assay is promising for applications in genetic toxicology