bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends and Determinants of Neonatal Mortality in Rural Ethiopia
Authors: Asaye Sintayehu , Saketa Dawit , Birhanu Dires , Gudeta Tadesse , Besho Merga , Getnet Masrie , Debelew Gurmesa Tura , Berhanu Negalign , Siraneh Yibeltal , Abamecha Fira , Tamiru Dessalegn 
Published: March 2024

AbstractBackgroundNeonatal mortality is a significant challenge that affects babies within the first 28 days of life. The issue is particularly challenging for healthcare systems in developing countries, where interventions are required. Although there has been a decline in neonatal mortality worldwide, comprehensive data on the patterns of neonatal mortality and the contributing factors in rural regions of Ethiopia is lacking.ObjectiveTo determine neonatal mortality trends and mortality in rural Ethiopia using 2011-2019 DHS dataMethodsEthiopian demographic health survey (EDHS) program conducted a cross-sectional community-based study in rural Ethiopia in 2011, 2016, and 2019. The study included women who gave birth within the specified timeframe and agreed to participate. Sampling was done through a multistage cluster approach, and STATA version 17 was used to analyze the data. Predictor variables were validated through multiple logistic regression analysis. Weighted estimates were used to derive population-level statistics and a p-value less than 0.05 was considered significant.ResultsThe study analyzed data from 22,755 women who participated in EDHS surveys between 2011 and 2019. Neonatal mortality rates decreased from 7.5% to 6.03%. Regional variations were observed, with Gambela and Tigrai having the lowest rates, and Dire Dawa and the Somali region having higher rates. Factors like mother’s age, wealth index, birth order, neonate’s sex, and presence of twins, immediate breastfeeding, and baby’s size were associated with neonatal mortality.Conclusion and recommendationDespite significant advancements that have been made to decrease neonatal mortality, there remain challenges that need to be addressed. Therefore, regional health bureaus should strengthen their strategies to enhance antenatal care (ANC) visits and promote birth delivery at health facilities.
Patient Preferences for Diagnostic Imaging Services: Decentralize or not?
Authors: van den Broek-Altenburg Eline M. , Benson Jamie S. , Atherly Adam J. , DeStigter Kristen K. 
Published: March 2024

AbstractThe objective of this study was to identify patient preferences for outpatient diagnostic imaging services and analyze how patients make trade-offs between attributes of these services using a discrete choice experiment (DCE).We used a DCE with 14 choice questions asking which imaging locations patients would prefer. We used latent class analysis to analyze preference heterogeneity between different patient groups and to estimate the relative value they assign to different attributes of imaging services.Our analysis showed that the “Experienced Patients” subgroup generally value diagnostic imaging services in both acute and chronic situations and had a strong preference for hospital outpatient radiology departments (HORD) that would provide services at lower costs, where their images would be interpreted by a specialty radiologist, the clinic would be recommended by their PCP, online scheduling would be available, service rating were higher, and travel and wait times would be shorter. New Patients significantly valued the service rating of the hospital outpatient radiology departments (HORD) and online scheduling.HORDs can be more competitive by providing services that live up to expectations better than available retail radiology clinics (RRCs). Most RRCs do not currently offer online scheduling so ease of use may also steer patients towards HORDs. HORDs have the advantage of being linked to the main medical center which has the reputation of having clinical expertise and more sophisticated technology. We conclude that there is room for medical centers to build HORDs that provide an appealing and competitive alternative to current RRC.
Characterising the stimulus-response function of mouse C-Low threshold mechanoreceptors to mechanical stimuliin vivo
Authors: Semizoglou Evangelia , Lo Re Laure , Middleton Steven J. , Perez-Sanchez Jimena , Tufarelli Tommaso , Bennett David L. , Chisholm Kim I. 
Published: March 2024

AbstractC-low threshold mechanoreceptors (C-LTMRs) in animals (termed C-tactile (CT) fibres in humans) are a subgroup of C-fibre primary afferents, which innervate hairy skin and respond to low threshold punctate indentations and brush stimuli. These afferents respond to gentle, touch stimuli and are implicated in mediating pleasant/affective touch. These afferents have traditionally been studied using low-throughput, technically challenging approaches, including microneurography in humans and teased fibre electrophysiology in other mammals. Here we suggest a new approach to studying genetically labelled C-LTMRs usingin vivocalcium imaging. We used an automated rotating brush stimulus and Von Frey filaments, applied to the hairy skin of anaesthetised mice to mirror light and affective touch. Simultaneously we visualised changes in C-LTMR activity and confirmed that these neurons are sensitive to low-threshold punctate mechanical stimuli and brush stimuli with a strong preference for slow brushing speeds. We also reveal that C-LMTRs are directionally sensitive, showing more activity when brushed against the natural orientation of the hair. We presentin vivocalcium imaging of genetically labelled C-LTMRs as a useful approach that can reveal new aspects of C-LTMR physiology.
Limb connective tissue is organized in a continuum of promiscuous fibroblast identities during development
Authors: Hirsinger Estelle , Blavet Cédrine , Bonnin Marie-Ange , Bellenger Léa , Gharsalli Tarek , Duprez Delphine 
Published: March 2024

AbstractTight developmental coordination of muscle attachments with skeletal muscle is fundamental for building functional limbs and allowing locomotion. Muscle attachments include connective tissue fibroblasts of tendon and muscle connective tissue. Although muscle attachments play critical roles in development, our understanding of connective tissue fibroblast developmental programs lags behind that of other components of the musculoskeletal system, mainly because fibroblasts are highly heterogeneous and poorly characterized. Combining single-cell RNA-sequencing-based strategies including trajectory inference andin situhybridization analyses, we address the diversity of connective tissue fibroblasts and their developmental trajectories during chicken limb fetal development. We show that fibroblasts switch from a program providing positional information to a program of lineage diversification at the onset of fetal period. Muscle connective tissue and tendon contain several fibroblast populations that emerge asynchronously. Once the final muscle pattern is set,in silicofibroblast populations that are close in transcriptional identity are found in neighbouring locations in limbs, prefiguring the adult fibroblast layers associated to muscle. We propose that the limb connective tissue is organised in a continuum of promiscuous fibroblast identities, allowing for the robust and efficient connection of the muscular system to bone and skin.HighlightsDissection of connective tissue heterogeneity using single-cell RNA-sequencing andin situRNA stainingIn silicofibroblast populations map to distinct fibroblast layers in limbsMolecular signatures of fetal fibroblast populations at the origin of limb adult connective tissueEpimysium and endomysium fibroblasts are transcriptionally distinct at fetal stageLimb fibroblasts display promiscuous identities reflecting their interconnected 3D-networkFibroblasts switch from providing positional information to differentiation during development
2-oxoglutarate triggers assembly of active dodecamericMethanosarcina mazeiglutamine synthetase
Authors: Herdering Eva , Reif-Trauttmansdorff Tristan , Kumar Anuj , Habenicht Tim , Hochberg Georg , Bohn Stefan , Schuller Jan , Schmitz Ruth A. 
Published: March 2024

AbstractGlutamine synthetases (GS) are central enzymes essential for the nitrogen metabolism across all domains of life. Consequently, they have been extensively studied for more than half a century. Based on the ATP dependent ammonium assimilation generating glutamine, GS expression and activity are strictly regulated in all organisms. In the methanogenic archaeonMethanosarcina mazei, it has been shown that the metabolite 2-oxoglutarate (2-OG) directly induces the GS activity. Besides, modulation of the activity by interaction with small proteins (GlnK1and sP26) has been reported. Here, we show that the strong activation ofM. mazeiGS (GlnA1) by 2-OG is based on the 2-OG dependent dodecamer assembly of GlnA1by using mass photometry (MP) and single particle cryo-electron microscopy (cryo-EM) analysis of purified strep-tagged GlnA1. The dodecamer assembly from dimers occurred without any detectable intermediate oligomeric state and was not affected in the presence of GlnK1. The 2.39 Å cryo-EM structure of the dodecameric complex in the presence of 12.5 mM 2-OG demonstrated that 2-OG is binding between two monomers. Thereby, 2-OG appears to induce the dodecameric assembly in a cooperative way. Furthermore, the active site is primed by an allosteric interaction cascade caused by 2-OG-binding towards an adaption of an open active state conformation. In the presence of additional glutamine, strong feedback inhibition of GS activity was observed. Since glutamine dependent disassembly of the dodecamer was excluded by MP, feedback inhibition most likely relies on an allosteric binding of glutamine to the catalytic site.Based on our findings, we propose that under nitrogen limitation the induction ofM. mazeiGS into a catalytically active dodecamer is not affected by GlnK1and crucially depends on the presence of 2-OG.
Scaled and Efficient Derivation of Loss of Function Alleles in Risk Genes for Neurodevelopmental and Psychiatric Disorders in Human iPSC
Authors: Zhang Hanwen , Peyton Lilia , McCarroll Ada , de León Guerrerro Sol Díaz , Zhang Siwei , Gowda Prarthana , Sirkin David , Achwah Mahmoud El , Duhe Alexandra , Wood Whitney G. , Jamison Brandon , Tracy Gregory , Pollak Rebecca , Hart Ronald P. , Pato Carlos N. , Mulle Jennifer G. , Sanders Alan R. , Pang Zhiping P. , Duan Jubao 
Published: March 2024

SummaryTranslating genetic findings for neurodevelopmental and psychiatric disorders (NPD) into actionable disease biology would benefit from large-scale and unbiased functional studies of NPD genes. Leveraging the cytosine base editing (CBE) system, here we developed a pipeline for clonal loss-of-function (LoF) allele mutagenesis in human induced pluripotent stem cells (hiPSCs) by introducing premature stop-codons (iSTOP) that lead to mRNA nonsense-mediated-decay (NMD) or protein truncation. We tested the pipeline for 23 NPD genes on 3 hiPSC lines and achieved highly reproducible, efficient iSTOP editing in 22 NPD genes. Using RNAseq, we confirmed their pluripotency, absence of chromosomal abnormalities, and NMD. Interestingly, for three schizophrenia risk genes (SETD1A, TRIO,CUL1), despite the high efficiency of base editing, we only obtained heterozygous LoF alleles, suggesting their essential roles for cell growth. We replicated the reported neural phenotypes ofSHANK3-haploinsufficiency and foundCUL1-LoF reduced neurite branches and synaptic puncta density. This iSTOP pipeline enables a scaled and efficient LoF mutagenesis of NPD genes, yielding an invaluable shareable resource.
Unraveling a novel dual-function regulatory element showing epistatic interaction with a variant that escapes genome-wide association studies
Authors: Adjemout Mathieu , Nisar Samia , Escandell Amélie , Huu Hong Thu Nguyen , Torres Magali , Thiam Alassane , Manosalva Iris , Mbengue Babacar , Dieye Alioune , Spicuglia Salvatore , Rihet Pascal , Marquet Sandrine 
Published: March 2024

Regulation of gene expression has recently been complexified by the identification of Epromoters, a subset of promoters with enhancer function. Here, we uncovered the first dual cis-regulatory element, "ESpromoter," exhibiting both enhancer and silencer function, as a regulator of the nearby genesATP2B4andLAX1in single human T cells. Through integrative approach, we pinpointed functional rs11240391, a severe malaria risk variant that escapes detection in genome-wide association studies, challenging conventional strategies for identifying causal variants. CRISPR-modified cells demonstrated the regulatory effect of ESpromoter and rs11240391 onLAX1expression and T cell activation. Furthermore, our findings revealed an epistatic interaction between ESpromoter SNPs and rs11240391, impacting severe malaria susceptibility by further reducingLAX1expression. This groundbreaking discovery challenges the conventional enhancer-silencer dichotomy. It highlights the sophistication of transcriptional regulation and argues for an integrated approach combining genetics, epigenetics, and genomics to identify new therapeutic targets for complex diseases.HIGHLIGHTSNovel dual enhancer-silencer element (ESpromoter) in a single human cell typeFunctional SNP for severe malaria risk that escapes genome-wide association studiesGenome editing at the SNP demonstrates a regulatory effect onLAX1and T cell activationEpistatic interaction between SNPs increases the risk of severe malariaIn briefEpistatic interaction between common variants within a novel dual enhancer-silencer regulatory element and theLAX1promoter variant is responsible for severe malaria susceptibility through T-cell activation.
Cardiac Outflow tract septation defects in a DiGeorge syndrome model respond to Minoxidil treatment
Authors: Aurigemma Ilaria , Ferrentino Rosa , Krishnan Varsha Poondi , Lanzetta Olga , Angelini Claudia , Illingworth Elizabeth , Baldini Antonio 
Published: March 2024

ABSTRACTBackgroundThe T-BOX transcription factor TBX1 is essential for the development of the pharyngeal apparatus and it is haploinsufficient in DiGeorge syndrome (DGS), a developmental anomaly associated with congenital heart disease and other abnormalities. The murine model recapitulates the heart phenotype and showed collagen accumulation.MethodsWe first used a cellular model to study gene expression during cardiogenic differentiation of WT andTbx1-/-mouse embryonic stem cells. Then we used a mouse model of DGS to test whether interfering with collagen accumulation using an inhibitor of lysyl hydroxylase would modify the cardiac phenotype of the mutant.Results and conclusionsIn the cell differentiation model, loss ofTbx1was associated with up regulation of a subset of ECM-related genes, including several collagen genes. In thein vivomodel, early prenatal treatment with Minoxidil, a lysyl hydroxylase inhibitor, ameliorated the cardiac outflow tract septation phenotype inTbx1mutant fetuses, but it had no effect on septation in WT fetuses. We conclude that TBX1 suppresses a subset of ECM-related genes. The partial rescue of the septation phenotype through Minoxidil treatment suggests that inhibiting collagen cross-linking reduces the impact of the phenotypic consequences ofTbx1mutation.
TheCandida aurisHog1 MAP kinase is essential for the colonization of murine skin and intradermal persistence
Authors: Shivarathri Raju , Chauhan Manju , Datta Abhishek , Das Diprasom , Karuli Adela , Jenull Sabrina , Kuchler Karl , Thangamani Shankar , Chowdhary Anuradha , Desai Jigar V. , Chauhan Neeraj 
Published: March 2024

AbstractCandida auris, a multidrug-resistant human fungal pathogen, was first identified in 2009 in Japan. Since then, systemicC. aurisinfections have now been reported in more than 50 countries, with mortality rates of 30-60%. A major contributing factor to its high inter- and intrahospital clonal transmission is thatC. auris,unlike mostCandidaspecies, displays unique skin tropism and can stay on human skin for a prolonged period. However, the molecular mechanisms responsible forC. aurisskin colonization, intradermal persistence, and systemic virulence are poorly understood. Here, we report thatC. aurisHog1 mitogen-activated protein kinase (MAPK) is essential for efficient skin colonization, intradermal persistence, as well as systemic virulence. RNA-seq analysis of wildtype parental andhog1Δ mutant strains revealed marked down-regulation of genes involved in processes such as cell adhesion, cell-wall rearrangement, and pathogenesis inhog1Δ mutant compared to the wildtype parent. Consistent with these data, we found a prominent role for Hog1 in maintaining cell-wall architecture, as thehog1Δ mutant demonstrated a significant increase in cell-surface β-glucan exposure and a concomitant reduction in chitin content. Additionally, we observed that Hog1 was required for biofilm formationin vitroand fungal survival when challenged with primary murine macrophages and neutrophilsex vivo. Collectively, these findings have important implications for understanding theC. aurisskin adherence mechanisms and penetration of skin epithelial layers preceding bloodstream infections.ImportanceCandida aurisis a World Health Organization (WHO) fungal priority pathogen and an urgent public health threat recognized by the Centers for Disease Control and Prevention (CDC).C. aurishas a unique ability to colonize human skin. It also persists on abiotic surfaces in healthcare environments for an extended period of time. These attributes facilitate the inter- and intrahospital clonal transmission ofC. auris. Therefore, understandingC. aurisskin colonization mechanisms are critical for infection control, especially in hospitals and nursing homes. However, despite its profound clinical relevance, the molecular and genetic basis ofC. aurisskin colonization mechanisms are poorly understood. Herein, we present data on the identification of the Hog1 MAP kinase as a key regulator ofC. aurisskin colonization. These findings lay foundation for further characterization of unique mechanisms that promote fungal persistence on human skin.
Structure and Functions of Gesture Sequences in Wild Bonnet Macaques (Macaca radiata)
Authors: Gupta Shreejata , Sinha Anindya 
Published: March 2024

AbstractCompositionality, a hallmark of human language, involves generating novel meaning by combining existing units. Nonhuman primates (mostly apes) are known to combine gestural units in non-random ways, but they do not make novel meaning with these combinations. What could, however, be the functional roles of these gesture sequences and whether they bear any significance to language evolution is still unclear. Moreover, studies on gesture-sequences in non-ape primate species is almost non-existent. Here, we investigated for the first time, the structure and functions of gesture sequences in the naturally occurring communication of wild bonnet macaques (Macaca radiata), using analyses akin to ape gesture studies (Genty & Byrne, 2010; Hobaiter & Byrne, 2011). Bonnet macaque gesture sequences exhibit non-random combinations of gestures and non-gesture units – certain gestures are significantly more common in sequences, they associate preferentially with specific other components and certain components are more likely to appear either at the beginning or at the end of a sequence. Interplay of these sequences form distinct gestural clusters, corresponding to affiliative/play and agonistic contexts. Although, the overall functions of bonnet macaque gesture sequences remain obscure, as in apes, we found that gesture sequences were specifically used as a persistence strategy, after the initial single gestures have failed to initiate and sustain social interactions. We discuss our findings in the light of a possibility that primate gesture sequences, coordinating the flow of social interactions, may be evolutionary precursors to pragmatic gestures in human language.
Stability and affinity evaluation of aptamers as a biorecognition system for testosterone and its analogs
Authors: Medina-Benítez Ariadna , García-Alonso Claudia A. , Fragoso-Rodríguez Roberto , Torres-Huerta Ana Laura , Antonio-Pérez Aurora 
Published: March 2024

ABSTRACTThe present project results from the need to develop a biosensor for the detection of testosterone and synthetic analogs in nutritional supplements. A biosensor is composed of two systems: (1) the biorecognition system and (2) the transducer system. We propose the use of aptamers as a biorecognition system, given their functional capacities to recognize and “capture” specific small analytes. For this study, eight aptamers sequences with previous reports of interaction with testosterone were evaluated to select the best candidate on regard with the best affinity and structural stability at different ionic concentrations and temperature values.In silicoanalysis involves predicting secondary and tertiary structures in different conditions and molecular docking.In vitroanalysis. tracks the changes in the folded and unfolded aptamer dimensions monitored by dynamic light scattering under the previouslyin silicoconditions, and performs relative capture tests with testosterone and testosterone undecanoate by immobilized aptamers on gold nanoparticles. The outcomes of thein silicoapproach aligned with the experimental data collected, exhibit that the nucleotide composition and aptamers binding structure, intervene in their affinity and biosensor functionality. The aptamers apT5 and P4G13 were discarded as possible candidates because they did not show stability in experimental conditions (temperature and ion plug). TESS2, TESS3, T4, T5.1, and T6 proved to be functional aptamers because they showed good affinity with the three analytes, however, TESS1 turned out to be the best candidate because of its stability and number of interactions, which translates into a greater affinity, compared to the rest.