bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated Neuroprognostication via Machine Learning in Neonates with Hypoxic-Ischemic Encephalopathy
Authors: Lewis John D. , Miran Atiyeh A. , Stoopler Michelle , Branson Helen M. , Danguecan Ashley , Raghu Krishna , Ly Linh G. , Cizmeci Mehmet N. , Kalish Brian T. 
Published: May 2024

AbstractObjectivesNeonatal hypoxic-ischemic encephalopathy is a serious neurologic condition associated with death or neurodevelopmental impairments. Magnetic resonance imaging (MRI) is routinely used for neuroprognostication, but there is substantial subjectivity and uncertainty about neurodevelopmental outcome prediction. We sought to develop an objective and automated approach for the analysis of newborn brain MRI to improve the accuracy of prognostication.MethodsWe created an anatomical MRI template from a sample of 286 infants treated with therapeutic hypothermia, and labeled the deep gray-matter structures. We extracted quantitative information, including shape-related information, and information represented by complex patterns (radiomic measures), from each of these structures in all infants. We then trained an elastic net model to use either only these measures, only the infants’ clinical data, or both, to predict neurodevelopmental outcomes, as measured by the Bayley Scales of Infant and Toddler Development at 18 months of age.ResultsAmongst those infants who survived and for whom Bayley scores were available for cognitive, language, and motor outcomes, we found sets of MRI-based measures that could predict their Bayley scores with correlations that were more than twice the correlations based on only the clinical data, and explained more than four times the variance in the observed scores; predictions based on the combination of the clinical and MRI-based measures were similar or marginally better.InterpretationOur findings show that machine learning models using MRI-based measures can predict neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy across all neurodevelopmental domains and across the full spectrum of outcomes.
Rapid spread of the SARS-CoV-2 Omicron XDR lineage derived from recombination between XBB and BA.2.86 subvariants circulating in Brazil in late 2023
Authors: Arantes Ighor , Ito Kimihito , Gomes Marcelo , de Carvalho Felipe Cotrim , de Almeida Walquiria Aparecida Ferreira , Khouri Ricardo , Miyajima Fabio , Wallau Gabriel Luz , Naveca Felipe Gomes , Pereira Elisa Cavalcante ,   COVID-19 Fiocruz Genomic Surveillance Network, Siqueira Marilda Mendonça , Resende Paola Cristina , Bello Gonzalo 
Published: May 2024

ABSTRACTRecombination plays a crucial role in the evolution of SARS-CoV-2. The Omicron XBB* recombinant lineages are a noteworthy example, as they have been the dominant SARS-CoV-2 variant worldwide in the first half of 2023. Since November 2023, a new recombinant lineage between Omicron subvariants XBB and BA.2.86, designated XDR, has been detected mainly in Brazil. In this study, we reconstructed the spatiotemporal dynamics and estimated the absolute and relative transmissibility of the XDR lineage. The XDR lineage displayed a recombination breakpoint in the ORF1a coding region, and the most closely related sequences to the 5’ and 3’ ends of the recombinant correspond to JD.1.1 and JN.1.1 lineages, respectively. The first XDR sequences were detected in November 2023 in the Northeastern Brazilian region, and their prevalence rapidly surged from <1% to 25% by February 2024. The Bayesian phylogeographic analysis supports that the XDR lineage likely emerged in the Northeastern Brazilian region around late October 2023 and rapidly disseminated within and outside Brazilian borders from mid-November onwards. The median effective reproductive number of the XDR lineage in Brazil during the initial expansion phase was estimated to be around 1.5. In contrast, the average relative instantaneous reproduction numbers of XDR and JN* lineages were estimated to be 1.37 and 1.29 higher than that of co-circulating XBB* lineages. In summary, these findings support that the recombinant lineage XDR arose in the Northeastern Brazilian region in October 2023, shortly after the first detection of JN.1 sequences in the country. In Brazil, the XDR lineage exhibited a higher transmissibility level than its parental XBB.* lineages and is spreading at a rate similar to or slightly faster than the JN.1* lineages.
Dopey-dependent regulation of extracellular vesicles maintains neuronal morphology
Authors: Park Seungmee , Noblett Nathaniel , Pitts Lauren , Colavita Antonio , Wehman Ann M. , Jin Yishi , Chisholm Andrew D. 
Published: May 2024

ABSTRACTMature neurons maintain their distinctive morphology for extended periods in adult life. Compared to developmental neurite outgrowth, axon guidance, and target selection, relatively little is known of mechanisms that maintain mature neuron morphology. Loss of function inC. elegansDIP-2, a member of the conserved lipid metabolic regulator Dip2 family, results in progressive overgrowth of neurites in adults. We find thatdip-2mutants display specific genetic interactions withsax-2, theC. elegansortholog of Drosophila Furry and mammalian FRY. Combined loss of DIP-2 and SAX-2 results in severe disruption of neuronal morphology maintenance accompanied by increased release of neuronal extracellular vesicles (EVs). By screening for suppressors ofdip-2 sax-2double mutant defects we identified gain-of-function (gf) mutations in the conserved Dopey family protein PAD-1 and its associated phospholipid flippase TAT-5/ATP9A. Indip-2 sax-2double mutants carrying eitherpad-1(gf)ortat-5(gf)mutation, EV release is reduced and neuronal morphology across multiple neuron types is restored to largely normal. PAD-1(gf) acts cell autonomously in neurons. The domain containingpad-1(gf) is essential for PAD-1 function, and PAD-1(gf) protein displays increased association with the plasma membrane and inhibits EV release. Our findings uncover a novel functional network of DIP-2, SAX-2, PAD-1, and TAT-5 that maintains morphology of neurons and other types of cells, shedding light on the mechanistic basis of neurological disorders involving human orthologs of these genes.
Interresponse time and run length shaping by discrete-trial percentile schedule incorporating fixed consecutive number procedure
Authors: Orihara Tomotaka , Tanno Takayuki 
Published: May 2024

AbstractThe effect of incorporating a fixed consecutive number (FCN) procedure in interresponse time (IRT) shaping using a discrete-trial percentile schedule was examined. Eight pigeons were used. On each trial, pigeons were required to peck the IRT start key and then the IRT end key. Reinforcers were presented according to the percentile schedule based on the time interval (IRT) or the cumulative response count to the IRT start key during those two key pecks. Multiple responses to the IRT start key were allowed only in the condition incorporating the FCN procedure. Results showed that incorporating the FCN procedure improved the success of IRT shaping from 1/8 to 7/8 of the pigeons. The procedure developed in this study provides an ideal baseline for studying response shaping with IRT as the dependent variable.
E-cadherin tunes tissue mechanical behavior before and during morphogenetic tissue flows
Authors: Wang Xun , Cupo Christian M. , Ostvar Sassan , Countryman Andrew D. , Kasza Karen E. 
Published: May 2024

SummaryAdhesion between epithelial cells enables the remarkable mechanical behavior of epithelial tissues during morphogenesis. However, it remains unclear how cell-cell adhesion influences mechanics in static as well as in dynamically flowing epithelial tissues. Here, we systematically modulate E-cadherin-mediated adhesion in theDrosophilaembryo and study the effects on the mechanical behavior of the germband epithelium before and during dramatic tissue remodeling and flow associated with body axis elongation. Before axis elongation, we find that increasing E-cadherin levels produces tissue comprising more elongated cells and predicted to be more fluid-like, providing reduced resistance to tissue flow. During axis elongation, we find that the dominant effect of E-cadherin is tuning the speed at which cells proceed through rearrangement events, revealing potential roles for E-cadherin in generating friction between cells. Before and during axis elongation, E-cadherin levels influence patterns of actomyosin-dependent forces, supporting the notion that E-cadherin tunes tissue mechanics in part through effects on actomyosin. Taken together, these findings reveal dual—and sometimes opposing—roles for E-cadherin-mediated adhesion in controlling tissue structure and dynamicsin vivothat result in unexpected relationships between adhesion and flow.
Fast-spiking interneuron detonation drives high-fidelity inhibition in the olfactory bulb
Authors: Burton Shawn D. , Malyshko Christina M. , Urban Nathaniel N. 
Published: May 2024

AbstractInhibitory circuits in the mammalian olfactory bulb (OB) dynamically reformat olfactory information as it propagates from peripheral receptors to downstream cortex. To gain mechanistic insight into how specific OB interneuron types support this sensory processing, we examine unitary synaptic interactions between excitatory mitral and tufted cells (MTCs), the OB projection cells, and a conserved population of anaxonic external plexiform layer interneurons (EPL-INs) using pair and quartet whole-cell recordings in acute mouse brain slices. Physiological, morphological, neurochemical, and synaptic analyses divide EPL-INs into distinct subtypes and reveal that parvalbumin-expressing fast-spiking EPL-INs (FSIs) perisomatically innervate MTCs with release-competent dendrites and synaptically detonate to mediate fast, short-latency recurrent and lateral inhibition. Sparse MTC synchronization supralinearly increases this high-fidelity inhibition, while sensory afferent activation combined with single-cell silencing reveals that individual FSIs account for a substantial fraction of total network-driven MTC lateral inhibition. OB output is thus powerfully shaped by detonation-driven high-fidelity perisomatic inhibition.
Development of Retinotopic Feedback: Layer 6 Pyramids to Lateral Geniculate Principal Cells
Authors: Levy William B. , Baxter Robert A. 
Published: May 2024

AbstractThe development of many feedforward pathways in the brain, from sensory inputs to neocortex, have been studied and modeled extensively, but the development of feedback connections, which tend to occur after the development of feedforward pathways, have received less attention. The abundance of feedback connections within neocortex and between neocortex and thalamus suggests that understanding feedback connections is crucial to understanding connectivity and signal processing in the brain. It is well known that many neural layers are arranged topologically with respect to sensory input, and many neural models impose a symmetry of connections between layers, commonly referred to as reciprocal connectivity. Here, we are concerned with how such reciprocal, feedback connections develop so that the topology of the sensory input is preserved. We focus on feedback connections from layer 6 of visual area V1 to primary neurons in the Lateral Geniculate Nucleus (LGN). The proposed model is based on the hypothesis that feedback connections from V1-L6 to LGN use voltage-activated T-channels to appropriately establish and modify synapses in spite of unavoidable temporal delays. We also hypothesize that developmental spindling relates to synaptogenesis and memory consolidation.
The microbiome shapes immunity in a sex-specific manner in mouse models of Alzheimer’s disease
Authors: Bostick John W. , Connerly T. Jaymie , Thron Taren , Needham Brittany D. , de Castro Fonseca Matheus , Kaddurah-Daouk Rima , Knight Rob , Mazmanian Sarkis K. 
Published: May 2024

AbstractINTRODUCTION: Preclinical studies reveal that the microbiome broadly affects immune responses and deposition and/or clearance of amyloid-beta (Aβ) in mouse models of Alzheimer’s disease (AD). Whether the microbiome shapes central and peripheral immune profiles in AD models remains unknown.METHODS: We examined adaptive immune responses in two mouse models containing AD- related genetic predispositions (3xTg and 5xFAD) in the presence or absence of the microbiome.RESULTS: T and B cells were altered in brain-associated and systemic immune tissues between genetic models and wildtype mice, with earlier signs of immune activity in females. Systemic immune responses were modulated by the microbiome and differed by sex. Further, the absence of a microbiome in germ-free mice resulted in reduced cognitive deficits, primarily in females.DISCUSSION: These data reveal sexual dimorphism in early signs of immune activity and microbiome effects, and highlight an interesting interaction between sex and the microbiome in mouse models of AD.
Epidermal Collagen Reduction Drives Selective Aspects of Aging in Sensory Neurons
Authors: Krishna Meera M. , Waghmare Swapnil G. , Franitza Ariel L. , Maccoux Emily C. , Lezi E 
Published: May 2024

ABSTRACTDespite advances in understanding molecular and cellular changes in the aging nervous system, the upstream drivers of these changes remain poorly defined. Here, we investigate the roles of non-neural tissues in neuronal aging, using the cutaneous PVD polymodal sensory neuron inCaenorhabditis elegansas a model. We demonstrate that during normal aging, PVD neurons progressively develop excessive dendritic branching, functionally correlated with age-related proprioceptive deficits. Our study reveals that decreased collagen expression, a common age-related phenomenon across species, triggers this process. Specifically, loss-of-function indpy-5orcol-120, genes encoding cuticular collagens secreted to the epidermal apical surface, induces early-onset excessive dendritic branching and proprioceptive deficits. Adulthood-specific overexpression ofdpy-5orcol-120mitigates excessive branching in aged animals without extending lifespan, highlighting the specific role of these collagens in promoting neuronal healthspan. Notably, collagen reduction specifically drives excessive branching in select sensory neuron subclasses but does not contribute to dendritic beading, another aging-associated neurodegenerative phenotype distinctively associated with a different mechanosensitive dysfunction. Lastly, we identify thatrig-3, an Immunoglobulin Superfamily member expressed in interneurons, acts upstream of collagen genes to maintain PVD dendritic homeostasis during aging, with downstream requirement ofdaf-16/FOXO. These findings reveal that age-related collagen reduction cues neuronal aging independently of collagen’s traditional structural support function, potentially involving bi-directional communication processes between neurons and non-neuronal cells. Our study also offers new insights into understanding selective neuron vulnerability in aging, emphasizing the importance of multi-tissue strategies to address the complexities of neuronal aging.
Transcriptional Signatures Associated with the Survival ofEscherichia coliBiofilm During Treatment with Plasma-Activated Water
Authors: Vyas Heema Kumari Nilesh , Hoque M. Mozammel , Xia Binbin , Alam David , Cullen Patrick J. , Rice Scott A. , Mai-Prochnow Anne 
Published: May 2024

AbstractBiofilm formation on surfaces, tools and equipment can damage their quality and lead to high repair or replacement costs. Plasma-activated water (PAW), a new technology, has shown promise in killing biofilm and non-biofilm bacteria due to its mix of reactive oxygen and nitrogen species (RONS), and in particular superoxide. However, the specific genetic mechanisms behind PAW’s effectiveness, especially against biofilms, are not yet fully understood. Here, we examined the stress responses ofEscherichia colibiofilms when exposed to sub-lethal PAW treatment with and without superoxide (by adding the scavenger Tiron to remove it). A 40% variation in gene expression was observed for PAW treated biofilms when compared to PAW-Tiron and controls. Specifically, PAW treatment resulted in 478 upregulated genes (> 1.5 log2FC) and 186 downregulated genes (< −1.5 log2FC) compared to the control. Pathway enrichment and biological process enrichment analysis revealed significant upregulation of sulfur metabolism, ATP-binding cassette transporter genes, amino acid metabolic/biosynthesis pathways, hypochlorite response systems and oxidative phosphorylation for biofilms treated with PAW compared to control. Knockout mutants of significantly upregulated genes associated with these pathwaystrxC(4.23-fold),cysP(1.58-fold) andnuoM(1.74-fold) were compared to the wild-type (WT) for their biofilm viability and intracellular RONS accumulation. Relative to PAW-treated WT,ΔtrxCandΔnuoMknockout mutants displayed significantly reduced biofilm viability (P ≤ 0.05) confirming their role in PAW-mediated response. Interestingly,ΔtrxCbiofilms had the highest intracellular ROS accumulation, as revealed by DCFDA staining after PAW treatment. This study gives a detailed insight into howE. colibiofilms respond to oxidative stress induced by PAW. It highlights the significance of superoxide in PAW’s bactericidal effects. Overall, our findings shed light on the specific genes and pathways that helpE. colibiofilms survive and respond to PAW treatment, offering a new understanding of plasma technology and its anti-biofilm mechanisms.
STECode: an automated virulence barcode generator to aid clinical and public health risk assessment of Shiga toxin-producingEscherichia coli
Authors: Sim Eby M. , Fong Winkie , Suster Carl , Agius Jessica E. , Chandra Shona , Suliman Basel , Wang Qinning , Ngo Christine , Finemore Connor , Chen Sharon C-A. , Basile Kerri , Sintchenko Vitali 
Published: May 2024

AbstractShiga Toxin (Stx) producingEscherichia coli(STEC) is a subset of pathogenicE. colithat can produce two types of Stx, Stx1 and Stx2, which can be further subtyped into four and 15 subtypes respectively. Not all subtypes, however, are equal in virulence potential, and the risk of severe disease including haemolytic uraemic syndrome has been linked to certain Stx2 subtypes e.g. Stx2a, Stx2d, highlighting the importance to surveystxsubtypes. Previously, we developed a STEC virulence barcode to capture pertinent information on virulence genes to infer pathogenic potential. However, the process required multiple manual curation steps to determine the barcode. Here we introduce STECode, a bioinformatic tool to automate the STEC virulence barcode generation from sequencing reads or genomic assemblies. The development, and validation of STECode is described using a set of publicly available completed STEC genomes, along with their corresponding short reads. STECode was applied to interrogate the virulence landscape and molecular epidemiology of human STEC isolated during the period of the international border closures related to COVID-19 in the state of New South Wales, Australia.Impact statementWhole genome sequencing has been used to great effect in the genomic surveillance of STEC for public health purposes via the tracking of outbreaks. With STECode, we present a method to generate a STEC virulence barcode which captures pertinent subtyping information, useful for genomic inference of pathogenic potential. A key blind spot generated in short-read sequencing is the inability to detect the presence of multiple, isogenicstxcopies in STEC. STECode mitigates this by inferring and reporting on the possibility of this occurrence. We envisage that this tool will value-add current genomic surveillance workflows through the ability to infer pathogenic potential.
Factors affecting contact tracing for the early detection of Leprosy cases: A qualitative study in Ho, Volta Region, Ghana
Authors: Ahiabu Araba Aseye , Tabong Philip Teg-Neefah 
Published: May 2024

AbstractIntroductionDespite Ghana being at the elimination phase of Leprosy, new cases of Leprosy are recorded in the country annually. These cases are usually detected in the advanced stages when Grade 2 disabilities (G2D) have set in. The WHO regards high G2D rates as an indication that measures need to be taken especially with regard to early detection. Late detection of cases raises concern about the spread of the infection. Contact tracing of index cases of Leprosy is therefore key in containing the spread. If the current situation is left unattended, Ghana faces the challenge of retrogressing in its fight against Leprosy. The general objective is to explore the factors affecting contact tracing for early case detection of Leprosy.MethodsThis study employed a qualitative research methodology. Specifically, the study adopted the phenomenology study design. Maximum variation purposive sampling technique was used for people affected by Leprosy who were either on treatment at the Ho Polyclinic or had completed treatment, health workers of the Polyclinic and community members at Ho, in the Volta Region of Ghana. Data was collected using in-depth interviews and focus group discussions among selected participants. All IDIs and FGDs were audio-recorded and transcribed verbatim. The data was coded using NVivO version 14 and analysed thematically.ResultsThe results of this study showed that a majority of the community members and people affected by Leprosy perceived that Leprosy is caused by supernatural forces and hence the disease is not transmissible. Factors such as the stigma associated with the disease, reliance on divine forms of healing, use of herbs and poor symptom recognition hinder early detection. The study also revealed gaps in contact tracing efforts such as the inadequacy of funds for contact tracing as well as the reluctance of some contacts to be involved in the process.ConclusionThe study concluded that both community and health system factors affect early detection of Leprosy cases in Ho. This has the potential to undermine Ghana’s quest to eliminate Leprosy. There is a need to increase awareness of the importance of contact tracing for early detection of Leprosy.
Child diarrhea in Cambodia: A descriptive analysis of temporal and geospatial trends and logistic regression-based examination of factors associated with diarrhea in children under five years
Authors: Um Samnang , Phan Channnarong , Sakha Sok , Dany Leng 
Published: May 2024

AbstractDiarrhea is a global public health problem that is the third leading cause of death in under five years, with an estimated 1.7 billion cases in 2023 and 1.8 million deaths from diarrhea diseases every year. To better understand child diarrhea in Cambodia, we examined descriptively temporal and geospatial trends of diarrhea and used multivariate logistic regression to analyze its association with individual and household characteristics and diarrhea among children aged 0-59 months using data from the Cambodia Demographic and Health Survey for 2005 to 2022. The prevalence of diarrhea among children aged 0–59 months decreased from 19.7% in 2005 to 6.2% in 2022. The highest prevalence of childhood diarrhea in Kampong Cham (30.1%), in Mondul Kiri/Ratanak Kiri (24.6%), Battambang/Pailin (20.9%), and Mondul Kiri/Ratanak Kiri (12.9%) for 2005, 2010, 2014 and 2022. After adjusting for other variables, factors independently associated with childhood diarrhea included mothers aged 25-34 years (adjusted odds ratio (AOR) = 0.68; 95% CI: 0.48–0.96), 35-49 years (AOR = 0.60; 95% CI: 0.42–0.87), completed higher education (AOR = 0.61; 95% CI: 0.41–0.91), and employed (AOR = 0.79; 95% CI: 0.72– 0.96). Children were less likely to have diarrhea if they were older than 36 months, richest household (AOR = 0.69; 95% CI: 0.55–0.86), coastal region (AOR = 0.53; 95% CI: 0.41–0.69), born to smoker mothers (AOR = 1.61; 95% CI: 1.25–2.08), had barrier access to healthcare services (AOR = 1.20; 95% CI: 1.07–1.35), or children aged 6–23 months. Diarrhea remains highly prevalent among children in Cambodia. Public health interventions and policies to alleviate diarrhea should be prioritized to address these factors across geographical.