bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pseudogenisation of NK3 Homeobox 2 (Nkx3.2) in Monotremes Provides Insight into Unique Gastric Anatomy and Physiology
Authors: Dann Jackson , Qu Zhipeng , Shearwin-Whyatt Linda , van der Ploeg Rachel , Grützner Frank 
Published: March 2024

AbstractDevelopment of the vertebrate antral stomach and pyloric sphincter (antropyloric region) – involved in enzymatic breakdown and thoroughfare of food - is underpinned by a highly conserved developmental pathway involving the hedgehog, bone morphogenetic protein (BMP) and Wingless/Int-1 (Wnt) protein families. Monotremes are a unique lineage where acid-based digestion has been lost, and this correlates with a lack of genes for gastric acid and enzymes in the genomes of the platypus (Ornithorhynchus anatinus) and short-beaked echidna (Tachyglossus aculeatus). Furthermore, these species feature unique gastric phenotypes, both with truncated and aglandular antral stomachs and the platypus with no pylorus. Here, we explore the genetic underpinning of monotreme gastric phenotypes, investigating genes important in antropyloric development using the newest monotreme genome sequences (mOrnAna1.pri.v4 and mTacAcu1) together with RNA-seq data. We found that the pathway is generally conserved but, NK3 homeobox 2 (Nkx3.2) was pseudogenised in both platypus and echidna. We speculate that pyloric-like restriction in the echidna may correlate with independent evolution ofGrem1andBmp4sequences, and that the convergent loss of gastric acid and stomach size genotypes and phenotypes in teleost and monotreme lineages may be a result of eco-evolutionary dynamics. These findings reflect the effects of gene loss on phenotypic evolution and further elucidate the genetic control of monotreme stomach anatomy and physiology.
Does Intermittent Nutrition Enterally Normalise hormonal and metabolic responses to feeding in critically ill adults? A protocol for the DINE-Normal proof-of-concept randomised parallel group study
Authors: Beattie Clodagh E , Thomas Matt , Borislavova Borislava , Smith Harry A , Ambler Michael , White Paul , Hayes Kati , Milne Danielle , Ramesh Aravind V , Gonzalez Javier T , Betts James A , Pickering Anthony E 
Published: March 2024

ABSTRACTIntroductionOver half of patients who spend >48 hours in the intensive care unit (ICU) are fed via a nasogastric (NG) tube. Current guidance recommends continuous delivery of feed throughout the day and night. Emerging evidence from healthy human studies shows that NG feeding in an intermittent pattern (rather than continuous) promotes phasic hormonal, digestive and metabolic responses that are important for effective nutrition. It is not yet known whether this will translate to the critically ill population. Here we present the protocol for a proof-of-concept study comparing diurnal intermittent versus continuous feeding for patients in the intensive care unit.Methods and AnalysisThe study is a single-centre, prospective, randomised, open-label trial comparing intermittent enteral nutrition with the current standard practice of continuous enteral feeding. It aims to recruit participants (n=30) needing enteral nutrition via an NG tube for >24 hours who will be randomised to a diurnal intermittent or a continuous feeding regime with equivalent nutritional value. The primary outcome is peak plasma insulin / c-peptide within 3 hours of delivering the morning bolus feed on the second study day, compared to that seen in the continuous feed delivery group at the same timepoint. Secondary outcomes include feasibility, tolerability, efficacy and metabolic / hormonal profiles.Ethics and DisseminationThis trial has been registered prospectively with the Clinical Trials Registry (clinicaltrials.govNCT06115044). We obtained ethical approval from the Wales Research Ethics Committee 3 prior to data collection (reference 23/WA/0297). We will publish the results of this study in an open-access peer-reviewed journal.Strengths and Limitations of this StudyHaving studied metabolic consequences of intermittent versus continuous nasogastric feed delivery in healthy volunteers, our trial team is well positioned to explore the direct ‘bench-to-bedside’ exploration of the interaction between critical illness and the mode of feed delivery through detailed profiling of metabolic hormones.The intermittent feeding intervention in this study has been carefully considered to replicate diurnal rhythms, with sufficient fasting between feeding cycles, to allow us to capture a difference in response to continuous feeding if one exists.The findings of this study will inform the feasibility and design of a trial of the effectiveness of intermittent diurnal nutrition in critically ill adults.This is an open-label, single-centre study, which may bias the interpretation and limit the generalisability of the results.
Increasing intra- and inter-subtype HIV diversity despite declining HIV incidence in Uganda
Authors: Kim Seungwon , Kigozi Godfrey , Martin Michael A. , Galiwango Ronald M. , Quinn Thomas C. , Redd Andrew D. , Ssekubugu Robert , Bonsall David , Ssemwanga Deogratius , Rambaut Andrew , Herbeck Joshua T. , Reynolds Steven J. , Foley Brian , Abeler-Dörner Lucie , Fraser Christophe , Ratmann Oliver , Kagaayi Joseph , Laeyendecker Oliver , Grabowski M. Kate 
Published: March 2024

AbstractHIV incidence has been declining in Africa with scale-up of HIV interventions. However, there is limited data on HIV evolutionary trends in African populations with waning epidemics. We evaluated changes in HIV viral diversity and genetic divergence in southern Uganda over a twenty-five-year period spanning the introduction and scale-up of HIV prevention and treatment programs using HIV sequence and survey data from the Rakai Community Cohort Study, an open longitudinal population-based HIV surveillance cohort.Gag(p24) andenv(gp41) HIV data were generated from persons living with HIV (PLHIV) in 31 inland semi-urban trading and agrarian communities (1994 to 2018) and four hyperendemic Lake Victoria fishing communities (2011 to 2018) under continuous surveillance. HIV subtype was assigned using the Recombination Identification Program with phylogenetic confirmation. Inter-subtype diversity was estimated using the Shannon diversity index and intra-subtype diversity with the nucleotide diversity and pairwise TN93 genetic distance. Genetic divergence was measured using root-to-tip distance and pairwise TN93 genetic distance analyses. Evolutionary dynamics were assessed among demographic and behavioral sub-groups, including by migration status. 9,931 HIV sequences were available from 4,999 PLHIV, including 3,060 and 1,939 persons residing in inland and fishing communities, respectively. In inland communities, subtype A1 viruses proportionately increased from 14.3% in 1995 to 25.9% in 2017 (p<0.001), while those of subtype D declined from 73.2% in 1995 to 28.2% in 2017 (p<0.001). The proportion of viruses classified as recombinants significantly increased by more than four-fold. Inter-subtype HIV diversity has generally increased. While p24 intra-subtype genetic diversity and divergence leveled off after 2014, diversity and divergence of gp41 increased through 2017. Inter- and intra-subtype viral diversity increased across all population sub-groups, including among individuals with no recent migration history or extra-community sexual partners. This study provides insights into population-level HIV evolutionary dynamics in declining African HIV epidemics following the scale-up of HIV prevention and treatment programs. Continued molecular surveillance may provide a better understanding of the dynamics driving population HIV evolution and yield important insights for epidemic control and vaccine development.
Refining the scope of genetic influences on alcohol misuse through environmental stratification and gene-environment interaction
Authors: Savage Jeanne E. , de Leeuw Christiaan A. , Werme Josefin ,   Spit for Science Working Group, Dick Danielle M. , Posthuma Danielle , van der Sluis Sophie 
Published: March 2024

AbstractBackgroundGene-environment interaction (G×E) is likely an important influence shaping individual differences in alcohol misuse (AM), yet it has not been extensively studied in molecular genetic research. In this study, we utilize a series of genome-wide gene-environment interaction (GWEIS) andin silicoannotation methods with the aim of improving gene identification and biological understanding of AM.MethodsWe carried out GWEIS for four AM phenotypes in the large UK Biobank sample (N= 360,314), with trauma exposure and socioeconomic status (SES) as moderators of the genetic effects. Exploratory analyses compared stratified GWAS and GWEIS modelling approaches. We applied functional annotation, gene- and gene-set enrichment, and polygenic score analyses to interpret the GWEIS results.ResultsGWEIS models showed few genetic variants with significant interaction effects across all gene-environment pairs. Enrichment analyses identified moderation by SES of the genesNOXA1,DLGAP1, andUBE2L3,on drinking quantity and the geneIFIT1Bon drinking frequency. Except forDLGAP1, these genes have not previously been linked to AM. The most robust results (GWEIS interactionp= 4.59e-09) were seen for SES moderating the effects of variants linked to immune-related genes on a pattern of drinking with versus without meals.ConclusionsEven in large samples, G×E effects are difficult to detect at the molecular level. Our results highlight several genes and a potential mechanism of immune system functioning behind the moderating effect of SES on the genetic influences on AM. While GWEIS seems to be a preferred approach over stratified GWAS, modelling molecular G×E effects remains a challenge that will require larger consortia and more in-depth phenotypic measurement.
Forecasting the spatial spread of an Ebola epidemic in real-time: comparing predictions of mathematical models and experts
Authors: Munday James D , Rosello Alicia , Edmunds W. John , Funk Sebastian 
Published: March 2024

AbstractEbola virus disease outbreaks can often be controlled, but require rapid response efforts frequently with profound operational complexities. Mathematical models can be used to support response planning, but it is unclear if models improve the prior understanding of experts.We performed repeated surveys of Ebola response experts during an outbreak. From each expert we elicited the probability of cases exceeding four thresholds between two and 20 cases in a set of small geographical areas in the following calendar month. We compared the predictive performance of these forecasts to those of two mathematical models with different spatial interaction components.An ensemble combining the forecasts of all experts performed similarly to the two models. Experts showed stronger bias than models forecasting two-case threshold exceedance. Experts and models both performed better when predicting exceedance of higher thresholds. The models also tended to be better at risk-ranking areas than experts.Our results support the use of models in outbreak contexts, offering a convenient and scalable route to a quantified situational awareness, which can provide confidence in or to call into question existing advice of experts. There could be value in combining expert opinion and modelled forecasts to support the response to future outbreaks.
The Impact of Alcohol Misuse in Trauma Patients: A Scoping Review Protocol
Authors: Garland Chantae , Abdulla Nhayan , Lee Donghyun , Spiwak Rae , Logsetty Sarvesh , Nantais Jordan 
Published: March 2024

AbstractBackgroundAlcohol use is a contributing factor in many cases of traumatic injury. There is conflicting evidence on the impact of alcohol use at the time of physical trauma on severity of injury and hospital course. Similarly, the significance of alcohol use disorder on outcomes in hospitalized trauma patients is unclear. This scoping review aims to provide a concise overview of the current literature surrounding peri-trauma alcohol use and alcohol use disorder on injury severity, in-hospital complications, patient outcomes, and long-term health impact of alcohol use in trauma. We will also explore the associated healthcare costs of this patient population.MethodsA systematic search of the following databases MEDLINE, EMBASE, and Cochrane Library will be completed to extract all studies that meet our inclusion criteria from January 2000 onwards. Case reports will be excluded. Two reviewers will screen all citations, abstracts, and full text articles. A third reviewer will act as tiebreaker at each stage of the screening process. A narrative synthesis without meta-analysis will be conducted and assessed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines.DiscussionThis review will contribute to the literature by providing a concise overview of the current data on the impact of alcohol on outcomes following trauma. We will explore the overall themes in the literature, limitations, and future directions to focus forthcoming research in this patient population.Scoping review registrationOpen Science Framework (https://doi.org/10.17605/OSF.IO/Z84WK)SupportThere were no funders or sponsors involved in the development of this protocol
WGBS of Differentiating Adipocytes Reveals Variations in DMRs and Context-Dependent Gene Expression
Authors: Yadav Binduma , Singh Dalwinder , Mantri Shrikant , Rishi Vikas 
Published: March 2024

AbstractObesity, characterised by the accumulation of excess fat, is a complex condition resulting from the combination of genetic and epigenetic factors. Recent studies have found correspondence between DNA methylation and cell differentiation, suggesting a role of the former in cell fate determination. There is a lack of comprehensive understanding concerning the underpinnings of preadipocyte differentiation, specifically when cells are undergoing terminal differentiation (TD). To gain insight into dynamic genome-wide methylation, 3T3 L1 preadipocyte cells were differentiated by a hormone cocktail. The genomic DNA was isolated from undifferentiated cells and 4 hrs (4H), 2 days (2D) post-differentiated cells, and 15 days (15D) TD cells. We employed whole-genome bisulfite sequencing (WGBS) to ascertain global genomic DNA methylation alterations at single base resolution as preadipocyte cells differentiate. The genome-wide distribution of DNA methylation showed similar overall patterns in pre- and post- and terminally differentiated adipocytes, according to WGBS analysis. DNA methylation decreases at 4H after differentiation initiation, followed by methylation gain as cells approach TD. Studies revealed novel differentially methylated regions (DMRs) associated with adipogenesis. DMR analysis suggested that though DNA methylation is global, noticeable changes are observed at specific sites known as ‘hotspots.’ Hotspots are genomic regions rich in transcription factor (TF) binding sites and exhibit methylation-dependent TF binding. Subsequent analysis indicated hotspots as part of DMRs. The gene expression profile of key adipogenic genes in differentiating adipocytes is context-dependent, as we found a direct and inverse relationship between promoter DNA methylation and gene expression.
Effective Gene Therapy for Metachromatic Leukodystrophy Achieved with Minimal Lentiviral Genomic Integrations
Authors: Tricoli Lucas , Sase Sunetra , Hacker Julia , Pham Vi , Smith Sidney , Chappell Maxwell , Breda Laura , Hurwitz Stephanie , Tanaka Naoto , Castracani Carlo Castruccio , Guerra Amaliris , Hou Zhongqi , Schlotawa Lars , Radhakrishnan Karthikeyan , Kurre Peter , Ahrens-Nicklas Rebecca , Adang Laura , Vanderver Adeline , Rivella Stefano 
Published: March 2024

ABSTRACTMetachromatic leukodystrophy (MLD) is a fatal lysosomal storage disease (LSD) characterized by the deficient enzymatic activity of arylsulfatase A (ARSA). Combined autologous hematopoietic stem cell transplant (HSCT) with lentiviral (LV) based gene therapy has great potential to treat MLD. However, if enzyme production is inadequate, this could result in continued loss of motor function, implying a high vector copy number (VCN) requirement for optimal enzymatic output. This may place children at increased risk for genomic toxicity due to higher VCN. We increased the expression of ARSA cDNA at single integration by generating novel LVs, optimizing ARSA expression, and enhancing safety. In addition, our vectors achieved optimal transduction in mouse and human HSC with minimal multiplicity of infection (MOI). Our top-performing vector (EA1) showed at least 4X more ARSA activity than the currently EU-approved vector and a superior ability to secrete vesicle-associated ARSA, a critical modality to transfer functional enzymes from microglia to oligodendrocytes. Three-month-oldArsa-KO MLD mice transplanted withArsa-KO BM cells transduced with 0.6 VCN of EA1 demonstrated behavior and CNS histology matching WT mice. Our novel vector boosts efficacy while improving safety as a robust approach for treating early symptomatic MLD patients.
Convergence of inputs from the basal ganglia with layer 5 of motor cortex and cerebellum in mouse motor thalamus
Authors: Koster Kevin P. , Sherman S. Murray 
Published: March 2024

AbstractA key to motor control is the motor thalamus, where several inputs converge. One excitatory input originates from layer 5 of primary motor cortex (M1L5), while another arises from the deep cerebellar nuclei (Cb). M1L5terminals distribute throughout the motor thalamus and overlap with GABAergic inputs from the basal ganglia output nuclei, the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr). In contrast, it is thought that Cb and basal ganglia inputs are segregated. Therefore, we hypothesized that one potential function of the GABAergic inputs from basal ganglia is to selectively inhibit, or gate, excitatory signals from M1L5in the motor thalamus. Here, we tested this possibility and determined the circuit organization of mouse (both sexes) motor thalamus using an optogenetic strategy in acute slices. First, we demonstrated the presence of a feedforward transthalamic pathway from M1L5through motor thalamus. Importantly, we discovered that GABAergic inputs from the GPi and SNr converge onto single motor thalamic cells with excitatory synapses from M1L5and, unexpectedly, Cb as well. We interpret these results to indicate that a role of the basal ganglia is to gate the thalamic transmission of M1L5and Cb information to cortex.Significance StatementIn this study, we extend the common conception of the basal ganglia as an information loop: flowing from cortex to basal ganglia, to thalamus, and back to cortex. We used tricolor viral labeling and an optogenetic approach to reveal that projections from the output nuclei of the basal ganglia converge with inputs from both layer 5 of primary motor cortex and the deep cerebellar nuclei onto individual thalamic relay cells. Not only do these findings add nuance to the notion that cerebellar and basal ganglia circuits through motor thalamus are independent, but also highlight a novel intersection between basal ganglia and cortex that countervails long-held conceptions of how the brain handles motor commands.
PEACOC - Detecting and classifying a wide range of epileptiform activity patterns in rodents
Authors: Heining Katharina , Kilias Antje , Janz Philipp , Haas Carola A , Egert Ulrich 
Published: March 2024

AbstractEpileptiform activity (EA) manifests in diverse patterns of hypersynchronous network activity. Fundamental research mostly addresses two extreme patterns, individual epileptiform spikes and seizures. We developed PEACOC to detect and classify a wide range of EA patterns in local field potentials. PEACOC delimits EA patterns as bursts of epileptiform spikes, and classifies these bursts according to spike load. In EA from kainate-injected mice, burst patterns displayed a continuum of spike loads. With PEACOC, we partitioned this continuum into bursts of high, medium and low spike load. High-load bursts resembled electrographic seizures. The EA patterns automatically retrieved by PEACOC were reproducible and comparable across animals and laboratories. PEACOC has been employed to diagnose the overall burden of EA in individual mice, and to describe epileptic dynamics at multiple time-scales. We here further report that the rate of high-load bursts was anti-correlated to granule cell dispersion in the dentate gyrus.
Microscopic optical potentials for medium-mass isotopes derived at the first order of Watson multiple-scattering theory
Authors: Vorabbi M. , Barbieri C. , Somà V. , Finelli P. , Giusti C. 
Published: March 2024

We perform a first-principles calculation of optical potentials for nucleon elastic scattering off medium-mass isotopes. Fully based on a saturating chiral Hamiltonian, the optical potentials are derived by folding nuclear density distributions computed with self-consistent Green's function theory with a nucleon-nucleon t matrix computed with a consistent chiral interaction. The dependence on the folding interaction as well as the convergence of the target densities are investigated. Numerical results are presented and discussed for differential cross sections and analyzing powers, with focus on elastic proton scattering off calcium and nickel isotopes. Our optical potentials generally show a remarkable agreement with the available experimental data for laboratory energies in the range 65–200 MeV. We study the evolution of the scattering observables with increasing proton-neutron asymmetry by computing theoretical predictions of the cross section and analyzing power over the calcium and nickel isotopic chains.

Published by the American Physical Society
2024
Modeling resilient functions in perishable food supply chains: transition for sustainable food system development
Authors: Daultani Yash , Dwivedi Ashish , Pratap Saurabh , Sharma Akshay 
Published: March 2024

PurposeNatural disasters cause serious operational risks and disruptions, which further impact the food supply in and around the disaster-impacted area. Resilient functions in the supply chain are required to absorb the impact of resultant disruptions in perishable food supply chains (FSC). The present study identifies specific resilient functions to overcome the problems created by natural disasters in the FSC context.Design/methodology/approachThe quality function deployment (QFD) method is utilized for identifying these relations. Further, fuzzy term sets and the analytical hierarchy process (AHP) are used to prioritize the identified problems. The results obtained are employed to construct a QFD matrix with the solutions, followed by the technique for order of preference by similarity to the ideal solution (TOPSIS) on the house of quality (HOQ) matrix between the identified problems and functions.FindingsThe results from the study reflect that the shortage of employees in affected areas is the major problem caused by a natural disaster, followed by the food movement problem. The results from the analysis matrix conclude that information sharing should be kept at the highest priority by policymakers to build and increase resilient functions and sustainable crisis management in a perishable FSC network.Originality/valueThe study suggests practical implications for managing a FSC crisis during a natural disaster. The unique contribution of this research lies in finding the correlation and importance ranking among different resilience functions, which is crucial for managing a FSC crisis during a natural disaster.