bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic QT Score and Sleep Apnea as Predictors of Sudden Cardiac Death in the UK Biobank
Authors: Arora Amit , Zareba Wojciech , Woosley Raymond L. , Klimentidis Yann C. , Patel Imran Y. , Quan Stuart F. , Wendel Christopher , Shamoun Fadi , Guerra Stefano , Parthasarathy Sairam , Patel Salma I. 
Published: November 2023

ABSTRACTIntroductionThe goal of this study was to evaluate the association between a polygenic risk score (PRS) for QT prolongation (QTc-PRS), QTc intervals and mortality in patients enrolled in the UK Biobank with and without sleep apnea.MethodsThe QTc-PRS was calculated using allele copy number and previously reported effect estimates for each single nuclear polymorphism SNP. Competing-risk regression models adjusting for age, sex, BMI, QT prolonging medication, race, and comorbid cardiovascular conditions were used for sudden cardiac death (SCD) analyses.Results500,584 participants were evaluated (56.5 ±8 years, 54% women, 1.4% diagnosed with sleep apnea). A higher QTc-PRS was independently associated with the increased QTc interval duration (p<0.0001). The mean QTc for the top QTc-PRS quintile was 15 msec longer than the bottom quintile (p<0.001). Sleep apnea was found to be an effect modifier in the relationship between QTc-PRS and SCD. The adjusted HR per 5-unit change in QTc-PRS for SCD was 1.64 (95% CI 1.16 – 2.31, p=0.005) among those with sleep apnea and 1.04 (95% CI 0.95 – 1.14, p=0.44) among those without sleep apnea (p for interaction =0.01). Black participants with sleep apnea had significantly elevated adjusted risk of SCD compared to White participants (HR=9.6, 95% CI 1.24 - 74, p=0.03).ConclusionIn the UK Biobank population, the QTc-PRS was associated with SCD among participants with sleep apnea but not among those without sleep apnea, indicating that sleep apnea is a significant modifier of the genetic risk. Black participants with sleep apnea had a particularly high risk of SCD.
Regional 4D Cardiac Magnetic Resonance Strain Predicts Cardiomyopathy Progression in Duchenne Muscular Dystrophy
Authors: Earl Conner C. , Jauregui Alexa M. , Lin Guang , Hor Kan N. , Markham Larry W. , Soslow Jonathan H. , Goergen Craig J. 
Published: November 2023

AbstractBackgroundCardiomyopathy (CMP) is the leading cause of death in Duchenne muscular dystrophy (DMD). Characterization of disease trajectory can be challenging, especially in the early stage of CMP where onset and clinical progression may vary. Traditional metrics from cardiovascular magnetic resonance (CMR) imaging such as LVEF (left ventricular ejection fraction) and LGE (late gadolinium enhancement) are often insufficient for assessing disease trajectory.We hypothesized that strain patternsfrom a novel 4D (3D+time) CMR regional strain analysis methodcan be used to predictthe rate of DMD CMP progression.MethodsWe compiled 115 short-axis cine CMR image stacks for n=40 pediatric DMD patients (13.6±4.2 years) imaged yearly for 3 consecutive visits and computed regional strain metrics using custom-built feature tracking software. We measured regional strain parameters by determining the relative change in the localized 4D endocardial surface mesh using end diastole as the initial reference frame.ResultsWe first separated patients into two cohorts based on their initial CMR: LVEF≥55% (n=28, normal cohort) and LVEF<55% (n=12, abnormal cohort). Using LVEF decrease measured two years following the initial scan, we further subclassified these cohorts into slow (ΔLVEF%≤5) or fast (ΔLVEF%>5) progression groups for both the normal cohort (n=12, slow; n=15, fast) and the abnormal cohort (n=8, slow; n=4, fast). There was no statistical difference between the slow and fast progression groups in standard biomarkers such as LVEF, age, or LGE status. However, basal circumferential strain (Ecc) late diastolic strain rate and basal surface area strain (Ea) late diastolic strain rate magnitude were significantly decreased in fast progressors in both normal and abnormal cohorts (p<0.01,p=0.04 andp<0.01,p=0.02, respectively). Peak Eaand Eccmagnitudes were also decreased in fast progressors, though these only reached statistical significance in the normal cohort (p<0.01,p=0.24 andp<0.01,p=0.18, respectively).ConclusionRegional strain metrics from 4D CMR can be used to differentiate between slow or fast CMP progression in a longitudinal DMD cohort. These results demonstrate that 4D CMR strain is useful for early identification of CMP progression in patients with DMD.Clinical PerspectiveCardiomyopathy is the number one cause of death in Duchenne muscular dystrophy, but the onset and progression of the disease are variable and heterogeneous. In this study, we used a novel 4D cardiovascular magnetic resonance regional strain analysis method to evaluate 40 pediatric Duchenne patients over three consecutive annual visits. From our analysis, we found that peak systolic strain and late diastolic strain rate were early indicators of cardiomyopathy progression. This method offers promise for early detection and monitoring, potentially improving patient outcomes through timely intervention and management.
The immune landscape of murine skeletal muscle regeneration and aging
Authors: Sousa Neuza S. , Bica Marta , Brás Margarida F. , Antunes Inês B. , Encarnação Isabel A. , Costa Tiago , Martins Inês B. , Barbosa-Morais Nuno L. , Sousa-Victor Pedro , Neves Joana 
Published: November 2023

ABSTRACTAge-related alterations in the immune system are starting to emerge as key contributors to impairments found in aged organs. A decline in regenerative capacity is a hallmark of tissue aging, however the contribution of immune aging to regenerative failure is just starting to be explored. Here, we applied a strategy combining single-cell RNA-sequencing with flow cytometry and functional assays to perform a complete analysis of the immune environment in the aged regenerating skeletal muscle, with time and single cell resolution. Our results identified previously undescribed immune cell types in the skeletal muscle and revealed an unanticipated complexity and functional heterogeneity in immune populations, that have been regarded as homogeneous. Furthermore, we uncovered a profound remodeling of both myeloid and lymphoid compartments in aging. These discoveries challenge established notions on immune regulation of skeletal muscle regeneration, providing a new set of potential targets to improve skeletal muscle health and regenerative capacity in aging.
Unlocking the Mechanism of Action: A Cost-Effective Flow Cytometry Approach for Accelerating Antimicrobial Drug Development
Authors: Mermans Fabian , Baets Hanna De , García-Timermans Cristina , Teughels Wim , Boon Nico 
Published: November 2023

AbstractAntimicrobial resistance is one of the greatest challenges to global health. While the development of new antimicrobials can combat resistance, low profitability is reducing the number of new compounds brought to the market. Elucidating the mechanism of action is crucial for developing new antimicrobials. This process can become expensive as there are no universally applicable pipelines and scientific expertise in different fields is required. One way to determine the mechanism of action is the use of predictive modeling, as antimicrobials can be classified into limited groups.. We demonstrate a cost-effective flow cytometry approach for determining the mechanisms of action of new compounds. Cultures ofActinomyces viscosusandFusobacterium nucleatumwere treated with a range of antimicrobials and measured by flow cytometry. A Gaussian mixture mask was applied over the data to construct a phenotypic fingerprint. The fingerprints were used to train random forest classifiers, and classifiers were used to predict the mechanism of action of cephalothin. Significant statistical differences were found among the 10 different treatment groups. A pairwise comparison between treatment groups showed a statistical difference for 35 out of 45 pairs forActinomyces viscosusand 32 out of 45 pairs forFusobacterium nucleatumafter 3.5h of treatment. The best performing random forest classifier yielded a Matthews correlation coefficient of 0.92 and the mechanism of action of cephalothin could be successfully predicted. These findings suggest that flow cytometry can be a cheap and fast alternative for determining the mechanism of action of new antimicrobials.
The Spatial Frequency Representation Predicts Category Coding in the Inferior Temporal Cortex
Authors: Toosi Ramin , Karami Behnam , Koushki Roxana , Shakerian Farideh , Noroozi Jalaledin , Rezayat Ehsan , Vahabie Abdol-Hossein , Akhaee Mohammad Ali , Dehaqani Mohammad-Reza A. 
Published: November 2023

AbstractUnderstanding the neural representation of spatial frequency (SF) in the primate cortex is vital for unraveling visual processing mechanisms in object recognition. While numerous studies concentrate on the representation of SF in the primary visual cortex, the characteristics of SF representation and its interaction with category representation remain inadequately understood. To explore SF representation in the inferior temporal (IT) cortex of macaque monkeys, we conducted extracellular recordings with complex stimuli systematically filtered by SF. Our findings disclose an explicit SF coding at single-neuron and population levels in the IT cortex. Moreover, the coding of SF content exhibits a coarse-to-fine pattern, declining as the SF increases. Temporal dynamics analysis of SF representation reveals that low SF (LSF) is decoded faster than high SF (HSF), and the SF preference dynamically shifts from LSF to HSF over time. Additionally, the SF representation for each neuron forms a profile that predicts category selectivity at the population level. IT neurons can be clustered into four groups based on SF preference, each exhibiting different category coding behaviors. Particularly, HSF-preferred neurons demonstrate the highest category decoding performance for face stimuli. Despite the existing connection between SF and category coding, we have identified uncorrelated representations of SF and category. In contrast to the category coding, SF is more sparse and places greater reliance on the representations of individual neurons. Comparing SF representation in the IT cortex to deep neural networks, we observed no relationship between SF representation and category coding. However, SF coding, as a category-orthogonal property, is evident across various ventral stream models. These results dissociate the separate representations of SF and object category, underscoring the pivotal role of SF in object recognition.
Mitochondrial One-Carbon Metabolism is Required for TGF-β-Induced Glycine Synthesis and Collagen Protein Production
Authors: Meliton Angelo Y. , Cetin-Atalay Rengül , Tian Yufeng , Szafran Jennifer C. Houpy , Shin Kun Woo D. , Cho Takugo , Sun Kaitlyn A. , Woods Parker S. , Shamaa Obada R. , Chen Bohao , Muir Alexander , Mutlu Gökhan M. , Hamanaka Robert B. 
Published: November 2023

ABSTRACTA hallmark of Idiopathic Pulmonary Fibrosis is the TGF-β-dependent activation of lung fibroblasts, leading to excessive deposition of collagen proteins and progressive scarring. We have previously shown that synthesis of collagen by lung fibroblasts requiresde novosynthesis of glycine, the most abundant amino acid in collagen protein. TGF-β upregulates the expression of the enzymes of thede novoserine/glycine synthesis pathway in lung fibroblasts through mTORC1 and ATF4- dependent transcriptional programs. SHMT2, the final enzyme of thede novoserine/glycine synthesis pathway, transfers a one-carbon unit from serine to tetrahydrofolate (THF), producing glycine and 5,10-methylene-THF (meTHF). meTHF is converted back to THF in the mitochondrial one-carbon (1C) pathway through the sequential actions of MTHFD2 (which converts meTHF to 10-formyl-THF), and either MTHFD1L, which produces formate, or ALDH1L2, which produces CO2. It is unknown how the mitochondrial 1C pathway contributes to glycine biosynthesis or collagen protein production in fibroblasts, or fibrosisin vivo. Here, we demonstrate that TGF-β induces the expression ofMTHFD2,MTHFD1L, andALDH1L2in human lung fibroblasts.MTHFD2expression was required for TGF-β-induced cellular glycine accumulation and collagen protein production. Combined knockdown of bothMTHFD1LandALDH1L2also inhibited glycine accumulation and collagen protein production downstream of TGF-β; however knockdown of either protein alone had no inhibitory effect, suggesting that lung fibroblasts can utilize either enzyme to regenerate THF. Pharmacologic inhibition of MTHFD2 recapitulated the effects ofMTHFD2knockdown in lung fibroblasts and ameliorated fibrotic responses after intratracheal bleomycin instillationin vivo. Our results provide insight into the metabolic requirements of lung fibroblasts and provide support for continued development of MTHFD2 inhibitors for the treatment of IPF and other fibrotic diseases.
Hitching a ride in the phyllosphere: Surfactant production ofPseudomonasspp. causes co-swarming ofPantoea eucalypti299R
Authors: Kunzler Michael , Schlechter Rudolf O. , Schreiber Lukas , Remus-Emsermann Mitja N.P. 
Published: November 2023

AbstractHere we demonstrate the beneficial effect of surfactant-producing Pseudomonads on the phyllosphere model strainPantoea eucalypti299R. To do so, we conducted a series of experiments in environments of increasing complexity.P. eucalypti299R andPseudomonassp. FF1 (Pff1) orP. eucalypti299R and the surfactant-deficient mutantP. sp. FF1::ΔviscB (Pff1ΔviscB) were co-inoculated in broth, on swarming agar plates, and on plants. In broth, there were no differences in the growth dynamics ofP. eucalypti299R when growing in the presence of Pff1 or Pff1ΔviscB. By contrast, on swarming agar plates,P. eucalyptiwas able to co-swarm with Pff1. Co-swarming led to a significant increase in the area colonized and, consequently, a boost in total biomass when compared toP. eucalyptigrowing with Pff1ΔviscB or in monoculture. Finallyin planta, there were no significant effects on the population density ofP. eucalypti299R during co-colonization ofArabidopsis thaliana. However, utilizing the single cell bioreporter for reproductive success (CUSPER), we found a temporally distinct beneficial effect of Pff1 on co-inoculatedP. eucalypti299R subpopulations that did not occur in presence of Pff1ΔviscB. This led us to formulate a model for the positive effect of surfactant production during leaf colonization. To generalize our results, we tested the effect of three additional surfactant-producing Pseudomonads and their respective surfactant knockout mutants onP. eucalypti299R on swarming agar. Resulting in similar co-swarming patterns inP. eucalypti299R and showing that this organism is able to take advantage of competitors during surface colonization. Our results indicate that surfactant-dependent co-motility might be common during leaf colonization and add yet another facet to the already manyfold roles of surfactants.
Globally-deployed sorghum aphid resistance geneRMES1is vulnerable to biotype shifts but being bolstered byRMES2
Authors: VanGessel Carl , Rice Brian , Felderhoff Terry J. , Charles Jean Rigaud , Pressoir Gael , Nalam Vamsi , Morris Geoffrey P. 
Published: November 2023

ABSTRACTDurable host plant resistance (HPR) to insect pests is critical for sustainable agriculture. Natural variation exists for aphid HPR in sorghum (Sorghum bicolor) but the genetic architecture and phenotype has not been clarified for most sources. To assess the threat of a sorghum aphid (Melanaphis sorghi) biotype shift, we characterized the phenotype ofResistance to Melanaphis sorghi 1(RMES1) and contributing HPR architecture in globally-admixed populations selected under severe aphid infestation in Haiti. We foundRMES1reduces sorghum aphid fecundity but not bird cherry-oat aphid (Rhopalosiphum padi) fecundity, suggesting a discriminant HPR response typical of gene-for-gene interaction. A second resistant gene,RMES2, were more frequent thanRMES1resistant alleles in landraces and historic breeding lines.RMES2contributes early and mid-season aphid resistance in a segregating F2population, howeverRMES1was only significant with mid-season fitness. In a fixed population with high aphid resistance,RMES1andRMES2were selected for demonstrating a lack of significant antagonistic pleiotropy. Associations with resistance co-located with cyanogenic glucoside biosynthesis genes support additional HPR sources. Globally, therefore, a vulnerable HPR source (RMES1) is bolstered by a second common source of resistance in breeding programs (RMES2) which may be staving off a biotype shift.HIGHLIGHTThe globally-deployed sorghum aphid resistance gene,RMES1, reduces aphid reproduction and therefore is vulnerable to a biotype shift. A second major gene,RMES2, and cyanogenesis may increase global durability of resistance.
Inhibition of noradrenaline-dependent synaptic transmission in the dorsal raphe nucleus by alpha2-adrenergic receptors
Authors: Gugel Aleigha , Ingebretsen Erik A. , Hake Holly S. , Gantz Stephanie C. 
Published: November 2023

AbstractIn the central nervous system, noradrenaline transmission controls the degree to which we are awake, alert, and attentive. Aberrant noradrenaline transmission is associated with pathological forms of hyper- and hypo-arousal that present in numerous neuropsychiatric disorders often associated with dysfunction in serotonin transmission.In vivo,noradrenaline regulates the release of serotonin because noradrenergic input drives the serotonin neurons to fire action potentials via activation of excitatory α1-adrenergic receptors (α1-AR). Despite the critical influence of noradrenaline on the activity of dorsal raphe serotonin neurons, the source of noradrenergic afferents has not been resolved and the presynaptic mechanisms that regulate noradrenaline-dependent synaptic transmission have not been described. Using an acute brain slice preparation from male and female mice and electrophysiological recordings from dorsal raphe serotonin neurons, we found that selective optogenetic activation of locus coeruleus terminals in the dorsal raphe was sufficient to produce an α1-AR-mediated excitatory postsynaptic current (α1-AR-EPSC). Activation of inhibitory α2-adrenergic receptors (α2-AR) with UK-14,304 eliminated the α1-AR-EPSC via presynaptic inhibition of noradrenaline release, likely via inhibition of voltage-gated calcium channels. In a subset of serotonin neurons, activation of postsynaptic α2-ARproduced an outward current through activation of potassium conductance. Further,in vivoactivation of α2-ARby systemic administration of clonidine reduced the expression of c-fos in the dorsal raphe serotonin neurons, indicating reduced neural activity. Thus, α2-ARare critical regulators of serotonin neuron excitability.
Elucidating the Synergistic Role of Elm1 and Gin4 Kinases in Regulating Septin Hourglass Assembly
Authors: Marquardt Joseph , Chen Xi , Bi Erfei 
Published: November 2023

ABSTRACTThe septin cytoskeleton is extensively regulated by post-translational modifications such as phosphorylation to achieve the diversity of architectures including rings, hourglass, and gauzes. While many of the phosphorylation events of septins have been extensively studied in the budding yeastSaccharomyces cerevisiae, the regulation of the kinases involved remains poorly understood. Here we show that two septin-associated kinases, the LKB1/PAR-4-related kinase Elm1 and the Nim1/PAR-1-related kinase Gin4, regulate each other at two discrete points of the cell cycle. During bud emergence, Gin4 targets Elm1 to the bud neck via direct binding and phosphorylation to control septin hourglass assembly and stability. During mitosis, Elm1 maintains Gin4 localization via direct binding and phosphorylation to enable timely remodeling of the septin hourglass into a double ring. This unique synergy ensures that septin architecture is assembled and remodeled in a temporally controlled manner to perform distinct functions during the cell cycle.SUMMARYMarquardt et al. show that the septin-associated kinases Elm1 and Gin4 regulate each other via both direct binding and phosphorylation to control septin hourglass assembly and remodeling at different points of the cell cycle in the budding yeastSaccharomyces cerevisiae.
Adoption of digital payment FinTech service by Gen Y and Gen Z users: evidence from India
Authors: Srivastava Shanu , Mohta Anu , Shunmugasundaram V. 
Published: November 2023

Purpose
This study aims to evaluate the users’ behavioral intention toward the acceptance and adoption of digital payment FinTech services in India. The study also compares the differences in Gen Y and Gen Z’s intention to adopt digital payment FinTech services.

Design/methodology/approach
The present study adopted both the unified theory of acceptance and use of technology (UTAUT) and the technology acceptance model (TAM) as its theoretical base and also added financial literacy and customer satisfaction. The data was analyzed by applying structural equation modeling using SmartPLS 4.

Findings
The outcomes of the study imply that customer satisfaction, effort expectancy and performance expectancy had a significant effect on behavioral intention. Moreover, effort expectancy, performance expectancy and perceived enjoyment had a significant influence on customer satisfaction, and effort expectancy and performance expectancy is significantly influenced by perceived enjoyment, while self-efficacy significantly influenced perceived enjoyment. Also, financial literacy does not moderate the relationship between effort expectancy, performance expectancy, facilitating condition and behavioral intention. Furthermore, the association of effort expectancy → customer satisfaction; perceived enjoyment → customer satisfaction; and perceived enjoyment → effort expectancy is moderated by age factor.

Originality/value
This study contributes by developing a more cohesive and unified model for assessing users’ behavioral intention toward acceptance and adoption of FinTech services by adopting constructs from the UTUAT and TAM and incorporating financial literacy and customer satisfaction to expand and enhance the theoretical prospect of the existing literature.
Understanding the link between HRM and innovation in SMEs through a multi-level approach
Authors: Adla Ludivine , Gallego-Roquelaure Virginie 
Published: November 2023

PurposeFrom a relational perspective, this research aims to answer the following question: How can human resource management (HRM) and innovation in small and medium-sized enterprises (SMEs) be articulated at different levels through gift/counter–gift relationships?Design/methodology/approachThe authors' longitudinal and exploratory study was conducted in an innovative SME that constitutes an “emblematic” case. The data were gathered from diverse sources: 2 life stories, 21 semi-structured interviews, observations and documentary analyses.FindingsThe results provide a dynamic view of the relationship between HRM and innovation through multi-level analysis. The authors consequently propose a three-step process: freeing up, mobilizing and rethinking gifts.Originality/valueThis article examines how to articulate HRM and innovation in SMEs through gift/counter-gift theory. This relationship is analyzed from a relational and multi-level perspective.