bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the Microtubule Cytoskeleton on Insulin Transport in Beta Cells: A 3D Computational Study
Authors: Thieu Thoa , Holmes William R. 
Published: February 2025

ABSTRACTGlucose-stimulated insulin secretion (GSIS) in pancreaticβcells is vital to metabolic homeostasis. Recent evidence has highlighted the critical role of the cells’ microtubule (MT) cytoskeleton in regulating transport and availability of insulin containing vesicles. How these vesicles move within the cell and how that mobility is influenced by the MT network is however not well understood. The MT network in these cells is dense and randomly oriented. Further insulin vesicles are relatively large compared to the spaces in this dense meshwork. Here we develop a 3D computational model that simulates vesicle motions in the dense MT network of theβcell. The structure of this MT network, along with the dynamics of vesicle motions, are calibrated to microscopy data fromβcells to ensure physiological relevance. Our results reveal a number of key observations. 1) The MT network inβcells likely impairs motion of larger vesicles (200 − 300nmin diameter). 2) This is in part a consequence of their “caging” by the MT network. 3) This results in a substantial reduction in the likelihood of vesicles transiting from the cells interior to the plasma membrane, a pre-cursor to GSIS. 4) Dynamic remodeling of the MT network reduces the strength of these effects. 5) That same remodeling however introduces anomalous (sub-diffusion) motion characteristics. Taken together, these results indicate that the dense MT network of theβcell substantially inhibits mobility and availability (for GSIS) of insulin. It further sheds light on how the complex filament network in cells leads to statistically anomalous motions. Finally, this modeling further provides a test-bed for determining how potential manipulations of the structure and dynamics of this network would tune GSIS.SIGNIFICANCEInsulin release from pancreaticβcells is crucial for blood sugar regulation, and recent research suggests the microtubule network inside these cells plays a key role in how insulin is transported and released. This study developed a 3D computational model to explore how insulin vesicles move through this dense network. Results show that the microtubules can “cage” larger vesicles, making it difficult for them to reach the cell surface for insulin release. Dynamic remodeling of the network can however increase insulin mobility and availability. These findings highlight the impact of the microtubule network on insulin transport and secretion and provide insight into potential ways to tune this process.
Exploiting attP landing sites and gypsy retrovirus insulators to identify and study viral suppressors of RNA silencing
Authors: Gupta Adarsh K. , Chennuri Pratima R. , Monfardini Raquel D. , Myles Kevin M. 
Published: February 2025

ABSTRACTRNA interference (RNAi) pathways are crucial for regulating viral infections in both animals and plants, acting as defense mechanisms that limit pathogen replication. This has led to the evolution of viral suppressors of RNA silencing (VSRs) across various plant and insect viruses, with potential analogs in arthropod-borne human pathogens. However, while functionally similar, VSRs often lack genetic conservation due to convergent evolution. Research on VSRs typically involves analyzing individual proteins expressed in host cells with secondary reporter constructs, but the lack of a standardized system can lead to inconsistent findings. Our study examined how genomic insertion sites affect VSR activity using a transgenicDrosophila melanogasterreporter system. We integrated the VSR protein DCV-1A into three different attP sites and assessed silencing. The results showed significant variation in VSR activity across loci due to position effects. However, by flanking the transgenes with gypsy retrovirus insulators, we achieved consistent high-level silencing across all sites. These findings suggest the potential for establishing a standardized reporter system inDrosophila, facilitating the identification, study and comparison of VSR proteins. However, our results also highlight the limitations of using isolated proteins in reporter systems, emphasizing the need for a comprehensive holistic approach to definitively determine VSR functions.
Impact of the establishment of a national lead agency on the emergency medical service system in Khon Kaen Province, Thailand
Authors: Yapanan Papawadee , Impool Tawatchai , Pattanarattanamolee Ratrawee , Thanakanjanaphakdee Wuttikul , Tokuno Shinichi , Nakahara Shinji 
Published: February 2025

AbstractPurposeNational Institute for Emergency Medicine (NIEM) was established as the national lead agency for emergency medicine in 2008 in Thailand. This study aimed to evaluate the longitudinal effect of establishing NIEM on emergency medical service (EMS) use and case fatalities among patients with severe trauma.MethodData were extracted from Khon Kaen Hospital’s Injury Surveillance Database. The analysis included injured patients with an Injury Severity Score of >15, directly transferred to its emergency department between January 1997 and December 2021. Changes in formal EMS use, total EMS use, and in-hospital deaths were investigated using segmented regression analysis. The change point in 2008 divided the study period into two segments.ResultThe proportion of formal EMS use among severely injured patients increased by approximately 1.5% annually before 2008, with a level change of 52.9 percentage point (pp) increases in 2008, and without a significant slope change. The total EMS use, including informal EMS, increased by approximately 3.4% annually before 2008, with a level change of 17.9ppincrease in 2008, and a significant slope change in the decreasing direction of the increasing trend. The proportion of in-hospital deaths showed no significant changes before 2008, with an increase of 8.0ppin 2008, with significant slope change and decreasing trends after 2008.ConclusionsThe trends indicated a significant increase in EMS use among patients with severe trauma after establishing NIEM in 2008, which reflects the integration of informal EMS units into the formal system. However, a reduction in fatalities in 2008 was not observed.
Inequities in Effective Coverage of Family Planning Services in Low-and Middle-Income Countries: Linking Households and Facility Surveys
Authors: Tian Shenning , Hazel Elizabeth A , Munos Melinda , Maïga Abdoulaye , Jiwani Safia S , Wilson Emily B , Mady Gouda Roland Mesmer , Amouzou Agbessi 
Published: February 2025

AbstractBackgroundDespite decades of family planning (FP) program successes in low-and middle-income countries (LIMCs), unmet need for contraceptives persists with inequalities in coverage. Including elements of service readiness in family planning intervention coverage measures will better inform population-level program performance.MethodsFive LMICs countries were identified with a health facility and household survey conducted within five years of one another within the last 10 years: Bangladesh, Haiti, Malawi, Nepal and Tanzania, with time trend data available for Nepal. We used ecological linking methods to develop quality readiness adjusted FP coverage measures by linking health facility assessments (readiness) and household surveys (intervention coverage). Linking units were defined by facility type, managing authority and geographic location using women’s reported source of contraceptives. Intervention coverage was defined as the percentage of women 15-49 years of age in need of contraceptive services who were using a modern method and we used the average FP readiness score in each linking unit to calculate readiness-adjusted intervention coverage. We used a coverage cascade model to understand gaps in health service readiness and access, and performed a health equity analysis for wealth, locality and age.FindingsWe found large gaps in FP intervention coverage and readiness in all settings. Facility readiness scores ranged from 0.60 and 0.75 with gaps in coverage and readiness-adjusted coverage ranging from 49 percentage points (pp) in Bangladesh to 34pp in Malawi. Urban, wealthier and adolescent women had lower readiness-adjusted coverage since they also obtained their contraceptives outside of health facilities. We found little change in the coverage cascades for Nepal from 2015 to 2021.ConclusionsThis analysis demonstrates calculating readiness-adjusted FP coverage using a cascade model in five geographically diverse countries with time trends in one country. As previous studies have shown, we found large gaps in intervention and readiness-adjusted coverage with related inequalities.
Identification of novel vertebral development factors through UK Biobank driven genetic and body imaging analysis reveals markers for back pain
Authors: Sun Zhuopin , Han Jiru , Fearnley Liam G. , McGlinn Edwina , Bahlo Melanie 
Published: February 2025

AbstractNumerical variations and transitional anatomy in the human vertebral column, observed in up to 36% of individuals, represent a significant yet understudied aspect of skeletal development with potential effects on multiple physiological systems. Utilising UK Biobank data, we integrated genetic analysis with deep learning-based multi-modal body imaging to investigate genetic factors associated with thoracic and lumbar spine anatomy. We identified three key genes—GPC3,NR6A1, andVRTN—associated with numerical variations of the lumbar vertebrae and ribs, withVRTNreported for the first time in humans as influencing vertebral development. Our findings reveal significant associations between these genetic variants, vertebral and rib anomalies, and increased prevalence of chronic pain. This study highlights the genetic underpinnings of vertebral development and demonstrates the utility of combining imaging and genetic data to uncover skeletal variation and its health implications for population health.TeaserIntegration of genetic and imaging data uncovers novel genetic factors in human vertebral variations and their link to chronic pain.
A Latent Variable Approach for the Investigation of the Multi-factor Impact on Sleep Problems in Individuals with Mild Cognitive Impairment
Authors: Nega Chrysanthi , Moustaka Kleio , Beratis Ion N. 
Published: February 2025

AbstractThe present study aims to explore the impact of neuropsychiatric symptoms, cognitive functioning, and medical status on sleep problems in individuals with Mild Cognitive Impairment (MCI), focusing on insomnia, by implementing a latent variable approach. The 131 Greek patients with MCI, who are consecutive visitors of the Alzheimer’s day clinic, underwent comprehensive assessments in cognitive functioning, neuropsychiatric symptoms, sleeping disturbances, and medical health status. The model was estimated by applying a Partial Least Squares (PLS) approach to structural equation modeling (SEM), incorporating the following latent variables: “psychological burden” (3 indicators: depressive symptoms, anxiety, and stress), “cognitive status” (5 indicators: general cognitive status, phonemic and semantic fluencies, psychomotor speed, and episodic memory), and “sleep problems” (5 indicators: overnight and earlier final awakening(s), decreased daytime functioning and well-being, and insufficient sleep duration). The results supported the SEM effectiveness, with good model fit and high predictive power. The “psychological burden” played the most significant role in the development of sleep problems within the clinical group of MCI, while “cognitive status” appeared to be the second most important SEM predictor, showing a negative association with “sleep problems”. Additionally, MCI age of onset and sleep problems severity were negatively associated. This latent-variable approach allowed us to capture the multidimensional complexity of sleep problems in MCI. Thus, applying integrative evaluations and interventions that target the cognitive status and psychological well-being, may improve the sleep quality of individuals with MCI, and further contribute to a slower cognitive decline course.
Field-Programmable Gate Array-Based Ultra-Low Power Discrete Fourier Transforms for Closed-Loop Neural Sensing
Authors: Yang Richard , Orser Heather D. , Ludwig Kip A. , Coventry Brandon S. 
Published: February 2025

AbstractDigital implementations of discrete Fourier transforms (DFT) are a mainstay in feature assessment of recorded biopotentials, particularly in the quantification of biomarkers of neurological disease state for adaptive deep brain stimulation. Fast Fourier transform (FFT) algorithms and architectures present a substantial power demand from onboard batteries in implantable medical devices, necessitating the development of ultra-low power Fourier transform methods in resource-constrained environments. Numerous FFT architectures aim to optimize power and resource demand through computational efficiency; however, prioritizing the reduction of logic complexity at the cost of additional computations can be equally or more effective. This paper introduces a minimal architecture single-delay feedback discrete Fourier transform (mSDF-DFT) for use in ultra-low-power field programmable gate array applications and shows energy and power improvements over state-of-the-art FFT methods. We observe a 33% reduction in dynamic power and 4% reduction in resource utilization in a neural sensing application when compared to state-of-the-art FFT algorithms. While designed for use in closed-loop deep brain stimulation and medical device implementations, the mSDF-DFT is also easily extendable to any ultra-low power embedded application.
Inhibition of MAPK signaling suppresses cytomegalovirus reactivation in CD34+Kasumi-3 cells
Authors: Baruah Vargab , Krishna Benjamin A. , Kelly Michael C. , Qi Xu , O’Connor Christine M. 
Published: February 2025

AbstractReactivation of latent human cytomegalovirus (CMV) can lead to severe complications in individuals with dysregulated immune systems. While antiviral therapies for CMV are approved, these compounds are limited by their toxicity and inability to specifically target the latent reservoir or prevent reactivation. Herein we show that CMV reactivation in Kasumi-3 cells, a CD34+hematopoietic cell line, requires mitogen-activated protein kinase (MAPK) activation. Importantly, pharmacological inhibition of the MAPK signaling pathway, including MEK and ERK, restricts viral reactivation in Kasumi-3 cells. In sum, our findings show MAPK signaling is critical for CMV reactivation, revealing a potential avenue for therapeutic intervention to prevent viral reactivation and downstream pathogenesis that is often detrimental for immunosuppressed and immunocompromised patients.
A paradigm to study the learning of muscle activity patterns outside of the natural repertoire
Authors: Ghavampour Ali , Emanuele Marco , Sayyid Shuja R. , Orban de Xivry Jean-Jacques , Michaels Jonathan A. , Pruszynski J. Andrew , Diedrichsen Jörn 
Published: February 2025

AbstractThe acquisition of novel muscle activity patterns is a key aspect of motor skill learning which can be seen at play, for example, when beginner musicians learn new guitar or piano chords. To study this process, here we introduce a new paradigm that requires quick and synchronous flexion and extension of multiple fingers. First, participants practiced all the 242 possible combinations of isometric finger flexion and extension around the metacarpophalangeal joint (i.e., chords). We found that some chords were initially extremely challenging, but participants could eventually achieve them with practice, showing that the initial difficulty did not reflect hard biomechanical constraints imposed by the interaction of tendons and ligaments. In a second experiment we found that chord learning was largely chord-specific and did not generalize to untrained chords. Finally, we explored which factors make some chords more difficult than others. Difficulty was well predicted by the muscle activity pattern required by that chord. Interestingly, difficulty related to how similar chords’ muscle activity patterns are to the muscle activity patterns required by everyday hand use, and to the overall size of the muscle activity. Together, our results suggest that the new paradigm introduced in this work may provide a valuable tool to study the neural processes underlying the acquisition of novel muscle activity patterns in the human motor system.
Transcriptomic analysis ofC9orf72-mutated iPSC-derived microglia implicates cell-autonomous upregulation of selected NLRP3 inflammasome genes in motor neuron degeneration
Authors: Pulimood Nisha S , Thiry Louise , Tang Ye Man , Stifani Stefano 
Published: February 2025

AbstractHexanucleotide repeat expansion (HRE) in the non-coding region of the geneC9orf72is the most prevalent mutation in Amyotrophic Lateral Sclerosis (ALS) and frontotemporal dementia. TheC9orf72HRE contributes to motor neuron degeneration in ALS both through cell-autonomous mechanisms and non-cell autonomous disease processes involving glial cells such as microglia. The molecular mechanisms by whichC9orf72HRE microglia contribute to motor neuron death in ALS remain to be fully elucidated. In this study, we generated microglia from humanC9orf72HRE and isogenic iPSCs using three different microglia derivation methods that can generate microglia with distinct intrinsic inflammatory profiles. RNA sequencing analysis reveals a consistent dysregulation of specific genes involved in pathways underlying NLRP3 inflammasome activation inC9orf72HRE microglia independent of priming with any activating cues. In agreement with elevated expression of NLRP3 inflammasome components, conditioned media fromC9orf72HRE microglia enhance the death ofC9orf72HRE motor neurons implicating microglia-secreted molecules in non-cell autonomous mechanisms ofC9orf72HRE pathology. These findings provide evidence thatC9orf72HRE microglia have a cell-autonomous pro-inflammatory phenotype that contributes to non-cell autonomous mechanisms of motor neuron degeneration in ALS through dysregulated expression of specific genes involved in NLRP3 inflammasome-mediated mechanisms.
Dehalobacterdechlorinates dichloroanilines and contributes to the natural attenuation of dichloronitrobenzenes at a complex industrial site
Authors: Araújo Sofia P. , Lomheim Line , Kraus Suzana P. Q. , Mack E. Erin , Spain Jim C. , Gavazza Sávia , Edwards Elizabeth A. 
Published: February 2025

ABSTRACTThe potential for bioremediation of dichloroanilines (2,3- and 3,4-DCA) and dichloronitrobenzenes (3,4-, 2,5- and 2,3-DCNB) was investigated using inocula from an industrial site in northeast of Brazil. Anaerobic biotransformation of these chlorinated compounds was observed in microcosms simulating site conditions, particularly when electron donor was added. To disentangle specific transformation reactions, sub-cultures from active anaerobic microcosms were enriched with individual DCA or DCNB isomers. In these single-compound enrichment cultures, DCNB isomers were completely reduced to the corresponding DCA isomers. Each DCA isomer was stoichiometrically dechlorinated to the corresponding monochloroaniline (CA) isomers. Further dechlorination of CA to aniline was noted. The reduction of DCNB to DCA was sustained by known fermenters and possiblyDesulfitobacterium, whileDehalobacterwas clearly responsible for dechlorination of DCAs. These findings helped to attribute function to microbial community data retrieved from field samples to inform the conceptual site model and enable identification of bioactive zones and rate-limiting conditions at a complex site. More generally, these data broaden the understanding of the metabolic repertoire ofDehalobacterand provide a model for incorporating microbial community data into site remediation efforts.Graphical AbstractShort synopsis statementA diverse microbial community contributes to natural attenuation at a complex contaminated site. Notably, dichloroanilines produced by biologically-mediated nitroreduction of dichloronitrobenzenes were dechlorinated byDehalobacter.
What’s in a name? Examining the impact of upper caste surname on wages and employment in Indian information technology sector
Authors: Prakash Arjun 
Published: February 2025

PurposeThis study examines the impact of caste on salary levels and job positions within Kerala’s Information Technology sector, aiming to challenge the meritocratic perception of this critical area for India’s economic growth.Design/methodology/approachThe study utilises a dataset of 24,590 employees from 21 IT firms, classified by ownership into Indian and foreign firms. Caste-based disparities are analysed by identifying employees with upper-caste surnames and distinguishing between Kerala Upper Caste and non-Kerala Upper Caste. Generalised Linear Model (GLM) are used to quantify salary disparities and provide deeper insights into how caste, gender and ownership influence salaries.FindingsThe findings reveal significant wage gaps, with individuals bearing upper-caste surnames earning more than their non-upper-caste counterparts, especially in Indian-owned firms. Kerala Upper Caste employees enjoy a salary premium, which is reduced in foreign-owned firms. Moreover, upper-caste individuals are likelier to hold senior roles, indicating potential barriers for non-upper-caste employees.Research limitations/implicationsThese results highlight the need for targeted policies to address caste-based inequalities, promoting inclusiveness and fairness in the IT workplace. Wage-setting practices and promotion criteria, particularly the recent trend of employee recommendations for recruitment, may risk amplifying existing disparities if not carefully managed. Industry leaders must recognise and mitigate these risks to ensure equitable employment practices. Limitation: The study’s reliance on surname-based caste identification may underestimate the extent of caste disparities. Further, the absence of additional human capital controls, and focus on Kerala limit the generalizability of findings.Originality/valueThis study is the first to analyse caste dynamics within the IT sector using a rich dataset of corporate firms and wages, offering a novel methodological approach to understanding how social identity intersects with economic outcomes.
A study of inclusive supervisory behaviors, workplace social inclusion and turnover intention in the context of employee age
Authors: Ali Muhammad , Baker Marzena , Grabarski Mirit K. , Islam Ranjita 
Published: February 2025

PurposeThe Australian retail industry is facing skills shortages while mature and old-age workers are experiencing high unemployment rates. This study focuses on understanding organizational inclusion and turnover intentions in the context of employee age.Design/methodology/approachSurvey data were collected from 502 retail supervisors and employees.FindingsDrawing on socioemotional selectivity theory and social exchange theory, the findings indicate: no difference in inclusive supervisory behaviors perceptions for different age groups; a significantly higher workplace social inclusion perceptions among employees aged 55 plus than among employees aged 35–44; a significantly lower turnover intention among employees aged 55 plus and 45–54 years than other age groups; a positive relationship between inclusive supervisory behaviors and workplace social inclusion and a negative relationship between workplace social inclusion and turnover intention which was stronger for older employees than for younger employees.Practical implicationsThe findings present a business case for hiring older employees and indicate that managers need to prioritize inclusion.Originality/valueThis study addresses the underexplored area of employee age differences in inclusion and turnover perceptions among retail employees. It links inclusive supervisory behaviors, social inclusion and turnover intention.