bluuebunny/crossref_metadata_2025_split huggingface dataset:
The performance of AlphaMissense to identify genes causing disease
Authors: Chen Yiheng , Butler-Laporte Guillaume , Liang Kevin Y. H. , Ilboudo Yann , Yasmeen Summaira , Sasako Takayoshi , Langenberg Claudia , Greenwood Celia M.T. , Richards J Brent 
Published: March 2024

AbstractA novel algorithm, AlphaMissense, has been shown to have an improved ability to predict the pathogenicity of rare missense genetic variants. However, it is not known whether AlphaMissense improves the ability of gene-based testing to identify disease-causing genes. Using whole-exome sequencing data from the UK Biobank, we compared gene-based association analysis strategies including sets of deleterious variants: predicted loss-of-function (pLoF) variants only, pLoF plus AlphaMissense pathogenic variants, pLoF with missense variants predicted to be deleterious by any of five commonly utilized annotation methods (Missense (1/5)) or only variants predicted to be deleterious by all five methods (Missense (5/5)). We measured performance to identify 519 previously identified positive control genes, which can cause Mendelian diseases, or are the targets of successfully developed medicines. These strategies identified 850k pLoF variants and 5 million deleterious missense variants, including 22k likely pathogenic missense variants identified exclusively by AlphaMissense. The gene-based association tests found 608 significant gene associations (atP<1.25×10−7) across 24 common traits and diseases. Compared to pLOFs plus Missense (5/5), tests using pLoFs and AlphaMissense variants found slightly more significant gene-disease and gene-trait associations, albeit with a marginally lower proportion of positive control genes. Nevertheless, their overall performance was similar. Merging AlphaMissense with Missense (5/5), whether through their intersection or union, did not yield any further enhancement in performance. In summary, employing AlphaMissense to select deleterious variants for gene-based testing did not improve the ability to identify genes that are known to cause disease.
Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity
Authors: Roederer Alex L. , Cao Yi , St. Denis Kerri , Sheehan Maegan L. , Li Chia Jung , Lam Evan C. , Gregory David J. , Poznansky Mark C. , Iafrate A. John , Canaday David H. , Gravenstein Stefan , Garcia-Beltran Wilfredo F. , Balazs Alejandro B. 
Published: March 2024

SUMMARYSince the COVID-19 pandemic began in 2020, viral sequencing has documented 131 individual mutations in the viral spike protein across 48 named variants. To determine the ability of vaccine-mediated humoral immunity to keep pace with continued SARS-CoV-2 evolution, we assessed the neutralization potency of sera from 76 vaccine recipients collected after 2 to 6 immunizations against a comprehensive panel of mutations observed during the pandemic. Remarkably, while many individual mutations that emerged between 2020 and 2022 exhibit escape from sera following primary vaccination, few escape boosted sera. However, progressive loss of neutralization was observed across newer variants, irrespective of vaccine doses. Importantly, an updated XBB.1.5 booster significantly increased titers against newer variants but not JN.1. These findings demonstrate that seasonal boosters improve titers against contemporaneous strains, but novel variants continue to evade updated mRNA vaccines, demonstrating the need for novel approaches to adequately control SARS-CoV-2 transmission.
Predictors of mortality among COVID-19 patients at Kilimanjaro Christian Medical Centre in Northern Tanzania: A hospital-based retrospective cohort study
Authors: Waria Gilbert G. , Muro Florida J. , Jonas Norman , Sakita Francis , Shirima Laura , Mlay Henry L. , Ngowi Michael , Meela Elvis B. , Mboya Innocent B. , Kilonzo Kajiru G. 
Published: March 2024

AbstractBackgroundCOVID-19 disease is a global public health disaster causing a range of social, economic, and healthcare difficulties, border restrictions, high human loss, lockdown, and transportation challenges. Despite it being a global pandemic, there are few studies conducted in Tanzania to examine the predictors of mortality. This disease has caused a significant number of mortalities worldwide but literature shows low mortality and better survival in Africa than in other WHO regions. Therefore, this study aimed to determine the predictors of mortality among COVID-19 patients at KCMC Hospital in Northern Tanzania.MethodologyThis was the hospital-based retrospective cohort study, conducted at KCMC Hospital in Northern Tanzania among all admitted patients with confirmed COVID-19, from 10thMarch 2020 to 26thJanuary 2022. The main study event was COVID-19 mortality. The predictors of mortality were determined by using the Weibull survival regression model and the statistically significant results were declared at a p-value of <0.05.ResultsA total of 547 confirmed COVID-19 patient records were included in the study. Their median age was 63 (IQR; 53-83), about 60% were aged 60 years and above, and 56.7% were males. The most common clinical features were; fever (60.8%), a severe form of the disease (44.4%), difficulty in breathing (73.3%), chest pain (46.1%), and generalized body weakness (71.3%). Of all participants, over one-third (34.6%) died (95%CI; 0.31-0.39). The median survival time was 7 days (IQR; 3-12). The overall mortality rate was 32.33 per 1000 person-days while the independent predictors of higher mortality risk were age ≥60 years (AHR=2.01; 95%CI 1.41-2.87; P<0.001), disease severity (AHR=4.44; 95%CI 2.56-7.73; P<0.001) and male sex (AHR=1.28; 95%CI; 0.93-1.73; P=0.128).ConclusionMortality was higher in elderly male patients, with a severe form of the disease and those with any comorbidities. Therefore, more attention should be provided to older patients including uptake of the current vaccine and ensuring standard and supportive care at primary health facilities is available.
Roles of TYRO3 Family Receptors in Germ Cell Development During Mouse Testis Formation
Authors: Ming Zhenhua , Bagheri-Fam Stefan , Frost Emily R , Ryan Janelle M , Binder Michele D , Harley Vincent R 
Published: March 2024

Structured AbstractObjectiveTo investigate the role of a potential SOX9 target gene,Tyro3, along with its family members,AxlandMertk(TAM family) in mouse testis development.DesignExperimental laboratory study.SettingResearch institute units.Subject(s)Embryonic day (E)11.5 Swiss mouse gonads forex vivogonad culture;Tyro3knockout mouse embryos.Intervention(s)E11.5 Swiss mouse gonads were cultured in hanging droplets of 30 µL DMEM medium supplemented with 10% FBS and 1% antibiotic-antimycotic. A pair of gonads were treated with 20 μM of BMS-777607 or 30 μM of LDC1267 and an equivalent volume of the vehicle control DMSO.Main Outcome Measure(s)Immunofluorescence to measure morphological changes ofex vivocultured gonads andin vivo Tyro3mouse testes; qRT-PCR to measure gene expressions.Result(s)Inhibition of the TAM family in E11.5ex vivocultured male mouse gonads led to reduced germ cell numbers caused by reduced proliferation and increased apoptosis of the germ cells.Tyro3knockout mice exhibited reduced expression levels of the germ cell genesDdx4,DazlandPou5f1and increased expression levels of the Sertoli cell genesSox9andAmhat E12.5. However, by E14.5, the expression ofDdx4,Dazl,Sox9andAmhhad returned to normal levels inTyro3knockout testes.Tyro3knockout testes displayed normal morphology and structures during fetal testis development.Conclusion(s)TAM family members have redundant roles in regulating germ cell development during early testis development.Attestation StatementData regarding any of the subjects in the study has not been previously published unless specified.Data will be made available to the editors of the journal for review or query upon request.Data Sharing StatementN/ACapsuleInhibition of the TAM family led to loss of germ cells in fetal gonads and deletion ofTyro3alone disturbed gene expressions of germ cells and Sertoli cells.
The developing mouse dopaminergic system: Cortical-subcortical shift in D1/D2 receptor balance and increasing regional differentiation
Authors: Bjerke Ingvild E. , Carey Harry , Bjaalie Jan G. , Leergaard Trygve B. , Kim Jee Hyun 
Published: March 2024

AbstractThe dopaminergic system of the brain is involved in complex cognitive functioning and undergoes extensive reorganization during development. Yet, these changes are poorly characterized. We have quantified the density of dopamine 1- and 2-receptor (D1 and D2) positive cells across the forebrain of male and female mice at five developmental stages. Our findings show a cortico-subcortical shift in D1/D2 balance, with increasing D1 dominance in cortical regions as a maturational pattern that occurs earlier in females. We describe postnatal trajectories of D1 and D2 cell densities across major brain regions and observe increasing regional differentiation of D1 densities through development. Our results provide the most comprehensive overview of the developing dopaminergic system to date, and an empirical foundation for further experimental and computational investigations of dopaminergic signaling.
The costs and cost-effectiveness of different service models of palliative care, focusing on end of life care: A rapid review
Authors: Spencer Llinos Haf , Anthony Bethany Fern , Davies Jacob , Pisavadia Kalpa , Gillen Liz , Noyes Jayne , Fitzsimmons Deborah , Lewis Ruth , Cooper Alison , Hughes Dyfrig , Edwards Rhiannon Tudor , Edwards Adrian 
Published: March 2024

AbstractSome people receive palliative or end of life care at home, others in hospitals or hospices, or a combination of home and hospice/home and hospital models. This rapid review aims to determine the costs and cost-effectiveness of different service models of palliative care or end of life care. These studies are mostly conducted from the perspective of the healthcare system, disregarding costs related to patients/caregivers economic burden (Perea-Bello et al., 2023).Research Implications and Evidence GapsMore UK research is needed on cost impacts of new services such as Enhanced Supported Care (ESC). Future research should consider which methods are most appropriate to evaluate palliative care models. Standard methodology, such as the calculation of quality-adjusted life years (QALYs), may not be most appropriate for this end of life population.Improving QALYs may not be the intended aim of palliative care or end of life interventions, and prolonging death may be inconsistent with patient preferences and wishes. The quality and applicability of the evidence we found in our rapid review were variable, and therefore, uncertainty remains, especially when the perspective of analysis was not stated clearly.Therefore, it was difficult to ascertain whether all relevant costs were considered. Assumptions on costs were not varied in many studies, and most studies had different time horizons.Policy and Practice ImplicationsThis rapid review has shown thathospital-based palliative care costs are higher than hospice or home-basedpalliative care. This suggests thathome-based palliative care should be available to allpatients in a recognisable end of life phase who desire to remain and die at home. Healthcare planners shouldaim to reduce hospitalisation at the end of lifebutonly if access to quality home careat the end of life is guaranteed.Patients should have a choiceabout where they prefer to die without moving the costs from the healthcare system to the home caregivers, rendering the costs invisible.Funding StatementThe Bangor Institute for Medical and Health Research, was funded for this work by the Health and Care Research Wales Evidence Centre, itself funded by Health and Care Research Wales on behalf of Welsh Government.
Low-frequency hearing thresholds improve as high-frequency hearing sensitivity deteriorates between young adulthood and middle age in normally hearing people
Authors: Izmaylova Tatiana , Undurraga Jaime A. , Sowman Paul F. 
Published: March 2024

AbstractHearing sensitivity changes throughout a person’s lifetime. This work aimed to describe changes in pure-tone audiometric (PTA) thresholds that occur in the transition from young adulthood to middle age in 121 adults with normal or nearly normal hearing. Results showed that older people had worse high-frequency (4000-8000 Hz) thresholds and better low-frequency (125-500 Hz) thresholds than younger individuals, suggesting that hearing sensitivity in the low-frequency range may improve with age. The improvement of low-frequency thresholds may be part of a central compensation for age-related deterioration of high-frequency hearing sensitivity. Further investigation of age-related changes in low-frequency hearing sensitivity is needed to confirm our findings.
Molecular mechanism of α-latrotoxin action
Authors: Klink BU , Alavizargar A , Subramaniam KK , Chen M , Heuer A , Gatsogiannis C 
Published: March 2024

AbstractThe potent neurotoxic venom of the black widow spider contains a cocktail of seven phylum-specific latrotoxins (LTXs), but only one, α-LTX, targets vertebrates. This 130 kDa toxin binds to receptors at presynaptic nerve terminals and triggers a massive release of neurotransmitters. It is widely accepted that LTXs tetramerize and insert into the presynaptic membrane, thereby forming Ca2+-conductive pores, but the underlying mechanism remains poorly understood. LTXs are homologous and consist of an N-terminal region with three distinct domains, along with a C-terminal domain containing up to 22 consecutive ankyrin repeats. Here we report the first high resolution structures of the vertebrate-specific α-LTX tetramer in its prepore and pore state. Our structures, in combination with AlphaFold2-based structural modeling and molecular dynamics simulations, reveal dramatic conformational changes in the N-terminal region of the complex. Four distinct helical bundles synchronously rearrange to progressively form a highly stable 15 nm cation-impermeable coiled-coil stalk. This stalk, in turn, positions an N-terminal pair of helices within the membrane, thereby enabling the assembly of a cation-permeable channel. Taken together, these data unveil a unique mechanism for membrane insertion and channel formation, characteristic of the LTX family, and provide the necessary framework for advancing novel therapeutics and biotechnological applications.
Doped semiconductor devices for sub-MeV dark matter detection
Authors: Du Peizhi , Egaña-Ugrinovic Daniel , Essig Rouven , Sholapurkar Mukul 
Published: March 2024

Dopant atoms in semiconductors can be ionized with ∼10  meV energy depositions, allowing for the design of low-threshold detectors. We propose using doped semiconductor targets to search for sub-MeV dark matter scattering or sub-eV dark matter absorption on electrons. Currently unconstrained cross sections could be tested with a 1 g-day exposure in a doped detector with backgrounds at the level of existing pure semiconductor detectors, but improvements would be needed to probe the freeze-in target. We discuss the corresponding technological requirements and lay out a possible detector design.

Published by the American Physical Society
2024
A human-centered perspective on individual risks for digital innovation management: an integrative conceptual review
Authors: Du Plooy Hilda , Tommasi Francesco , Furlan Andrea , Nenna Federica , Gamberini Luciano , Ceschi Andrea , Sartori Riccardo 
Published: March 2024

PurposeFollowing the imperative for human-centric digital innovation brought by the paradigm of Industry 5.0, the article aims to integrate the dispersed and multi-disciplinary literature on individual risks for workers to define, explain and predict individual risks related to Industry 4.0 technologies.Design/methodology/approachThe paper follows the question, “What is the current knowledge and evidence base concerning risks related to Industry 4.0 technologies, and how can this inform digital innovation management in the manufacturing sector through the lens of the Industry 5.0 paradigm?” and uses the method of systematic literature review to identify and discuss potential risks for individuals associated with digital innovation. N = 51 contributions met the inclusion criteria.FindingsThe literature review indicates dominant trends and significant gaps in understanding risks from a human-centric perspective. The paper identifies individual risks, their interplay with different technologies and their antecedents at the social, organizational and individual levels. Despite this, the paper shows how the literature concentrates in studying risks on only a limited number of categories and/or concepts. Moreover, there is a lack of consensus in the theoretical and conceptual frameworks. The paper concludes by illustrating an initial understanding of digital innovation via a human-centered perspective on psychological risks.Practical implicationsFindings yield practical implications. In investing in the adoption, generation or recombination of new digital technologies in organizations, the paper recommends managers ensure to prevent risks at the individual level. Accordingly, the study’s findings can be used as a common starting point for extending the repertoire of managerial practices and interventions and realizing human-centric innovation.Originality/valueFollowing the paradigm of Industry 5.0, the paper offers a holistic view of risks that incorporates the central role of the worker as crucial to the success of digital innovation. This human-centric perspective serves to inform the managerial field about important factors in risk management that can result in more effective targeted interventions in risk mitigation approaches. Lastly, it can serve to reinterpret digital innovation management and propose future avenues of research on risk.
Business model innovation and Industry 5.0: a possible integration in GLAM institutions
Authors: Botti Antonio , Baldi Giovanni 
Published: March 2024

PurposeThis research delves into the realm of Business Model Innovation (BMI), integrating it with the human-centric, sustainable, and resilient principles of Industry 5.0, proposing a new theoretical framework.Design/methodology/approachAn abductive approach has been chosen to expand existing knowledge developing new ideas based on emerging phenomena. Data were gathered via semi-structured interviews with directors, managers and curators of public institutions in Italy, Switzerland, Germany and Spain encompassing Galleries, Libraries, Archives, and Museums (GLAM). These data were subsequently subjected to thematic analysis.FindingsThe findings indicate that the main enablers for Business Model Innovation (BMI) in combination with Industry 5.0 encompassed stakeholder, customer and organizational engagement, collaborative environment, knowledge and innovation management, and sustainability. These drivers were effectively leveraged through three pivotal facilitators-inhibitors: technology, resources, and leadership.Research limitations/implicationsThe principal constraints are rooted in the narrow contextual focus and the limited participants number. However, upcoming research efforts may broaden the horizons of this multifaceted and extensive investigation.Originality/valueThis study is groundbreaking as it fills a significant gap in the existing literature by integrating Business Model Innovation (BMI) with the Industry 5.0 paradigm, a novel approach that has not been explored previously. Additionally, the inclusion of GLAM institutions in this research adds a unique dimension, as they have been largely overlooked in both research domains.
Consumer and brand value formation, value creation and co-creation in social media brand communities
Authors: Marchowska-Raza Magdalena , Rowley Jennifer 
Published: March 2024

Purpose
Social media has significantly impacted the value creation processes within the consumer–brand relationship. This study aims to examine value formation processes within a cosmetics social media brand community and to establish the types of value formation associated with different categories of interactions within a social media brand community.

Design/methodology/approach
The research adopted a netnographic approach and followed the operational protocols of netnography. Conversations in one large cosmetics social media brand community were observed and downloaded for analysis over a two-month period. Examples of value-creation and formation processes were identified using netnographic interpretative procedures to develop higher-order themes.

Findings
The findings supported the creation of a “Consumer and brand value creation and co-creation framework” highlighting disparate value types within the following interactions: consumer-to-consumer; brand-to-consumer; and consumer-to-brand. The identified value types were specific to the actors (i.e. consumers and brands) involved in value formation processes. The analysis also revealed consumers’ ability to independently generate value through direct interaction with a social media brand community and the brands’ role in supporting consumers in value formation through value facilitation.

Originality/value
The pivotal role of disparate actors’ interactions in value formation processes is highlighted, alongside the autonomous ability to form value with the aid of resources stored and shared within the social media brand community. The network of interactions and value-creation processes contribute to a holistic understanding of the interactions in a social media brand community. Furthermore, the research explores and highlights the emerging role of social media brand communities as “value vestiges”.
The influence of service quality on student satisfaction and student loyalty in Vietnam: the moderating role of the university image
Authors: Nguyen Hoang Viet , Vu Tuan Duong , Saleem Muhammad , Yaseen Asif 
Published: March 2024

PurposeImproving service quality, student satisfaction and student loyalty is important to higher education institutions’ sustainable growth. The objectives of this study are a twofold: first, the study seeks to determine the dimensions of higher education service quality with a specific focus on Vietnam. Second, it examines how the service quality dimensions impact student satisfaction and student loyalty, with the moderating role of the university image.Design/methodology/approachThis study followed a rigorous procedure, including interviews, a survey, exploratory factor analysis (EFA) and reliability analysis to identify higher education service quality dimensions and their measures. After that, using the data obtained from 1,550 university students in Vietnam, confirmatory factor analysis was used to validate the identified dimensions and structural equation modeling was used to test a proposed model explaining the outcomes of higher education service quality.FindingsThe findings reveal five dimensions of higher education service quality: academic aspect, nonacademic aspect, programming issues, facilities and industry interaction. Most of these factors have a positive influence on student satisfaction. In addition, the university image moderates the positive relationship between student satisfaction and student loyalty.Practical implicationsThis study’s findings highlight the complexity of service quality in the higher education context and encourage higher education institutions to improve their service quality in image to enhance student satisfaction and loyalty.Originality/valueThis study suggests a unique measure of higher education service quality dimensions and provides fresh insights into how they impact student satisfaction and loyalty in Vietnam.