bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of novel Kv1.3 channel-interacting proteins using proximity labelling in T-cells
Authors: Kour Dilpreet , Bowen Christine A. , Srivastava Upasna , Nguyen Hai M. , Kumari Rashmi , Kumar Prateek , Brandelli Amanda D. , Bitarafan Sara , Tobin Brendan R , Wood Levi , Seyfried Nicholas T. , Wulff Heike , Rangaraju Srikant 
Published: January 2025

ABSTRACTPotassium channels regulate membrane potential, calcium flux, cellular activation and effector functions of adaptive and innate immune cells. The voltage-activated Kv1.3 channel is an important regulator of T cell-mediated autoimmunity and microglia-mediated neuroinflammation. Kv1.3 channels, via protein-protein interactions, are localized with key immune proteins and pathways, enabling functional coupling between K+ efflux and immune mechanisms. To gain insights into proteins and pathways that interact with Kv1.3 channels, we applied a proximity-labeling proteomics approach to characterize protein interactors of the Kv1.3 channel in activated T-cells. Biotin ligase TurboID was fused to either N or C termini of Kv1.3, stably expressed in Jurkat T cells and biotinylated proteins in proximity to Kv1.3 were enriched and quantified by mass spectrometry. We identified over 1,800 Kv1.3 interactors including known interactors (beta-integrins, Stat1) although majority were novel. We found that the N-terminus of Kv1.3 preferentially interacts with protein synthesis and protein trafficking machinery, while the C-terminus interacts with immune signaling and cell junction proteins. T- cell Kv1.3 interactors included 335 cell surface, T-cell receptor complex, mitochondrial, calcium and cytokine-mediated signaling pathway and lymphocyte migration proteins. 178 Kv1.3 interactors in T-cells also represent genetic risk factors of T cell-mediated autoimmunity, including STIM1, which was further validated using co-immunoprecipitation. Our studies reveal novel proteins and molecular pathways that interact with Kv1.3 channels in adaptive (T-cell) and innate immune (microglia), providing a foundation for how Kv1.3 channels may regulate immune mechanisms in autoimmune and neurological diseases.
Elucidating distinct and common fMRI-complexity patterns in pre-adolescent children with Attention-Deficit/Hyperactivity Disorder, Oppositional Defiant Disorder, and Obsessive-Compulsive Disorder diagnoses
Authors: Zhang Ru , Cen Steven , Wijesinghe Dilmini , Aksman Leon , Murray Stuart B. , Duval Christina J. , Wang Danny J.J. , Jann Kay 
Published: January 2025

AbstractImportanceThe pathophysiology of ADHD is complicated by high rates of psychiatric comorbidities, thus delineating unique versus shared functional brain perturbations is critical in elucidating illness pathophysiology.ObjectiveTo investigate resting-state fMRI (rsfMRI)-complexity alterations among children with ADHD, oppositional defiant disorder (ODD), and obsessive-compulsive disorder (OCD), respectively, and comorbid ADHD, ODD, and OCD, within the cool and hot executive function (EF) networks.DesignWe leveraged baseline data (wave 0) from the Adolescent Brain and Cognitive Development (ABCD) Study.SettingThe data was collected between September 2016 and September 2019 from 21 sites in the USA.ParticipantsChildren who singularly met all DSM-5 behavioral criteria for ADHD (N= 61), ODD (N= 38), and OCD (N= 48), respectively, were extracted, alongside children with comorbid ADHD, ODD, OCD, and/or other psychiatric diagnoses (N= 833). A control sample of age-, sex-, and developmentally-matched children was also extracted (N= 269).Main Outcomes and MeasuresVoxel-wise sample entropy (SampEn) was computed using the LOFT Complexity Toolbox. Mean SampEn within all regions of the EF networks was calculated for each participant and hierarchical models with Generalized Estimating Equations compared SampEn of comorbid-free and comorbid ADHD, ODD, and OCD within the EF networks.ResultsSampEn was reduced in comorbid-free ADHD and ODD in overlapping regions of both EF networks, including the bilateral superior frontal gyrus, anterior/posterior cingulate gyrus, and bilateral caudate (Wald statistic = 5.682 to 10.798,p< 0.05 & BH corrected), with ADHD additionally affected in the right inferior/middle frontal gyrus and bilateral frontal orbital cortex (Wald statistic = 7.231 to 9.420,p< 0.05 & BH corrected). Among comorbid presentations, the additional presence of ADHD symptomatology was associated with significantly lower SampEn in every region of interest (z= -3.973 to -2.235,p< 0.05 & BH corrected).Conclusions and RelevanceADHD and ODD shared common impairments underlying the EF networks in the comorbid-free presentations, with ADHD showing more widespread complexity reduction. When ADHD co-occurred with other psychiatric disorders, the reduction in SampEn extended beyond the regions affected in comorbid-free ADHD, indicating that comorbidities amplify neural complexity deficits.
Distinct Classes of Gut Bacterial Molybdenum-Dependent Enzymes Produce Urolithins
Authors: Bae Minwoo , Dong Xueyang , Avila-Pacheco Julian , Inyama Fechi , Hill-Maini Vayu , Clish Clary , Balskus Emily P. 
Published: January 2025

AbstractUrolithin A is an anti-aging and anti-inflammatory gut bacterial metabolite derived from ellagic acid (EA), a polyphenol abundant in berries and nuts. The conversion of EA to urolithin A involves multiple chemically challenging phenol dehydroxylation steps that produce urolithins with varying bioactivities. Despite their biological and chemical significance, the bacterial enzymes responsible for urolithin production remain unidentified. Here, we use differential gene expression analysis, anaerobic protein expression, and enzyme assays to identify members of two distinct molybdenum enzyme families (the DMSO reductase family and the xanthine oxidase family) capable of regioselective dehydroxylation and urolithin generation. These two enzyme families have distinct substrate requirements, suggesting they employ different catalytic mechanisms for phenol dehydroxylation. Multi-omics analysis of a human cohort uncovers decreased levels of urolithin A and genes encoding urolithin A-producing enzymes in patients with inflammatory bowel disease (IBD), implying reduced health effects of EA consumption in this setting. Together, this study elucidates the molecular basis of urolithin production, expands the known enzymatic repertoire of the human gut microbiome, and suggests a potential link between gut bacterial urolithin production and host inflammation.Significance statementThe human gut microbiome modulates the health effects of dietary compounds by modifying their chemical structures. For example, gut microbes extensively metabolize polyphenols, a group of diverse plant-derived compounds associated with positive health outcomes. Urolithin A, a gut bacterial metabolite derived from a polyphenol abundant in berries and nuts, exhibits potent anti-inflammatory activity. However, the gut bacterial enzymes involved in its production remain largely unknown. Here, we report urolithin-producing gut bacterial enzymes, including four phenol dehydroxylases from two distinct molybdenum-dependent enzyme families. Analyzing human gut microbiomes suggests a potential link between genes encoding these enzymes and host inflammation. Together, our findings fully map urolithin A production to enzymes, increasing our understanding of how the gut microbiome can alter the impacts of diet on human health.
Interplay between innovation-oriented HRM and leadership to promote intrapreneurial behavior for innovation performance in small- and medium-sized enterprises
Authors: Rasheed Muhammad Athar , Elahi Natasha Saman , Nisar Qasim Ali , Nasir Nadia 
Published: January 2025

PurposeDrawing on ability-motivation-opportunity (AMO) framework, this study investigates the direct effect of innovation-oriented HRM on SMEs’ innovation performance, both directly and through intrapreneurial behavior. Besides, the study assesses the moderating role of innovation-oriented leadership in the relationship between innovation-oriented HRM and intrapreneurial behavior.Design/methodology/approachA two-wave dataset collected from 183 SMEs was used to test the proposed hypotheses by partial least squares structural equation modeling (PLS-SEM).FindingsFindings suggest that innovation-oriented HRM positively impacts SMEs’ innovation performance directly and through intrapreneurial behavior. Evidence also confirms that innovation-oriented leadership positively moderates the effect of innovation-oriented HRM on intrapreneurial behavior.Research limitations/implicationsThrough the AMO framework, this study advances our understanding of how the interaction between innovation-oriented HRM and leadership fosters intrapreneurial behavior, ultimately contributing to superior innovation performance in SMEs.Practical implicationsThe study recommends that SMEs implement innovation-oriented HRM practices to encourage intrapreneurial behavior and achieve superior innovation performance in SMEs.Originality/valueLimited research has addressed the contributions of innovation-oriented HRM and leadership toward realizing strategic innovation objectives. Our study offers valuable insights into the functions of innovation-oriented HRM and leadership in stimulating intrapreneurial behavior, thereby enhancing the innovation performance of SMEs.
Persistence of the armed conflict in Colombia: an agreement without peace
Authors: Rivera-Lozada Isabel Cristina , Gómez Sánchez Andrés Mauricio , Uni-Chilito Jennifer 
Published: January 2025

PurposeThe aim is to analyze the armed conflict persistence in Colombia from 2008 to 2018 based on the financial viability hypothesis (rebellion occurs when war net revenue is nonnegative).Design/methodology/approachThe methodology is quantitative. Firstly, a nonparametric Kaplan–Meier functions and survival risk functions are developed as initial approximation. Subsequently, a Probit model with panel data is implemented and the covariates are grouped into three dimensions: opportunity, grievance and institutional-political.FindingsThe viability hypothesis boosts the continuity of the armed conflict, which is enhanced and perpetuated by the viability and financial incentives from public revenues and natural resources, while the grievance, political fragmentation and institutional dimensions contribute to the opportunity structure in Collier that makes the conflict militarily and economically viable.Research limitations/implicationsLack of information for some states in Colombia prevents a much more holistic analysis.Practical implicationsPostulate what is required by the Colombian State to cut off the sources of financing of armed groups and thus, one of the determinants of the continuity of the conflict.Social implicationsThe political fragmentation contributes to rebellion, and that variables representing the dimensions of grievance and institutional presence contribute to the opportunity structure that makes the conflict in Colombia militarily and economically viable.Originality/valueThis research proposes as a novelty to incorporate the viability hypothesis with some factors related to the grievance that explain the persistence of the armed conflict as a consequence of decreasing recruitment costs for the insurgent groups, a situation that contributes to the opportunity structure and financial viability of the conflict.
Assessing the impact of source credibility on fast fashion brand loyalty
Authors: Low Florence Cia Shane , Goh Yen-Nee , Lim Chee Ngee 
Published: January 2025

PurposeThis study assesses the impact of source (influencer’s) credibility on brand trust that leads to loyalty towards a fast fashion brand.Design/methodology/approachThe stimulus-organism-response (S-O-R) framework is adopted in this study. A quantitative study was conducted by administering questionnaires to target respondents. A partial least squares structural equation modeling (PLS-SEM) using SmartPLS is implemented to analyze 206 collected responses.FindingsSEM outcomes statistically support the suggested paths. Findings show that the order of importance of source credibility components in affecting consumer trust in a brand is trustworthiness, expertise, similarity and attractiveness. Additionally, brand loyalty is directly affected by brand trust.Research limitations/implicationsThe current study offers understanding into influencers' credibility and brand trust, which can lead to customer loyalty toward a brand. This study also aids marketing practitioners in keeping track of other attributes in deciding if influencers are a good fit for brands. Future research should explore the potential impacts of source credibility components on recommendation intention to build an effective word-of-mouth strategy.Originality/valueThis study explains the literature on brand trust and brand loyalty by justifying the S-O-R framework.
Innovative Insurance to Improve US Patient Access to Cell and Gene Therapy
Authors: CONTI RENA M. , DEMARTINO PATRICK , GRUBER JONATHAN , LO ANDREW W. , SUN YUTONG , WU JACKIE 
Published: January 2025

Policy Points
Cell and gene therapies (CGTs) offer treatment for rare and oftentimes deadly disease, but their prices are high, and payers may seek to limit spending.
Total annual costs of covering all existing and expected CGTs for the entire US population 2023–2035 to amount to less than $20 per person and concentrate in commercial and state Medicaid plans.
Reinsurance fees add to expected costs.
Policies that improve coverage and affordability are needed to assure patient access to CGTs.
ContextCell and gene therapies (CGTs) offer treatment to rare and oftentimes deadly diseases. Because of their high price and uncertain clinical outcomes, US insurers commonly restrain patient access to CGTs, and these barriers may create or perpetuate existing disparities. A reconsideration of existing insurance policies to improve access and reduce disparities is currently underway. One method insurers use to support access and protect them from large, unexpected claims is the purchase of reinsurance. In exchange for an upfront per‐member‐per‐month (PMPM) premium, the reinsurer pays the claim and rebates the insurer at the end of the contract period if there are funds leftover. However, existing reinsurance plans may not cover CGTs or charge exorbitant fees for coverage.MethodsWe simulate the incremental annual per‐person reinsurer costs to cover CGTs existing or expected between 2023 and 2035 for the US population and by payer type based on previously published estimates of expected US spending on CGTs, assumed US population of 330 persons, and current CGT reinsurance fees. We illustrate our methods by estimating the incremental annual per‐person costs overall payers and to state Medicaid plans of sickle cell disease–targeted CGTs.FindingsWe estimate annual incremental spending on CGTs 2023–2035 to amount to $20.4 billion, or $15.69 per person. Total annual estimated spending is expected to concentrate among commercial plans. Sickle cell–targeted CGTs add a maximum of $0.78 PMPM in costs to all payers and will concentrate within state Medicaid programs. Reinsurance fees add to expected costs.ConclusionsAnnual per‐person costs to provide access to CGTs are expected to concentrate in commercial and state Medicaid plans. Policies that improve CGT coverage and affordability are needed.
Public Functions of Political Parties in the United Kingdom
Authors: Trueblood Leah 
Published: January 2025

Political parties are both private and public bodies. Some actions of political parties must be categorised as private to protect freedom of speech and association. This article argues, however, that it is sometimes necessary that political parties are understood as exercising public functions as well. When parties are exercising public functions, their actions then may be subject to judicial review. Currently, political parties have not been held to exercise public functions in the UK either for purposes of the Human Rights Act 1998 or common law judicial review. This article challenges the approach in UK law, particularly in Tortoise Media v Conservative Party [2023], which held that it was not even arguable that the selection of a Prime Minister by a political party was a public function. This article challenges this finding by offering a framework, drawn from current case law, for establishing when political parties are exercising public functions. The case law says that functions are public when bodies are ‘operating as an integral part of a governmental framework’. These conditions were more than satisfied in Tortoise Media and offer a firm – albeit limited and context‐contingent – basis for judicial review of actions by political parties.
Dental Implant Rehabilitation in Patients Carrying WNT10A Mutations With Different Molecular Statuses and Phenotypes: A Retrospective Cohort Study
Authors: Dou Jiaqi , Dai Qinggang , Yu Xinbo , He Yining , Dai Yuwei , Wang Feng , Wu Yiqun 
Published: January 2025

ABSTRACTObjectivesWNT10A mutations are associated with tooth agenesis. This study aimed to assess the clinical outcomes of dental implants in patients carrying WNT10A mutations with different molecular statuses and phenotypes over a long‐term follow‐up period.Materials and MethodsPatients with tooth agenesis were screened by whole‐exome sequencing (WES) from January 2010 to September 2023. Carriers of pathogenic WNT10A mutations who underwent subsequent dental implant therapy were evaluated.ResultsWES identified 66 patients with tooth agenesis carrying WNT10A mutations. Of these, 27 patients (11 males/16 females; mean age 19.6 years) met the inclusion criteria. Homozygotes had significantly more missing teeth (24.4 ± 3.8) than heterozygotes (10.9 ± 5.1, p < 0.0001) and compound heterozygotes (13.8 ± 3.5, p = 0.001). A total of 160 conventional implants were placed. Seven implants were lost in four patients before final prosthesis placement, resulting in overall failure rates of 14.8% at the subject level and 4.4% at the implant level. The 5‐year cumulative survival rate (range: 0.23–12.74 years) was 85.2% and 95.6% at the subject and implant levels, respectively. The mean marginal bone loss (MBL) was 0.80 mm (95% CI: 0.59–1.02). Subgroup analysis revealed higher MBL in homozygotes (p = 0.002), sites requiring extensive bone augmentation (p = 0.016), anterior regions (p = 0.031), and full‐arch bridge cases (p < 0.0001). Patient satisfaction and OHIP‐C49 scores were favorable.ConclusionsImplant rehabilitation is predictable for patients with WNT10A mutations. However, increased MBL observed in homozygotes with severe tooth agenesis and in cases requiring extensive alveolar bone augmentation highlights the importance of genetic diagnosis prior to implant therapy in patients with severe tooth agenesis.
How Business‐Like Operations Shape Student Union Values and Accountability: Accounts of Publicness and Privateness Discourse in Universities
Authors: Jonathan Joane , Hoque Zahirul 
Published: January 2025

ABSTRACTThis study explores how business‐like operational models in public universities transform university student unions’ core values and accountability discourse. It builds on a publicness theory and an open‐ended interview‐based field study conducted in three student union bodies in Australia. Findings reveal a significant transformation in core (public) value(s) and accountability practices in university student unions over time. Implementing business‐like (privateness) models in public universities drove this transformational change. Contrary to expectations, student unions lost their public identity (publicness values) as a social service provider to its members while satisfying their corporate university stakeholders as a subunit through business‐like (privateness) accountability practices such as budgeting. These findings offer insight into how the commercialized operational model forces universities to use competing dimensions of organizational publicness (public values and privateness) when managing student unions through business‐like accountability mechanisms.
Pharmacological differences and switching among anti‐CGRP monoclonal antibodies: A narrative review
Authors: Romozzi Marina , Munafò Antonio , Burgalassi Andrea , De Cesaris Francesco , Vigani Giulia , Altamura Claudia , Rivi Veronica , Guerzoni Simona , Calabresi Paolo , Raffaelli Bianca , Iannone Luigi Francesco 
Published: January 2025

AbstractAntibodies targeting either the calcitonin gene–related peptide (CGRP), such as galcanezumab, fremanezumab, and eptinezumab, or the receptor (erenumab) have been approved for the prevention of episodic and chronic migraine. Although widely used and generally effective, a proportion of patients discontinue treatment due to lack of efficacy. In both randomized controlled trials and observational studies, all anti‐CGRP monoclonal antibodies (mAbs) have consistently demonstrated comparable efficacy and tolerability, suggesting a pharmacological class effect. However, differences in therapeutic targets, structure, and pharmacokinetic characteristics may influence their efficacy and safety differently. Therefore, in patients not achieving a clinically meaningful response with one anti‐CGRP antibody, switching to a different antibody may be a viable option. This review examines the pharmacological characteristics and distinctions among anti‐CGRP mAbs, highlighting their mechanisms of action and pharmacokinetic profiles, along with the clinical observational data of switching. Finally, we summarize suggestions from international guidelines.
The Role of Platelet–Neutrophil Interactions in Driving Autoimmune Diseases
Authors: Liu Qinyao , Zhu Wenjia , Wen Xinmei , Da Yuwei 
Published: January 2025

ABSTRACTPlatelets and neutrophils are among the most abundant cell types in peripheral blood. Beyond their traditional roles in thrombosis and haemostasis, they also play an active role in modulating immune responses. Current knowledge on the role of platelet–neutrophil interactions in the immune system has been rapidly expanding. Notably, circulating platelet–neutrophil complexes (PNCs) have been widely detected in various inflammatory diseases and infections, closely associated with inflammatory processes affecting multiple organs. These findings emphasise the critical role of platelet–neutrophil interactions in driving and sustaining inflammatory responses. In this review, we elucidate the mechanisms by which neutrophils and platelets physically interact, leading to mutual activation. Additionally, activated platelets release pro‐inflammatory factors that further modulate neutrophil effector functions, enhancing their immune response capabilities. We highlight the role of platelets in promoting the formation of neutrophil extracellular traps (NETs), which, in turn, promote local platelet activation, thereby exacerbating the immune response and sustaining chronic inflammation. Furthermore, we review current evidence on the role of platelet–neutrophil interactions in common autoimmune diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and rheumatoid arthritis (RA). Finally, we identify gaps in understanding the mechanisms of these interactions in the context of other autoimmune diseases and underscore the potential of targeting platelets and neutrophils as a therapeutic strategy for these conditions.