bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between vitamin D and autoimmune diseases: Mendelian randomization analysis
Authors: Zhao Sizheng Steven , Mason Amy , Gjekmarkaj Eva , Yanaoka Haruyuki , Burgess Stephen 
Published: April 2023

ABSTRACTObjectiveThe VITAL trial of vitamin D supplementation suggested a possible protective effect for autoimmune diseases but uncertainties remain. We investigated potential causal effects of vitamin D on composite and individual autoimmune diseases using Mendelian randomization.MethodsWe used data from 332,984 participants of the UK Biobank of whom 23,089 had at least one autoimmune disease defined using ICD code and/or self-report. Diseases were further considered in mechanistic subgroups driven by “autoimmunity” (n=12,774) or “autoinflammation” (n=11,164), then individually. We selected variants within gene regions implicated in vitamin D biology to generate a weighted genetic score. We performed population-wide analysis using the ratio method, then examined non-linear effects across five quantiles based on 25-hydroxycholecalciferol levels.ResultsGenetically-predicted vitamin D was associated with lower risk of diseases in the autoinflammation group (OR 0.95 per 10ng/ml increase in 25-hydroxycholecalciferol; 95%CI 0.91-0.99; p=0.03) but not the autoimmunity group (OR 0.99; 95%CI 0.95-1.03; p=0.64) or combined. When considering individual diseases, genetically-predicted vitamin D was associated with lower risk of psoriasis (OR 0.91; 95%CI 0.85-0.97; p=0.005), the most common disease in the autoinflammation group, and suggestively with systemic lupus erythematosus (OR 0.84; 95%CI 0.69-1.02; p=0.08); results were replicated using data from independent studies. We found no evidence for a plausible non-linear relationship between vitamin D and any outcome.ConclusionsWe found genetic evidence to support a causal link between 25-hydroxycholecalciferol concentrations and psoriasis and systemic lupus erythematosus. These results have implications for potential disease prevention strategies, and the interpretation and design of vitamin D supplementation trials.
Dose-response relationship for the resistance of human insulin to degradation by insulin-degrading enzyme
Authors: Okumura Masaki , Kuramochi Tsubura , Lin Yuxi , Furukawa Ran , Mizutani Kenji , Yokoyama Takeshi , Kim Mingeun , Lim Mi Hee , Yi Hyon-Seung , Arai Kenta , Yamaguchi Hiroshi , Hojo Hironobu , Iwaoka Michio , Tanaka Yoshikazu , Park Sam-Yong , Inaba Kenji , Kanemura Shingo , Lee Young-Ho 
Published: April 2023

SUMMARYDeeper understanding of the mechanism of the action of insulin and insulin-degrading enzyme (IDE) is a central theme in research into physiology and the pathophysiology of type 2 diabetes mellitus. Despite significant progress regarding the substrate recruitment, unfolding, digestion, and release by IDE, the structure and function of the insulin hexamer during the degradation cycle of IDE remain to be fully characterized. In the present study, we have characterized the behavior of human insulin hexamer in the absence of zinc. Using cryo-electron microscopy, we also observed that these hexamers represented a structure similar to that of T6insulin. More interestingly, we also observed complexes in which some of their monomeric insulin components are partially distorted at their hexametric symmetry. This ensures that insulin determines the kinetics of its degradation by IDE without the requirement for zinc. These findings provide new information regarding the molecular events in insulin assembly and disassembly that permit its selective digestion by IDE.
Risk of incident cardiovascular disease among patients with gastrointestinal disorder: prospective cohort study of 340,862 individuals
Authors: Chen Jie , Sun Yuhao , Fu Tian , Lu Shiyuan , Shi Wenming , Zhao Jianhui , Li Sen , Li Xue , Yuan Shuai , Larsson Susanna C. 
Published: April 2023

AbstractBackground and AimsThe associations between gastrointestinal diseases (GIs) and cardiovascular disease (CVD) were unclear. We conducted a prospective cohort study to explore their associations.MethodsThis study included 340,862 individuals without baseline CVD from the UK Biobank cohort. Individuals with and without GIs were followed up until the ascertainment of incident CVDs, including coronary heart disease (CHD), cerebrovascular disease (CeVD), and peripheral artery disease (PAD). The diagnosis of diseases was confirmed with combination of the nationwide inpatient data, primary care data, and cancer registries. A multivariable Cox proportional hazard regression model was used to estimate the associations between GIs and the risk of incident CVD.ResultsDuring a median follow-up of 12.4 years, 28,787 incident CVD cases were diagnosed. Individuals with GIs had an elevated risk of CVD (hazard ratio 1.38; 95% confidence interval 1.35-1.42,P<0.001). Eleven out of fifteen GIs were associated with an increased risk of CVD after Bonferroni-correction, including cirrhosis, non-alcoholic fatty liver disease, gastritis and duodenitis, irritable bowel syndrome, gastroesophageal reflux disease, peptic ulcer, celiac disease, pancreatitis, diverticular disease, biliary disease, and appendicitis. The associations were stronger among women, individuals aged ≤ 60 years, and those with body mass index ≥ 25 kg/m2.ConclusionsThis large-scale prospective cohort study revealed the associations of GIs with an increased risk of incident CVD, in particular CHD and PAD. These findings support the reinforced secondary CVD prevention among patients with gastrointestinal disorders.
Epistasis meets pleiotropy in shaping biophysical protein subspaces associated with antimicrobial resistance
Authors: Ogbunugafor C. Brandon , Guerrero Rafael F. , Shakhnovich Eugene I. , Shoulders Matthew D. 
Published: April 2023

AbstractProtein space is a rich analogy for genotype-phenotype maps, where amino acid sequence is organized into a high-dimensional space that highlights the connectivity between protein variants. It is a useful abstraction for understanding the process of evolution, and for efforts to engineer proteins towards desirable phenotypes. Few framings of protein space consider how higher-level protein phenotypes can be described in terms of their biophysical dimensions, nor do they rigorously interrogate how forces like epistasis—describing the nonlinear interaction between mutations and their phenotypic consequences—manifest across these dimensions. In this study, we deconstruct a low-dimensional protein space of a bacterial enzyme (dihydrofolate reductase; DHFR) into “subspaces” corresponding to a set of kinetic and thermodynamic traits [(kcat, KM,Ki, andTm(melting temperature)]. We then examine how three mutations (eight alleles in total) display pleiotropy in their interactions across these subspaces. We extend this approach to examine protein spaces across three orthologous DHFR enzymes (Escherichia coli, Listeria grayi, andChlamydia muridarum), adding a genotypic context dimension through which epistasis occurs across subspaces. In doing so, we reveal that protein space is a deceptively complex notion, and that the process of protein evolution and engineering should consider how interactions between amino acid substitutions manifest across different phenotypic subspaces.
The topology of interpersonal neural network in weak social ties
Authors: Kurihara Yuto , Takahashi Toru , Osu Rieko 
Published: April 2023

AbstractPeople often have opportunities to engage in social interactions with strangers, which have been reported to contribute to their well-being. Although strategies for social interaction between strangers differ from those between acquaintances, the differences in neural basis of social interaction have not been fully elucidated. In this study, we examined the geometrical properties of interpersonal neural networks in pairs of strangers and acquaintances during joint tapping using dual electroencephalography (EEG). Twenty-one pairs of participants performed antiphase joint tapping under four different conditions. Intra-brain synchronizations were calculated using the weighted phase lag index (wPLI) for all possible intra-brain pairs of the 29 channels (29C2= 406), and inter-brain synchronizations were calculated using the phase locking value (PLV) for all possible inter-brain pairs of the 29 channels (29 × 29 = 841) in the theta, alpha, and beta frequency bands. Electrode pairs with larger wPLI and PLV than their surrogates were defined as the nodes (EEG channels) and edges (connections between nodes) of the neural networks. We then calculated the global efficiency, local efficiency, clustering coefficient, and modularity derived from graph theory for the combined intra- and inter-brain networks of each pair. No significant differences in the tapping phase variance were identified between the stranger and acquaintance pairs. However, in the combined intra- and inter-brain theta EEG (4–7 Hz) networks, stranger pairs showed larger local efficiency and cluster coefficients than acquaintance pairs, indicating that the two brains of stranger pairs were more densely connected. Moreover, in the beta EEG bands, the modularity of the two brains was low in the fast condition, indicating that the two brains were coupled when the task demand was high. Our results show that weak social ties promote more extensive social interactions and result in dense brain-to-brain coupling.
Diverse gut pathogens exploit the host engulfment pathway via a conserved mechanism
Authors: Anandachar Mahitha Shree , Roy Suchismita , Sinha Saptarshi , Boadi Agyekum , Ibeawuchi Stella-Rita , Gementera Hobie , Amamoto Alicia , Katkar Gajanan D. , Ghosh Pradipta 
Published: April 2023

ABSTRACTMacrophages clear infections by engulfing and digesting pathogens within phagolysosomes. Pathogens escape this fate by engaging in a molecular arms race; they useWxxxEmotif-containing “effector” proteins to subvert the host cells they invade and seek refuge within protective vacuoles. Here we define the host component of the molecular arms race as an evolutionarily conserved polar ‘hotspot’ on the PH-domain of ELMO1 (Engulfment and CellMotility1), which is targeted by diverseWxxxE-effectors. Using homology modeling and site-directed mutagenesis, we show that a lysine triad within the ‘patch’ directly binds allWxxxE-effectors tested: SifA (Salmonella), IpgB1 and IpgB2 (Shigella), and Map (enteropathogenicE. coli). Using an integrated SifA•host protein-protein interaction (PPI) network,in-siliconetwork perturbation, and functional studies we show that the major consequences of preventing SifA•ELMO1 interaction are reduced Rac1 activity and microbial invasion. That multiple effectors of diverse structure, function, and sequence bind the same hotpot on ELMO1 suggests that theWxxxE-effector(s)•ELMO1 interface is a convergence point of intrusion detection and/or host vulnerability. We conclude that the interface may represent the fault line in co-evolved molecular adaptations between pathogens and the host and its disruption may serve as a therapeutic strategy.GRAPHICAL ABSTRACTIn briefThis work defines the nature of a conserved molecular interface, assembled between diverse WxxxEmotif-containing effector proteins encoded by gut pathogens and the host innate immune sensor, ELMO1, via which pathogens exploit the host’s engulfment machinery.
Photoswitchable Molecular Glues Enable Optical Control of Transcription Factor Degradation
Authors: Arp Christopher J. , Reynders Martin , Sreekanth Vedagopuram , Kokkonda Praveen , Pagano Michele , Choudhary Amit , Trauner Dirk 
Published: April 2023

AbstractImmunomodulatory drugs (IMiDs), which include thalidomide and its derivatives, have emerged as the standard of care against multiple myeloma. They function as molecular glues that bind to the E3 ligase cereblon (CRBN) and induce protein interactions with neosubstrates, including the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). The subsequent ubiquitylation and degradation of these transcription factors underlies the antiproliferative activity of IMiDs. Here, we introduce photoswitchable immunomodulatory drugs (PHOIMiDs) that can be used to degrade Ikaros and Aiolos in a light-dependent fashion. Our lead compound shows minimal activity in the dark and becomes an active degrader upon irradiation with violet light. It shows high selectivity over other transcription factors, regardless of its state, and could therefore be used to control the levels of Ikaros and Aiolos with high spatiotemporal precision.
HSP70 binds to specific non-coding RNA and regulates human RNA Polymerase III
Authors: Leone Sergio , Srivastava Avinash , Hummel Barbara , Tittel Lena , Aprile-Garcia Fernando , Herrero-Ruiz Andrés , Rawat Prashant , Willis Anne E. , Sawarkar Ritwick 
Published: April 2023

SUMMARYMolecular chaperones are critical for protein homeostasis and are implicated in several human pathologies such as neurodegeneration and cancer. While the binding of chaperones to nascent and misfolded proteins has been studied in great detail, the direct interaction between chaperones and RNA has not been systematically investigated. Here we provide the evidence for widespread interaction between chaperones and RNA in human cells. We show that the major chaperone Heat-Shock Protein 70 (HSP70) binds to non-coding RNA transcribed by RNA Polymerase III (Pol III) such as tRNA and 5S rRNA. Global chromatin profiling revealed that HSP70 binds genomic sites of transcription by Pol III. Detailed biochemical analyses showed that HSP70 facilitates transcription of its target non-coding RNA by binding to Pol III. Thus our study uncovers an unexpected role of HSP70-RNA interaction in the biogenesis of a specific class of non-coding RNA with wider implications in neurodegeneration and cancer.
Psychometric properties of the university student engagement inventory among Chinese students
Authors: She Long , Khoshnavay Fomani Fatemeh , Marôco João , Allen Kelly-Ann , Sharif Nia Hamid , Rahmatpour Pardis 
Published: April 2023

PurposeSince the onset of the COVID-19 pandemic in China, student engagement in online learning has been a critical issue for all educational institutions. The university student engagement inventory (USEI) is the most used scale for assessing the construct of student engagement. The present study aimed to evaluate the psychometric properties of the USEI among 1504 Chinese university students who completed a survey through an online platform between December 2020 and January 2021.Design/methodology/approachIn this cross-sectional study, content validity, construct validity and reliability of the scale were assessed.FindingsThe results supported the three-factor model with acceptable goodness of fit (χ2 (71) = 369.717, p = 0.13, χ2/df = 5.207, comparative fit index (CFI) = 0.967, normed fit index (NFI) = 0.960, Tucker–Lewis index (TLI) = 0.958, standardized root mean square residual (SRMR) = 0.030, root mean square error of approximation (RMSEA) (90% CI) = 0.053 [0.049, 0.057]), good internal consistency and construct reliability (Cronbach's alpha and omega coefficient >0.70) and strong convergent validity. Also, the measurement invariance was confirmed across gender.Originality/valueThis study showed that the 3-factor structure of USEI with Chinese university students had good construct validity, internal consistency and reliability. It could help measure student engagement in online learning in China.
Improvement research on the stability of explicit integration algorithms with 3D viscoelastic artificial boundary elements
Authors: Li Shutao , Bao Xin , Liu Jingbo , Wang Fei , Wang Dong 
Published: April 2023

PurposeWhen explicit integral analysis is performed on a numerical model with viscoelastic artificial boundary elements, an instability phenomenon is likely to occur in the boundary area, reducing the computational efficiency of the numerical calculation and limiting the use of viscoelastic artificial boundary elements in the explicit dynamic analysis of large-scale engineering sites. The main purpose of this study is to improve the stability condition of viscoelastic artificial boundary elements.Design/methodology/approachA stability analysis method based on local subsystems was adopted to analyze and improve the stability conditions of three-dimensional (3D) viscoelastic artificial boundary elements. Typical boundary subsystems that can represent the localized characteristics of the overall model were established, and their analytical stability conditions were derived with an analysis based on the spectral radius of the transfer matrix. Then, after analyzing the influence of each physical parameter on the analytical-stability conditions, a method for improving the stability condition of the explicit algorithm by increasing the mass density of the artificial boundary elements was proposed.FindingsNumerical wave propagation simulations in uniform and layered half-space models show that, on the premise of ensuring the accuracy of the viscoelastic artificial boundary, the proposed method can effectively improve the numerical stability and the efficiency of the explicit dynamic calculations for the overall system.Originality/valueThe stability improvement method proposed in this study are significant for improving the applicability of viscoelastic artificial boundary elements in explicit dynamic calculations and the calculation efficiency of wave analysis at large-scale engineering sites.
Mind the gap: an empirical analysis of pay discrimination in Hollywood
Authors: Kräft Charlotte , Kaimann Daniel , Frick Bernd 
Published: April 2023

Purpose
This study aims to identify and explain a possible gender pay gap in the creative industry. By using the salary information of Hollywood actors, this paper restricts the analysis to a relatively homogenous group of workers. In addition, actors' human capital endowments and past performance can be measured precisely. The factors that impact the salaries of movie stars are likely to influence the pay of other high-wage employees, such as athletes and executives.

Design/methodology/approach
This paper uses a rich panel data set including 178 female and male actors in 973 movies released between 1980 and 2019. Using a random-effects model and the Blinder–Oaxaca decomposition approach, this paper distinguishes between a fraction of the gender pay gap that can be explained and another fraction that cannot be explained. Hence, only the unexplained residual typically obtained by estimating two standard Mincer-type earnings functions is due to discriminatory pay practices.

Findings
This study reveals a pay difference between female and male actors. Gender-specific representation in leading roles and systematic differences in performance measures can explain this pay difference. While female actors' underrepresentation in leading roles reflects consumer tastes and, therefore, reflects discriminatory attitudes, no evidence can be found for direct pay discrimination in Hollywood's movie business.

Originality/value
To the best of the authors’ knowledge, this is the first Hollywood study to relying on a rich panel data set that includes various measures of the human capital characteristics of the different individual actors. This paper's theoretical contribution lies in applying classic labor economics reasoning to explain pay determination in Hollywood's movie business.
Contesting the boundaries of marianismoand entrepreneurial identity: meanings of motherhood amongst Latin American migrant women entrepreneurs
Authors: Cruz García Ana , Villares-Varela María 
Published: April 2023

PurposeTo critically analyse how Latin American migrant women entrepreneurs living in Ireland and the UK negotiate their entrepreneurial and motherhood identities in transnational settings. The paper explores (1) how motherhood influences the choices of becoming entrepreneurs; (2) how women reconcile the social imaginaries of motherhood from their country of origin in the new contexts of settlement; and (3) the impact of these transformations on their businesses.Design/methodology/approachThis paper draws on six biographical case studies (three in Ireland and three in the UK) and employs the theoretical lens of translocational positionality to analyse entrepreneurship as context-specific and relational processes that bring together a multiplicity of social and geographical locales.FindingsLatin American women entrepreneurs navigate their roles as “good mothers” and “good businesswomen” by simultaneously (1) complying with core values of marianismo that confine them to traditional gender roles and (2) renegotiating these values in ways that empower them through entrepreneurship. Finally, juxtaposing these two contexts (Ireland and the UK), this study (3) illuminates the similarities of the ever-continuing gender power struggles of egalitarianism for Latin American migrant women in both contexts.Originality/valueDespite the agreed need for exploring motherhood as one of the critical aspects shaping family and business cycles, this area needs to be sufficiently analysed in its intersection with ethnicity or migratory status, particularly with participants from the global South. This article aims at bridging that gap.
Government policy, IT capabilities, digital transformation, and innovativeness in Post-Covid context: case of Vietnamese SMEs
Authors: Mai Binh Tan , Nguyen Phuong V. , Ton Uyen Nu Hoang , Ahmed Zafar U. 
Published: April 2023

Purpose
COVID-19 has made businesses increasingly dependent on technology to be competitive and efficient. Small and medium enterprises (SME) digitalisation and innovation research are widespread. SME digital transformation and innovation require government policies, initiatives and assistance. How the government can help SMEs achieve these goals is unclear. So, this paper aims to investigate how government policy may assist Vietnamese SMEs to boost innovation performance and digital transformation.

Design/methodology/approach
The study will take a quantitative approach, with questionnaires distributed to 659 respondents from SMEs in Vietnam through snowball and convenience sampling procedures. The structural equational modelling method is used for data analysis.

Findings
The study indicated that government policies supported Vietnamese SMEs’ innovation and information technology (IT) capabilities. Government policy assistance also boosted IT capabilities and innovation. Furthermore, mediation effects show that digital transformation fully mediates the relationship between innovativeness and firm performance, whereas IT capabilities partially mediate this relationship.

Research limitations/implications
Further research that replicates the findings and analyses contextual heterogeneities between nations is advised because Vietnam’s pandemic setting was both similar and dissimilar.

Practical implications
The study demonstrated government-company interactions through supportive policy. It investigated whether SMEs seeking digital transformation and innovativeness might gain competitive benefits by implementing effective knowledge management and enhancing their IT capabilities.

Originality/value
A resource-based theoretical framework is extended to study how innovation, public policy and digital transformation for SMEs interact. The study confirms government policy strongly influences enterprises’ digital development. Specifically, the new mediating effects of IT capabilities and digital transformation are explored and provide new insights into the existing literature.