bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coxsackievirus B infection invokes unique cell-type specific responses in primary human pancreatic islets
Authors: Veronese-Paniagua Daniel A. , Hernandez-Rincon Diana C. , Taylor Jared P. , Tse Hubert M. , Millman Jeffrey R. 
Published: July 2024

AbstractCoxsackievirus B (CVB) infection has long been considered an environmental factor precipitating Type 1 diabetes (T1D), an autoimmune disease marked by loss of insulin-producing β cells within pancreatic islets. Previous studies have shown CVB infection negatively impacts islet function and viability but do not report on how virus infection individually affects the multiple cell types present in human primary islets. Therefore, we hypothesized that the various islet cell populations have unique transcriptional responses to CVB infection. Here, we performed single-cell RNA sequencing on human cadaveric islets treated with either CVB or poly(I:C), a viral mimic, for 24 and 48 hours. Our global analysis reveals CVB differentially induces dynamic transcriptional changes associated with multiple cell processes and functions over time whereas poly(I:C) promotes an immune response that progressively increases with treatment duration. At the single-cell resolution, we find CVB infects all islet cell types at similar rates yet induces unique cell-type specific transcriptional responses with β, α, and ductal cells having the strongest response. Sequencing and functional data suggest that CVB negatively impacts mitochondrial respiration and morphology in distinct ways in β and α cells, while also promoting the generation of reactive oxygen species. We also observe an increase in the expression of the long-noncoding RNAMIR7-3HGin β cells with high viral titers and reveal its knockdown reduces gene expression of viral proteins as well as apoptosis in stem cell-derived islets. Together, these findings demonstrate a cell-specific transcriptional, temporal, and functional response to CVB infection and provide new insights into the relationship between CVB infection and T1D.
Chiral mismatch in collagen-mimetic peptides modulates cell migration through integrin-mediated molecular recognition
Authors: Remson Alexandre , Dellemme David , Luciano Marine , Surin Mathieu , Gabriele Sylvain 
Published: July 2024

AbstractChirality influences essential biological processes such as molecular recognition and self- organization, impacting cell proliferation and differentiation mediated by interactions with the extracellular matrix (ECM). Despite extensive research on cell migration, the role of chirality on matrix-cell interactions has been largely overlooked. To explore this aspect, we engineered culture surfaces coated with natural collagen I or collagen-mimetic peptides (CMPs) with opposite chirality, i.e. with either L- or D-amino acids in their sequences. Here we show that D-surfaces impede epithelial keratocyte spreading, making cells more rounded, less adhesive, and slower. Further investigation through integrin inhibition assays and molecular dynamics simulations revealed that a chiral mismatch destabilizes the triple helix of heterochiral CMPs at the L/D junction. This study underscores the profound impact of ECM chirality on cellular behavior, providing new insights into the relationship between matrix (supra)molecular chirality, integrin-mediated molecular recognition, and cell migration dynamics.
Return to work and care use by long-COVID patients on Bonaire, Caribbean Netherlands: Are patients their needs met?
Authors: Berry DSF , Marchena G. , Tiemessen I. , Vegh A. , Jaspers L. , Geubbels E. 
Published: July 2024

ABSTRACTBackgroundSymptoms persisting ≥ 4 weeks after an acute SARS-CoV-2 infection (post-COVID condition, PCC) can have substantial consequences for the daily functioning and labor force participation of working age patients. We examined care consultations during PCC among patients on Bonaire, Caribbean Netherlands, identified activity limitations among patients who returned to work (RTW), and described the support that these patients indicated has or would have facilitated them in recovering and re-integrating.MethodsBivariate logistic regression was used to examine correlates of care consultations during PCC among 157 PCC patients on Bonaire, and to identify factors related to RTW among a subgroup of working age PCC patients with pre-pandemic employment (n=129). We applied in-depth qualitative analyses to assess patients’ lived experiences related to RTW and care during PCC.ResultsWe found 37% of PCC patients consulted at least one (para)medical professional during PCC, of whom one in three consulted multiple professionals. 26% of patients recovered within one month since their acute infection; for patients unrecovered at time of interview, median time since infection was 249 days (IQR 30). Patients with comorbidity (OR=2.90, p<0.01, 95% CI [1.40-5.53]), under care prior to the pandemic (OR=2.52, p<0.01, 95% CI [1.30-4.95]), who had been hospitalized during the acute phase (OR=9.16, p<0.01, 95% CI [3.41, 29.21]), and patients who were aware that their insurance covered certain medical costs related to COVID-19 (after)care (OR=3.99, p<0.01, 95% CI [1.87, 8.81]) were more likely to consult care during PCC. Of patients who RTW (81%), 13% were working reduced hours, 35% experienced worsening of their symptoms after carrying out any physical or cognitive activity, and 40% encountered situations where they were unable to carry out work activities since they had COVID-19. Outside of the workplace, about one in four patients faced issues in sports activities and maintaining social relations since having COVID-19.DiscussionOur findings highlight various factors related to care use during PCC by patients on Bonaire and patient identified needs related to support in the workplace and COVID-19 aftercare. Improving PCC related occupational and healthcare policies on Bonaire may prove beneficial for recovering patients their vitality and socio-economic vigor.
Clinical performance of cell free DNA for fetal RhD detection in RhD-negative pregnant individuals in the US
Authors: Mateus Nino Julio F. , Wynn Julia , Wiggins-Smith Jenny , Bryant J. Brett , Citty J. Kris , Citty J. Kyle , Ahuja Samir , Newman Roger 
Published: July 2024

AbstractObjectiveWe aimed to evaluate the performance of a cell free DNA (cfDNA) assay that uses next generation sequencing (NGS) with quantitative counting templates (QCT) for the clinical detection of the fetal RHD genotype in a diverse RhD-negative pregnant population in the United States (US).Study DesignThis retrospective cohort study was conducted in four US healthcare centers. The same NGS QCT cfDNA fetal RhD assay was offered to non-alloimmunized, RhD-negative pregnant individuals as part of clinical care. Rh immune globulin (RhIG) was administered at the discretion of the provider. The assay’s sensitivity, specificity, and accuracy were calculated considering the neonatal RhD serology results.ResultsA total of 401 non-alloimunized RhD-negative pregnancies who received clinical care in the period from August 2020 to November 2023 were included in the analysis. The D antigen cfDNA result was 100% concordant with the neonatal serology, resulting in 100% sensitivity, 100% positive predictive value (both 95% CI: 98.6%-100%), 100% specificity, and 100% negative predictive value (both 95% CI: 97.4%-100%). There were 10 pregnancies where the cfDNA analysis identified a non-RHD gene deletion, including RhDΨ (n=5) and RHD-CE-D hybrid variants (n=5). RhIG was administered to 93% of pregnant individuals with cfDNA results indicating an RhD-positive fetus compared to 75% of pregnant individuals with cfDNA results indicating an RhD-negative fetus, signifying providers were using the results to guide pregnancy management.ConclusionThis cfDNA analysis via NGS for detecting fetal RhD status is highly accurate with no false-positive or false-negative results in 401 racially and ethnically diverse pregnancies with 100% follow up of all live births. This study and prior studies of this assay support a recommendation to offer cfDNA screening for fetal Rh status as an alternative option to prophylactic RhIG for all non-alloimmunized RhD-negative individuals, which will result in more efficient and targeted prenatal care with administration of RhIG only when medically indicated.
Assessing Knowledge About Pregnancy Induced Hypertension Among Pregnant Women Attending Antenatal Care at Makole Health Center
Authors: Mrosso Dennis Francis , Dominick Baraka , Machimu Ally , Mwasi Hassan , Ramadhani Rehema , Daniel Tienyi Mnyoro 
Published: July 2024

AbstractAimTo assess the knowledge regarding pregnancy induced hypertension among pregnant mothers attending antenatal care at Makole health center.MethodsAnalytical cross-section study design involving 160 participants was conducted at Makole health center. Interviewer and self-administered structured questionnaire was used to assess the objectives of the study. coded, checked and then analyzed using Statistical Package for Social Science (SPSS) version 20 so as to develop descriptive statistical information presented inform of table, pie chart, histogram, and bar charts.ResultsAmong 160 participants who were recruited in the study pregnant women aged 25 years or less constituted the majority 53(33.2%) with participants’ mean age of 22.61 with interquartile range of 18 to 43 years. Majority of the respondents had secondary education level 81 (50.6), while majority of the participants 111 (69.4%) were married. A greater proportion 101 (63.1%) of the pregnant women were Christians. With regard to occupational status, majority were self-employed 74(46.2%). While the majority of the respondents 126(78.8%) had low level of knowledge, 12(7.5%) had moderate level of knowledge and 22(13.8%) had high knowledge of pregnancy induced hypertension. The study found that the prevalence of PIH among pregnant women attending at Makole health center to be 8.1%.ConclusionThough the prevalence of pregnancy induced hypertension was low, a bigger proportion of these women did not have good knowledge of the disease and its complications. The study found that majority of those participants who were found to have experienced PIH had low level of knowledge. However, older pregnant women were ranging from moderate level of knowledge to high level of knowledge compared to the younger pregnant women whom majority of them had low level of knowledge. Also, health care providers should strengthen the awareness of pregnant women about pregnancy-induced hypertension in antenatal care clinics
The m6A Reader ECT1 Mediates Seed Germination via the DAG2-ECT1-PHYB Regulatory Cascade inArabidopsis
Authors: Li Zenglin , Ma Yuhang , Sun Wen , Ding Pengjun , Bu Yifan , Qi Yuhong , Jia Chengchao , Lei Beilei , Ma Chuang 
Published: July 2024

AbstractTheN6-methyladenosine (m6A) RNA modification, a significant epitranscriptomic mark, is integral to plant growth and development. m6A reader proteins are capable of recognizing m6A modifications to impact RNA metabolic and biological processes. Here, we discovered ECT1 as an m6A reader protein that directly binds to the m6A site and plays a role in positively regulating seed germination in the context of gibberellins (GAs). ECT1 undergoes m6A modification to ensure its own stability and engages in self-interaction to enhance its protein stability. Moreover, ECT1 establishes a regulatory circuit with DAG2, which has been reported to play a positive regulatory role in GA-mediated seed germination. We found that DAG2 directly binds to theECT1promoter to control its transcription. ECT1 modulates the mRNA stability ofDAG2. Furthermore, we identifiedPHYB, which encodes a key photoreceptor controlling GA-regulated seed germination, as a common downstream target of DAG2 and ECT1. DAG2 and ECT1 regulate the expression ofPHYBat the transcriptional and post-transcriptional levels, respectively. ECT1 binds directly toPHYB, thereby influencing its stability. While DAG2 binds to thePHYBpromoter to regulate its transcription. Together, these results unveil that ECT1 participates in the m6A signaling pathway through complex and multifaceted molecular mechanisms, broadening the spectrum of m6A reader functions and deepening our insight into the m6A signaling network inArabidopsis.
Mapping the space of protein binding sites with sequence-based protein language models
Authors: Oruç Tuğçe , Kadukova Maria , Davies Thomas G. , Verdonk Marcel , Poelking Carl 
Published: July 2024

AbstractBinding sites are the key interfaces that determine a protein’s biological activity, and therefore common targets for therapeutic intervention. Techniques that help us detect, compare and contextualise binding sites are hence of immense interest to drug discovery. Here we present an approach that integrates protein language models with a 3D tesselation technique to derive rich and versatile representations of binding sites that combine functional, structural and evolutionary information with unprecedented detail. We demonstrate that the associated similarity metrics induce meaningful pocket clusterings by balancing local structure against global sequence effects. The resulting embeddings are shown to simplify a variety of downstream tasks: they help organise the “pocketome” in a way that efficiently contextualises new binding sites, construct performant druggability models, and define challenging train-test splits for believable benchmarking of pocket-centric machine-learning models.
Compromised chronic efficacy of a Glucokinase Activator AZD1656 in mouse models for common humanGCKRvariants
Authors: Ford Brian E , Chachra Shruti S , Alshawi Ahmed , Oakley Fiona , Fairclough Rebecca J. , Smith David M , Tiniakos Dina , Agius Loranne 
Published: July 2024

ABSTRACTGlucokinase activators (GKAs) have been developed as blood glucose lowering drugs for type 2 diabetes. Despite good short-term efficacy, several GKAs showed a decline in efficacy chronically during clinical trials. The underlying mechanisms remain incompletely understood. We tested the hypothesis that deficiency in the liver glucokinase regulatory protein (GKRP) as occurs with common humanGCKRvariants affects chronic GKA efficacy. We used aGckr-P446L mouse model for theGCKRexonic rs1260326 (P446L) variant and theGckr-del/wt mouse to model transcriptional deficiency to test for chronic efficacy of the GKA, AZD1656 in GKRP-deficient states. In theGckr-P446L mouse, the blood glucose lowering efficacy of AZD1656 (3 mg/kg body wt) after 2 weeks was independent of genotype. However after 19 weeks, efficacy was maintained in wild-type but declined in the LL genotype, in conjunction with raised hepatic glucokinase activity and without raised liver lipids. Sustained blood glucose lowering efficacy in wild-type mice was associated with qualitatively similar but more modest changes in the liver transcriptome compared with the P446L genotype, consistent with GKA therapy representing a more modest glucokinase excess than the P446L genotype. Chronic treatment with AZD1656 in theGckr-del/wt mouse was associated with raised liver triglyceride and hepatocyte microvesicular steatosis. The results show that in mouse models of liver GKRP deficiency in conjunction with functional liver glucokinase excess as occurs in association with common humanGCKRvariants, GKRP-deficiency predisposes to declining efficacy of the GKA in lowering blood glucose and to GKA induced elevation in liver lipids.
Different Roles of D1/D2 Medium Spiny Neurons in the Nucleus Accumbens in Pair Bond Formation of Male Mandarin Voles
Authors: Zhang Lizi , Qu Yishan , Young Larry J , Hou Wenjuan , Liu Limin , Liu Jing , Wang Yuqian , Li Lu , Guo Xing , Li Yin , Huang Caihong , Lv Zijian , Li Yitong , Jia Rui , Lian Ting , Feng Hao , He Zhixiong , Tai Fadao 
Published: July 2024

AbstractThe mesolimbic dopamine (DA) system has been implicated in pair bond formation. However, involvements of DA release, real time activities, and electrophysiological activities of D1/D2 medium spiny neurons (MSNs) in the nucleus accumbens (NAc) shell in pair bonding remain unclear. This work verified that male mandarin voles after pair bonding released higher levels of DA in the NAc shell and displayed higher levels of D1 MSNs activity and lower levels of D2 MSNs activity upon sniffing their partners compared to upon sniffing an unknown female. Moreover, pair bonding induced differential alterations in both synaptic plasticity and neuronal intrinsic excitability in both D1 MSNs and D2 MSNs. In addition, chemogenetic inhibition of ventral pallidum (VP) -projecting D2 MSNs in the NAc shell enhanced pair bond formation, while chemogenetic activation of VP-projecting D2 MSNs in the NAc shell inhibited pair bond formation. These findings suggest that different neuronal activity of NAc shell D1 MSNs / D2 MSNs regulated by increasing DA release after pair bonding may be a neurobiological mechanism underlying pair bond formation.
Exploring the psychology of price barriers in Baltic stock markets
Authors: Lobão Júlio , Lopes João G. 
Published: July 2024

PurposeThe purpose of this study is to investigate the presence of psychological barriers both in the main stock market indices of the Baltic states and the most actively traded individual stocks. A psychological barrier refers to a specific price point, often at round numbers (i.e. powers of 10), that investors believe is challenging to breach, influencing their behavior and trading decisions.Design/methodology/approachWe conduct uniformity tests and barrier tests, such as barrier proximity tests and barrier hump tests, to evaluate the presence of psychological barriers. Additionally, we explore variations in means and variances near these potential barriers using regression and GARCH analysis.FindingsThe findings reveal that psychological barriers do exist in the Baltic stock markets, particularly within market indices. The Estonian market index stands out with the most pronounced indications of psychological barriers. Individual stocks also display significant changes in means and variances related to potential barriers, albeit with less uniformity.Practical implicationsCollectively, our findings challenge the traditional assumption of random returns within the Baltic stock markets. For practitioners, the finding that psychological barriers exist opens up opportunities for investment strategies that can capitalize on them.Originality/valueThis study is the first to comprehensively investigate psychological barriers in the Baltic stock markets. Our results provide a valuable contribution to understanding the impact of that phenomenon on pricing dynamics, which is particularly pertinent in less-researched frontier markets like the Baltic states.
Hands-on sustainability: designing an engaging undergraduate sustainable business course
Authors: Abdou Yasmin , Ammar Nesma 
Published: July 2024

Purpose
This paper outlines the active learning methods used to develop and deliver a sustainable business course to undergraduate students. Moreover, the paper aims to investigate the effect of the sustainable business course on the students’ engagement in sustainable consumption.

Design/methodology/approach
From a pedagogical perspective, the paper describes the active learning methods applied in a newly introduced sustainable business course via numerous distinctive assessment techniques. On the empirical front, the research investigates the impact of the sustainable business course on the students’ engagement in sustainable consumption. To test such impact, an online survey was distributed among students who completed the sustainable business course, and as a control group for comparison, students who did not take the course.

Findings
The research results indicate a positive relationship between completion of the sustainable business course and engagement in sustainable consumption. Furthermore, the data revealed that female students exhibited more engagement in sustainable consumption than male students.

Research limitations/implications
The study contributes to the literature on student-centered pedagogy, active learning techniques and the relationship between sustainable business education and engagement with sustainable consumption.

Practical implications
The study contributes to the literature on student-centered pedagogy, active learning techniques and the relationship between sustainable business education and engagement with sustainable consumption. Pedagogically, the nonconventional course curricula and assessment methods described in this study can be used as a reference by instructors aiming to integrate active and experiential teaching methods into their sustainable business curricula. For decision makers in higher education who are working in line with the global direction to achieve sustainability, this research provides preliminary evidence that students’ engagement with sustainability is influenced by their course curricula.

Originality/value
By depicting innovative approaches to teaching sustainability in business, the research enriches the field of sustainable business pedagogy which remains under-researched in many countries. Furthermore, the research goes further by investigating the effect of the course on students’ sustainable consumption. This acts as evidence of the effectiveness of teaching sustainable business in changing future leaders’ perspectives and priorities to include environmental and social aspects, which has become a global goal. Accordingly, the research has the potential to encourage more business schools to make sustainable business education mandatory.
Strategy for sustainable supply chain transformation: a resource orchestration perspective
Authors: Yan Xiaoyu , Chen Xiaohong , Lu Chunfang , Liu Weihua , Shi Xiaoran , Gong Yu 
Published: July 2024

PurposeWith the popularization of sustainable concepts, how to transform into a sustainable supply chain has received widespread attention in practice. Under this circumstance, this paper aims to propose a theoretical framework of sustainable supply chain transformation (SSCT) from a perspective of resource identification and utilization, investigates resources/capabilities that can be used to promote SSCT and explores how to use resources/capabilities to achieve SSCT effectively.Design/methodology/approachAn inductive multi-case analysis is applied to this paper. Four state-owned/non-state-owned enterprises from the manufacturing sector are selected as the research objectives, which are all leaders in the industry based on the 2022 China TOP 500 Enterprises Ranking. Meanwhile, to guarantee the diversities of enterprises, the four selected enterprises are respectively positioned in upstream and downstream of the supply chain.FindingsA theoretical framework of SSCT is proposed with following research findings: (1) Technology resources, facilities and equipment resources, and business process reengineering capability are the key resources/capabilities to promote SSCT. (2) From the supply chain structure perspective, there exists a leader-participant structure in SSCT. The enterprise with dominant resources/capabilities should actively transfer to a SSCT leader. From the supply chain function perspective, specific sustainability assessment indicators and special teams are two necessary settings for SSCT. From the supply chain lifecycle perspective, SSCT should be promoted in a phased manner and dynamically adjusted in each stage. (3) Digital transformation degree and enterprise ownership play a moderating role in the implementation of strategies.Originality/valueThis paper proposes a conceptual framework of SSCT based on the resource orchestration perspective, which provides decision support for enterprises in practice.