bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteome-wide Mendelian Randomization Analysis Identified Potential Drug Targets for Myocardial Infarction
Authors: Ye Xufeng , Wang Xinpei , Jia Jinzhu 
Published: December 2023

AbstractBackgroundMyocardial infarction (MI) is a leading cause of global mortality. Finding effective drugs to treat MI is an urgent concern for clinicians. Proteome-wide Mendelian randomization (MR) analysis provides a new way to investigate invaluable therapeutic drug targets more efficiently.MethodsUsing a proteome-wide MR approach, we assessed the genetic predictive causality between thousands of plasma proteins and MI risk. First, by adopting several principles to judge genetic variants associated with plasma proteins and MI risk, we selected a series of suitable variants utilized as instrumental variables (IVs) for the latter Mendelian Randomization (MR) analysis. Second, we performed a proteome-wide MR analysis to select candidate proteins. Third, sensitivity tests including heterogeneity test, reverse causality test, and colocalization analyses were conducted to ensure the robustness of our selected protein. Last, we assessed the drugability of the identified potential drug targets for MI using databases including DrugBank, PharmGKB, and TTD.ResultsOf the identified IVs, 3,156 associated with 1,487 plasma proteins were validated. 15 proteins exhibited significant genetically predicted causal associations(P − value < 3.362∗10−5) with MI risk, including Plasmin, MSP, Apo B, TAGLN2, LRP4, C1s, Angiostatin, Apo C-III, PCSK9, ANGL4, FN1.4,Apo B, IL-6 sRa, SWAP70, FN, FN1.3. Sensitivity analyses pinpointed Plasmin and Angiostatin for heterogeneity and proteins MSP, Apo B, and Angiostatin for reverse causality effects. Colocalization analysis found several proteins sharing genetic variants with MI, notably Apo B, TAGLN2, LRP4, C1s, Apo C-III, PCSK9 and ANGL4. When the threshold was lowered to 0.7, additional variants SWAP70 could be contained. 7 potential drug targets for MI were identified: SWP70, TAGLN2, LRP4, C1s, Apo C-III, PCSK9, and ANGL4. Drugability assessment categorized these proteins into varying therapeutic potential categories, from successfully drugged targets to those only reported in the literature.ConclusionOur comprehensive study elucidated 7 promising drug targets offering profound insights into its molecular dynamics and presenting potential pathways for therapeutic interventions against MI.Clinical Perspective1) What Is New?★ The analysis of thousands of proteins has identified 7 proteins that have a potential causal role in myocardial infarction risk.★ Four of these ten proteins have drugs approved or in development that target them, and three 5 have not been previously reported to be associated with atrial fibrillation risk.2) What Are the Clinical Implications?★ The results of the present study demonstrate new potential drug/therapeutic targets for myocardial infarction.
Targeting the Histone Methyltransferase SETD7 Rescues Diabetes-induced Impairment of Angiogenic Response by Transcriptional Repression of Semaphorin 3G
Authors: Mohammed Shafeeq A. , Gorica Era , Albiero Mattia , Karsai Gergely , Mengozzi Alessandro , Caravaggi Carlo Maria , Ambrosini Samuele , Masi Stefano , Vinci Maria Cristina , Spinetti Gaia , Rajagopalan Sanjay , El-Osta Assam , Pelisek Jaroslav , Ruschitzka Frank , Fadini Gian Paolo , Costantino Sarah , Paneni Francesco 
Published: December 2023

AbstractBackgroundPeripheral artery disease (PAD) is highly prevalent in patients with diabetes (DM) and associates with a poor prognosis. Revascularization strategies failed to improve outcome, suggesting that new strategies to promote blood vessel growth are needed. Histone modifications have emerged as key modulators of gene expression, however their role in angiogenic response in DM remains poorly understood. Here we investigate the role of chromatin remodelling in DM-related impairment of angiogenic response.MethodologyPrimary human aortic endothelial cells (HAECs) were exposed to normal glucose (NG, 5 mM) or high glucose (HG, 25 mM) for 48 hours. Gene expression profiling was performed by RNA sequencing (RNA-seq). Cell migration and tube formation were employed to study angiogenic properties in HAECs. Levels of the histone methyltransferase SETD7 and its chromatin signature at histone 3 on lysine 4 (H3K4me1) were investigated by Western blot and chromatin immunoprecipitation (ChIP). Pharmacological blockade of SETD7 was achieved by using the selective inhibitor(R)-PFI-2 while the inactive enantiomer (S)-PFI-2 was used as a control. Mice with streptozotocin-induced DM were orally treated with (R)-PFI-2 or vehicle and underwent hindlimb ischemia by femoral artery ligation. Our experimental findings were translated in endothelial cells and gastrocnemius muscle samples obtained from DM patients with PAD.ResultsRNA-seq in HG-treated HAECs unveiled the histone methyltransferase SETD7 as the top-ranking transcript. SETD7 upregulation was associated with increased H3K4me1 levels as well as with impaired HAECs migration and tube formation. Both SETD7 silencing and inhibition by(R)PFI-2 rescued hyperglycemia-induced impairment of HAECs migration and tube formation, while SETD7 overexpression blunted the angiogenic response. RNA-seq and ChIP assays showed that SETD7-induced H3K4me1 enables the transcription of the angiogenesis inhibitor semaphorin-3G (SEMA3G) by increasing chromatin accessibility to PPARγ. Moreover, SEMA3G overexpression mimicked the impairment of angiogenic response observed during hyperglycemia. In DM mice with hindlimb ischemia, (R)-PFI-2 improved limb perfusion by suppressing SEMA3G. Finally, RNAseq and immunofluorescence in vascular specimens from two cohorts of DM patients with PAD confirmed the upregulation of SETD7/SEMA3G signalling. Of note, (R)-PFI-2 restored angiogenic properties in HAECs collected from DM patients.ConclusionSETD7 is a druggable epigenetic target to promote neovascularization in DM.
Ancestry Specific Polygenic Risk Score, Dietary Patterns, Physical Activity, and Cardiovascular Disease
Authors: Hardy Dale S. , Garvin Jane T. , Mersha Tesfaye B. 
Published: December 2023

ABSTRACTBackgroundIt is unknown whether the impact of high diet-quality and physical activity (PA) depends on the level of polygenic risk score (PRS) in different ancestries.ObjectiveDetermine the associations and interactions between high-risk PRSs, dietary patterns, and high PA with atherosclerotic cardiovascular disease (ASCVD) in European Americans (EAs) and African Americans (AAs). Another aim determined the molecular pathways of PRS-mapped genes and their relationships with dietary intake.MethodsCross-sectional analyses utilized de-identified data from 1987-2010 from 7-National Heart, Lung, and Blood Institute Candidate Gene Association Resource studies from the Database of Genotypes and Phenotypes studies for EAs (n=6,575) and AAs (n=1,606).ResultsThe high-risk PRS increased ASCVD risk by 59% (Risk Ratio=1.59;95% Confidence Interval:1.16-2.17) in the highest tertile for AAs and by 15% (RR=1.15;1.13-1.30) and 18% (RR=1.18;1.04-1.35) in the second and highest tertiles compared to the lowest tertile in EAs. Within the highest PRS tertiles, high PA-diet combinations (Dietary Approaches to Stop High Blood Pressure (DASH), or Mediterranean, or Southern) reduced ASCVD risks by 9% (RR=0.91;0.85-0.96) to 15% (RR=0.85;0.80-0.90) in EAs; and by 13% (RR=0.87;0.78-0.97) and 18% (RR=0.82;0.72-0.95) for the DASH and Mediterranean diets, respectively in AAs. Top molecular pathways included fructose metabolism and catabolism linked to obesity, insulin resistance, and type 2 diabetes in both ancestries. Additional molecular pathways for AAs were Vitamin D linked to depression and aging acceleration; and death signaling associated with cancer.ConclusionsEffects of high diet-quality and high PA can counterbalance the influences of genetically high-risk PRSs on ASCVD risk, especially in AAs.
Nanoscale Imaging and Microanalysis of Ice Age Bone Offers New Perspective on “Subfossils” and Fossilization
Authors: Anderson Landon A. 
Published: December 2023

AbstractThe 3-D structure and organization of type-1 collagen protein and vasculature for a set of ancient permafrost bones is extensively documented at the nanoscale (up to 150,000× magnification) for the first time. The chemical mapping technique ToF-SIMS is additionally used to directly localize chemical signal to these structures; C:N and isotope measurements are also reported for the bulk organic bone matrix. These analyses test the hypothesis that biomolecular histology of collagen and vasculature from the permafrost bones supports their taphonomic classification as “subfossils” rather than “fossils”. Results indicate the original collagenous scaffolding and vasculature are still present, the former of which is well-preserved, thus supporting the hypothesis. This study is the first to taphonomically classify a set of pre-Holocene bones as “subfossils” based on the preserved state of their biomolecular histology. These methods can be readily expanded to specimens of warmer thermal settings and earlier geologic strata. Doing so has potential to establish/formalize at what point a bone has been truly “fossilized”; that is, when it has transitioned from “subfossil” status to being a true “fossil” bone. This will elucidate the fossilization process for ancient vertebrates and lead to a deeper understanding of what it means to be a “fossil”.
Trait responsiveness to verbal suggestions predicts nocebo responding: A meta-analysis
Authors: Stein Madeline V. , Heller Monika , Chapman Sarah , Rubin James , Terhune Devin B. 
Published: December 2023

AbstractNocebo responding involves the experience of adverse health outcomes in response to contextual cues. These deleterious responses impact numerous features of mental and physical health but are characterized by pronounced heterogeneity. Suggestion is widely recognised as a contributing factor to nocebo responding but the moderating role of trait responsiveness to verbal suggestions (suggestibility) in nocebo responding remains poorly understood. We conducted a pre-registered meta-analysis (PROSPERO registration number CRD42023425605) to quantitatively synthesize available research on the relationship between suggestibility and nocebo responding. Four electronic databases were searched for original studies involving both the assessment of suggestibility and symptom reports in response to an inactive stimulus. Of 7,729 search results, 10 articles presenting 13 correlations between suggestibility and nocebo responding were analysed. A random-effects meta- analysis revealed a significant, albeit weak, positive correlation,r=0.21 [95% CI: 0.04, 0.37], between suggestibility and nocebo responses, such that more highly suggestible individuals displayed larger responses. Sensitivity and meta-regression analyses demonstrated that studies of higher methodological quality, including those that maintained experimenter blinding, exhibited stronger effect sizes. These results corroborate proposals that trait responsiveness to verbal suggestions confers greater response to nocebos and warrants renewed attention to the role of suggestibility in symptom induction and perception.
Item generation for a new patient-reported outcome measure: The non-traumatic anterior knee pain (AKP)-YOUTH scale
Authors: Nielsen Marie Germund , Lyng Kristian Damgaard , Holden Sinead , Johansen Simon Kristoffer , Winters Marinus , Rathleff Michael Skovdal 
Published: December 2023

QuestionWhich domains are important to develop a preliminary item bank for a new patient-reported outcome measure relating to adolescents with non-traumatic anterior knee pain?DesignMultiple methods: semi-structured interviews,ParticipantsTwenty-one adolescents with anterior knee pain participated in semi-structured interviews which explored their experience of living with knee pain. Following thematic analysis, we generated an item bank based on the domains which emerged from the impact their knee pain had on their daily life. Ten clinical experts provided input on the preliminary item bank via an online survey. Cognitive interviews were conducted using the think-aloud approach with ten adolescents to evaluate the comprehensibility and face validity of the items.ResultsFrom the interviews we identified four overarching domains where adolescents were impacted by their knee pain: knee symptoms, limitations in physical activity/sport, limitations in social activities, and emotional impact of pain. Eighteen items was initially developed and expanded to 23 following clinical expert input. The cognitive interviews with adolescents demonstrated that the items were comprehensive, understandable, and relevant for adolescents.ConclusionThis study developed an item bank of 23 items. These spanned four domains of impact for adolescents with anterior knee pain. The items had good face validity and were deemed relevant and understandable for adolescents with knee pain. Further steps are needed to validate and reduce the items for the non-traumatic anterior knee pain (AKP)-YOUTH scale.
Unlocking the Full Potential of Nanopore Sequencing: Tips, Tricks, and Advanced Data Analysis Techniques
Authors: Meyer Daria , Goettsch Winfried , Spannenberg Jannes , Stieber Bettina , Krautwurst Sebastian , Hölzer Martin , Brandt Christian , Linde Jörg , Höner zu Siederdissen Christian , Srivastava Akash , Zarkovic Milena , Wollny Damian , Marz Manja 
Published: December 2023

ABSTRACTNucleic acid sequencing is the process of identifying the sequence of DNA or RNA, with DNA used for genomes and RNA for transcriptomes. Deciphering this information has the potential to greatly advance our understanding of genomic features and cellular functions. In comparison to other available sequencing methods, nanopore sequencing stands out due to its unique advantages of processing long nucleic acid strands in real time, within a small portable device, enabling the rapid analysis of samples in diverse settings. Evolving over the past decade, nanopore sequencing remains in a state of ongoing development and refinement, resulting in persistent challenges in protocols and technology. This article employs an interdisciplinary approach, evaluating experimental and computational methods to address critical gaps in our understanding in order to maximize the information gain from this advancing technology. Here we present both overview and analysis of all aspects of nanopore sequencing by providing statistically supported insights. Thus, we aim to provide fresh perspectives on nanopore sequencing and give comprehensive guidelines for the diverse challenges that frequently impede optimal experimental outcomes.
Brand addiction and compulsive buying in female consumers' relationships with food brands
Authors: Hegner Sabrina , Schaumann Janina Magdalena , Francioni Barbara , Curina Ilaria 
Published: December 2023

PurposeThe aim of this paper is to respond to the call for exploring and empirically testing both antecedents and outcomes of brand addiction and compulsive buying behaviour. The focus of the study is on the food habits of young female consumers.Design/methodology/approachTo test the hypotheses, a survey design gathering cross-sectional primary data from 325 female Italian consumers and a structural equation modelling have been adopted.FindingsFindings show that brand addiction is positively influenced by consumer resilience, leading to increased life happiness and self-esteem, while compulsive buying behaviour is negatively influenced by consumer resilience and positively influenced by impulsivity. Compulsive buying is also associated with brand addiction and emotional overeating. Emotional overeating is additionally influenced by impulsivity and the control variables of enjoyment of food and loneliness. Moreover, loneliness has a negative impact on life happiness and self-esteem.Originality/valueThe study applies the proposed theory by Mrad and Cui (2020) on the relationship between brand addiction and compulsive buying to food consumption. Furthermore, it expands on this research by investigating consumer characteristics as determinants and behavioural outcomes.
Enabling social change: a case study of complex adaptive leadership within an informal settlement in Iran
Authors: Shams Keyhan , Barahouei Mehrnegar , Priest Kerry L. 
Published: December 2023

PurposeThis paper introduces a conceptual lens for leading social change in slums and informal settlements. In line with this aim, the purpose of this case study is to describe the public problem-solving approach of a social change organization situated in an informal settlement through the lens of adaptive leadership, complexity theory and social change leadership (SCL).Design/methodology/approachThis paper follows an engaged reflection tradition. First, the author-practitioners describe an informal settlement case hereafter called ISC in southeast Iran where many people have historically remained undocumented and uneducated. Using complex adaptive systems theory, adaptive leadership and SCL as the conceptual lens, the paper analyzes ISC as a complex adaptive context in which the community and the government are in tension in solving problems, particularly illiteracy. The instrumental case study draws from participant observation and document analysis to describe and examine the endeavors of a community office operating within ISC. Through this reflective analysis, the authors illustrate how a social change organization can effectively tackle public issues like illiteracy within informal settlements.FindingsThis paper applies complexity leadership theory to a social context. The study illustrates how social change organizations can support the transformation of informal spaces into adaptive spaces to enact social change.Originality/valueThis paper reflects on engagement activity near the insecure borders of Iran, Afghanistan and Pakistan. By extending an organizational-level theory to the public sphere, this paper contributes theoretically to the complexity theory literature. Moreover, it provides a practical insight for community development and slum upgrading projects.
Dark side of decentralised finance: a call for enhanced AML regulation based on use cases of illicit activities
Authors: Benson Vladlena , Turksen Umut , Adamyk Bogdan 
Published: December 2023

Purpose
This paper aims to focus on the need for an enhanced anti-money laundering (AML) regulation for decentralised finance (DeFi) to protect the integrity of global financial systems against illicit activities. Research highlights the requirement for a robust regulatory strategy for the fast-paced DeFi evolvement.

Design/methodology/approach
This study used doctrinal legal research by analysing legislation, which involved creating use cases to illustrate different aspects of potential illicit activities via the DeFi ecosystem. Various DeFi applications were assessed for the potential regulatory responses and outcomes.

Findings
This paper offers valuable insight into the regulatory challenges presented by DeFi. This study addresses the blind spots leveraged by criminals afforded by the DeFi’s decentralised nature. This paper offers a comprehensive examination of DeFi regulatory challenges based on use-case scenarios and provides recommendations for regulators on how to address them effectively.

Originality/value
This paper proposes measures for regulatory authorities to minimise money laundering risks through new channels such as decentralised exchanges, non-custodial wallets and cross-chain bridges. This study concludes with the future directions for DeFi regulation and AML compliance.
The welfare of Ghanaian women in trade: the role of English and French language literacy
Authors: Yegblemenawo Stella Afi Makafui , Ntsiful Enoch 
Published: December 2023

PurposeThe study aims to assess the effect of English and French language literacy on the welfare of Ghanaian women in trade. Also, this study analyses the geographical variations of such effects from rural to urban areas.Design/methodology/approachUsing the latest living standards survey data, the standard two-stage least squares instrumental variable approach was used to estimate the causal effects.FindingsThe results show that Ghanaian women in trade who are both English and French literate or only English literate are able to improve their welfare significantly relative to their fellows who are illiterate in both English and French or only English, whilst those who are solely French literate do not experience any significant improvement in welfare from trade compared with their counterparts. From the heterogeneous analysis, the findings indicate that the effect is significantly concentrated amongst rural traders but insignificant amongst urban traders.Practical implicationsThe findings of this study inform government and policymakers to consider the effectiveness of the free senior high school (SHS) education policy in improving English and French language literacy and the welfare of women in Ghana. It also informs educational institutions on the importance of adult education in English and French, especially amongst women.Originality/valueThe study quantitatively estimates the effect of English and French language literacy on the welfare of Ghanaian women in trade by employing an instrumental variable approach to assess the causal effect. Uniquely, the study finds that language literacy is a significant tool in improving the welfare of rural women engaged in trade in Ghana.
Tourists' willingness to contribute to smart tourism: a construal level theory perspective
Authors: Sun Hao , Sano Kaede 
Published: December 2023

PurposeSmart tourism has become an inevitable trend in future tourism development. However, despite significant investment in its technological foundation, little is known about whether and when tourists are willing to be involved in smart tourism. This study explores tourists' willingness to contribute to smart tourism development by empirically examining their intention to share personal information and use smart technology.Design/methodology/approachBased on construal level theory (CLT), a 2 (far/near spatial distance) × 2 (gain/loss persuasive information frame) × 2 (altruistic/egoistic value orientation) laboratory experiment with different contextual features was designed to examine tourists' willingness to contribute to smart tourism.FindingsTourists are most willing to share personal information and use smart technologies when spatial distance aligns with information framing, spatial distance aligns with value orientation and information framing aligns with value orientation.Practical implicationsThis study provides essential insights for destination management organizations (DMOs) about tourists' perceptions of smart tourism, enabling DMOs to develop more precise marketing strategies to encourage tourists to contribute to smart tourism development and enrich tourists' travel experiences.Originality/valueThis study enriches theoretical knowledge of DMOs' boundaries in encouraging tourists to contribute to smart tourism and provides critical insights into future smart tourism development for researchers and practitioners.