bluuebunny/crossref_metadata_2025_split huggingface dataset:
Culture-centric narratives of influenza vaccination among high-risk groups in Hong Kong
Authors: Ka Lai Lee Danielle , Jiang Crystal Li 
Published: January 2023

Summary
Despite the effectiveness of influenza vaccination, the vaccine coverage rate among high-risk groups in Hong Kong is less than optimal. Guided by the Health Belief Model (HBM) and culture-centric narrative approach, we examined the role of cultural specificities in implicit assumptions held by at-risk individuals when the individuals decided whether to receive the vaccine. Data were collected from 29 in-depth interviews with people from high-risk groups in Hong Kong. From their decision narratives, it is evident that the local socio-cultural characteristics and collectivistic ideology are useful in understanding the perceptions of influenza severity, susceptibility to infection, perceived barriers and benefits, and self-efficacy of accepting or rejecting the vaccine among the high-risk individuals. Implications of vaccination message designs are discussed.
Challenges in evaluating implementation and effectiveness in real-world settings: evaluation proposal for school-based health-promoting intervention
Authors: Hahnraths Marla T H , Willeboordse Maartje , van Schayck Onno C P 
Published: January 2023

Summary
There are various research designs and approaches to investigate how health-promoting activities are implemented in complex, real-world systems, and to identify potential health effects that might occur following implementation. Although literature describes guidelines to perform and report about implementation research and effect evaluations, no specific guidelines exist on analysing and reporting about the combination of effectiveness data and implementation data collected as part of intervention evaluation in complex and diverse settings. This paper describes the evaluation of primary school-based health-promoting activities in complex systems. Furthermore, an approach for data categorization inspired by Rogers’ Diffusion of Innovations theory is presented that can facilitate structuring the study’s results and relating the degree of implementation to any impact on effectiveness outcomes that might be observed. Researchers interested in using this approach for data categorization have to ensure that the following three conditions are met: (i) data on an intervention’s efficacy in a controlled setting with optimal implementation is available; (ii) key points that define an intervention’s optimal implementation are available and (iii) an evaluation study is performed, collecting both effectiveness data and implementation data in a real-world context. This data categorization approach can be useful to generate more insight into an intervention’s effectiveness under varying circumstances, and optimal support and advice can be provided to stakeholders to achieve maximum impact of population-based health-promoting interventions in complex, real-world systems. However, the proposed approach is a first suggestion and further testing and adaptation is necessary to increase its usefulness. Knowledge and experience sharing among researchers performing comparable research can increase the knowledge base regarding this subject.
Health(care) matters: where do the transgender individuals of Kashmir situate themselves?
Authors: Jahangir Mohmad Saleem , Gadda Zakir Hussain , Ganayee Shameem Ahamad , Kumar Hilal Ahmad , Ahmad Mansoor , Shafi Aneesa 
Published: January 2023

Summary
While employing a phenomenological perspective, the present study aimed to explore the varied experiences of transgender individuals in Kashmir, concerning their health-seeking behavior, and the constraints they face while accessing healthcare resources on a day-to-day basis in their life world. Participants were recruited through the purposive and snowball sampling strategies and the sufficiency of sample size was determined by data saturation. Data were collected using face-to-face in-depth interviews and analyzed through Colaizzi’s procedure of extracting recurrent themes and their interwoven relationships in qualitative research. Three main themes of awareness and the preferences for healthcare, gender identity and persistent stigmatization in care settings, and intra-community support and the resultant caregiving were prominent. Results of the study revealed that the transgender individuals in Kashmir experience inappropriate health-seeking behaviour primarily due to their unawareness regarding health, diseases and public healthcare programs/schemes, financial constraints, social exclusion, improper support and social stigma. They often prefer treating their health issues, mostly through local pharmacies or patent medicine vendors (PMVs), instead of visiting the medical professionals in the organized sector. Moreover, in many instances, they were also found to delay their decisions to seek care or simply decided to remain far from any medical intervention. As a result, the transgender individuals in Kashmir usually experience underutilization of formal healthcare services, which undermines their right to proper health and well-being.
Therapeutic reduction of GGGGCC repeat RNA levels by hnRNPA3 suppresses neurodegeneration in Drosophila models of C9orf72-linked ALS/FTD
Authors: Taminato Tomoya , Takeuchi Toshihide , Ueyama Morio , Mori Kohji , Ikeda Manabu , Mochizuki Hideki , Nagai Yoshitaka 
Published: January 2023

Abstract
The abnormal expansion of GGGGCC hexanucleotide repeats within the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The accumulation of GGGGCC repeat-containing RNAs as RNA foci, and the deposition of dipeptide repeat proteins (DPR) produced from these repeat RNAs by unconventional translation are major pathological hallmarks of C9orf72-linked ALS/FTD (C9-ALS/FTD), and are both thought to play a crucial role in the pathogenesis of these diseases. Because GGGGCC repeat RNA is likely to be the most upstream therapeutic target in the pathogenic cascade of C9-ALS/FTD, lowering the cellular level of GGGGCC repeat RNA is expected to mitigate repeat RNA toxicity, and will therefore be a disease-modifying therapeutic strategy for the treatment of C9-ALS/FTD. In this study, we demonstrated using a Drosophila model of C9-ALS/FTD that elevated expression of a subset of human RNA-binding proteins that bind to GGGGCC repeat RNA, including hnRNPA3, IGF2BP1, hnRNPA2B1, hnRNPR and SF3B3, reduces the level of GGGGCC repeat RNA, resulting in the suppression of neurodegeneration. We further showed that hnRNPA3-mediated reduction of GGGGCC repeat RNA suppresses disease pathology, such as RNA foci and DPR accumulation. These results demonstrate that hnRNPA3 and other RNA-binding proteins negatively regulate the level of GGGGCC repeat RNA, and mitigate repeat RNA toxicity in vivo, indicating the therapeutic potential of the repeat RNA-lowering approach mediated by endogenous RNA-binding proteins for the treatment of C9-ALS/FTD.
Epigenetic gestational age and the relationship with developmental milestones in early childhood
Authors: Polinski Kristen J , Robinson Sonia L , Putnick Diane L , Guan Weihua , Gleason Jessica L , Mumford Sunni L , Sundaram Rajeshwari , Mendola Pauline , London Stephanie , Yeung Edwina H 
Published: January 2023

Abstract
Shorter gestational age (GA) is a risk factor of developmental delay. GA is usually estimated clinically from last menstrual period and ultrasound. DNA methylation (DNAm) estimates GA using sets of cytosine-guanine-sites coupled with a clock algorithm. Therefore, DNAm-estimated GA may better reflect biological maturation. A DNAm GA greater than clinical GA, known as gestational age acceleration (GAA), may indicate epigenetic maturity and holds potential as an early biomarker for developmental delay risk. We used data from the Upstate KIDS Study to examine associations of DNAm GA and developmental delay within the first 3 years based on the Ages & Stages Questionnaire® (n = 1010). We estimated DNAm GA using two clocks specific to the Illumina Methylation EPIC 850K, the Haftorn clock and one developed from the Effects of Aspirin in Gestation and Reproduction study, in which women were followed to detect pregnancy at the earliest time possible. Among singletons, each week increase in DNAm GA was protective for overall delay (odds ratio:0.74; 95% confidence interval:0.61–0.90) and delay in all domains except for problem-solving skills. Among twins, we observed similar point estimates but lower precision. Results were similar for clinical GA. GAA was largely not associated with developmental delays. In summary, either DNAm GA or clinical GA at birth, but not epigenetic maturity (i.e. GAA), was associated with decreased odds of developmental delay in early childhood. Our study does not support using DNAm GA or GAA as separate risk factors for future risk of developmental delay within the first 3 years of age.
Direct evaluation of neuroaxonal degeneration with the causative genes of neurodegenerative diseases in Drosophila using the automated axon quantification system, MeDUsA
Authors: Nitta Yohei , Kawai Hiroki , Maki Ryuto , Osaka Jiro , Hakeda-Suzuki Satoko , Nagai Yoshitaka , Doubková Karolína , Uehara Tomoko , Watanabe Kenji , Kosaki Kenjiro , Suzuki Takashi , Tavosanis Gaia , Sugie Atsushi 
Published: January 2023

Abstract
Drosophila is an excellent model organism for studying human neurodegenerative diseases (NDs). However, there is still almost no experimental system that could directly observe the degeneration of neurons and automatically quantify axonal degeneration. In this study, we created MeDUsA (a ‘method for the quantification of degeneration using fly axons’), a standalone executable computer program based on Python that combines a pre-trained deep-learning masking tool with an axon terminal counting tool. This software automatically quantifies the number of retinal R7 axons in Drosophila from a confocal z-stack image series. Using this software, we were able to directly demonstrate that axons were degenerated by the representative causative genes of NDs for the first time in Drosophila. The fly retinal axon is an excellent experimental system that is capable of mimicking the pathology of axonal degeneration in human NDs. MeDUsA rapidly and accurately quantifies axons in Drosophila photoreceptor neurons. It enables large-scale research into axonal degeneration, including screening to identify genes or drugs that mediate axonal toxicity caused by ND proteins and diagnose the pathological significance of novel variants of human genes in axons.
Biochemical characterization of two novel mutations in the human high-affinity choline transporter 1 identified in a patient with congenital myasthenic syndrome
Authors: Rizvi Midhat , Truong Tina K , Zhou Janet , Batta Manav , Moran Ellen S , Pappas John , Chu Mary Lynn , Caluseriu Oana , Evrony Gilad D , Leslie Elaine M , Cordat Emmanuelle 
Published: January 2023

AbstractCongenital myasthenic syndrome (CMS) is a heterogeneous condition associated with 34 different genes, including SLC5A7, which encodes the high-affinity choline transporter 1 (CHT1). CHT1 is expressed in presynaptic neurons of the neuromuscular junction where it uses the inward sodium gradient to reuptake choline. Biallelic CHT1 mutations often lead to neonatal lethality, and less commonly to non-lethal motor weakness and developmental delays. Here, we report detailed biochemical characterization of two novel mutations in CHT1, p.I294T and p.D349N, which we identified in an 11-year-old patient with a history of neonatal respiratory distress, and subsequent hypotonia and global developmental delay. Heterologous expression of each CHT1 mutant in human embryonic kidney cells showed two different mechanisms of reduced protein function. The p.I294T CHT1 mutant transporter function was detectable, but its abundance and half-life were significantly reduced. In contrast, the p.D349N CHT1 mutant was abundantly expressed at the cell membrane, but transporter function was absent. The residual function of the p.I294T CHT1 mutant may explain the non-lethal form of CMS in this patient, and the divergent mechanisms of reduced CHT1 function that we identified may guide future functional studies of the CHT1 myasthenic syndrome. Based on these in vitro studies that provided a diagnosis, treatment with cholinesterase inhibitor together with physical and occupational therapy significantly improved the patient’s strength and quality of life.
Nuclear modifier YARS2 allele correction restored retinal ganglion cells-specific deficiencies in Leber’s hereditary optic neuropathy
Authors: Chen Jia-Rong , Chen Chao , Chen Jie , Ji Yanchun , Lian Yanna , Zhang Juanjuan , Yu Jialing , Li Xiang-Yao , Qu Jia , Guan Min-Xin 
Published: January 2023

Abstract
Leber’s hereditary optic neuropathy (LHON) is a maternally transmitted eye disease due to the degeneration of retinal ganglion cells (RGCs). Mitochondrial 11778G &gt; A mutation is the most common LHON-associated mitochondrial DNA (mtDNA) mutation. Our recent studies demonstrated some LHON families manifested by synergic interaction between m.11778G &gt; A mutation and YARS2 allele (c.572G &gt; T, p.Gly191Val) encoding mitochondrial tyrosyl-tRNA synthetase. However, the RGC-specific effects of LHON-associated mtDNA mutations remain elusive and there is no highly effective therapy for LHON. Here, we generated patients-derived induced pluripotent stem cells (iPSCs) from fibroblasts derived from a Chinese LHON family (both m.11778G &gt; A and c.572G &gt; T mutations, only m.11778G &gt; A mutation, and control subject). The c.572G &gt; T mutation in iPSC lines from a syndromic individual was corrected by CRISPR/Cas9. Those iPSCs were differentiated into neural progenitor cells and subsequently induced RGC-like cells using a stepwise differentiation procedure. Those RGC-like cells derived from symptomatic individual harboring both m.11778G &gt; A and c.572G &gt; T mutations exhibited greater defects in neuronal differentiation, morphology including reduced area of soma, numbers of neurites and shortened length of axons, electrophysiological properties than those in cells bearing only m.11778G &gt; A mutation. Furthermore, these RGC-like cells revealed more drastic reductions in oxygen consumption rates, levels of mitochondrial ATP and increasing productions of reactive oxygen species than those in other cell models. These mitochondrial dysfunctions promoted the apoptotic process for RGC degenerations. Correction of YARS2 c.572G &gt; T mutation rescued deficiencies of patient-derived RGC-like cells. These findings provide new insights into pathophysiology of LHON arising from RGC-specific mitochondrial dysfunctions and step toward therapeutic intervention for this disease.
Loss of TMCC2 activates endoplasm reticulum stress and causes auditory hair cell death
Authors: Ren Rui , Xing Haiyue , Wang Xiaoying , Du Haibo , Wang Yanfei , Xu Zhigang 
Published: January 2023

Abstract
As the auditory and balance receptor cells in the inner ear, hair cells are responsible for converting mechanical stimuli into electrical signals, a process referred to as mechano-electrical transduction. Hair cell development and function are tightly regulated, and hair cell deficits are the main reasons for hearing loss and balance disorders. TMCC2 is an endoplasmic reticulum (ER)-residing transmembrane protein whose physiological function largely remains unknown. In the present work, we show that Tmcc2 is specifically expressed in the auditory hair cells of mouse inner ear. Tmcc2 knockout mice were then established to investigate its physiological role in hearing. Auditory brainstem responses measurements show that Tmcc2 knockout mice suffer from congenital hearing loss. Further investigations reveal progressive auditory hair cell loss in the Tmcc2 knockout mice. The general morphology and function of ER are unaffected in Tmcc2 knockout hair cells. However, increased ER stress was observed in Tmcc2 knockout mice and knockdown cells, suggesting that loss of TMCC2 leads to auditory hair cell death through elevated ER stress.
The class B heat shock factor HSFB1 regulates heat tolerance in grapevine
Authors: Chen Haiyang , Liu Xinna , Li Shenchang , Yuan Ling , Mu Huayuan , Wang Yi , Li Yang , Duan Wei , Fan Peige , Liang Zhenchang , Wang Lijun 
Published: January 2023

Abstract
Grape is a widely cultivated crop with high economic value. Most cultivars derived from mild or cooler climates may not withstand increasing heat stress. Therefore, dissecting the mechanisms of heat tolerance in grapes is of particular significance. Here, we performed comparative transcriptome analysis of Vitis davidii ‘Tangwei’ (heat tolerant) and Vitis vinifera ‘Jingxiu’ (heat sensitive) grapevines after exposure to 25°C, 40°C, or 45°C for 2 h. More differentially expressed genes (DEGs) were detected in ‘Tangwei’ than in ‘Jingxiu’ in response to heat stress, and the number of DEGs increased with increasing treatment temperatures. We identified a class B Heat Shock Factor, HSFB1, which was significantly upregulated in ‘Tangwei’, but not in ‘Jingxiu’, at high temperature. VdHSFB1 from ‘Tangwei’ and VvHSFB1 from ‘Jingxiu’ differ in only one amino acid, and both showed similar transcriptional repression activities. Overexpression and RNA interference of HSFB1 in grape indicated that HSFB1 positively regulates the heat tolerance. Moreover, the heat tolerance of HSFB1-overexpressing plants was positively correlated to HSFB1 expression level. The activity of the VdHSFB1 promoter is higher than that of VvHSFB1 under both normal and high temperatures. Promoter analysis showed that more TATA-box and AT~TATA-box cis-elements are present in the VdHSFB1 promoter than the VvHSFB1 promoter. The promoter sequence variations between VdHSFB1 and VvHSFB1 likely determine the HSFB1 expression levels that influence heat tolerance of the two grape germplasms with contrasting thermotolerance. Collectively, we validated the role of HSFB1 in heat tolerance, and the knowledge gained will advance our ability to breed heat-tolerant grape cultivars.
Single-cell Transcriptomics Reveal the Importance of Distinct Epithelial Cell Populations in Ileal-specific, Treatment-naïve, and Treated Crohn’s Disease Patients
Authors: Corridoni Daniele , Pizarro Theresa T 
Published: January 2023

Lay Summary
The advent of single-cell technologies has revolutionized analyses of IBD-specific processes by identifying important, often novel, mucosal cells subpopulations and their associated functions. We discuss recent findings reporting transcriptomic and cellular diversity of treatment-naïve and treated patients with ileal-specific CD.
The power of modularity today: 20 years of “Design Rules”
Authors: Brusoni Stefano , Henkel Joachim , Jacobides Michael G , Karim Samina , MacCormack Alan , Puranam Phanish , Schilling Melissa 
Published: January 2023

Abstract
In 2000, Carliss Baldwin and Kim Clark published “Design Rules: The Power of Modularity,” a book that introduced new ways of understanding and explaining the architecture of complex systems This Special Issue of Industrial and Corporate Change celebrates this seminal work, the research it has inspired, and the insights that these collective efforts have generated. In this introductory essay, we review the impact of “Design Rules” across numerous fields, including organization theory, competitive strategy, industry structure, and innovation management. We offer perspectives on key themes that emerge from contributions in this issue, including the alignment between organizational and technical designs (“mirroring”), the dynamics of industry evolution, and the role that individuals play in shaping and responding to system designs. We close by highlighting opportunities to apply the theory in Design Rules to new phenomena and puzzles that have emerged in the past 20 years.
Influence of maternal age on birth and infant outcomes at 6 months: a cohort study with quantitative bias analysis
Authors: Gebreegziabher Elisabeth , Bountogo Mamadou , Sié Ali , Zakane Alphonse , Compaoré Guillaume , Ouedraogo Thierry , Lebas Elodie , Nyatigo Fanice , Glymour Maria , Arnold Benjamin F , Lietman Thomas M , Oldenburg Catherine E 
Published: January 2023

Abstract

Background
Maternal age is increasingly recognized as a predictor of birth outcomes. Given the importance of birth and growth outcomes for children’s development, wellbeing and survival, this study examined the effect of maternal age on infant birth and growth outcomes at 6 months and mortality. Additionally, we conducted quantitative bias analysis (QBA) to estimate the role of selection bias and unmeasured confounding on the effect of maternal age on infant mortality.

Methods
We used data from randomized–controlled trials (RCTs) of 21 555 neonates in Burkina Faso conducted in 2019–2020. Newborns of mothers aged 13–19 years (adolescents) and 20–40 years (adults) were enrolled in the study 8–27 days after birth and followed for 6 months. Measurements of child’s anthropometric measures were collected at baseline and 6 months. We used multivariable linear regression to compare child anthropometric measures at birth and 6 months, and logistic regression models to obtain the odds ratio (OR) of all-cause mortality. Using multidimensional deterministic analysis, we assessed scenarios in which the difference in selection probability of adolescent and adult mothers with infant mortality at 6 months increased from 0% to 5%, 10%, 15% and 20% if babies born to adolescent mothers more often died during the first week or were of lower weight and hence were not eligible to be included in the original RCT. Using probabilistic bias analysis, we assessed the role of unmeasured confounding by socio-economic status (SES).

Results
Babies born to adolescent mothers on average had lower weight at birth, lower anthropometric measures at baseline, similar growth outcomes from enrolment to 6 months and higher odds of all-cause mortality by 6 months (adjusted OR = 2.17, 95% CI 1.35 to 3.47) compared with those born to adult mothers. In QBA, we found that differential selection of adolescent and adult mothers could bias the observed effect (OR = 2.24, 95% CI 1.41 to 3.57) towards the null [bias-corrected OR range: 2.37 (95% CI 1.49 to 3.77) to 2.84 (95% CI 1.79 to 4.52)], whereas unmeasured confounding by SES could bias the observed effect away from the null (bias-corrected OR: 2.06, 95% CI 1.31 to 2.64).

Conclusions
Our findings suggest that delaying the first birth from adolescence to adulthood may improve birth outcomes and reduce mortality of neonates. Babies born to younger mothers, who are smaller at birth, may experience catch-up growth, reducing some of the anthropometric disparities by 6 months of age.
How Can Pro-regime Online Comments Influence Chinese Netizens’ Attitudes and Opinion Expressions? Normative or Informational Social Influence?
Authors: Pan Yating , Shu Zhan 
Published: January 2023

Abstract
China, as an authoritarian regime that has tight control over social media, has always sought to manipulate public opinion. In addition to censorship, the state mobilizes undercover paid posters to manufacture a pro-regime opinion environment. In this study, we examine the effectiveness of this adaptation by conducting an online survey experiment. We explore whether pro-regime comments accompanying a news post can effectively affect viewers’ private and expressed thoughts, as well as whether these are driven by normative or informational social influence. The results indicate that pro-regime comments cannot significantly influence individuals’ attitudes in favor of the authorities. Moreover, uniform pro-regime comments can even produce counterproductive effects. However, pro-regime comments do have an impact on individuals’ opinion expressions. Respondents who take dissenting viewpoints tend to avoid expressing themselves when facing a climate of pro-regime opinion. Additionally, the persuasive effects of high-quality pro-regime arguments were found to be better compared to low-quality arguments.