bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pathogenic roles of the p.R130S prestin variant in DFNB61 hearing loss
Authors: Takahashi Satoe , Zhou Yingjie , Cheatham Mary Ann , Homma Kazuaki 
Published: March 2024

AbstractDFNB61 is a recessively inherited nonsyndromic hearing loss caused by mutations in SLC26A5, the gene that encodes the voltage‐driven motor protein, prestin. Prestin is abundantly expressed in the auditory outer hair cells that mediate cochlear amplification. Two DFNB61‐associated SLC26A5 variants, p.W70X and p.R130S, were identified in patients who are compound heterozygous for these nonsense and missense changes (SLC26A5W70X/R130S). Our recent study showed that mice homozygous for p.R130S (Slc26a5R130S/R130S) suffer from hearing loss that is ascribed to significantly reduced motor kinetics of prestin. Given that W70X‐prestin is nonfunctional, compound heterozygous Slc26a5R130S/− mice were used as a model for human SLC26A5W70X/R130S. By examining the pathophysiological consequences of p.R130S prestin when it is the sole allele for prestin protein production, we determined that this missense change results in progressive outer hair cell loss in addition to its effects on prestin's motor action. Thus, this study defines the pathogenic roles of p.R130S prestin and identifies a limited time window for potential clinical intervention.
imageKey points
The voltage‐driven motor protein, prestin, is encoded by SLC26A5 and expressed abundantly in cochlear outer hair cells (OHCs).
The importance of prestin for normal hearing was demonstrated in mice lacking prestin; however, none of the specific SLC26A5 variants identified to date in human patients has been experimentally demonstrated to be pathogenic.
In this study we used both cell lines and a mouse model to define the pathogenic role of compound heterozygous p.W70X (c.209G>A) and p.R130S (c.390A>C) SLC26A5 variants identified in patients with moderate to profound hearing loss.
As in patients, mice carrying one copy of p.R130S Slc26a5 showed OHC dysfunction and progressive degeneration, which results in congenital progressive hearing loss.
This is the first functional study reporting pathogenic SLC26A5 variants and pointing to the presence of a therapeutic time window for potential clinical interventions targeting the affected OHCs before they are lost.
Cathodal bilateral transcranial direct‐current stimulation regulates selenium to confer neuroprotection after rat cerebral ischaemia–reperfusion injury
Authors: Wang Hui , Ma Wenlong , Hu Wenjie , Li Xiaohua , Shen Na , Li Zhuo , Kong Xiangyi , Lin Tao , Gao Jingchen , Zhu Ting , Che Fengyuan , Chen Juan , Wan Qi 
Published: March 2024

AbstractNon‐invasive transcranial direct‐current stimulation (tDCS) is a safe ischaemic stroke therapy. Cathodal bilateral tDCS (BtDCS) is a modified tDCS approach established by us recently. Because selenium (Se) plays a crucial role in cerebral ischaemic injury, we investigated whether cathodal BtDCS conferred neuroprotection via regulating Se‐dependent signalling in rat cerebral ischaemia–reperfusion (I/R) injury. We first showed that the levels of Se and its transport protein selenoprotein P (SEPP1) were reduced in the rat cortical penumbra following I/R, whereas cathodal BtDCS prevented the reduction of Se and SEPP1. Interestingly, direct‐current stimulation (DCS) increased SEPP1 level in cultured astrocytes subjected to oxygen‐glucose deprivation reoxygenation (OGD/R) but had no effect on SEPP1 level in OGD/R‐insulted neurons, indicating that DCS may increase Se in ischaemic neurons by enhancing the synthesis and secretion of SEPP1 in astrocytes. We then revealed that DCS reduced the number of injured mitochondria in OGD/R‐insulted neurons cocultured with astrocytes. DCS and BtDCS prevented the reduction of the mitochondrial quality‐control signalling, vesicle‐associated membrane protein 2 (VAMP2) and syntaxin‐4 (STX4), in OGD/R‐insulted neurons cocultured with astrocytes and the ischaemic brain respectively. Under the same experimental conditions, downregulation of SEPP1 blocked DCS‐ and BtDCS‐induced upregulation of VAMP2 and STX4. Finally, we demonstrated that cathodal BtDCS increased Se to reduce infract volume following I/R. Together, the present study uncovered a molecular mechanism by which cathodal BtDCS confers neuroprotection through increasing SEPP1 in astrocytes and subsequent upregulation of SEPP1/VAMP2/STX4 signalling in ischaemic neurons after rat cerebral I/R injury.
imageKey points
Cathodal bilateral transcranial direct‐current stimulation (BtDCS) prevents the reduction of selenium (Se) and selenoprotein P in the ischaemic penumbra.
Se plays a crucial role in cerebral ischaemia injury.
Direct‐current stimulation reduces mitochondria injury and blocks the reduction of vesicle‐associated membrane protein 2 (VAMP2) and syntaxin‐4 (STX4) in oxygen‐glucose deprivation reoxygenation‐insulted neurons following coculturing with astrocytes.
Cathodal BtDCS regulates Se/VAMP2/STX4 signalling to confer neuroprotection after ischaemia.
Postprandial glucose variability and clusters of sex hormones, liver enzymes, and cardiometabolic factors in a South African cohort of African ancestry
Authors: Masango Bontle , Goedecke Julia H , Ramsay Michèle , Storbeck Karl-Heinz , Micklesfield Lisa K , Chikowore Tinashe 
Published: March 2024

IntroductionThis study aimed to, first, determine the clusters of sex hormones, liver enzymes, and cardiometabolic factors associated with postprandial glucose (PPG) and, second to evaluate the variation these clusters account for jointly and independently with polygenic risk scores (PRSs) in South Africans of African ancestry men and women.Research design and methodsPPG was calculated as the integrated area under the curve for glucose during the oral glucose tolerance test (OGTT) using the trapezoidal rule in 794 participants from the Middle-aged Soweto Cohort. Principal component analysis was used to cluster sex hormones, liver enzymes, and cardiometabolic factors, stratified by sex. Multivariable linear regression was used to assess the proportion of variance in PPG accounted for by principal components (PCs) and type 2 diabetes (T2D) PRS while adjusting for selected covariates in men and women.ResultsThe T2D PRS did not contribute to the PPG variability in both men and women. In men, the PCs’ cluster of sex hormones, liver enzymes, and cardiometabolic explained 10.6% of the variance in PPG, with PC1 (peripheral fat), PC2 (liver enzymes and steroid hormones), and PC3 (lipids and peripheral fat) contributing significantly to PPG. In women, PC factors of sex hormones, cardiometabolic factors, and liver enzymes explained a similar amount of the variance in PPG (10.8%), with PC1 (central fat) and PC2 (lipids and liver enzymes) contributing significantly to PPG.ConclusionsWe demonstrated that inter-individual differences in PPG responses to an OGTT may be differentially explained by body fat distribution, serum lipids, liver enzymes, and steroid hormones in men and women.
Persistence and safety of anti-TNF biosimilars versus originators in immune-mediated inflammatory diseases: an observational study on the French National Health Data System
Authors: Jourdain Hugo , Hoisnard Léa , Sbidian Emilie , Zureik Mahmoud 
Published: March 2024

ObjectivesBiosimilar-originator equivalence has been demonstrated in phase 3 trials in a few indications of infliximab, etanercept and adalimumab. The objective of our study was to compare the persistence and safety of biosimilars versus originators in all the licensed indications of these molecules.MethodsWe used data from the French National Health Data System (SNDS), covering 99% of the French population, to identify infliximab, etanercept and adalimumab initiators from biosimilar launch (January 2015, May 2016 and October 2018, respectively) to 30 June 2021. Patients were then followed for 1 year. Treatment persistence (duration without treatment discontinuation or modification) and safety (including severe infections, all-cause hospitalisation and death) were compared between originator and biosimilar users by Cox regressions weighting the populations on the inverse probability of treatment. Analyses were performed by molecule, by disease and by biosimilar product.ResultsFrom January 2015 to June 2021, 86 776 patients were included in the study: 22 670, 24 442 and 39 664 patients had initiated infliximab, etanercept and adalimumab, respectively; 49 752 (53%) were biosimilar initiators. We did not find any risk of discontinuation (HRs were below or around 1, here all pathologies and products together: infliximab 0.88 (0.80–0.97), etanercept 0.85 (0.81–0.90) and adalimumab 0.96 (0.91–1.00)) or safety event (infection: infliximab 0.97 (0.78–1.21), etanercept 1.04 (0.81–1.33) and adalimumab 0.98 (0.83–1.16); hospitalisation: infliximab 1.08 (0.96–1.23), etanercept 0.99 (0.87–1.11) and adalimumab 0.91 (0.83–0.99)) associated with biosimilar versus originator use.ConclusionsOur study shows reassuring results regarding the persistence and safety of biosimilar tumour necrosis factor-alpha inhibitors compared with originators in all licensed indications.
Why Do Young Muslims Study Islamic Theology?
Authors: Aysel Asligül 
Published: March 2024

Abstract
What motivates young Muslims to study Islamic theology or religious education? Are they aiming for a specific professional qualification that requires the study of Islamic theology, or do they want to deepen their faith and aim for further personal development? The question of motives for studying Islamic theology is linked to the life goals and biographies of young Muslims, which opens up the issue of migration and Islam. This article aims to investigate the relationship between the study motives, professional aspirations, and life goals of Islamic theology students within the context of migration. Additionally, it seeks to explore their experiences with foreign and self-positioning in society. Empirical data gathered through qualitative and quantitative research methods will serve as the basis for this examination.
The Prevalence and Correlates of Internet Addiction in India as Assessed by Young’s Internet Addiction Test: A Systematic Review and Meta-analysis
Authors: Tadpatrikar Ashwini , Sharma Manoj Kumar , Amudhan Senthil , Desai Geetha 
Published: March 2024

Background: Earlier research on internet addiction (IA) in the adult population in India has concentrated on isolated prevalence surveys conducted nationwide. A systematic grasp of pooled prevalence necessitates a meta-level evaluation of all prior literature. This study aims to investigate the prevalence of IA and its correlates among adults in India. Methods: We searched EBSCOhost, PubMed, PsycInfo, PsycArticles, and ProQuest for the studies published from 1990 to 2022 and included studies using Young’s Internet Addiction Test criteria (age range 18–40 years). The authors obtained a total of 358 non-duplicate records after a thorough search, and they found 10 pertinent epidemiological studies involving 12,286 adults. Results: The pooled prevalence for mild, moderate, severe, and any level of IA was 36.33% (95% confidence interval [CI]: 30.72%–42.13%), 18.04% (95% CI: 13.49%–23.08%), 0.88% (95% CI:0.50%–1.36%), and 58.34% (95% CI:49.34%–67.07%), respectively. The review of correlates suggested psychosocial factors like male gender, single-parent families, co-morbidities like depression, stress, anxiety, interpersonal issues, andmediating factors like loneliness. Conclusions: Based on the synthesis of findings, this review underlines the common factors of IA and emphasizes the significance of psycho-social factors in IA; thus, to promote healthy use of technology and to manage IA, a multi-modal psychotherapeutic intervention module for mental health practitioners needs to be developed in line with this review.
Early Career Nurses’ Experiences of Engaging in a Leadership Role in Hospital Settings
Authors: Ting Justine Jeanelle , Babenko-Mould Yolanda , Garnett Anna 
Published: March 2024

Background Early career nurses (ECNs) can be expected to assume shift charge nurse leadership roles quickly upon entering practice. Since the emergence of the COVID-19 pandemic, junior nurses may find their leadership capabilities tested further as the challenges of leadership are made increasingly complex in the context of an infectious disease outbreak. Purpose The purpose of this qualitative study was to explore early career registered nurses’ (RNs) experiences of engaging in shift charge nurse roles in hospital settings. Methods This study used an interpretive descriptive (ID) approach. Semi-structured, in-depth interviews were conducted with 14 RNs across Ontario, who had up to three years of experience and who had engaged in a shift charge nurse role in a hospital setting. Recruitment and data collection took place from January to May 2021 during the COVID-19 pandemic. Interviews were recorded, transcribed, and analyzed following the principles of content analysis. Results Content analysis of the 14 participant interviews revealed four main themes: nominated and necessitated into leadership, diverse and demanding responsibilities, factors that help and hinder, and leadership as an impactful experience. Conclusions Study findings provide insights into potential strategies to support ECNs in shift charge nurse roles, during the remaining course of the COVID-19 pandemic and beyond. Greater support for nurses who engage in these roles may be achieved by promoting collaborative unit and organizational cultures, prioritizing leadership training programs, and strengthening policies to provide greater clarity regarding charge nurse role responsibilities.
Effect-based monitoring of chemical hazards in drinking water from source to tap: seasonal trends over 2 years of sampling
Authors: Lundqvist Johan , Lavonen Elin , Mandava Geeta , Selin Erica , Ejhed Helene , Oskarsson Agneta 
Published: March 2024

AbstractDrinking water producers have a far-reaching responsibility to provide safe, clean and wholesome drinking water, using water resources possibly effected by the thousands of chemicals used in societies’ daily life. This study has monitored chemical hazards in drinking water from source to tap, using effect-based methods. The study was conducted at a Swedish drinking water treatment plant sourcing lake water and aimed to investigate potential seasonal variations in both the raw water and water after different treatment steps. Furthermore, a granular activated carbon (GAC) pilot facility was evaluated. Samples were analyzed for estrogenicity, androgenicity, aryl hydrocarbon receptor (AhR) activity, oxidative stress (Nrf2) response and genotoxicity (micronucleus formation). We observed seasonal differences in oxidative stress and genotoxic effects in both raw and drinking water with higher activities during the late fall of each year. The removal efficiency for both oxidative stress and genotoxicity was limited in the full-scale treatment process and occasionally the genotoxicity was also detected in outgoing drinking water from the treatment plant and in samples collected at consumers tap on the distribution network. AhR activity was present in all raw water samples and the removal was limited. Estrogenic activities were observed in most of the raw water samples but in contrast to the other parameters estrogenicity was effectively reduced by the full-scale conventional treatment. The GAC pilot treatment was generally more efficient than the full-scale conventional treatment in removing all observed bioactivities and could be a viable complement to the current treatment to assure drinking water free from genotoxic compounds. Genotoxic activities in drinking water was observed while all currently regulated chemical parameters were fulfilled. This highlights the need for effect-based monitoring in efforts to ensure the chemical safety of drinking water, as target chemical analysis of single compounds will overlook both unknown hazardous compounds as well as potential mixture effects.
Graphical Abstract
Efficacy of acupuncture as an adjunctive treatment to patients with stable COPD: a multicenter, randomized, sham-controlled trial protocol
Authors: Huang Liuyang , Yang Sha , Xu Guixing , Luo Qin , Yang Chunyan , Tian Hao , Liu Yilin , Zhou Zhuo , Huang Fengyuan , Gong Siyao , Li Qian , Yu Xin , Chen Ming , Huang Dan , Liu Yunyu , Tang Juan , Zhang Ruixin , Sun Xin , Lu Guangbing , Zeng Chunfang , Ai Shuangchun , Li Bin , Chen Jian qin , Luo Quan , Xiong Chan , Zou Zhi , Hu Qiang , Luo Xiaochao , Li Ling , Sun Mingsheng , Zeng Fang , Liang Fanrong 
Published: March 2024

Abstract
Background
Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose–effect relationship of acupuncture.

Methods/design
This is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period.

Discussion
This study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD.

Trial registration
This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.
Learning to teach with patients and caregivers: a focused ethnography
Authors: Alberti Sara , Vannini Valeria , Ghirotto Luca , Bonetti Loris , Rovesti Sergio , Ferri Paola 
Published: March 2024

Abstract
Background
Little is known about what happens when patients and caregivers are involved in an academic setting as co-teachers and how healthcare professionals approach a new model of partnership-based teaching. This study aimed to explore the learning and behavioural patterns of a group of healthcare professionals who were learning to teach with patients and caregivers as co-teachers in a post-graduate course.

Methods
A focused ethnographic study involving 11 health professionals was conducted. Data were collected through participatory observation during the course, individual semi-structured interviews, and a follow-up focus group. Taxonomic analysis was performed.

Results
Three categories were identified: ‘group’, ‘role of narration’ and ‘applying co-teaching with patients and caregivers ’. Specifically, heterogeneity, absence of hierarchies, and balanced relationships characterised the group dynamic and promoted partnership. Narration played a key role both in learning and in healthcare professionals’ relationship with patients and caregivers and promoted emotional skills and self-awareness. Project planning and lessons simulations were essential aspects of the implementation process.

Conclusions
This focused ethnography helped further understanding of the context of a specific project involving patients and caregivers as co-teachers in healthcare professional education. The development of emotional skills and self-awareness are the main learning patterns of co-teaching, and interprofessionalism and balanced relationships are the basis of the behavioural patterns. These patterns facilitated the involvement of patients and caregivers in health education.
Natural language processing to identify lupus nephritis phenotype in electronic health records
Authors: Deng Yu , Pacheco Jennifer A. , Ghosh Anika , Chung Anh , Mao Chengsheng , Smith Joshua C. , Zhao Juan , Wei Wei-Qi , Barnado April , Dorn Chad , Weng Chunhua , Liu Cong , Cordon Adam , Yu Jingzhi , Tedla Yacob , Kho Abel , Ramsey-Goldman Rosalind , Walunas Theresa , Luo Yuan 
Published: March 2024

Abstract
Background
Systemic lupus erythematosus (SLE) is a rare autoimmune disorder characterized by an unpredictable course of flares and remission with diverse manifestations. Lupus nephritis, one of the major disease manifestations of SLE for organ damage and mortality, is a key component of lupus classification criteria. Accurately identifying lupus nephritis in electronic health records (EHRs) would therefore benefit large cohort observational studies and clinical trials where characterization of the patient population is critical for recruitment, study design, and analysis. Lupus nephritis can be recognized through procedure codes and structured data, such as laboratory tests. However, other critical information documenting lupus nephritis, such as histologic reports from kidney biopsies and prior medical history narratives, require sophisticated text processing to mine information from pathology reports and clinical notes. In this study, we developed algorithms to identify lupus nephritis with and without natural language processing (NLP) using EHR data from the Northwestern Medicine Enterprise Data Warehouse (NMEDW).

Methods
We developed five algorithms: a rule-based algorithm using only structured data (baseline algorithm) and four algorithms using different NLP models. The first NLP model applied simple regular expression for keywords search combined with structured data. The other three NLP models were based on regularized logistic regression and used different sets of features including positive mention of concept unique identifiers (CUIs), number of appearances of CUIs, and a mixture of three components (i.e. a curated list of CUIs, regular expression concepts, structured data) respectively. The baseline algorithm and the best performing NLP algorithm were externally validated on a dataset from Vanderbilt University Medical Center (VUMC).

Results
Our best performing NLP model incorporated features from both structured data, regular expression concepts, and mapped concept unique identifiers (CUIs) and showed improved F measure in both the NMEDW (0.41 vs 0.79) and VUMC (0.52 vs 0.93) datasets compared to the baseline lupus nephritis algorithm.

Conclusion
Our NLP MetaMap mixed model improved the F-measure greatly compared to the structured data only algorithm in both internal and external validation datasets. The NLP algorithms can serve as powerful tools to accurately identify lupus nephritis phenotype in EHR for clinical research and better targeted therapies.