bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated analyses reveal unexpected complex inversion and recombination in RH genes
Authors: Li Minghao , Wang Liping , Li Aijing , Wang Bo , Yang Xiaohong , Zhang Yue , Chen Chaoqiong , Sun Futing , Zhu Ziyan , Ye Luyi 
Published: March 2024

Abstract
Phenotype D-- is associated with severe hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. It is typically caused by defective RHCE genes. In this study, we identified a D-- phenotype proband and verified Rh phenotypes of other 6 family members. However, inconsistent results between the phenotypic analysis and Sanger sequencing revealed intact RHCE exons with no mutations in the D-- proband, but the protein was not expressed. Subsequent whole-genome sequencing by Oxford Nanopore Technologies of the proband revealed an inversion with ambiguous breakpoints in intron 2 and intron 7 and copy number variation loss in the RHCE gene region. Given that the RHCE gene is highly homologous to the RHD gene, we conducted a comprehensive analysis using Pacific Biosciences long-read target sequencing, Bionano optical genome mapping, and targeted next-generation sequencing. Our findings revealed that the proband had 2 novel recombinant RHCE haplotypes, RHCE∗Ce(1-2)-D(3-10) and RHCE∗Ce(1-2)-D(3-10)-Ce(10-8)-Ce(3-10), with clear-cut breakpoints identified. Furthermore, the RH haplotypes of the family members were identified and verified. In summary, we made, to our knowledge, a novel discovery of hereditary large inversion and recombination events occurring between the RHD and RHCE genes, leading to a lack of RhCE expression. This highlights the advantages of using integrated genetic analyses and also provides new insights into RH genotyping.
Transcriptional and metabolic effects of aspartate-glutamate carrier isoform 1 (AGC1) downregulation in mouse oligodendrocyte precursor cells (OPCs)
Authors: Balboni Nicola , Babini Giorgia , Poeta Eleonora , Protti Michele , Mercolini Laura , Magnifico Maria Chiara , Barile Simona Nicole , Massenzio Francesca , Pignataro Antonella , Giorgi Federico M. , Lasorsa Francesco Massimo , Monti Barbara 
Published: March 2024

AbstractAspartate–glutamate carrier isoform 1 (AGC1) is a carrier responsible for the export of mitochondrial aspartate in exchange for cytosolic glutamate and is part of the malate–aspartate shuttle, essential for the balance of reducing equivalents in the cells. In the brain, mutations inSLC25A12gene, encoding for AGC1, cause an ultra-rare genetic disease, reported as a neurodevelopmental encephalopathy, whose symptoms include global hypomyelination, arrested psychomotor development, hypotonia and seizures. Among the biological components most affected by AGC1 deficiency are oligodendrocytes, glial cells responsible for myelination processes, and their precursors [oligodendrocyte progenitor cells (OPCs)]. The AGC1 silencing in an in vitro model of OPCs was documented to cause defects of proliferation and differentiation, mediated by alterations of histone acetylation/deacetylation. Disrupting AGC1 activity could possibly reduce the availability of acetyl groups, leading to perturbation of many biological pathways, such as histone modifications and fatty acids formation for myelin production. Here, we explore the transcriptome of mouse OPCs partially silenced for AGC1, reporting results of canonical analyses (differential expression) and pathway enrichment analyses, which highlight a disruption in fatty acids synthesis from both a regulatory and enzymatic stand. We further investigate the cellular effects of AGC1 deficiency through the identification of most affected transcriptional networks and altered alternative splicing. Transcriptional data were integrated with differential metabolite abundance analysis, showing downregulation of several amino acids, including glutamine and aspartate. Taken together, our results provide a molecular foundation for the effects of AGC1 deficiency in OPCs, highlighting the molecular mechanisms affected and providing a list of actionable targets to mitigate the effects of this pathology.
Effect of temperature-humidity index on the evolution of trade-offs between fertility and production in dairy cattle
Authors: Vinet Aurélie , Mattalia Sophie , Vallée Roxane , Bertrand Christine , Barbat Anne , Promp Julie , Cuyabano Beatriz C. D. , Boichard Didier 
Published: March 2024

Abstract
Background
In the current context of climate change, livestock production faces many challenges to improve the sustainability of systems. Dairy farming, in particular, must find ways to select animals that will be able to achieve sufficient overall production while maintaining their reproductive ability in environments with increasing temperatures. With future forecasted climate conditions in mind, this study used data from Holstein and Montbeliarde dairy cattle to: (1) estimate the genetic-by-temperature-humidity index (THI) interactions for female fertility, and (2) evaluate the production-fertility trade-off with increasing values of THI.

Results
Two-trait random regression models were fitted for conception rate (fertility) and test-day protein yield (production). For fertility, genetic correlations between different THI values were generally above 0.75, suggesting weak genotype-by-THI interactions for conception rate in both breeds. However, the genetic correlations between the conception rate breeding values at the current average THI (THI = 50, corresponding to a 24-h average temperature of 8 °C at 50% relative humidity) and their slopes (i.e., potential reranking) for heat stress scenarios (THI > 70), were different for each breed. For Montbeliarde, this correlation tended to be positive (i.e., overall the best reproducers are less affected by heat stress), whereas for Holstein it was approximately zero. Finally, our results indicated a weak antagonism between production and fertility, although for Montbeliarde this antagonism intensified with increasing THI.

Conclusions
Within the range of weather conditions studied, increasing temperatures are not expected to exacerbate the fertility-production trade-off. However, our results indicated that the animals with the best breeding values for production today will be the most affected by temperature increases, both in terms of fertility and production. Nonetheless, these animals should remain among the most productive ones during heat waves. For Montbeliarde, the current selection program for fertility seems to be adequate for ensuring the adaptation of fertility traits to temperature increases, without adverse effects on production. Such a conclusion cannot be drawn for Holstein. In the future, the incorporation of a heat tolerance index into dairy cattle breeding programs would be valuable to promote the selection of animals adapted to future climate conditions.
Mice lacking DIO3 exhibit sex-specific alterations in circadian patterns of corticosterone and gene expression in metabolic tissues
Authors: Wu Zhaofei , Martinez M. Elena , Hernandez Arturo 
Published: March 2024

AbstractDisruption of circadian rhythms is associated with neurological, endocrine and metabolic pathologies. We have recently shown that mice lacking functional type 3 deiodinase (DIO3), the enzyme that clears thyroid hormones, exhibit a phase shift in locomotor activity, suggesting altered circadian rhythm. To better understand the physiological and molecular basis of this phenotype, we used Dio3+/+ and Dio3-/- mice of both sexes at different zeitgeber times (ZTs) and analyzed corticosterone and thyroxine (T4) levels, hypothalamic, hepatic, and adipose tissue expression of clock genes, as well as genes involved in the thyroid hormone action or physiology of liver and adipose tissues. Wild type mice exhibited sexually dimorphic circadian patterns of genes controlling thyroid hormone action, including Dio3. Dio3-/- mice exhibited altered hypothalamic expression of several clock genes at ZT12, but did not disrupt the overall circadian profile. Expression of clock genes in peripheral tissues was not disrupted by Dio3 deficiency. However, Dio3 loss in liver and adipose tissues disrupted circadian profiles of genes that determine tissue thyroid hormone action and physiology. We also observed circadian-specific changes in serum T4 and corticosterone as a result of DIO3 deficiency. The circadian alterations manifested sexual dimorphism. Most notable, the time curve of serum corticosterone was flattened in Dio3-/- females. We conclude that Dio3 exhibits circadian variations, influencing the circadian rhythmicity of thyroid hormone action and physiology in liver and adipose tissues in a sex-specific manner. Circadian disruptions in tissue physiology may then contribute to the metabolic phenotypes of DIO3-deficient mice.
What works to support carers of older people and older carers? an international evidence map of interventions and outcomes
Authors: Spiers Gemma , Tan Michelle M.C. , Astbury Jayne L , Hall Alex , Ahmed Nisar , Lanyi Kate , Williams Oleta , Beyer Fiona , Craig Dawn , Hanratty Barbara 
Published: March 2024

Abstract
Background
Unpaid carers of older people, and older unpaid carers, experience a range of adverse outcomes. Supporting carers should therefore be a public health priority. Our understanding of what works to support carers could be enhanced if future evaluations prioritise under-researched interventions and outcomes. To support this, we aimed to: map evidence about interventions to support carers, and the outcomes evaluated; and identify key gaps in current evidence.

Methods
Evidence gap map review methods were used. Searches were carried out in three bibliographic databases for quantitative evaluations of carer interventions published in OECD high-income countries between 2013 and 2023. Interventions were eligible if they supported older carers (50 + years) of any aged recipient, or any aged carers of older people (50 + years).

Findings
205 studies reported across 208 publications were included in the evidence map. The majority evaluated the impact of therapeutic and educational interventions on carer burden and carers’ mental health. Some studies reported evidence about physical exercise interventions and befriending and peer support for carers, but these considered a limited range of outcomes. Few studies evaluated interventions that focused on delivering financial information and advice, pain management, and physical skills training for carers. Evaluations rarely considered the impact of interventions on carers’ physical health, quality of life, and social and financial wellbeing. Very few studies considered whether interventions delivered equitable outcomes.

Conclusion
Evidence on what works best to support carers is extensive but limited in scope. A disproportionate focus on mental health and burden outcomes neglects other important areas where carers may need support. Given the impact of caring on carers’ physical health, financial and social wellbeing, future research could evaluate interventions that aim to support these outcomes. Appraisal of whether interventions deliver equitable outcomes across diverse carer populations is critical.
Study on the measurement of coupling and coordinated development level between China’s internet and elderly care services and its influencing factors
Authors: Yangming Hu , Sha Li , Hui Liu , Yanda Yang 
Published: March 2024

Abstract
Background
With the intensification of China’s aging population, the demand for elderly care services has become increasingly prominent. At the same time, rapid development of internet technology provides more convenience and possibilities for the elderly. However, the coordinated development between the internet and elderly care services still faces challenges. This study aims to measure the level of coupling and coordinated development between the internet and elderly care services in China, and analyze the influencing factors, in order to provide reference for promoting elderly care services.

Methods
In this paper, the entropy method and coupling coordination degree model were used to measure the coupling coordination development index of the internet and elderly care services in China from 2012 to 2021. In addition, considering that the coordinated development between the two is affected by many factors, the Tobit model was used to analyze the main factors affecting the integration of the internet and elderly care services.

Results
(1) The coupling and coordination of the Internet and senior care services is in its infancy, but the coupling and coordination of the two is on the rise, and there is still a lot of room for development in the future. (2) In terms of time scale, the coupling coordination development level between the internet and elderly care services in China has gone through three stages of “disorder recession-transition coordination-coordinated development”. (3) In terms of influencing factors, government management ability has a more positive impact on the development of the integration of the Internet and senior care services, financial support, scientific and technological investment and the level of innovation play a mild pulling role, while the level of informatization to a certain extent restricts the level of integration of the Internet and senior care services.

Conclusion
In order to promote the coordinated development of China’s Internet and senior care services, it is necessary to comprehensively understand the current situation and development space of China’s Internet and senior care services coupling coordination degree, accurately grasp the dynamic trend of China’s Internet and senior care services coupling and coordinated development, promote the stage of leapfrogging, and fully consider the influencing factors, so as to realize the optimal allocation of policies and resources. These measures will help to promote a more coordinated and sustainable development of the internet and elderly care services in China.
Influenza vaccine coverage and factors associated with non-vaccination among caregiving and care-receiving adults in the Canadian Longitudinal Study on Aging (CLSA)
Authors: Gravagna Katie , Wolfson Christina , Basta Nicole E. 
Published: March 2024

Abstract
Background
Influenza vaccination is recommended for those at increased risk of influenza complications and their household contacts to help reduce influenza exposure. Adults who require care often experience health issues that could increase the risk of severe influenza and have close contact with caregivers. Assessing influenza vaccination prevalence in caregivers and care recipients can provide important information about uptake.

Objectives
We aimed to (1) estimate influenza non-vaccination prevalence and (2) assess factors associated with non-vaccination among caregivers aged ≥ 45 years and among care recipients aged ≥ 65 years.

Methods
We conducted an analysis of cross-sectional data from the Canadian Longitudinal Study on Aging collected 2015–2018. We estimated non-vaccination prevalence and reported adjusted odds ratios with 95% confidence intervals from logistic regression models to identify factors associated with non-vaccination among caregivers and care recipients.

Results
Of the 23,500 CLSA participants who reported providing care, 41.4% (95% CI: 40.8%, 42.0%) reported not receiving influenza vaccine in the previous 12 months. Among the 5,559 participants who reported receiving professional or non-professional care, 24.8% (95% CI: 23.7%, 26.0%) reported not receiving influenza vaccine during the same period. For both groups, the odds of non-vaccination were higher for those who had not visited a family doctor in the past year, were daily smokers, and those who identified as non-white.

Discussion
Identifying groups at high risk of severe influenza and their close contacts can inform public health efforts to reduce the risk of influenza. Our results suggest sub-optimal influenza vaccination uptake among caregivers and care recipients. Efforts are needed to increase influenza vaccination and highlight the direct and indirect benefits for caregiver-care recipient pairs.

Conclusion
The proportions of both caregivers and care recipients who had not been vaccinated for influenza was high, despite the benefits of vaccination. Influenza vaccination campaigns could target undervaccinated, high-risk groups to increase coverage.
Knowledge, attitude, and practice toward weight management among diabetic patients in Qidong City, Jiangsu Province
Authors: Li Xiaofeng , Shi Yu , Wei Dongqin , Gong Yan , Yan Xinyi , Cai Shengnan 
Published: March 2024

Abstract
Background
Weight management is an effective prevention and treatment strategy for diabetes mellitus. This study aimed to assess the knowledge, attitude, and practice (KAP) of diabetic patients towards weight management.

Methods
Diabetic patients treated at Qidong City, Jiangsu Province, between January 2023 and June 2023 were included in this cross-sectional study. A self-designed questionnaire was used to collect their demographic characteristics and KAP toward weight management. Structural equation modeling (SEM) was employed to examine the inter-relationships among KAP scores.

Results
Among a total of 503 valid questionnaires that were collected, 55.07% were filled out by men and 54.67% by those aged < 60 years. The mean scores for knowledge, attitude, and practice were 8.03 ± 3.525 (possible range: 0–13), 31.88 ± 3.524 (possible range: 10–50), and 22.24 ± 3.318 (possible range: 9–45), respectively. Pearson’s correlation analysis revealed the knowledge was positively associated with attitude (r = 0.295, P < 0.001) and practice (r = 0.131, P < 0.001), and attitude was positively associated with practice (r = 0.140, P = 0.002). SEM demonstrated positive associations between knowledge and attitude (β = 0.28, P < 0.001), and attitude and practice (β = 0.09, P = 0.019). Moreover, older age was negatively associated with knowledge (β=-0.04, P = 0.001), while higher education (β = 1.220, P < 0.001), increased monthly income (β = 0.779, P < 0.001), diagnosis of fatty liver (β = 1.03, P = 0.002), and screening for excess visceral fat (β = 1.11, P = 0.002) were positively associated with knowledge.

Conclusion
Diabetic patients showed moderate knowledge, neutral attitudes, and inappropriate practices toward weight management. Knowledge was positively associated with attitude and practice. These findings provided valuable directions for healthcare interventions targeting improved KAP status of weight management among diabetic patients.
Effect of metformin on anti-mullerian hormone levels in women with polycystic ovarian syndrome: a systematic review and meta-regression analysis of randomized controlled trials with
Authors: Mehdinezhad Roshan Mehdi , Sohouli Mohammad Hassan , Izze da Silva Magalhães Elma , Hekmatdoost Azita 
Published: March 2024

Abstract
Background
Several interventional studies have evaluated the potential anti-Mullerian hormone (AMH)-reduction effect of metformin. However, the results are still contradictory. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of metformin on AMH in the women with with polycystic ovarian syndrome (PCOS).

Methods
Scopus, PubMed/Medline, Web of Science, Cochrane, and Embase databases were searched using standard keywords to identify all controlled trials investigating the AMH levels following metformin administration. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis for the best estimation of outcomes.

Results
Sixteen studies with 484 participants’ were included in this article. The pooled findings showed that AMH levels in the single arm clinical trials were significantly reduced (pooled WMD of -3.06 ng/ml; 95% confidence interval [CI] -4.03 to -2.10; P < 0.001) after use of metformin. Furthermore, compared to the control group, in randomized clinical trials, a reduced significant effect on AMH levels was observed following use of metformin (pooled WMD of -3.47 ng/ml; 95% CI -7.14 to -0.19; P = 0.047). Furthermore, higher reduction in the AMH levels with a metformin dosage ≤ 1500 mg/day and duration of treatment ≤ 12 weeks when compared to higher dosages and duration of intervention, observed in this meta-analysis.

Conclusions
In conclusion, results this meta-analysis of clinical trials confirms the beneficial effect of the treatment with metformin in the reduction of the AMH levels in women.
Sociodemographic disadvantage in the burden of stress and academic performance in medical school: implications for diversity in medicine
Authors: Eames Danielle , Thomas Shelby , Norman Kaden , Simanton Edward , Weisman Anne 
Published: March 2024

Abstract
Background
Nontraditional students bring to medicine inherent characteristics and perspectives that enrich the learning environment and contribute to expanding diversity in medicine. However, research has shown that these students, by virtue of their sociodemographic backgrounds, face unique challenges in medical education, which ultimately place them at a disadvantage compared to their peers. The purpose of this study is to explore relationships between sociodemographic characteristics, stress, and academic performance, in the context of outcomes that may be undermining efforts to diversify the physician workforce.

Methods
Using a retrospective observational cohort methodology, we examined institutional and USMLE exam performance data in conjunction with Perceived Stress Scale-4 survey results from six cohorts of students at Kirk Kerkorian School of Medicine at UNLV (n = 358). Using independent samples t-test, mean stress and academic performance were compared between four sociodemographic groups: first-generation college students, underrepresented in medicine (URM), socioeconomically disadvantaged, and age 30 + at matriculation. Results were considered significant where P ≤ .05.

Results
First-generation college students had significantly higher stress at the end of third year clerkships (mean 7.8 vs. 6.8, P* = .03). URM students had significantly lower scores on preclinical exams (mean 81.37 vs. 83.07, P* = .02). The students who were age 30 + at matriculation had significantly lower exam scores on all academic performance measures.

Conclusion
Our results echo historic trends in academic performance for racial and ethnic minority students, and we present recent evidence of academic performance disparities based on age at matriculation. Residency program directors continue to use test scores as a primary metric to screen applicants and thus, poor academic performance has profound consequences on career trajectory. Finally, significantly higher stress in the first-generation students may be evidence of underlying psychological distress. Expanding the sociodemographic diversity among physicians, and by extension, medical students, has long been recognized as fundamental to addressing inequities in healthcare. However, results from our study suggest that aspects of medical education are unfavorable and disadvantageous for first-generation, URM, and older medical students. A deeper understanding of the interplay between sociodemographic characteristics and success in medical school is paramount as we pursue diversity in medicine.