bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel homozygous HES7 splicing variant causing spondylocostal dysostosis 4: a case report
Authors: Lv Shaoguang , Wu Yuanyuan , Liu Fang , Jiao Baoquan 
Published: August 2023

BackgroundSpondylocostal dysostosis 4 (SCDO4) is characterized by short stature (mainly short trunk), dyspnea, brain meningocele, and spina bifida occulta, which is caused by homozygous or compound heterozygous HES7 (HES family bHLH transcription factor 7) variants. The incidence of SCDO4 remains unknown due to the extremely low number of cases. This study reveals a novel homozygous HES7 splicing variant causing SCDO4 and reviews all the previously reported HES7 variants and corresponding symptoms, providing a comprehensive overview of the phenotypes and genotypes of HES7 variants.Case presentationThis case report focuses on a Chinese neonate who was first hospitalized for tachypnea, cleft palate, and short trunk. After a series of auxiliary examinations, the patient was also found to have deformities of vertebrae and rib, left hydronephrosis, and patent foramen ovale. He underwent surgery for congenital hydronephrosis at 5 months old and underwent cleft palate repair when he was 1 year old. After two and half years of follow-up, the boy developed normally. A novel homozygous HES7 splicing variant (c.226+1G&gt;A, NM_001165967.2) was identified in the proband by whole-exome sequencing and verified by Sanger sequencing. The variant was inherited from both parents and minigene assays demonstrated that this variant resulted in the retention of intron3 in the HES7 transcript. Including this case, a total of six HES7 variants and 13 patients with SCDO4 have been reported.ConclusionsOur findings expand the genotype-phenotype knowledge of SCDO4 and provide new evidence for genetic counseling.
Mapping the regulatory landscape of AI in healthcare in Africa
Authors: Townsend Beverley Alice , Sihlahla Irvine , Naidoo Meshandren , Naidoo Shiniel , Donnelly Dusty-Lee , Thaldar Donrich Willem 
Published: August 2023

Introduction: Artificial intelligence (AI)-enhanced technology has seen unprecedented expansion in the recent past. This growth brings with it huge opportunities for the positive transformation of the economy, business, healthcare, and society. However, a critical question is whether, and to what extent, regulatory measures and mechanisms have been implemented to safeguard its design, development, and deployment. This paper offers a scoping exercise that maps the regulatory landscape of AI in healthcare (including health research) in certain African countries.Methods: This research is conducted across 12 African countries: Botswana, Cameroon, The Gambia, Ghana, Kenya, Malawi, Nigeria, Rwanda, South Africa, Tanzania, Uganda, and Zimbabwe. As limited specific AI legislation is found in these African countries, and because AI is informed by ancillary regulatory frameworks, we include data protection, digital health, consumer protection, and intellectual property in our research. A scoping review method was applied with a manual search of digital libraries with search terms customised for each repository consisting of core search terms for the various topics, including, among others, “law,” “regulation,” “artificial intelligence,” “data protection,” “intellectual property,” and “digital health”.Results and discussion: Analysis of the data demonstrated that while in the African countries under investigation there is no sui generis AI regulation, recent developments were found in areas that inform AI adoption, including in digital health, data protection, consumer protection, and intellectual property. Our findings highlight the fragmentation of the African AI regulatory landscape and illustrate the importance of continued AI regulatory development to ensure that Africa is well positioned for future AI adoption in health.
Long-term proton pump inhibitors use and its association with premalignant gastric lesions: a systematic review and meta-analysis
Authors: Zheng Zeyi , Lu Ziyu , Song Yani 
Published: August 2023

Background: Long-term maintenance therapy with proton pump inhibitors (PPIs) is a common treatment strategy for acid-related gastrointestinal diseases. However, concerns have been raised about the potential increased risk of gastric cancer and related precancerous lesions with long-term PPI use. This systematic review and meta-analysis aimed to evaluate this potential risk.Methods: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials published before 1 March 2023, with no language restrictions. The primary endpoint was the occurrence and progression of gastric mucosal atrophy, intestinal metaplasia, Enterochromaffin-like (ECL) cell hyperplasia, gastric polyps, and gastric cancer during the trial and follow-up. Data were analysed using a random effects model.Results: Of the 4,868 identified studies, 10 met the inclusion criteria and were included in our analysis, comprising 27,283 participants. Compared with other treatments, PPI maintenance therapy for more than 6 months was associated with an increased risk of ECL cell hyperplasia (OR 3.01; 95% CI 1.29 to 7.04; p = 0.01). However, no significant increase was found in the risk of gastric mucosal atrophy (OR 1.01; 95% CI 0.55 to 1.85; p = 0.97), intestinal metaplasia (OR 1.14; 95% CI 0.49 to 2.68; p = 0.76), gastric polyps (OR 1.13; 95% CI 0.68 to 1.89; p = 0.64), or gastric cancer (OR 1.06; 95% CI 0.79 to 1.43; p = 0.71).Conclusion: This systematic review and meta-analysis does not support an increased risk of gastric cancer or related precancerous lesions with long-term PPI maintenance therapy. However, long-term PPI use should be monitored for potential complications such as ECL cell hyperplasia. Further studies are needed to confirm these findings and evaluate the safety of PPI maintenance therapy for acid-related gastrointestinal diseases.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, Identifier: PROSPERO (CRD42022379692).
The identification and expression pattern of the sex determination genes and their sex-specific variants in the egg parasitoid Trichogramma dendrolimi Matsumura (Hymenoptera: Trichogrammatidae)
Authors: Ning Su-Fang , Huo Liang-Xiao , Lv Lin , Wang Ying , Zhang Li-Sheng , Che Wu-Nan , Dong Hui , Zhou Jin-Cheng 
Published: August 2023

Introduction:Trichogramma wasps are egg parasitoids of agricultural lepidopteran pests. The sex of Trichogramma is determined by its ploidy as well as certain sex ratio distorters, such as the endosymbiotic bacteria Wolbachia spp. and the paternal sex ratio (PSR) chromosome. The sex determination systems of hymenopterans, such as Trichogramma spp., involve cascades of the genes transformer (tra), transformer-2 (tra2), and doublesex (dsx) and are associated with sex-specific tra and dsx splicing. First, these genes and their sex-specific variants must be identified to elucidate the interactions between the sex ratio disorders and the sex determination mechanism of Trichogramma.Methods: Here, we characterized the sex determination genes tra, tra2, and dsx in Trichogramma dendrolimi. Sex-specific tra and dsx variants were detected in cDNA samples obtained from both male and female Trichogramma wasps. They were observed in the early embryos (1–10 h), late embryos (12–20 h), larvae (32 h and 48 h), pre-pupae (96 h), and pupae (144 h, 168 h, 192 h, and 216 h) of both male and female T. dendrolimi offspring.Results: We detected female-specific tra variants throughout the entire early female offspring stage. The male-specific variant began to express at 9–10 h as the egg was not fertilized. However, we did not find any maternally derived, female-specific tra variant in the early male embryo. This observation suggests that the female-specific tra variant expressed in the female embryo at 1–9 h may not have originated from the maternal female wasp.Discussion: The present study might be the first to identify the sex determination genes and sex-specific gene splicing in Trichogramma wasps. The findings of this study lay the foundation for investigating the sex determination mechanisms of Trichogramma and other wasps. They also facilitate sex identification in immature T. dendrolimi and the application of this important egg parasitoid in biological insect pest control programs.
Comparative analysis of wild-type and chloroplast MCU-deficient plants reveals multiple consequences of chloroplast calcium handling under drought stress
Authors: Corti Francesca , Festa Margherita , Stein Frank , Stevanato Piergiorgio , Siroka Jitka , Navazio Lorella , Vothknecht Ute C. , Alboresi Alessandro , Novák Ondřej , Formentin Elide , Szabò Ildikò 
Published: August 2023

IntroductionChloroplast calcium homeostasis plays an important role in modulating the response of plants to abiotic and biotic stresses. One of the greatest challenges is to understand how chloroplast calcium-permeable pathways and sensors are regulated in a concerted manner to translate specific information into a calcium signature and to elucidate the downstream effects of specific chloroplast calcium dynamics. One of the six homologs of the mitochondrial calcium uniporter (MCU) was found to be located in chloroplasts in the leaves and to crucially contribute to drought- and oxidative stress-triggered uptake of calcium into this organelle.MethodsIn the present study we integrated comparative proteomic analysis with biochemical, genetic, cellular, ionomic and hormone analysis in order to gain an insight into how chloroplast calcium channels are integrated into signaling circuits under watered condition and under drought stress.ResultsAltogether, our results indicate for the first time a link between chloroplast calcium channels and hormone levels, showing an enhanced ABA level in the cmcu mutant already in well-watered condition. Furthermore, we show that the lack of cMCU results in an upregulation of the calcium sensor CAS and of enzymes of chlorophyll synthesis, which are also involved in retrograde signaling upon drought stress, in two independent KO lines generated in Col-0 and Col-4 ecotypes. ConclusionsThese observations point to chloroplasts as important signaling hubs linked to their calcium dynamics. Our results obtained in the model plant Arabidopsis thaliana are discussed also in light of our limited knowledge regarding organellar calcium signaling in crops and raise the possibility of an involvement of such signaling in response to drought stress also in crops.
The impact of social support and emotion dysregulation on COVID-19 depressive symptoms
Authors: Dhruve Deepali M. , Russo Jenna E. , Oliveros Arazais D. 
Published: August 2023

IntroductionStress resulting from the global COVID-19 pandemic has been linked to psychological consequences, such as depressive symptoms, for individuals worldwide. Outbreaks and pandemics are known to accentuate stressors or generate new ones owing to health-related worries, reduced mobility, and social activity due to quarantine, and sudden life changes. Although post-lockdown U.S. research findings suggest a greater risk of depression among 18- to 25-year-olds, familiarity with technology and virtual socializing may offer college students some protective effect, warranting research with such groups.MethodsThe current study thus explored emotion dysregulation (ED) and perceived social support (PSS) as potential mechanisms for the relationship between COVID-19 stress and depressive symptoms among students at a southern university in the United States. Participants (N = 489) completed a cross-sectional survey assessing their current levels of COVID-19 stress, ED, PSS, and depressive symptoms.ResultsPath analysis showed that PSS buffered the effect of ED on depressive symptoms. The results support the explanatory role of ED in the relationship between COVID-19 stress and depressive symptoms.DiscussionThe perceived social connection may be an essential factor for psychological outcomes during periods of stress and isolation, particularly for those reporting high ED.
Cognitive aging in rural communities: preliminary memory characterization of a community cohort from Southern Nevada
Authors: Miller Justin B. , Wong Christina G. , Caldwell Jessica Z. K. , Rodrigues Jessica , Pudumjee Shehroo , John Samantha E. , Ritter Aaron 
Published: August 2023

IntroductionRural-dwelling older adults face unique health challenges that may increase risk for Alzheimer's disease and dementia but are underrepresented in aging research. Here, we present an initial characterization of a rural community cohort compared to an urban cohort from the same region.MethodsAdults over age 50 living in a non-metropolitan area are clinically characterized using the Uniform Data Set, enriched with additional measures of verbal and non-verbal memory measures. Neighborhood disadvantage is also assessed. Clinical and cognitive differences between cohorts were explored after stratifying by cognitive impairment.ResultsBetween group comparisons found that rural-dwellers demonstrated better verbal memory than urban-dwellers on primary indices of learning, recall, and recognition, with small to medium effects in overall comparisons. When stratified by impairment, rural-urban differences were notably larger among cognitively normal individuals. Within-group comparisons found that the magnitude of impairment between cognitively normal and impaired groups was greater among rural-dwellers compared to urban-dwellers. No differences in non-verbal memory or overall clinical status were found, and there were no effects of neighborhood disadvantage on any cognitive measure.DiscussionLiving in a rural community presents a complex set of contextual factors that for some, may increase risk for dementia. In this study, we found small to moderate memory advantages for rural-dwellers, leaving open the possibility that late-life rural living may be advantageous for some and promote resilience. Additional prospective research is critically needed to better understand the factors that influence aging outcomes in this underrepresented population.
The effect of Tuina based on the concept of hip-knee-ankle conjugation in patients with chronic ankle instability: study protocol for a randomized controlled trial
Authors: Wen Zonglin , Lyu Ruoyun , Wang Wei , Hua Xia , Yu Yifeng , Zeng Ke , Kong Lingjun , Wang JianWei 
Published: August 2023

BackgroundChronic ankle instability (CAI) is a common sports injury disease and characterized by limited mobility, perceived instability and muscle weakness, combined treatment of hip-knee-ankle is a common rehabilitation method. Tuina, as a traditional Chinese manual therapy, is usually used for CAI, but many of them only focus on the local ankle joint rather than the combination of hip and knee joint. Therefore, we have designed a randomized controlled trial (RCT) to investigate the effects of Tuina base on the concept of hip-knee-ankle conjugation on the stability and balance of lower limbs and ankle function in patients with CAI.MethodsWe have designed a randomized controlled trial. A total of 72 participants with CAI will be randomly divided into functional training groups and hip-knee-ankle Tuina combined with functional training group in a 1:1 ratio. Participants in control group will receive 8 sessions of functional training (30 min per session, twice a week for 4 weeks). Participants in intervention group will receive 8 sessions of Tuina combined with functional training (twice a week for 4 weeks). The primary outcomes include the Y-Balance Test (YBT) and Cumberland Ankle Instability Tool (CAIT). The Secondary outcomes include the Foot and Ankle Ability Measure (FAAM) and ankle range of motion (ROM). The outcome assessments will be conducted before the first intervention and after the last intervention.DiscussionThe aim of this study is to explore a safe and effective manipulation program and serve as reference for clinical treatment of CAI and expect to provide the necessary theoretical and practical support to our future research.Clinical Trial RegistrationChinese Clinical Trail Registry ChiCTR2300068274.
The VA National TeleNeurology Program implementation: a mixed-methods evaluation guided by RE-AIM framework
Authors: Damush Teresa M. , Wilkinson Jayne R. , Martin Holly , Miech Edward J. , Tang Qing , Taylor Stanley , Daggy Joanne K. , Bastin Grace , Islam Robin , Myers Laura J. , Penney Lauren S. , Narechania Aditi , Schreiber Steve S. , Williams Linda S. 
Published: August 2023

IntroductionThe Veteran Affairs (VA) Office of Rural Health (ORH) funded the Veterans Health Administration (VHA) National TeleNeurology Program (NTNP) as an Enterprise-Wide Initiative (EWI). NTNP is an innovative healthcare delivery model designed to fill the patient access gap for outpatient neurological care especially for Veterans residing in rural communities. The specific aim was to apply the RE-AIM framework in a pragmatic evaluation of NTNP services.Materials and methodsWe conducted a prospective implementation evaluation. Guided by the pragmatic application of the RE-AIM framework, we conceptualized a mixed-methods evaluation for key metrics: (1) reach into the Veteran patient population assessed as total NTNP new patient consult volume and total NTNP clinical encounters (new and return); (2) effectiveness through configurational analysis of conditions leading to high Veteran satisfaction and referring providers perceived effectiveness; (3) adoption and implementation by VA sites through site staff and NTNP interviews; (4) implementation success through perceived management, implementation barriers, facilitators, and adaptations and through rapid qualitative analysis of multiple stakeholders’ assessments; and (5) maintenance of NTNP through monitoring quarterly TeleNeurology consultation volume.ResultsNTNP was successfully implemented in 13 VA Medical Centers over 2 years. The total NTNP new patient consult volume in fiscal year 2021 (FY21) was 836 (58% rurally residing); this increased to 1,706 in fiscal year 2022 (FY22) (55% rurally residing). Total (new and follow-up) NTNP clinical encounters were 1,306 in FY21 and 3,730 in FY22. Overall, the sites reported positive experiences with program implementation and perceived that the program was serving Veterans with little access to neurological care. Veterans also reported high satisfaction with the NTNP program. We identified the patient level of perceived excellent teleneurologist–patient communications, reduced need to drive to get care, and that NTNP provided care that the Veteran otherwise could not access as key factors related to high Veteran satisfaction.ConclusionsThe VA NTNP demonstrated substantial reach, adoption, effectiveness, implementation success, and maintenance over the first 2 years of the program. The NTNP was highly acceptable to both the clinical providers making the referrals and the Veterans receiving the referred video care. The pragmatic application of the RE-AIM framework to guide implementation evaluations is appropriate, comprehensive, and recommended for future applications.
Duration of intermittent hypoxia impacts metabolic outcomes and severity of murine NAFLD
Authors: Barnes Laura A. , Xu Yinuo , Sanchez-Azofra Ana , Moya Esteban A. , Zhang Michelle P. , Crotty Alexander Laura E. , Malhotra Atul , Mesarwi Omar 
Published: August 2023

RationaleObstructive sleep apnea (OSA) is associated with metabolic dysfunction, including progression of nonalcoholic fatty liver disease (NAFLD). Chronic intermittent hypoxia (IH) as a model of OSA worsens hepatic steatosis and fibrosis in rodents with diet induced obesity. However, IH also causes weight loss, thus complicating attempts to co-model OSA and NAFLD. We sought to determine the effect of various durations of IH exposure on metabolic and liver-related outcomes in a murine NAFLD model. We hypothesized that longer IH duration would worsen the NAFLD phenotype.MethodsMale C57BL/6J mice (n = 32) were fed a high trans-fat diet for 24 weeks, to induce NAFLD with severe steatohepatitis. Mice were exposed to an IH profile modeling severe OSA, for variable durations (0, 6, 12, or 18 weeks). Intraperitoneal glucose tolerance test was measured at baseline and at six-week intervals. Liver triglycerides, collagen and other markers of NAFLD were measured at sacrifice.ResultsMice exposed to IH for 12 weeks gained less weight (p = 0.023), and had lower liver weight (p = 0.008) relative to room air controls. These effects were not observed in the other IH groups. IH of longer duration transiently worsened glucose tolerance, but this effect was not seen in the groups exposed to shorter durations of IH. IH exposure for 12 or 18 weeks exacerbated liver fibrosis, with the largest increase in hepatic collagen observed in mice exposed to IH for 12 weeks.DiscussionDuration of IH significantly impacts clinically relevant outcomes in a NAFLD model, including body weight, fasting glucose, glucose tolerance, and liver fibrosis.
Effects of local nitrogen supply and nitrogen fertilizer variety coupling on rice nitrogen transport and soil nitrogen balance in paddy fields
Authors: Hu Ren , Xiao Dakang , Ding Zijuan , Cao Yuxian , Hou Jun , Wang Xuexia 
Published: August 2023

IntroductionThis study aimed to provide the theoretical basis for formulating scientific and reasonable on-farm nitrogen (N) management measures and efficient strategic fertilization to understand the effects of localized N supply (LNS) and N fertilizer variety coupling on N transport and soil N balance in rice fields.MethodsA 2-year field experiment (2020 and 2021) was conducted in Jingzhou, Hubei Province, which included the following six treatments: no N application (CK), farmers' fertilizer practice (FFP), and four LNS treatments, including two N application methods including mechanical side-deep fertilization (M) and root-zone fertilization (R), two N fertilizer types with urea (U), and controlled-release urea (CRU).ResultsCompared with FFP, LNS increased the N apparent translocation level from stems, sheathes, and leaves (TNT) and N uptake by 10.70–50.59% and 11.28–29.71%, respectively. In LNS, the levels of nitrite reductase (NR), glutamine synthetase (GS), and glutamate synthase (GOGAT) under R increased by 13.81, 9.56, and 15.59%, respectively, compared with those under M, resulting in a significant increase in TNT by 8.58% and N uptake by 1.87%. Regarding the N fertilizer type, CRU significantly increased chlorophyll content by 7.27%, superoxide dismutase (SOD) and catalase (CAT) by 14.78 and 29.95% (p &lt; 0.05), and NR, GS, and GOGAT by 44.41, 16.12, and 28.41% (p &lt; 0.05), respectively, compared with that in U, which contributed to N absorption and transport. Moreover, CRUR significantly decreased N apparent loss by 50.04% compared with CRUM (p &lt; 0.05).DiscussionConsidering the risk of soil N leaching and environmental protection, R should be selected as the recommended fertilization method. The combination of CRU and R is the most effective fertilization approach.