bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perceptions and experiences of undergraduate medical students regarding social accountability: a cross-sectional study at a Subsaharan African medical school
Authors: Oriokot Lorraine , Munabi Ian Guyton , Kiguli Sarah , Mubuuke Aloysius Gonzaga 
Published: April 2024

Abstract
Background
Medical schools are called to be socially accountable by medical education and healthcare system stakeholders. Social accountability is a feature of excellent medical education. Medical students are essential to the development of socially accountable medical schools. Therefore, understanding the perceptions and experiences of medical students regarding social accountability is critical for efforts to improve social accountability practices and outcomes.

Methods
This cross-sectional online questionnaire-based survey used Google Forms and involved medical students in their fourth and fifth years of study at the Makerere University School of Medicine. The survey was conducted between September 2022 and October 2023. We used a study questionnaire and a validated toolkit designed by students as part of The Training for Health Equity Collaborative to gauge a school’s progress towards social accountability in medical schools to collect data on demographics, perceptions and experiences and evaluate social accountability.

Results
Out of 555 eligible medical students, 426 responded to the online questionnaire. The response rate was 77%. The mean age of the students was 25.24 ± 4.4 years. Almost three fourths of the students were male (71.3%), and slightly less than two thirds were in their fourth year of study (65%). Almost half of the students (48.1%%) evaluated the school as doing well with regard to social accountability. The evaluation items referring to community-based research and positive impact on the community had the highest mean scores. Only 6 (3.6%) students who reported hearing of social accountability had a clear understanding of social accountability. Students receiving career guidance in secondary school was associated with evaluating social accountability in the medical school as strong (p-0.003).

Conclusions
Medical students evaluated the medical school favorably forsocial accountability despite lacking a clear understanding of social accountability. Receiving career guidance in secondary school was significantly associated with a positive evaluation of social accountability.
Outpatient geriatric health care in the German federal state of Mecklenburg-Western Pomerania: a population-based spatial analysis of claims data
Authors: Pfeuffer Nils , Radicke Franziska , Leiz Maren , Moon Kilson , Hoffmann Wolfgang , van den Berg Neeltje 
Published: April 2024

Abstract
Background
Due to unidentified geriatric needs, elderly patients have a higher risk for developing chronic conditions and acute medical complications. Early geriatric screenings and assessments help to identify geriatric needs. Holistic and coordinated therapeutic approaches addressing those needs maintain the independence of elderly patients and avoid adverse effects. General practitioners are important for the timely identification of geriatric needs. The aims of this study are to examine the spatial distribution of the utilization of outpatient geriatric services in the very rural Federal State of Mecklenburg-Western Pomerania in the Northeast of Germany and to identify regional disparities.

Methods
Geographical analysis and cartographic visualization of the spatial distribution of outpatient geriatric services of patients who are eligible to receive basic geriatric care (BGC) or specialized geriatric care (SGC) were carried out. Claims data of the Association of Statutory Health Insurance Physicians in Mecklenburg-Western Pomerania were analysed on the level of postcode areas for the quarter periods between 01/2014 and 04/2017. A Moran’s I analysis was carried out to identify clusters of utilization rates.

Results
Of all patients who were eligible for BGC in 2017, 58.3% (n = 129,283/221,654) received at least one BCG service. 77.2% (n = 73,442/95,171) of the patients who were eligible for SGC, received any geriatric service (BGC or SGC). 0.4% (n = 414/95,171) of the patients eligible for SGC, received SGC services. Among the postcode areas in the study region, the proportion of patients who received a basic geriatric assessment ranged from 3.4 to 86.7%. Several regions with statistically significant Clusters of utilization rates were identified.

Conclusions
The widely varying utilization rates and the local segregation of high and low rates indicate that the provision of outpatient geriatric care may depend to a large extent on local structures (e.g., multiprofessional, integrated networks or innovative projects or initiatives). The great overall variation in the provision of BGC services implicates that the identification of geriatric needs in GPs’ practices should be more standardized. In order to reduce regional disparities in the provision of BGC and SGC services, innovative solutions and a promotion of specialized geriatric networks or healthcare providers are necessary.
A cilia-bound unconventional secretory pathway for Drosophila odorant receptors
Authors: Dzaki Najat , Alenius Mattias 
Published: April 2024

Abstract
Background
Post-translational transport is a vital process which ensures that each protein reaches its site of function. Though most do so via an ordered ER-to-Golgi route, an increasing number of proteins are now shown to bypass this conventional secretory pathway.

Results
In the Drosophila olfactory sensory neurons (OSNs), odorant receptors (ORs) are trafficked from the ER towards the cilia. Here, we show that Or22a, a receptor of various esters and alcoholic compounds, reaches the cilia partially through unconventional means. Or22a frequently present as puncta at the somatic cell body exit and within the dendrite prior to the cilia base. These rarely coincide with markers of either the intermediary ER-Golgi-intermediate-compartment (ERGIC) or Golgi structures. ERGIC and Golgi also displayed axonal localization biases, a further indication that at least some measure of OR transport may occur independently of their involvement. Additionally, neither the loss of several COPII genes involved in anterograde trafficking nor ERGIC itself affected puncta formation or Or22a transport to the cilium. Instead, we observed the consistent colocalization of Or22a puncta with Grasp65, the sole Drosophila homolog of mammalian GRASP55/Grh1, a marker of the unconventional pathway. The numbers of both Or22a and Grasp65-positive puncta were furthermore increased upon nutritional starvation, a condition known to enhance Golgi-bypassing secretory activity.

Conclusions
Our results demonstrate an alternative route of Or22a transport, thus expanding the repertoire of unconventional secretion mechanisms in neurons.
Targeting of REST with rationally-designed small molecule compounds exhibits synergetic therapeutic potential in human glioblastoma cells
Authors: Panina Svetlana B. , Schweer Joshua V. , Zhang Qian , Raina Gaurav , Hardtke Haley A. , Kim Seungjin , Yang Wanjie , Siegel Dionicio , Zhang Y. Jessie 
Published: April 2024

Abstract
Background
Glioblastoma (GBM) is an aggressive brain cancer associated with poor prognosis, intrinsic heterogeneity, plasticity, and therapy resistance. In some GBMs, cell proliferation is fueled by a transcriptional regulator, repressor element-1 silencing transcription factor (REST).

Results
Using CRISPR/Cas9, we identified GBM cell lines dependent on REST activity. We developed new small molecule inhibitory compounds targeting small C-terminal domain phosphatase 1 (SCP1) to reduce REST protein level and transcriptional activity in glioblastoma cells. Top leads of the series like GR-28 exhibit potent cytotoxicity, reduce REST protein level, and suppress its transcriptional activity. Upon the loss of REST protein, GBM cells can potentially compensate by rewiring fatty acid metabolism, enabling continued proliferation. Combining REST inhibition with the blockade of this compensatory adaptation using long-chain acyl-CoA synthetase inhibitor Triacsin C demonstrated substantial synergetic potential without inducing hepatotoxicity.

Conclusions
Our results highlight the efficacy and selectivity of targeting REST alone or in combination as a therapeutic strategy to combat high-REST GBM.
Nuclear lamina component KAKU4 regulates chromatin states and transcriptional regulation in the Arabidopsis genome
Authors: Cao Yaxin , Yan Hengyu , Sheng Minghao , Liu Yue , Yu Xinyue , Li Zhongqiu , Xu Wenying , Su Zhen 
Published: April 2024

Abstract
Background
The nuclear lamina links the nuclear membrane to chromosomes and plays a crucial role in regulating chromatin states and gene expression. However, current knowledge of nuclear lamina in plants is limited compared to animals and humans.

Results
This study mainly focused on elucidating the mechanism through which the putative nuclear lamina component protein KAKU4 regulates chromatin states and gene expression in Arabidopsis leaves. Thus, we constructed a network using the association proteins of lamin-like proteins, revealing that KAKU4 is strongly associated with chromatin or epigenetic modifiers. Then, we conducted ChIP-seq technology to generate global epigenomic profiles of H3K4me3, H3K27me3, and H3K9me2 in Arabidopsis leaves for mutant (kaku4-2) and wild-type (WT) plants alongside RNA-seq method to generate gene expression profiles. The comprehensive chromatin state-based analyses indicate that the knockdown of KAKU4 has the strongest effect on H3K27me3, followed by H3K9me2, and the least impact on H3K4me3, leading to significant changes in chromatin states in the Arabidopsis genome. We discovered that the knockdown of the KAKU4 gene caused a transition between two types of repressive epigenetics marks, H3K9me2 and H3K27me3, in some specific PLAD regions. The combination analyses of epigenomic and transcriptomic data between the kaku4-2 mutant and WT suggested that KAKU4 may regulate key biological processes, such as programmed cell death and hormone signaling pathways, by affecting H3K27me3 modification in Arabidopsis leaves.

Conclusions
In summary, our results indicated that KAKU4 is directly and/or indirectly associated with chromatin/epigenetic modifiers and demonstrated the essential roles of KAKU4 in regulating chromatin states, transcriptional regulation, and diverse biological processes in Arabidopsis.
The effects of telehealth-delivered mindfulness meditation, cognitive therapy, and behavioral activation for chronic low back pain: a randomized clinical trial
Authors: Day Melissa A. , Ciol Marcia A. , Mendoza M. Elena , Borckardt Jeffrey , Ehde Dawn M. , Newman Andrea K. , Chan Joy F. , Drever Sydney A. , Friedly Janna L. , Burns John , Thorn Beverly E. , Jensen Mark P. 
Published: April 2024

Abstract
Background
Chronic low back pain (CLBP) is a significant problem affecting millions of people worldwide. Three widely implemented psychological techniques used for CLBP management are cognitive therapy (CT), mindfulness meditation (MM), and behavioral activation (BA). This study aimed to evaluate the relative immediate (pre- to post-treatment) and longer term (pre-treatment to 3- and 6-month follow-ups) effects of group, videoconference-delivered CT, BA, and MM for CLBP.

Methods
This is a secondary analysis of a three-arm, randomized clinical trial comparing the effects of three active treatments—CT, BA, and MM—with no inert control condition. Participants were N = 302 adults with CLBP, who were randomized to condition. The primary outcome was pain interference, and other secondary outcomes were also examined. The primary study end-point was post-treatment. Intent-to-treat analyses were undertaken for each time point, with the means of the changes in outcomes compared among the three groups using an analysis of variance (ANOVA). Effect sizes and confidence intervals are also reported.

Results
Medium-to-large effect size reductions in pain interference were found within BA, CT, and MM (ds from − .71 to − 1.00), with gains maintained at both follow-up time points. Effect sizes were generally small to medium for secondary outcomes for all three conditions (ds from − .20 to − .71). No significant between-group differences in means or changes in outcomes were found at any time point, except for change in sleep disturbance from pre- to post-treatment, improving more in BA than MM (d =  − .49).

Conclusions
The findings from this trial, one of the largest telehealth trials of psychological treatments to date, critically determined that group, videoconference-delivered CT, BA, and MM are effective for CLBP and can be implemented in clinical practice to improve treatment access. The pattern of results demonstrated similar improvements across treatments and outcome domains, with effect sizes consistent with those observed in prior research testing in-person delivered and multi-modal psychological pain treatments. Thus, internet treatment delivery represents a tool to scale up access to evidence-based chronic pain treatments and to overcome widespread disparities in healthcare.

Trial registration
Clinicaltrials.gov, NCT03687762.
New frontiers in salivary extracellular vesicles: transforming diagnostics, monitoring, and therapeutics in oral and systemic diseases
Authors: Cui Li , Zheng Jiarong , Lu Ye , Lin Pei , Lin Yunfan , Zheng Yucheng , Xu Rongwei , Mai Zizhao , Guo Bing , Zhao Xinyuan 
Published: April 2024

AbstractSalivary extracellular vesicles (EVs) have emerged as key tools for non-invasive diagnostics, playing a crucial role in the early detection and monitoring of diseases. These EVs surpass whole saliva in biomarker detection due to their enhanced stability, which minimizes contamination and enzymatic degradation. The review comprehensively discusses methods for isolating, enriching, quantifying, and characterizing salivary EVs. It highlights their importance as biomarkers in oral diseases like periodontitis and oral cancer, and underscores their potential in monitoring systemic conditions. Furthermore, the review explores the therapeutic possibilities of salivary EVs, particularly in personalized medicine through engineered EVs for targeted drug delivery. The discussion also covers the current challenges and future prospects in the field, emphasizing the potential of salivary EVs in advancing clinical practice and disease management.
Preoperative risk factors and cumulative incidence of temporary ileostomy non-closure after sphincter-preserving surgery for rectal cancer: a meta-analysis
Authors: He Fan , Tang Chenglin , Yang Fuyu , Chen Defei , Xiong Junjie , Zou Yu , Zhao Dongqin , Qian Kun 
Published: April 2024

Abstract
Background
Temporary ileostomy (TI) has proven effective in reducing the severity of anastomotic leakage after rectal cancer surgery; however, some ileostomies fail to reverse over time, leading to conversion into a permanent stoma (PS). In this study, we aimed to investigate the preoperative risk factors and cumulative incidence of TI non-closure after sphincter-preserving surgery for rectal cancer.

Materials and methods
We conducted a meta-analysis after searching the Embase, Web of Science, PubMed, and MEDLINE databases from their inception until November 2023. We collected all published studies on the risk factors related to TI non-closure after sphincter-preserving surgery for rectal cancer.

Results
A total of 1610 studies were retrieved, and 13 studies were included for meta-analysis, comprising 3026 patients. The results of the meta-analysis showed that the identified risk factors included older age (p = 0.03), especially > 65 years of age (p = 0.03), male sex (p = 0.009), American Society of Anesthesiologists score ≥ 3 (p = 0.004), comorbidity (p = 0.001), and distant metastasis (p < 0.001). Body mass index, preoperative hemoglobin, preoperative albumin, preoperative carcinoma embryonic antigen, tumor location, neoadjuvant chemoradiotherapy, smoking, history of abdominal surgery, and open surgery did not significantly change the risk of TI non-closure.

Conclusion
We identified five preoperative risk factors for TI non-closure after sphincter-preserving surgery for rectal cancer. This information enables surgeons to identify high-risk groups before surgery, inform patients about the possibility of PS in advance, and consider performing protective colostomy or Hartmann surgery.
Dual rare genetic diseases in five pediatric patients: insights from next-generation diagnostic methods
Authors: Liu Yupeng , Ma Xue , Chen Zhehui , He Ruxuan , Zhang Yao , Dong Hui , Ma Yanyan , Wu Tongfei , Wang Qiao , Ding Yuan , Li Xiyuan , Li Dongxiao , Song Jinqing , Li Mengqiu , Jin Ying , Qin Jiong , Yang Yanling 
Published: April 2024

Abstract
Background
Clinicians traditionally aim to identify a singular explanation for the clinical presentation of a patient; however, in some cases, the diagnosis may remain elusive or fail to comprehensively explain the clinical findings. In recent years, advancements in next-generation sequencing, including whole-exome sequencing, have led to the incidental identification of dual diagnoses in patients. Herein we present the cases of five pediatric patients diagnosed with dual rare genetic diseases. Their natural history and diagnostic process were explored, and lessons learned from utilizing next-generation diagnostic technologies have been reported.

Results
Five pediatric cases (3 boys, 2 girls) with dual diagnoses were reported. The age at diagnosis was from 3 months to 10 years. The main clinical presentations were psychomotor retardation and increased muscular tension, some accompanied with liver dysfunction, abnormal appearance, precocious puberty, dorsiflexion restriction and varus of both feet, etc. After whole-exome sequencing, nine diseases were confirmed in these patients: Angelman syndrome and Krabbe disease in case 1, Citrin deficiency and Kabuki syndrome in case 2, Homocysteinemia type 2 and Copy number variant in case 3, Isolated methylmalonic acidemia and Niemann-Pick disease type B in case 4, Isolated methylmalonic acidemia and 21-hydroxylase deficiency in case 5. Fifteen gene mutations and 2 CNVs were identified. Four novel mutations were observed, including c.15292de1A in KMT2D, c.159_164inv and c.1427G > A in SLC25A13, and c.591 C > G in MTHFR.

Conclusions
Our findings underscore the importance of clinicians being vigilant about the significance of historical and physical examination. Comprehensive clinical experience is crucial for identifying atypical clinical features, particularly in cases involving dual rare genetic diseases.
CAPN2 correlates with insulin resistance states in PCOS as evidenced by multi-dataset analysis
Authors: Luo Xi , Dong Yunhua , Zheng Haishan , Zhou Xiaoting , Rong Lujuan , Liu Xiaoping , Bai Yun , Li Yunxiu , Wu Ze 
Published: April 2024

AbstractObjectiveIR emerges as a feature in the pathophysiology of PCOS, precipitating ovulatory anomalies and endometrial dysfunctions that contribute to the infertility challenges characteristic of this condition. Despite its clinical significance, a consensus on the precise mechanisms by which IR exacerbates PCOS is still lacking. This study aims to harness bioinformatics tools to unearth key IR-associated genes in PCOS patients, providing a platform for future therapeutic research and potential intervention strategies.MethodsWe retrieved 4 datasets detailing PCOS from the GEO, and sourced IRGs from the MSigDB. We applied WGCNA to identify gene modules linked to insulin resistance, utilizing IR scores as a phenotypic marker. Gene refinement was executed through the LASSO, SVM, and Boruta feature selection algorithms. qPCR was carried out on selected samples to confirm findings. We predicted both miRNA and lncRNA targets using the ENCORI database, which facilitated the construction of a ceRNA network. Lastly, a drug-target network was derived from the CTD.ResultsThirteen genes related to insulin resistance in PCOS were identified via WGCNA analysis. LASSO, SVM, and Boruta algorithms further isolated CAPN2 as a notably upregulated gene, corroborated by biological verification. The ceRNA network involving lncRNA XIST and hsa-miR-433-3p indicated a possible regulatory link with CAPN2, supported by ENCORI database. Drug prediction analysis uncovered seven pharmacological agents, most being significant regulators of the endocrine system, as potential candidates for addressing insulin resistance in PCOS.ConclusionsThis study highlights the pivotal role of CAPN2 in insulin resistance within the context of PCOS, emphasizing its importance as both a critical biomarker and a potential therapeutic target. By identifying CAPN2, our research contributes to the expanding evidence surrounding the CAPN family, particularly CAPN10, in insulin resistance studies beyond PCOS. This work enriches our understanding of the mechanisms underlying insulin resistance, offering insights that bridge gaps in the current scientific landscape.
Probiotic supplementation and risk of necrotizing enterocolitis and mortality among extremely preterm infants—the Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial: study protocol for a multicenter, double-blinded, placebo-controlled, and registry-based randomized controlled trial
Authors: Kruth Sofia Söderquist , Willers Carl , Persad Emma , Sjöström Elisabeth Stoltz , Lagerström Susanne Rautiainen , Rakow Alexander 
Published: April 2024

Abstract
Background
Extremely preterm infants, defined as those born before 28 weeks’ gestational age, are a very vulnerable patient group at high risk for adverse outcomes, such as necrotizing enterocolitis and death. Necrotizing enterocolitis is an inflammatory gastrointestinal disease with high incidence in this cohort and has severe implications on morbidity and mortality. Previous randomized controlled trials have shown reduced incidence of necrotizing enterocolitis among older preterm infants following probiotic supplementation. However, these trials were underpowered for extremely preterm infants, rendering evidence for probiotic supplementation in this population insufficient to date.

Methods
The Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial is a multicenter, double-blinded, placebo-controlled and registry-based randomized controlled trial conducted among extremely preterm infants (n = 1620) born at six tertiary neonatal units in Sweden and four units in Denmark. Enrolled infants will be allocated to receive either probiotic supplementation with ProPrems® (Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus) diluted in 3 mL breastmilk or placebo (0.5 g maltodextrin powder) diluted in 3 mL breastmilk per day until gestational week 34. The primary composite outcome is incidence of necrotizing enterocolitis and/or mortality. Secondary outcomes include incidence of late-onset sepsis, length of hospitalization, use of antibiotics, feeding tolerance, growth, and body composition at age of full-term and 3 months corrected age after hospital discharge.

Discussion
Current recommendations for probiotic supplementation in Sweden and Denmark do not include extremely preterm infants due to lack of evidence in this population. However, this young subgroup is notably the most at risk for experiencing adverse outcomes. This trial aims to investigate the effects of probiotic supplementation on necrotizing enterocolitis, death, and other relevant outcomes to provide sufficiently powered, high-quality evidence to inform probiotic supplementation guidelines in this population. The results could have implications for clinical practice both in Sweden and Denmark and worldwide.

Trial registration
(Clinicaltrials.gov): NCT05604846