bluuebunny/crossref_metadata_2025_split huggingface dataset:
In situ analysis of CCR8+ regulatory T cells in lung cancer: suppression of GzmB+ CD8+ T cells and prognostic marker implications
Authors: Hayashi Yoshinori , Ueyama Azumi , Funaki Soichiro , Jinushi Koichi , Higuchi Naoko , Morihara Hitomi , Hirata Michinari , Nagira Yoji , Saito Takuro , Kawashima Atsunari , Iwahori Kota , Shintani Yasushi , Wada Hisashi 
Published: May 2024

Abstract
Background
CCR8-expressing regulatory T cells (Tregs) are selectively localized within tumors and have gained attention as potent suppressors of anti-tumor immunity. This study focused on CCR8+ Tregs and their interaction with CD8+ T cells in the tumor microenvironment of human lung cancer. We evaluated their spatial distribution impact on CD8+ T cell effector function, specifically granzyme B (GzmB) expression, and clinical outcomes.

Methods
A total of 81 patients with lung squamous cell carcinoma (LSCC) who underwent radical surgical resection without preoperative treatment were enrolled. Histological analyses were performed, utilizing an automated image analysis system for double-stained immunohistochemistry assays of CCR8/Foxp3 and GzmB/CD8. We investigated the association of CCR8+ Tregs and GzmB+ CD8+ T cells in tumor tissues and further evaluated the prognostic impact of their distribution profiles.

Results
Histological evaluation using the region of interest (ROI) protocol showed that GzmB expression levels in CD8+ T cells were decreased in areas with high infiltration of CCR8+ Tregs, suggesting a suppressive effect of CCR8+ Tregs on T cell cytotoxicity in the local tumor microenvironment. Analysis of the association with clinical outcomes showed that patients with more CCR8+ Tregs and lower GzmB expression, represented by a low GzmB/CCR8 ratio, had worse progression-free survival.

Conclusions
Our data suggest that local CCR8+ Treg accumulation is associated with reduced CD8+ T cell cytotoxic activity and poor prognosis in LSCC patients, highlighting the biological role and clinical significance of CCR8+ Tregs in the tumor microenvironment. The GzmB/CCR8 ratio may be a useful prognostic factor for future clinical applications in LSCC.
Causal relationship between thyroid dysfunction and ovarian cancer: a two-sample Mendelian randomization study
Authors: Wang Tingting , Wang Xiaoqin , Wu Jun , Li Xin 
Published: May 2024

Abstract
Purpose
Observational studies and clinical validation have suggested a link between thyroid dysfunction and an elevated ovarian cancer (OC) risk. However, whether this association indicates a cause-and-effect relationship remains uncertain. We aimed to investigate the plausible causal impact of thyroid dysfunction on OC through a Mendelian randomization (MR) study.

Methods
Genome-wide association study (GWAS) data for thyrotropin (TSH), free thyroxine (FT4), hypothyroidism, and hyperthyroidism were obtained as exposures and those for OC (N = 199,741) were selected as outcomes. Inverse variance-weighted method was used as the main estimation method. A series of sensitivity analyses, including Cochran’s Q test, MR-Egger intercept analysis, forest plot scatter plot, and leave-one-out test, was conducted to assess the robustness of the estimates.

Results
Genetic prediction of hyperthyroidism was associated with a potential increase in OC risk (odds ratio = 1.094, 95% confidence interval: 1.029–1.164, p = 0.004). However, no evidence of causal effects of hypothyroidism, TSH, and FT4 on OC or reverse causality was detected. Sensitivity analyses demonstrated consistent and reliable results, with no significant estimates of heterogeneity or pleiotropy.

Conclusions
This study employed MR to establish a correlation between hyperthyroidism and OC risk. By genetically predicting OC risk in patients with hyperthyroidism, our research suggests new insights for early prevention and intervention of OC.
Gender differences in plasma S100B levels of patients with major depressive disorder
Authors: Wu Yifan , Lu Yihui , Kong Lingtao , Xie Yu , Liu Wen , Yang Anqi , Xin Kaiqi , Yan Xintong , Wu Longhai , Liu Yilin , Zhu Qianying , Cao Yang , Zhou Yifang , Jiang Xiaowei , Tang Yanqing , Wu Feng 
Published: May 2024

Abstract
Background
Low concentrations of S100B have neurotrophic effects and can promote nerve growth and repair, which plays an essential role in the pathophysiological and histopathological alterations of major depressive disorder (MDD) during disease development. Studies have shown that plasma S100B levels are altered in patients with MDD. In this study, we investigated whether the plasma S100B levels in MDD differ between genders.

Methods
We studied 235 healthy controls (HCs) (90 males and 145 females) and 185 MDD patients (65 males and 120 females). Plasma S100B levels were detected via multifactor assay. The Mahalanobis distance method was used to detect the outliers of plasma S100B levels in the HC and MDD groups. The Kolmogorov–Smirnov test was used to test the normality of six groups of S100B samples. The Mann–Whitney test and Scheirer-Ray-Hare test were used for the comparison of S100B between diagnoses and genders, and the presence of a relationship between plasma S100B levels and demographic details or clinical traits was assessed using Spearman correlation analysis.

Results
All individuals in the HC group had plasma S100B levels that were significantly greater than those in the MDD group. In the MDD group, males presented significantly higher plasma S100B levels than females. In the male group, the plasma S100B levels in the HC group were significantly higher than those in the MDD group, while in the female group, no significant difference was found between the HC and MDD groups. In the male MDD subgroup, there was a positive correlation between plasma S100B levels and years of education. In the female MDD subgroup, there were negative correlations between plasma S100B levels and age and suicidal ideation.

Conclusions
In summary, plasma S100B levels vary with gender and are decreased in MDD patients, which may be related to pathological alterations in glial cells.
Experiences of living with idiopathic pulmonary fibrosis in relation to physical activity - “How the hills became steeper and steeper”: a qualitative interview study
Authors: Jernås Anna , Fagevik Olsén Monika , Holmqvist Emma , Danielsbacka Jenny 
Published: May 2024

Abstract
Introduction
Idiopathic pulmonary fibrosis (IPF) is a progressive disease presenting with symptoms like dyspnoea, dry cough, and fatigue, which affect physical function and quality of life. No earlier qualitative studies have investigated physical activity in IPF. This study aims to explore experiences of living with IPF in relation to physical activity.

Materials and methods
Qualitative interviews were conducted with 14 participants living with IPF. The participants were 77 years old (range: 56–86) and diagnosed with IPF between 2 and 9 years ago. The analysis was performed by qualitative content analysis according to Graneheim and Lundman.

Results
The results indicated that life and one’s ability to be physically active is affected by IPF. Despite this, it seems possible to navigate past obstacles, which was illustrated by an overall theme: “My life is constrained, but I am hanging on”. Two major categories cover topics of IPF being a life changing diagnosis with changes in self-image and changed future plans regarding physical activity, as well as life. Physical activity was perceived to be challenging, yet in many ways used as a strategy, developed to manage life.

Conclusions
IPF affects physical activity as well as life, from onset onwards. By developing strategies for facilitating physical activity as well as identifying barriers, it seems possible to maintain an active life despite the disease. The healthcare system needs to create support systems that meet different needs during different phases of the disease.

Trial registration
“FoU in Sweden” Research and Development in Sweden (id: 227081).
Extending the intermedullary nail will not reduce the potential risk of femoral head varus in PFNA patients biomechanically: a clinical review and corresponding numerical simulation
Authors: Cha Xiaofeng , Zhou Qin , Li Jujie , Xu Hong , Xu Wenqiang , Li Jingchi 
Published: May 2024

AbstractFemoral head varus is an important complication in intertrochanteric fracture patients treated with proximal femoral nail anti-rotation (PFNA) fixation. Theoretically, extending the length of the intramedullary nail could optimize fixation stability by lengthening the force arm. However, whether extending the nail length can optimize patient prognosis is unclear. In this study, a review of imaging data from intertrochanteric fracture patients with PFNA fixation was performed, and the length of the intramedullary nail in the femoral trunk and the distance between the lesser trochanter and the distal locking screw were measured. The femoral neck varus status was judged at the 6-month follow-up. The correlation coefficients between nail length and femoral neck varus angle were computed, and linear regression analysis was used to determine whether a change in nail length was an independent risk factor for femoral neck varus. Moreover, the biomechanical effects of different nail lengths on PFNA fixation stability and local stress distribution have also been verified by numerical mechanical simulations. Clinical review revealed that changes in nail length were not significantly correlated with femoral head varus and were also not an independent risk factor for this complication. In addition, only slight biomechanical changes can be observed in the numerical simulation results. Therefore, commonly used intramedullary nails should be able to meet the needs of PFNA-fixed patients, and additional procedures for longer nail insertion may be unnecessary.
Ceramic soft tissue trimming bur gingival depigmentation: clinical performance and patient experience. A split mouth randomized controlled trial
Authors: Nassar Sally K , Abuel-Ela Hala Ahmed , Fouad Yasmine Ahmed 
Published: May 2024

Abstract
Background
The ceramic soft tissue trimming bur (CeraTip™) was initially introduced for use in gingivoplasty but has recently been used for gingival depigmentation. The aim of this study is to compare the efficacy of depigmentation between the novel CeraTip™ and the gold-standard surgical scalpel technique.

Methods
Eight healthy, nonsmokers with moderate to severe gingival hyperpigmentation in both arches were randomly assigned for CeraTip™ depigmentation in one arch as the test group (TG) and scalpel depigmentation in the opposite arch as the control group (CG). Pigmentation indices were used to assess clinical performance. Treatment time, pain level, and esthetic satisfaction were the parameters of patient experience. The assessments were performed at baseline, one week, one month, and three months.

Results
At all assessment visits, pigmentation intensity represented by the Dummet oral pigmentation index (DOPI), and pigmentation distribution represented by the Hedin melanin index (MI), were significantly lower than those at baseline (p < 0.001) in both groups. When comparing the two groups, Scalpel depigmentation had better initial clinical outcomes, while CeraTip™ had less visible repigmentation, pain scores, treatment time, and greater esthetic satisfaction. However, none of the differences were statistically significant.

Conclusion
Both techniques successfully removed gingival hyperpigmentation with comparable clinical performance. The patients preferred CeraTip™ depigmentation.

Trial registration
The study protocol was registered on 11/09/2023 on the www.clinicaltrials.gov database (NCT06031116) after the approval of the Ethics Committee, Faculty of Dentistry, Ain Shams University (FDASU-Rec012124).
Investigating racial/ethnic differences in procedure experience in obstetrics & gynecology trainees at a single academic institution: a retrospective cohort study
Authors: GiglioAyers Patricia , Foley Christine E. , Cronin Beth , Burrell Dayna 
Published: May 2024

Abstract
Background
Discrimination is common in medical education. Resident physicians of races and ethnicities underrepresented in medicine experience daily discrimination which has been proven to negatively impact training. There is limited data on the impact of resident race/ethnicity on OB/GYN surgical training. The objective of this study was to investigate the impact of race/ethnicity on procedural experience in OB/GYN training.

Methods
A retrospective analysis of graduated OB/GYN resident case logs from 2009 to 2019 was performed at a single urban academic institution. Self-reported race/ethnicity data was collected. Association between URM and non-URM were analyzed using t-tests. Trainees were categorized by self-reported race/ethnicity into underrepresented in medicine (URM) (Black, Hispanic, Native American) and non-URM (White, Asian).

Results
The cohort consisted of 84 residents: 19% URM (N = 16) and 79% non-URM (n = 66). Difference between URM and non-URM status and average case volume was analyzed using t-tests. There was no difference between non-URM and URM trainees and reported mean number of Total GYN (349 vs. 334, p = 0.31) and Total OB (624 vs. 597, P = 0.11) case logs. However, compared with non-URM, on average URM performed fewer Total procedures (1562 vs. 1469, P = 0.04). Analyzing individual procedures showed a difference in average number of abortions performed between URM and non-URM (76 vs. 53, P = 0.02). There were no other statistically significant differences between the two groups.

Conclusions
This single institution study highlights potential differences in trainee experience by race/ethnicity. Larger national studies are warranted to further explore these differences to identify bias and discrimination, and to ensure equitable experience for all trainees.
Integrating the social determinants of health into graduate medical education training: a scoping review
Authors: Nour Nehal , Onchonga David , Neville Siobhan , O’Donnell Patrick , Abdalla Mohamed Elhassan 
Published: May 2024

Abstract
Background
The social determinants of health (SDH) play a key role in the health of individuals, communities, and populations. Academic institutions and clinical licensing bodies increasingly recognize the need for healthcare professionals to understand the importance of considering the SDH to engage with patients and manage their care effectively. However, incorporating relevant skills, knowledge, and attitudes relating to the SDH into curricula must be more consistent. This scoping review explores the integration of the SDH into graduate medical education training programs.

Methods
A systematic search was performed of PubMed, Ovid MEDLINE, ERIC, and Scopus databases for articles published between January 2010 and March 2023. A scoping review methodology was employed, and articles related to training in medical or surgical specialties for registrars and residents were included. Pilot programs, non-SDH-related programs, and studies published in languages other than English were excluded.

Results
The initial search produced 829 articles after removing duplicates. The total number of articles included in the review was 24. Most articles were from developed countries such as the USA (22), one from Canada, and only one from a low- and middle-income country, Kenya. The most highly represented discipline was pediatrics. Five papers explored the inclusion of SDH in internal medicine training, with the remaining articles covering family medicine, obstetrics, gynecology, or a combination of disciplines. Longitudinal programs are the most effective and frequently employed educational method regarding SDH in graduate training. Most programs utilize combined teaching methods and rely on participant surveys to evaluate their curriculum.

Conclusion
Applying standardized educational and evaluation strategies for SDH training programs can pose a challenge due to the diversity of the techniques reported in the literature. Exploring the most effective educational strategy in delivering these concepts and evaluating the downstream impacts on patient care, particularly in surgical and non-clinical specialties and low- and middle-income countries, can be essential in integrating and creating a sustainable healthcare force.
Challenges of care coordination for complex patients among family medicine residents in a community ambulatory clinic: a qualitative study
Authors: Heng Moses Tan Mong , Seng Gilbert Yeo Tian , Lee Eng Sing 
Published: May 2024

Abstract
Background
Care coordination has been identified as one of five focuses of HealthierSG. Family medicine residents are expected to collaborate with other healthcare professionals for complex patients by the end of residency. However, many residents felt that it was challenging to coordinate care effectively among healthcare stakeholders. However, to date, no qualitative studies have explored these challenges. Therefore, this study aimed to understand the challenges encountered by family medicine residents when coordinating care for complex patients.

Methods
This was a qualitative descriptive study in which semi structured in-depth interviews were conducted and guided by a topic guide. Total population sampling of 15 third-year family medicine residents in the National Healthcare Group Polyclinics was performed. The interviews were performed over Zoom and were transcribed. Thematic analysis was subsequently performed to analyse the transcripts. Coding was performed iteratively by two independent researchers. Disagreements were adjudicated by a third coder. A coding framework was agreed upon. Potential themes were then independently developed based on the coding framework.

Results
Six themes emerged from the data, namely, interprofessional communications, accessibility, personal knowledge, time constraints, patient factors and caregiver dissent.

Conclusion
Challenges faced by family medicine residents are multifaceted. While a few are systemic and pertain to the broader healthcare framework, others, such as issues of unfamiliarity with institutional workflows, community resources, and confidentiality, pertain to the microcosm of residency itself. These are reversible areas for improvement. These challenges can be addressed during planning of residency curricula to better equip family medicine residents with coordinating care for complex patients in the future.
Pass or fail: Teachers’ experience of assessment of postgraduate critical care nursing students’ competence in placement. A qualitative study
Authors: Øvrebø Line J. , Dyrstad Dagrunn Nåden , Hansen Britt Sætre 
Published: May 2024

Abstract
Background
Learning in placement is essential to postgraduate critical care nursing students’ education. Assessment of students’ competence in placement is important to ensure highly qualified postgraduate critical care nurses. The placement model applied in Norway involves students being assessed by a preceptor in practice and a teacher from the university. The teacher has a more distant role in placement, and the aim of this study was to explore how the teachers experience the assessment of postgraduate critical care nursing students’ competence in placement. Additionally, to explore the content of assessment documents used for postgraduate critical care nursing placement education in Norway.

Methods
This study has a qualitative design with main data collection from individual interviews with 10 teachers from eight universities and colleges in Norway. Additionally, we performed a document analysis of assessment documents from all 10 universities and colleges providing postgraduate critical care nursing education in Norway. We followed the Consolidated Criteria for Reporting Qualitative Research.

Results
The teachers experienced the assessment of postgraduate critical care nursing students’ competence in placement as important but complex, and some found it difficult to determine what critical care nursing competence is at advanced level. A thematic analysis resulted in one main theme: “Teacher facilitates the bridging between education and practice.” Furthermore, three themes were identified: “Assessment based on trust and shared responsibility”; “The teacher’s dual role as judge and supervisor”; and “A need for common, clear and relevant assessment criteria”.

Conclusions
Teachers have a key role in placement as they contribute to the bridging between education and practice by providing valuable pedagogical and academic input to the assessment process. We suggest that more teachers should be employed in joint university and clinical positions to enhance the collaboration between practice and education. Clear and relevant assessment criteria are essential for providing assessment support for both students and educators. Education and practice should collaborate on developing assessment criteria. Further, there is a need to collaborate on developing, both nationally and internationally, common, clear, relevant and user-friendly assessment tools.
Identification of mitochondria-related biomarkers in childhood allergic asthma
Authors: Zhao Wei , Fang Hongjuan , Wang Tao , Yao Chao 
Published: May 2024

Abstract
Background
The mechanism of mitochondria-related genes (MRGs) in childhood allergic asthma (CAS) was unclear. The aim of this study was to find new biomarkers related to MRGs in CAS.

Methods
This research utilized two CAS-related datasets (GSE40888 and GSE40732) and extracted 40 MRGs from the MitoCarta3.0 Database. Initially, differential expression analysis was performed on CAS and control samples in the GSE40888 dataset to obtain the differentially expressed genes (DEGs). Differentially expressed MRGs (DE-MRGs) were obtained by overlapping the DEGs and MRGs. Protein protein interactions (PPI) network of DE-MRGs was created and the top 10 genes in the degree ranking of Maximal Clique Centrality (MCC) algorithm were defined as feature genes. Hub genes were obtained from the intersection genes from the Least absolute shrinkage and selection operator (LASSO) and EXtreme Gradient Boosting (XGBoost) algorithms. Additionally, the expression validation was conducted, functional enrichment analysis, immune infiltration analysis were finished, and transcription factors (TFs)-miRNA-mRNA regulatory network was constructed.

Results
A total of 1505 DEGs were obtained from the GSE40888, and 44 DE-MRGs were obtained. A PPI network based on these 44 DE-MRGs was created and revealed strong interactions between ADCK5 and MFN1, BNIP3 and NBR1. Four hub genes (NDUFAF7, MTIF3, MRPS26, and NDUFAF1) were obtained by taking the intersection of genes from the LASSO and XGBoost algorithms based on 10 signature genes which obtained from PPI. In addition, hub genes-based alignment diagram showed good diagnostic performance. The results of Gene Set Enrichment Analysis (GSEA) suggested that hub genes were closely related to mismatch repair. The B cells naive cells were significantly expressed between CAS and control groups, and MTIF3 was most strongly negatively correlated with B cells naive. In addition, the expression of MTIF3 and MRPS26 may have influenced the inflammatory response in CAS patients by affecting mitochondria-related functions. The quantitative real-time polymerase chain reaction (qRT‒PCR) results showed that four hub genes were all down-regulated in the CAS samples.

Conclusion
NDUFAF7, MTIF3, MRPS26, and NDUFAF1 were identified as an MRGs-related biomarkers in CAS, which provides some reference for further research on CAS.