bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter randomized trial of deferred cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma receiving checkpoint inhibitors: the NORDIC-SUN-Trial
Authors: Iisager Laura , Ahrenfeldt Johanne , Donskov Frede , Ljungberg Börje , Bex Axel , Lund Lars , Lyskjær Iben , Fristrup Niels 
Published: February 2024

Abstract
Background
Primary tumor removal by cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma patients has been investigated in the context of various treatment regimens. Two randomized controlled trials investigated the role and timing of cytoreductive nephrectomy in the era of targeted therapy and demonstrated that upfront nephrectomy should no longer be performed when patients require systemic therapy. Superiority of checkpoint immunotherapy agents has led to a paradigm change from targeted therapies to immunotherapy-based first-line treatment in patients with primary metastatic disease; thus, deferred cytoreductive nephrectomy needs to be verified in the immunotherapy setting. Furthermore, a need exists for personalizing treatment choices for the individual patient to avoid unnecessary overtreatment.

Methods/design
To explore the impact of cytoreductive nephrectomy in this patient group receiving checkpoint immunotherapy, we initiated a randomized, controlled trial comparing deferred cytoreductive nephrectomy with no surgery. The trial integrates a comprehensive translational research program with specimen sampling for biomarker analysis.

Discussion
The trial aims to show that deferred cytoreductive nephrectomy improves overall survival in patients with synchronous metastatic renal cell carcinoma, and furthermore, to identify relevant biomarkers for personalized renal cancer management.

Trial registration
ClinicalTrials.gov NCT03977571 June 6, 2019.
Gut microbiota in patients with prostate cancer: a systematic review and meta-analysis
Authors: Huang Haotian , Liu Yang , Wen Zhi , Chen Caixia , Wang Chongjian , Li Hongyuan , Yang Xuesong 
Published: February 2024

Abstract
Background
Increasing evidence indicates that gut microbiota are closely related to prostate cancer. This study aims to assess the gut microbiota composition in patients with prostate cancer compared to healthy participants, thereby advancing understanding of gut microbiota's role in prostate cancer.

Methods
A systematic search was conducted across PubMed, Web of Science, and Embase databases, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The methodological quality of included studies was evaluated using the Newcastle–Ottawa Scale (NOS), and pertinent data were analyzed. The kappa score assessed interrater agreement.

Results
This study encompassed seven research papers, involving 250 prostate cancer patients and 192 controls. The kappa was 0.93. Meta-analysis results showed that alpha-diversity of gut microbiota in prostate cancer patients was significantly lower than in the control group. In terms of gut microbiota abundance, the ratio of Proteobacteria, Bacteroidia, Clostridia, Bacteroidales, Clostridiales, Prevotellaceae, Lachnospiraceae, Prevotella, Escherichia-Shigella, Faecalibacterium, and Bacteroides was higher in prostate cancer patients. Conversely, the abundance ratio of Actinobacteria, Bacteroidetes, Firmicutes, Selenomonadales, Veillonella, and Megasphaera was higher in the control group.

Conclusion
Our study reveals differences in alpha-diversity and abundance of gut microbiota between patients with prostate cancer and controls, indicating gut microbiota dysbiosis in those with prostate cancer. However, given the limited quality and quantity of selected studies, further research is necessary to validate these findings.
Zonulin and copeptin relation to some metabolic markers in school-aged obese children
Authors: El-Raufe El-Masry Sahar Abd , Mahmoud Rehab A. , Hassan Nayera E , Aly Manal M. , Abdallah Hanaa Reyad , Hamdy Sherin , Megahed Safinaz , Elalfy Dina Y. 
Published: February 2024

Abstract
Background
Using Zonulin and Copeptin as potential obesity markers in children, hasn’t yet been focused.

Aim
To evaluate the association between serum levels of both Zonulin and Copeptin with the obesity markers, and to assess their role as metabolic disturbance predictors in obese children.

Methods
A case-control study comprised 111 Egyptian children (45 males and 66 females); aged 6–10 years to avoid the effect of puberty (prepubertal). They were classified according to their body mass index (BMI) percentiles into: 72 obese (BMI ≥ 95th ), and 39 control ones (BMI > 15th - <85th ), based on the Egyptian Growth Charts for children and adolescents. Anthropometric parameters and blood pressure were measured, and body composition analysis, lipid profile, Zonulin, and Copeptin levels were assessed.

Results
The obese group showed a significantly higher value of Copeptin and a lower value of Zonulin than the control one Also, the obese group showed significant negative correlations between Zonulin and both anthropometric obesity markers and body composition, whereas Copeptin showed significant positive ones. Moreover, significant positive correlations were found between Copeptin and both body weight and fat distribution. Insignificant correlations were observed between both serum Zonulin and Copeptin levels and blood pressure and lipid profile.

Conclusion
Zonulin and Copeptin cannot be used as metabolic disturbance predictors, among Egyptian children, as they were insignificantly correlated with lipid profile or blood pressure.
Perinatal anxiety disorders screening study: a study protocol
Authors: Fairbrother Nichole , Stagg Bryn , Scoten Olivia , Keeney Cora , Cargnelli Claudia 
Published: February 2024

AbstractBackgroundThe anxiety and their related disorders (AD) are the most common of all mental health conditions, and affect approximately 20% of pregnant and postpartum people. They are associated with significant distress and life interference for sufferers, as well as negative consequences for fetal and infant development. At present, little if any routine screening for prenatal AD is being conducted and data regarding the most effective tools to screen for these disorders is lacking. The majority of screening studies suffer from methodological difficulties which undermine the confidence needed to recommend measures for population distribution. The primary purpose of this research is to identify the most accurate self-report tool(s) to screen for perinatal AD.MethodsA large, prospective cohort of pregnant people (N = 1,000) is being recruited proportionally across health service delivery regions in British Columbia (BC). The screening accuracy of a broad range of perinatal AD self-report measures are being assessed using gold standard methodology. Consenting individuals are administered online questionnaires followed by a semi-structured diagnostic interview between 16- and 36-weeks’ gestation, and again between 6 and 20 weeks postpartum. Questionnaires include all screening measures, measures of sleep and unpaid family work, and questions pertaining to demographic and reproductive history, COVID-19, gender role burden, and mental health treatment utilization. Interviews assess all current anxiety disorders, as well as obsessive–compulsive disorder, and posttraumatic stress disorder.DiscussionThis research is in response to an urgent demand for accurate perinatal AD screening tools based on high quality evidence. AD among perinatal people often go unidentified and untreated, resulting in continued suffering and life impairment. Findings from this research will inform healthcare providers, policymakers, and scientists, about the most effective approach to screening for anxiety and related disorders in pregnancy in the postpartum period.
Identifying causal associations between women’s reproductive traits and risk of schizophrenia: a multivariate validated two-sample Mendelian randomization analysis
Authors: Sun Wenxi , Wu Xiaohui , Yang Haidong , Yuan Shiting , Chen Jun , Fang Yiru , Zhang Xiaobin 
Published: February 2024

Abstract
Background
A significant association between women’s reproductive traits and the risk of schizophrenia (SCZ) has been discovered, but the causalities remain unclear. We designed a two-sample univariate Mendelian randomization (MR) study using female-specific SNPs collected from a large-scale genome-wide association study as a genetic tool to explore the causal effect of female reproductive traits on the risk of SCZ, and conducted a multivariate MR study to re-validate the above findings.

Methods
From extensive genome-wide association studies (GWAS) of people with European ancestry (n = 176,881 to 418,758 individuals), summary-level data on five female reproductive variables were extracted. Summary-level information on SCZ was taken from a GWAS meta-analysis involving 320,404 people with European ancestry. The inverse variance weighting estimations for both univariable MR (UVMR) and multivariable MR (MVMR) were presented as the primary results. MR-Egger, weighted median, simple mode, and weighted mode regression methods for UVMR, and MVMR-Egger, MVMR-Lasso, and MVMR-median methods for MVMR were used for sensitivity analyses.

Results
The UVMR produced compelling proof for a connection between genetically predicted later age at first sexual intercourse (AFS) (OR, 0.632; 95% CI, 0.512–0.777; P < 0.01) and decreased SCZ risk. Pleiotropy analysis of the AFS-SCZ association confirmed the robustness of the MR results (P > 0.05). Consistent, substantial causal effects of AFS (OR, 0.592; 95%CI, 0.407–0.862; P < 0.01) on the risk of SCZ were demonstrated after adjusting for body mass index, years of schooling, and smoking initiation using MVMR.

Conclusions
Our findings provide convincing evidence that early AFS is a risk factor for SCZ. SCZ risk may be decreased by raising awareness of reproductive healthcare for women.
Superior predictive value of estimated pulse wave velocity for all-cause and cardiovascular disease mortality risk in U.S. general adults
Authors: Cheng Wenke , Kong Fanliang , Pan Huachun , Luan Sisi , Yang Shumin , Chen Siwei 
Published: February 2024

Abstract
Background
Estimated pulse wave velocity (ePWV) has been proposed as a potential approach to estimate carotid-femoral pulse wave velocity. However, the potential of ePWV in predicting all-cause mortality (ACM) and cardiovascular disease mortality (CVM) in the general population is unclear.

Methods
We conducted a prospective cohort study using the data of 33,930 adults (age ≥ 20 years) from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014 until the end of December 2019. The study outcomes included ACM and CVM. Survey-weighted Cox proportional hazards models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association between ePWV and ACM and CVM. To further investigate whether ePWV was superior to traditional risk factors in predicting ACM and CVM, comparisons between ePWV and the Framingham Risk Score (FRS) and Pooled Cohort Equations (PCE) models were performed. Integrated Discriminant Improvement (IDI) and Net Reclassification Improvement (NRI) were employed to analyze differences in predictive ability between models.

Results
The weighted mean age of the 33,930 adults included was 45.2 years, and 50.28% of all participants were men. In the fully adjusted Cox regression model, each 1 m/s increase in ePWV was associated with 50% and 49% increases in the risk of ACM (HR 1.50; 95% CI, 1.45–1.54) and CVM (HR 1.49; 95% CI, 1.41–1.57), respectively. After adjusting for FRS, each 1 m/s increase in ePWV was still associated with 29% (HR 1.29; 95% CI, 1.24–1.34) and 34% (HR 1.34; 95% CI, 1.23–1.45) increases in the risk of ACM and CVM, respectively. The area under the curve (AUC) predicted by ePWV for 10-year ACM and CVM were 0.822 and 0.835, respectively. Compared with the FRS model, the ePWV model improved the predictive value of ACM and CVM by 5.1% and 3.8%, respectively, with no further improvement in event classification. In comparison with the PCE model, the ePWV model’s ability to predict 10-year ACM and CVM was improved by 5.1% and 3.5%, and event classification improvement was improved by 34.5% and 37.4%.

Conclusions
In the U.S. adults, ePWV is an independent risk factor for ACM and CVM and is independent of traditional risk factors. In the general population aged 20 to 85 years, ePWV has a robust predictive value for the risk of ACM and CVM, superior to the FRS and PCE models. The predictive power of ePWV likely originates from the traditional risk factors incorporated into its calculation, rather than from an indirect association with measured pulse wave velocity.
Physical activity improves stress load, recovery, and academic performance-related parameters among university students: a longitudinal study on daily level
Authors: Teuber Monika , Leyhr Daniel , Sudeck Gorden 
Published: February 2024

AbstractBackgroundPhysical activity has been proven to be beneficial for physical and psychological health as well as for academic achievement. However, especially university students are insufficiently physically active because of difficulties in time management regarding study, work, and social demands. As they are at a crucial life stage, it is of interest how physical activity affects university students' stress load and recovery as well as their academic performance.MethodsStudent´s behavior during home studying in times of COVID-19 was examined longitudinally on a daily basis during a ten-day study period (N = 57, agedM = 23.5 years,SD = 2.8, studying between the 1st to 13th semester (M = 5.8,SD = 4.1)). Two-level regression models were conducted to predict daily variations in stress load, recovery and perceived academic performance depending on leisure-time physical activity and short physical activity breaks during studying periods. Parameters of the individual home studying behavior were also taken into account as covariates.ResultsWhile physical activity breaks only positively affect stress load (functional stress b = 0.032,p < 0.01) and perceived academic performance (b = 0.121,p < 0.001), leisure-time physical activity affects parameters of stress load (functional stress: b = 0.003,p < 0.001, dysfunctional stress: b = -0.002,p < 0.01), recovery experience (b = -0.003,p < 0.001) and perceived academic performance (b = 0.012,p < 0.001). Home study behavior regarding the number of breaks and longest stretch of time also shows associations with recovery experience and perceived academic performance.ConclusionsStudy results confirm the importance of different physical activities for university students` stress load, recovery experience and perceived academic performance in home studying periods. Universities should promote physical activity to keep their students healthy and capable of performing well in academic study: On the one hand, they can offer opportunities to be physically active in leisure time. On the other hand, they can support physical activity breaks during the learning process and in the immediate location of study.
Multifaceted ORganizational InterventiONs (M-ORION) project for prevention of depression and anxiety among workers: study protocol for a five-arm cluster randomized controlled trial
Authors: Watanabe Kazuhiro , Hikichi Hiroyuki , Imamura Kotaro , Sakuraya Asuka , Yoshikawa Toru , Izawa Shuhei , Eguchi Hisashi , Inoue Akiomi , Yoshida Kengo , Orihashi Yasushi , Tsutsumi Akizumi 
Published: February 2024

Abstract
Background
Depression and anxiety are the most common mental health issues experienced by workers. Although organizational intervention has been extensively evaluated as a primary prevention of depression and anxiety, the corresponding scientific evidence remains limited because of the lack of cluster randomized controlled trials (cRCT) and failure to detect organizational-level effects. Therefore, the present study aims to assess the preventive effects of four types of interventions on depression and anxiety among workers in an open, five-arm, parallel-group cRCT.

Methods
Overall, 140 worksites and 18,200 nested employees will be recruited from September 2023. The eligible worksites will be randomly assigned to each of the five arms, and programs will be offered for 6–12 months. The five arms are 1) psychoeducation for workers, 2) psychoeducation for supervisors, 3) work environment improvement, 4) physical activity promotion, and 5) active control. The primary outcomes of interest are depression and anxiety. We will also assess psychosocial factors at work, work engagement, health-related quality of life, well-being, economic outcomes, physiological outcomes of health checkups, cortisol levels extracted from fingernails, and indices representing the process and implementation outcomes, including program completion rates. Follow-up surveys will be conducted at 6, 12, and 18 months from baseline, and the primary endpoint is set at the 6-month follow-up. Repeated-measures multi-level mixed modeling will be used to evaluate the effect of each intervention compared with the control.

Ethics and dissemination
The study protocol was approved by the Research Ethics Committee of the Kitasato University Medical Ethics Organization (C22-082). The results and findings of this study will be published in a scientific journal and disseminated to companies that participate in the study.

Trial registration number
UMIN000050949.
Primary endobronchial melanoma: a case report and clinical management indications
Authors: Barisione Emanuela , Boutros Andrea , Mora Marco , Spagnolo Francesco , Tanda Enrica Teresa , Genova Carlo , Tagliabue Elena 
Published: February 2024

Abstract
Background
While cutaneous melanomas are well-documented, primary melanoma of the lung (PMML), particularly with endobronchial origin, remains rare and poorly characterized. This case report addresses gaps in understanding by presenting a comprehensive case of a 71-year-old male with primary endobronchial melanoma and conducting a systematic review of PMML cases.

Case Presentation
The patient, a former smoker, presented with dyspnea, cough, and hemoptysis. Imaging revealed left lung atelectasis and a suspicious nodule. Bronchoscopy identified an endobronchial mass, subsequently treated with argon plasma coagulation and resection. Biopsy confirmed melanoma. Extensive examinations ruled out a primary skin lesion. Despite initial treatment, recurrence led to pneumonectomy. Histopathology confirmed melanoma. The patient received treatment with pembrolizumab and ipilimumab, but with poor clinical benefit.

Conclusions
Primary endobronchial melanoma is a rare entity, comprising 0.01% of lung tumors. This case underscores diagnostic challenges and emphasizes histological criteria to distinguish primary from metastatic lesions. The pathogenesis remains unclear, with theories proposing foetal melanocyte migration or squamous metaplasia. Prognosis varies, necessitating radical surgical extirpation. A systematic review revealed diverse outcomes, supporting the need for further research. In conclusion, endobronchial melanoma involves an endoscopic and surgical management, but evolving therapies, such as immunotherapy, may reshape treatment paradigms. This case contributes to our understanding of PMML, guiding future research and clinical management. As therapeutic options evolve, continued research is crucial to refine our understanding and improve outcomes for this rare malignancy.
Comparative evaluation of treatment of angular bone defect related to over-erupted tooth using guided tissue regeneration (GTR) followed by orthodontic intrusion (OI) versus OI followed by GTR: a controlled clinical trial
Authors: Ghouraba Rehab F. , Abotaha Neveen Fakhry , Sagha Sara Mohamed Ahmed 
Published: February 2024

Abstract
Background
Prematurity resulted from pathological migration of periodontally involved teeth with the loss of vertical stopping points between teeth, which can lead to teeth over eruption with dimensional changes favoring occlusal discrepancies. Therefore, evaluating and comparing the effect of guided tissue regeneration followed by orthodontic intrusion as opposed to orthodontic intrusion tracked by guided tissue regeneration in the treatment of an over-erupted tooth with angular bone loss.

Methods
Twenty teeth in ten cases were selected with at least two teeth with vertical over-eruption and angular bone loss with the presence of their opposing. In group one, ten teeth over-erupted were treated by guided tissue regeneration followed by orthodontic intrusion, whereas, in group two, ten teeth over-erupted were treated by orthodontic intrusion followed by guided tissue regeneration. They were evaluated clinically for pocket depth, bleeding on probing, and tooth mobility. Radiographical evaluation assessed by cone beam computed tomography.

Results
Clinically, there existed a statistically significant difference (P value ≤ 0.05) in favor of group one at six months post and in favor of group two at one year from re-evaluation regarding pocket depth and tooth mobility. Radiographically, in group one, there was a statistically significant improvement (P value ≤ 0.05) at six months post-guided tissue regeneration or orthodontic intrusion regarding defect depth and dimensional changes of the defect area, with a statistically significant difference (P value ≤ 0.05) in favor of group two at one year from re-evaluation phase regarding defect depth and defect area dimensional changes.

Conclusion
There was a short-term improvement in group one, which deteriorated over a long period compared with group two, so it is preferable to start orthodontic intrusion before guided tissue regeneration.
Artificial intelligence for radiographic imaging detection of caries lesions: a systematic review
Authors: Albano Domenico , Galiano Vanessa , Basile Mariachiara , Di Luca Filippo , Gitto Salvatore , Messina Carmelo , Cagetti Maria Grazia , Del Fabbro Massimo , Tartaglia Gianluca Martino , Sconfienza Luca Maria 
Published: February 2024

Abstract
Background
The aim of this systematic review is to evaluate the diagnostic performance of Artificial Intelligence (AI) models designed for the detection of caries lesion (CL).

Materials and methods
An electronic literature search was conducted on PubMed, Web of Science, SCOPUS, LILACS and Embase databases for retrospective, prospective and cross-sectional studies published until January 2023, using the following keywords: artificial intelligence (AI), machine learning (ML), deep learning (DL), artificial neural networks (ANN), convolutional neural networks (CNN), deep convolutional neural networks (DCNN), radiology, detection, diagnosis and dental caries (DC). The quality assessment was performed using the guidelines of QUADAS-2.

Results
Twenty articles that met the selection criteria were evaluated. Five studies were performed on periapical radiographs, nine on bitewings, and six on orthopantomography. The number of imaging examinations included ranged from 15 to 2900. Four studies investigated ANN models, fifteen CNN models, and two DCNN models. Twelve were retrospective studies, six cross-sectional and two prospective. The following diagnostic performance was achieved in detecting CL: sensitivity from 0.44 to 0.86, specificity from 0.85 to 0.98, precision from 0.50 to 0.94, PPV (Positive Predictive Value) 0.86, NPV (Negative Predictive Value) 0.95, accuracy from 0.73 to 0.98, area under the curve (AUC) from 0.84 to 0.98, intersection over union of 0.3–0.4 and 0.78, Dice coefficient 0.66 and 0.88, F1-score from 0.64 to 0.92. According to the QUADAS-2 evaluation, most studies exhibited a low risk of bias.

Conclusion
AI-based models have demonstrated good diagnostic performance, potentially being an important aid in CL detection. Some limitations of these studies are related to the size and heterogeneity of the datasets. Future studies need to rely on comparable, large, and clinically meaningful datasets.

Protocol
PROSPERO identifier: CRD42023470708