bluuebunny/crossref_metadata_2025_split huggingface dataset:
A non-inferiority randomized phase III trial of standard immunotherapy by checkpoint inhibitors vs. reduced dose intensity in responding patients with metastatic cancer: the MOIO protocol study
Authors: Gravis Gwenaelle , Marino Patricia , Olive Daniel , Penault-LLorca Frederique , Delord Jean-Pierre , Simon Clotilde , Lamrani-Ghaouti Assia , Sabatier Renaud , Ciccolini Joseph , Boher Jean-Marie 
Published: May 2023

Abstract
Background
Immunotherapy (IO) has become a standard of care for treating various types of metastatic cancers and has significantly improved clinical outcome. With the exception of metastatic melanoma in complete response for which treatment can be stopped at 6 months, these treatments are currently administered until either disease progression for some IO, 2 years for others, or unacceptable toxicity. However, a growing number of studies are reporting maintenance of response despite discontinuation of therapy. There is currently no evidence of a dose effect of IO in pharmacokinetic studies. Maintaining efficacy despite a reduction in treatment intensity by decreasing the frequency of administration in patients with highly selected metastatic cancer, is the hypothesis evaluated in the MOIO study.

Method/design
This non-inferiority, randomized phase III study aims to compare the standard regimen to a 3 monthly regimen of variousIO drugs in adult patients with metastatic cancer in partial (PR) or complete response (CR) after 6 months of standard IO dosing (except melanoma in CR). This is a French national study conducted in 36 centers. The main objective is to demonstrate that the efficacy of a three-monthly administration is not unacceptably less efficacious than a standard administration. Secondary objectives are cost-effectiveness, quality of life (QOL), anxiety, fear of relapse, response rate, overall survival and toxicity.
After 6 months of standard IO, patients with partial or complete response will be randomized 1:1 between standard IO or a reduced intensity dose of IO, administered every 3 months. The randomization will be stratified on therapy line,, tumor type, IO type and response status. The primary endpoint is the hazard ratio of progression-free survival. With a planned study duration of 6 years, including 36 months enrolment time, 646 patients are planned to demonstrate with a statistical level of evidence of 5% that the reduced IO regimen is non-inferior to the standard IO regimen, with a relative non-inferiority margin set at 1.3.

Discussion
Should the hypothesis of non-inferiority with an IO reduced dose intensity be validated, alternate scheduling could preserve efficacy while being cost-effective and allowing a reduction of the toxicity, with an increase in patient’s QOL.

Trial registration
NCT05078047.
Evaluation of biometric indicators of anterior segment parameters after ICL implantation by swept-source optical coherence tomography
Authors: Tang Chuhao , Sun Tong , Sun Zhengze , Duan Hongyu , Liu Yilin , Zhao Lu , Li Wenlong , Bian Linbo , Qi Hong 
Published: May 2023

Abstract
Background
To evaluate anterior segment structural alterations after implantable collamer lens (ICL) implantation in myopic patients using swept-source quantitative optical coherence tomography (SS-OCT).

Methods
This prospective study included 47 eyes in 24 patients with preoperative spherical equivalent ≥ -3.00 D. Patients underwent ICL implantation at Department of Ophthalmology, Peking University Third Hospital, from May 2021 to December 2022. SS-OCT was used to measure anterior chamber width (ACW), angle opening distance (AOD), angle recess area (ARA), trabecular-iris area (TISA), trabecular-iris angle (TIA), iridotrabecular contact (ITC) area, and ITC Index before ICL implantation surgery and at 1 month follow-up. The correlations among the ITC index, vault, and angle parameters were analysed. Receiver operating characteristic (ROC) analysis was used to explore the ability of the vault to identify eyes with suspected angle-closure.

Results
At one month following ICL implantation, the ITC area was 0.396 ± 0.37 mm2, and the ITC index is 8.143 ± 5.439%. All angle parameters, except ACW, showed a statistically significant reduction on SS-OCT (P < 0.05). Mean AOD500, AOD750, ARA500, ARA750, TISA500, TISA750, TIA500, and TIA750 values at one month postoperatively decreased by 60.0%, 60.4%, 58.1%, 59.2%, 57.3%, 58.7%, 48.8%, and 50.7%, respectively. The vault was positively correlated with the ITC index and percent change in anterior chamber angle parameters. A vault of > 0.659 mm was found to be optimal for angle-closure suspect with a sensitivity of 85.2% and a specificity of 53.9%.

Conclusions
Anterior chamber angle parameters decreased one month after ICL implantation, and their percentage changes and ITC index correlated with the vault. When the vault is larger than 0.659 mm, it is necessary to be alert to possible closed angle suspicion.
Candidate genes identification and RNA-seq based pathway analysis associated with primary angle-closure glaucoma with cataract
Authors: Liu Min , Hu Fei , Lei Caifeng , Fu Min , Li Xue , Yu Ling 
Published: May 2023

AbstractBackgroundCataract is commonly observed in patients with primary angle-closure glaucoma; however, its underlying pathological mechanisms remain unclear. This study aimed to improve our knowledge on the pathological processes involved in primary angle-closure glaucoma (PACG) by identifying potential prognostic genes associated with cataract progression.MethodsThirty anterior capsular membrane samples were collected from PACG patients with cataracts and age-related cataracts. Differentially expressed genes (DEGs) between these two cohorts were analyzed using high-throughput sequencing. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to screen the DEGs, and potential prognostic markers and their coexpression network were then predicted by bioinformatic analyses. The DEGs were further validated by reverse transcription-quantitative polymerase chain reaction.ResultsA total of 399 DEGs were found to be specifically associated with cataracts development in PACG patients, among which 177 and 221 DEGs were upregulated and downregulated, respectively. STRING and Cytoscape network analyses revealed seven genes—CTGF,FOS,CAV1,CYR61,ICAM1,EGR1, andNR4A1—that were remarkably enriched and mainly involved in the MAPK, PI3K/Akt, Toll-like receptor, and TNF signaling pathways. RT-qPCR-based validation further confirmed that the sequencing results were accurate and reliable.ConclusionsHerein, we identified seven genes and their signaling pathways that may contribute to cataract progression in patients with high intraocular pressure. Taken together, our findings highlight new molecular mechanisms that may explain the high incidence of cataracts in PACG patients. In addition, the genes identified herein may represent new foundations for the development of therapeutic strategies for PACG with cataract.
Comparison of long-term effects of metformin on longevity between people with type 2 diabetes and matched non-diabetic controls
Authors: Stevenson-Hoare Joshua , Leonenko Ganna , Escott-Price Valentina 
Published: May 2023

Abstract
Background
Metformin, a medication for type 2 diabetes, has been linked to many non-diabetes health benefits including increasing healthy lifespan. Previous work has only examined the benefits of metformin over periods of less than ten years, which may not be long enough to capture the true effect of this medication on longevity.

Methods
We searched medical records for Wales, UK, using the Secure Anonymised Information Linkage dataset for type 2 diabetes patients treated with metformin (N = 129,140) and sulphonylurea (N = 68,563). Non-diabetic controls were matched on sex, age, smoking, and history of cancer and cardiovascular disease. Survival analysis was performed to examine survival time after first treatment, using a range of simulated study periods.

Findings
Using the full twenty-year period, we found that type 2 diabetes patients treated with metformin had shorter survival time than matched controls, as did sulphonylurea patients. Metformin patients had better survival than sulphonylurea patients, controlling for age. Within the first three years, metformin therapy showed a benefit over matched controls, but this reversed after five years of treatment.

Interpretation
While metformin does appear to confer benefits to longevity in the short term, these initial benefits are outweighed by the effects of type 2 diabetes when patients are observed over a period of up to twenty years. Longer study periods are therefore recommended for studying longevity and healthy lifespan.

Evidence before this study
Work examining the non-diabetes outcomes of metformin therapy has suggested that there metformin has a beneficial effect on longevity and healthy lifespan. Both clinical trials and observational studies broadly support this hypothesis, but tend to be limited in the length of time over which they can study patients or participants.

Added value of this study
By using medical records we are able to study individuals with Type 2 diabetes over a period of two decades. We are also able to account for the effects of cancer, cardiovascular disease, hypertension, deprivation, and smoking on longevity and survival time following treatment.

Implications of all the available evidence
We confirm that there is an initial benefit to longevity of metformin therapy, but this benefit does not outweigh the negative effect on longevity of diabetes. Therefore, we suggest that longer study periods are required for inference to be made about longevity in future research.
Prevalence and factors associated with sexual and reproductive health services use among reproductive age women with disabilities: a community based cross-sectional study
Authors: Rade Bayew Kelkay , Tamiru Animut Tagele , Aynalem Getie Lake , Taye Eden Bishaw , Melkie Mamaru , Abera Alamirew , Cherkos Endeshaw Admassu , Asaye Mengstu Melkamu 
Published: May 2023

Abstract
Background
According to International Convention on the Right of Person with Disabilities (CRPD), all nations should discern Sexual and Reproductive Health (SRH) as human rights and needs of all people living with disabilities. Women and girls with disabilities are highly vulnerable to SRH disparities including unintended pregnancy, acquiring sexual transmitted infections and unsafe abortion. Little has known about SRH service uptake and influencing factors among reproductive aged women living with disabilities.

Methods
A community-based cross-sectional study was conducted from January 1–30, 2021, the central Gondar zone selected districts. A total of 535 reproductive-age (18–49 years) women with disabilities had been interviewed through face-to-face using structured questionnaire. Multistage cluster sampling method was applied. A binary logistic regression model was computed to look the relationship between independent variables and uptake of SRH, and p-value < 0.05 was a cut-off point to declare statistical significance.

Results
A total of 33.27% (178/535) women with disabilities used at least one SRH service in the last twelve months preceding the survey. Those who had three or more children [AOR = 4.85; 95% CI (1.24–9.71)], autonomy to visit health care facilities [AOR = 3.30; 95% CI (1.45–6.92)], lived with sexual partner [AOR = 9.2; 95% CI (2.84–13.60)], subjected to radio/television in daily bases [AOR = 5.9; 95% CI (1.26–13.04)], autonomy to visit friends and relatives [AOR = 3.95; 95% CI (1.28–12.17)], had a discussion with family members about sexual and reproductive health [AOR = 9.36; 95% CI (3.44–17.47)], and engaged in sexual activity after the age of 18 years [AOR = 7.2; 95% CI (2.51–14.45)] were important predictors for service uptake.

Conclusions
Only one in three reproductive age women with disabilities used at least one SRH service. These findings suggest that accessing information through mainstream media exposure, having full autonomous to visit friends and families, open discussion with family members, live with sexual partner, having optimal family size and starting sexual act at the recommended age improve the uptake of SRH services. Therefore, the stakeholders (both governmental and non-governmental) need to make efforts to increase the uptake of SRH services.
Effective formative assessment for pharmacy students in Thailand: lesson learns from a school of pharmacy in Thailand
Authors: Sottiyotin Tida , Uitrakul Suriyon , Sakdiset Pajaree , Sukkarn Bhudsaban , Sangfai Thanachaporn , Chuaboon Litavadee , Palee Patsamon 
Published: May 2023

Abstract
Introduction
: Formative assessment (FA) is an assessment concept that is of interest in education. The Doctor of Pharmacy program is one of the programs in which FA is usually implemented. This study aimed to describe the correlation between FA scores and summative assessment (SA) scores and to suggest possible key success factors that affect the effectiveness of FA.

Methods
This study employed a retrospective design using mixed methods for data collection. Data in the semesters 1/2020 and 2/2020 of the Doctor of Pharmacy curriculum in a Thailand pharmacy school were used. Three sets of data were gathered, including the course information (e.g. FA methods, FA scores, and SA scores) from 38 records, self-reports from 326 students and 27 teachers, and 5 focus group discussions. The quantitative data were statistically analyzed using descriptive statistics and Pearson correlation, while the qualitative data were analyzed using a content analysis framework.

Results
The analysis revealed five main methods that were used for FA, including individual quizzes, individual reports, individual skill assessments, group presentations, and group reports. Of all 38 courses, 29 (76.32%) had significant correlations between FA and SA scores at p-values < 0.05. The individual FA score was related to the correlation coefficient of the courses (p-value = 0.007), but the group FA score was not related (p-value = 0.081). In addition, only the frequency of individual quiz had a significant effect on the correlation coefficient. Moreover, the key success factors which affected the effectiveness of FA were divided into six themes, including the appropriate method, an effective reflection, frequency of assessment, the appropriate score, the adequate support system, and teacher knowledge management.

Conclusion
The subjects that used individual FA methods provided a significant correlation between FA and SA, while those who used group FA methods did not show a significant correlation. Additionally, the key success factors in this study were appropriate assessment methods, frequency of assessment, effective feedback, appropriate scoring, and a proper support system.
Assessing cultural safety in general practice consultations for Indigenous patients: protocol for a mixed methods sequential embedded design study
Authors: Brumpton Kay , Ward Raelene , Evans Rebecca , Neill Henry , Woodall Hannah , McArthur Lawrie , Sen Gupta Tarun 
Published: May 2023

AbstractBackgroundAssessment of cultural safety in general practice consultations for Indigenous patients is a complex notion. Design and development of any assessment tool needs to be cognizant that cultural safety is determined by Indigenous peoples and incorporates defined components of cultural safety and current educational theory. Consideration of how social, historical, and political determinants of health and well-being impact upon the cultural safety of a consultation is also important. Given this complexity, we assume that no single method of assessment will be adequate to determine if general practice (GP) registrars are demonstrating or delivering culturally safe care. As such, we propose that development and assessment of cultural safety can be conceptualised using a model that considers these variables. From this, we aim to develop a tool to assess whether GP registrars are conducting a culturally safe consultation, where cultural safety is determined by Aboriginal and Torres Strait Islander peoples.MethodsThis protocol will be situated in a pragmatic philosophical position to explore cultural safety primarily from the Australian Aboriginal and Torres Strait Islander patients’ perspective with triangulation and validation of findings with the GP and GP registrar perspective, the Aboriginal and Torres Strait Islander community, and the medical education community. The study will integrate both quantitative and qualitative data through three sequential phases. Data collection will be through survey, semi-structured interviews, an adapted nominal group technique, and a Delphi questionnaire. We aim to recruit approximately 40 patient and 20 GP participants for interviews, conduct one to five nominal groups (seven to 35 participants) and recruit fifteen participants for the Delphi process. Data will be analysed through a content analysis approach to identify components of an assessment of cultural safety for GP registrars.DiscussionThis study will be one of the first to explore how cultural safety, as determined by Indigenous peoples, can be assessed in general practice consultations. This protocol is shared to stimulate awareness and discussion around this significant issue and prompt other studies in this area.
The reliability and validity of the training elements scale for clinicians in the new era——based on the perspective of Chinese doctors’ job demands
Authors: Jin Weiqiong , Fang Yinghui , Zhang Yuchen , Lv Yijun 
Published: May 2023

Abstract
Objective
The purpose of this study was to develop a scale of clinician training elements in the new period and test its reliability and validity.

Methods
Our approach was based on interdisciplinary theory, systematology, collaborative innovation theory, and whole person education theory combined with the existing post competency model of Chinese doctors and the responsibilities and requirements endowed clinicians in the new historical period. The scale elements were extracted by referring to the relevant literature, and the training elements scale for clinicians in the new period were preliminarily formed. From July to August 2022, 1,086 clinicians from tertiary medical institutions in eastern, central, and western China were sampled and investigated. The questionnaire was revised via the critical ratio method and homogeneity test method, and the reliability and validity of the scale were also tested.

Results
The training elements scale for clinicians in the new period included the following eight dimensions: basic clinical knowledge, interdisciplinary knowledge, clinical skill operation, public health knowledge, technological innovation capability, lifelong learning needs, medical humanistic literacy, and international exchange vision, as well as 51 other items. The Cronbach’s α coefficient of the scale was 0.981, the half-reliability was 0.903, and the average variance extraction of each dimension was greater than 0.5. An exploratory factor analysis extracted eight main factors, and the cumulative variance contribution rate was 78.524%. Confirmatory factor analysis showed that the model fit was ideal and the factor structure was stable.

Conclusion
The clinician training factor scale in the new era can fully meet the current training needs of r clinicians, and has good reliability and validity. It can be widely used in medical colleges and universities as a reference to reform the content of medical training and education, and can also be used in the continuing education of clinicians after graduation to compensate for gaps in knowledge during clinical work.
Style and influencing factors of tutors-postgraduates’ interactions in Chinese medical colleges: a cross-sectional survey in Heilongjiang Province
Authors: Wang Mingsi , Wang Yanping , Fang Ming , Zhang Shue , Li Yilan , Cao Depin , Jin Yan 
Published: May 2023

Abstract
Objectives
This study assesses the style of tutor-postgraduate interactions in Chinese medical colleges and explores the association between postgraduates’ demographic factors and tutors’ demographic characteristics.

Methods
With the stratified sampling method, a cross-sectional online survey was used. A total of 813 medical postgraduates were recruited as participants, with an effective response rate of 85.49%. The two dimensions of “Professional Ability Interaction” and “Comprehensive Cultivation Interaction” in the self-developed “Instructor-Graduate Interaction Scale for Medical Colleges” were used as dependent variables. And tutors’ demographic characteristics and postgraduates’ demographic characteristics were taken as independent variables. Logistic regression analysis was used to explore the influencing factors of Tutor-Postgraduates Interactions in medical colleges.

Results
The Tutor-Postgraduates Interaction scale consists of 14 items from the two dimensions of “Professional Ability Interaction” and “Comprehensive Cultivation Interaction”. The results of the logistic regression analysis show the reasons for selecting the mentor students (industry recognition, the tutor’s research direction, charm in attracting mentors, and recommendations for mentor selection); student to mentor satisfaction; student to study life satisfaction; and regular academic seminars. Indirect guidance and a high postgraduate grade high are the protective factors of interaction between tutors and postgraduates of medical colleges and universities postgraduates. Older mentors and more graduate tutors are the risk factors for Tutor-Postgraduates Interaction in medical colleges (P < 0.05).

Conclusion
The current study proposes that managers should pay more attention to the double-track promotion of “Professional Ability Interaction” and “Comprehensive Cultivation Interaction”. We should not only pay attention to the cultivation of postgraduates’ professional ability but also pay more attention to the comprehensive cultivation including postgraduates’ mental and psychological aspects. The interaction between tutors and postgraduates in medical colleges is generally good, but much attention should be given to the dual-track promotion mentioned above. Regular academic seminars play an important role in the process of postgraduate training. The research findings, including the influencing factors regarding tutor-postgraduate interactions, the Professional Ability Interaction and Comprehensive Cultivation Interaction, are very informative and can contribute to strategies for postgraduate management systems that enhance this relationship.