bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Measurement of Developmental Dysplasia of the Hip: Comparing Two Approaches for Measuring the Alpha Angle Using the Graf Technique
Authors: Dindar Fırat , Aylanç Nilüfer , Aylanç Hakan , Ertem Şenay Bengin , Sıddıkoğlu Duygu , Reşorlu Mustafa 
Published: February 2025

Objective: The Graf method, in ultrasonography screening of developmental hip dysplasia, is based on angle measurements. Using different reference points may cause varied results. The aim of this study was to investigate to what extent the alpha angle obtained, varied at different reference points. Materials and Methods: There were 178 hips evaluated by two trained observers. Both measured the alpha angle with different reference points and these were labeled as methods A and B, for all the hips evaluated. The statistical analysis was performed with SPSS Version 21. Results: The average of observer 1, based on measurements with method A, were 65.63 (SD ±5.95) and based on method B were 73.39 (SD ±6.29). The average of the measurements of observer 2, utilizing method A were 64.39 (SD ±4.85) and based on method B were 69.92 (SD ±6.08). It was observed that method B showed higher mean and variability compared to method A. The agreement between observers was moderate in method A and poor in method B. The intraobserver correlation coefficient (ICC) was 0.69 for method A and 0.47 for method B. The ICC was considered good (e.g., 95%) for both observers in terms of using methods A and B. Conclusion: The use of ultrasonography still maintains its place in the diagnosis of developmental hip dysplasia. The Graf method is based on precise measurements, and the most decisive parameter is the alpha angle. Reference points in method A would be more useful in patient management and may increase the diagnostic accuracy.
Radiological outcomes of surgical techniques for spastic hip in cerebral palsy: a systematic review and meta-analysis
Authors: Menbari Oskouie Iman , Hakiminejad Alireza , Yazdanmehr Amirali , Mostafavi Keihan , Mafhoumi Asma , Sajedi Amir H. , Roosta Ali , Arvin Alireza , Presedo Ana , Nabian Mohammad Hossein , Kasaeian Amir 
Published: February 2025

Abstract

Background
In patients with cerebral palsy (CP), spastic hip is a prevalent complication. Various surgical approaches,, including pelvic osteotomy (PO), femoral osteotomy (FO), combined femoral and pelvic osteotomy (CFPO), and soft tissue surgery (STS), have been used to address this problem. This systematic review and meta-analysis was designed to compare the radiologic outcomes of these interventions for spastic hip in patients with CP.

Methods
To identify relevant studies, databases were searched using specific keywords. Initially, duplicates were removed, then the titles and abstracts were screened, followed by a comprehensive full-text review. Data extraction took place from the studies that met the inclusion criteria. Subsequently, a meta-analysis was conducted.

Results
The analysis of 6116 hips from 4546 patients across 81 studies demonstrated that PO significantly enhanced the center–edge angle (CEA), reduced the acetabular index (AI) and migration percentage (MP), and improved the Sharp and Tönnis angles. FO led to a substantial decrease in AI and MP, though CEA did not show a significant change, while CFPO resulted in significant improvements across AI, MP, neck-shaft angle (NSA), CEA, Sharp angle, and Tönnis angle. STS did not show significant changes in AI or CEA, but MP was notably reduced. Tone-decreasing procedures, such as selective dorsal rhizotomy and botulinum toxin injections, did not significantly alter MP, whereas guided growth techniques showed a significant reduction. MP improvements in FO decreased over time, with other radiologic parameters remaining relatively stable as follow-up increased. Age-specific trends indicated that children under 6 years primarily underwent tone-decreasing procedures and STS, while those around 7 years favored FO and guided growth, and older children (over 9 years) more commonly underwent PO, CFPO, or percutaneous osteotomy. Comparative analysis showed PO and percutaneous osteotomy were particularly more effective in reducing MP, with PO also being superior for AI improvement; whereas CFPO provided better outcomes for enhancing CEA. No significant differences were found among surgical methods for improving NSA.

Conclusions
This systematic review and meta-analysis underscores the superior efficacy of PO and CFPO in correcting spastic hip deformity in children with CP. Radiological outcomes demonstrate significant improvements following these procedures. The findings suggest that these approaches are particularly effective for complex cases where procedures such as FO, STS, or TDS may fall short. Future studies should focus on refining surgical protocols and exploring the long-term functional outcomes of these interventions.
Assessing non-inferiority for binary matched-pairs data with missing values: a powerful and flexible GEE approach based on the risk difference
Authors: Hengelbrock Johannes , Konietschke Frank , Herm Juliane , Audebert Heinrich , Aigner Annette 
Published: February 2025

Abstract

Background
Clinical studies often aim to test the non-inferiority of a treatment compared to an alternative intervention with binary matched-pairs data. These studies are often planned with methods for completely observed pairs only. However, if missingness is more frequent than expected or is anticipated in the planning phase, methods are needed that allow the inclusion of partially observed pairs to improve statistical power.

Methods
We propose a flexible generalized estimating equations (GEE) approach to estimate confidence intervals for the risk difference, which accommodates partially observed pairs. Using simulated data, we compare this approach to alternative methods for completely observed pairs only and to those that also include pairs with missing observations. Additionally, we reconsider the study sample size calculation by applying these methods to a study with binary matched-pairs setting.

Results
In moderate to large sample sizes, the proposed GEE approach performs similarly to alternative methods for completely observed pairs only. It even results in a higher power and narrower interval widths in scenarios with missing data and where missingness follows a missing (completely) at random (MCAR / MAR) mechanism. The GEE approach is also non-inferior to alternative methods, such as multiple imputation or confidence intervals explicitly developed for missing data settings. Reconsidering the sample size calculation for an observational study, our proposed approach leads to a considerably smaller sample size than the alternative methods.

Conclusion
Our results indicate that the proposed GEE approach is a powerful alternative to existing methods and can be used for testing non-inferiority, even if the initial sample size calculation was based on a different statistical method. Furthermore, it increases the analytical flexibility by allowing the inclusion of additional covariates, in contrast to other methods.
An early evaluation of team consistency and scope optimization in team-based cancer care
Authors: Lambert Leah K. , Havaei Farinaz , Beck Scott M. , Ma Andy , Larmet John , Kaur Jagbir , Adhami Nassim , Le Dan , Woods Ryan 
Published: February 2025

Abstract

Background
The British Columbia (BC) government has made significant investments towards the implementation of team-based care (TBC) in its provincial comprehensive cancer control program. TBC implementation involves purposeful efforts towards: (a) establishing/expanding multidisciplinary care teams, (b) optimizing scope of practice, and (c) increasing care team consistency. Study objectives include an early-phase evaluation of (i) the association between TBC elements and team effectiveness and (ii) staff perceptions of barrier and facilitators of team effectiveness.

Methods
A series of five surveys over a 2-year period will be administered to prospectively evaluate the ongoing implementation of TBC. This study draws on data from the first of the five planned surveys, administered in May 2023. Eligible respondents included 299 program employees—spanning various roles such as physicians, nurses, and unit clerks—working within TBC at the time of survey deployment. The survey included both validated and researcher-developed questions that were either closed or open-ended, including measures of team composition, team consistency, team effectiveness, scope of practice, and demographics. Quantitative data were analyzed using descriptive and regression analysis; qualitative data were analyzed guided by interpretive description methodology.

Results
Collected responses totaled 121, with the majority of respondents being women (76%), full-time employees (90%), and working in direct patient care (77%). Regression analyses indicated that (i) higher frequency of consistently working with the same team members and (ii) lower proportion of shifts practicing below scope are both significant predictors of higher team effectiveness ratings. Qualitative data highlighted staffing levels as a driver of under- and over-utilized scopes of practice. Furthermore, effective communication, enhanced knowledge of each team member’s scope of practice, and strong interpersonal relationships were highlighted as contributing factors to effectiveness among multidisciplinary care teams.

Conclusions
Preliminary findings from the first of five prospective surveys highlight team consistency and role optimization as drivers of effective teamwork in the early implementation of a team-based model of cancer care. Future research should explore contextual factors that influence cancer care staff and clinicians’ perceptions of effectiveness.
The potential radiosensitization target PFKFB3 is related to response to radiotherapy in SweBCG91RT: a randomized clinical trial with long-term follow-up
Authors: Egelberg Moa , De Marchi Tommaso , Schultz Niklas , Tran Lena , Karlsson Per , Holmberg Erik , Pekar Gyula , Killander Fredrika , Niméus Emma 
Published: February 2025

Abstract

Background
Several cancer types have increased PFKFB3, a glycolytic enzyme for which potent inhibitors have been found. Inhibition of PFKFB3 impairs DNA repair after irradiation of cancer cells, making it a possible radiosensitization target. The SweBCG91RT trial, in which breast cancer patients were randomized to postoperative radiotherapy or not, was used to investigate PFKFB3 as a clinical marker of sensitivity to adjuvant radiotherapy.

Methods
Nuclear protein levels of PFKFB3 were assessed with immunohistochemistry in primary breast tumors (n = 970) and whole-cell RNA levels with microarray gene expression (n = 765). Multivariable competing risks regression analysis was employed for the effect of radiotherapy on incidence of ipsilateral breast tumor recurrence (IBTR), depending on PFKFB3 levels.

Results
Tumors with high levels of nuclear protein and RNA had the largest effect on incidence of IBTR of adjuvant radiotherapy, however without evidence of an interaction. PFKFB3 RNA correlated with subtype, as high levels were more common among the human epidermal growth factor receptor 2 (HER2) positive and Luminal A subtypes than Luminal B and triple negative tumors.

Conclusion
High PFKFB3 is associated with a larger reduction of IBTR after radiotherapy but PFKFB3 cannot reliably be used as a predictive marker of sensitivity to adjuvant radiotherapy in breast cancer. PFKFB3 expression differed with subtype, indicating that it may be a better marker among Luminal A and HER2 positive tumors, but this is yet to be investigated.

Trial registration
The trial has been retrospectively registered at clinicaltrials.gov 2024-10-03 (NCT06637202).
Implementing the flipped classroom model to enhance knowledge retention in pharmacology: a local case study at Semmelweis university
Authors: Onódi Zsófia , Riba Pál , Ferdinandy Péter , Görbe Anikó , Varga Zoltán V. 
Published: February 2025

Abstract

Background
The flipped classroom (FC) approach has demonstrated efficacy in enhancing the learning process, including within higher education contexts such as medical education. Recently, FC has emerged as potential alternative to traditional teaching models across various disciplines, particularly due to its more engaging nature. However, there is limited data available regarding its impact on student performance, particularly in the context of long-term knowledge retention in pharmacology. In this study, our objective was to assess the short- and long-term impact of FC on student performance in Hungarian pharmacology teaching at medical faculty in Semmelweis University (Budapest, Hungary).

Methods and results
161 medical students and 10 teachers were involved in this study. We flipped four seminars, then we assessed the academic performance by using multiple choice tests immediately and two weeks after the flipped class. A follow-up assessment was conducted six months after the initial two FC sessions. Our findings indicated that the FC approach enhanced both short- and long-term knowledge retention across most topics. Notably, this long-term improvement was evident even six months after the original seminars on specific subjects. However, despite these topic-specific benefits, the overall performance, including exam grades, did not show significant improvement when compared to the conventional teaching approach. Additionally, we assessed student and teacher perceptions using two questionnaires immediately after practice and at the end of the year. According to the questionnaire responses, students perceived positively the FC approach, emphasizing its interactive and thought-provoking aspects. However, they identified the time-consuming nature of preparation as a significant concern. Teachers also viewed the FC approach favorably, particularly appreciating its interactivity and potential for greater effectiveness. Interestingly, more experienced teachers were less receptive to the FC method, and their perceptions of it were less favorable compared to those of their younger colleagues.

Conclusions
The flipped classroom approach presents a viable strategy for teaching pharmacology, with the potential to enhance student performance and engagement. However, student occupation and faculty resistance may pose significant challenges to the implementation of such alternative teaching methods.
Between duty and despair: the ethical toll of brain drain on Nepalese nurse managers
Authors: Ghimire Animesh , Neupane Mamata Sharma 
Published: February 2025

Abstract

Background
The relentless exodus of skilled healthcare professionals from low- and middle-income countries to wealthier nations, known as the 'brain drain,' poses a grave threat to global health equity. Nepal, a prime example of a source country, faces a critical shortage of nurses due to this migration. Nurse managers, uniquely positioned at the intersection of leadership and frontline care, face considerable challenges in times of crisis. These challenges encompass ethical dilemmas associated with resource allocation, staffing shortages, and maintaining quality care standards. Additionally, nurse managers must navigate their own experiences of moral distress, further complicating their decision-making processes and overall effectiveness in managing healthcare teams and patient outcomes. This study delves into their lived experiences, aiming to expose the far-reaching consequences of brain drain and spark a global dialogue on ethical and sustainable healthcare workforce practices.

Methods
This qualitative descriptive study examined the lived experiences of ten nurse managers in Nepal, employing semi-structured interviews and inductive content analysis. Participants were chosen through a combination of purposive, snowball, and convenience sampling methods, ensuring representation from both urban and rural settings.

Results
Thematic analysis revealed five core themes: (1) Moral Distress on the Frontlines; (2) Unequal Burden, Unequal Access; (3) The Ripple Effects of Exodus; (4) Beyond the Hippocratic Oath; and (5) Policy at the Crossroads.

Conclusion
Policy interventions prioritizing improving working conditions, investing in the domestic healthcare workforce, and promoting ethical recruitment practices are essential to ensure equitable and sustainable healthcare. The voices of nurse managers at the forefront of this crisis provide a powerful call to action. Their experiences and insights urge national and global stakeholders to recognize the human cost of brain drain and work collaboratively towards a more just and resilient healthcare system.
Molecular evolution of dietary shifts in ladybird beetles (Coleoptera: Coccinellidae): from fungivory to carnivory and herbivory
Authors: Huang Yu-Hao , Escalona Hermes E. , Sun Yi-Fei , Zhang Pei-Fang , Du Xue-Yong , Gong Sen-Rui , Tang Xue-Fei , Liang Yuan-Sen , Yang Dan , Chen Pei-Tao , Yang Huan-Ying , Chen Mei-Lan , Hüttel Bruno , Hlinka Ondrej , Wang Xingmin , Meusemann Karen , Ślipiński Adam , Zwick Andreas , Waterhouse Robert M. , Misof Bernhard , Niehuis Oliver , Li Hao-Sen , Pang Hong 
Published: February 2025

Abstract

Background

Dietary shifts are major evolutionary steps that shape ecological niches and biodiversity. The beetle family Coccinellidae, commonly known as ladybirds, first transitioned from a fungivorous to an insectivorous and subsequently a plant diet. However, the molecular basis of this dietary diversification remained unexplored.

Results
We investigated the molecular evolution of dietary shifts in ladybirds, focusing on the transitions from fungivory to carnivory (Coccinellidae) and from carnivory to herbivory (Epilachnini), by comparing 25 genomes and 62 transcriptomes of beetles. Our analysis shows that chemosensory gene families have undergone significant expansions at both nodes of diet change and were differentially expressed in feeding experiments, suggesting that they may be related to foraging. We found expansions of digestive and detoxifying gene families and losses of chitin-related digestive genes in the herbivorous ladybirds, and absence of most plant cell wall-degrading enzymes in the ladybirds dating from the transition to carnivory, likely indicating the effect of different digestion requirements on the gene repertoire. Immunity effector genes tend to emerge or have specific amino acid sequence compositions in carnivorous ladybirds and are downregulated under suboptimal dietary treatments, suggesting a potential function of these genes related to microbial symbionts in the sternorrhynchan prey.

Conclusions
Our study provides a comprehensive comparative genomic analysis to address evolution of chemosensory, digestive, detoxifying, and immune genes associated with dietary shifts in ladybirds. Ladybirds can be considered a ubiquitous example of dietary shifts in insects, and thus a promising model system for evolutionary and applied biology.
Non-invasive diagnosis of vulvar dysplasia using cervical methylation markers—a case control study
Authors: Becker Sabeth , Dübbel Lena , Behrens Dana , Knoll Kristin , Hippe Juliane , Loser Karin , Malik Eduard , Schild-Suhren Meike 
Published: February 2025

Abstract

Background
Diagnostic screenings for vulvar squamous intraepithelial lesions (VSIL) are limited and without information on disease trends. A panel of six methylation markers (ASTN1, DLX1, ITGA4, RXFP3, SOX17, ZNF671; GynTect® assay) has shown promise in diagnosing cervical intraepithelial neoplasia (CIN). Given the similarities between the carcinogenesis of cervix and vulva, this study aimed to investigate the suitability of these markers for diagnosing vulvar lesions.

Methods
One hundred twenty-one vulvar FFPE samples and 237 vulvar cell smears with different VSIL grades, HPV status, and with or without lichen sclerosus and planus were tested. Additionally, dysplasia-free vulvar cell smears from patients with cervical dysplasia were analyzed. The expression of DNA methyltransferases (DNMTs) in the FFPE samples was measured.

Results
The markers demonstrated high specificity in vulvar smears, with sole 5.45% of dysplasia-free smears testing positive. Yet, 75.00% of vulvar carcinoma smears appear positive in the methylation kit, similar to VHSIL (VIN III) smears with 77.78%. In FFPE samples, dysplasia-free samples from the tumor microenvironment of high-grade vulvar neoplasia showed 43.75% positivity. The positivity rates for VSIL and carcinoma samples were 76.92%, 64.71%, 64.71%, and 80.49%, respectively. DNMT3a expression was the highest in VLSIL (VIN I) samples, while DNMT1 was only expressed in VHSIL (VIN III) and carcinoma samples. Lichen sclerosis and planus showed a high false positive rate of 45.45% for dysplasia-free and 54.54% for smears with dVIN. Cervical HSIL was associated with a significantly higher number of positive results in the kit than in patients without cervical dysplasia.

Conclusions
The findings suggest that the methylation markers comprising GynTect® may be suitable for detecting vulvar neoplasia, as they exhibit high sensitivity. Nonetheless, adjustments are needed for comparable specificity. Lichen should be considered in result interpretation, and the kit should be used with caution for patients with lichen. Moreover, we observed methylation changes as an early event with the highest positivity of VLSIL. Surprisingly, changes in methylation pattern are not as local as presumed. Cervical SIL led to changed methylation in the vulva. Patients with positive kit results should be monitored regularly for all genital dysplasia. This sheds new light on the epigenetics in cancer.