bluuebunny/crossref_metadata_2025 huggingface dataset:
A generative model for evaluating missing data methods in large epidemiological cohorts
Authors: Radosavljević Lav , Smith Stephen M. , Nichols Thomas E.
Published: February 2025

Background

The potential value of large scale datasets is constrained by the ubiquitous problem of missing data, arising in either a structured or unstructured fashion. When imputation methods are proposed for large scale data, one limitation is the simplicity of existing evaluation methods. Specifically, most evaluations create synthetic data with only a simple, unstructured missing data mechanism which does not resemble the missing data patterns found in real data. For example, in the UK Biobank missing data tends to appear in blocks, because non-participation in one of the sub-studies leads to missingness for all sub-study variables.

Methods

We propose a tool for generating mixed type missing data mimicking key properties of a given real large scale epidemiological data set with both structured and unstructured missingness while accounting for informative missingness. The process involves identifying sub-studies using hierarchical clustering of missingness patterns and modelling the dependence of inter-variable correlation and co-missingness patterns.

Results

On the UK Biobank brain imaging cohort, we identify several large blocks of missing data. We demonstrate the use of our tool for evaluating several imputation methods, showing modest accuracy of imputation overall, with iterative imputation having the best performance. We compare our evaluations based on synthetic data to an exemplar study which includes variable selection on a single real imputed dataset, finding only small differences between the imputation methods though with iterative imputation leading to the most informative selection of variables.

Conclusions

We have created a framework for simulating large scale data with that captures the complexities of the inter-variable dependence as well as structured and unstructured informative missingness. Evaluations using this framework highlight the immense challenge of data imputation in this setting and the need for improved missing data methods.
Association between a publicly funded universal drug program and antipsychotic and antidepressant medication dispensing to children
Authors: Kitchen Sophie A. , Gomes Tara , Tadrous Mina , Pajer Kathleen , Gardner William , Lunsky Yona , Penner Melanie , Juurlink David , Mamdani Muhammad , Antoniou Tony
Published: February 2025

Background

The prescribing of antidepressants and antipsychotics to children has increased worldwide, but little is known about how changes in drug funding policy influence the practice. In 2018, Ontario introduced a universal pharmacare program (OHIP+) for children and youth, amending it in April 2019 to cover only those without private insurance. We examined the association of these policy changes with antipsychotic and antidepressant medication prescribing.

Methods

We conducted a population-based study of antidepressant and antipsychotic medication dispensing to children ≤ 18 years old between September 1, 2014, and February 29, 2020. We obtained dispensing data from the IQVIA Geographic Prescription Monitor database, and used interventional autoregressive integrated moving average models to examine whether the implementation of OHIP + and its subsequent revision were associated with changes in dispensing.

Results

The implementation of OHIP + was not associated with changes in the rate of antidepressants (-19.3 units per 1,000 population; 95% confidence interval [CI]: -41.7 to 3.1) or antipsychotics (+ 1.0 unit per 1,000 population; 95% CI: -5.4 to 7.5) dispensed. Similarly, subsequent changes to the program restricting coverage to children without private insurance were not associated with antidepressant (0.3 units per 1,000; 95% CI: -7.4 to 7.9) or antipsychotic (1.0 units per 1,000; 95% CI: -0.9 to 2.9) dispensing trends.

Conclusion

Implementation of a publicly-funded pharmacare program did not influence trends in antidepressant or antipsychotic medication dispensing among children.
COVID-19 in the years 2020 to 2022 in Germany: effects of comorbidities and co-medications based on a large-scale database analysis
Authors: Linder Roland , Peltner Jonas , Astvatsatourov Anatoli , Gomm Willy , Haenisch Britta
Published: February 2025

Background

The SARS-CoV-2 pandemic was a challenge for health care systems worldwide. People with pre-existing chronic diseases have been identified as vulnerable patient groups. Furthermore, some of the drugs used for these chronic diseases such as antihypertensive drugs have been discussed as possible influencing factors on the progression of COVID-19. This study examines the effect of medication- and morbidity-associated risk factors suspected to moderate the disease course and progression of COVID-19.

Methods

The study is based on claims data of the Techniker Krankenkasse, Germany’s largest statutory health insurance. The data cover the years 2020 to 2022 and include insured persons with COVID-19 diagnosis from both the outpatient and inpatient sectors and a control of insured persons without COVID-19 diagnosis. We conducted a matched case-control study and matched each patient with an inpatient diagnosis of COVID-19 to (a) 10 control patients and (b) one patient with an outpatient diagnosis of COVID-19 to form two study cohorts. We performed a descriptive analysis to describe the proportion of patients in the two cohorts who were diagnosed with comorbidities or medication use known to influence the risk of COVID-19 progression. Multiple logistic regression models were used to identify risk factors for disease progression.

Results

In the first study period the first study cohort comprised a total of 150,018 patients (13,638 cases hospitalised with COVID-19 and 136,380 control patients without a COVID-19 infection). Study cohort 2 included 27,238 patients (13,619 patients hospitalised with COVID-19 and 13,619 control patients with an outpatient COVID-19 diagnosis). Immunodeficiencies and use of immunosuppressives were strongest risk modifying factors for hospitalization in both study populations. Other comorbidities associated with hospitalization were diabetes, hypertension, and depression.

Conclusion

We have shown that hospitalisation with COVID-19 is associated with past medical history and medication use. Furthermore, we have demonstrated the ability of claims data as a timely available data source to identify risk factors for COVID-19 severity based on large numbers of patients. Given our results, claims data have the potential to be useful as part of a surveillance protocol allowing early-stage access to epidemiological data in future pandemics.
The mediating effect of air pollution on the association between meteorological factors and influenza-like illness in China
Authors: Yan Qinling , Cheke Robert A. , Tang Sanyi
Published: February 2025

Purpose

Although numerous studies have explored the complex relationship between air pollution, meteorological factors and respiratory infections, evidence for a mediating effect of air pollutants being involved in the association between meteorological factors and Influenza-like illness (ILI) is limited.

Methods

Correlations among ILI cases, air pollutants and meteorological factors were examined with Pearson correlation analyses. Further, we formulated six candidate mediation models to explore the mediating effect of air pollutant on the association between meteorological factors and ILI infections.

Results

The meteorological factors minimum temperature/maximum humidity moderated by maximum humidity/minimum temperature and pressure directly affect ILI infections, and that some of meteorological factors can also indirectly affect them through air pollutants. Increases in maximum humidity and minimum temperature can directly reduce the numbers of ILI cases, or indirectly reduce them by reducing the concentration of air pollutants.

Conclusion

When the haze with low temperature, low humidity is forecasted by the meteorological agency, the environmental protection departments can take effective control measures to reduce the concentration of air pollutants, and public health departments should advocate human behavioral changes in order to mitigate and control ILI prevalence.
One stage transanal versus one stage laparoscopic-assisted transanal endorectal pull-through in managing Hirschsprung’s disease in pediatric age group; a retrospective study
Authors: Elrouby Ahmed , Shehata Sameh , Waheeb Saber , Khairi Ahmed , AbdAl-Aziz Doaa , Looka Baher
Published: February 2025

Background

The management of Hirschsprung’s disease has evolved from the conventional route to the minimally invasive route in one stage either from the pure transanal route or with the assistance of laparoscopy. Our study compared the surgical and functional outcomes of both approaches.

Methods

Our retrospective study included 72 pediatric patients presented with Hirschsprung’s Disease to Elshatby University Hospital, 40 patients were treated by TAERPT (Group A) and 32 patients were treated by LAERPT (Group B). The two groups were compared as regards the personal data, the operative data, and the post-operative outcomes including the time of passage of stools, time of tolerating oral feeding, the duration of hospital stay, and the development of any early postoperative complications. Moreover, the frequency of defecation, constipation, enterocolitis, anastomotic stricture, and continence were assessed.

Results

The age at operation was significantly lower (p < 0.001*) in patients of Group A (13.95 ± 18.18) than in patients of Group B (32.03 ± 16.20). The total operative duration was not different between the two groups, however, a significantly shorter duration of the anal part (p < 0.001*) in Group B (47.81 ± 18) than in Group A (96.50 ± 38.60) was recorded. A significantly longer colonic segment (p < 0.001*) was resected in Group A (28 ± 4.05) than in Group B (22.70 ± 8.12). The hospital stay was significantly shorter in Group B (5.78 ± 2.41) than in Group A (7.20 ± 2.78). (p = 0.001*) The excised segment revealed a proximal aganglionic zone in four patients denoting a missed segment; three in Group B and only one patient in Group A. There were no differences as regards the early and late follow-up parameters.

Conclusions

Endorectal pull-through for the treatment of Hirschsprung’s disease could be approached either completely transanal or with the assistance of laparoscopy with nearly similar surgical and functional outcomes, however a longer operative duration with a shorter anal stage is recorded with the laparoscopic assistance. Furthermore, a shorter hospital stay could be achieved with the aid of laparoscopy.

Trial registration

Protocol ID: 0306356, Registration number: NCT06419998, 20/05/2024 - Retrospectively registered
Clinical anxiety among a sample of dental students in South Sinai
Authors: Mikhail Christine Raouf George , Ragab Mai Hamdy , Ahmed Yousra , El Desouky Eman D. , Hassanein Fatma E. A. , Bekhit Mohamed , Mostafa Marwa Hassan
Published: February 2025

Background

Anxiety may be induced in the dental clinics, which is an essential learning environment for undergraduate dental students. This could have a negative impact on clinical performance. This study aimed to estimate the incidence of clinical anxiety among a sample of Dental students and to determine possible precipitating factors for clinical anxiety among them.

Methods

A cross-sectional study was carried out among 3rd and 4th year dental students at King Salman International University using the modified 34 items of Moss and McManus clinical anxiety questionnaire.

Results

263 students participated. Dental students reported higher incidence of clinical anxiety (60.8%), particularly with different dental treatment plan procedures related clinical situations fulfilling 31.2 out of mean score of anxiety all (74.0 ). Females had higher anxiety score in all domains than males, the same trend noticed in students who reported dental phobia and previous bad dental experiences (P < 0.001, P 0.016, P 0.003 respectively). Participants rated the clinical anxiety precipitating situations in a descending order as follows: extracting wrong tooth (39.5%), giving wrong treatment (37.6%), tearing of the cheek/lips due to catching on a dental burr (35.7%), fracturing a tooth (34.4%), wrong diagnosis (28.1%), inadvertently hurting the patient (22.1%), inability to meet requirements before exams (19.1%), dealing with a fainting patient during dental treatment (18.7%). Two clinical anxiety precipitating situations had almost the same score including restoration failure/recurrent caries and endodontic retreatment procedures 14.8% and 14.4% respectively. Also, extracting tooth and arresting postoperative bleeding had the same score of 13.7%, while the rest of other clinical situations ranged from 11.8 to 1.1%.

Conclusions

dental students had a comparatively high level of anxiety during clinical classes especially females and those with dental phobia and previous bad dental experiences. Dental students may benefit from stress management classes, mentorship programs, and improved clinical supervision in order to reduce clinical anxiety and build resilience.
Clinical study on horizontal bone augmentation using an alveolar mucosa-periosteal bone flap
Authors: Xu Xinghuanyu , Xu Pu , Liu Shuangxi , Yang Yanlan , Cheng Yanan , Zhang WenBai , Yu Dou , Lu Liying
Published: February 2025

The current study aimed to assess the effectiveness of the alveolar bone mucosa- periosteal bone flap technique in horizontally augmenting the alveolar ridge during dental implant placement. This retrospective analysis included 20 patients with a total of 45 implants, and was designed to evaluate the alveolar ridge widths both before and after surgery. Preoperative measurements indicated an average alveolar ridge width of 3.62 ± 0.90 mm, which increased to 6.58 ± 1.16 mm postoperatively. Statistical analysis revealed a significant increase in alveolar ridge width following the procedure (P < 0.05), with an average gain of 2.96 ± 1.21 mm. In summary, these findings suggest that the alveolar bone mucosa-periosteal bone flap technique is an effective approach for widening the alveolar ridge while placing dental implants, meriting its consideration for clinical application.
AI versus human-generated multiple-choice questions for medical education: a cohort study in a high-stakes examination
Authors: Law Alex KK , So Jerome , Lui Chun Tat , Choi Yu Fai , Cheung Koon Ho , Kei-ching Hung Kevin , Graham Colin Alexander
Published: February 2025

Background

The creation of high-quality multiple-choice questions (MCQs) is essential for medical education assessments but is resource-intensive and time-consuming when done by human experts. Large language models (LLMs) like ChatGPT-4o offer a promising alternative, but their efficacy remains unclear, particularly in high-stakes exams.

Objective

This study aimed to evaluate the quality and psychometric properties of ChatGPT-4o-generated MCQs compared to human-created MCQs in a high-stakes medical licensing exam.

Methods

A prospective cohort study was conducted among medical doctors preparing for the Primary Examination on Emergency Medicine (PEEM) organised by the Hong Kong College of Emergency Medicine in August 2024. Participants attempted two sets of 100 MCQs—one AI-generated and one human-generated. Expert reviewers assessed MCQs for factual correctness, relevance, difficulty, alignment with Bloom’s taxonomy (remember, understand, apply and analyse), and item writing flaws. Psychometric analyses were performed, including difficulty and discrimination indices and KR-20 reliability. Candidate performance and time efficiency were also evaluated.

Results

Among 24 participants, AI-generated MCQs were easier (mean difficulty index = 0.78 ± 0.22 vs. 0.69 ± 0.23, p < 0.01) but showed similar discrimination indices to human MCQs (mean = 0.22 ± 0.23 vs. 0.26 ± 0.26). Agreement was moderate (ICC = 0.62, p = 0.01, 95% CI: 0.12–0.84). Expert reviews identified more factual inaccuracies (6% vs. 4%), irrelevance (6% vs. 0%), and inappropriate difficulty levels (14% vs. 1%) in AI MCQs. AI questions primarily tested lower-order cognitive skills, while human MCQs better assessed higher-order skills (χ² = 14.27, p = 0.003). AI significantly reduced time spent on question generation (24.5 vs. 96 person-hours).

Conclusion

ChatGPT-4o demonstrates the potential for efficiently generating MCQs but lacks the depth needed for complex assessments. Human review remains essential to ensure quality. Combining AI efficiency with expert oversight could optimise question creation for high-stakes exams, offering a scalable model for medical education that balances time efficiency and content quality.
Nurses retention: the impact of transformational leadership, career growth, work well-being, and work-life Balance
Authors: AbdELhay Eman Sameh , Taha Samah Mohamed , El-Sayed Mona Metwally , Helaly Sahar Hassan , AbdELhay Islam Sameh
Published: February 2025

Background

Nurse retention is critical for healthcare systems worldwide, as high turnover rates adversely affect patient care and organizational stability.

Aim

Examines the impact of transformational leadership, career growth opportunities, work well-being, and work-life balance on nurse retention.

Methods

A cross-sectional study was conducted with 297 nurses employed in inpatient wards at Mansoura University Hospital. The study measured variables using the Nursing Retention Index, Global Transformational Leadership Scale, Career Growth Scale, Work Well-Being Scale, and Work-Life Balance Scale.

Results

A linear regression analysis identified significant predictors of nurse retention. Work-life balance was found to be a strong predictor, with an unstandardized coefficient (B) of 0.255 (p < 0.001) and a standardized coefficient (β) of 0.426, indicating a positive relationship with retention, transformational leadership also significantly influenced retention, with a B of 0.082 (p = 0.002) and a β of 0.171. In contrast, Career Growth and Work-Life Balance did not significantly predict retention, showing coefficients of -0.082 (p = 0.154) and -0.042 (p = 0.482). The model explained 23.4% of the variance in nurse retention (R-squared = 0.234) and demonstrated statistical significance (F = 22.294, p < 0.001).

Conclusion

This study highlights the critical role of transformational leadership and work-life balance in enhancing nurse retention. However, career growth and work well-being did not significantly predict retention in this study. Healthcare institutions should focus on transformational leadership and work-life balance to enhance nurse retention. Future studies should explore factors related to career growth and work well-being to determine their potential impact on retention.
Effect of the application of humanized nursing care on the clinical outcomes of neonates with hyperbilirubinemia
Authors: Abdelgawad Sahar Mahmoud Elkhedr , Galalah Eman Salah Elmetwaly Abdelrahman , El-mahdy Heba Saied , Elmahdy Nagafa Hafez Farag
Published: February 2025

Background

Neonatal hyperbilirubinemia is a potentially fatal condition that has toxic effects on the brain and may have negative effects. Humanized care is a comprehensive approach that focuses on the nutritional, therapeutic and hygienic needs of neonates, which helps in the resolution of hyperbilirubinemia.

Method

A quasi-experimental design was utilized in this study to evaluate the effect of humanized nursing care application on the clinical outcomes of neonates with hyperbilirubinemia. It was carried out at the Neonatal Intensive Care Unit at Tanta Main University Hospital. A total of 120 neonates with hyperbilirubinemia who fit the inclusion criteria were randomly assigned to both the study and control groups. The data were collected using the biosocial-demographic characteristics of the studied neonates and neonatal clinical outcome measures for humanized care.

Results

On the seventh day after receiving humanized care, total bilirubin levels in the study group decreased to 4.03 ± 1.48 compared to 10.21 ± 2.08 in the control group; there was also a decline in the time of jaundice regression with a mean of 3.966 ± 1.09 in the study group compared to 4.66 ± 1.29. in the control group. The mean days of phototherapy were 1.83 ± 0.73 in the study group and 2.41 ± 1.01 in the control group. Additionally, oxygen saturation increased significantly on the 7th day in the study group compared to the control group; the mean amount of daily milk intake was 752.8 ± 262.9 ml in the study group compared with 600.76 ± 290.31 ml in the control group.

Conclusion

Applying humanized care improved neonatal clinical outcomes, including O2 saturation, jaundice regression, enhanced newborn feeding and decreased duration of phototherapy.
ANO7 expression in the prostate modulates mitochondrial function and lipid metabolism
Authors: Löf Christoffer , Sultana Nasrin , Goel Neha , Heron Samuel , Wahlström Gudrun , House Andrew , Holopainen Minna , Käkelä Reijo , Schleutker Johanna
Published: February 2025

Background

Prostate cancer (PrCa) is a significant health concern, ranking as the second most common cancer in males globally. Genetic factors contribute substantially to PrCa risk, with up to 57% of the risk being attributed to genetic determinants. A major challenge in managing PrCa is the early identification of aggressive cases for targeted treatment, while avoiding unnecessary interventions in slow-progressing cases. Therefore, there is a critical need for genetic biomarkers that can distinguish between aggressive and non-aggressive PrCa cases. Previous research, including our own, has shown that germline variants in ANO7 are associated with aggressive PrCa. However, the function of ANO7 in the prostate remains unknown.

Methods

We performed RNA-sequencing (RNA-seq) on RWPE1 cells engineered to express ANO7 protein, alongside the analysis of a single-cell RNA-sequencing (scRNA-seq) dataset and RNA-seq from prostate tissues. Differential gene expression analysis and gene set enrichment analysis (GSEA) were conducted to identify key pathways. Additionally, we assessed oxidative phosphorylation (OXPHOS), glycolysis, and targeted metabolomics. Image analysis of mitochondrial morphology and lipidomics were also performed to provide further insight into the functional role of ANO7 in prostate cells.

Results

ANO7 expression resulted in the downregulation of metabolic pathways, particularly genes associated with the MYC pathway and oxidative phosphorylation (OXPHOS) in both prostate tissue and ANO7-expressing cells. Measurements of OXPHOS and glycolysis in the ANO7-expressing cells revealed a metabolic shift towards glycolysis. Targeted metabolomics showed reduced levels of the amino acid aspartate, indicating disrupted mitochondrial function in the ANO7-expressing cells. Image analysis demonstrated altered mitochondrial morphology in these cells. Additionally, ANO7 downregulated genes involved in fatty acid metabolism and induced changes in lipid composition of the cells, characterized by longer acyl chain lengths and increased unsaturation, suggesting a role for ANO7 in regulating lipid metabolism in the prostate.

Conclusions

This study provides new insights into the function of ANO7 in prostate cells, highlighting its involvement in metabolic pathways, particularly OXPHOS and lipid metabolism. The findings suggest that ANO7 may act as a key regulator of cellular lipid metabolism and mitochondrial function in the prostate, shedding light on a previously unknown aspect of ANO7’s biology.
Immune profiling of human vestibular schwannoma secretions identifies TNF-α and TWEAK as cytokines with synergistic potential to impair hearing
Authors: Vasilijic Sasa , Seist Richard , Yin Zhenzhen , Xu Lei , Stankovic Konstantina M.
Published: February 2025

Background

Vestibular schwannoma (VS) is an intracranial tumor arising from the Schwann cells of the vestibular nerve and is an important cause of sensorineural hearing loss (SNHL) in humans. The mechanisms underlying this SNHL are incompletely understood and currently, there are no drugs FDA approved specifically for VS. This knowledge gap significantly limits the development of effective treatments aimed at preventing, stabilizing, or reversing VS-induced SNHL.

Methods

To identify effector molecules involved in VS-induced SNHL, we analyzed 47 immune-related factors secreted by tumor tissue in over 50 patients with sporadic VS and studied their correlation with preoperative hearing ability and tumor size. The most promising effector molecules were validated in vivo in an anatomically accurate mouse model of VS, and in vitro with mouse fibroblasts (L929) and auditory cell lines representing pro-sensory precursors of hair cells (UB-OC1) and auditory neuroblasts (US-VOT-N33).

Results

We demonstrated that VS-induced SNHL was linked to increased secretion of TNF-α, IL-2R, CD163, eotaxin, and HGF, while larger tumor size was associated with higher levels of TNF-α, TNF-R2, IL-1α, IFN-α, MIP-1β, and IL-21 secretion. We identified heterogeneity among VS tumors in their capacity to secrete TNF-α. Tumors with high levels of TNF-α secretion released cytokines and chemokines that significantly correlated with poor hearing (TWEAK and eotaxin) or better hearing (LIF, GRO-α, MIP-1α, MIP-3α, and IL-1α). Among these, TWEAK was notably abundant, with levels exceeding those in normal nerve tissue, elevated in patients with non-serviceable hearing and strongly linked to poor hearing in patients with TNF-α high-secreting tumors. In vivo, we demonstrated that VS-secreted factors reach the inner ear, with elevated TNF-α and TWEAK in the perilymph and blood of tumor-bearing mice with impaired hearing. In vitro, TWEAK amplified TNF-α -mediated cytotoxicity in TNF-α sensitive cells (L929) and auditory cell lines (UB-OC1 and US-VOT-N33) at tumor-secreted concentrations.

Conclusion

This study provides compelling evidence that VS-secreted TNF-α and TWEAK act synergistically to drive tumor-induced SNHL. Targeting the TNF-α/TWEAK axis presents a promising new avenue for preventing VS-induced SNHL.
Diagnostic value of the appendicitis inflammatory response (AIR) score. A systematic review and meta-analysis
Authors: Andersson Roland E. , Stark Joachim
Published: February 2025

Background

Clinical scoring algorithms are cost efficient in patients with suspicion of acute appendicitis. This is a systematic review and meta-analysis of the diagnostic properties of the Appendicitis Inflammatory Response (AIR) score compared with the Alvarado score.

Methods

The PubMed, EMBASE, Web of Science and Google Scholar databases were searched for reports on the diagnostic properties of the AIR score from 2008 to July 18, 2024. A meta-analysis of the receiver operating characteristic (ROC) area and the sensitivity and specificity for all and advanced appendicitis patients was performed. Advanced appendicitis was defined as perforated or gangrenous appendicitis or appendicitis abscess or phlegmon or if described as complicated appendicitis. The risk of bias was estimated via the QUADAS-2 tool. The ROC areas of the AIR score and the Alvarado score were compared.

Results

A total of 26 reports with a total of 15.699 patients were included. The area under the ROC curve for the AIR score was 0.86 (95% CI 0.83–0.88) for all patients with appendicitis and 0.93 (CI 0.91–0.96) for those with advanced appendicitis, which was greater than the corresponding areas for the Alvarado score (0.79, CI 0.76; 0.81) and 0.88, CI 0.82; 0.95), respectively.

At > 4 points, the sensitivity was 0.91 (CI 0.88; 0.94) for all patients with appendicitis and 0.95 (CI 0.94; 0.97) for those with advanced appendicitis. At > 3 points, the sensitivity was 0.95 (0.90; 0.97) for all patients with appendicitis and 0.99 (0.97; 0.99) for those with advanced appendicitis.

At > 8 points, the specificity was 0.98 (0.97; 0.99) for all patients with appendicitis and 0.99 (0.97; 0.99) for those with advanced appendicitis. The included studies had a low risk for bias and low heterogeneity.

Conclusion

The AIR score has a better diagnostic capacity than the Alvarado score does. The AIR score is a safe and efficient basis for risk-stratified management of patients suspected of having appendicitis.
Clinical spectrum, treatment and outcomes of the m.10197G>A mutation in MT-ND3: a case report, systematic review and meta-analysis
Authors: Shi YuZhi , Chen Bin , Niu SongTao , Wang XinGao , Zhang ZaiQiang
Published: February 2025

Background

A correlation between various sites or types of mutations in mitochondrial DNA ND3 and the development of a specific mitochondrial disease or phenotype has yet to be fully established.

Methods

This study reports a rare case of adult-onset Leigh syndrome (LS) and Leber hereditary optic neuropathy and dystonia (LDYT) overlap syndrome caused by the m.10197G>A mutation in ND3. A review of the literature was conducted to investigate the clinical spectrum, treatment and outcome resulting from the m.10197G>A mutation. Phenotypes associated with the m.10197G>A mutation were classified into three categories: LS/LS+ (LS-involved overlap syndrome), Leber hereditary optic neuropathy (LHON)/LHON+ (LHON-involved overlap syndrome) and other mitochondrial encephalopathies or presentations.

Results

A total of 84 participants (78 patients and 6 asymptomatic carriers) with the m.10197G>A mutation retrieved from 33 articles and the patient whose case we reported were included in the review and meta-analysis. Among all the participants, 55.3% (47/85) and 28.2% (24/85) presented with LS/LS+ and LHON/LHON+, respectively. The median age at onset for LS/LS+ was significantly younger than that for LHON/LHON+ [median, (Q1–Q3), 3.0 (0.58–9.5) vs. 13.5 (5.75–41.75), P = 0.001]. A negative linear correlation was observed between mutation load and age of onset in patients who presented with LS/LS+ (R2 = 0.592, P < 0.001), with the age of onset ranging from infancy to adulthood. Patients with an older age at onset [OR (95% CI), 1.46 (1.12–1.91), P = 0.005] or higher mutation loads [OR (95% CI), 1.14 (1.03–1.26), P = 0.011] were more likely to present with LHON/LHON+ than with LS/LS+. A total of 17 patients were documented as having received a combination of mitochondrial cofactor treatments. Compared with patients with LHON/LHON+, patients with LS/LS+ exhibited an exceedingly high probability of a stable or worsen outcome (93.8% vs. 33.3%, P = 0.006).

Conclusions

LS/LS+ and LHON/LHON+ are the predominant presentations of the m.10197G>A mutation. An older age at onset and greater mutation load increases the probability of an LHON/LHON+ presentation. Patients presenting with LS/LS+ have an exceedingly high possibility of an unfavorable outcome. The identification of factors and outcomes associated with phenotypes in patients with the m.10197G>A mutation facilitates the provision of improved prognostic counseling for patients and their family members who are carriers of this mutation.
Flexible assessment of biosecurity in small- and medium scale poultry farms in low and middle income countries
Authors: Nielsen Søren Saxmose , Kemunto Naomi P. , Muloi Dishon M. , Bojesen Anders Miki , Knight-Jones Theodore , Ayebare Dreck , Dione Michel , Ibayi Eugine L. , Poulsen Louise Ladefoged , Moodley Arshnee
Published: February 2025

Background

Biosecurity measures are essential for mitigating the risk of pathogen introduction and spread in farms. While standardised tools for monitoring biosecurity implementation exist, they are often not tailored to the specific needs of low and middle income countries (LMICs), where pathogen occurrence and farming practices can be highly variable compared to intensive high income country settings. The aim of our study was to develop a flexible risk assessment tool for evaluating biosecurity practices on small and medium-scale poultry farms in LMICs. The methodology described here allows local experts to adapt the tool to current conditions.

Results

The development process began by combining two existing questionnaires. These were evaluated by nine experts with expertise in diverse farming systems in LMICs. The experts conducted a knowledge aggregation process to assign weights to the different areas and individual questions within the questionnaires. The median scores from the final expert elicitation informed the weighting of questions in the newly developed questionnaire. These weights are adaptable and can be adjusted to reflect population-specific conditions, which may vary in pathogen load and farming practices.

Conclusions

We have developed a flexible biosecurity assessment tool tailored to small-and medium-scaled poultry farms in LMICs. This tool can be used as presented or adapted to local conditions through the input of local experts, allowing for effective and context-specific biosecurity monitoring.
Mesenchymal stem cells from perinatal tissues promote diabetic wound healing via PI3K/AKT activation
Authors: Huang Jiawei , Deng Qingwen , Tsang Lai Ling , Chang Guozhu , Guo Jinghui , Ruan Ye Chun , Wang Chi Chiu , Li Gang , Chan Hon Fai , Zhang Xiaohu , Jiang Xiaohua
Published: February 2025

Background

Diabetic foot ulcers (DFUs) represent a major complication of diabetes, often leading to poor healing outcomes with conventional treatments. Mesenchymal stem cell (MSC) therapies have emerged as a promising alternative, given their potential to modulate various pathways involved in wound healing. This study evaluates and compares the therapeutic potential of MSCs derived from perinatal tissues—human umbilical cord MSCs (hUCMSCs), human chorionic villi MSCs (hCVMSCs), and human decidua basalis MSCs (hDCMSCs)—in a diabetic wound healing model.

Methods

We performed in vitro and in vivo studies to compare the efficacy of hUCMSCs, hCVMSCs, and hDCMSCs. Mass spectrometry was used to analyze the secreted proteins of the MSCs. We incorporated the MSCs into a polyethylene glycol diacrylate (PEGDA) and sodium alginate (SA) hydrogel matrix with collagen I (Col-I) to evaluate their effects on wound healing.

Results

All three types of MSCs promoted wound healing, with hUCMSCs and hCVMSCs showing stronger effects compared to hDCMSCs. Both hUCMSCs and hCVMSCs demonstrated robust wound healing kinetics, with enhanced keratinocyte proliferation (KRT14+/Ki67+ cells), maturation (KRT10/KRT14 ratio), and angiogenesis. In vitro studies demonstrated that the MSC-derived secretome enhanced keratinocyte proliferation and migration, endothelial cell function and stem cell recruitment, indicating robust paracrine effects. Mass spectrometry revealed a conserved set of proteins including THBS1 (thrombospondin 1), SERPINE1 (serpin family E member 1), ANXA1 (annexin A1), LOX (lysyl oxidase), and ITGB1 (integrin beta-1) which are involved in extracellular matrix (ECM) organization and wound healing, with the PI3K/AKT signaling pathway playing a central role. The PEGDA/SA/Col-I hydrogel demonstrated a unique balance of mechanical and biological properties and an optimal environment for MSC viability and function. Application of either hUCMSC- or hCVMSC-laden hydrogels resulted in accelerated wound closure, improved re-epithelialization, increased collagen deposition, and enhanced vascularization in vivo.

Conclusions

MSCs From perinatal tissues particularly hUCMSCs and hCVMSCs significantly enhance diabetic wound healing through PI3K/AKT pathway activation while hDCMSCs exhibited weaker efficacy. The PEGDA/SA/Col-I hydrogel supports MSC viability and function offering a promising scaffold for DFU treatment. These findings underscore the potential of specific perinatal MSCs and optimized hydrogel formulations in advancing diabetic wound care.
Canine circovirus: an emerging virus of dogs and wild canids
Authors: Beikpour Farzad , Letafati Arash , Fakhr Zahra Ahmadi , Decaro Nicoal , Mozhgani Sayed-Hamidreza
Published: February 2025

Canine Circovirus (CanineCV) is an emerging viral pathogen affecting dogs and wild canids worldwide. Belonging to the Circoviridae family, CanineCV exhibits genetic variability and has been associated with various clinical manifestations, including gastroenteritis, respiratory symptoms, and neurological disorders. While its prevalence is notable, gaps persist in understanding its pathogenicity and evolutionary origins. CanineCV often co-infects with other canine viruses, complicating diagnosis and treatment. Prevention strategies are hindered by the lack of targeted vaccines and the virus's resilience in the environment. This review paper summarizes the current knowledge on CanineCV and discusses the virus's genetic features and taxonomy, epidemiology in both domestic and wild populations, clinical manifestations, diagnosis methods, and prevention strategies. Additionally, the article highlights gaps in knowledge regarding CanineCV's pathogenicity, evolutionary aspects, and potential zoonotic transmission risks. Overall, it underscores the importance of further research to better understand and mitigate the impact of CanineCV on canine health and public health.
Comparison of anesthetic effects of xylazine combined with alfaxalone or ketamine and maintained with isoflurane in captive Formosan Reeve’s Muntjac (Muntiacus reevesi micrurus)
Authors: Chang Li-Jen , Wang Zixuan , Lien Chen-Yeh , Wen Amanda H.C.
Published: February 2025

Formosan Reeve’s muntjac is a Cervidae species endemic to Southeast China and Taiwan. However, research on different anesthetic protocols, their effects, and their safety in Formosan Reeve’s muntjac is limited. This study evaluated the effects of ketamine-xylazine (KX) and alfaxalone-xylazine (AX) administered via blow darts to nine muntjacs. Induction and recovery times as well as the quality were assessed by a blinded observer. Peripheral oxygen saturation (SpO2), heart rate, respiratory rate, and rectal temperature were recorded for at least 30 min. Tolazoline (4 mg/kg) was used post-procedure to reverse xylazine’s effects. The mean doses were 4.68 ± 2.18 mg/kg for ketamine and 3.22 ± 1.33 mg/kg for xylazine in the KX group. In the AX group, the mean doses were 4.38 ± 0.31 mg/kg for alfaxalone and 1.19 ± 0.26 mg/kg for xylazine. The median induction times were 339.5 s (range 180.0-375.0) for KX and 125.0 s (range 71.0–334.0) for AX, with both groups scoring 3.0 for induction quality. The recovery times were 507.5 s (range 266.0–1081.0) for KX and 243.0 s (range 92.0–480.0) for AX, with recovery scores of 2.3 and 3.0, respectively, showing no significant difference. Hypoxemia (SpO2 < 90%) was more severe in the KX group when compared to the AX group (SpO2 > 92%), and rectal temperatures were higher in the former during the first 15 min. Heart and respiratory rates showed no significant differences between groups. Our findings demonstrate that both anesthetic combinations achieve reliable induction and satisfactory recovery in Formosan Reeve’s muntjac, with the ketamine-xylazine combination causing a more profound hypoxemia post-induction compared to the alfaxalone-xylazine combination.
A broad assessment of forty-one skin phenotypes reveals complex dimensions of skin ageing
Authors: Ng Jun Yan , Wong Qi Yi Ambrose , Lim Jun Jie , Cen Dingyu , Wong Jia Yi Karen , Lim Yi Ying Eliza , Sio Yang Yie , Reginald Kavita , Say Yee-How , Chew Fook Tim
Published: February 2025

Background

Skin ageing takes on many different forms. Despite this diversity in skin ageing phenotypes, literature published to date is limited in scope, as many research studies either focus on one single phenotype or just a few specific phenotypes. Presently, phenotypes such as wrinkles, pigment spots, and photo-ageing are receiving most of the research attention. We therefore wonder whether the current discourse on skin ageing places a disproportionate amount of focus on a few selected phenotypes, leaving other skin ageing phenotypes underexplored.

Methods

In this cross-sectional study, we performed a broad assessment of forty-one signs of skin ageing and characterised the phenotypes that constituted key components of skin ageing. We also explored the interrelationship among forty-one skin ageing phenotypes using Spearman’s Correlation and Principal Component Analysis.

Results

We analysed our study population, which is composed of 3281 ethnic Chinese participants from the Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES). The first ten principal components cumulatively explain 46.88% of the variance of skin ageing phenotypes in our study population. We discovered that the commonly discussed forms of skin ageing (i.e., wrinkles, pigmentation, and photo-ageing) only accounted for a small portion (24.39%) of the variance of all skin ageing phenotypes in our study population. Telangiectasia, a poor lip fullness, a lighter skin colour, xerosis, ephelides (freckles), ptosis of eyelids (droopy eyelids), eyebags, and a low eyebrow positioning were other key components of skin ageing, accounting for a further 22.49% of the variance of skin ageing phenotypes in our study population. We found that each of these ten skin ageing phenotypes characterises a key and important aspect of skin ageing. In this broad assessment of skin ageing, we first described the prevalence of forty-one signs of skin ageing and then characterised in detail both the prevalence and severity distribution of ten key skin ageing phenotypes.

Conclusions

We presented clear evidence that skin ageing is much more than just wrinkles, pigmentation and photo-ageing. The addition of telangiectasia, poor lip fullness, a lighter skin colour, xerosis, ephelides, ptosis of eyelids, eyebags, and a low eyebrow positioning added more dimensions to skin ageing phenotype presentations.
Association between Loa loa microfilaremia and anatomical hyposplenia in a rural area of the Republic of Congo: a population-based cross-sectional study
Authors: Boullé Charlotte , Lebredonchel Elodie , Campillo Jérémy T. , Dupasquier Valentin , Hemilembolo Marlhand C. , Pion Sébastien D. S. , Djontu Jean Claude , Rancé Ludovic , Souteyrand Philippe , Missamou François , Boussinesq Michel , Ntoumi Francine , Chesnais Cédric B.
Published: February 2025

Background

Data suggest excess mortality is associated with loiasis, which is endemic to Central Africa, although the underlying mechanisms remain unknown. We hypothesized that there could be an association between Loa loa microfilarial densities (MFD) and lower spleen volume (SV) due to micro-obstruction linked to circulating microfilariae (mf). This could result in functional hyposplenia and a higher burden of infections. Our objective was to investigate the impact of L. loa MFD and malaria on spleen’s bi-dimensional dimensions, volume, and parenchymal lesions.

Methods

We included 981 participants aged 18–88 years in a cross-sectional study conducted in May–June 2022 in the Republic of the Congo. Centralized ultrasonographic examination was performed. The primary outcomes included SV, splenomegaly (cranio-caudal-distance ≥ 13 cm), and anatomical hyposplenia (AH) (SV ≤ 80, ≤ 110 or ≤ 150 cm3). Blood samples were analyzed for L. loa MFD, Plasmodium-PCR, Anti-Plasmodium falciparum-IgG, total IgM, sickle-cell disease status, and hematological abnormalities. Linear and logistic regressions were used to assess these associations.

Results

Among 981 participants, 139 (14.1%) had splenomegaly, and 26 (2.7%) and 175 (17.8%) had SV ≤ 80 and ≤ 150 cm3, respectively. L. loa microfilariae were detected in 353 (35.6%) participants. A gradient effect was observed in each model, with the highest MFD (> 30,000 mf/ml) having the highest adjusted odds ratio of 17.94 (95% CI: 2.91–110.76, P = 0.002), 5.94 (95% CI: 1.40–25.17, P = 0.016), and 5.77 (95% CI: 1.95–17.12, P = 0.002) for SV ≤ 80, 110, and 150 cm3, respectively. Anti-P. falciparum-IgG levels were gradually associated with splenomegaly. Fourteen participants met the criterion for hyper-reactive malarial splenomegaly (HMS). Conversely, higher L. loa MFD was correlated with AH, with an attributable fraction of 25%, and the presence of splenic parenchymal lesions.

Conclusions

This study provides a detailed description of spleen morphology and the factors influencing its size in a rural central African population. It demonstrates a strong association between L. loa MFD and reduced SV, suggesting that loiasis may lead to AH, and potentially to functional hyposplenia, with consequences such as increased susceptibility to bacterial infections. Malaria was associated with splenomegaly, with a figure of HMS consistent with estimates from other African countries.

Graphical Abstract
Enhancing foster care relationships through attachment-based intervention: the safe families study protocol, a randomized controlled trial of the circle of security parenting program®
Authors: Pereira Mathieu , Sedes Lauriane , Gadéa Emilie , Shankland Rebecca
Published: February 2025

Background

Children in out-of-home care constitute a vulnerable population often experiencing mental health challenges related to early adversity and placement disruptions. The Circle of Security Parenting program® (COS-P) is an attachment-based intervention designed to enhance carer sensitivity and reflective competence, ultimately improving the quality of carer-child relationships.

Methods

This study protocol follows a mixed-methods randomized controlled trial evaluating the effectiveness of the COS-P program for foster carers in France. A total of 70 foster carers will be randomly assigned to either the intervention group (receiving COS-P in addition to Treatment as Usual) or the waitlist control group (receiving Treatment as Usual only). Quantitative measures, including the Caregiving Composite Questionnaire, Parenting Stress Index, and the Marschak Interaction Method, will be administered at baseline and at follow-up). Qualitative data will be collected through focus groups with foster carers and COS-P facilitators, and through self-confrontation interviews with a subset of foster carers.

Discussion

This study is the first to evaluate the COS-P program for foster carers in France. Findings will provide valuable insights into the program’s effectiveness in improving carer-child relationships and foster carer well-being, ultimately contributing to better outcomes for children in out-of-home care. The study will also explore potential moderators of treatment outcome, and shed light on the subjective experiences of participants.

Trial registration

This trial is registered on ClinicalTrials.gov : NCT06701877.
Assessment of bacteria-based self-healing concrete through experimental investigations — a sustainable approach
Authors: Vishal Akula , Chepuri Akhilesh , Chandana N.
Published: February 2025

This study aims to evaluate the destructive and non-destructive strength parameters of bacterial concrete with different grades (M20, M25, M30) and cell counts (10^5 and 10^6 cells/ml) using Bacillus subtilis. Additionally, cost analysis and cost–benefit comparisons were conducted for each mix. The effectiveness of B. subtilis in resisting high temperatures was also examined. Findings indicate a 25–40% increase in strength parameters in bacterial concrete compared to conventional concrete. Bacterial mixes consistently showed velocities above 4.45 km/s, indicating excellent quality, surpassing conventional concrete. Notably, bacteria with a cell count of 10^5 cells/ml exhibited greater strength than 10^6 cells/ml across all grades. Cantabro loss tests revealed a 15–25% reduction in wear and tear for bacterial concrete. The bacterial specimens also showed significantly lower strength loss at higher temperatures. This study underscores the potential of bacterial-based self-healing concrete for specific construction applications, offering high temperature resistance, increased strength, and reduced wear and tear.