bluuebunny/crossref_metadata_2025 huggingface dataset:
Interim analysis of the multinational, post-authorization safety study (NISSO) to assess the long-term safety of sonidegib in patients with locally advanced basal cell carcinoma
Authors: Gutzmer Ralf , Leiter Ulrike , Mohr Peter , Kähler Katharina C. , Ascierto Paolo Antonio , Scalvenzi Massimiliano , Peris Ketty , Pérez-Pastor Gemma María , Fernández-de-Misa Ricardo , Botella-Estrada Rafael , Hunger Robert E. , Martelli Serena , Güneli Nur , Arntz Ramon , Hauschild Axel
Published: November 2024

Background

Following the pivotal phase II trial BOLT, the Hedgehog (Hh) inhibitor sonidegib was approved in the EU to treat locally advanced basal cell carcinoma (laBCC) in patients not amenable to surgery or radiotherapy. We report safety data from the interim analysis of the real-world NISSO study.

Methods

NISSO is an ongoing non-interventional, multinational, post-authorization safety study (NCT04066504). Patients with laBCC are treated with sonidegib 200 mg orally once daily and followed for 3 years. Dose modifications were allowed according to the local prescribing information.

Results

Between May 6, 2019, and March 15, 2022, 321 patients with laBCC were enrolled at 46 European sites (data cut-off: June 22, 2023). Treatment was discontinued in 241 (75.1%) patients, with the main reasons being the patient/guardian decision (n = 69, 28.6%), treatment success (n = 40, 16.6%) and the physician decision (n = 35, 14.5%). The median duration of sonidegib exposure was 8.8 months (4.4–13.7 months). Overall, 284 (88.5%) patients had ≥ one treatment-emergent adverse event (TEAE). Most TEAEs were ≤ grade 2 and the most common were muscle spasms (n = 141; 43.9%), dysgeusia (n = 119; 37.1%), and alopecia (n = 97; 30.2%). After 3 months of treatment, the cumulative rates of muscle spasms, dysgeusia, and alopecia were 21.8%, 16.2%, and 3.7%, respectively. TEAEs led to treatment discontinuation in 59 (18.4%) patients, while 149 (46.4%) patients had at least one TEAE leading to dose reduction or interruption. Serious drug-related TEAEs were reported in 13 (4.1%) patients.

Conclusions

These results confirm the safety profile previously observed. Most patients experienced the onset of common TEAEs after 3 months of treatment, and the cumulative incidence of most common TEAEs was 10–20% lower compared to the BOLT study, except for dysgeusia and fatigue that had a similar incidence. The percentage of patients experiencing TEAEs requiring interruption or dose reduction was similar to the BOLT study, while the proportion of patients with TEAE leading to discontinuation of sonidegib was lower. This study demonstrates that the tolerability of sonidegib is manageable in routine clinical practice.

Trial registration.

NCT04066504.
Impact of New York City’s 4-year multi-component natural experiment to improve elementary school physical education on student cardiorespiratory fitness
Authors: Thompson Hannah R. , Madsen Kristine A. , Nguyen Caroline , McKenzie Thomas L. , Picciotto Sally
Published: November 2024

Background

School physical education is an important population-level health intervention for improving youth fitness. This study estimated the impact of New York City’s PE Works program - which included providing PE teachers, training for classroom teachers, and administrative/ teacher support for PE - on student cardiorespiratory fitness as measured by the FitnessGram’s 15-meter PACER test for aerobic capacity.

Methods

This longitudinal study (2014/15-2018/19) includes 581 elementary schools (n = 315,999 4th /5th -grade students; 84% non-white; 74% who qualify for free or reduced-price meals, a proxy for socioeconomic status). We apply the parametric g-formula to address schools’ time-varying exposure to intervention components and time-varying confounding.

Results

After four years of staggered PE Works implementation, 49.7% of students/school (95% CI: 42.6%, 54.2%) met age/sex-specific Healthy Fitness Zone (HFZ) aerobic capacity standards set by the FitnessGram. Had PE Works not been implemented, we estimate 45.7% (95% CI: 36.9%, 52.1%) would have met aerobic capacity HFZ standards. Had PE Works been fully implemented in all schools from the program’s inception, we estimate 57.4% (95% CI: 49.1%, 63.3%) would have met aerobic capacity HFZ standards. Adding a PE teacher, alone, had the largest impact (6.4% (95% CI: 1.0, 12.0) increase).

Conclusion

PE Works positively impacted student cardiorespiratory fitness. Mandating and funding multicomponent PE programs is an important public health intervention to increase children’s cardiorespiratory fitness.
Osteosynthesis using Scorpion plate for neer type V distal clavicle fracture
Authors: Furuhata Ryogo , Matsumura Noboru , Kamata Yusaku , Tanji Atsushi
Published: November 2024

Background

Neer type V distal clavicle fractures are considered the most unstable fracture type and are characterized by the disruption of continuity between the coracoclavicular (C-C) ligaments and proximal or distal bone fragments. However, owing to the rarity of such fractures, there is currently no universally accepted surgical procedure for their treatment. Recently, the scorpion plate, an anatomical, non-locking, pre-contoured plate with two grasping arms to fix the distal or inferior clavicular fragments, was introduced. This study aimed to investigate the postoperative functional and radiological outcomes of osteosynthesis using only scorpion plates in Neer type V fractures.

Methods

We retrospectively identified 23 patients who underwent scorpion plate fixation for Neer type V fractures at two general hospitals. All patients underwent only plate fixation without C-C ligament augmentation. Subsequently, we investigated their postoperative functional outcomes, complication rates, and modified C-C distance ratio at 1 year.

Results

The mean postoperative Constant score was 96 ± 5, with all cases achieving bone union. Complications within 1 year postoperatively included plate loosening in one patient (4.3%) and plate irritation in two patients (8.7%). Additionally, the modified C-C distance ratio averaged 114 ± 15%.

Conclusions

This study offers novel insights into the management of Neer type V distal clavicle fractures. Our findings indicate that osteosynthesis using only scorpion plates can lead to satisfactory functional outcomes with minimal complications.
Analysing premature cardiovascular disease mortality in the United States by obesity status and educational attainment
Authors: Li Han , Adair Tim
Published: November 2024

Background

In the United States (US), premature cardiovascular disease (CVD) mortality rates (35–74 years) have exhibited increases in recent years, particularly in younger adults, and large differentials by educational attainment. This trend has occurred concurrently with high and increasing obesity prevalence, which also show significant differences by education. This study aims to jointly model premature CVD mortality trends in the US according to obesity status and educational attainment.

Methods

We used multiple cause of death data from the National Center for Health Statistics, obesity prevalence data from the National Health and Nutrition Examination Survey (NHANES), and educational attainment data from the American Community Survey and NHANES. We applied Bayes’ theorem to these data to calculate the conditional probability of premature CVD mortality given obesity status and educational attainment for 2003–2019. We then projected this conditional probability for 2020–2029 using the Lee-Carter model.

Results

The probability of premature CVD mortality was greatest for obesity and low education (not graduated high school) and was substantially higher (females 6.7 times higher, males 5.9) compared with non-obesity and high education (Bachelor’s degree or higher) in 2019. There was a widening of the gap in premature CVD mortality from 2003 to 2019 between the obese and non-obese populations, which occurred at each education level and was projected to continue in 2020–2029, especially for males. The conditional probability of premature CVD death for obesity and middle education (finished high school but no Bachelor’s degree) increased substantially and was projected to surpass the level for non-obesity and low education in coming years for males and in younger age groups. At high education, the conditional probability of premature CVD death for the obese population was projected to increase to 2029, while for non-obesity it was projected to remain steady for females and fall for males; this projected widening is greatest at older age groups.

Conclusions

The findings demonstrate the public health challenge to reduce premature US CVD mortality posed by continued high obesity prevalence, especially for younger ages, lower education groups and males. The relative importance of obesity in influencing premature CVD mortality trends has risen partly due to the decline in CVD mortality attributable to other risk factors.
Enhanced antiviral defense against begomoviral infection in Nicotiana benthamiana through strategic utilization of fluorescent carbon quantum dots to activate plant immunity
Authors: Farooq Tahir , Hussain Muhammad Dilshad , Wang Yuan , Kamran Ali , Umar Muhammad , Tang Yafei , He Zifu , She Xiaoman
Published: November 2024

Background

Owing to their unique physiochemical properties, low toxicity, antipathogenic effects and tunability, fluorescent carbon quantum dots (CQDs) represent a new generation of carbon-based nanomaterials. Despite the mounting research on the efficacy of CQDs against resilient plant pathogens, their potential ability to mitigate viral pathogens and the underlying molecular mechanism(s) remain understudied. In this study, we optimized the CQDs to maximize their antiviral effects against a highly pathogenic Begomovirus (cotton leaf curl Multan virus, CLCuMuV) and elucidated the mechanistic pathways associated with CQDs-mediated viral inhibition. To fine-tune the CQDs-induced antiviral effects against CLCuMuV and investigate the underlying molecular mechanisms,we used HR-TEM, XRD, FT-IR, XPS, and UV‒Vis spectrophotometry to characterize the CQDs. SPAD and FluorCam were used for physiological and photosynthetic performance analysis. Transcriptome, RT‒qPCR, integrated bioinformatics and molecular biology were employed to investigate gene expression, viral quantification and data validation.

Results

The application of fluorescent, hexagonal crystalline, UV-absorptive and water-soluble CQDs (0.01 mg/ml) significantly reduced the CLCuMuV titer and mitigated viral symptoms in N. benthamiana at the early (5 dpi) and late (20 dpi) stages of infection. CQDs significantly increased the morphophysiological properties, relative chlorophyll contents and photosynthetic (Fv/Fm, QY_max, NPQ and Rfd) performance of the CLCuMuV-infected plants. While CLCuMuV infection disrupted plant immunity, the CQDs improved the antiviral defense response by regulating important immunity-related genes involved in endocytosis/necroptosis, Tam3-transposase, the ABC transporter/sphingolipid signaling pathway and serine/threonine protein kinase activities. CQDs potentially triggered TSS and TTS alternative splicing events in CLCuMuV-infected plants.

Conclusions

Overall, these findings underscore the antiviral potential of CQDs, their impact on plant resilience, and their ability to modulate gene expression in response to viral stress. This study’s molecular insights provide a foundation for further research on nanomaterial applications in plant virology and crop protection, emphasizing the promising role of CQDs in enhancing plant health and combating viral infections.

Graphical Abstract
Metabolic-driven analytics of traumatic brain injury and neuroprotection by ethyl pyruvate
Authors: Golovachev Nikita , Siebold Lorraine , Sutton Richard L. , Ghavim Sima , Harris Neil G. , Bartnik-Olson Brenda
Published: November 2024

Background

Research on traumatic brain injury (TBI) highlights the significance of counteracting its metabolic impact via exogenous fuels to support metabolism and diminish cellular damage. While ethyl pyruvate (EP) treatment shows promise in normalizing cellular metabolism and providing neuroprotection, there is a gap in understanding the precise metabolic pathways involved. Metabolomic analysis of the acute post-injury metabolic effects, with and without EP treatment, aims to deepen our knowledge by identifying and comparing the metabolite profiles, thereby illuminating the injury's effects and EP's therapeutic potential.

Methods

In the current study, an untargeted metabolomics approach was used to reveal brain metabolism changes in rats 24 h after a controlled cortical impact (CCI) injury, with or without EP treatment. Using principal component analysis (PCA), volcano plots, Random Forest and pathway analysis we differentiated the brain metabolomes of CCI and sham injured animals treated with saline (Veh) or EP, identifying key metabolites and pathways affected by injury. Additionally, the effect of EP on the non-injured brain was also explored.

Results

PCA showed a clear separation of the four study groups (sham-Veh, CCI-Veh, sham-EP, CCI-EP) based on injury. Following CCI injury (CCI-Veh), 109 metabolites belonging to the amino acid, carbohydrate, lipid, nucleotide, and xenobiotic families exhibited a twofold change at 24 h compared to the sham-Veh group, with 93 of these significantly increasing and 16 significantly decreasing (p < 0.05). CCI animals were treated with EP (CCI-EP) showed only 5 metabolites in the carbohydrate, amino acids, peptides, nucleotides, lipids, and xenobiotics super families that exhibited a twofold change, compared to the CCI-Veh group (p < 0.05). In the non-injured brain, EP treatment (sham-EP) resulted in a twofold change in 6 metabolites within the amino acid, peptide, nucleotide, and lipid super families compared to saline treated sham animals (sham-Veh, p < 0.05).

Conclusions

This study delineates the unique metabolic signatures resulting from a CCI injury and those related to EP treatment in both the injured and non-injured brain, underscoring the metabolic adaptations to brain injury and the effects of EP. Our analysis uncovers significant shifts in metabolites associated with inflammation, energy metabolism, and neuroprotection after injury, and demonstrates how EP intervention after injury alters metabolites associated with mitigating inflammation and oxidative damage.
Predicting the prognosis of Wilms tumor by peripheral blood cells: a real-world study of more than 30 years
Authors: Jie Lin , Qin-Lin Shi , Xiao-Mao Tian , Peng Hong , Zhuang-Cheng Wang , Zai-Hong Hu , Kong-Kong Cui , Zhi-Qiang Gao , Feng Liu , Tao Lin , Guang-Hui Wei
Published: November 2024

Background

Despite established excellent treatment strategies for Wilms tumor (WT), effective prognostic evaluation methods were lacking. This study aims to examine prognostic factors for WT through real-world peripheral blood cell profiling.

Methods

Basic data and pre-treatment laboratory indices from WT and non-WT children underwent Wilcoxon test analysis. Chi-square tests assessed the correlation between blood cells and the overall survival (OS) and event-free survival (EFS) of WT. Further the Log-rank test and multivariate Cox were used to identify independent prognostic factors for OS. Traditional accepted factors were included in multi-Cox and the nomogram was constructed to further validate the outcome.

Results

Blood cells significantly differed between WT and non-WT groups (P < 0.05). Univariate analysis revealed that NLR above 1.380, stage IV, M below 0.325 × 103/μL were linked with lower OS, and PLR below 94.632, LB above 3.570 × 103/μL, stage IV, M above 0.325 × 103/μL,age ≤ 3 years were meaningful for higher EFS (P < 0.05). While in the multifactorial COX, only M (HR:0.220, HR95%CI: 0.080 ~ 0.620, P = 0.004 and HR: 0.437, HR95%CI: 0.202 ~ 0.947, P = 0.036, respectively) and stage IV (HR: 7.890, HR95%CI: 1.650 ~ 37.770, P = 0.010 and HR: 3.720, HR95%CI: 1.330 ~ 10.408, P = 0.012, respectively) were independent prognostic factors for OS and EFS. These two variables also were significant after including recognized risk factors, and were demonstrated the predictability via nomogram.

Conclusions

OS and EFS were poorer in WT children with M below 0.325 × 103/μL, suggesting the potential as a prognostic predictor for WT.
Antibiotics and lectin C for diarrhea control intervention in piglets and influences
Authors: Trung Hoang Dinh , Hoang Ha Viet , Thong Nguyen Thach , Chitana Kenthalangsy , Hoai Dinh Thi Thu , Linh Nguyen Quang
Published: November 2024

The study was conducted on 60 L of suckling piglets out of 775 piglets, of which 227 piglets had diarrhea litres of piglets, and out of 775 piglets, 227 piglets had diarrhoea syndrome. There were 3 interventions in separate trials as follows: 1 and 2 involved antibiotic use (Enrofloxacin and Gentamicin); Trial 3 used the supplement Lectin C (LvCLT3 and LvCLT4) for a treatment period of 3–7 days. Intervention results on 227 piglets with diarrhea showed the highest cure rate when supplemented with Lectin C, with no mortality rate, longer treatment time, and no reinfection rate. While the two antibiotic trials still had lower cure rates, mortality and reinfection rates were higher. After 05 days of recovery, piglets were tested for MCV, MCH, and MCHC, showing an apparent decrease in the group supplemented with Lectin C, while the two groups using antibiotics still had high rates, with a confidence level of P < 0.05; 0.01 and 0.001. Antibiotics treat piglets in their early stages, so there is a risk of immunodeficiency and low infection response. It is necessary to supplement substances derived from dietary supplements. Supplementing Lectin C increases resistance, enhances immune response, improves the effectiveness of treating diarrhoea syndrome in piglets, and ensures safe meat quality in the future. Lectin C supplementation will improve piglet health and breed quality efficiency. This heralds a promising future for the pig industry with improved meat quality and reduced environmental impact.
An in-depth understanding of stakeholders’ experiences about their participation in the co-production of ‘Maze Out’: a serious game for the treatment of eating disorders
Authors: Guala Maria Mercedes , Bikic Aida , Bul Kim , Clinton David , Nielsen Anette Søgaard , Nielsen Helene Nygaard , Scarpelli Martina , Schneider Luciana , Christiansen Regina
Published: November 2024

Background

Co-production is increasingly used in mental health research and clinical settings. Maze Out is a digital game co-produced by clinicians, patients with eating disorders (EDs), an art director with lived experience in EDs, and a game-developing company. Maze Out is based on everyday challenges when suffering from EDs and is currently being evaluated as a supplement tool in EDs treatment. Several studies on co-producing mental health interventions focus on design and effectiveness, but the experiences of those involved in the co-production process remain unexplored. An in-depth exploration of stakeholders’ experiences offers valuable insights into the impact of co-production on different groups and generates crucial knowledge for successful implementation.

Objectives

This study evaluated and explored the co-production process and the meaning that EDs patients, clinicians, and game designers attributed to their participation in the co-production of Maze Out. The objectives were to determine (1) how stakeholders experienced their collaboration in the co-production of Maze Out.; and (2) to what extent the stakeholders involved in developing Maze Out followed Cahn’s principles of equality, diversity, accessibility, and reciprocity.

Methods

Five stakeholders (two patients, two clinicians, and a game designer) who participated in the co-production completed semi-structured interviews. Two patients and one clinician’s diaries supplemented the interviews. Reflexive thematic analysis was used to interpret the data.

Results

The results of this study highlight the importance of building a common language between clinicians, patients, and other professionals involved in developing new forms of treatment and interventions. A recommendation for researchers and clinicians to implement co-production in the future is that Cahn’s principles: equality, reciprocity, accessibility, and diversity, serve as a strong foundation for successful co-production. In this study, three and partially one of the four Cahn’s principles about co-production were identified: equality, reciprocity, and accessibility. When applied in an ED context, these principles provided stakeholders with valuable insights, enriching practice-based knowledge, using the knowledge applicable to clinical practice, and demonstrating their crucial role in fostering effective co-production processes.
Pathophysiology and preclinical relevance of experimental graft-versus-host disease in humanized mice
Authors: Ehx Grégory , Ritacco Caroline , Baron Frédéric
Published: November 2024

Graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantations (allo-HCT) used for the treatment of hematological malignancies and other blood-related disorders. Until recently, the discovery of actionable molecular targets to treat GVHD and their preclinical testing was almost exclusively based on modeling allo-HCT in mice by transplanting bone marrow and splenocytes from donor mice into MHC-mismatched recipient animals. However, due to fundamental differences between human and mouse immunology, the translation of these molecular targets into the clinic can be limited. Therefore, humanized mouse models of GVHD were developed to circumvent this limitation. In these models, following the transplantation of human peripheral blood mononuclear cells (PBMCs) into immunodeficient mice, T cells recognize and attack mouse organs, inducing GVHD. Thereby, humanized mice provide a platform for the evaluation of the effects of candidate therapies on GVHD mediated by human immune cells in vivo. Understanding the pathophysiology of this xenogeneic GVHD is therefore crucial for the design and interpretation of experiments performed with this model. In this article, we comprehensively review the cellular and molecular mechanisms governing GVHD in the most commonly used model of xenogeneic GVHD: PBMC-engrafted NOD/LtSz-PrkdcscidIL2rγtm1Wjl (NSG) mice. By re-analyzing public sequencing data, we also show that the clonal expansion and the transcriptional program of T cells in humanized mice closely reflect those in humans. Finally, we highlight the strengths and limitations of this model, as well as arguments in favor of its biological relevance for studying T-cell reactions against healthy tissues or cancer cells.
Virtual surgical plan with custom surgical guide for orthognathic surgery: systematic review and meta-analysis
Authors: Lee Yoon-Jo , Oh Ji-Hyeon , Kim Seong-Gon
Published: November 2024

Background

The shift from traditional two-dimensional (2D) planning to three-dimensional (3D) virtual surgical planning (VSP) has revolutionized orthognathic surgery, offering new levels of precision and control. VSP, combined with computer-aided design/computer-aided manufacturing (CAD/CAM) technology, enables the creation of patient-specific surgical guides and implants that translate preoperative plans into more precise surgical outcomes. This review examines the comparative accuracy and operative efficiency of VSP, especially when used with custom surgical guides, against conventional 2D planning in orthognathic surgery.

Main text

The study systematically reviewed and analyzed published literature comparing the accuracy and operative time between VSP and conventional planning methods. The meta-analysis included clinical trials, controlled trials, and observational studies on patients undergoing orthognathic surgery, focusing on the degree of alignment between planned and postoperative bone positions and total surgery time. Results indicate that VSP consistently reduces discrepancies between planned and actual surgical outcomes, particularly when integrated with custom surgical guides. Additionally, while VSP demonstrated potential time-saving advantages over conventional planning, these differences were not statistically significant across studies, likely due to high variability among study protocols and designs.

Conclusions

VSP with custom surgical guides enhances surgical accuracy in orthognathic procedures, marking a significant advancement over traditional methods. However, the reduction in operative time was not conclusively significant, underscoring the need for further studies to evaluate time efficiency. These findings emphasize VSP’s role in improving surgical precision, which holds substantial implications for future orthognathic surgical practices.
Plasmodium falciparum genetic diversity and multiplicity of infection among asymptomatic and symptomatic malaria-infected individuals in Uganda
Authors: Mwesigwa Alex , Ocan Moses , Cummings Bryan , Musinguzi Benson , Kiyaga Shahid , Kiwuwa Steven M. , Okoboi Stephen , Castelnuovo Barbara , Bikaitwoha Everd Maniple , Kalyango Joan N. , Karamagi Charles , Nankabirwa Joaniter I. , Nsobya Samuel L. , Byakika-Kibwika Pauline
Published: November 2024

Background

Plasmodium falciparum(P. falciparum) remains a significant public health challenge globally, especially in sub-Saharan Africa (SSA), where it accounts for 99% of all malaria infections. The outcomes ofP. falciparuminfection vary, ranging from asymptomatic to severe, and are associated with factors such as host immunity, parasite genetic diversity, and multiplicity of infection (MOI). Using seven neutral microsatellite markers, the current study investigatedP. falciparumgenetic diversity and MOI in both asymptomatic and symptomatic malaria individuals in Uganda.

Methods

This cross-sectional study analyzed 225P. falciparumisolates from both asymptomatic and symptomatic malaria patients, ranging in age from 6 months to ≥ 18 years.P. falciparumgenetic diversity, MOI, and multi-locus linkage disequilibrium (LD) were assessed through genotyping of seven neutral microsatellite markers: Poly-α, TA1, TA109, PfPK2, 2490, C2M34–313, and C3M69–383. Genetic data analysis was performed using appropriate genetic analysis software.

Results

P. falciparuminfections exhibited high genetic diversity in both asymptomatic and symptomatic individuals. The mean expected heterozygosity (He) ranged from 0.79 in symptomatic uncomplicated malaria cases to 0.81 in asymptomatic individuals. There was no significant difference (p = 0.33) in MOI between individuals with asymptomatic and symptomatic infections, with the mean MOI ranging from 1.92 in symptomatic complicated cases to 2.10 in asymptomatic individuals. Polyclonal infections were prevalent, varying from 58.5% in symptomatic complicated malaria to 63% in symptomatic uncomplicated malaria cases. A significant linkage disequilibrium (LD) was observed between asymptomatic and symptomatic uncomplicated/complicated infections (p < 0.01). Genetic differentiation was low, with FSTvalues ranging from 0.0034 to 0.0105 amongP. falciparumparasite populations in asymptomatic and symptomatic uncomplicated/complicated infections.

Conclusion

There is a high level ofP. falciparumgenetic diversity and MOI among both symptomatic and asymptomatic individuals in Uganda. Asymptomatic carriers harbor a diverse range of parasites, which poses challenges for malaria control and necessitates targeted interventions to develop effective strategies.
Autosomal recessive polycystic kidney disease: late-onset renal enlargement and proteinuria with rare PKHD1 mutation—a case report
Authors: Zeraati Tina , Abbaszadegan Mohammad Reza , Azarfar Anoush , Ghayoor Karimiani Ehsan , Lotfi Malihe , Zeraati Abbas Ali
Published: November 2024

Background

Autosomal recessive polycystic kidney disease (ARPKD) is a genetically inherited pediatric disorder. It is caused by a mutation in the PKHD1 gene located on chromosome 6. The predominant phenotype is characterized by early-onset bilateral enlarged kidneys, as well as fibrocystic changes in the kidney and liver. Fetuses or infants usually present with Potter syndrome, and they are more likely to develop severe renal insufficiency. Generally, patients die perinatally or in infancy. Liver involvement has been reported in adults with ARPKD who have survived the neonatal period and childhood. However, renal involvement is rarely expected in adulthood. The case is being presented for its clinical rarity, in addition to emphasize the critical role of NGS approaches in diagnosis.

Case presentation

We hereby describe a 33-year-old female with adult-onset proteinuria and nephromegaly. She had a rare homozygous missense mutation of the PKHD1 gene with autosomal recessive inheritance. The proband has consanguineous heterozygote parents. The mutation was identified by whole-exome sequencing, and the results were confirmed by segregation analysis.

Conclusion

Here, we reported a thorough literature review of late-onset autosomal recessive polycystic kidney disease. Furthermore, we explored the importance of genetic work-up in families with genetic disorders and consanguineous marriages, particularly in underdeveloped countries.
Metabolic syndrome severity z-score in non-diabetic non-obese Egyptian patients with chronic hepatitis c virus infection
Authors: Askar Safaa R. , Hagag Radwa S. , Ismail Moamen A. , Aly Heba I.
Published: November 2024

Background

The risks of heart disease, resistance of insulin, and diabetes mellitus type II are increased in individuals diagnosed with metabolic syndrome. Furthermore, there is an increase in the vascular and neurological effects. This study aimed to assess the isolated independent impact of hepatitis C virus (HCV) on metabolic syndrome, excluding obesity and diabetes mellitus as common risks, this impact was assessed using the metabolic syndrome Severity Z-score (MetS Z-Score) which was initially designed to assess metabolic disease severity itself. Fifty-one HCV patients non-obese and non-diabetic who visited the Tropical Medicine Department from July 2023 to June 2024 were included in our prospective cross sectional study.

Results

After calculation of MetS Z-Score, strong correlations were observed between MetS Z-score and the following data: HDL, fasting insulin, fasting blood sugar, HOMA-IR and hypertension (P value < 0.05). Moreover, The MetS Z-Score was found to have higher values in hypertensive patients. Jaundice shows a near to significance correlation with the MetS Z-Score. Anemia, hypoalbuminemia and thrombocytopenia were observed in the included HCV patients. Low density lipoprotein, alanine aminotransferase, aspartate aminotransferase, cholesterol and triglycerides have shown higher levels than normal in the included HCV patients.

Conclusion

The MetS Z-score can be used for determining the severity of metabolic abnormalities in HCV patients who are neither diabetic nor obese.
Impact of empirical treatment in patients with extrapulmonary tuberculosis and their outcome
Authors: Rajagopal Jayakumar , S Lavanya , S Ruthra kumar
Published: November 2024

Background

Tuberculosis (TB), primarily caused by mycobacterium tuberculosis (Mtb), remains a significant public health concern globally, particularly in low-resource settings. Extrapulmonary tuberculosis (EPTB), which affects organs beyond the lungs, presents diagnostic and treatment challenges, necessitating improved clinical management strategies. This work was aimed to assess the impact of empirical anti-TB treatment on the outcomes of patients with extrapulmonary tuberculosis and to analyze the demographic and risk factors associated with EPTB.

Methods

A retrospective cohort study was conducted over three years (2020–2023) at PSG Hospitals, Coimbatore. Ninety-two subjects, all with negative microbiological results but symptoms indicative of EPTB, were carefully selected.

Results

A total of 92 patients were included in the study, all of whom had negative microbiological diagnosis with symptoms suggestive of EPTB. The mean age of patients was 58.14 years, with a male predominance (59.78%). Pleural effusion was the most common EPTB site, with many patients having no co-morbidities. Occupational factors, such as cotton millwork, and lifestyle factors, including alcohol use and malnutrition, were prominent risk factors. Clinical manifestations varied, with fever being the most common symptom. Treatment completion was 65.22%, falling below National Tuberculosis Elimination Program (NTEP) guidelines, with notable loss to follow-up and mortality rates.

Conclusion

Empirical treatment for EPTB showed notable improvement in the patient's symptoms and overall health. However, challenges persist in treatment completion, especially among socioeconomically disadvantaged populations. Early detection, prompt treatment initiation, and comprehensive management are essential to address the multifaceted challenges posed by EPTB effectively.
We must teach both sets of skills
Authors: Zúñiga González Carmen Gloria
Published: November 2024

The interview with Carmen Gloria Zúñiga González from Pontifical Catholic University of Chile addresses key questions about transcultural dialogue, the role of historical thinking, and the challenges of teaching history. The starting point is the question of how transcultural dialogue and historical thinking have changed in recent years from the perspective of the interviewee. The interview also discusses how transcultural academic exchange can be promoted, taking into account different educational contexts and social values. It further considers how to ensure that the academic debate is not dominated only by socially or economically privileged groups. Other topics include the role of digitalisation and online communities in history education, and the benefits of cross-disciplinary approaches. The extent to which current global challenges such as pandemics, wars and climate change underline the need for increased transcultural exchange in history education will also be addressed.
The genome sequence of bronze sap hoverfly, Ferdinandea cuprea (Scopoli, 1763)
Authors: Thomas Sam , Hawkes William L.S. ,   Natural History Museum Genome Acquisition Lab,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life Management, Samples and Laboratory team,   Wellcome Sanger Institute Scientific Operations: Sequencing Operations,   Wellcome Sanger Institute Tree of Life Core Informatics team,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: November 2024

We present a genome assembly from an individual Ferdinandea cuprea (bronze sap hoverfly; Arthropoda; Insecta; Diptera; Syrphidae). The genome sequence has a total length of 560.20 megabases. Most of the assembly (99.92%) is scaffolded into 5 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 16.0 kilobases in length. Gene annotation of this assembly on Ensembl identified 12,662 protein-coding genes.
Prywatyzacja małżeństwa. Wybrane stanowiska libertariańskie
Authors: Mirocha Łukasz
Published: November 2024

"Out of love" − this is the most common answer at a divorce hearing to the question asked by the court concerning the reason why the parties seeking a divorce got married. In turn, during legal consultations preceding a divorce case, you can often hear a question that contradicts this statement: "Why did I even get married?" To trivialise a bit, it can be said that this publication asks a more far-reaching question: "What is marriage for at all (at least in the currently applicable legal form)?" The work is not an attempt to attack the family or the institution of marriage, but it analyses the possibility of reforming them and functioning in a non-statutory form, i.e. one that would not be sanctioned by the state or would not enjoy the privileges associated with it (compared to relationships without the status of marriage); in other words, it would be privatised.
Ikony z kolekcji Profesora Wiesława Litewskiego w zbiorach Muzeum Uniwersyteckiego w Toruniu. Katalog
Authors: Waszak Przemysław
Published: November 2024

The monograph devoted to the collection of 19th-century, pre-revolutionary Russian icons donated by Professor Wiesław Litewski to Nicolaus Copernicus University in Toruń presents the world of the sacred in relation to Eastern Christianity in 37 extensive catalogue notes. The book is based on studies of icons found in the University Museum's warehouses conducted by the author, as well as on thorough studies of sources and numerous subject literature concerning icons themselves and related to them contextually.  The publication is characterised by an extensive scientific apparatus. Stylistic-iconographic, historical and contextual analyses are supplemented with quotes from various language versions of the Bible, fragments of sources, literary works, and inscriptions. The extensive first chapter introduces the reader to the world of art originating from early Byzantine times, with a long artistic tradition. The second outlines the profile of the Donor. This richly illustrated book allows one to get to know each icon more carefully and study the details, scenes, figures, or inscriptions, while simultaneously reading the explanations and examinations of the Orthodox paintings.
Leksyka północnokresowa w tefsirze Tatarów Wielkiego Księstwa Litewskiego. Zapożyczenia niesłowiańskie
Authors: Kulwicka-Kamińska Joanna
Published: November 2024

About the book The monograph entitled Leksyka północnokresowa w tefsirze Tatarów Wielkiego Księstwa Litewskiego. Zapożyczenia niesłowiańskie [Northern Borderland Lexis in the Tafsir of the Grand Duchy of Lithuanian Tatars. Non-Slavic Borrowings] concerns an important problem that has not been recognised in scientific research, which is the language of the educated Tatar nobility, living in the territories of the Grand Duchy of Lithuania since the 14th century. The subject of detailed analyses is the lexis of this community, which was formed in the period from the 16th to the first half of the 19th century and is documented in handwritten copies of the first translation of the Quran into Polish. The work collects and analyses the non-Slavic borrowings present in them, which constitute evidence of the confessional, class and education of the creators of Tatar religious literature. It presents them in the form of a lexicon, taking into account etymology, orthographic and phonetic variants, inflectional paradigm, source explication and information on dictionary notations from Old Polish to the most recent times. The dictionary consists of 470 excerpts (excluding phonetic variants), including 368 words of oriental origin, 73 from Latin and Greek, 26 from German and 3 from Italian. In addition, 159 derivatives were analysed (this number does not include variant forms). The lexicon includes a total of 629 units. However, the monograph is not only a collection and description of a number of lexical units, but also, on the basis of them, conclusions important for the humanities were drawn, including: • the determination of Tatars’ special place in the multilingual and multicultural communicative community of the Grand Duchy of Lithuania; • the presentation of the adaptation of lexis of foreign origin to the Polish of the Northern Borderlands as a result of contacts between Polish and East Slavic and Oriental languages, as well as Slavic-Oriental interference, which, among other things, serves to supplement the current state of research on the formation and development of this language variety; • it was found that, apart from the features characteristic of the Polish of the Northern Borderlands, the Tatar manuscript contains elements characteristic of the languages ​​and dialects of southwestern Belarus, northwestern Ukraine, and numerous borrowings from oriental languages ​​– translocated or Slavicised. It has been established that this "mixture" of languages ​​and dialects also characterises manuscripts of Muslim minorities from other regions of the world, such as the Iberian Peninsula, the Balkans, as well as Asia and Africa. Researchers, trying to identify the language of these monuments, oscillate between concepts such as language, dialect, and even register, which in turn correspond to the specific style of these monuments. Linguistic issues are therefore presented here against a broad historical and cultural background.
Muzyczne narracje o kochankach z Werony. Wprowadzenie do narratologii muzycznej
Authors: Pawłowska Małgorzata
Published: November 2024

Książka opowiada o jednym z podstawowych mitównowożytnej Europy i jego funkcjonowaniu w muzyce, w szerokim kontekście kultury. Podejmuje zarazem problematykę narracyjności dzieła muzycznego. Jest wynikiem poszukiwania odpowiedzi na dwa pytania: po pierwsze – jak topos Romea i Julii kształtuje się w historii muzyki, po drugie – czy kategoria narracji może być przydatna w badaniu muzyki? Ekspansja tej „megakategorii”, jaką jest narracja, z teorii literatury do wielu różnych dziedzin, w tym muzykologii, zachęcała do podjęcia próby zgłębienia jej zakresu znaczeniowego i konsekwencji metodologicznych. Monografia stanowi zarazem rekonesans narratologii muzycznej, wraz z przeglądem teorii i słownikiem terminów. Rozważania na temat narracji muzycznej oraz semantyki miłości, zarys dziejów tematu Romea i Julii w kulturze i muzyce oraz interpretacje dziewięciu reprezentatywnych dzieł muzycznych różnych gatunków – od genezy do rezonansu, przez pryzmat tytułowej kategorii narracji – zakorzenione zostały w obszernej literaturze narratologicznej, filozoficznej i muzykologicznej.
Introducción
Authors: Olmos Vega Francisco
Published: November 2024

La presente sección se compone de cuatro capítulos que exploran diferentes enfoques del aprendizaje en el campo de las profesiones de la salud. En el capítulo 1 se examina un seminario de semiología respiratoria, una estrategia desarrollada para los estudiantes del quinto semestre del programa de Medicina de la Universidad Cooperativa de Colombia. El capítulo 2 presenta un estudio de caso sobre el diagnóstico comunicacional en una situación problemática específica, en el contexto de la rotación clínica de cirugía y especialidades quirúrgicas de estudiantes de medicina de pregrado. El capítulo 3 aborda el uso de la discusión de casos clínicos como método de enseñanza en instituciones de salud. Por último, el capítulo 4 explora una comunidad virtual de aprendizaje que se creó en un servicio de neurología pediátrica debido a la pandemia de covid-19. Cada capítulo ofrece una visión de los retos y oportunidades de la enseñanza y el aprendizaje de los profesionales de la salud. Los autores se basan en su propia investigación y experiencia para ofrecer recomendaciones sobre cómo mejorar el proceso de aprendizaje. Es así como esta sección es un valioso recurso para cualquiera que esté interesado en aprender más sobre cómo enseñar y aprender en el campo de la educación para profesionales de la salud.
Evaluación programática en rotación de especialidad quirúrgica electiva para estudiantes de medicina
Authors: Téllez Rodríguez Luis J. , Rueda Gutiérrez Jorge A. , Girón-Luque Fernando
Published: November 2024

Para dar luces sobre este asunto, este estudio se enfoca en herramientas de evaluación para rotaciones de estudiantes de medicina en especialidades quirúrgicas electivas. Realizamos una revisión de los métodos de evaluación utilizados en rotaciones de especialidades quirúrgicas y después analizamos su aplicación y la percepción de los docentes sobre estas evaluaciones.
Board Gender Diversity Reforms Around the World: The Impact on Corporate Innovation
Authors: Wang Kun Tracy , Cui Lin , Zhu Nathan Zhenghang , Sun Aonan
Published: November 2024

In response to persistent gender inequality in corporate leadership, many countries have implemented board gender diversity reforms, either through legislation or by revising governance codes for board appointments. Whereas these reforms aim to enhance women’s representation and influence in leadership roles, their effects on corporate outcomes, such as innovation, remain unclear. This study develops a two-mechanism institutional contingency model to investigate how board gender diversity reforms affect firm innovation through representation and empowerment mechanisms. Using a unique hand-collected data set on worldwide board gender diversity reforms and a quasi-experimental difference-in-differences design, we find that these reforms significantly improve innovation outcomes, with the empowerment mechanism having a stronger positive effect than the representation mechanism. Additionally, we show that rule-based reforms, although they are effective at increasing female board representation, often lead to symbolic compliance and tokenism, which limits their ability to enhance innovation. In contrast, comply-or-explain reforms, which emphasize empowerment and genuine engagement, yield more meaningful progress in firm innovation. Our findings also reveal that countries with higher prereform gender disparities and a larger pool of qualified female directors experience greater innovation gains following the implementation of these reforms. By distinguishing between the effects of representation and empowerment, this study provides a nuanced understanding of how gender diversity regulations can serve as catalysts for innovation and offers valuable insights for policymakers designing reforms to promote gender equality and economic outcomes.

Funding: K. T. Wang and L. Cui gratefully acknowledge financial support from the College of Business and Economics at the Australian National University, and N. Z. Zhu acknowledges financial support from the School of Management at Zhejiang University.

Supplemental Material: The online appendix is available at https://doi.org/10.1287/orsc.22.16956 .
Educação Sexual na formação de professores: o papel da extensão universitária no diálogo sobre as nuances da sexualidade
Authors: Melo Beatriz dos Santos , Magalhães Vitória Areias , Lage Débora de Aguiar
Published: November 2024

Nos últimos anos, a extensão universitária, um dos pilares do tripé acadêmico nas universidades brasileiras, tem proporcionado a ampliação da cultura de criação de ligas acadêmicas para diferentes áreas do campo biomédico. Nesse contexto, a LESex – Liga de Educação Sexual da Uerj, atua desde 2015 no desenvolvimento de ações extensionistas voltadas para o debate sobre os múltiplos aspectos que envolvem a sexualidade humana. Este trabalho apresenta um relato dos grupos de estudo abertos ao público, realizados de forma remota, que possibilitaram aos professores em formação inicial e continuada um espaço de acolhimento, onde o diálogo sobre mitos e tabus ligados à sexualidade puderam ser debatidos de modo respeitoso e embasados cientificamente. Por fim, é discutida a relevância do debate e da troca de saberes sobre as três grandes temáticas abordadas nos 16 encontros realizados, a fim de proporcionar um olhar menos biologizante para as diversas nuances e perspectivas que abarcam a educação sexual.