bluuebunny/crossref_metadata_2025 huggingface dataset:
Serotonin 2A Receptor Attenuates Psoriatic Inflammation by Suppressing IL-23 Secretion in Monocyte-derived Langerhans Cells
Authors: Lee Yungling , Tan Yeh Fong , Yeh Chen-Yun , Hsu Sheng-Yun , Lu Chun-Hao , Tsai Ching-Hui , Chiang Pei-Chuan , Weng Hao-Jui , Tsai Tsen-Fang
Published: January 2025

Anecdotal evidence has suggested an association between psychiatric drugs and psoriasis but consensus is absent due to contradicting reports and the mechanism remains poorly defined. Here, we investigated the role played by serotonin 2A receptor (HTR2A), a receptor commonly targeted by psychiatric drugs, in regulating psoriasis. HTR2A antagonistic drugs worsened psoriatic outcome and HTR2A modulation reduced psoriatic inflammation. Using Imiquimod-induced psoriasiform model, HTR2A-deficient mice experienced exacerbated inflammation. Hematopoietic cells, particularly monocyte-derived Langerhans cells (moLC), were responsible for this phenotype. Mechanistically, the exacerbated inflammation is due to increased interleukin-23 (IL-23) secretion and HTR2A suppresses it by inhibiting activation of the non-canonical NFkB pathway. Serotonin is the putative agonist modulating HTR2A attenuating psoriatic inflammation. Lastly, our findings in mice were also validated clinically. Our data demonstrate serotonin modulates HTR2A, attenuating psoriatic inflammation by suppressing IL-23 secretion via inhibiting non-canonical NFkB pathway in moLCs.
Synergistic Effects of Diabetes and Smoking on Ticagrelor Antiplatelet Activity in ACS Patients Undergoing PCI
Authors: Elkenay Nasima Mohamed , Almasswary Adel , Sabah Zia ul , Agiba Nadia Ahmad , Elmahdy Hanaa Kamel , Elsherbiny Eman Aziz Yousef , Said Salwa Rashad Aly , Ewis Ahmed Mohamed , Ahmed Marwan Sayed Mohamed , Saleh Rayyh Abdelazeem Mohammad , Saleh Bothayna I , Alghamdi Huda S , Tahs Randa Sabour Elshahat , Radwan Enas Elsebaee Elsaid , Elmalah Abeer Ahmed
Published: January 2025

Background:Diabetes and smoking are well-established risk factors that enhance platelet reactivity in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).
Objective:To compare the combined (synergistic), individual effects of smoking and diabetes, and the absence of these risk factors on the antiplatelet efficacy of ticagrelor in ACS patients undergoing PCI.
Methods: A total of 400 patients participated in this study. Patients were stratified into four groups based on their smoking and diabetes status: Group I (diabetic Smokers), Group II (diabetic non-smokers), Group III (non-diabetic smokers), and Group IV (non-diabetic non-smokers), with 100 patients in each group. All patients received a 180 mg loading dose of ticagrelor immediately prior to PCI. Maximum platelet aggregation (MPA) and Platelet Reactivity Index (PRI) were assessed at baseline and at four hours post-loading dose administration of ticagrelor to evaluate antiplatelet activity.
Results: Baseline characteristics were comparable across all groups except for smoking and diabetes status. Group I (diabetic smokers) had a significantly higher proportion of individuals with high PRI compared to Group II (p=0.002), Group III (p=0.001), and Group IV (p=0.001), with no significant differences between Group II and Group III (p=1.000), Group II and Group IV (p=0.758), or Group III and Group IV (p=0.798). For high MPA, Group I also had significantly higher percentages compared to Group II (p=0.0005), Group III (p<0.0001), and Group IV (p=0.002), with no significant differences between Group II and Group III (p=0.712), Group II and Group IV (p=1.000), or Group III and Group IV (p=0.943). Multivariate logistic regression identified the combination of diabetes and smoking as a significant independent predictor for high PRI (adjusted OR: 2.24; 95% CI: 1.21-4.16; p=0.010) and high MPA (adjusted OR: 2.65; 95% CI: 1.08-6.48; p=0.031).
Conclusion: ACS patients who are both smokers and diabetics undergoing PCI may exhibit reduced responsiveness to the antiplatelet effects of ticagrelor, warranting closer clinical attention to optimize their management.
GWAS highlights the neuronal contribution to multiple sclerosis susceptibility
Authors: De Jager Philip , Zeng Lu , Khan Atlas , Lama Tsering , Chitnis Tanuja , Weiner Howard , Wang Gao , Fujita Masashi , Zipp Frauke , Taga Mariko , Kiryluk Krzysztof
Published: January 2025

Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative disease affecting the brain and spinal cord. Genetic studies have identified many risk loci, that were thought to primarily impact immune cells and microglia. Here, we performed a multi-ancestry genome-wide association study with 20,831 MS and 729,220 control participants, identifying 236 susceptibility variants outside the Major Histocompatibility Complex, including four novel loci. We derived a polygenic score for MS and, optimized for European ancestry, it is informative for African-American and Latino participants. Integrating single-cell data from blood and brain tissue, we identified 76 genes affected by MS risk variants. Notably, while T cells showed the strongest enrichment, inhibitory neurons emerged as a key cell type. The expression of IL7 and STAT3 are affected only in inhibitory neurons, highlighting the importance of neuronal and glial dysfunction in MS susceptibility.
Benchmarking State of the Art Website Embedding Methods for Effective Processing and Analysis in the Public Sector
Authors: Gerber Jonathan , Saxer Jasmin , Kreiner Bruno , Weiler Andreas
Published: January 2025

The ability to understand and process websites is crucial across various domains. It lays the foundation for machine understanding of websites. Specifically, website embedding proves invaluable when monitoring local government websites within the context of digital transformation. In this paper, we present a comparison of different state-of-the-art website embedding methods and their capability of creating a reasonable website embedding for our specific task. The models consist of visual, mixed, and textual-based embedding methods. We compare the models with a baseline model which embeds the header section of a website. We measure the performance of the models using zero-shot and transfer learning. We evaluate the performance of the models on three different datasets. Additionally to the embedding scoring, we evaluate the classification performance on these datasets. From the zero-shot models Homepage2Vec with visual, a combination of visual and textual embedding, performs best in general over all datasets. When applying transfer learning, MarkupLM, a markup language-based model, outperforms the others in both cluster scoring as well as precision and F1-score in the classification task. However, time is an important factor when it comes to processing large data quantities. Thus, when additionally considering the time needed, our baseline model is a good alternative, being 1.88 times faster with a maximum decrease of 10 % in the F1-score.
Transcriptional regulation of the non-homologous end joining gene Ligase IV by an intronic regulatory element directs thymocyte development
Authors: Collins Patrick , Estrada Matthew , Gebhardt Christopher , Salem Mariam , Sharma Kruthika , Bassing Craig , Oltz Eugene
Published: January 2025

Double-strand breaks represent the most dangerous form of DNA damage, and in resting cells, these breaks are sealed via the non-homologous end joining (NHEJ) factor Ligase IV (LIG4). Excessive NHEJ may be genotoxic, necessitating multiple mechanisms to control NHEJ activity. However, a clear mechanism of transcriptional control for them has not yet been identified. Here, we examine mechanisms governing Lig4 transcription in mammals, finding that most tissues maintain very low levels of LIG4 production. Select tissues upregulate LIG4, employing different strategies for genomic regulation. In developing lymphocytes, the Lig4 locus is devoid of long-range chromatin contacts; instead, its expression and role in immune development depend upon a promoter-proximal intronic regulatory element. Deletion of the Lig4 intronic regulatory element results in thymocyte-specific loss of Lig4 upregulation, defects in lymphocyte development and altered antigen receptor rearrangement. Our findings show the NHEJ gene, Lig4, is transcriptionally controlled to support stage-specific function concurrent with programmed DSBs. Moreover, we provide an example of how DNA cis-regulatory elements very close to a promoter can have substantial transcriptional effects.
The impact of pediatric obsessive-compulsive disorder on school attendance and school functioning: a case for supported education
Authors: Cruz Lorena Fernández de la , Rautio Daniel , Wickberg Frida , Gordan Cecilia , Silverberg-Mörse Maria , Mataix-Cols David
Published: January 2025

School-related functional impairment is common in children and adolescents with obsessive-compulsive disorder (OCD). However, little is known about the characteristics of youth with OCD who struggle in school, whether these struggles interfere with treatment outcomes, and whether treatment improves school-related function. Among 385 youth with OCD at a specialist clinic (mean age [sd] = 13.7 [2.5]; 63.1% girls), 21.6% had partial or no school attendance at intake. Among those who received specialist treatment (n = 322), outcomes were similar in those with no or partial attendance vs. those with full attendance, although the latter group needed fewer treatment sessions and were less likely to be on psychotropic medication. At post-treatment, 10.5% still had partial or no school attendance, and 22.8% of youths and 33.3% of parents reported significant school impairment, regardless of response status. Some youth with OCD may benefit from specific supported education and return to school strategies to complement regular evidence-based interventions.
Leveraging Information Technology Tools to Create Cost-Effective Alternatives: Using Google Sheets as a Platform for Competitive Debate and Public Speaking Tabulation.
Authors: Osei-Wusu Franco , Asiedu William , Yeboah Donald , Kar Shuvajyoti , Muntaka Siddique Abubakr , Appiah Joel Kwesi
Published: January 2025

Traditional web-based tabulation systems used for extracurriculars like debate competitions, while offering robust features, usually pose cost and accessibility challenges for respective stakeholders in the debate community within academic settings. Such challenges tend to limit participation, frequency of organization, or the smooth running of such events. In this paper, we leverage Google Sheets’ inherent features like Apps Script, Google Forms, real-time collaboration, and cloud functionality to create a cost-effective alternative, Tab XYZ, for debate and public speaking tabulation purposes. We examine and compare the proposed system’s key functionalities and architecture to a widely used conventional web-based platform, Tabbycat, through a comprehensive evaluation via metrics such as user satisfaction, ease of setup, cost-effectiveness, system reliability, data security and privacy, and error handling and management. After rigorous testing involving a diverse group of 435 users across five different debate and public speaking tournaments, results confirmed Tab XYZ's superior cost-effectiveness, comparable user satisfaction, robust data security through Google's infrastructure, and timely setup process. Additionally, the experiments revealed that the proposed system presented user-friendly and robust error handling and data recovery capabilities through offline functionality. Finally, this study presents a pathway for leveraging the integration of readily available Information Technology tools, such as Google Sheets and its features, to create innovative solutions for specialized problems within educational settings, to elude the burden of cost and accessibility that usually come with conventional approaches
Competencies for Undergraduate Dental Education in the African Context: A Qualitative Study in Four Dental Schools
Authors: Mutebi Annet Kutesa , Boamah Matthew Owusu , Ogundipe Olufemi Kolawole , Maart Ronel D
Published: January 2025

Background: Core competencies for new dental graduates have been established in various regions globally to harmonise educational standards and facilitate the migration of health workers. This has led to numerous curricular comparison studies, such as North America, Western Europe, and Asia. However, such efforts across the African continent are scarce. It is unclear how dental curricula in Sub-Saharan Africa compare, leading to potential variations in the skills and attributes of dental graduates from different countries. This study aimed to explore dental educators' views on the competencies required for dental graduates to practice in the 21st century at four Sub-Saharan African dental schools.
Methods: A cross-sectional qualitative study employing an exploratory descriptive approach was conducted between January and June 2023. Focus group discussions were held at four dental schools: University of the Western Cape (South Africa), Makerere University (Uganda), University of Ghana, and Obafemi Awolowo University (Nigeria). Dental educators were purposively sampled. Data were collected using unstructured interview guides focusing on competencies required upon graduation, their appropriateness to society, and suitability for 21st-century practice in Africa. Data were transcribed verbatim and analyzed using content analysis.
Findings: The study included 34 participants, with an even distribution of males and females. Seven themes emerged as essential competencies for dental graduates: clinical competence and skills, global and local competencies, technology and advanced tools, community and preventive dentistry, professionalism and ethical values, educational structure and assessment, and business aspects of dentistry. Participants emphasized the need for practical skills in various fields of dentistry, community diagnosis, and practice. They highlighted the importance of incorporating advanced technologies, professionalism, ethical standards, communication, and business skills into the curriculum.
Conclusion: The study revealed a consensus among dental educators on the necessity for more practical skills and community-oriented practice for dental graduates in Sub-Saharan Africa. The findings underscore the need for a unified curriculum across the continent to ensure consistent competency standards. Incorporating advanced technologies, professionalism, ethical standards, communication, and business skills into dental education is crucial for preparing graduates to meet the demands of modern dental practice while being responsive to the African context and maintaining global relevance.
Exploring the Association Between Hemoglobin Glycation Index and Cognitive Function in Older Adults with Hypertension: A Cross-Sectional Study
Authors: Ding Hong , Kang Tingyue , Gao Wenbo , Wang Qi , Liu Shu , Zhang Xiaowei , Yu Jing
Published: January 2025

Background
The Hemoglobin Glycation Index (HGI) quantifies the difference between the actual and expected values of glycosylated hemoglobin (HbA1c), a marker that has been closely linked to various adverse health outcomes. Nonetheless, a significant gap exists in the current literature concerning the association between HGI and cognitive function. This study aims at testing such association in older adults with hypertension, a topic that has not yet been extensively investigated.
Methods
A linear regression model between glycated hemoglobin A1c (HbA1c) levels and fasting plasma glucose (FPG) was constructed for the calculation of the HGI. The cross-sectional study focused on evaluating the cognitive function of hypertensive individuals (≥ 60 years old), based on the data from the 2011–2014 National Health and Nutrition Examination Survey (NHANES), by using a series of standardized tests, including the Word List Learning (CERAD-WL) and Delayed Recall (CERAD-DR) tests from the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). Weighted logistic and linear regression models served for evaluating the effect of HGI on hypertensive patients’ cognitive function. Restricted cubic spline (RCS) curves assisted in detecting the underlying nonlinear associations between HGI and cognitive outcomes. Furthermore, subgroup analyses and interaction tests were performed to gain deeper insights into these associations.
Results
The study included 1023 participants ≥ 60 years old from 2011–2014 NHANES. Higher HGI was accompanied by lower DSST score (P = 0.009). In the fully adjusted model, participants in the highest quartile (Q4) of HGI possessed a lower DSST score (β = 0.01, 95% CI 0.00–0.41) versus the lowest quartile (Q1), and were more likely to exhibit low cognitive function as evaluated by the DSST (OR = 2.21, 95% CI 0.98–5.03). According to the results from RCS analysis, HGI presented a linear relevance to cognitive function scores in older adults with hypertension. No significant statistical interaction was detected between these variables.
Conclusion
High HGI was an important risk factor leading to reduced cognitive performance in hypertensive patients, ensuring HGI to be used for effectively predicting patients’ cognitive decline.
Patterns and PredictOrS of HIV Treatment FaIlures in Pediatric EnrOlled ClieNts in a Tertiary HeAlth Care FaciLity in Southeast Nigeria - POSITIONAL study
Authors: Ogbuagu Chukwuanugo , Ogbuagu Ekenechukwu , Emelumadu Obiageli , Edokwe Emeka , Okereke Uzoma , Okwuchukwu Heavenah , Ezeama Nkiru , Uwakwe Richard
Published: January 2025

Introduction:
Managing pediatric HIV remains a critical challenge, especially in low- and middle-income countries like Nigeria, where healthcare resources are limited, and the HIV burden is high. This study explored the prevalence and determinants of antiretroviral treatment (ART) failure among children in the region. Key factors such as demographic characteristics, clinical parameters, and adherence levels were analyzed to identify predictors of treatment failure. By addressing these factors, the research aims to enhance management strategies, improve outcomes, and contribute to achieving viral suppression. This effort underscores the importance of targeted interventions to improve the quality of life for children living with HIV in resource-limited settings.
Method:
A retrospective cross-sectional study aimed to identify the patterns and predictors of pediatric HIV treatment failure at Nnamdi Azikiwe University Teaching Hospital (NAUTH) in Nnewi, Southeast Nigeria using medical records data of enrolled pediatric HIV patients over five years, from January 2019 to December 2023.
Result:
The study population comprised individuals enrolled in the pediatric clinic of the healthcare facility. Most participants were female (50.6%) and students (44.8%). The pattern showed that most participants were underweight at baseline (81.0%), most respondents adhered well to their regimen (99.7%), and a high percentage achieved undetectable viral loads (76.4%). The data indicated significant improvements in both CD4 counts and BMI over time, highlighting the positive impact of the treatment and management strategies employed. Virological failure was the most common predictor of treatment failure. Also, younger age at ART initiation, higher baseline viral load, and lower baseline CD4 count were significant predictors of treatment failure. Limited access to second-line ART options and inconsistent viral load monitoring were significant healthcare system-related barriers, reflecting the resource challenges in many LMICs.
Conclusion:
The findings from the study provided valuable insights into the patterns and predictors of pediatric HIV treatment failure at NAUTH Nnewi, Southeast Nigeria, highlighted the complex interplay between patient-related and healthcare system factors in managing pediatric HIV, and underscored the need for targeted interventions to improve treatment outcomes in this vulnerable population.
COLLAR: Combating Low-rank Temporal Latent Representation for High-dimensional Multivariate Time Series Prediction using Dynamic Koopman Regularization
Authors: Nie Siyu , An Simin , Peng Qifa , Su Yong
Published: January 2025

Recent advancements in high-dimensional multivariate time series forecasting have yielded promising outcomes by effectively capturing temporal dynamics within a low-dimensional latent subspace. While Recurrent Neural Networks (RNNs) excel at learning temporal models in reduced-dimensional spaces, the simplistic structure of the decoder fails to capture the diversity present in the observed data. Conversely, introducing a more intricate encoder might exacerbate the risk of overfitting. In response to this susceptibility, we propose COLLAR – an innovative architecture that employs dynamic linearized regularization. COLLAR aims to reconcile the inherent nonlinear temporal structures present in low-dimensional subspaces with the linear evolution of multivariate time series. Specifically, we utilize the Auto-Encoder (AE) as the backbone, facilitating the factorization of multivariable time series into a low-dimensional subspace. We construct a nonlinear prediction model for latent sequences using Gated Recurrent Units (GRU). To learn linear dynamics, we integrate the data-driven Koopman operator with a modified AE architecture to generate linear dynamics regularization terms, thereby constraining the uncertainty in nonlinear prediction. The eigenfunctions derived from the Koopman operator provide intrinsic coordinates that globally linearize the dynamics, enabling the prediction of the next state to depend solely on the current state. The proposed approach is evaluated across five publicly available datasets and outperforms several competitive baselines. The code and models are available at https://github.com/Nsyyyy/COLLAR.
Bio Fabrication of Zinc oxide nanoparticles using Dillenia indica (Elephant apple) Core extract and its Antimicrobial properties.
Authors: Hussain Sameer , Agarwala Satyakam , Sharma Deboja , Suiam Gwyneth Rachel
Published: January 2025

At present, the focus on bringing change via green synthesis of nanoparticles is peak field in research and development. In this study, biosynthesis of ZnO nanoparticles from fruit gel extracts of Dillenia indica natively known as "ou tenga" is used as a key reducing agents and reported as eco-friendly, rapid, and cost-effectiveness. The Characterization for synthesized nanoparticles were done by transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), UV–visible spectroscopy (UV–vis), X-ray diffraction (XRD) and fourier transform infrared spectroscopy (FTIR). The nanoparticles were exclusively ZnO, beaned shape with dimensions scaling from 12 nm to 15 nm. In current work, the green synthesized ZnO nanoparticles have been engaged for antimicrobial activity. The antimicrobial activity of characterized samples was determined using different concentrations of biosynthesized ZnO nanoparticles 10 ml, 20 ml, 30 ml, and 50 ml against Gram-positive bacteria Staphylococcus aureus (ATCC-BAA976) and fungi Aspergillus niger (ATCC-10535) 50 ml via well diffusion technique, grown using broth incubation method. The analysis revealed that the bacterial inhibition escalates with increasing concentration of bio derived - ZnO nanoparticles. Likewise, fungi Aspergillus niger was apparently sensitive to a set proportion of the nanoparticles. In this research, the idea of amalgamating beneficiary gel with ZnO retaining the biochemical properties of the gel, post-synthesis, combining the theme of tradition and science, this can play a crucial role in the eliminating prime skin infection and dandruff causing microbes, and use in some sort of cosmetic and skin health products.
Predictors of depression and suicidal behaviors among in-school adolescents in Nigeria: A Cross-sectional Study
Authors: IGHAEDE-EDWARDS Isabella G. , ALLOGO Idriss François NTSAME , LIU Xiaoqun , BOUNDA Guy Armel , DAVID-OLAWADE Aanuoluwapo CLEMENT , OLAWADE David B.
Published: January 2025

Aim: This study investigates the prevalence and determinants of depression and suicidal behavior among secondary school adolescents in Edo State, Nigeria.
Subject and Methods: A descriptive, cross-sectional study was conducted with 621 in-school adolescents, selected through multistage random sampling. Depression and suicidal ideation were assessed using the Patient Health Questionnaire-9 (PHQ-9) and Suicidal Behavior Questionnaire-Revised (SBQ-R). Statistical analyses, including chi-squared tests, Fisher’s exact tests, and logistic regression, explored correlations, with significance set at p < 0.05
Results: Among participants, 26.09% reported mild depressive symptoms, while 10.9% exhibited moderate-to-severe symptoms; 6.1% had suicidal ideation. Depression risk factors included school type, residential area, and frequency of parental discipline. Adolescents in public schools had a 5.03 times higher likelihood of depression compared to their private school counterparts (AOR: 5.03; CI: 2.02–12.54), and those frequently disciplined by parents were 3.18 times more likely to experience depression (OR: 3.18; CI: 1.30–7.81). Senior students showed a higher risk of suicidal behavior (OR: 0.15; CI: 0.07–0.34), as did those in public schools (OR: 3.67; CI: 1.70–8.37) and those frequently punished (OR: 6.67; CI: 2.15–20.73). Depression and suicidality were strongly correlated (p ≤ 0.01).
Conclusion: The notable rates of depression and suicidal behavior in Nigerian adolescents underscore the need for targeted mental health interventions. Establishing support structures and policy interventions in schools and communities could help identify and support at-risk adolescents, reducing the risk of adverse mental health outcomes.
Influence of Time of Day, Breaks, and Physical Activity on Injuries in Recreational Alpine Skiers
Authors: Kolarić Dinko , Kolarić Ana , Sirovec Domagoj , Ružić Lana
Published: January 2025

Objectives: This study aims to identify significant risk factors contributing to injuries in recreational alpine skiers using a validated questionnaire.
Design: Retrospective cohort study.
Methods: Participants were categorized into two groups: the injured group (N = 212) and the uninjured group (N = 206). The injured skiers completed a questionnaire that identified potential risk factors, while the control group answered the same questionnaire, excluding injury-related questions. General questions were used to assess the likelihood of injury and additional questions for the injured group helped evaluate injury severity using the Injury Severity Score (ISS).
Results: The analysis revealed several key risk factors. Skiers aged over 40 years were identified as a higher-risk group. Women were found to experience more severe injuries and had a higher incidence of knee injuries. The highest risk of injury was observed on the third day of skiing, with injuries most likely occurring between noon and 2 p.m. Additionally, injuries were more frequent after three hours of skiing. An increase in the average duration of breaks was associated with a 14% reduction in the likelihood of injury for every additional 10 minutes of break time. Body mass index (BMI), regular physical training throughout the year, regardless of the duration or intensity of the training, and warming up before skiing did not significantly reduce injury risk or affect injury severity.
Conclusions: Gender, age, time of day, skiing duration, and break duration are identified as significant potential risk factors for injuries in recreational alpine skiing.
Polypharmacy and pharmacogenomics in high-acuity behavioral health care for autism spectrum disorder: A retrospective study
Authors: Garrison Sheldon R. , Schweinert Sophie A. , Boyer Matthew W. , Singh Maharaj , Vadapalli Sreya , Engelmann Jeffery M. , Schwartz Rachel A. , Hartig Madeline M.
Published: January 2025

Purpose
This study evaluated pharmacogenomic (PGx) testing in children and adolescents with autism spectrum disorder (ASD). ASD frequently presents with co-occurring depression and anxiety. This complex phenotype often results in psychotropic medication polypharmacy. Incorporating PGx testing into the medical work-up may reduce polypharmacy and improve quality of life with symptom reduction.
Methods
A retrospective electronic health record review between January 2017 to May 2023. Individuals either received PGx testing or treatment as usual (TAU). The co-primary outcomes were polypharmacy and the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q). Secondary outcomes included length of stay and assessments measuring severity or behavioral impact.
Results
A total of 99 individuals with ASD were analyzed. At the time of admission, 93% of individuals were prescribed at least one psychotropic medication and over half of these individuals were prescribed medications with potential gene-drug interactions. Following PGx testing, there was an overall reduction in prescribed medications with a potential gene-drug interaction. Quality of life and symptom assessments of depression, anxiety, obsessive-compulsive disorder and body-focused repetitive behaviors revealed similar improvements in the PGx and TAU groups. Subanalysis comparing congruent (“use as directed”) or incongruent (“use with caution”), as well as analysis of only CYP2D6 and CYP2C19 gene-drug interactions, were observed to have a similar profile.
Conclusion
Combinatorial PGx testing was utilized as a clinical decision-making tool for medication selection and dosage adjustment. As a result, all treatment groups were able to achieve similar levels of polypharmacy, improvement in quality of life and symptom reduction.
Management and Outcome of a 14-Week-6-Day Ruptured Interstitial Ectopic Pregnancy with Intact Amniotic Sac in a Resource-Limited Setting
Authors: Achangwa Chabeja , Cheuyem Fabrice Zobel Lekeumo , Nche Charlotte Bih , Buhari Shanunu Mohamed , Ateh Stanislas Ketum
Published: January 2025

Background: Interstitial ectopic pregnancy is a rare form of ectopic pregnancy, accounting only for 2 to 3 % of cases. The mortality rate is 6-7 times higher than that in classic ectopic pregnancy. Most cases of interstitial ectopic pregnancy always present with rupture due to the challenges of clinical and radiologic diagnosis. Surgery remains the treatment of choice when rupture and hemodynamic instability occur. This report aimed at presenting a very rare case of ruptured interstitial ectopic pregnancy.
Case Presentation: A 27-year-old sub–Saharan African woman presented to our health facility with cramping abdominal pain associated with vomiting, fatigue, and dizziness. She was diagnosed with an advanced ruptured interstitial ectopic pregnancy at 14 weeks 6 days with a pelvic ultrasound. A laparotomy was done, and her recovery was uneventful.
Conclusion: Interstitial ectopic pregnancy remains a rare type of ectopic pregnancy that is rarely reported, let alone extending beyond the early second trimester. Early diagnosis and timely surgical intervention are essential to prevent life-threatening complications. This case highlights the importance of integrating clinical, imaging, and laboratory findings in the diagnosis of advanced ectopic pregnancy.
Research on ZWD Forecasting Model Based on Improved Random Forest Algorithm
Authors: Lin He , Hong Wang , Hui Zhang , Wenjie Peng , Bao Zhang
Published: January 2025

When electromagnetic wave signals from the Global Navigation Satellite System (GNSS) pass through the troposphere, they are impeded by atmospheric conditions, thereby affecting positioning efficiency. The atmosphere is rich in water vapor information, which can typically be studied quantitatively through tropospheric zenith wet delay (ZWD). Therefore, high-precision forecasting models of ZWD are of significant research importance in GNSS positioning enhancement, weather forecasting, and water vapor inversion. The Random Forest (RF) algorithm has advantages in terms of improving accuracy, resistance to overfitting, and assessing feature importance. Aiming at the complex spatiotemporal patterns of global ZWD and the difficulty in establishing high-precision models, this paper develops a high-precision ZWD forecasting model based on the RF algorithm. In this study, we processed global ZWD data from 2021 to 2024, studied the spatiotemporal distribution characteristics of ZWD from 2021 to 2023, analyzed the spatial distribution patterns and temporal variation trends of ZWD, and the time series data of ZWD was used as input for the RF algorithm to construct a global ZWD forecasting model, plotted the testing set prediction results, regression charts, error histograms, feature importance diagrams, and error curves, and calculated precision indicators such as mean absolute error, root mean square error, mean percentage error, and coefficient of determination to comprehensively evaluate the model's accuracy. The results indicate that the ZWD forecasting model based on the RF algorithm has a higher accuracy in the equatorial region, with an optimal value reaching 96.14%. When predicting for stations worldwide, the testing set's mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE) are all relatively small, while the R2 value is comparatively large, with average values of 1.623 cm, 2.146 cm, 19.478%, and 0.691, respectively. Compared to similar models, the new model developed in this study shows a significantly improved forecasting performance. In the current landscape of ZWD forecasting models, there is a scarcity of models that offer global coverage and extended forecast durations. The model developed in this study is capable of providing one-month ahead forecasts for ZWD across the globe, thereby providing theoretical and data support for the establishment of additional long-term global forecasting models in the future.
Preproinsulin-specific regulatory T cell-derived exosomes loaded with immune checkpoint ligands can suppress autoimmune responses in type 1 diabetes
Authors: Basak Preetam , Dayal Devi , Bhadada Sanjay , Kumar Rakesh , Sachdeva Naresh
Published: January 2025

Background
Type 1 diabetes (T1D) is an autoimmune disease, caused by selective destruction of pancreatic beta cells, mediated mainly by infiltrating CD8 + T cells. These CD8 + T cells also express immune checkpoint molecules (ICMs) which can be targeted by specific immune checkpoint ligands (ICLs) as well as beta cell-specific regulatory T cells (Tregs) to induce immunosuppression.
Methods
We first performed profiling of various ICMs on the peripheral CD8 + T cells in 40 recent-onset T1D and 20 age-matched healthy subjects by flow cytometry. Tregs were isolated from the same subjects and stimulated with preproinsulin (PPI) in vitro to generate PPI-specific Tregs. Exosomes were isolated from PPI-specific Tregs and characterized by western blotting, transmission electron microscopy, zeta potential, and particle size analysis. Based on flow cytometry data, we chose ICLs binding to the 3 most abundant ICMs (PD-1, TIGIT, BTLA) expressed on the peripheral CD8 + T cells for loading exosomes. The loading of ICLs was optimized by sonication and ICL-loaded exosomes (PPI-T-EXOL) were recharacterized. The PPI-T-EXOL and Tregs infused with PPI-T-EXOL were assessed separately in suppressing T cell proliferation, activation of autologous PPI-pulsed CD8 + T cells, and beta cell protection. Finally, mice-specific PPI-T-EXOL were administered in STZ-induced diabetic C57BL/6 mice to inhibit T1D pathogenesis.
Results
The PPI-T-EXOL showed similar size and stability as naive exosomes and the efficiency of incorporation of ICL on PPI-Treg exosomes was almost 50%. The PPI-T-EXOL inhibited the proliferation of autologous CD8 + and CD4 + T cells in vitro. The PPI-T-EXOL and PPI-Tregs infused with PPI-T-EXOL showed significant suppression of perforin, granzyme B, and IFN-gamma and activation markers, C69 and CD71 in autologous PPI-pulsed CD8 + T cells. The PPI-T-EXOL-infused Tregs also protected pancreatic beta cells (1.1B4 cell line) from CD8 + T cell-mediated apoptosis. Further, in STZ-induced diabetic C57BL/6 mice, the mice-specific PPI-T-EXOL delayed the onset of hyperglycemia, particularly when administered before the onset of diabetes. The treatment with PPI-T-EXOL partially controlled hyperglycemia, prolonged survival, reduced perivascular intra-islet lymphocytic infiltration, and greater preservation of beta cells.
Conclusions
Our results suggest that PPI-Treg-derived exosomes loaded with ICL can suppress beta cell-specific T cell responses, offering a promising therapeutic intervention in T1D.
HuD and Alpha-crystallin A Axis Protects Neuro-Retinal Cells in Early Diabetes
Authors: Kim Chongtae , Oh Subeen , Park Young-Hoon
Published: January 2025

Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes; however, neuro-retinal degeneration is also observed in patients with diabetes without signs of DR. The mechanisms leading to neuro-retinal cell loss before vascular complications manifest in diabetes remain poorly understood. In this study, we investigated the neuronal RNA-binding protein HuD as a novel regulator of neuro-retinal degeneration in the early stage of diabetes. We determined the expression of HuD and alpha-crystallin A (CRYAA) in the retinal ganglion cell layer. HuD and CRYAA were down-regulated in the retinas of streptozotocin-induced diabetic rats and in neuro-retinal cells (R-28) treated with high glucose. Cryaa mRNA was identified as a novel target transcript of HuD, and we demonstrated that HuD post-transcriptionally regulates the expression of Cryaa mRNA by binding to its 3′-untranslated region. Silencing and overexpression of HuD positively regulated the expressions of Cryaa mRNA and protein. We demonstrated that the increase in inflammatory cytokines such as TNFα, IL-1β, and IL-6 in R-28 cells under hyperglycemic conditions was a result of both CRYAA and HuD levels. Silencing HuD and CRYAA enhanced high glucose-induced R-28 cell death, whereas their overexpression alleviated this effect. HuD post-transcriptionally regulates CRYAA expression, influencing the function and viability of neuro-retinal cells under diabetic conditions. Our results suggest that the HuD/CRYAA axis plays a crucial role in neuro-retinal cells and has the potential to serve as a prognostic factor and therapeutic target for diabetic neuro-retinal degeneration.
Low-frequency oscillations in the magnetic nozzle of a Helicon Plasma Thruster
Authors: Maddaloni Davide , Bayón-Buján Borja , Navarro-Cavallé Jaume , Terragni Filippo , Merino Mario
Published: January 2025

Oscillations within the plume of a Helicon Plasma Thruster are experimentally characterized. An array of electrically-floating probes is used to resolve the power spectral density, the coherence, and the wavevector components along both the azimuthal and parallel directions relative to the magnetic field, at various locations and for two mass flow rates. Two main features are identified: a very low-frequency (~4 kHz), global oscillation mode, attributed to an ionization instability in the source; and a broadband, low-coherence, essentially-azimuthal, ion-acoustic-like spectrum at <200 kHz. Within this range, a mild peak of larger coherence is found ~50 kHz, followed by a weak secondary peak at ~100 kHz at some locations. A bi-coherence analysis discards any nonlinear interaction within the <1 MHz band. However, significant coupling is found between the broadband fluctuations and the Helicon driving frequency of 13.56 MHz, which suggests that the former are likely the result of a parametric decay instability.
System biology based integrative analysis to predict early biomarkers for COVID-related MIS in children
Authors: Verma Awadhesh Kumar , Singh Tanya
Published: January 2025

The outbreak of COVID-19 caused by SARS-CoV-2 has introduced unparalleled difficulties, including the appearance of a rare but serious condition in children referred to as Multisystem Inflammatory Syndrome in Children (MIS-C). This syndrome, marked by an overactive immune response resulting in extensive inflammation throughout various organ systems, has underscored the pressing necessity for predictive biomarkers to enhance early diagnosis and treatment. This research aimed to fill this gap using a comprehensive bioinformatics approach, applying fold-change and adjusted p-value techniques to detect differentially expressed genes (DEGs). DESeq2 was utilized to enhance these biomarkers, ensuring a strong and precise selection procedure. To accurately predict MIS-C biomarkers, numerous machine learning classifiers were evaluated, and the Random Forest model excelled compared to the rest. It showed a significant accuracy of 0.81 for moderate DEGs, confirming its appropriateness for biomarker prediction in COVID-19-related MIS-C. The results highlight the strength of computational biology in understanding the molecular processes associated with intricate conditions such as MIS-C, facilitating focused exploration of treatment approaches. Through in silico analysis and visualisation, a particular drug ligand named Methylprednisolone came out to an ideal candidate that shows favourable binding affinity with the genes deduced from ML analysis. This study not only clarifies the pathophysiology of MIS-C but also opens avenues for utilizing advanced statistical and machine learning techniques in clinical studies. By connecting computational and clinical fields, this study marks an important advancement in reducing the effects of severe COVID-19-related issues in children.
Sicherheit und Wirksamkeit des Rituximab-Biosimilars Truxima® bei CD20-positiven Non-Hodgkin-Lymphomen und chronisch lymphatischer Leukämie im Rahmen der TRUDY-Registerstudie
Authors:   , Schmidt Sarah
Published: January 2025

In dieser Arbeit soll basierend auf der nichtinterventionellen TRUDY Studie die therapeutische Effektivität und Arzneimittelsicherheit des Rituximab-Biosimilars Truxima® evaluiert werden. Bei TRUDY handelte es sich um eine einarmige, unizentrische Studie, die die routinemäßige Anwendung des anti-CD20 Biologicals bei CD20-positiven Non-Hodgkin-Lymphomen und chronisch lymphatischer Leukämie im ambulanten Sektor wiedergeben soll. Darüber hinaus werden in dieser Arbeit Aspekte der Versorgungsforschung berücksichtigt.
Methoden
60 Patientinnen und Patientenwurden in die Analyse eingeschlossen.Hierbei wurden Behandlungserfolg, sowie unerwünschte Ereignisse innerhalb eines Zeitraumes von sechs Monaten retrospektiv anhand der Patientenakten erhoben und ausgewertet. Bezüglich der Arzneimittelsicherheit wurden Ereignisse auf einen Zusammenhang zu Truxima® überprüft und gesondert dargestellt.
Es erfolgte eine deskriptive statistische Darstellung sowie eine Analyse möglicher Risikofaktoren hinsichtlich des Therapieerfolges.
Ergebnisse
Für das Gesamtkollektiv wurde eine Overall Response Rate von insgesamt 86,7% erhoben. Die Rate an Komplettremissionen betrug definitionsabhängig zwischen 58,3% und 31,7% (Erläuterung siehe 2.3.3. Remissionskriterien).
Die Evaluation unerwünschter Ereignisse ergab durchschnittlich 4 Ereignisse pro Patient/Patientin innerhalb des beobachteten Zeitraumes. Davon war jedoch nur ein geringer Anteil der Ereignisse pro Person (0-7; im Median 0) kausal auf Truxima® zurückzuführen. Meist handelte es sich um unerwünschte Wirkungen der konventionellen Chemotherapie. Die häufigsten unerwünschten Arzneimittelwirkungen von Truxima® waren infusionsassoziierte Reaktionen im Rahmen eines Cytokine Release Syndroms, sowie Reaktivierungen viraler Infektionen. Dabei war die überwiegende Mehrheit der Ereignisse als nicht schwerwiegend zu bewerten.
Schlussfolgerung
Die Beobachtungen belegen eine gute therapeutische Effektivität, die mit vorangegangenen Studien zu Truxima® und Mabthera® kongruent ist. Darüber hinaus erwies sich Truxima® als sicheres Biosimilar.
Bei vergleichbarem Sicherheits- und Effektivitätsprofil ermöglichte Truxima eine Kosteneinsparung, die den Zugang zu einer adäquaten anti-CD20 Therapie verbessert und zur Deckung eines steigenden Bedarfes zielgerichteter antineoplastischer Therapien beitragen kann.
Exploring the paradoxical national projection in small and secluded island realities: The case of the Canary Islands
Authors: Montesdeoca Pérez Jorge Antonio
Published: January 2025

This study explores the paradox of nationalism in small insular communities isolated in seas, particularly oceans. Despite their distinct identity, unique history, exclusive connection between people and territory, and strong association between local symbology and landscape, these communities often resist attaining national status, perceiving it as a precursor to statehood. This paradox manifests as an internal conflict between embracing and rejecting a national image. Historically, this resistance has prevailed, subtly shaping the political and social development of such islands.
The Canary Islands serve as a prime example of this dynamic. While the archipelago is not currently pursuing nationhood, it presents a unique case for studying nationalism within these insular contexts, with evidence of this paradox in both historical and recent times. Therefore, this article argues for maintaining the scope of nationalism studies within these insular contexts, regardless of whether the communities have become nations. More specifically, this article demonstrates that owing to their interaction with paradox, it can be very beneficial to analyse such insular contexts using established theories that focus on explaining the nation-formation process.
Comparative Insights on Workcation Providers: Applying Japanese Models to Korean Islands
Authors: Lee Tae Gyeom , Lee Jae Ho
Published: January 2025

The relational population concept, which includes individuals engaging with regions without residing there, is key to combating regional extinction and population decline in island areas. This study explores strategies for introducing workcations in island regions by analyzing promotional materials from South Korea and Japan. Through a comprehensive analysis of promotional data using Latent Dirichlet Allocation and cluster analysis, the study identifies significant themes in workcation attraction strategies, highlighting differences and similarities between the two countries. The findings emphasize the importance of leveraging unique regional characteristics, providing excellent facilities, and promoting long-term stay programs. South Korea focuses on maintaining work efficiency in diverse settings, while Japan adopts a more holistic approach integrating work into a nature-oriented lifestyle. Recommendations include turning infrastructure challenges into advantages and diversifying workcation programs. This research contributes to the development of effective workcation policies and serves as a resource for enhancing the sustainability of island regions. By examining successful practices in South Korea and Japan, the study offers valuable insights for policymakers and regional planners seeking innovative approaches to address depopulation issues and revitalize island communities in the context of evolving work patterns and digital connectivity.