Extensive Studies Research Articles

Prevalence of bluetongue virus disease in a small ruminant population in Kalat, Balochistan, Pakistan

Background and Aim: Bluetongue is a vector-borne, emerging disease that poses a severe threat to most domesticated animals. A cross-sectional study was conducted to estimate the prevalence of bluetongue virus (BTV) disease in apparently healthy sheep and goats in Kalat, Balochistan. Materials and Methods: A total of 270 serum samples (sheep: 150 and goat: 120) were collected and screened for the detection of anti-BTV antibodies using a competitive enzyme-linked immunosorbent assay. The data regarding different contributory risk factors were also collected using a predesigned questionnaire. Results: It revealed that overall, 27.4% (74/270, 95% confidence interval, χ2 = 1.71, p = 0.12) prevalence in both sheep and goat populations. The highest prevalence of 47% (32/68) was recorded in Surab city with the lowest prevalence of 15.49% (11/71) in the Manguchar area. In contrast, in Kalat 28.1% (9/32), Daan area 24% (12/50), and Marap area 22.44% (11/49), seropositivity was recorded. Upon sex bases, antibodies were almost equally found in both male 28.57% (8/28) and female 27.27% (66/242) animal populations. Moreover, all four breeds (Balochi, Khurasani, Lehri, and Rakhshani) were equally and potentially seropositive. The Khurasani breed was the most susceptible to 34.69% (17/49), followed by the Balochi breed, 45/145 (31%) seropositivity. The prevalence of BTV was 16.66% (1/6) in Rakhshani breed and 15.71% (11/70) in Lehri breed., Ticks were found in almost 21% of animals, while 93% of animals were reared on open grazing in rangelands. Conclusion: This study clearly indicates widespread BTV infection in small ruminants in the study area that may pose serious threats to livestock farming. Further extensive studies are recommended to study the prevalence of disease in different agroecological zones of the province. This also warns the high-ups to manage concrete efforts to eradicate and control the disease in the area. Keywords: antibodies, Balochistan, bluetongue virus, competitive enzyme-linked immunosorbent assay, Kalat.

52676 Safety and efficacy over one year of spesolimab treatment in patients with hidradenitis suppurativa (HS): Interim analysis of an open-label extension (OLE) study

52676 Safety and efficacy over one year of spesolimab treatment in patients with hidradenitis suppurativa (HS): Interim analysis of an open-label extension (OLE) study

51876 Impact of Long-Term Abrocitinib Treatment on Patient-Reported Outcomes and Quality of Life for Approximately 2 Years in Patients With Moderate-to-Severe Atopic Dermatitis: An Interim Analysis of JADE EXTEND, a Long-Term Extension Study

51876 Impact of Long-Term Abrocitinib Treatment on Patient-Reported Outcomes and Quality of Life for Approximately 2 Years in Patients With Moderate-to-Severe Atopic Dermatitis: An Interim Analysis of JADE EXTEND, a Long-Term Extension Study

50342 Serum Protein Biomarkers May Reveal Clues to Early Immune Activity Upon Ruxolitinib Cream Withdrawal in the TRuE-V Long-Term Extension Study

50342 Serum Protein Biomarkers May Reveal Clues to Early Immune Activity Upon Ruxolitinib Cream Withdrawal in the TRuE-V Long-Term Extension Study

52650 Dupilumab Treatment Shows Rapid and Consistent Improvement in Atopic Dermatitis in All Anatomical Regions in Patients Aged 6 Months to 17 Years: Results From an Open-Label Extension Study

52650 Dupilumab Treatment Shows Rapid and Consistent Improvement in Atopic Dermatitis in All Anatomical Regions in Patients Aged 6 Months to 17 Years: Results From an Open-Label Extension Study

52636 Remibrutinib improves hive severity in patients with chronic spontaneous urticaria: 52-week results from a Phase 2b extension study

52636 Remibrutinib improves hive severity in patients with chronic spontaneous urticaria: 52-week results from a Phase 2b extension study

52697 Incidence of Injection-Site Reactions With Dupilumab Treatment in a 5-Year Open-Label Extension Study of Adults With Moderate-to-Severe Atopic Dermatitis

52697 Incidence of Injection-Site Reactions With Dupilumab Treatment in a 5-Year Open-Label Extension Study of Adults With Moderate-to-Severe Atopic Dermatitis

Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy.

Long-term safety and efficacy of mavacamten in patients with obstructive hypertrophic cardiomyopathy (HCM) are unknown. MAVA-LTE (NCT03723655) is an ongoing, 5-year, open-label extension study designed to evaluate the long-term effects of mavacamten. Participants from EXPLORER-HCM (NCT03470545) could enrol in MAVA-LTE upon study completion. At the latest data cut-off, 211 (91.3%) of 231 patients originally enrolled in MAVA-LTE still received mavacamten. Median (range) time on study was 166.1 (6.0-228.1) weeks; 185 (80.1%) and 99 (42.9%) patients had completed the week 156 and 180 visits, respectively. Sustained reductions from baseline to week 180 occurred in left ventricular outflow tract gradients (mean [standard deviation]: resting, -40.3 [32.7] mmHg; Valsalva, -55.3 [33.7] mmHg), NT-proBNP (median [interquartile range]: -562 [-1162.5, -209] ng/L), and EQ-5D-5L score (mean [standard deviation]: 0.09 [0.17]). Mean left ventricular ejection fraction (LVEF) decreased from 73.9% (baseline) to 66.6% (week 24) and 63.9% (week 180). At week 180, 74 (77.9%) of 95 patients improved by at least one New York Heart Association class from baseline. Over 739 patient-years exposure, 20 patients (8.7%; exposure-adjusted incidence: 2.77/100 patient-years) experienced 22 transient reductions in LVEF to <50% resulting in temporary treatment interruption (all recovered LVEF of ≥50%). Five (2.2%) patients died (all considered unrelated to mavacamten). Long-term mavacamten treatment resulted in sustained improvements in cardiac function and symptoms in patients with obstructive HCM, with no new safety concerns identified. Transient, reversible reductions in LVEF were observed in a small proportion of patients during long-term follow-up.

52859 Time to first relapse during treatment-free follow-up without remibrutinib in patients with chronic spontaneous urticaria (CSU): subgroup analysis by baseline disease status and CSU duration from a Phase 2b extension study

52859 Time to first relapse during treatment-free follow-up without remibrutinib in patients with chronic spontaneous urticaria (CSU): subgroup analysis by baseline disease status and CSU duration from a Phase 2b extension study

53683 Remibrutinib provides sustained improvement in itch severity in patients with chronic spontaneous urticaria: Phase 2b open-label extension study

53683 Remibrutinib provides sustained improvement in itch severity in patients with chronic spontaneous urticaria: Phase 2b open-label extension study

Employing a synergistic bioinformatics and machine learning framework to elucidate biomarkers associating asthma with pyrimidine metabolism genes.

Asthma, a prevalent chronic inflammatory disorder, is shaped by a multifaceted interplay between genetic susceptibilities and environmental exposures. Despite strides in deciphering its pathophysiological landscape, the intricate molecular underpinnings of asthma remain elusive. The focus has increasingly shifted toward the metabolic aberrations accompanying asthma, particularly within the domain of pyrimidine metabolism (PyM)-a critical pathway in nucleotide synthesis and degradation. While the therapeutic relevance of PyM has been recognized across various diseases, its specific contributions to asthma pathology are yet underexplored. This study employs sophisticated bioinformatics approaches to delineate and confirm the involvement of PyM genes (PyMGs) in asthma, aiming to bridge this significant gap in knowledge. Employing cutting-edge bioinformatics techniques, this research aimed to elucidate the role of PyMGs in asthma. We conducted a detailed examination of 31 PyMGs to assess their differential expression. Through Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA), we explored the biological functions and pathways linked to these genes. We utilized Lasso regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) to pinpoint critical hub genes and to ascertain the diagnostic accuracy of eight PyMGs in distinguishing asthma, complemented by an extensive correlation study with the clinical features of the disease. Validation of the gene expressions was performed using datasets GSE76262 and GSE147878. Our analyses revealed that eleven PyMGs-DHODH, UMPS, NME7, NME1, POLR2B, POLR3B, POLR1C, POLE, ENPP3, RRM2B, TK2-are significantly associated with asthma. These genes play crucial roles in essential biological processes such as RNA splicing, anatomical structure maintenance, and metabolic processes involving purine compounds. This investigation identifies eleven PyMGs at the core of asthma's pathogenesis, establishing them as potential biomarkers for this disease. Our findings enhance the understanding of asthma's molecular mechanisms and open new avenues for improving diagnostics, monitoring, and progression evaluation. By providing new insights into non-cancerous pathologies, our work introduces a novel perspective and sets the stage for further studies in this field.

Transforming higher education: a decade of integrating wikipedia and wikidata for literacy enhancement and social impact

AbstractThis study examines a decade-long implementation of a course model leveraging Wikipedia and Wikidata as primary educational platforms in higher education. In alignment with the UNs’ SDG 4, this initiative emphasized inclusive, equitable education and lifelong learning opportunities. The study scrutinizes the formulation and deployment of three elective courses, rooted in this model, which were designed to augment students’ academic, digital, collaborative, and communication skills through the creation of Open Educational Resources (OERs), achieving significant social impact—evidenced by over 2000 new and 7000 edited articles, accruing 75 million public views. The research addresses three principal areas: the development and application of the model; course outcomes, including OERs produced, academic achievements, and students’ learning experiences; perceived challenges and benefits from the perspective of both students and faculty. A mixed-methods approach was employed to examine data from 17 iterations, involving 616 participants. Students’ learning experience was extracted from post-course questionnaires completed by 70% (n = 429). Findings demonstrate the role of Wikipedia and Wikidata in fostering knowledge creation, digital and data literacies and critical thinking, with the research contributing to the conversation surrounding Open Educational Practices. Findings include details on incorporating issues of diversity, equity, inclusion (DEI) and knowledge gaps into the curriculum design, and map challenges and benefit for students and faculty. This extensive study offers valuable insights into the effectiveness of embedding OERs in higher education, spotlighting the pedagogical implications and social impact of this approach. It discusses the relevance of this educational strategy in the context of Generative AI technologies.

Association between antibiotics use and osteoporotic fracture risk: a nationally representative retrospective cohort study.

This study aims to examine the association between antibiotic usage and osteoporotic fractures in a large cohort of Korean adults, with a specific focus on the duration of antibiotic exposure and the number of antibiotic classes used. This retrospective cohort study from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database from January 1, 2002, to December 31, 2019, included 167,370 Korean adults aged 50years or older (mean [SD] age, 59.3 [7.82] years; 65,425 [39.09%] women). The cumulative antibiotic prescription days and the classes of antibiotics prescribed between 2004 and 2008 were exposure variables, respectively. The main outcome was a newly diagnosed osteoporotic fracture during follow-up. Cox proportional hazard regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the incident osteoporotic fractures associated with antibiotic exposure. The antibiotic user group with 91days had a higher risk of osteoporotic fracture in comparison to the antibiotic non-user group (aHR, 1.12; 95% CI, 1.03-1.21). Additionally, those who used more than four different antibiotic classes had an elevated risk of osteoporotic fracture compared to the non-user group (aHR, 1.10; 95% CI, 1.02-1.18). This extensive population-based cohort study conducted on a large population has identified an association between the utilization of antibiotics and an elevated risk of osteoporotic fractures. The cumulative days exposed to antibiotics and osteoporotic fractures may be positively associated.

Evolution of Confinement Stress in Axially Loaded Concrete-Filled Steel Tube Stub Columns: Study on Enhancing Urban Building Efficiency

In the context of green building and sustainable urban development, understanding the mechanical behavior of structural components like concrete-filled steel tube (CFST) columns is crucial due to their improved load-bearing capacity, energy efficiency, and optimized material usage, which enhance structural resilience and sustainability. This research addresses the complex development of confining stress and its impact on the concrete core (CC) behavior within these columns, which are essential for urban infrastructure. Through extensive numerical studies, this study proposes a model to estimate the confining stress in axially loaded CFST short columns. Study findings reveal that the confinement effectiveness is influenced by variables such as compressive strength (CS) of the concrete, cross-sectional shape, and depth-to-wall thickness percentage. Additionally, the confinement is also significantly affected by the yield strain of steel εy/εc to the peak strain of unconfined concrete εc. A three-dimensional finite element model (FEM) was built for the simulation of the columns’ nonlinear behavior and was rigorously validated against experimental data. This model aids in the design and implementation of more efficient and resilient urban structures, supporting the principles of sustainable construction. The study underscores the importance of structural integrity in sustainable urban development and provides valuable insights for improving the design of green building materials.

Advancements in NMN biotherapy and research updates in the field of digestive system diseases.

Nicotinamide mononucleotide (NMN), a crucial intermediate in NAD + synthesis, can rapidly transform into NAD + within the body after ingestion. NMN plays a pivotal role in several important biological processes, including energy metabolism, cellular aging, circadian rhythm regulation, DNA repair, chromatin remodeling, immunity, and inflammation. NMN has emerged as a key focus of research in the fields of biomedicine, health care, and food science. Recent years have witnessed extensive preclinical studies on NMN, offering valuable insights into the pathogenesis of age- and aging-related diseases. Given the sustained global research interest in NMN and the substantial market expectations for the future, here, we comprehensively review the milestones in research on NMN biotherapy over the past 10 years. Additionally, we highlight the current research on NMN in the field of digestive system diseases, identifying existing problems and challenges in the field of NMN research. The overarching aim of this review is to provide references and insights for the further exploration of NMN within the spectrum of digestive system diseases.

O-PTIR spectroscopy for characterizing active pharmaceutical ingredient specific particle size distributions of nasal spray suspension products.

Evaluation of the particle size distribution (PSD) of active pharmaceutical ingredients (APIs) in nasal suspension products is challenging due to the presence of both API and excipients. To characterize these intricate formulations, it is essential to have sophisticated analytical methods that offer high spatial resolution and the ability to chemically pinpoint and map out the presence of API particles. However, such advanced techniques have not been documented for nasal formulations yet. In this proof-of-concept study, we investigated the utility of optical photothermal infrared spectroscopy (O-PTIR) to analyze the PSD of commercially available Nasonex® and its generic Azonaire® nasal mometasone furoate (MM) suspensions. Simultaneous O-PTIR and Raman spectra, as well as IR chemical maps, were collected from the particles in both formulations. Spatially resolved spectra from the particles confirmed the presence of peaks related to MM (1727 cm-1, 1661 cm-1, and 1122 cm-1) and excipient microcrystalline cellulose (MCC) (1061 cm-1). The PSD of MM particles was characterized using chemical maps specific to MM (1661 cm-1) and automated imaging. Results confirmed that the PSD of both formulations were comparable. Spectral analysis also revealed the presence of free MM, free MCC, and particles containing co-localized MM and MCC. For suspension-based nasal products, O-PTIR enables the measurement of API PSD, which is critical for formulators in developing nasal suspension products. This approach holds potential as an innovative complimentary analytical tool that could diminish the need for extensive clinical endpoint bioequivalence studies when evaluating the comparability of generic and brand-name nasal suspension products.

Heatmap Design for Probabilistic Driver Repositioning in Crowdsourced Delivery

This paper proposes the use of heatmaps as a control lever to manage the probabilistic repositioning of independent drivers in crowdsourced delivery platforms. The platform aims to maximize order fulfillment by dynamically matching drivers and orders and selecting heatmaps that trigger the probabilistic flow of unmatched drivers to balance driver supply and delivery requests across the service region. We develop a Markov decision process (MDP) model to sequentially select matching and heatmap decisions in which the repositioning behavior of drivers is captured by a multinomial logit discrete choice model. Because of the curse of dimensionality and the endogenous uncertainty of driver repositioning, the MDP model is solved using a rolling-horizon stochastic lookahead policy. This policy decomposes matching and heatmap decisions into two optimization problems: a two-stage stochastic programming upper bounding problem for matching decisions and a mixed-integer programming problem for heatmap decisions. We also propose a simple policy for efficiently solving large-scale problems. An extensive computational study on instances derived from the Chicago ride-hailing data set is conducted. Computational experiments demonstrate the value of heatmaps in improving order fulfillment beyond the level achieved by matching alone (up to 25%) and identify conditions that affect the benefit of using heatmaps to guide driver repositioning. Funding: The authors gratefully acknowledge the support of the Natural Sciences and Engineering Research Council of Canada through Discovery Grants [Grants RGPIN-2024-04881, RGPIN-2020-04498, and RGPIN-2019-06207] awarded to the first, second, and third authors, respectively. Supplemental Material: The online appendix is available at https://doi.org/10.1287/trsc.2022.0418 .

Exploring the immunometabolic potential of Danggui Buxue Decoction for the treatment of IBD-related colorectal cancer.

Danggui Buxue (DGBX) decoction is a classical prescription composed of Astragali Radix (AR) and Angelicae Sinensis Radix (ASR), used to enrich blood, and nourish Qi in Chinese medicine, with the potential to recover energy and stimulate metabolism. Chronic inflammation is a risk factor in the development of inflammatory bowel disease (IBD)-related colorectal cancer (CRC). More importantly, AR and ASR have anti-inflammatory and anti-cancer activities, as well as prefiguring a potential effect on inflammation-cancer transformation. We, therefore, aimed to review the immunometabolism potential of DGBX decoction and its components in this malignant transformation, to provide a helpful complement to manage the risk of IBD-CRC. The present study investigates the multifaceted roles of DGBX decoction and its entire components AR and ASR, including anti-inflammation effects, anti-cancer properties, immune regulation, and metabolic regulation. This assessment is informed by a synthesis of scholarly literature, with more than two hundred articles retrieved from PubMed, Web of Science, and Scopus databases within the past two decades. The search strategy employed utilized keywords such as "Danggui Buxue", "Astragali Radix", "Angelicae Sinensis Radix", "Inflammation", and "Metabolism", alongside the related synonyms, with a particular emphasis on high-quality research and studies yielding significant findings. The potential of DGBX decoction in modulating immunometabolism holds promise for the treatment of IBD-related CRC. It is particularly relevant given the heterogeneity of CRC and the growing trend towards personalized medicine, but the precise and detailed mechanism necessitate further in vivo validation and extensive clinical studies to substantiate the immunometabolic modulation and delineate the pathways involved.

Unraveling Childhood Obesity: A Grounded Theory Approach to Psychological, Social, Parental, and Biological Factors

Childhood obesity is a major medical and public health issue of global interest, which is influenced by a diverse array of factors and carries significant medical and psychosocial implications. Despite the extensive studies that have been conducted to explore the specific issue, the impact of several factors that influence, generate, worsen, and make chronic the phenomenon needs further exploration. This study aimed to construct a grounded theory that includes and connects the psychological, social, parental, and biological factors affecting childhood obesity. Key psychological factors include mental health issues such as depression and emotional eating, while social factors encompass socioeconomic status and cultural influences. Parental factors involve parenting styles and feeding practices, and biological factors relate to genetic predispositions and prenatal conditions. These factors interact in complex ways, highlighting the multifactorial nature of childhood obesity. The study employed a qualitative grounded theory approach, using research articles to achieve a thorough understanding. Qualitative analysis of the articles was conducted using Atlas.ti 24.0 software. Twenty-five research articles were required to reach theoretical saturation. The analysis resulted in 336 codes that were grouped into seven broad categories and twenty-four different subcategories. Through the construction of the theoretical framework, it was recognized that obesity in minors is a complex and multifactorial issue and that the network of causes and influencing factors covers a broad spectrum ranging from the individual to the family, and subsequently to society at large, which interact with each other.

Molecular dynamics simulations of high-energy radiation damage in hcp-titanium considering electronic effects

Abstract Titanium and its alloys are widely used as structural materials under extreme conditions due to their exceptional specific strength. However, comprehensive studies on their high-energy radiation damage remain limited. Considering electronic effects, molecular dynamics (MD) simulations were performed to explore high-energy radiation damage in hcp-titanium (hcp-Ti), focusing on displacement cascades induced by primary knock-on atoms (PKAs) with energies ranging from 1 to 40 keV. This study investigates the generation and evolution of point defects resulting from collisional cascades, particularly examining the influence of PKA energy. Additionally, the distribution and morphology of clustering defects from these events were quantitatively investigated and qualitatively visualized. The results show a significant dependence of surviving defects on PKA energies, highlighting a critical range that exhibits a shift in cascade morphology. Furthermore, it is demonstrated that PKA energy significantly influences the formation and growth of defect clusters, with both interstitials and vacancies showing increased cluster fraction and sizes at higher PKA energies, albeit with different tendencies in their formation and aggregation behaviors. Morphological analysis emphasizes the role of subcascades and provides further insights into the mechanisms of defect evolution behind high-energy radiation damage. Our extensive study across a broad range of PKA energies provides essential insights into the understanding of high-energy radiation damage in hcp-Ti.