Search

Abstract Background Exercise in healthy individuals is associated with a hypercoagulable phase, leading to a temporary increase in clot mass and strength, which are controlled by an effective fibrinolytic system. Conversely, people with cardiovascular diseases often have a reduced fibrinolytic pathway, increased clot mass and abnormal clot contraction, resulting in poorer outcomes. We assessed clot microstructure, particularly the contractile forces of clot formation, in response to two exercise intensities in middle-aged/older runners. Methods Twenty-eight habitual male and female runners aged over 40 years completed a 10 km moderate-intensity run; 14 of them performed a 3 km high-intensity run. Blood samples were collected at baseline, immediately postexercise and after 1 h of rest. Clot structural biomarkers d f, gel time, and measurements of mature clot mechanical properties (gel time, G’ Max and CF max ) were analysed alongside conventional plasma markers. Results Both exercise intensities altered markers of coagulant activity (PT, APTT and FVIII) and fibrinolysis (D-dimer), indicating hypercoagulability. Compared with longer-duration lower-intensity exercise, d f was greater after short-duration intensified exercise bouts. Following an hour of rest, d f dropped to baseline levels. Additionally, CF max decreased across timepoints at both exercise intensities. This effect was noted after one hour of rest compared with baseline, suggesting continuous fibrinolytic activity postexercise. Conclusion Exercise transiently induces an intensity-dependent hypercoagulable state, resulting in denser clot formation and a reduced clot contractile force due to fibrinolysis. These findings can help guide the safe commencement of rehabilitation exercise programs for cerebrovascular patients.

Context: Diabetic retinopathy (DR) is a major cause of vision impairment among diabetics, with significant regional variations in its prevalence and associated risk factors across India. Aims: This study aims to assess the variation in risk factors for DR, including demographic and behavioral characteristics, and to identify regional differences in the severity of DR across four geographic zones in India. Settings and Design: Data were sourced from the INDO EYE registry, encompassing six tertiary eye care hospitals across India. The study was designed to analyze and compare DR-related variables among different geographic zones: south, central, west, and east. Subjects and Methods: The study analyzed data from 7112 eyes of 3699 patients diagnosed with DR. Demographic, clinical, and behavioral data were collected, including age, gender, substance abuse history, comorbidities, and DR severity . Statistical Analysis Used: Descriptive statistics summarized demographic and clinical characteristics. Chi-square tests assessed associations between categorical variables, and one-way ANOVA evaluated continuous variables across zones. Statistical significance was set at P < 0.05, with analysis performed using the IBM SPSS Statistics 28. Results: The study revealed significant regional differences in DR severity and risk factors. The central zone had the highest proportion of proliferative DR and diabetic macular edema, while the south and west zones showed better visual outcomes and higher proportions of certain comorbidities. The east zone exhibited higher substance abuse rates and a broader range of visual acuity outcomes. Conclusions: Regional disparities in DR prevalence and severity highlight the need for targeted public health strategies to address local risk factors and improve diabetes management across India. Enhanced healthcare access and tailored interventions are crucial for reducing DR-related vision loss.

The rise of electric vehicles (EVs) in the transportation sector aids in curbing global greenhouse gas emissions yet efficiently integrating them into the existing infrastructure presents challenges in guaranteeing the real-time availability of charging points and the dynamic nature of electric mobility. This paper presents a novel dynamic demand scheduling framework that utilizes predictive analytics to address the issue of emergency charging requests; situations where an EV urgently require to reach a charging point due to critically low battery levels. The framework is integrated with advanced dynamic demand scheduling algorithm (ADDSA), which utilizes real-time charging data collected from Trivandrum, Kerala state, India. Using the comprehensive dataset, the framework identifies delayed EVs and considers the charging point status (active, idle or faulty) and charging point pricing to optimize the charging station allocation. By employing the K-Means clustering algorithm, the ADDSA categorizes charging points based on their performance and availability. To evaluate the effectiveness of these clusters, we utilize internal metrics such as the Silhouette score, Calinski-Harabasz (CH) index, and Davies-Bouldin (DB) index. Our findings demonstrate that K-Means outperforms other clustering algorithms, including DBSCAN, K-Medoids, Agglomerative clustering, and Gaussian mixture models (GMM), with a CH score of 1200, a Silhouette score of 0.45, and a DB score of 0.74. In the final stage of ADDSA, groups of available charging points along with their pricing information is generated, facilitating informed decision-making for EV users. With the rapid growth of the EV population, our unique dynamic demand scheduling framework, featuring real-time constraints, offers a promising solution for efficiently addressing the emergency charging needs of EVs.

Abstract: Patients with cytotoxic T-lymphocyte-associated protein 4 (CTLA4) deficiency exhibit profound humoral immune dysfunction, yet the basis for the B-cell defect is not known. We observed a marked reduction in transitional-to-follicular (FO) B-cell development in patients with CTLA4 deficiency, correlating with decreased CTLA4 function in regulatory T cells, increased CD40L levels in effector CD4+ T cells, and increased mammalian target of rapamycin complex 1 (mTORC1) signaling in transitional B cells (TrBs). Treatment of TrBs with CD40L was sufficient to induce mTORC1 signaling and inhibit FO B-cell maturation in vitro. Frequent cell-to-cell contacts between CD40L+ T cells and immunoglobulin D-positive CD27- B cells were observed in patient lymph nodes. FO B-cell maturation in patients with CTLA4 deficiency was partially rescued after CTLA4 replacement therapy in vivo. We conclude that functional regulatory T cells and the containment of excessive T-cell activation may be required for human TrBs to mature and attain metabolic quiescence at the FO B-cell stage., (© 2025 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

PD-1 contributes to memory B cell development and robust antibody responses through B cell extrinsic and intrinsic mechanisms.

Molybdenum disulfide (MoS 2 ) is a notable two-dimensional (2D) transition metal dichalcogenide (TMD) with properties ideal for nanoelectronic and optoelectronic applications. With growing interest in the material, it is critical to understand its layer-number-dependent properties and develop strategies for controlling them. Here, we demonstrate a photo-modulation of MoS 2 flakes and elucidate layer-number-dependent charge transfer behaviors. We fabricated hybrid structures by functionalizing MoS 2 flakes with a uniform layer of photochromic diarylethene (DAE) molecules that can switch between closed- and open-form isomers under UV and visible light, respectively. We discovered that the closed-form DAE quenches the photoluminescence (PL) of monolayer MoS 2 when excited at 633 nm and that the PL fully recovers after DAE isomerization into the open-form. Similarly, the electric conductivity of monolayer MoS 2 is drastically enhanced when interacting with the closed-form isomers. In contrast, photoinduced isomerization did not modulate the properties of the hybrids made of MoS 2 bilayers and trilayers. Density functional theory (DFT) calculations revealed that a hole transfer from monolayer MoS 2 to the closed-form isomer took place due to energy level alignments, but such interactions were prohibited with open-form DAE. Computational results also indicated negligible charge transfer at the hybrid interfaces with bilayer and trilayer MoS 2 . These findings highlight the critical role of layer-number-dependent interactions in MoS 2 -DAE hybrids, offering valuable insights for the development of advanced photoswitchable devices.

Dasatinib is a common treatment for chronic myeloid leukaemia with numerous side effects including gastrointestinal. We report a woman in her 50s who presented with haematochezia, weight loss and a positive faecal occult blood test. She was being treated for chronic myeloid leukaemia with dasatinib without the use of any concurrent medications, including non-steroidal anti-inflammatory drugs. Initial colonoscopy demonstrated moderate patchy left-sided inflammation, with biopsies revealing mild chronic inflammation and prominent eosinophilia. Dasatinib was subsequently ceased, and a repeat colonoscopy 3 months later demonstrated completely resolved inflammation both endoscopically and histologically., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Introduction: Premature infants treated for inguinal hernias after hospital discharge require overnight post-operative observation for apnea monitoring until 50-60 weeks adjusted gestational age (AGA). This study aimed to compare costs associated with early (at time of diagnosis) versus delayed (at AGA not requiring overnight observation) repair of inguinal hernia in premature infants., Methods: Costs were estimated using the average hospital charges at a single institution for three scenarios: 1) delayed repair 2) early repair requiring overnight observation, and 3) incarcerated inguinal hernia reduced but requiring delayed repair at 48 h. A decision analysis model was used to estimate the cost for premature infants undergoing delayed repair of inguinal hernia while considering the risk of incarceration and associated costs. The base model used 50 weeks AGA for delayed repair and an incarceration rate of 0.5%/week. Sensitivity analyses varied incarceration rate from 0.1 to 4%/week and delayed repair to 55 and 60 weeks AGA., Results: In the base model, delayed repair incurred lower estimated costs than early repair at all time points of diagnosis. In sensitivity analyses, estimated cost for delayed repair only rose above the estimated cost for early repair when estimated incarceration risk reached 3%/week with repair at 60 weeks AGA (if repair before 38 weeks AGA) or 4%/week with repair at 55 weeks AGA (if repair before 39 weeks AGA)., Conclusions: Using solely cost as a deciding factor, repair of premature inguinal hernias diagnosed as an outpatient should be delayed until overnight observation is no longer necessary., Type of Study: Decision Analysis model., Level of Evidence: III., (Copyright © 2024 Elsevier Inc. All rights reserved.)