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Ex vivo mucosal cultures: an emerging player in vaccine development
Get PDFIncreased awareness of pathogens with pandemic potential, especially respiratory viruses, is driving research on next-generation mucosal vaccines. However, clinical translation is still hampered by the lack of relevant experimental systems. Here, we review advances in human mucosal ex vivo cultures and their eligibility for vaccine development as an alternative to animal models. Ranging from organotypic air-liquid interface cultures to lymphoid organoids and microfluidics-based co-cultures, several breakthroughs occurred in recent years in modeling mucosa architecture and physiology, as well as adaptive immune responses. Advancing recent progress for clinical developments may require high-throughput approaches to validate the representativeness of the immune response within models, benchmark best practices for regulatory standardization, and investigate the influence of microbiota on mucosal immune responses
Jugando a la pelota: Los conjuntos de los jugadores, el público y las canchas en Tzikin Tzakan y en los centros vecinos de las tierras bajas mayas
Get PDFResumen: Las antiguas élites mayas jugaban a la pelota. Esta acción y las actividades asociadas se enfatizan para complementar las interpretaciones simbólicas de estudios anteriores. Basándose en la teoría de conjuntos, se discute cómo las interacciones recurrentes y causales institucionalizaron el juego de pelota. Los análisis multiescalares y multidimensionales permiten estudiar las relaciones parasociales, asimétricas y co-constitutivas entre los jugadores, el público y la cancha. En el este de las tierras bajas mayas, se encuentra el centro de Tzikin Tzakan, donde se documentaron dos canchas de juego de pelota. Debajo de la parte de las superficies originales de la cancha oeste, se encontraron varias capas de lascas de pedernal. Su presencia infiere la furia y el dolor que ocurría durante el juego de pelota. Los nobles jugaban sabiendo que sufrirían y hasta podrían fallecer. Se documentó un basurero que probablemente refleja las fiestas asociadas al juego y que apunta al rol del público en crear y gozar un espectáculo. Comparadas con 50 canchas cercanas, las canchas de juego de pelota de Tzikin Tzakan destacan por su orientación, su forma y sus dimensiones. Sus características regionalmente únicas y localmente compartidas ejemplifican el juego de pelota como una totalidad emergente
Safety and efficacy of ticagrelor versus clopidogrel for carotid artery stenting: propensity score matched analysis
Get PDFBackground: Dual antiplatelet therapy (DAPT) is recommended around carotid artery stenting (CAS) to reduce periprocedural stroke risk. Clopidogrel is widely used, but response variability related to pharmacokinetics and CYP2C19 polymorphisms may limit its effectiveness. Ticagrelor is a more potent, direct acting P2Y12 inhibitor, but its comparative effectiveness in CAS remains uncertain. Methods: We conducted a retrospective cohort study in the TriNetX database, identifying adults with carotid artery stenosis who underwent CAS between January 2016 and August 2025 and received either ticagrelor or clopidogrel. Primary outcomes at 180 days included ischemic stroke, major hemorrhage, intracranial hemorrhage, and all cause mortality. Secondary outcomes included inpatient readmission and emergency department (ED) visits. Propensity score matching (1:1), Kaplan–Meier survival, and Cox proportional hazards analysis were used. Results: Among 6996 patients, 378 received ticagrelor and 6618 received clopidogrel; aspirin co-use was similar (89.7% vs 91.7%). After matching, 377 patients remained in each cohort. Ischemic stroke (2.7% vs 4.2%; HR 0.56, 95% CI 0.25 to 1.27; P=0.159) and major hemorrhage (2.9% vs 4.8%; HR 0.61, 95% CI 0.29 to 1.30; P=0.197) were numerically lower with ticagrelor. Rates of intracranial hemorrhage were similar (2.7% vs 2.7%; HR 0.61, 95% CI 0.14 to 2.53; P=0.488). Mortality was numerically higher with ticagrelor (3.4% vs 2.7%; HR 1.64, 95% CI 0.68 to 3.97; P=0.263). ED visits were similar (14.3% vs 14.6%; HR 0.97, 95% CI 0.67 to 1.42; P=0.895). Inpatient readmission was numerically lower with ticagrelor (15.9% vs 19.1%; HR 0.81, 95% CI 0.57 to 1.14; P=0.223). Conclusion: Ticagrelor and clopidogrel showed comparable safety and effectiveness following CAS. Future prospective genotype informed trials are warranted to confirm these findings
Do climate models agree on seasonal rainfall patterns and future changes over Southern Africa?
Get PDFUnderstanding how rainfall will change over the southern Africa is a challenge, in part, due to large uncertainties in climate model projections. Using a large set of 201 global climate model simulations from the Coupled Model Intercomparison Project Phases 5 and 6 (CMIP5 and CMIP6) and 2018 UK Climate Projections (UKCP18), this study provides an in-depth investigation into future changes in southern African precipitation. Specifically, the spatial and temporal variation of model agreement, the intra- and inter-model uncertainties and the roles of interdecadal variability are examined. Model projections show agreement on drying over most of southern Africa in the dry season and the onset of the rainy season. Meanwhile in the main rainfall season, there is less agreement between models regarding the direction and magnitude of change over much of southern Africa, including in Zimbabwe, Mozambique, Zambia and Malawi. The range in future projections is not linked with biases in the historical climatology, and intra-model uncertainty analysis shows that multiple simulations of the same model often produce disagreeing projections in the sign of precipitation change when compared to the historical period. This highlights the importance of internal variability in influencing rainfall projections over southern Africa. For many models, this substantial interdecadal variability is greater than the projected future change. Given the large variability and uncertainty in models over southern Africa, impact and adaptation studies should consider the strong probability of both wet and dry years, and wet and dry decades, in the future
The FBDSE approach to sine–Gordon up to 6π
No full textWe develop a stochastic analysis of the sine-Gordon Euclidean quantum field (cos(βφ))2 on the full space up to the second threshold, i.e. for β 2 < 6π. The basis of our method is a forward-backward stochastic differential equation (FBSDE) for a decomposition (Xt )t⩾0 of the interacting Euclidean field X∞ along a scale parameter t ⩾ 0. This FBSDE describes the optimiser of the stochastic control representation of the Euclidean QFT introduced by Barashkov and one of the authors. We show that the FBSDE provides a description of the interacting field without cut-offs and that it can be used effectively to study the sine-Gordon measure to obtain results about large deviations, sub-gaussian tails, decay of correlations for local observables, singularity with respect to the free field, Osterwalder–Schrader axioms and other properties
Navigating reservations for transgender persons under the Indian Constitution
Get PDFReservations for transgender and intersex persons has become one of the primary demands on the path to (trans)gender equality. Building on the work done in laying out a case for its implementation in higher education and public employment, this piece seeks to explore four legal issues in implementing reservations. Specifically, we argue (1) that Courts can and should recognise a clear rationale for horizontal transgender reservations; (2) that transgender reservations is a core socio-economic right that courts can enforce without any conditional implementation by the government or legislature; (3) that the category 'transgender' should not become a new orthodoxy and remain contingent and flexible; and (4) that the right to privacy, particularly of trans identity, can and should be prioritised in any reservation schemes
Microfabricated Neural Biosensors for Detection of Neurotransmitters, Biomarkers, and Small Molecules: Emerging Trends on Self‐Sustained Systems and Energy Harvesting
Get PDFThe rapid evolution of neuroscience and bioelectronics has intensified the demand for highly sensitive, selective, and miniaturized biosensors capable of monitoring neurochemical activity with high spatial and temporal resolution. Among these, microfabricated thin‐film biosensors have emerged as a powerful platform for the detection of neurotransmitters and small molecules, owing to their ultrathin form factor, mechanical flexibility, and compatibility with implantable systems. Design strategies, material innovations, and functional surface chemistries are now central to enabling real‐time, in vivo monitoring with minimal tissue disruption and long‐term stability. This review covers the recent progress in microfabricated biosensors, focusing on electrochemical, optical, acoustic, and magnetic modalities for the detection of key neurotransmitters, such as dopamine, serotonin, glutamate, and acetylcholine, as well as biologically relevant small molecules, including glucose, lactate, hydrogen peroxide, and nitric oxide. The integration of thin‐film sensors for inflammatory and neurodegenerative disease biomarkers, such as cytokines (e.g., IL‐6, TNF‐α), amyloid‐β, and tau proteins, is also discussed. Key challenges such as drift, biofouling, and signal specificity are critically examined alongside emerging solutions. Finally, current and future applications ranging from fundamental neuroscience and brain‐machine interfaces to personalized medicine emphasize the potential of thin‐film biosensing technologies in real‐world biomedical scenarios
“See me for me”: an intersectional approach exploring sexual and gender minority medical students’ experiences of role models
Get PDFPhenomenon: Sexual and/or gender minority-identifying (SGM) medical students report lower levels of belonging and heightened discrimination in medical schools, especially amongst those who hold intersecting identities that are underrepresented in medicine (URM). Role modelling has been identified as a tool to combat this phenomenon. We used an intersectional approach to explore how interacting URM identities in relation to SGM identity mediate the experience of role models to influence feelings of belonging. Approach: We employed interpretative phenomenological analysis to explore nuanced and heterogeneous role modelling experiences. We conducted semi-structured interviews with 10 medical students from six medical schools in the United Kingdom. Findings: Participants described how cisheteronormativity often led to loss of identity control, fragmentation, and accompanying selfinauthenticity to protect their sense of belonging. Intersecting URM identities heightened feelings of otherness, and mediating multiple URM identities was cognitively taxing to many participants, even within traditionally inclusive spaces. Role models empowered participants to reclaim control over their narratives, engage in activism, and enact disruptive visibility that challenged hierarchical norms. Participants valued role models who shared their intersecting identities, though many also emphasised that anyone who visibly respected SGM and URM identities could equally effectively foster belonging. Hierarchy and power imbalances prioritised by medicine limited the positive effects of role modelling and perpetuated identity fragmentation and inauthenticity. Accordingly, role models were consistently most visible and positive when in positions of influence. Overall, when positive and available, role modelling relationships provided practical pathways for students to integrate fractured identity threads into a coherent, authentic self. What this paper adds: This study is the first to apply an intersectional lens to role modelling experiences of SGM medical students with multiple URM identities in the UK. We offer some practical steps for medical schools to cultivate inclusive role modelling
Physical activity in relation to risk of chronic obstructive pulmonary disease among Chinese adults: an 11-year prospective study
Get PDFBackground: Chronic obstructive pulmonary disease (COPD) is a leading cause of chronic morbidity and mortality worldwide. Despite its significant public health burden, few studies have reported on the association of physical activity with incident COPD. This study aimed to determine the association between physical activity and the risk of incident COPD. Methods: This prospective cohort study analyzed data from 49,482 participants aged 30–79 years enrolled in the China Kadoorie Biobank study in Tongxiang. Baseline assessments were carried out between August 2004 and January 2008. Physical activity was measured using an interviewer-administered questionnaire and quantified as metabolic equivalent of task hours per day (MET-h/day). Participants were categorized into quartile-based activity groups for analyses. All participants were followed up from the date of baseline survey until the date of COPD diagnosis, death, loss to follow-up, or 31 December 2017, whichever occurred first. Incident COPD events were obtained periodically through linkage with national insurance electronic systems and death registries. Cox proportional hazards regression was employed to estimate adjusted hazard ratios of COPD in relation to physical activity. Results: The average of the physical activity level of participants was 31.1 ± 15.1 MET-hours/day. During 551,266 person-years (median 11.5 years) of follow-up, 1,470 incident COPD cases (744 men and 726 women) were documented. After adjusting for socio-demographic status, lifestyle factors (cigarette and alcohol consumption, secondhand smoke exposure, meat and fresh fruit consumption, sleep duration), BMI, and household cooking fuel type, participants with physical activity levels in the highest vs. lowest quartile exhibited a 30% reduced risk of incident COPD (HR = 0.70, 95%CI, 0.54–0.91) in smoking men. However, no significant association was observed in women (HR = 0.99, 95%CI, 0.77–1.27) or non-smoking men (HR = 1.05, 95%CI, 0.41–2.46). Conclusion: Physical activity is inversely associated with incident COPD risk in smoking men but not in women or non-smoking men
Gaps Between European Crohn's Colitis Organisation Quality Standards of Care and the Real World in Special Situations in Inflammatory Bowel Disease Across Europe: Results From E‐QUALITY Survey
Get PDFPlain Language Summary: The E‐QUALITY survey conducted by the European Crohn's and Colitis Organisation (ECCO) across 245 European hospitals showed significant variations in how doctors manage key situations in inflammatory bowel disease (IBD), both among institutions and among European geographical regions.The results showed that although most hospitals (72%) use less invasive laparoscopic surgery, important steps are often missed. For example, only 40% of institutions regularly check a patient's nutrition before surgery and less than half (43%) consistently work to prevent the disease from coming back after an operation. The survey also revealed that a formal plan for managing severe flare‐ups is followed in just 30% of hospitals and only 35% have a structured program to help young patients transition from children to adult care. These findings highlight a substantial gap between what is recommended and what happens in real life, suggesting an urgent need to standardise care across Europe