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As aging-in-place policies gain global adoption, community parks are vital for older adults' health. Therapeutic landscapes offer a promising framework for understanding how park environments support well-being. However, how these dimensions contribute to therapeutic outcomes and whether they operate through a structured hierarchy remain theoretically underdeveloped. The aim of this systematic review is to determine how therapeutic landscape dimensions collectively and sequentially support geriatric health. Following PRISMA guidelines, a systematic search of Web of Science and Scopus synthesized data from 25 studies across 14 countries. Two principal findings emerge. First, the interaction between older adults and park environments emerges as a cyclical process where users actively shape their therapeutic experiences. Second, a Hierarchical Priority Framework is proposed in which physical, social, activity and immediate health features form a foundation leading to the symbolic dimension. This symbolic level represents the highest therapeutic experience, reachable only through sustained engagement. The main conclusion establishes that physical infrastructure alone cannot sustain therapeutic value. Park design and policy must continuously support both physical spaces and social activities to maintain long-term health benefits.

Structural variations (SVs) represent a significant source of genomic diversity, with demonstrated roles in livestock gene expression and traits. However, a comprehensive understanding of the SV landscape across large sample sets and its impact on gene regulation in cattle remains incomplete. This study aimed to construct high-fidelity pangenome graphs by integrating both assembly-based and whole-genome sequencing (WGS) derived SV catalogs. We evaluated the efficacy of pangenome graphs for SV genotyping and identified 80,328 high-quality SVs from a cohort of 2929 samples. We systematically characterized these SVs, including their linkage disequilibrium with single nucleotide polymorphisms (SNPs), functional annotations, formation mechanisms, and genomic distributions. Furthermore, we generated paired WGS (24.4 ×) and blood RNA-seq data in 170 Simmental cattle. Utilizing our pangenome graphs, we identified 637 SV-expression quantitative trait loci (SV-eQTL), which accounted for 10.81% of expression heritability of target genes, with 38.09% of the effects linked to promoter/enhancer regions. Forty-six of these SV-eQTL were replicated using CattleGTEx results through SV imputation using a joint SNP-SV reference panel. Notably, insertions in the GHSR gene were significantly associated with its expression levels, likely linked to Bos indicus cattle adaptation to heat tolerance. Our findings provide novel insights into the SV landscape and its contribution to gene regulation, underscoring its importance in cattle genetics and genomics.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of death from a single infectious agent worldwide, with 10.7 million new cases and 1.23 million deaths reported globally in 2024. Although conventional chemotherapy cures most drug-susceptible TB, the rising burden of multidrug-resistant TB (MDR-TB), prolonged treatment regimens, and suboptimal patient adherence continue to undermine control efforts. Against this background, immunotherapeutic approaches have gained renewed interest as rational complements to chemotherapy, building on decades of mechanistic work that has mapped host-pathogen interactions at unprecedented resolution. This review integrates recent advances across the immunotherapy landscape, including next-generation vaccines (M72/AS01E, MTBVAC, VPM1002, BNT164 mRNA candidates), host-directed therapies (HDTs) targeting autophagy, metabolic and inflammatory pathways, cytokine-based and antimicrobial peptide strategies, and adoptive cell therapies. We place particular emphasis on the dual, context-dependent roles of immune checkpoints such as PD-1/PD-L1 in TB, where checkpoint blockade can paradoxically trigger reactivation, and on the cellular heterogeneity revealed by single-cell and spatial transcriptomics of the granuloma. Key translational challenges-the absence of reliable correlates of protection, the demand for precision immunomodulation in comorbid populations (HIV, diabetes), and chronic underfunding of TB research-are discussed alongside emerging opportunities offered by mRNA platforms, repurposed drugs, and multi-omics-guided patient stratification. Collectively, immunotherapy is evolving from an adjunctive concept into a strategic pillar of TB control, with the potential to shorten treatment, prevent relapse, and address drug-resistant disease.

Influenza A viruses (IAVs) have a remarkable ability to adapt to new host species, which has been attributed to the specificity of the viral hemagglutinin (HA) for sialylated glycans and the functional balance between HA and the viral neuraminidase (NA). For decades, sialic acids on N- and O-linked glycans and glycosphingolipids were considered the only receptors that govern IAV entry, tropism, and species specificity. However, the discovery of bat-derived H17N10 and H18N11 viruses, followed by the identification of an avian H19 subtype, has fundamentally challenged this concept. These viruses use major histocompatibility complex class II (MHC-II) molecules as entry receptors independent of sialic acid binding. Moreover, recent studies demonstrate that certain H2N2 and H3N2 viruses exhibit dual receptor specificity, engaging both sialic acids and MHC-II, thereby expanding the conceptual understanding of IAV receptor usage. In this review, we discuss the evolving landscape of IAV receptor specificity by integrating classical insights on glycan-dependent attachment with emerging data on MHC-II-mediated entry. We discuss the structural determinants of sialic acid and MHC-II receptor engagement, the plasticity of HA receptor-binding sites, and the consequences of exclusive or dual receptor usage on host range and zoonotic potential. We further examine how MHC-II tropism shifts cellular targeting toward antigen-presenting cells and intestinal immune niches, and how this shift may relax selective constraints on NA function.

Termites represent a critical but poorly constrained source in the global methane (CH4) budget. This commentary addresses the "scaling paradox" highlighted by Yatsko et al. (2026), demonstrating that the primary drivers of CH4 emissions shift dramatically between individual species, single mounds, and broader landscapes. We expand on this framework using field data from massive Macrotermes mounds in South Africa, which reveals complex intra-mound spatial heterogeneity. Furthermore, expansive subterranean foraging networks frequently flip surrounding matrix soils from net methane sinks into localized emission sources. To resolve this scaling paradox and account for such spatial variation, we propose integrating traditional emission factors with multi-scale technologies to accurately map and model termite CH4 dynamics.

The prevalence of obesity is steadily increasing worldwide. Obesity profoundly alters the composition, structure, and function of adipose tissue (AT), the largest endocrine organ in the body. Adipose-derived mesenchymal stem cells (ASCs) are central to AT plasticity and become dysfunctional in obesity. In this review, we outline the molecular regulation of ASCs in self-renewal and differentiation, and their roles in regulating AT expansion, modulating immune and inflammatory response, and remodeling the extracellular matrix (ECM), positioning ASCs as decisive homeostatic regulators of AT. By integrating recent findings from cutting-edge studies and performing extensive bioinformatic analyses, we delineate ASC differentiation trajectories and propose a fundamentally revised view of ASCs with a heterogeneous hierarchy of functionally distinct subpopulations. Obesity impairs ASC subsets in their self-renewal and differentiation, driving fibro-inflammatory phenotypes that promote maladaptive immune response, ECM stiffening and fibrosis, and premature cellular senescence, acting as central hubs of obesity-associated tissue dysfunction. These alterations likely arise from reprogrammed ASC epigenomic landscapes and obesogenic niches characterized by an inflammatory milieu, toxic metabolites, and oxidative stress. Interestingly, substantial weight loss attenuates fibro-inflammatory stromal states and partially restores ASC pools, whereas fibrosis-associated transcriptional programs and niche memory persist, indicating incomplete reversal of obesity-induced stromal remodeling. Drawing on human, mouse, and experimental single-cell datasets, we provide mechanistic insights into the ASC-immune cell-ECM regulatory network, highlighting how obesity reshapes ASC identity, lineage trajectories, and niche signaling. Finally, we propose that therapeutic restoration of ASC plasticity may represent a promising strategy to reestablish AT homeostasis and limit the progression of metabolic disease.

Cellular RNA abundance reflects synthesis and decay rates, which can differ among transcripts of the same gene. Understanding nonsense-mediated mRNA decay and other RNA turnover pathways requires isoform-resolved kinetic measurements, but existing bioinformatic tools cannot robustly estimate isoform-specific degradation rate constants. We extend the EZbakR-suite to infer isoform-level kinetics from nucleotide-recoding RNA-seq data, uncovering unexpected variability in nonsense-mediated decay efficiency among transcripts with premature termination codons and rapid decay of select mRNAs lacking premature termination codons. Our findings highlight the competition between nonsense-mediated decay and other decay pathways and provide mechanistic insights into transcript features promoting efficient decay.

Sex hormones and reproductive transitions profoundly shape immune, metabolic, neuropsychological, and mucosal biology, as well as HIV persistence, across women's lives. Although women constitute the majority of people with HIV worldwide, hormonal and reproductive biology are still not sufficiently incorporated into HIV cure research. Cisgender women, transgender women on gender-affirming hormone therapy (GAHT), and gender-diverse individuals assigned female at birth are underrepresented in cure studies, despite experiencing unique and changing hormonal states that influence estrogen signaling, tissue-specific hormone exposure, and immune function. Estradiol, progesterone, and hormone-based therapies, including contraception, GAHT, and menopausal hormone therapy, influence innate and adaptive immunity, inflammatory responses, epithelial barrier function, and cardiometabolic and neurocognitive pathways. These processes also shape tissue-specific HIV reservoir formation and maintenance, modulate proviral transcription, and affect immune effector functions. However, most HIV cure strategies have been developed without systematically considering these hormone-dependent mechanisms, which limits mechanistic understanding, broad applicability, and translational relevance. In this review, we synthesize emerging evidence at the intersection of reproductive endocrinology and HIV immunovirology, identify critical knowledge gaps, and propose priorities for life-course, hormone-informed HIV cure strategies. We argue that meaningful inclusion of women and gender-diverse individuals is essential not only for ethically grounded, equity-centered, community-engaged research practices but also for the scientific rigor needed to achieve durable ART-free virologic control and cure.

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Living donor kidney transplantation (LDKT) offers superior outcomes for most patients with end-stage kidney disease (ESKD), yet its uptake across Europe remains highly variable. This proceedings article summarizes key themes from a pan-European symposium held in November 2025 in Prague, organized by the European Kidney Transplant Association (EKITA) in collaboration with the DESCaRTES Working Group. Discussions highlighted substantial heterogeneity in LDKT activity across Europe, driven by differences in healthcare capacity, legal frameworks, donor evaluation practices, and access to kidney exchange programmes. Marked inequities persist between regions, particularly in the Balkans and Western Balkans, for women those who are socioeconomically disadvantaged, ethnic minority populations, paediatric and elderly patients and individuals with obesity. The symposium identified wide variation in donor selection criteria, risk assessment, informed consent practices, and long-term donor follow-up, despite existing international guidelines. Emerging strategies to address these challenges include harmonisation of donor evaluation and consent, expansion of paired and cross-border kidney exchange programmes, increased use of unspecified kidney donation, and adoption of innovative surgical and immunological approaches to safely broaden donor eligibility. Advances in outcome measurement, including validated surrogate endpoints, machine learning methods, and integrated, harmonised transplant registries, were discussed as critical tools to improve quality, transparency, and research efficiency. Collectively, the proceedings underscore the need for coordinated clinical, policy, and data-driven solutions to reduce inequities and unlock the full potential of LDKT across Europe, with implications for international transplant practice.

The article aimed to elucidate the United Kingdom government's proposed direction for the "Public Money for Public Goods" approach and future implications for livestock systems post-Brexit by identifying the overall coherence between post-Brexit livestock policies. A systematic policy review of post-Brexit livestock policies on gov.uk was undertaken. Of 505 policy documents initially identified, 44 were included in the final review after removing duplicates and applying exclusion criteria. A policy document analysis was conducted to iteratively build an a priori list of thematic categories discussing livestock and post-Brexit changes. Policy Narratives were produced, supporting these data with grey and academic literature. UK livestock policy overlooks the diverse needs of different farming systems. Public goods definitions related to livestock systems remain ill-defined. Policies often conflict and lack ambition for a comprehensive public goods transition. The rapid pace at which government policy evolves imposed difficulty in reviewing new or updated policies. Also, policy terminology varied between documents, including an inherent vagueness of language. Both factors required substantial interpretation, potentially introducing bias. Failure to address the gaps identified across policies will lead to uneven social, economic and environmental outcomes for the animal-based farming sectors. Agricultural policy design needs to incorporate a critical food systems approach to ensure post-Brexit livestock policies and the public goods transition support different scales and types of farming businesses.

BackgroundAnticoagulation has been the cornerstone for stroke prevention in patients with atrial fibrillation (AF). This study aims to describe the research trends and research hotspots in anticoagulation and AF.MethodsPublications on AF and anticoagulation were retrieved from the Web of Science Core Collection from 2004 to 2024 for bibliometric analyses.ResultsA total of 12,551 articles were retrieved. The number of publications increased each year, reaching its peak in 2021. The United States has the largest number of published articles (country appearances, 18,181), followed by Italy (6525) and Japan (6,235). The most productive institutions were Harvard University (658), McMaster University (570), and the University of Birmingham (550). LIP GYH was the most prolific author, with 707 articles published. 'Circulation' has the highest H-index (77), followed by the 'Thrombosis and Hemostasis' (73), 'Journal of the American College of Cardiology' (72). The keyword analysis revealed that the research focused on warfarin, stroke, dabigatran, direct oral anticoagulants, rivaroxaban, antithrombotic therapy, prevention, safety, apixaban, and venous thromboembolism.ConclusionsResearch in AF and anticoagulation has expanded rapidly. Coagulation contact phase (such as coagulation factor XI and XII) inhibitors have emerged as a promising future therapeutic target, and there is a critical need for global collaboration to validate these strategies across diverse populations.

Mosquito-borne diseases remain a major public health concern in sub-Saharan Africa, yet the ecological drivers of mosquito community structure in intra-urban environments are poorly understood. This study aimed to assess how habitat heterogeneity, seasonality, and environmental gradients shape mosquito communities in Franceville. A longitudinal survey was conducted from July 2023 to July 2024 using 10 CDC light traps deployed weekly for three consecutive nights. Mosquitoes were identified morphologically and environmental, climatic, and urban variables were recorded. Community structure was analysed using diversity indices, principal component analysis (PCA), canonical correspondence analysis (CCA), and Variation Partitioning (VarPar). Species sensitivity to environmental gradients was quantified, and variation partitioning was used to assess the relative contributions of predictor groups. A total of 6794 mosquitoes representing 24 species across 7 genera were collected. Community composition varied significantly across habitat and season, with higher diversity in forest-associated habitats and more even assemblages in savannah environments. Multivariate analyses revealed distinct ecological responses among genera: Anopheles species showed high sensitivity to environmental gradients, whereas dominant Culex species exhibited broad ecological tolerance. Aedes aegypti was associated with savannah habitats and the rainy periods, while Ae. albopictus displayed marked ecological plasticity. Variation partitioning indicated that environmental variables explained a larger share of community variation than climatic and urban predictors, with additional effects from their interactions. Mosquito communities in southeastern Gabon are primarily structured by fine-scale habit heterogeneity and seasonal dynamics. These findings highlight the importance of integrating ecological complexity and species-specific responses into vector surveillance and control strategies in rapidly urbanising African settings.