Frozen shoulder, also known as adhesive capsulitis, is a common and disabling condition that causes shoulder pain and progressive stiffness. Patient information leaflets (PILs) are produced by UK National Health Service (NHS) Trusts to help patients understand frozen shoulder and treatment options. However, the content and consistency of these PILs and their alignment with national clinical guidance are currently unclear. This study aimed to identify, analyse and describe the non-surgical management recommendations presented in publicly available NHS Trust PILs for frozen shoulder and to assess their alignment with the National Institute for Health and Care Excellence (NICE) Clinical Knowledge Summary and British Elbow and Shoulder Society (BESS) best practice resources. An online search was undertaken by one reviewer to identify publicly available PILs produced by NHS Trusts detailing non-surgical management of frozen shoulder. Relevant data were extracted and analysed by one reviewer and verified by five reviewers. Descriptive statistics were used to summarise findings. Thirty-eight PILs were identified from 38 NHS Trusts with publication dates ranging from April 2013 to March 2025. Considerable variation was observed in the content, including reference to analgesia, activity modification, exercise prescription and corticosteroid injections. No single PIL reflected all key elements recommended in the NICE Clinical Knowledge Summary and BESS best practice. The findings demonstrate substantial variation in content, frequent misalignment with current national guidance and best practice exercise recommendations. Such variation may limit and may reduce the clarity, consistency and usefulness of information provided to patients.
Global health cooperation is undergoing recalibration. The 2025 America First Global Health Strategy does not introduce entirely new governance instruments but more explicitly prioritizes bilateral agreements, co-financing requirements, and performance-based partnerships within global health cooperation. This commentary examines how the strategy formalizes and intensifies existing dynamics of strategic bilateralism and analyses its implications for low- and middle-income countries. We argue that the significance of the strategy lies less in new governance mechanisms than in the scale, visibility, and political framing of existing ones. While this approach may strengthen domestic ownership and programme integration, it may also reshape bargaining dynamics, fiscal responsibilities, and coordination structures within global health systems.
暂无摘要（点击查看详情）
Total concentrations of cadmium (Cd), lead (Pb), and arsenic (As) in commercial rice varieties from Kashan, Iran, were measured via ICP-OES, with bioaccessibility assessed using an in vitro gastrointestinal digestion model. Results indicated that Cd levels (0.051-0.068 mg/kg) exceeded the FAO/WHO limit but were close to the Iranian standard. Pb concentrations (0.258-0.62 mg/kg) surpassed both national and international limits, while As levels (0.018-0.028 mg/kg) remained below permissible thresholds. Bioaccessibility ranged from 29% to 55% for Cd, 38%-43% for Pb, and 42%-61% for As, indicating that only a fraction of the metals is released during digestion. Health risk assessment showed Hazard Quotients (HQ) for individual metals below 1, suggesting no significant non-carcinogenic risk. Lifetime Cancer Risk (LCR) values for Cd and As were within acceptable limits (10⁻⁶ to 10⁻⁴). It is concluded that although total concentrations of Cd and Pb exceed regulatory standards, their low bioaccessibility significantly reduces potential health risks under typical consumption patterns.
Controlling agricultural ammonia (NH3) and nitrous oxide (N2O) emissions is vital for air quality and climate goals, yet policy synergies and trade-offs in mitigating these reactive nitrogen (Nr) remain unclear. Here, through an integrated framework combining high-resolution emission inventories with policy-specific scenario analysis, we evaluate China's national agricultural policies for abating Nr emissions (2000-2022) and estimate synergies between NH3 and N2O abatements. China's NH3 and N2O emissions peaked around 2015 and subsequently declined by 16% and 30% by 2022, respectively. Post-2015 synergistic achievements were driven mainly by fertilizer-reduction policies (~90% of abatements) with a sixfold increase in their synergetic level. Manure-management and straw-utilization policies showed limited overall effectiveness and trade-offs, though post-2015 synergies emerged in non-pastoral regions, highlighting spatial and sectoral heterogeneity. Optimized full-chain livestock management could reverse the overall trade-offs in this sector in the short term, achieving synergetic levels comparable to the fertilizer-reduction policies.
In the context of mating, individuals of the same sex often act as rivals in the pursuit, attraction, and retention of desirable partners. This study explored the relationships between intrasexual competition and various aspects of human mating psychology across three countries: Canada, Hungary, and Indonesia. A total of 661 adults (including women, men, non-binary, and gender-unspecified individuals) completed an online questionnaire assessing sensation seeking, aggression, beauty-enhancing behavior, openness to cosmetic surgery, sexual motivation, and sociosexuality. Hypotheses were tested via Bayesian multilevel modeling. Measurement invariance testing and alignment procedures were conducted to address potential cross-cultural non-invariance. Results indicated that the superiority enjoyment component of intrasexual competition showed consistent positive associations with the examined psychological variables. Associations involving inferiority frustration were generally weaker and less consistent. The findings for openness to cosmetic surgery, sociosexuality, and aggression replicate prior research, whereas the links with sensation seeking, beauty-enhancing behavior, and sexual motivation extend the literature. Cross-national comparisons revealed no significant country differences in superiority enjoyment, whereas Canadian participants scored significantly lower than Hungarian and Indonesian participants in inferiority frustration, with no significant difference between the latter two groups. Overall, the findings suggest that intrasexual competition-particularly its superiority enjoyment component-shows consistent associations with mating-relevant psychological traits across cultural contexts, even when mean levels differ between societies.
Malignant mesothelioma (MM) in Spain reflects historical asbestos consumption that peaked in the 1970s. Despite a 2002 ban, the absence of a national registry complicates burden estimation. We aimed to characterise incidence trends and generational risk patterns over 25 years. This ecological study analysed Global Burden of Disease 2023 incidence data for Spain (1999-2023). Age-standardised incidence rates (ASIR) were calculated using the 2013 European Standard Population. Temporal trends were assessed via joinpoint regression. Age-period-cohort (A-P-C) modelling disentangled the independent effects of age, period, and birth cohort by sex. In men, ASIRs increased from 1·55 to 1·94 per 100,000 (1999-2012), followed by a significant decline after 2016 (annual percentage change [APC] - 2·3%, 95% CI - 3·9- - 1·3; p < 0·001). In women, rates remained low and stable (0.45-0.50 per 100,000), with a modest increase over time (average annual percentage change 0.6%, p < 0.001). A-P-C modelling in men revealed a significant negative net drift (- 1·45% per year, p < 0·001) and strong birth cohort effects peaking in the 1944 cohort, with marked risk reduction in those born after 1964 (relative risk < 0·70). Women showed no significant cohort or period effects and minimal temporal variation. Spain shows evidence of a meaningful epidemiological transition in its mesothelioma epidemic. The significant decline in male incidence since 2016 is consistent with the 2002 asbestos ban and the progressive ageing-out of heavily exposed cohorts.
Intracerebral hemorrhage (ICH) remains associated with high mortality and treatment variability. Current workflows rely on fragmented imaging interpretation and operator-dependent surgical planning. The objective was to develop and validate an agentic artificial intelligence (AI) framework integrating automated imaging analysis, guideline-based reasoning, and trajectory optimization for ICH treatment. Fifty consecutive computed tomography (CT) and computed tomography angiography (CTA) datasets from patients with spontaneous ICH were retrospectively analyzed. The system performed multi-class anatomical segmentation of skin, skull, brain, ventricles, and hematoma, followed by volumetric quantification and JavaScript Object Notation (JSON) based structured encoding of imaging biomarkers. A knowledge-based module incorporating international ICH guidelines generated risk stratification and treatment recommendations. When evacuation was indicated, an automated trajectory modeling module proposed a patient-specific minimally invasive surgical corridor. Overall agreement between AI-generated and expert treatment recommendations was 82% (41/50 cases), with substantial agreement beyond chance (Cohen's κ = 0.71). Discrepancies occurred primarily in borderline surgical indication scenarios. In evacuation candidates, the automated planner generated feasible trajectories in all 50 cases. Median angular deviation between AI-generated and expert-defined trajectories was 7.6°, interquartile range (IQR) 5.1-9.8°. AI-generated trajectories demonstrated equal or greater safety margins relative to expert planning in the majority of cases. End-to-end processing has a potential to substantially reduce simulated decision-support time compared with manual workflow. The proposed agentic AI framework enables structured, explainable, and workflow-integrated decision support for ICH management. This system may reduce operator variability and enhance precision in minimally invasive evacuation planning.
Seasonal effects on sleep have been documented but remain poorly characterised at a global scale. Using wearable-derived data from 697 individuals contributing 185,143 nights across 49 countries, we examined how sleep duration varies with season, day length, latitude, and country using Bayesian hierarchical models. Across the dataset, sleep duration decreased with increasing day length, with a reduction of roughly 4.4 minutes per additional hour of daylight. In contrast, categorical season indicators contributed little explanatory power once individual- and country-level differences were modelled, suggesting that coarse season labels do not capture consistent structure in globally distributed samples. We found limited evidence that photoperiod sensitivity scales with latitude, despite large differences in seasonal light amplitude. At the same time, country-level variability emerged in both baseline sleep duration and estimated photoperiod responses. These findings indicate that global variation in sleep duration is shaped more strongly by individual and national differences than by calendar season.
Chimeric antigen receptor (CAR) T cell therapy can result in impressive remissions in hematological malignancies, but relapse is common because a minority of infused cells acquire a long-lived, memory-like state. All US Food and Drug Administration-approved CAR T cell products incorporate either 4-1BB or CD28 costimulatory domains, each conferring distinct phenotypic outcomes, but how these signals control early fate decisions is incompletely understood. Here we show that costimulatory domains control memory fate acquisition through asymmetric cell division. CD28 CAR T cells have higher CAR surface expression and enhanced surface proteome asymmetry after the first division, yet paradoxically they show muted transcriptional, epigenetic and metabolic divergence between daughter cells, correlating with reduced long-term persistence. Conversely, 4-1BB CAR T cells have less surface polarization but more pronounced transcriptional, metabolic and epigenetic divergence, yielding proximal effector-prone and distal persistence-prone daughters. Integrating surface proteomics, transcriptomics, metabolomics and chromatin accessibility, we show how costimulatory domains tune asymmetric cell division to shape CAR T cell fate, providing a mechanistic foundation for optimizing cellular immunotherapy.
To address the insufficient bearing capacity of roadside backfill bodies and the tilting or failure induced by uneven pressure relief of the coal seam during gob-side entry retaining in thick coal seams with hard roofs, combined compression-shear loading tests incorporating rapid resistance build-up and varying inclination angles were performed. A novel Compression Shear Coupling Test system (CSCT) was developed, and a fitted relationship between backfill width and roof subsidence was established. The strength degradation behavior of backfill specimens subjected to different shear stress components was systematically investigated. The results reveal that the peak strength of the specimens declines with increasing shear stress component, and the failure mode transitions progressively from compressive to shear-dominated failure. The high-resistance backfill material derived from this study was implemented at the N2302 gob-side entry retaining working face, accompanied by an anti-tilting design for the backfill wall. The measured roof subsidence was reduced by 59.4% relative to the theoretically predicted value, and no evident signs of failure or deterioration were observed in the backfill body. These findings provide both data support and theoretical reference for gob-side entry retaining under similar mining conditions.
There is a complex relationship between gastroesophageal reflux disease (GORD), hiatus hernia, obesity, and metabolic bariatric surgery. We report the outcomes of laparoscopic hiatus hernia repair (HHR) with BIO-A® mesh in the management of GORD post LSG in patients who developed a hiatus hernia with migration of the proximal gastric sleeve. A retrospective review of 50 patients who previously underwent LSG and revisional surgery (HHR, n = 25; RYGB, n = 25) between 2011 and 2022. The modified DeMeester scoring system was used to assess the severity of the patient's GORD symptoms pre-HHR/pre-RYGB and 6 months post-op. Twenty-five patients underwent HHR with BIO-A® mesh following a previous LSG. The severity of GORD six months post-HHR was significantly lower (0.96 ± 0.84 vs. 2.60 ± 0.50, p = < 0.0001). After HHR, 3/25 (12%) patients had ongoing GORD symptoms that were not medically controlled and underwent conversion to RYGB. In contrast, 25 patients underwent direct conversion to RYGB following a previous LSG. The severity of GORD at 6 months post-RYBG was significantly lower (0.40 ± 0.50 vs. 2.36 ± 0.64, p = < 0.0001). At six months, there was no significant difference in GORD symptoms when HHR was compared with RYGB (3.32 ± 1.6 vs. 3.76 ± 1.54, p = 0.4296). In appropriately selected patients, HHR with BIO-A® mesh appears safe and effective in managing persistent GORD following LSG, within the limits of this study. However further research is needed to explore its role and the long-term outcomes.
Fair distribution of limited health funding is a universal challenge for health systems. Decisions about funding new technologies provide a helpful lens on this complex issue. This study examined how two of the world's most mature centralised review processes for health technology funding, namely the Australian Pharmaceutical Benefits and Medical Services Advisory Committees (PBAC and MSAC) have approached fairness over time. Using the Accountability for Reasonableness (A4R) framework, which defines fair priority-setting through four conditions (Relevance, Publicity, Revision, and Enforcement), we conducted (i) a detailed document review of policy changes (2014-2022) and (ii) semi-structured interviews with decision-makers at PBAC and MSAC in 2014 (n = 12) and 2021/22 (n = 11). In both the document review and the interviews, we found increased alignment with A4R principles over time, including enhanced Relevance through increased consumer representation, increased Publicity of decision rationales, and greater Enforcement through broader committee deliberation. However, Revision was not a pressing concern of committee members at either time point despite notable policy changes that improved Revision. Persistent barriers to Publicity were identified, particularly the redaction of decision rationales in public summary documents due to sponsor confidentiality requirements and challenges of explaining nuanced deliberations rather than formulaic criteria. Our findings illustrate how A4R principles are applied in practice and highlight the challenge of balancing procedural fairness with substantive ethical considerations, such as equity and cost effectiveness, that underlie the criterion of Relevance.
Single-fiber bidirectional transmission (Bidi transmission) enables efficient reuse of existing global communication cables for sensing, yet environmental disturbances induce link noise that fundamentally limits long-distance sensing performance. Despite extensive research efforts dedicated to Bidi transmission link noise suppression, existing methods fail to eliminate link noise, forcing the abandonment of the Bidi transmission scheme in large-scale deployments. Here, we uncover that the origin of this residual noise is the "ghost noise," which can be decomposed into polarization cross-coupling noise (PCN) and calculation cross-coupling noise (CCN). To address this ghost noise, we develop a polarization-traversal interrogation (PTI) technique integrated with pseudo-random binary sequence (PRBS) phase modulation. This hybrid approach achieves zero noise increase over a 7 km Bidi transmission link and realizes 94.8% background noise reduction in a 10 km Bidi transmission link. This breakthrough extends the low-noise Bidi analog transmission distance by six times, holding significant implications for the construction of sensing networks through global communication infrastructure.
The strawberry tree (Arbutus andrachne L.) is an underutilized Mediterranean fruit species with considerable potential as a source of nutritionally valuable and functionally important bioactive compounds. In the present study, 30 naturally growing genotypes collected from Defne district of Hatay Province, Türkiye, were comprehensively evaluated over two consecutive growing seasons (2024 and 2025) to determine the extent of variation in fruit pomological traits, color parameters, biochemical composition, antioxidant capacity, and mineral content. Fruit width, fruit length, fruit weight, CIELAB color coordinates (L*, a*, and b*), total phenolic content, total flavonoid content, total anthocyanin content, total antioxidant capacity, and 16 mineral elements were assessed. In addition to univariate comparisons, multivariate statistical approaches, including correlation analysis, principal component analysis, heat map analysis, and multiple regression analysis, were applied to reveal trait interrelationships and genotype differentiation. The results demonstrated significant genotype-dependent variation for all evaluated traits, indicating broad phenotypic diversity within the studied germplasm. Fruit weight ranged from 0.29 to 1.81 g, total phenolic content from 321.61 to 507.01 mg GAE 100 g⁻1 FW, total flavonoid content from 125.54 to 288.87 mg CAE 100 g⁻1 FW, total anthocyanin content from 7.22 to 20.07 mg C3G 100 g⁻1 FW, and antioxidant capacity from 31.54% to 64.09% inhibition. Potassium was the predominant mineral, varying between 2867.29 and 8134.66 mg kg⁻1 DW. Genotype 'AA-7' was distinguished by superior fruit size and weight, 'AA-19' by outstanding macro-mineral accumulation, 'AA-14' by the highest antioxidant capacity, 'AA-3' by elevated phenolic content, and 'AA-23' by the highest anthocyanin concentration. Multivariate analyses revealed strong coordination among fruit size traits, structured associations among color parameters, partial coupling among biochemical variables, and an integrated pattern of mineral accumulation. Multivariate analyses further revealed that several genotypes, particularly 'AA-7', 'AA-14', 'AA-19', and 'AA-23', occupied distinct positions in the multivariate space, reflecting unique combinations of pomological, biochemical, and mineral attributes. Overall, the findings highlight the substantial breeding, conservation, and functional food potential of naturally growing strawberry tree germplasm.
Regional diversity may influence the composition of human milk fat globule membrane (HMFGM) protein composition and protein glycosylation. Here, we first systematically evaluated the efficiency and stability of six methods for the extraction of HMFGM proteins from breast milk. The optimal method (methanol-chloroform precipitation of MFGM proteins, followed by solubilization in 0.4% SDS lysis buffer) was further applied to the proteome and N-glycoproteome analysis of 49 breast milk samples from five regions across China. Proteomic analysis revealed the geographically divergent expression of BST2, COCH, FUCA1 and FGFBP1 in MFGM. The parallel N-glycoproteomic profiling identified 4914 site-specific N-glycans mapping to 689 glycoproteins, 699 glycosylation sites, and 420 glycan structures. This multiomics study reveals region-specific variations in the molecular composition of HMFGM proteins and their N-glycoprotein derivatives, elucidating the structural and functional dynamics of the human HMFGM in representative regions of China.
The AHL (acyl-homoserine lactone)-mediated quorum-sensing (QS) regulatory mechanism is ubiquitously distributed in gram-negative pathogens. In Dickeya oryzae, N-(3-oxo-hexanoyl)-L-homoserine lactone (OHHL), synthesised by ExpIEcz, regulates bacterial swimming motility and virulence. However, the role of its putative cognate receptor ExpREcz has not yet been characterised. In this study, we showed that deletion of expREcz alone did not cause significant changes in various phenotypes associated with D. oryzae physiology and pathogenesis. However, in the absence of a functional OHHL synthase ExpIEcz, ExpREcz was a potent repressor modulating the production of cellulases, polygalacturonases and zeamines, biofilm formation and pathogenicity of D. oryzae EC1, and it was a positive regulator modulating bacterial swimming motility. Further analysis showed that the regulatory activity of ExpREcz was abolished by OHHL, and that the QS signal might relieve the regulation of ExpREcz by interacting with two conserved AHL-binding residues of ExpREcz. Moreover, we found that ExpREcz repressed its own expression through a region in the 5' noncoding region of expREcz that lacks a canonical lux box. These findings suggest that the mechanism may enable D. oryzae to relieve ExpREcz suppression and initiate infection at high cell density when the QS signal reaches a threshold level.
Chronic ocular graft-versus-host disease (coGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) may lead to irreversible ocular surface damage and even vision loss. Current management of coGVHD faces challenges, with frequent missed or misdiagnosed cases. This study aimed to leverage a multimodal large language model (MLLM) to develop an early warning and diagnostic system for coGVHD. A total of 666 post-allo-HSCT patients (early warning model) and 805 post-allo-HSCT patients (1574 eyes, diagnostic model) were enrolled for construction, internal validation, and external validation of the corresponding models. We proposed the GVHD-MLLM, a multitask multimodal network that fused latent representations from four modal sequences to provide high-precision, real-time predictions for two tasks. The GVHD-MLLM achieved high performance in internal testing, with AUROCs of 93.44% (95% CI: 91.85-95.03%) for early warning, 98.98% (95% CI: 98.59-99.36%) for diagnosis, and 98.24% (95% CI: 98.05-98.43%) for disease severity grading. In external validation, the early warning AUROC was 83.45%, while diagnostic AUROCs across three external sites were all above 96.0%. The disease severity of patients seeking medical treatment after using the early warning model was significantly lower. Junior ophthalmologists also improved diagnostic accuracy using the model as an auxiliary tool. The GVHD-MLLM can process rich multi-modal information collected in clinical practice, and is expected to become an effective tool for managing coGVHD.
暂无摘要（点击查看详情）
A novel major locus (Qgi.245.ahau-4B.3) controlling seed dormancy, and its candidate genes (TaF-box-B1 and TaF-box-B2), were identified by integrating association and linkage mapping with expression and sequence variation analyses. Moderate seed dormancy is essential for reducing pre-harvest sprouting (PHS) and ensuring uniform germination in cereal crops. In this study, seed dormancy was evaluated in 245 wheat varieties with diverse genetic backgrounds across seven environments, and genotypes were obtained using the Wheat 90 K SNP array. A genome-wide association study (GWAS) identified 55 loci associated with seed dormancy, including a novel major locus (Qgi.245.ahau-4B.3) on chromosome 4B. This locus was validated by integrating molecular marker development, re-GWAS, linkage mapping, and expression analysis. Two candidate F-box protein-encoding genes underlying this locus were identified: TraesCS4B03G0269800 (TaF-box-B1) and TraesCS4B03G0270500 (TaF-box-B2). The expression levels of TaF-box-B1 and TaF-box-B2 were significantly lower in the moderate dormancy wheat variety Annong 1124 (AN1124) than in weak dormancy variety Annong 8455 (AN8455). Sequence and haplotype analyses showed that variations in TaF-box-B1 and TaF-box-B2 were completely linked, forming two haplotypes: TaF-box-Hap1 for strong dormancy and TaF-box-Hap2 for weak dormancy. Frequency analysis further revealed that the favorable haplotype TaF-box-Hap1 was predominantly distributed in the Middle and Lower Yangtze River winter wheat region, characterized by relatively high rainfall and humidity. These findings establish a robust foundation for molecular marker-assisted breeding of wheat varieties with enhanced climate resilience and stable PHS resistance, thereby contributing substantively to global food security.