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Stroke is the third leading cause of death in women and a major driver of disability. Menopause is a universal transition for midlife women, which is accompanied by menstrual cycle changes, hormonal fluctuations, and, for many women, the occurrence of menopausal symptoms. An accumulating body of research underscores the importance of menopause and its features to stroke risk in women, including the type and timing of menopause, endogenous hormone profiles, and menopausal symptoms, including vasomotor symptoms and sleep problems. In addition, menopausal hormone therapy, a leading approach to managing menopausal symptoms, has implications for stroke risk, which varies depending on the menopausal hormone therapy formulation, route of delivery, and the age and health of the recipient, with transdermal menopausal hormone therapy formulations administered to younger midlife women showing a more favorable profile. This review summarizes the data linking menopause and stroke, and offers suggestions to inform clinical decision-making. Knowledge gaps and directions for future research are highlighted.

Topological entanglements are central to understanding and predicting the properties of polymer melts. Yet, they make equilibrium sampling computationally challenging, as decorrelation times grow rapidly with chain length. Here, we introduce a Monte Carlo scheme that bypasses typical computational bottlenecks by working in a self-assembly ensemble rather than at fixed composition. Strictly local moves efficiently propagate backbone reconnections across scales while conserving the number of linear chains, achieving near-linear scaling of decorrelation time with system size, τeq ~ V 1.0. With this method, formulated for a fully-packed lattice, we equilibrate periodic systems totalling up to  ≃ 1.1 × 109 monomers, accessing a universal melt regime insensitive to lattice details. We analyze intra- and inter-chain entanglements for chains of up to N ≃ 5 × 105 monomers, revealing that they manifest as localized knots and links rather than as global tangles. Finally, we show that the magnitude of the Gauss linking integral between neighbouring chains grows only as N1/4.

Ponds are biodiversity hotspots that harbor diverse macro-organisms and microbial communities, despite being isolated, highly variable environments with island-like features. These factors may give rise to unique biogeographic patterns and drivers of microbial community diversity. Here, we evaluated environmental and regional drivers of pond fungal and bacterial biodiversity to determine whether these communities follow commonly observed biogeographical trends. We collected water and muck from 40 ponds across 8 states in the Eastern USA and sequenced sections of the 16S rRNA and ITS1 genes to survey the bacterial and fungal communities and test (1) whether these communities follow latitudinal diversity gradients and distance decay relationships, and (2) if variation in community composition or richness was related to specific environmental or land-use factors. We found that pond microbial communities exhibit distinct distribution patterns and relationships with environmental drivers depending on the microhabitat and microbial taxa. For example, muck fungal communities followed latitudinal diversity gradients, but bacterial communities did not. Abiotic conditions explained more variation than surrounding land use or the distance between sites, with temperature universally linked to microbial biodiversity. However, all sample types displayed weak distance-decay relationships, likely because of low spatial autocorrelation in environmental conditions and the lack of connectivity across ponds.

Porphyromonas gingivalis is a primary pathogen causing periodontal disease. The cell has two kinds of type V pili, the Fim pilus and the Mfa pilus, both of which play essential roles in colonization, biofilm formation, and pathogenicity. The functional polymerized structure of the Fim pilus is known, whereas the structure and assembly mechanism of the Mfa pilus remain unclear. Here, we show the structure of the polymerized recombinant Mfa1 stalk pilin determined by cryo-electron microscopy at 3.0 Å resolution. The atomic model of the Mfa1 filament reveals that Mfa1 pilins polymerize by protease-mediated strand exchange and retain a Ca2+ ion in the metal-binding pocket, which modulates immune recognition of the Mfa pilus by human cells. Furthermore, we elucidated the three-dimensional architecture of the streptococcal-binding region on the Mfa pilus. Our results further strengthen evidence that protease-mediated strand exchange is the universal assembly mechanism of type V pili. Our structure of the polymerized Mfa pilus, which represents the functional state on the cell surface, provides targets for antimicrobial drug design to treat periodontal disease and P. gingivalis-related systemic diseases.

Early identification of discharge destination is an important aspect of hospital care for frail older adults. This retrospective cohort study examined whether physical, cognitive and social functioning assessments at admission are associated with discharge destination. Data from 114 community-dwelling patients aged ≥65 years, acutely admitted to a geriatric ward, were analyzed. Frailty was defined at admission by impaired Katz-Activities of Daily Living (ADL) or increased fall risk. Initial screening included Katz-ADL, fall risk and the Malnutrition Universal Screening Tool (MUST). Additional assessments comprised handgrip strength, Timed-Up-and-Go (TUG), Six-item Cognitive Impairment Test (6-CIT) and living situation. Multivariable logistic regression, adjusted for age and sex, showed that worse Katz-ADL scores (OR 1.45, 95% CI 1.18-1.78), lower handgrip strength (OR 2.28, 95% CI 1.02-5.10) and slower TUG performance (OR 11.19, 95% CI 3.40-36.89) were significantly associated with non-home discharge. Cognitive status and living situation were not. These findings indicate that these functional assessments are associated with discharge destination in frail older adults.

HER2-positive breast cancer is highly aggressive and has a poor prognosis in clinical treatment primarily due to the overexpression of HER2 protein. Trastuzumab can significantly improve the therapeutic outcome for HER2-positive breast cancer, but 70% of patients develop drug resistance. Trastuzumab-drug conjugates have emerged as a promising modality in the treatment of HER2-positive breast cancer, while their therapeutic efficacy remains limited. Herein, we report a multi-payload trastuzumab conjugate, QC-AA@Tra, prepared by attaching an AIPH-bearing NIR-II fluorophore (Q3) to trastuzumab via nucleophilic substitution. After intravenous administration, QC-AA@Tra selectively accumulates at tumor sites. Under 808 nm laser irradiation, it produces a strong photothermal-dynamic effect through thermal release of nitrogen gas and free radicals from AIPH. Combined with trastuzumab's targeting, this leads to marked suppression of HER2-positive BT474 xenograft tumors in mice. Our design may offer a powerful and universal modality for precise diagnosis and treatment of HER2-positive malignant tumors.

Intraoperative hypotension (IOH) has traditionally been regarded as a transient and largely reversible physiological disturbance inherent to the administration of general and regional anaesthesia. However, contemporary perioperative outcomes research consistently suggests that IOH behaves not as a binary, threshold-based phenomenon, but rather as a duration-dependent ischaemic exposure affecting vulnerable end-organs. This manuscript argues that IOH should be reframed as a perioperative type-2 ischaemic syndrome, rather than being treated merely as an expected haemodynamic variable that is easily corrected with fluid boluses or intermittent sympathomimetic administration. Rather than targeting historically derived universal mean arterial pressure (MAP) thresholds alone, perioperative teams should adopt a holistic myocardial-protection framework incorporating MAP, systolic pressure, diastolic pressure, pulse pressure, and markers of organ perfusion. This framework must be grounded in an understanding of the patient's specific baseline perfusion pressure, an avoidance of cumulative hypotensive burden, and the judicious implementation of titrated vasopressor therapy alongside optimisation of preload, contractility, and tissue perfusion. This reconceptualisation has important implications for intraoperative anaesthetic management, postoperative biomarker surveillance, and the design of interdisciplinary, patient-centred perioperative care pathways.

Pharmaceutical expenditures are rising rapidly, driven in part by the innovation of highly effective but very expensive drug therapies that treat multiple diseases, implying that payers face a critical trade-off between cost containment and access to new medicines. A key policy question is whether producers should be restricted to uniform pricing or allowed to use indication-based pricing, where prices vary across patient groups. We use a two-market model to analyse how this choice affects drug producers' incentives to invest in new indications, their pricing strategies, and the resulting surplus for health plans. In a monopoly setting, indication-based pricing yields higher profits and thus strengthens incentives to invest in new indications, while the payer prefers uniform pricing unless the fixed investment costs cannot be recouped. However, monopoly-based insights may not hold if the multi-indication producer faces therapeutic competition in one of the markets. Specifically, we identify a softening-of-competition effect, where a uniform pricing restriction serves as a credible commitment to raise prices in the competitive market. In this case, the health plan might favour indication-based pricing to reduce costs. Overall, our findings suggest that neither pricing scheme is universally optimal, underscoring the need for case-by-case assessments across drug classes.

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder. Neuropsychiatric manifestations (TSC-associated neuropsychiatric disorders [TAND]) are nearly universal and a key quality of life determinant but often overlooked. To adapt the validated TAND Checklist to Chinese, describe TAND profiles across age groups in Chinese TSC patients, and compare severity between TSC1 and TSC2 genotypes. Cross-sectional study of 311 consecutive patients meeting 2012 International TSC Consensus criteria. Data were collected March-December 2024 at two Chinese tertiary centers. TAND prevalence and profiles across six domains using the adapted Chinese TAND Checklist. Intellectual disability defined as IQ < 70. No sex differences in TAND prevalence were found. Patients averaged eight behavioral problems; most common were mood swings (67.8%), language impairment/delay (67.5%), and inattention (64.6%). Of 152 with formal IQ testing, 68.4% had intellectual disability. Autism spectrum disorder (22.2%) was the most prevalent psychiatric diagnosis. School-aged children had prominent academic difficulties, especially in mathematics (64.3%). Top concerns were memory problems (56.3%) and family stress (52.7%). Children had more language, self-care, and attention problems and adults had more anxiety and depression. TAND features differed significantly between TSC1 and TSC2 genotypes (P < 0.05). TAND was pervasive. The adapted Chinese TAND Checklist enabled systematic assessment. TSC2 variants were associated with more severe neuropsychiatric phenotypes. Routine TAND screening and genotype-aware, personalized management are warranted.

China has a large population, and the prevalence of dyslipidemia varies across regions. The prevalence of dyslipidemia is closely associated with the increasing burden of cardiovascular disease. Currently, there is a lack of high-quality data on early-onset dyslipidemia in Northwest China. This study aims to comprehensively assess the prevalence and risk factors of early-onset dyslipidemia among adults in this region, providing epidemiological evidence for disease prevention and health promotion. This is a cross-sectional study based on the universal health check-up program conducted in northwestern China from January to December 2019. Adults (aged 18 to 65 years old) living in both rural and urban areas were included. Participants received a questionnaire survey, physical examination, and laboratory tests, including liver and kidney function, complete blood count, fasting blood glucose, and lipid profile. This study included a total of 3,559,141 participants (43.2% male and 56.8% female). The prevalence of early-onset dyslipidemia was 25.7%, with hypercholesterolemia accounting for 3.6%, hypertriglyceridemia for 10.6%, elevated low-density lipoprotein cholesterol for 2.7%, and reduced high-density lipoprotein cholesterol for 14.5%. Abnormalities in a single lipid parameter were observed in 20.5% of participants, while abnormalities in two, three, and four lipid parameters were observed in 4.6%, 0.6%, and 0.1% of participants, respectively. Male sex, age, diabetes, hypertension, smoking, alcohol consumption, and overweight/obesity were all significant risk factors for early-onset dyslipidemia. The age-standardized prevalence of early-onset dyslipidemia and its subtypes in Northwest China remains lower than the national level. Existing evidence consistently indicates that males, advancing age, diabetes, hypertension, smoking, alcohol consumption, and overweight/obesity are independent risk factors for early-onset dyslipidemia. Therefore, systematic screening should be initiated for this population (<&#x2009;40 years old), with stratified management involving enhanced lifestyle interventions combined with evidence-based lipid-lowering medications.

Polymer dielectrics for capacitive energy storage face fundamental trade-offs between breakdown strength, energy density, efficiency, and mechanical robustness. Herein, we break this paradigm by designing a bioinspired strain-adaptive dielectric metamaterial with a multiscale "ligament-bone" architecture. The "ligament" phase epoxy-functionalized polyvinylidene fluoride-based polymer provides dynamic constraints to suppress ferroelectric loss, while the "bone" units, alumina-coated barium titanate nanocores (Al2O3@BaTiO3), engineered with a strain-responsive "periosteum" shell, mitigate interfacial distortion and carrier migration. This hierarchical design synergistically enables unprecedented electro-mechanical properties: a record-high energy density of 26.1 J cm-3 with 90.2% efficiency at 600 MV m-1, coupled with a Young's modulus of 2.13&#xa0;GPa. Operando characterizations and multiscale simulations reveal that strain-adaptive reconfiguration of polymer chains and core-shell interfaces dynamically optimizes field/charge distribution under extreme conditions. This biomimetic strategy establishes a universal framework for designing next-generation dielectrics for extreme-condition electronics.

Intimate partner violence (IPV) during pregnancy causes serious harm to both the mother and the child. The magnitude of the problem is likely underestimated due to the sensitive nature of the topic and lack of consensus on screening practices, including frequency, tools, and whether screening should be systematic or risk-based. This scoping review aimed to map existing screening tools and healthcare-based screening programmes for detecting IPV in European countries within antenatal and postpartum care. Joanna Briggs Institute methodology was used and reported following PRISMA-ScR guidelines. Seven databases (Embase, PsycINFO, SocINDEX, PubMed, Web of Science, Scopus, and CINAHL) were searched up to June 2025 to identify screening tools used in European countries. A quality assessment was conducted. To identify current screening programmes within antenatal and postpartum healthcare systems, representatives from 46 European countries were consulted. Twenty-four studies were included, and methodological quality ranged from low to serious risk of bias. Thirteen screening tools for physical, emotional, and sexual IPV were identified. No tools for stalking or digital violence were found. Most studies were cross-sectional. Data were received from 22 of 46 European countries (48%) regarding screening programmes in antenatal or post-partum care: 17 countries have screening programmes, while five reported none. The Abuse Assessment Screen (AAS) and the Woman Abuse Screening Tool (WAST) were the tools most commonly used in both the literature and screening programmes. Most countries with screening program recommendations, recommended a universal screening approach. Screening tools and practices for detecting IPV during antenatal and post-partum care vary substantially across Europe, highlighting a lack of evidence and consensus on screening tools for IPV within antenatal and postpartum care.

Retention of qualified health professionals is critical for achieving universal health coverage (UHC) in Lao People's Democratic Republic (Lao PDR). Despite policy commitments, the public health sector continues to experience high turnover, especially among non-permanent staff. This study examined key factors influencing health professionals' intention to remain in government service. A cross-sectional survey was conducted from June to August 2023 among 1,873 public-sector health professionals in five provinces representing high and low-turnover areas. A structured questionnaire developed with the Department of Health Personnel (DHP) and administered via KoboToolbox collected data on demographics, employment status, income, motivation, and job satisfaction. Descriptive, bivariate, and multivariate logistic-regression analyses identified predictors of attrition intention. Overall, 37.4% of respondents reported having considered leaving the public sector. Contractual (AOR = 2.24, 95% CI: 1.573.21) and volunteer (AOR = 2.90, 95% CI: 1.904.44) staff were significantly more likely to intend departure than civil servants. Late salary or bonus payments (AOR = 2.25, 95% CI: 1.543.31) strongly increased attrition intent. Conversely, perceiving salary incentives and career-development opportunities as effective was protective (AOR = 0.35, 95% CI: 0.210.58, for moderately effective). Health professionals outside Vientiane Capital showed 3540% lower odds of intending to leave. Retention in Lao PDR is driven by employment security, financial predictability, and professional-development opportunities. Regularizing contractual and volunteer positions, ensuring timely remuneration, and expanding career pathways are critical to implementing the national Human Resources for Health (HRH) Development Strategy 20212030 and achieving UHC by 2025.

The long-term retention of fiber posts in endodontically treated teeth is fundamentally dictated by the integrity of the adhesive bond between resin cement and the dentin hybrid layer, as any compromise in quality jeopardizes the post-cement-dentin interface. This study evaluates the bonding efficacy of total-etch, self-etch, and self-adhesive systems to root dentin for fiber post cementation. The findings provide evidence-based guidance for selecting an optimal adhesive strategy in clinical practice. This study compared the bonding potential of total-etch (TE), self-etch (SE), and self-adhesive systems for glass fiber post-to-root dentin. Sixty mandibular premolars with a single root extracted freshly were standardized to a root measuring 15 mm in length after decoronation. Root canal treatment was performed, with sodium hypochlorite and ethylenediaminetetraacetic acid as irrigating solutions. The canal was obturated with gutta-percha and sealer using the sectional obturation technique. Post space was prepared with fiber post drills. The samples were distributed into three groups (n = 20) based on the adhesive system applied to lute the glass fiber post: &#x2022; Group A: TE adhesive system, &#x2022; Group B: SE adhesive system, &#x2022; Group C: Self-adhesive system. Middle portion of sample was used to evaluate bond strength under a universal testing machine. The Statistical analysis was conducted using Stata Statistical Software, Version 18 (StataCorp, 2023; College Station, TX: StataCorp LLC). A one-way analysis of variance (ANOVA) was performed to compare the means among groups, with statistical significance set at P < 0.05. Post hoc comparisons were carried out using Tukey's honest significant difference test to determine significant differences between the groups. Therefore, found that group B (SE adhesive) exhibited the highest mean bond strength at 131.03 N, which was statistically highly significant (P = 0.001) compared to the other groups. Group A (TE adhesive) demonstrated a bond strength of 115.25 N, while Group C (self-adhesive) showed the lowest bond strength at 75.04 N. The SE adhesive system demonstrated superior bond strength compared to TE and Self-Adhesive systems, making it the best choice for fiber post luting.

The alternating copolymerization of chiral and achiral cyclic esters, such as commercial l-lactide (l-LA) and &#x3b5;-caprolactone (CL), remains a significant challenge in polymer synthesis. Here, we introduce an enantiomorphic site and chain-end synergistic control strategy to achieve the first highly alternating copolymerization of l-LA and CL. The polymerization proceeds via a dynamic mechanism: first, the chiral l-LA-terminated chain end and the enantiomorphic site of the catalyst synergistically preclude the homopropagation of highly reactive l-LA; subsequently, the rate-determining insertion of the less reactive achiral CL after the l-LA-terminated chain end, generating an achiral CL-terminated chain end, relieves steric hindrance, which allows the subsequent insertion of highly reactive l-LA. This dynamic control yields highly alternating poly(l-LA-alt-CL) (P alt up to 0.91). The highly alternating copolymerization of l-ethylglycolide (l-EG) and CL (P alt = 0.96) further validates the universality of this synergistic control for constructing alternating cyclic ester copolymers.

Interspecific mutualism is a universal phenomenon that exists in biological and social populations. The generation and maintenance of such mutualism have always been a hotspot in evolutionary biology. This study enriches the research on the evolution of mutualism in structured populations from a theoretical perspective. In particular, we develop an evolutionary model of arbitrary interdependent populations using the coalescent random walk theory and employ it to derive the conditions for mutualism under weak selection. We find that evolution favors mutualism when the strength of intraspecific interactions exceeds a threshold value, which depends on the structure of multiple populations and game parameters. We thus reveal the positive role of intraspecific interactions on the evolution of mutualism, which extends prior research that considered the single effect of interspecific interactions.

Wing evolution enabled insects to pioneer aerial niches, a key innovation driving their remarkable radiation. However, interordinal relationships among early-diverging winged insects remain contentious, largely owing to the enigmatic phylogenetic position of Zoraptera, a species-poor and morphologically cryptic order. Since its discovery over a century ago, the 'Zoraptera problem' has persisted as a crucial issue in insect evolution, as alternative placements imply fundamentally different scenarios for polyneopteran diversification and trait evolution. Here, we sequenced and assembled two zorapteran genomes, integrating them with public data to compile a dataset of 89 polyneopteran species and 23 outgroups. Using 1367 universal single-copy orthologous genes, we evaluated phylogenetic signal under different evolutionary models and data treatments. Model testing revealed that the prevailing Haplocercata-first hypothesis (Zoraptera + Dermaptera as the earliest polyneopteran branch) collapses when among-site compositional heterogeneity is modelled to reduce systematic errors. Critically, under the optimal site-heterogeneous model, Zoraptera emerges as the earliest-diverging polyneopteran lineage, with Dermaptera + Plecoptera forming the sister clade Dermoplectopterida to all other Polyneoptera, a topology corroborated by multispecies coalescent and gene jackknifing analyses. Our findings highlight the necessity of multi-model approaches in insect phylogenomics, providing a robust framework for early winged insect diversification.

Coupled mode theory (CMT) is a universal method for studying resonant systems in various disciplines in science. Combined with traditional fitting methods, implicit physical parameters of the resonant systems can be revealed. However, this methodology fails in tackling the scenario of multi-solution for a given resonant system, resembling a fundamental challenge that has not been addressed yet. In this work, we propose and experimentally demonstrate a CMT physics and data co-driven deep neural network (CMT-NN) that can predict the implicit physical parameters of complex resonant systems in a rapid and precise way. More importantly, the challenge of multi-solution is mitigated by incorporating physical eigenvalues and response of the system in evaluating the physics consistency of the neural network. The applicability and generality of CMT-NN are demonstrated by simulations and experiments, where the CMT-NN can capture subtle spectral features and learn the coupling physical properties effectively. Compared with the traditional fitting method, the average computation time has been reduced by three orders of magnitude and the prediction performance is improved by more than two orders of magnitude. Displacement sensing experiments further validate the robustness of CMT-NN. It is anticipated that the CMT-NN can provide a paradigm shift in using the CMT for studying resonant systems and shed new light on the understanding, design and optimization of various coupled resonant systems.

Dissipative dynamics across physical systems exhibit organizing structural boundaries. The dimensionless damping ratio [Formula: see text] defines a stability architecture in which the critical threshold [Formula: see text] marks a second-order non-Hermitian Exceptional Point (EP2). Within spatially flat &#x39b;CDM, an exact algebraic identity is demonstrated linking the onset of cosmic acceleration to critical damping of structure growth: [Formula: see text]. This identity is a structural reformulation of the standard Friedmann and growth equations, not a new physical law; its scientific value lies in recasting a known kinematic transition as a stability-phase transition and in generating the falsifiable prediction that departures from flat &#x39b;CDM produce a measurable, nonzero offset between the [Formula: see text] and [Formula: see text] transitions (identically zero under flat &#x39b;CDM, generically nonzero in extensions). A substrate inheritance relation is then proposed as a leading-order projection approximation, whereby emergent modes acquire effective parameters from substrate precursors. Within this framework, the observed particle distribution is consistent with stability organization: long-lived matter occupies localized stability basins at [Formula: see text], while short-lived resonances occupy a secondary [Formula: see text]-1 band whose sub-cluster evidence is suggestive rather than conclusive. The framework is presented as a structurally grounded classification with defined scope and testable consequences.