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Anxiety disorders, depressive disorders, migraine, and rheumatoid arthritis are common chronic conditions that contribute substantially to disability, recurrent care needs, and productivity losses, yet remain comparatively under-prioritised in health policy. In Mexico, these conditions disproportionately affect women, but their economic burden has not been comprehensively quantified from a gender perspective. To estimate the direct and indirect economic burden of anxiety disorders, depressive disorders, migraine, and rheumatoid arthritis in Mexico among adults aged 20 years and older between 2005 and 2021, from a societal perspective and by gender. We conducted a cost-of-illness analysis from a societal perspective. Direct costs were estimated by combining condition-specific prevalence from the Global Burden of Disease Study 2021 (GBD 2021) with normative per-case treatment costs derived from national clinical guidelines and official cost sources. Indirect costs were valued using three complementary approaches: the Human Capital Approach (HCA), based on predicted annual labour income from nationally representative employment surveys; a GDP-per-capita benchmark (1 DALY = 1 GDP per capita); and a willingness-to-pay approach using the value of a statistical life year (VSLY) transferred to Mexico following OECD methods. All costs were expressed in 2021 international dollars (Int$). Between 2005 and 2021, the four disorders accounted for 28.8 million DALYs lost. Migraine was the most prevalent condition, but depressive disorders generated the highest direct costs (Int$310.5 billion) and the largest share of indirect costs (41.1%). Indirect costs totalled Int$106.8 billion under the HCA, Int$582.2 billion under the GDP-per-capita valuation, and Int$2.9 trillion under the willingness-to-pay approach. Under the GDP-per-capita benchmark, the combined economic burden of the four disorders reached approximately Int$1.2 trillion over the study period. Women consistently bore a greater burden than men across all four conditions and under all valuation methods; total indirect costs borne by women were 2.0 times higher for anxiety disorders, 2.1 times higher for depressive disorders, 2.2 times higher for migraine, and 3.8 times higher for rheumatoid arthritis. Anxiety disorders, depressive disorders, migraine, and rheumatoid arthritis impose a substantial and unequally distributed economic burden in Mexico. The persistent excess burden among women indicates that these high-disability chronic disorders should be understood not only as a public health problem, but also as a health equity concern. More gender-responsive priority setting, stronger continuity of care, and better financial protection may help reduce both disability and its downstream economic consequences in Mexico and other LMICs with segmented health systems.

Lateral stability of distributed drive electric vehicles (DDEVs) under high-speed and low-adhesion conditions is often evaluated using autonomous phase-plane analysis, which does not explicitly account for closed-loop yaw-moment control and thus yields conservative stability limits. This paper proposes a unified lateral-stability framework that integrates controllable-region (CR) analysis with torque-distribution mode selection under closed-loop control. CRs associated with no control, the differential braking distribution mode (DBDM), and the balanced torque-vectoring distribution mode (BTVDM) are constructed on the sideslip-angle-sideslip-angle-rate phase plane, while control efficiency is assessed in terms of convergence time and execution cost. A gradient-boosted decision-tree ensemble trained on nonlinear vehicle simulations is distilled into a lightweight four-dimensional lookup table for real-time implementation. Results show that, under a representative high-speed and low-adhesion condition (vx=105km/h, μ=0.3), the uncontrolled vehicle fails to satisfy tcmax=3s, whereas DBDM and BTVDM converge within 2.17 s and 2.32 s, respectively. DBDM provides faster recovery near high-risk boundary states, while BTVDM reduces the maximum longitudinal speed loss from 5.96 m/s to 1.40 m/s in closed-loop simulation. The proposed adaptive distribution mode reduces the speed loss by approximately 57.4% compared with pure DBDM, while maintaining comparable peak and RMS sideslip-angle and yaw-rate errors in both simulation and HiL tests.

During the initial years of the COVID-19 pandemic, there was a rapid growth in virtual peer support interventions for health and social care workers. While these were often positively evaluated initially, there has been little research on their ongoing utility in the post-COVID response context, characterized by healthcare worker shortages and rising healthcare demands. This paper applies the Levesque Framework on access to healthcare to explore health and social care workers perspectives and experiences of virtual peer support services. Nine online focus groups were held with 52 health and social care workers in British Columbia, Canada. Transcripts were analyzed using a mixed inductive and deductive approach to reflexive thematic analysis. Most participants were unaware of existing services but favourable to the idea of virtual peer support initiatives, despite some skepticism that early interventions could meet current needs. Engaging in mental healthcare was viewed as acceptable, but participants wanted assurances of cultural safety and to be able to engage with peers from similar social locations. Health and social care workers noted that time and energy constraints restricted access and had concerns about confidentiality and data security. Virtual peer support interventions must evolve to meet the current mental health needs of health and social care workers. This includes ensuring services are designed with a diverse workforce in mind and are proactive in assuring confidentiality and data security.

Artificial intelligence (AI) has rapidly emerged as a transformative force in radiology, offering enhanced diagnostic accuracy, workflow optimization, and the potential to alleviate rising imaging demands. As radiology remains inherently dependent on pattern recognition and high-volume data interpretation, it represents an ideal domain for AI integration. This narrative review synthesizes current evidence on the clinical impact of AI across multiple dimensions of radiologic practice, including diagnostic performance, workflow efficiency, patient perspectives, and trainee education. AI systems have demonstrated performance approaching or exceeding that of radiologists in high-prevalence tasks, particularly in chest imaging and breast cancer screening, while also improving triage and reducing report turnaround times. However, these benefits are accompanied by significant challenges. Automation bias, over-reliance on algorithmic output, and anthropomorphic framing may compromise clinical judgment. Additionally, AI integration may paradoxically increase workload and contribute to radiologist burnout when poorly implemented. Patient-centered studies consistently indicate a preference for AI-augmented, rather than autonomous, diagnostic models, underscoring the enduring importance of physician oversight and communication. Among trainees, concerns regarding job security persist, though these are mitigated by increased AI literacy and structured educational initiatives. Ultimately, AI is best conceptualized not as a replacement for radiologists, but as a complementary tool. Thoughtful integration, combined with robust training, validation, and human oversight, will be essential to ensure that AI enhances rather than diminishes the quality of radiologic care.

In ADPKD renal function is corrupted by the accumulation and growth of fluid-filled cysts. Disruption of the PKD1 gene product, polycystin-1, is the most frequent cause of ADPKD, but the mechanisms that predispose PKD1 to recurrent somatic mutation remain poorly understood. Because current evidence for sequence- and structure-dependent mutational susceptibility is strongest at the human PKD1 locus, we will focus here on mechanisms that may promote somatic PKD1 inactivation. Experimental evidence for polycistin-1 inactivation supports a two-hit pathway, with the first hit being an inherited germline pathogenic mutation in PKD1 and the second hit mutation arising later in a somatic cell to inactivate the gene or lower the gene's dosage to lift a barrier to cyst initiation. An affected kidney can have thousands of cysts, each of which is a clonal lineage arising from an independent mutational second-hit event. Why human PKD1 is prone to inactivation and why the rodent orthologs escape similar mutagenesis is a mystery that, once solved, promises to provide important insights into the molecular mechanisms governing cyst initiation. A step toward that goal came from the characterization of the guanine-rich sequence architecture of human PKD1 that distinguishes it from rodent Pkd1. These guanine-rich tracts are intrinsically susceptible to oxidative damage and can adopt non-duplex secondary structures such as guanine-quadruplex DNA. Although guanine quadruplexes serve important regulatory functions, both oxidized guanine lesions and guanine quadruplex structures can interfere with faithful DNA replication and repair, thereby increasing mutation risk. Here, we discuss PKD1 mutagenesis in the context of the renal inflammatory microenvironment, integrating established principles of sequence-dependent mutagenesis and guanine-rich DNA structure biology with mechanisms of cyst initiation in ADPKD. This synthesis supports a conceptual model in which intrinsic sequence-dependent mutational susceptibility at the human PKD1 locus may interact with localized inflammatory microenvironments characterized by oxidative stress and epithelial proliferation to contribute to recurrent somatic second-hit formation.

The macrotrabecular-massive (MTM) subtype of hepatocellular carcinoma (HCC) is associated with aggressive biology and poor prognosis. We aimed to develop a CT-based artificial intelligence model (DeepCT-MTM) for the noninvasive prediction of MTM-HCC and investigate its prognostic utilities as well as biological underpinnings. A total of 3118 patients with HCC were included from 20 tertiary-care hospitals. DeepCT-MTM was developed and validated among 832 patients with early-stage HCC undergoing resection (the resection set) and extrapolated to 2286 patients (including 480 prospectively-collected ones) with intermediate/advanced-stage HCC receiving IATs. DeepCT-MTM's predictive performance for MTM-HCC was evaluated using the area under the receiver operating characteristic curve (AUC), and its prognostic values were investigated for progression-free survival (PFS) and overall survival (OS). In the external test cohort of the resection set, DeepCT-MTM predicted MTM-HCC with an AUC of 0.845. The DeepCT-MTM-predicted high-risk group had worse PFS and OS across all IAT sets (all P&#x2009;<&#x2009;0.05).. DeepCT-MTM is effective for noninvasively predicting MTM-HCC and may help selecting patients who benefit from a combination of IAT with immunotherapy and anti-angiogenic therapy. However, prospective validations are warranted for these hypothesis-generating findings.

The metabolic score for insulin resistance (METS-IR) is a non-insulin-based surrogate marker of insulin resistance. However, its utility for identifying gestational diabetes mellitus (GDM) risk in early pregnancy remains unclear. This study included 585 singleton pregnant women from a prospective cohort study in South Korea. METS-IR was assessed at 10-14 weeks of gestation. Multivariable logistic regression was used to examine the association between METS-IR and subsequent GDM. Subgroup and sensitivity analyses were performed to evaluate the robustness of the findings, and receiver operating characteristic curve analysis was used to assess the predictive performance of METS-IR. Among 585 participants, 36 women developed GDM. In the fully adjusted model, METS-IR remained positively associated with GDM when analyzed as a continuous variable (OR = 1.18, 95% CI: 1.10-1.26, P < 0.001). Compared with women in the lowest METS-IR tertile, those in the highest tertile had a higher risk of GDM (OR = 5.50, 95% CI: 1.43-21.06, P = 0.013). The association was consistent in subgroup and sensitivity analyses. METS-IR showed good discriminative ability for GDM, with an area under the curve of 0.808 (95% CI: 0.726-0.890). The optimal cutoff value was 34.5, with a sensitivity of 66.7% and specificity of 86.9%. Higher METS-IR at 10-14 weeks of gestation was independently associated with an increased risk of GDM. METS-IR may serve as a simple early-pregnancy marker to help identify women at high risk for GDM.

The widespread use of tetracycline and its consequent aquatic pollution pose significant risks to environmental and human health. Recently, microalgae have been demonstrated as a promising, environmentally friendly and non-chemical way to reduce tetracycline levels; however, biodegradation pathways and mechanisms remain elusive. Consequently, this study systematically investigated the pathways and functional enzyme-mediated mechanisms of tetracycline biodegradation by a marine model algal species (Phaeodactylum tricornutum). The results revealed that P. tricornutum exhibits reasonable physiological adaptation and tolerance to tetracycline exposure through cellular homeostasis and the activation of energy reallocation. Simultaneously, P. tricornutum was able to biodegrade tetracycline (e.g., 88.4% of a 4&#x202f;mg/L tetracycline solution). It was also proposed that this diatom degrades tetracycline via C-N bond cleavage of metallo-beta-lactamase, demethylation by cytochrome P450, deamination by cytochrome P450 and ornithine cyclodeaminase, oxygenation by flavin adenine dinucleotide (FAD)-dependent monooxygenase, reduction and ring-opening by antibiotic biosynthesis monooxygenase. This study provides multidimensional theoretical and empirical support for addressing antibiotic pollution in aquatic ecosystems.

Identifying diagnostic and prognostic biomarkers and therapeutic targets for hepatocellular carcinoma (HCC) is essential to improve risk stratification, guide individualized treatment, and enhance therapeutic efficacy.The expression of SAMM50 (Sorting and Assembly Machinery Component 50) was initially analyzed in publicly accessible curated genomic and proteomic databases, such as the Cancer Cell Line Encyclopedia, the Human Protein Atlas, and other HCC-specific repositories. This analysis revealed differential expression patterns between HCC and non-neoplastic liver tissue. Subsequently, clinicopathological data and tissue specimens were collected from 200 HCC patients who underwent treatment at our institution. The protein and transcript levels of SAMM50 were experimentally measured in paired HCC and adjacent non-tumorous tissues using immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The association between SAMM50 expression and key clinicopathological features was further evaluated. Univariate and multivariate Cox proportional hazards analyses were performed to determine the independent prognostic value of SAMM50 expression in HCC. Based on these results, a reproducible and clinically applicable nomogram, supported by a forest plot, was constructed to facilitate prognostic prediction and support individualized therapeutic decision-making. Finally, in vitro and in vivo experiments were conducted to characterize the phenotypic alterations in HCC cells after SAMM50 knockdown, thereby confirming its involvement in critical oncogenic behaviors.This research demonstrated that the mRNA and protein levels of SAMM50 in HCC tissues were elevated compared to those in normal liver and adjacent tissues. Immunohistochemistry findings confirmed that SAMM50 protein levels were persistently higher in HCC tissues than in paired adjacent tissues. High expression of SAMM50 was correlated with unfavorable clinicopathological factors, encompassing pretreatment alpha-fetoprotein (AFP) levels, tumor size, T stage, American Joint Committee on Cancer (AJCC) stage, histological grade, and worse overall survival.Specifically, high expression of SAMM50 was linked to shorter overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Moreover, univariate and multivariate Cox analyses were conducted to investigate the association between SAMM50 expression and clinicopathological features in HCC patients and to identify independent prognostic factors. The area under the receiver operating characteristic (ROC) curve (AUC) for SAMM50 was 0.863, suggesting its potential as a diagnostic marker for HCC, though further validation in independent cohorts is needed. Silencing of SAMM50 inhibited HCC cell proliferation, migration, and invasion, promoted apoptosis in vitro, and suppressed HCC growth in vivo.This research demonstrates that SAMM50 shows potential diagnostic value for HCC, though this observation requires further validation in larger, independent, and prospective cohorts. The results of this study not only contribute to the evaluation of baseline data and risk stratification in HCC but also offer novel approaches for the development of precise treatment strategies and targeted therapies.

Repetitive mild traumatic brain injury (rmTBI) produces cumulative cellular stress that can lead to progressive brain dysfunction, yet the mechanisms governing vulnerability to repeated injury remain unclear. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) regulates cellular proteostasis through the unfolded protein response and is implicated in neurodegeneration and acute brain injury. Here, we directly tested the role of PERK deficiency in shaping the brain's response to rmTBI. Using a mouse model of neuronal PERK deficiency, we combined spatial protein profiling and tissue analyses with resting-state functional MRI and diffusion tensor imaging to assess molecular, functional, and structural outcomes after rmTBI. PERK deficiency increased susceptibility to rmTBI-induced disruption of protein homeostasis, altered large-scale functional connectivity, and exacerbated white matter microstructural changes consistent with axonal and myelin damage. Molecular alterations were spatially aligned with imaging-defined network and white matter abnormalities. These findings identify PERK signaling as a key determinant of brain resilience to repetitive mild injury and link ER stress dysregulation to network-level dysfunction following rmTBI.

Hyperuricemia (HUA) is a major public health concern that is closely linked to obesity. The novel visceral adiposity index (METS-VF) demonstrates significant associations with multiple chronic diseases, yet its association with HUA risk in hypertensive patients remains unclear. This study aimed to investigate this association in a Chinese hypertensive population. This study utilized data from the Chinese Hypertension Registry Study, including 13,341 hypertensive patients. Data collection was conducted through standardized questionnaires, physical examinations, and laboratory tests. We evaluated the association between METS-VF and HUA using multivariate logistic regression models. Robustness was assessed via multivariable-adjusted models and subgroup analyses. The overall prevalence of HUA was 55.3%. Each unit increase in METS-VF was associated with a 8.48 (95% CI: 6.64, 10.32) &#xb5;mol/L increase in serum uric acid levels and a 25% higher risk of HUA (OR&#x2009;=&#x2009;1.25; 95% CI: 1.20, 1.30). HUA risk increased significantly across increasing METS-VF quartiles (P for trend&#x2009;<&#x2009;0.001). Further analysis revealed a non-linear, threshold relationship. Subgroup analysis indicated a stronger association in women (P for interaction&#x2009;<&#x2009;0.001). In patients with hypertension, the visceral adiposity index (METS-VF) was positively associated with the risk of hyperuricemia (HUA).

Ischemic stroke is a major cause of disability and mortality worldwide, accounting for approximately 66% of all stroke cases. Stroke has been reported to cause approximately 6.5&#xa0;million deaths annually, and the global disability-adjusted life years attributable to stroke are projected to exceed 200&#xa0;million by 2030. Therefore, identifying reliable diagnostic biomarkers for acute ischemic stroke (AIS) and exploring their underlying molecular mechanisms are of great importance for early disease recognition and clinical intervention. Transglutaminases (TGases) are widely distributed in the central nervous system and play important roles in inflammatory responses, neural repair, and vascular regulation. In this study, multiple bioinformatics approaches were used to identify TGM2 as a candidate gene associated with AIS. Single-cell RNA sequencing (scRNA-seq) data were further integrated to analyze the expression pattern of TGM2 across different cell types and to explore its potential intercellular communication context. Finally, TGM2 expression was validated in peripheral blood samples from patients with AIS. This study provides new evidence supporting the potential involvement of TGM2 in AIS and its value as a candidate biomarker.

Abuse of older people is a public health and human rights issue globally, with approximately 1 in 6 older adults experiencing abuse annually. This prevalence highlights the need for robust prevention strategies, even in Norway, despite its comprehensive healthcare systems. This study explored stakeholders' perceptions of existing legislation and guidelines, as well as the shortcomings that needs to be addressed to prevent abuse of older people in Norway. The exploratory qualitative design employed in-depth and formal natural group interviews with stakeholders and experts in the abuse of older people field. Through reflexive thematic analysis, three themes were identified: (1) Stakeholders experience with, and perspective on, abuse of older people; (2) System-level challenges in preventing abuse of older people; and (3) Pathways for systematic improvement and cultural change in preventing abuse of older people. Stakeholders identified key challenges including ambiguous definitions, complexity of the older adult population, and vulnerability to abuse. Findings emphasize the need to increase awareness and education, address insufficient competence, staffing, and resources, establish clear reporting guidelines, and improve interdisciplinary collaboration to prevent abuse of older people.

Phylogenetic relationships among members in the order Diplostomida remain contentious, with mitochondrial (mt) and nuclear genomic data often yielding conflicting topologies. A major limitation is the availability of only a few mt genomes from the type genus Strigea, hindering a robust test of the monophyly of the family Strigeidae and the order Diplostomida. The mt genome of S. falconis was completely sequenced for the first time, which was a circular molecule of 16,872&#xa0;bp in length, encoding the typical set of 36 mt genes and six duplicate tRNA-Glu genes. Notably, there were seven identical and consecutive tandem repeat units each consist of a 169&#xa0;bp non-coding region followed by a trnE gene in the newly assembled genome. Phylogenomic analyses based on concatenated predicted amino acid sequences of 12 proteins robustly placed S. falconis in the same clade as Apharyngostrigea pipientis. Crucially, the family Strigeidae was not recovered as monophyletic. Instead, two species within Strigeidae, Cardiocephaloides medioconiger and Cotylurus marcogliesei, clustered with representatives of Diplostomidae, providing mt evidence for the paraphyly of Strigeidae under the current sampling. The newly sequenced mt genome of S. falconis reveals a previously unreported six-copy tandem repeat of trnE-containing units among currently available diplostomoid mt genomes. Phylogenetic analyses based on mt protein-coding genes provide additional mt evidence that the family Strigeidae was not recovered as monophyletic under the present taxon sampling. However, because mt genomes represent a single maternally inherited linkage group, broader taxon sampling, independent nuclear phylogenomic data, and explicit sensitivity analyses will be required to confirm these relationships and guide any formal systematic revision.

Preferred therapies for NDM-producing E. coli include PBP3-targeting antibiotics. However, the global spread of amino acid insertions in PBP3 (PBP3i) among NDM-producing E. coli can compromise these antibiotics, causing near pan-&#x3b2;-lactam resistance. This study sought to determine if combinations targeting multiple PBPs provide enhanced activity against isolates with PBP3i. Clinical NDM-producing E. coli isolates with PBP3i (n&#x2009;=&#x2009;3) or wild-type PBP3 (n&#x2009;=&#x2009;1) underwent genomic and phenotypic characterization. PBP2 (zidebactam) and PBP3 inhibitors (aztreonam and cefepime), alone or in combination were evaluated. The activity of aztreonam/avibactam in time-kill assays correlated with each isolate's MIC, regardless of PBP3 allele. Cefepime and zidebactam were synergistic against isolates with wild-type PBP3 but not PBP3i. In E. coli with PBP3i, zidebactam and cefepime/zidebactam produced similar killing profiles, indicating cefepime was minimally active. Accordingly, E. coli with PBP3i displayed morphological changes associated with PBP2 inhibition during cefepime/zidebactam treatment whereas isolates with wild-type PBP3 exhibited morphology characteristic of dual PBP2/PBP3 inhibition. Remarkably, aztreonam was synergistic with zidebactam in E. coli with PBP3i, producing eradication. In summary, cefepime/zidebactam synergistically inhibits PBP2 and PBP3 in isolates harboring wild-type PBP3 but predominantly PBP2 in the presence of PBP3i. Aztreonam and zidebactam engage PBP2 and mutant variants of PBP3, causing synergistic eradication of NDM-producing E. coli with PBP3i.

Indoleamine 2,3-dioxygenase 1 (IDO1) facilitates tumoral immune evasion via the kynurenine (Kyn) pathway, while ABCB1-mediated efflux drives multidrug resistance. Previously, miconazoles were reported as potent IDO1 inhibitors and some azole antifungals inhibit efflux pumps. Herein, we report a miconazole analogue, 1g, which inhibits both mechanisms. An in-house library of miconazole analogues, incorporating oxime ether derivatives with imidazole and pyrazole rings, was screened against Kyn production in IDO1-expressing SK-OV-3 and HeLa cells, yielding the hit pyrazole derivative 1g (IC50(Kyn)&#x202f;=&#x202f;&#x223c;5.8&#xb5;M). In vitro LDH assay showed minimal cytotoxicity for 1g and it was well tolerated by in vivo zebrafish model at 2&#x202f;&#xd7;&#x202f;IC50(Kyn-SK-OV-3) concentrations. Molecular modelling and biochemical assays indicated apo-form preference for 1g, which suppressed Kyn production without affecting IDO1 protein levels or inducing apoptosis. In indirect co-cultured models, 1g reversed Kyn-mediated immunosuppression, significantly restoring pro-IL1B and TNF levels in LPS-induced THP-1 macrophages. Furthermore, 1g restored Jurkat T cell proliferation, aggregate formation, and PDCD1 expression independent of direct 1g exposure, confirming a Kyn-dependent mechanism. Finally, 1g inhibited ABCB1 function in a dose-dependent manner and enhanced the sensitivity of ABCB1-expressing cells to paclitaxel, demonstrating its efficacy as a multidrug resistance (MDR) reversal agent. Our findings characterised 1g as a promising low-micromolar dual inhibitor of apo-IDO1 and ABCB1 with minimal cytotoxicity. It simultaneously disrupts the immunosuppressive Kyn axis and modulates ABCB1-mediated efflux, which provides a robust pharmacological basis for further development of next-generation combinatorial therapies.

In this cross-sectional study, we aimed to explore the correlation between body composition and bone mineral density (BMD) in young and middle-aged people with different gender and different BMI groups. We selected 1,295 young and middle-aged people (20 to 50 years old) who underwent physical examination at the Health Management Center of the International Medical Service (Xidan Branch) of Peking Union Medical College Hospital from January 2020 to June 2024 as the study subjects, and demographic characteristics, laboratory examinations, body composition(assessed by bioelectrical impedance analysis, including measurements of skeletal muscle mass, skeletal muscle index, body fat mass, percent body fat, fat-free mass, and visceral Fat Area), and dual-energy X-ray bone absorptiometry (DXA) results were collected. Based on gender and body mass index (BMI), the study participants were categorized into three groups: normal weight (18.5&#xa0;kg/m&#xb2; &#x2264; BMI&#x2009;<&#x2009;24&#xa0;kg/m&#xb2;), overweight (24&#xa0;kg/m&#xb2; &#x2264; BMI&#x2009;<&#x2009;28&#xa0;kg/m&#xb2;), and obese (BMI&#x2009;&#x2265;&#x2009;28&#xa0;kg/m&#xb2;). One-way ANOVA was employed to assess differences among the three groups. The relationship between BMI and BMD was analyzed using multiple regression models along with natural cubic spline models. Additionally, multiple regression models were used to examine the association between body composition and BMD. There were 774 males (216 in the normal body composition group, 380 in the overweight group, and 178 in the obese group) and 521 females (386 in the normal body composition group, 99 in the overweight group, and 36 in the obese group), and there was a significant difference in the laboratory results, body composition, and BMD among the three groups of males and females (all P&#x2009;<&#x2009;0.05). Multiple regression analysis, after adjusting for age, smoking and alcohol consumption history, hypertension, and diabetes mellitus, revealed a significant positive correlation between BMI and BMD at all skeletal sites (all P&#x2009;<&#x2009;0.05). The obese group exhibited a more pronounced increase in BMD compared to the overweight group (lumbar spine BMD: &#x3b2;&#x2009;=&#x2009;0.04, 95% CI 0.02-0.07; femoral neck BMD: &#x3b2;&#x2009;=&#x2009;0.09, 95% CI 0.07-0.11; total hip BMD: &#x3b2;&#x2009;=&#x2009;0.11, 95% CI 0.09-0.13; all P&#x2009;<&#x2009;0.05). Further analysis of the nonlinear relationship between BMI and BMD demonstrated that in women, BMD at all sites increased with higher BMI. In contrast, men exhibited an inverted U-shaped nonlinear association, with a decline in BMD observed in the high BMI range (BMI&#x2009;&#x2265;&#x2009;30&#xa0;kg/m&#xb2;). The correlation between body composition and BMD, skeletal muscle mass (SMM), skeletal muscle index (SMI), and fat free mass (FFM) were significantly positively correlated with BMD at all sites in both males and females (P&#x2009;<&#x2009;0.05), and percent body fat (PBF) was negatively correlated with BMD at all sites in the obese group of males, the overweight groups of males and females (P&#x2009;<&#x2009;0.05). Among young and middle-aged individuals, men show a decline in BMD when BMI reaches 30 or above, whereas women continue to experience a gradual increase in BMD with rising BMI. Additionally, elevated PBF is negatively correlated with BMD. This suggests that maintaining an appropriate BMI and PBF may be beneficial for bone health in this age group.

Southeast Asia's international rivers sustain the livelihoods of hundreds of millions of people and represent globally important biodiversity hotspots and ecologically sensitive regions. The scarcity of hydrological station data has constrained our understanding of long-term hydrological evolution, water cycle dynamics, and hydrological modelling in these basins. Here, we present a compilation of historical daily records of streamflow (87 stations), sediment concentration (40 stations), and water level (118 stations) in the upper reaches of the Irrawaddy, Salween, Mekong, and Red River basins for the period 1958-1987. Based on these records, we derived 74 hydrological indices. For streamflow, data were available from 12 stations in the Irrawaddy basin (mean record length 23 years), 13 in the Salween basin (18.8 years), 34 in the Mekong basin (21.1 years), and 28 in the Red River basin (23.3 years). Water level records covered 14 Irrawaddy stations (mean 20.92 years), 20 Salween stations (15.57 years), 48 Mekong stations (18.75 years), and 35 Red River stations (19.68 years). Sediment concentration data were available for 5 Irrawaddy stations (mean 13 years), 7 Salween stations (15.85 years), 16 Mekong stations (14.37 years), and 12 Red River stations (17.25 years). Overall, water level stations are the most numerous across the four basins, whereas sediment concentration stations are the fewest. The derived hydrological indices are crucial for elucidating the historical hydrological evolution of the upper Irrawaddy, Salween, Mekong, and Red River basins. In addition, these data provide valuable support for interdisciplinary studies of transboundary river environments, hydrology, ecology, and natural flow reconstruction, and for calibrating and validating numerical models. This dataset fills a key gap in large-sample global hydrological studies by improving the representation of this previously underrepresented region.

PARP inhibitors (PARPi) are effective in tumors with homologous recombination repair (HRR) deficiency (HRD), typically identified by germline/tumor mutations. However, genetic testing may miss intrinsic PARPi sensitivity and resistance. We evaluated strategies to improve detection and longitudinal monitoring of HRD across >500 tumor samples and >20 paired liquid biopsies, integrating genetic, genomic, and functional readouts. HRD was more frequent in high-grade ovarian cancer (HGOC; 52%) than in metastatic breast (mBC; 12%) or prostate cancer (mPC; 20%). Assay concordance was low-to-moderate, underscoring complementarity. RAD51 testing and the genomic instability score identified HRD in tumors lacking pathogenic HRR mutations (6% and 30% in mBC, 38% and 46% in HGOC, 14% and 27% in mPC, respectively). Longitudinal ctDNA sequencing revealed BRCA1/BRCA2 reversion mutations in >30% of post-PARPi mBC samples, which were associated with poor response to subsequent platinum therapy. These findings support the use of complementary HRD biomarkers in tissue and liquid biopsy to guide PARPi use and monitor response.