Polymer films exhibit behaviour that cannot be explained by confinement effects alone. In 2001, Reiter and de Gennes proposed an alternative perspective, suggesting that preparation stages can imprint a form of conformational memory in polymer films. According to this view, polymers inherit nonequilibrium conformations during preparation, and the subsequent relaxation of this memory proceeds through a cascade of metastable states. This concept provided a rationale for several unusual behaviour, most notably the negative thermal expansion observed in freshly cast polymer films. Over the past two decades, experimental studies have accumulated strong evidence for preparation-induced conformational memory, often manifested through residual stresses and their slow relaxation. These advances have begun to establish preparation as a quantitative lever for probing nonequilibrium polymer physics. Despite this progress, several fundamental questions remain unanswered. In this article, I revisit the work of Reiter and de Gennes and summarize key experimental developments, emphasizing their continuing legacy. I will conclude by highlighting open questions whose answers would not only improve our fundamental understanding but also bring us closer to exploiting preparation as a quantitative lever to design programmable materials.
To improve access to care for serious illness, policy makers need evidence on how workforce capacity aligns with the need for palliative care. This study evaluated the palliative care workforce and policy environments at the state level, using a new data source: the 2024 Center to Advance Palliative Care's comprehensive Serious Illness Scorecard. We describe variation in the palliative care workforce relative to serious illness deaths across states and by five policy types related to serious illness: serious illness task forces, continuing medical education (CME), pediatric Medicaid waivers, adult payment policies, and Medicaid expansion. States varied from 2.91 to 19.86 hospice and palliative medicine-certified providers per 1,000 serious illness deaths, and seven states in the South census region had the lowest rates. CME for serious illness care and Medicaid expansion were significantly associated with higher rates. Between-state variation raises concerns about whether the workforce is sufficient to meet needs for people with serious illness in some southern states.
As global temperatures continue to rise, the incidence and mortality rates of heatstroke (HS) have significantly increased. However, the current forensic diagnostic standards lack clear pathological criteria for deaths caused by HS, and the mechanisms of multi-organ damage induced by HS are not yet fully understood. In this study, a rat model of HS-induced death was established under conditions of 39 ± 0.5 °C and 60% ± 5% humidity. Through histopathological observation, attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) spectroscopy, and machine learning algorithms, the most severely damaged organs in HS were identified, including the hypothalamus, hippocampus, liver, and spleen. Next, we performed transcriptomic (UID mRNA-seq) and proteomic (Data-Independent Acquisition technology, DIA) analyses on the key target organ-the hypothalamus. Transcriptomic analysis revealed 447 differentially expressed genes (DEGs), with 197 genes upregulated and 250 genes downregulated. Proteomic analysis identified 692 differentially expressed proteins (DEPs), with 241 proteins upregulated and 451 proteins downregulated. Integrated multi-omics analysis indicated significant enrichment of pathways such as endoplasmic reticulum protein processing, MAPK signaling, and apoptosis following HS. Further, three key genes/proteins (Hspb1, Dnaja1, Jun) were identified and their expression changes in the hypothalamus of HS rats were validated using quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry. Overall, this study provides new insights into the diagnosis and mechanisms of HS and offers scientific evidence for the clinical treatment of HS.
Heat stress (HS) poses a significant challenge to broiler welfare and growth. While the effects of constant (24 hr/day) HS are well documented, the consequences of HS duration at specific ages and the capacity for subsequent recovery, remain less understood. Therefore, 630 one-day-old Cobb500 broilers were assigned to 7 treatments and reared during a 6 week period to investigate the effects of varying HS duration on broiler growth, and recovery at different ages of exposure. Broilers were housed either in a climate-controlled (CC) barn or a natural cyclic HS open-sided (OS) barn. Treatments included broilers continuously housed for 6 weeks in CC (6CC) or OS (6OS). In addition, three other treatments were transferred from CC to OS for the final 3 weeks (3OS), 2 weeks (2OS), or 1 week (1OS) of the experiment. The last two recovery treatments (REC1, REC2) were placed in the CC house followed by 1 or 2 weeks in the OS house, from day 21 or 28 until 35, before returning to CC for the final week of the experiment. Each treatment included six replicates, with 15 broilers per replicate pen at the start of the experiment. Cloacal temperature, growth performance, mortality, plasma corticosterone, protein carbonyls, and histological morphology of the heart and lung were evaluated. Exposure to HS increased the cloacal temperature by at least 1.5°C at all ages (P < 0.001). Sudden exposure to HS at 36 days of age (1OS) resulted in severe mortality (67%) compared to control (6CC) and broilers exposed to HS at younger age (3OS and 2OS). HS consistently reduced body weight (BW) and average daily feed intake (ADFI); 6OS broilers finished 40.1% lighter than 6CC broilers (P < 0.001). Upon returning to thermoneutral conditions, REC1 and REC2 broilers immediately resumed growth rates comparable to controls but did not exhibit compensatory growth to recover the accumulated BW deficit. Very short-term HS exposure (1OS) triggered a spike in plasma corticosterone (25.42 nmol/L) and protein carbonyls (1.92 nmol/mg) compared to 6CC controls (P < 0.001). Descriptive histological examination revealed that subendocardial erythrocyte accumulations were increased in 6OS hearts and were absent in CC-housed broilers. Taken together, sudden HS exposure at 36 days of age poses an unmanageable threat to survival. While broilers recover from HS quickly, lost performance is not regained through compensatory growth within the 6 week period.
Open Dialogue (OD) is a social network-based, integrative approach to mental health care that encourages shared understanding between service users, their significant others, and professionals. This study aimed to explore staff experience of OD training delivered across services in planned, acute and urgent care, providing a multi-team approach. Focus groups were conducted with seventeen staff members across two time points: three months into training, and three months post-training. A thematic analysis was performed on the transcribed data. Four superordinate themes, each containing multiple subthemes, were identified across the data set: current practice versus paradigm shift, commitment of training, friction in experiential learning, and shifting power. Trainees offered mixed evaluations of the training in relation to its practical and experiential elements, with considerable value being found in the multi-team approach. The findings suggest a range of clinical, organisational, and personal benefits of OD training for members of staff through; renegotiating power dynamics, improving working relationships and continuity of care, and enhancing personal reflection and development.
We aim to investigate the relationship between iron metabolism and prediabetes using data from the National Health and Nutrition Examination Survey (NHANES) and the China Health and Nutrition Survey (CHNS) databases, and to identify prediabetes subgroups with distinct distinct iron-related biomarker profiles through cluster analysis, while examining both universal patterns and population-specific differences across U.S. and Chinese populations. Data from NHANES 2003-2010 and 2015-2020 were used for primary analysis; these cycles were selected based on the availability of complete iron metabolism biomarker data. Participants were classified into prediabetes group and normoglycemic group. Linear regression analysis was conducted to evaluate the association between clinical indicators and iron metabolism markers. K-means cluster analysis was performed in the NHANES prediabetes subsample to identify phenotypically distinct subgroups. The identified cluster structure was subsequently validated by independently applying the same algorithm to the CHNS 2009 prediabetes subsample. Between-group comparisons were performed using the t-test or Mann-Whitney U test for continuous variables and the χ² test for categorical variables, as appropriate. A two-sided P-value of < 0.05 was considered statistically significant. Among 7110 participants from NHANES, 1528 were classified into the prediabetes group. Compared with the normoglycemic group, the prediabetes group exhibited significantly higher ferritin [82.0 (IQR 40.1-158.0) vs. 47.00 (IQR 26.1-89.3) µg/L, P < 0.001] and lower serum iron (14.9 ± 6.3 vs. 16.0 ± 7.2 µmol/L, P = 0.031), reflecting a pattern of sub-clinical iron redistribution rather than clinically defined iron overload. Three distinct prediabetes phenotypes were identified: Cluster 1 (obesity-related insulin resistant-younger phenotype, N = 424), cluster 2 (mild insulin secretion impairment-younger phenotype, N = 456), and cluster 3 (high iron store-older phenotype, N = 648). Cluster 3 demonstrated older phenotype with higher ferritin concentrations within the normal reference range and showed the highest ferritin and serum iron concentrations among the identified clusters, while Cluster 1 has intermediate ferritin levels and Cluster 2 has the lowest levels (P < 0.001). A comparable three-cluster structure was replicated in the CHNS 2009 cohort, with Cluster 3 representing a higher proportion (48.89% vs. 42.41%) and retaining the highest ferritin levels [92.6 (IQR 52.0-155.3) µg/L, P < 0.001]. Variation in iron-related markers is present in the prediabetes stage, with distinct patterns across subgroups. We identified three distinct prediabetes phenotypes characterized by different ferritin profiles within the normal reference range, providing novel insights for individualized clinical practice and risk stratification.
Implantable medical devices (IMDs) increasingly integrate continuous monitoring with autonomous therapeutic functions, transforming clinical practice while raising significant ethical concerns. As these technologies expand - particularly among vulnerable populations such as individuals with substance use disorders - the tension between patient safety and autonomy intensifies. This article examines the ethical and legal implications of IMDs, emphasizing ongoing consent, data governance, and neurorights. We conducted a narrative and normative bioethical analysis grounded in interdisciplinary literature. Empirical and conceptual studies on IMDs, neurotechnologies, and opioid overdose interventions were reviewed alongside regulatory frameworks, including the European General Data Protection Regulation (GDPR), Brazil's General Data Protection Law (LGPD), and the United States Health Insurance Portability and Accountability Act (HIPAA). Highly autonomous IMDs challenge traditional informed consent models, particularly regarding revocation, device deactivation, and continuous data processing. Vulnerable populations may face stigma and expanded secondary uses of sensitive data, while existing regulations leave gaps in neural and biometric data protection. Ethical implementation requires patient-centered frameworks ensuring ongoing consent, secure data governance, and protection of mental privacy.
Goal-directed walking involves regulating foot placements to achieve specific tasks. This requires visuomotor integration. Perceptual, cognitive, and contextual salience guide attention and motor planning for navigation. Here, we quantified how perceptual salience informs lateral foot placement while walking. Participants walked along prescribed virtual paths (straight or winding), thus keeping contextual salience (the task itself) constant. We manipulated perceptual salience by systematically altering environment richness (rich vs. sparse) and path color contrast (high vs. low). We quantified head pitch angle to approximate gaze direction. We quantified lateral stepping regulation from a Goal Equivalent Manifold framework. Our guiding hypothesis was that stepping arises from continuous decision-making action-perception processes: each step taken affects the decision of where to step next. This generated three testable predictions. First, that contextual salience alone (merely "seeing" the path) is sufficient for people to regulate stepping. However, while substantial between-path differences largely supported this, within-path differences in both head angle and stepping demonstrated that visual information (perceptual salience) also informs stepping. Second, we predicted perceptual salience of task-relevant visual information (here, of the path itself) is sufficient to guide stepping. However, while changing path color contrast did elicit more and greater changes than manipulating environmental richness, path visual saliency alone was not sufficient. Third, we predicted perceptual salience from peripheral vision also contributes to stepping. This prediction was supported, though less strongly than manipulating path visual saliency or contextual salience (straight vs. winding paths). Thus, both contextual and perceptual salience interact to influence step-to-step control of walking.
In 2009, the first recovery college (RC) was established in England, and has since been established and implemented in various countries worldwide. Although literature exists on the effects and benefits of RCs, there has yet to be a systematic examination of their implementation experiences. This scoping review provides an overview of the facilitators and barriers to the implementation of RCs. A comprehensive search was conducted across CINAHL, ProQuest Dissertations, PubMed, PsycINFO, Scopus, and Web of Science, targeting English-language publications from January 2000 to August 2025. The scoping review identified and examined 43 studies. Facilitators included: (1) regular operation considerations; (2) considerations for effective co-creation; (3) continued development; (4) importance of visibility. Barriers included: (1) management challenges; (2) logistical challenges; (3) course implementation difficulties; (4) misalignment of RC principles. We highlight issues in RCs' everyday operations and emphasize the need for them to adopt a flexible, adaptable stance. However, several areas of research require greater attention, including RC hiring practices, policies for continued development, and research on RCs from Asian and non-Western perspectives.
Cardiovascular diseases continue to be the leading cause of morbidity and mortality worldwide. Reducing LDL cholesterol (LDL-c) is one of the fundamental pillars of cardiovascular prevention; however, a significant percentage of patients do not reach the recommended therapeutic targets with first-line treatment. PCSK9 inhibitors have demonstrated significant reductions in LDL-c and decreased cardiovascular events in high- and very high-risk patients. The 2025 update of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) guidelines for the management of dyslipidemias reinforces the concept of the earlier and the lower, the better, as well as the need for early combination therapies.
We describe a semidefinite relaxation method which finds lower bounds to the ground state energy of a quantum Hamiltonian subject to Hermitian linear constraints along with approximations of ground state expectation values. We show that symmetry can be used to significantly reduce the computational requirements, and we include unitary, antiunitary, discrete, and continuous symmetries in our analysis. We demonstrate our method using the 1D Hubbard model and find quantitative agreement with both exact diagonalization and the Bethe ansatz.
The aim of this study was to evaluate scanning electron microscopy (SEM) combined with energy-dispersive X-ray spectroscopy (EDS) as complementary analytical tools for supporting continuous improvement in pharmaceutical granule manufacturing. Pilot-scale cefixime granules for oral suspension were prepared as defined process scenarios, including placebo, reference, intermediate, stress-exposed, and optimised batches. SEM was used to compare granule morphology, surface integrity, and agglomeration behaviour, whereas EDS provided qualitative and semi-quantitative information on localised elemental composition, with emphasis on sulfur as an API-related marker and oxygen-to--sulfur trends as surface-sensitive indicators of process- or stress-related variability. Intermediate and stress-exposed batches showed increased surface roughness, microstructural deterioration, and higher oxygen-to-sulfur ratios, whereas reference and optimised batches showed more uniform morphology and comparable elemental profiles. The findings indicate that SEM/EDS can provide useful material-level insight into process-related variability and may support root--cause investigation and process refinement. Overall, SEM/EDS is proposed as a complementary, localised, and semi-quantitative approach for supporting continuous improvement in pharmaceutical granule manufacturing.
To evaluate whether postmenopausal females with vasomotor symptoms (VMS) exhibit altered nitric oxide synthase (NOS)-dependent cutaneous vasodilation during local heating, and whether these responses vary by body region. Cutaneous vascular conductance normalized to maximum vasodilation (percentage of the maximal conductance [%CVCmax]) was assessed at the chest, abdomen, forearm, and calf using laser-Doppler flowmetry in 18 postmenopausal females (9 with current VMS, 9 without VMS). Local skin temperature was increased from 33 °C to 42 °C (~30 min) to elicit a vasodilatory plateau. NG-nitro-L-arginine methyl ester (20 mM), a NOS inhibitor, was then perfused during continued heating (~40 min). The NOS contribution was assessed by the difference in %CVCmax mediated by NG-nitro-L-arginine methyl ester. Baseline %CVCmax was higher at the chest compared with the calf across groups (10.0 [3.3, 16.6]%; P = 0.0013). During the 42 °C heating plateau, females with VMS exhibited greater %CVCmax than those without VMS when responses were pooled across regions (7.2 [1.7, 23.5]%; P = 0.013), and at the abdomen (8.7 [0.6, 18.4]%), chest (10.3 [2.3, 18.4]%), and calf (8.4 [0.4, 16.5]%; all P < 0.036). However, the NOS-mediated contribution did not differ between groups or across regions (all P > 0.15). Although postmenopausal females with VMS exhibit heightened cutaneous vasodilatory responses to local heating, NOS-dependent vasodilation is preserved. These findings suggest that enhanced microvascular reactivity in VMS is not attributable to altered endothelial NOS function.
The ICH E9(R1) estimands framework requires precise specification of the treatment effects (estimands) a trial is designed to estimate. A recent article by Troxel et al. [1] has advanced a narrow view that only estimands using the treatment-policy strategy are scientifically defensible. In particular, the article recommends that journals adopt a new policy with regard to reporting results from clinical trials, advocating that only results based on the treatment policy strategy should appear in the main body of the paper with estimates based on other strategies relegated to supplementary materials. Treatment-policy estimands target the effect of assignment to treatment and are defined to include outcomes after non-terminal post-randomization events, such as treatment discontinuation or initiation of alternative or rescue medications. Use of this estimand requires that outcome collection continues following these intercurrent events. In the presence of missing data, estimation of effects using the treatment policy strategy typically relies on strong, unverifiable assumptions [2]. While using treatment policy strategies to address all intercurrent events is appropriate for certain scientific objectives, these estimands do not address all clinically relevant questions. Results based on estimands using alternative strategies for primary and key secondary objectives should therefore also be presented in the main body of the published paper when they address important clinical questions that are relevant to patient care or decision-making.
Temozolomide (TMZ) is an oral alkylating agent that represents a cornerstone therapy for glioblastoma and other high-grade gliomas. Although TMZ is generally well tolerated, hypersensitivity reactions (HSRs), including urticaria, have rarely been reported and may lead to treatment interruption. Rapid drug desensitization (RDD) offers a potential strategy to enable continuation of essential therapy; however, standardized protocols for TMZ are limited. Here, we present a 46-year-old woman with glioblastoma who developed widespread urticaria during maintenance TMZ therapy. The reaction developed within four hours of the last dose and completely resolved following treatment with corticosteroids and antihistamines within 24 h. Based on clinical history and lesion characteristics, an immediate HSR to TMZ was considered. As no alternative treatment options were available, an oral RDD protocol targeting a dose of 240 mg was prepared. The protocol included stepwise dose escalation using diluted oral solutions followed by capsule administration, with premedication using cetirizine and methylprednisolone. Desensitization was successfully completed without breakthrough reactions, and the protocol was repeated in two consecutive cycles without complications. Our protocol provides detailed information on drug preparation, dose increments, and administration intervals, supporting its reproducibility and feasibility. This case contributes to the limited literature by demonstrating that oral RDD can be safely and effectively performed in patients with TMZ-induced urticaria. The successful repetition of desensitization further supports the safety of this approach. This protocol may assist clinicians in maintaining first-line TMZ therapy in patients with HSRs, thereby preventing unnecessary treatment interruptions and improving clinical outcomes.
Adoption of improved crop technologies is widely recognized as essential for enhancing agricultural productivity, yet their validation under real farming conditions remains limited. The scaling trial was aimed to provide an interesting agronomic challenge through introducing a new technology that contradicts the established local field production practice. The trial was conducted over four consecutive production years (2019-2022) involving 109 (22 female) purposively selected farmers who managed a collective 32.5 ha of farmland. The farmers were strategically selected to promote the dissemination of new technologies, create demand, strengthen stakeholder linkages, and establish a sustainable technology multiplication system in the area. The comprehensive quantitative and qualitative data were collected and analyzed using proper statistical methods. The results demonstrated that the improved field pea technology was provided a 71.1% yield advantage compared to the existing local practices. With continuous expert support, 75% of farmers applied the full technology package, although 62.5% perceived it as labor-intensive, particularly during planting and thinning stages. Despite this, 95.9% of participants expressed a strong interest in cultivating the new technology in the future. Farmer-to-farmer diffusion was evident, with 1520 kg of improved seed distributed by 75% of involved farmers and stakeholders to non-participant but interested farmers. The farmers and stakeholders who attended different field days were also impressed and committed to adopting the new technology, recognizing its potential adaptation to moisture-deficient areas. These findings hence confirm the agronomic and social viability of the new technology. Therefore, it is recommended that scaling up and out of this improved field pea technology in similar areas be facilitated by the establishment of viable seed-multiplying cooperatives and strengthened stakeholder linkages.
Burn injuries represent a challenge in the Gaza Strip, where access to rehabilitation services is constrained by ongoing conflict and limited healthcare resources. This study describes the implementation and outcomes of rehabilitation and physiotherapy services for patients with post-surgical skin grafts (SSG) scars treated in Médecins Sans Frontières (MSF) outpatient clinics in Gaza. We conducted a retrospective descriptive study using routinely collected programmatic data from patients with SSG scars enrolled in MSF post-operative outpatient clinics in the Gaza Strip (Gaza City, Beit Lahia, and Khan Younis), between January 2018 and December 2020. Outcomes were assessed using five measures: reducibility score, Functional Activity for Burn (FAB) score, Vancouver Scar Scale (VSS), Visual Analogue Scale (VAS) for pain, and an itching score. A total of 177 patient records were included. Most patients were children under 18 years (n = 136, 76.8%), and scald burns were the most common injury mechanism (n = 119, 67.6%). Improvements were observed across several clinical and patient-reported outcomes during follow-up. Mean pain scores decreased from 5.3 (SD: 2.5) to 1.4 (SD: 1.8), itching scores from 3.7 (SD: 2.7) to 2.7 (SD: 2.2), and VSS scores from 7.1 (SD: 1.8) to 5.7 (SD: 1.7). Functional outcomes improved, with mean FAB scores increasing from 25.6 (SD: 7.1) to 34.6 (SD: 2.3), while reducibility scores decreased from 2.3 (SD: 1.4) to 0.8 (SD: 0.9). Our findings describe the implementation of rehabilitation and physiotherapy services and document improvements observed during follow-up among burn patients in the Gaza Strip. Despite the challenging environment, MSF's clinic in Gaza demonstrated the feasibility of delivering rehabilitation care to burn survivors in a conflict-affected area. Further research is needed to refine and validate best practices in rehabilitation interventions tailored to the specific needs of patients in conflict-affected and resource-constrained settings and to continue improving the quality of care for burn survivors.
Lossless full text indexes are utilized in a myriad of applications in bioinformatics. The continuously decreasing cost of generating biological data has resulted in the need to build full text indexes on biological datasets of increasing size. Many compressed full text indexes have been developed to address this problem. In particular, run-length Burrows-Wheeler transform (RLBWT) based compressed full text indexes have seen wide development and adoption. However, the construction of these RLBWT-based compressed full text indexes is still computationally expensive, sometimes prohibitively so, even for current dataset sizes. Therefore, we present algorithms for the construction of RLBWT-based compressed full text indexes and their supporting data structures in compressed space. The algorithms have a space complexity of O(r) words and run in O(n) time for repetitive datasets, where r is the number of runs in the BWT, n is the length of the text, and repetitive datasets implies nr∈Ω(log n). We provide the first algorithm to compute LCP-related information for repetitive datasets in optimal time and O(r) space, greatly reducing memory requirements. The key idea behind this algorithm is the utilization of r samples of the inverse suffix array at regular intervals. For example, on the Human Pangenome Reference Consortium Release 2 dataset, this reduces peak memory from 2135 GiB to 170 GiB (12.6x reduction) compared to the previous best method (pfp-thresholds). The implementation is available at https://github.com/ucfcbb/TeraTools.
Despite advances in lipid-lowering and anti-inflammatory medications, atherosclerotic cardiovascular disease (ASCVD) continues to be the leading cause of morbidity and mortality worldwide. Recent studies have identified the gut microbiota as a key modulator of cardiovascular health via the gut-heart axis. This review investigates the molecular processes by which microbial metabolites affect atherogenesis. Proatherogenic substances like trimethylamine-N-oxide (TMAO), which are produced from dietary precursors through gut microbial and hepatic metabolism, aggravate foam cell production, platelet aggregation, and vascular inflammation. Short chain fatty acids (SCFAs), such as butyrate and propionate, have been shown to protect against atherosclerosis by activating G-protein-coupled receptors, regulating gene expression, and improving endothelial function. Additionally, secondary bile acids, tryptophan derivatives, and phenylacetylglutamine have emerged as important microbial metabolites involved in vascular disease. The review also summarizes various therapeutic strategies such as use of probiotics, prebiotics, postbiotics, precision microbiome editing (using bacteriophages and CRISPR-Cas systems), and fecal microbiota transplantation (FMT) for targeting gut-heart axis. Multi-omic systems combined with artificial intelligence can now detect disease-specific microbial signatures, improving risk stratification and paving the way for precision microbiome-based therapeutics. However, challenges such as determining causality, regulatory intricacies, and inter-individual variability in host-microbiome interactions remain. Despite these obstacles, the gut-heart axis provides a disruptive paradigm in preventive cardiology by emphasizing tailored microbiome therapies as a complement to traditional ASCVD care.
Rheumatoid arthritis (RA) is a well-recognised risk factor for fractures. However, short-term fracture risk factors remain unclear. This study aimed to elucidate factors useful for short-term fracture prevention. Patients were enrolled in the National Database of Rheumatic Diseases in Japan (2002-2020) were analysed. Modifiable risk factors included changes in disease activity, modified health assessment questionnaire (mHAQ) scores and oral glucocorticoid usage. Of the 37,466 patients with RA enrolled, 1655 experienced a first fracture. Sex, age, disease duration, disease activity, mHAQ score and glucocorticoid usage significantly differed between patients with and without fractures. Among 734 with 4-year pre-fracture data, mHAQ scores gradually increased over consecutive years before the fracture. When classified into four groups according to mHAQ changes over 2 consecutive years, patients with continuous increases had significantly higher fracture incidence (2.13%) than those with increases only in years 1-2 (1.43%), only in years 2-3 (1.59%) or with no increase across 2 consecutive years). A consecutive 2-year increase in mHAQ score is associated with an increased risk of subsequent fracture in patients with RA, offering valuable insight for targeted fracture prevention strategies.