The amorphous form of poorly water-soluble drugs can be stabilized using low- molecular weight co-formers in co-amorphous systems. However, the limited choice of suitable co-formers and the need to understand the underlying stabilization mechanism remain challenges for the widespread adoption of this formulation approach. In this study, a number of commercially available and custom-designed oligo- (di/tri)-peptides were used as co-formers to prepare stable co-amorphous systems of the BCS class II drug dipyridamole (DPM), using spray drying. Feed solutions were prepared by dissolving drug and co-former in a 1:1 M ratio in methanol-water mixtures. The spray drying process was evaluated and solid-state properties of the resulting formulations were compared to assess the effectiveness of different co-formers in preparing stable co-amorphous systems. Stability was investigated at 25 °C/60% RH and 40 °C/75% RH using non-ambient X-ray powder diffraction (XRPD), with performance quantified by the point of failure (POF), a time when co-amorphous systems exhibit crystalline peaks in the XRPD diffractograms.Spectroscopic techniques, together with molecular docking, were employed to investigate the underlying stabilization mechanisms. A direct correlation between the increasing number of amino acids in the peptide chain with the co-amorphous properties could not established within the range of co-formers investigated. It was found however that co- formers with more complex molecular structures and lower hygroscopicity were generally associated with improved stability. In addition, a correlation between higher binding affinity and increased POF time was observed, suggesting that computational screening may support the selection of suitable drug-co-former combinations prior to experimental development.
Hostile co-parenting can escalate during separation and divorce with significant ramifications on family relationships. The relational and private nature of this behavior can make it hard to document, study, and understand. The purpose of the present study was to determine how relational aggression targeting the co-parent (and former romantic partner), is associated with relational aggression targeting the parent-child bond. The sample consisted of 103 divorced/separated parents (45% fathers) who were co-parenting at least one child with their former partner (Mage years = 43.66, SD = 9.39). Parents completed measures assessing their engagement in different forms of relational aggression (toward their former partner and the child(ren)), relational abuse (from their romantic partner and their child(ren)), maladaptive personality traits, and vignettes assessing perceptions of loyalty/betrayal. Results suggest that parents who reported elevated levels of romantic relational abuse and who had stronger beliefs about betrayal (rating it as morally unacceptable) also reported more frequent engagement in both forms of relational aggression. Maladaptive personality traits (both psychopathic and narcissistic traits) were linked with romantic relational aggression. Perceptions of loyalty moderated the link between parental narcissistic traits and romantic relational aggression; and the link between parental psychopathic traits and excluding the co-parent, with parents more strongly opposed, engaging in these behaviors. The positive association among the two forms of relational aggression suggest that parent-child bond-breaking behaviors are best understood in the context of wider engagement in relational aggression, however each form of relational aggression has its unique nuances which need to be considered when developing prevention and intervention programs.
Remediation of former wood treatment sites is challenging due to the presence of contaminants with distinct physicochemical properties, such as arsenic (As) and polycyclic aromatic hydrocarbons (PAHs). This study evaluated a low-voltage electricity-induced soil remediation method designed to immobilize As while simultaneously degrading PAH in situ. A field pilot experiment was conducted at a highly contaminated site using iron (Fe) electrodes supplying pulsed direct current to promote PAH oxidation and Fe release from electrodes for As immobilization. Groundwater in five wells was monitored for concentrations of contaminants, their degradation byproducts, and microbial and fungal community structures. Over two years, dissolved PAH16 concentrations decreased by 62-94% across wells, with no accumulation of oxygenated or nitrogen-containing PAH. Dissolved As concentrations declined by up to 88% at low PAH levels, but reductions were weaker (55-57%) and more variable at very high PAH concentrations (hundreds to thousands μg L-1). Microbial communities, both prokaryotic and fungal, were characterized by taxa often found in contaminated aquifers and soils, with enrichment of PAH-degrading and As-tolerant Pseudomonas, Rugosibacter, and Duganella, but showed no adverse effect of the treatment. Overall, the method promoted concurrent PAH degradation and As immobilization with minimal secondary impacts, demonstrating potential for remediation of mixed-pollutant soils.
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Nanopore sensing holds transformative potential for revolutionizing protein and glycan sequencing. However, translating this potential into practical, high-fidelity identification is severely bottlenecked by the challenge of processing massive amounts of highly similar nanopore ionic-current data, spurring an urgent need for robust, AI-driven solutions. Prevailing deep learning methods suffer from two limitations: they often fail to capture the fine-grained temporal dynamics essential for distinguishing structurally similar analytes, and their generic training strategies inadequately extract weak discriminative features, thus limiting classification precision. Here, we present SEDA-Former (Signal Enhancement and Dynamic Attention Transformer), a deep temporal learning framework designed for high-resolution nanopore single-molecule identification. SEDA-Former incorporates a multi-window sliding standard-deviation method for feature enhancement, a multi-channel temporal convolutional network to mine weak features in temporal dynamics, and a progressive adaptive attention training strategy that dynamically reweights sample losses based on learning difficulty. Across a diverse set of challenging benchmark datasets, including nanopore signals of 15 glycosides, 24 ginsenosides, 8 DNA molecules, and 17 cholic acid conjugates, spanning varying levels of signal complexity, SEDA-Former consistently achieves substantially higher classification accuracy than state-of-the-art methods and demonstrates robust cross-dataset transferability. SEDA-Former provides a versatile and scalable solution to facilitate single-molecule identification in nanopore sensing.
Small cell lung cancer (SCLC) represents approximately 15% of all lung cancers and is characterized by poor survival. This study describes SCLC cases diagnosed in Spain and analyzes differences in patient characteristics and outcomes according to tobacco use. A cross-sectional study was conducted using data from the Thoracic Tumor Registry of the Grupo Español de Cáncer de Pulmón. All SCLC cases diagnosed between 2016 and 2025 were included. Sociodemographic and clinical variables were described and compared according to tobacco use (never smoker, former smoker, current smoker) and sex. Survival was assessed using Kaplan-Meier curves and multivariable Cox regression models. A total of 4920 cases were analyzed: 91 never smokers (1.8%), 1872 former smokers (38.1%), and 2957 current smokers (60.1%). Men accounted for 78.9% of cases, and the median age was 66 years. At diagnosis, 68.2% of patients had extensive-stage SCLC. Current smokers were more frequently female and younger. The most common symptoms were cough (36.7%) and dyspnea (36.0%). Five-year survival was 9.4% (95%CI, 8.3-10.5): 15.4% in never smokers, 10.8% in former smokers, and 8.2% in current smokers. Survival was higher in women than in men regardless of tobacco use. Higher mortality was associated with male sex (HR, 1.10; 95%CI, 1.01-1.20), current smoking (HR, 1.30; 95%CI, 1.01-1.68), older age (HR, 1.03 per year; 95%CI, 1.02-1.03), and extensive-stage disease (HR, 2.96; 95%CI, 2.72-3.22). The clinical characteristics and survival outcomes of SCLC differ according to tobacco use and sex. Current smokers have a poorer prognosis than never smokers, and women have higher survival across all groups.
Recent studies show that former professional football players have an increased mid-life risk of cardiovascular disease (CVD), including hypertension related to their prior concussion exposure while playing football. Adolescent football players at risk of concussion are exposed to biopsychosocial risk factors of CVD, and increase likelihood of stroke in adulthood. This study aims to examine the association between concussion history and hypertension among adolescent football athletes, adjusting for health-related anthropometric measures, post-concussion symptoms, and behavioral/environmental factors. Data were drawn from a prospective cohort study's cross-sectional baseline with self-reported concussion history. A total of 390 adolescent football athletes (mean age = 15.8 ± 1.2 years) in secondary schools participated in the study. The primary exposure included concussion history (yes/no). Other independent variables included post-concussion symptom scale (PCSS) severity, subjective social status (SSS), sleep disturbance score, and anthropometric measures (waist circumference, BMI, body fat, obesity level). The main outcome variable was blood pressure in the hypertensive range, defined as a binary-coded variable (SBP ≥ 130 mmHg, DBP ≥ 80 mmHg). A multivariable logistic regression model was conducted with complete cases (n = 327). A total of 31.4% of individuals (n = 121) had blood pressure in the hypertensive range. The multivariable logistic regression analysis showed that body fat is significantly and positively associated with blood pressure in the hypertensive range (AOR = 1.06, p = 0.03). However, concussion history, PCSS severity, SSS, sleep disturbance, waist circumference, and obesity level were not significantly associated (all ps > 0.05). Body fat percentage was positively associated with blood pressure in the hypertensive range in this sample, whereas no association with concussion history was observed. The results suggest that risk factors noted in former professional football athletes may not strongly impact blood pressure in adolescence but could raise concerns for increased CVD risk as these athletes move through the lifespan.
Anemia's high global prevalence and socio-economic burden necessitate early diagnosis, yet reliance on invasive blood testing creates significant barriers to diagnosis and treatment. To address this, we developed a deep learning model using the Detection Transformer framework for the rapid, non-invasive assessment of anemia severity in a real-world emergency department setting. Comparing a lip-focused model to a full-face approach, the former proved superior, achieving 85.0% accuracy. This significantly outperformed the full-face model (77.0%) and clinical judgments by both senior (59.3%) and junior (49.95%) physicians, with a rapid processing time of 127.50 ms. By integrating key medical knowledge to classify anemia into three severity levels, our model surpasses clinician performance, demonstrating its potential as a powerful, automated tool for clinical decision support.
Auditory dysfunction such as tinnitus is a common sequelae of traumatic brain injury (TBI), and has been associated with neurobehavioral outcomes, including cognitive decline, depression, and anxiety. Few studies have examined associations between concussion history and tinnitus independent of confounding by blast injury or occupational noise exposure. This study investigated concussion history and tinnitus among former professional American-style football (ASF) players, and evaluated whether tinnitus mediates associations between concussion history and neurobehavioral outcomes. This cross-sectional study included former ASF players who contracted with a professional league after 1960 and completed self-administered questionnaires between 2019-2025. Surveys assessed football exposure, auditory dysfunction, and mental health. Cumulative head injury exposure was measured using self-reported concussion signs and symptoms during play. Tinnitus was self-reported and assessed concurrently with validated measures of perceived cognition, depression, and anxiety. Logistic regression evaluated associations between concussion symptom history and tinnitus, and linear regression models assessed mediation and interaction effects. Among 1085 participants (mean age 57.9 ± 13.5 years; 32.4% Black; 6.1 ± 3.7 seasons), greater concussion symptom history was associated with increased odds of tinnitus (highest vs. lowest quintile: OR = 2.90; 95%CI 1.91-4.43; p < 0.0001). Tinnitus did not mediate associations between concussion symptom history and neurobehavioral outcomes. However, associations with perceived cognition (p-interaction = 0.1), depression (p-interaction < 0.01), and anxiety (p-interaction < 0.01) were larger among participants reporting tinnitus. Greater concussion symptom history was associated with increased reporting of tinnitus, and neurobehavioral associations were stronger among those with tinnitus. Clinicians should consider tinnitus when evaluating long-term cognitive and mental health outcomes following repeated head injury.
While single-molecule (SM) experiments using fluorescent probes have provided critical insight for molecular and polymeric glass formers, the microscopic mechanism of probe transport remains largely unexplored in such systems at the molecular length scale. Here, we report SM translational dynamics of molecular probes in high molecular weight polystyrene at three temperatures near the glass transition temperature (T_{g}). The probes exhibit quasistationary position fluctuations, non-Gaussian displacement distributions, subdiffusive transport with anticorrelated displacements, and a characteristic translational relaxation time. The observations are quantitatively described using a microscopic framework based on the generalized Langevin equation and supported by numerical modeling for heterogeneous transport. The probe dynamics reveal a progressive softening of effective viscoelastic confinement with increasing temperature and direct microscopic evidence of dynamic heterogeneity and suggest a pathway to more fully understand glassy dynamics in glass formers near T_{g}.
This paper presents a methodology to help decision-makers assess the environmental relevance of maintaining local livestock in their territories rather than relying on animal products imported from regions where production may be more efficient. Using the case of Reunion Island, we first conducted an attributional LCA to compare local and imported animal products, and second, a consequential territorial approach to assess the impacts of removing local livestock at the food system level. The attributional LCA showed that the impacts of imported animal products were lower than the impacts of local ones on global warming (-24%) and land use (-17%). However, the consequential territorial LCA showed that removing local livestock and relying on imports is not always environmentally beneficial, as the impacts depend largely on the fate of grassland. If current crops expand onto former grasslands, removing local livestock increases the impact of the food system on global warming by +3%, thereby contradicting the conclusions that could be drawn from attributional LCA alone. Other grassland conversion pathways were also tested, including return to natural vegetation, and the introduction of new crops to enhance crops-based food self-sufficiency. The consequential territorial approach accounts for effects of local livestock removal beyond the livestock sector itself and provides a systemic assessment of the role of local livestock in carbon storage and biomass recycling within the territory, by evaluating these services both in the presence and absence of local livestock.
In the rapidly evolving healthcare delivery, patient engagement in clinical research is emerging as a prerequisite for developing patient-centred care models, implementing value-based care, and creating metrics to enhance learning healthcare systems. In a high-acuity setting like critical care, this practice represents a paradigm shift from medical paternalism and the traditional disease-centred approach. It acknowledges the experiences and expertise of patients and families in the research cycle and clinical practice. However, patient engagement is a relatively new practice in critical care research with limited evidence. Our aim was to share insights and strategies from our qualitative study on women's experiences of critical care to advance the science of patient engagement adoption in critical care research. We collaborated with five patient partners, including two former intensive care unit patients and three informal caregivers, to design and conduct a qualitative study exploring the psychological distress experienced by women in critical care. Our engagement approach was guided by the Canadian Institute of Health Research principles: mutual respect, inclusivity, a supportive environment, and coproduction. Patient partners' input was facilitated through scheduled consultations, email correspondence, and flexible participation options. A designated research coordinator managed the process, ensuring meeting materials were shared in advance and notes were documented. We utilised the Saskatchewan Centre for Patient-Oriented Research level of engagement tool to tailor activities across project stages. Patient partners played important, self-determined roles such as assisting in proposal refinement, ensuring the cultural and linguistic relevance of research materials, coproducing data collection material, and developing engagement tools (such as terms of reference). They also copresented our engagement strategy at a conference. A trauma-informed approach was used to prevent retraumatisation. Patient partners received compensation and were offered opportunities for study dissemination. Patient partners possess valuable resources and insights that can enrich the research process. Emerging themes include the importance of defining expectations, relationship building, engagement as a cyclical process, and working with a diversity of perspectives. Through ongoing revision, our patient engagement strategies and lessons learned would be invaluable for researchers seeking to adopt patient engagement in critical care research. This project was not registered.
Immune checkpoint inhibitor (ICI) monotherapy for patients with recurrent, unresectable, or metastatic (RUM) head and neck squamous cell carcinoma (HNSCC) is associated with poor outcomes. Low-dose, hypofractionated, quad-shot radiotherapy (QSRT) may enhance the efficacy of ICIs. To evaluate the efficacy and toxic effects of ICIs in combination with QSRT for patients with RUM HNSCC that is amenable to QSRT. This single-arm, phase 2, nonrandomized clinical trial was conducted at a single, academic, National Cancer Institute-designated Comprehensive Cancer Center and included patients with RUM HNSCC who were going to receive treatment with pembrolizumab monotherapy and had a targetable site in the head and neck that was amenable to QSRT (based on location, prior radiotherapy dose, and tolerance). Patients were enrolled and treated between February 2021 and May 2024. Pembrolizumab (200 mg/m2) was administered every 3 weeks until disease progression, intolerance, or a maximum duration of 2 years. QSRT comprised 14.8 Gy in four 3.7-Gy fractions that were delivered twice daily on consecutive days. QSRT courses were delivered cyclically between pembrolizumab cycles. The primary outcome was overall response rate per Response Evaluation Criteria in Solid Tumors, version 1.1, in patients with at least 1 response assessment. Secondary outcomes were progression-free survival (PFS), overall survival (OS), and clinician-rated (Common Terminology Criteria for Adverse Events, version 5.0) and patient-reported (patient-reported outcomes version of the Common Terminology Criteria for Adverse Events, version 1.0) adverse effects (AEs). Of the 29 individuals who were screened, 21 enrolled, and 15 patients (median [range] age, 61 [33-86] years) were eligible for response analysis: 5 women (33.3%), 10 men (66.7%), 9 individuals with oropharyngeal/oral cavity primary tumors, and 14 current/former smokers (93.3%). Fourteen patients had received prior systemic therapy, and 11 had received prior RT. Among evaluable patients, the overall response rate was 47% (95% CI, 21%-73%). Median PFS and OS among the treated patients (n = 20) were 9.2 months (95% CI, 3-17) and 14.9 months (95% CI, 5 to not estimable), respectively. For the 15 patients who were evaluable for the primary end point, median PFS was 11.5 months (95% CI, 5.1 to not estimable), and median OS was 15.3 months (95% CI, 6.3 to not estimable). Grade 3 and 4 AEs occurred for 6 and 2 patients, respectively. Patient-reported AEs did not substantially change over time. This nonrandomized trial demonstrated the feasibility of pembrolizumab plus QSRT for patients with RUM HNSCC and provides preliminary evidence of a potential benefit to this novel combination that warrants investigation in future randomized clinical trials. ClinicalTrials.gov Identifier: NCT04454489.
Trainees provide a large proportion of neurologic care at academic medical centers in the United States. However, compared with their corresponding faculty practices, traditional trainee practices are often physically separate, serve primarily government-insured patients, and provide poorer continuity-of-care and reduced access to subspecialty services. We attempted to mitigate these challenges by merging the trainee and faculty practices at the Columbia University Department of Neurology over the 2022-2023 academic years. Over the 2022-2023 academic years, the Department merged the neurology trainee and faculty practices by embedding trainees fully within faculty clinics. We describe our integration process and share preliminary data on its effects on continuity of care and access to subspecialty services. We also share results from preintegration and postintegration surveys to residents and faculty demonstrating improvement in education and mentorship experience. By the 2023 academic year, trainees were fully embedded in faculty clinics and paired with longitudinal faculty mentors. This improved continuity of care for the patients in the former trainee clinics from 87.3% to 99.6% (p < 0.001) and a trend toward increase of subspecialty referrals from 41.5% to 45.5% (p = 0.142). It also significantly improved the educational and mentorship experience for residents and faculty. This study shows that integration of trainee and faculty practices is feasible and can improve continuity of care for patient groups who often receive inequitable neurologic care in academic centers. It can also significantly enhance the educational and mentorship experience for both trainees and faculty.
This study explores linkages between daily locomotor cycles to structural and material biomechanical variables in four sympatric West African cercopithecid species. While functional studies of primate postcrania typically rely on locomotor and activity profiles to create a context for biomechanical interpretation, two variables not typically included in such studies are stride counts and rest intervals. The former provide information on cumulative daily loads, while the latter have been shown to have positive osteogenic effects. Daily stride cycle counts in four adult females representing four sympatric cercopithecid species were collected over 30-day periods. Individuals of the western red colobus (Piliocolobus badius), black and white (king or pied) colobus (Colobus polykomos), Diana monkey (Cercopithecus diana), and sooty mangabey (Cercocebus atys) were followed in the Taï Forest, Côte d'Ivoire. We also recruited existing data on activity patterns to provide a qualitative assessment of the amount of daily rest among these species. We utilized existing data on femoral mechanical properties from individuals within these populations to discern whether the number of daily locomotor cycles corresponded with indices of bone robusticity. Differences in daily stride counts distinguish the four individuals, with higher stride counts characterizing the representatives of the two cercopithecine species. We do not observe a correspondence between stride counts and measures of long bone robusticity. Cumulative daily loads do not correspond to stronger or denser bones. The inclusion of information on rest duration and spacing may clarify functional linkages between locomotor behavior and skeletal mechanical properties.
The concept of field cancerization highlights spatially diffuse, pre-malignant changes in carcinogen-exposed lung tissue, yet current screening rarely captures such effects regionally. This exploratory study aims to quantify field cancerization via lobar-level radiomic clustering and assess its association with lung cancer risk in high-risk smokers. A total of 10,280 male current or former smokers (mean age, 62.1 ± 6.34 years) were enrolled from a high-risk population undergoing lung cancer screening. Unsupervised clustering of CT-derived radiomic features was performed for each lobe. A logistic regression-derived weighted spatial risk score was developed to quantify cumulative lobar risk. Cancer incidence associations were assessed after adjusting for polygenic risk and epidemiological factors, with stratified analyses by genetic risk and smoking duration. Distinct radiomic clusters were observed across all lobes, with the right upper lobe demonstrating a significantly higher lung cancer incidence in the high-risk cluster (0.997% vs 0.593%, p = 0.020). The weighted spatial risk score was independently associated with cancer risk (OR = 1.09, 95% CI: 1.02-1.16, p = 0.010). There was no significant interaction between the score and PRS (p = 0.938), suggesting a genetic background-independent effect. In stratified analysis, the score was significantly associated with lung cancer among long-term smokers (OR = 1.08, 95% CI: 1.00-1.17, p = 0.049), with a similar but nonsignificant trend in short-term smokers. Unsupervised clustering of lobar radiomics reveals background pulmonary alterations, supporting field cancerization and the "seed-and-soil" hypothesis, and offers an exploratory imaging-based framework for cancer risk stratification in screening. Unsupervised clustering of radiomic features at the pulmonary lobe level identified distinct background patterns associated with nodule and cancer incidence. A derived weighted lobe score was independently associated with lung cancer risk, especially among individuals with prolonged smoking histories. Lobar radiomic clustering identifies background lung changes related to cancer risk. Weighted lobe spatial risk score predicts lung cancer risk independently of genetic background. Longer smoking duration strengthens the link between lung damage and cancer risk.
A laboratory experiment was carried out aimed at testing novel biocovers and quantifying the mitigation of diffuse landfill gas (LFG) emissions into the atmosphere. The experiment, lasting 40 days, was designed to simulate a laboratory-scale landfill environment, using four integrated prototypes consisting of (i) a digester, representing the landfill waste body under predominant anaerobic degradation (AD) conditions, connected to (ii) a soil column, representing the landfill biocover with different mixtures of natural soil, anaerobically stabilized and dewatered sewage sludge (SS) and landfill leachate (LL). Gas samples were periodically collected from the digester headspaces and from four sampling ports located along each soil column. Experimental data showed that biodegradation processes of reduced biogas compounds increased upward along the biocover soil columns, whereas CO2 and O-substituted compounds, being produced by degradation of former compounds, showed opposite trends. To estimate the benefits on biogas abatement provided by the soil treatments, a novel index was proposed. The index considered the biogas biodegradation referred to bacterial activity, excluding the reduction of biogas due to dilution with atmospheric air occurring within the cover soil. Noteworthily, the tested novel biocovers with soil treated only with SS showed higher biogas abatement efficiencies relative to both the untreated natural soil and that with concurrent LL addition. These results support the hypothesis that treated soils, specifically with sewage sludge as a potential resource, represent a reliable option to improve the mitigation of gaseous species and functional groups released by diffuse LFG emissions.
Mitochondrial deenergization by lipophilic uncouplers is known to be reversed by 6-ketocholestanol (kCh), whereas with 2,4-dinitrophenol (DNP), a hydrophilic uncoupler, kCh does not cause mitochondrial recoupling. Here, we synthesized 2-alkylamino-4,6-dinitrophenol derivatives, varying alkyl from ethyl to dodecyl. All of them exhibited uncoupling of isolated rat mitochondria, with the most potent 2,4-dinitro-6-octylaminophenol acting at submicromolar concentrations. The octylamino derivative showed 100 times higher ability to induce electric current through planar bilayer lipid membrane than DNP. Mitochondrial recoupling by kCh was found for hexylamino and octylamino derivatives, whereas kCh-induced noticeable stimulation of the uncoupling, probably due to membrane dipole potential elevation, instead of the recoupling, was observed for the ethylamino analogue and DNP itself. By measuring a kCh-induced decrease in surface tension at the air-water interface in parallel with an increase in ANS fluorescence upon binding to kCh, we showed an ability of kCh to form micelles with CMC of 10 μM. The micelles readily bound hydrophobic uncouplers, such as the octylamino DNP analogue and CCCP, but less effectively bound DNP and its ethylamino analogue. Therefore, the recoupling by kCh could be associated with direct interaction between hydrophobic protonophores and kCh micelles, preventing the former from binding to mitochondrial membranes.
Soviet-era theory touted by Putin's former campaign manager claims oil deposits can form without organic matter.
The HAND-Q is a condition-specific, patient-reported outcome measure assessing health-related quality of life and satisfaction in individuals with hand conditions. Normative data from a global healthy population would improve clinical and research interpretation. Therefore, we aimed to provide normative values for the four most important HAND-Q scales-appearance, function, life impact, and symptoms-capturing key physical and psychosocial aspects of hand health. A web-based cross-sectional survey (August 1 to September 9, 2024) included healthy participants via the international Prolific platform and through convenience sampling, excluding individuals with hand conditions or trauma. A total of 1373 participants from 44 countries were included. Age (life impact p=0.002 and symptoms p=0.001), smoking status (appearance p=0.009, function p=0.007, and symptoms p<0.001), skin type (appearance p<0.001, life impact p=0.016, and symptoms p=0.002), and occupational factors showed significant associations with specific HAND-Q scales. Former smokers demonstrated incremental improvement in function (p=0.08) and life impact (p=0.018) scores with increasing time since cessation. No significant gender differences were observed. This study provides the first normative data for the HAND-Q scales obtained from a global population of healthy individuals. These reference values enhance the interpretability of HAND-Q scores and support their use in clinical and research settings to inform treatment planning and evaluate and interpret patient-centered outcomes. II.