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This cross-sectional study evaluated the knowledge, skills, attitudes, and perceived barriers of dentists from the Federal District, Brazil, regarding Minimal Intervention Dentistry (MID). A validated online questionnaire was administered using non-probabilistic snowball sampling, and 404 dentists participated (74% female; mean professional experience: 12 &#xb1; 10.9 years). Data were analyzed using descriptive and inferential statistics, including multiple linear regression (p < 0.05). The dependent variables were knowledge, skills, attitudes, and barriers, while the independent variables included administrative region, years of professional experience, type of graduation institution, academic qualification, professional role, and information-seeking behavior. Overall, participants demonstrated high levels of competency in MID, particularly in the preventive and diagnostic domains; however, selective carious tissue removal was the procedure performed least frequently (38.6%). Regression analyses showed that dentists involved in teaching or research reported significantly fewer barriers (&#x3b2; = -2.56; 95% CI: -3.90 to -1.23; p < 0.001). Dentists who had received formal training in MID achieved higher scores in knowledge (&#x3b2; = 2.95; 95%CI: 2.31 to 3.59; p < 0.001) and in skills and attitudes (&#x3b2; = 3.40; 95%CI: 2.18 to 4.62; p < 0.001), as well as fewer perceived barriers (&#x3b2; = -1.52; 95%CI: -2.35 to -0.68; p < 0.001). Information-seeking behavior was positively associated with greater knowledge (&#x3b2; = 2.35; 95%CI: 1.56 to 3.14; p < 0.001) and improved skills and attitudes (&#x3b2; = 3.06; 95%CI: 1.55 to 4.56; p < 0.001). Graduates from public universities presented higher scores for skills and attitudes (&#x3b2; = 2.17; 95%CI: 1.15 to 3.18; p < 0.001) and reported fewer barriers (&#x3b2; = -0.88; 95%CI: -1.61 to -0.15; p < 0.01). Brazilian dentists demonstrated a strong theoretical understanding of MID; however, practical implementation remains limited. Academic background, involvement in education and research, and proactive learning behaviors were key determinants of higher competency levels and reduced barriers to the adoption of MID.

Survivors of ischemic stroke face a persistently high risk of recurrent cerebrovascular and cardiovascular events. Intensive lipid-lowering therapy is central to secondary prevention, yet substantial residual risk remains despite statins &#xb1; ezetimibe. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab and alirocumab, produce large additional reductions in LDL cholesterol (LDL-C) and may mitigate recurrent stroke. This study aims to synthesize randomized and high-quality evidence on efficacy and safety of PCSK9 inhibitors for secondary prevention in adults with a prior ischemic stroke or Transient Ischemic Attack (TIA) using a PRISMA-guided approach. PubMed/MEDLINE and the Cochrane Library (inception to September 7, 2025) were searched for Randomized Controlled Trials (RCTs), prespecified subgroup analyses, and systematic reviews/meta-analyses reporting stroke outcomes with PCSK9 inhibitors. Outcomes included total/ischemic/hemorrhagic stroke, Major Adverse Cardiovascular Events (MACE), mortality, and safety signals (e.g., neurocognition, intracranial hemorrhage). A systematic review with narrative synthesis was conducted; no de novo meta-analysis was performed due to heterogeneity in stroke outcome definitions, secondary endpoint reporting, and overlap across existing pooled analyses. Of 535 records identified, seven studies met inclusion criteria: two large cardiovascular outcomes RCTs-FOURIER (evolocumab) and ODYSSEY OUTCOMES (alirocumab), plus five systematic reviews/meta-analyses. Both RCTs reduced ischemic stroke and MACE without increasing hemorrhagic stroke; prespecified analyses in participants with prior ischemic stroke were directionally consistent, though underpowered for stroke-specific endpoints. Meta-analyses (>45,000 participants) confirm reduced total/ischemic stroke with no signal for intracranial hemorrhage. Current guidelines recommend adding a PCSK9 inhibitor in very-high-risk patients not achieving LDL-C goals on maximally tolerated statins &#xb1; ezetimibe. PCSK9 inhibitors produce large, durable LDL-C reductions and are associated with fewer atherosclerotic events, with a consistent signal toward fewer ischemic strokes, although stroke was largely a secondary endpoint in the available trials. PCSK9 inhibitors produce large, durable LDL-C reductions and are linked to fewer atherosclerotic events, with a favorable signal for ischemic stroke and no observed excess in hemorrhagic or cognitive harms. These findings, though derived mainly from secondary endpoints, support use in high-risk secondary prevention when LDL-C remains above target on optimal therapy. Clinical benefit will be greatest in patients with higher baseline risk and deeper LDL-C lowering. Further stroke-specific trials, extended follow-up in older populations, and harmonized outcome definitions are needed to strengthen certainty and optimize patient selection and value.

Intranasal delivery is a method of administering medications through the nasal cavity. It offers several advantages, such as rapid absorption, bypassing first-pass metabolism, direct nose-to-brain transport and localized effects. These benefits make it a promising approach for drug delivery in Parkinson's disease, a progressive neurological disorder characterized by the degeneration of nerve cells in the brain. This review evaluates the efficacy and safety of intranasal delivery for Parkinson's disease treatment. Several studies on intranasal apomorphine reported rapid clinical response, improved UPDRS motor scores, tapping scores, and median Webster's scores, suggesting its effectiveness as a rescue therapy during "off" states. Intranasal recombinant erythropoietin was well tolerated and showed cognitive benefits. intranasal glutathione was safe and showed better bioavailability. Intranasal insulin improved cognitive performance without hypoglycemia, indicating a localized effect. Intranasal cholecystokinin and ipratropium bromide did not show significant benefits. Intranasal desmopressin is a safe and effective medication for nocturnal polyuria in Parkinson disease. Intranasal transplantation of neural stem cells is safe and is associated with functional improvement. Finally, Rivastigmine nasal spray offered better bioavailability and fewer side effects compared with conventional forms. The most common adverse effect was mild transient nasal or throat irritation. This review highlights the potential applications, efficacy, and side effects of various intranasal medications for Parkinson's disease and proposes using new interventions for future studies. The general benefits of nasal administration for Parkinson's disease treatment include localized effects, fewer side effects, faster onset of action, improved bioavailability, and enhanced therapeutic effectiveness.

Autonomic dysfunction is a common sequela of mild traumatic brain injury (mTBI). Physical activity progression is an integral component of mTBI rehabilitation, particularly in addressing autonomic dysfunction. However, clinicians often rely on point-in-time evaluation of orthostatic and exercise intolerance to guide activity recommendations. Commercially available wearable devices (e.g., Fitbits) provide an opportunity to evaluate heart rate response to activity in a real-world setting. Previous work has used physiologic (heart rate) and activity (step count) data to identify subgroups of adults with stroke that may be used to guide activity recommendations. This method may be useful to subgroup youth post-mTBI to identify those who have abnormal physiologic responses to activity. We aimed to identify subgroups using heart rate and step count data in adolescents presenting for specialty care after diagnosed mTBI. Eighty participants aged 13-18 within six months of mTBI diagnosis were recruited to wear a Fitbit Sense 2. Data from seven days and two nights collected within fourteen days of enrollment were included. A group-based steps per minute (SPM) threshold (25th percentile; 10 SPM) and individualized heart rate threshold (20% heart rate reserve (HRR)) were used to classify each minute of active daytime data into one of four quadrants: SPM>10 & HRR>20% (QI), SPM&#x2264;10 & HRR>20% (QII), SPM&#x2264;10 & HRR&#x2264;20% (QIII), and SPM>10 & HRR&#x2264;20% (QIV). We used percentage of minutes in each quadrant, mean steps per day, percentage of minutes with zero steps, mean SPM in QI, and resting heart rate in a k-means clustering algorithm to identify subgroups. We evaluated subgroup differences by clustering variables using Kruskal-Wallis tests. Sixty-one participants were included. Three subgroups emerged: Sedentary (n=12), Active (n=23), and Atypically Elevated Heart Rate (AEHR; n=26). Subgroups varied significantly on all clustering variables ( p <0.01). The Active subgroup took a high number of steps per day, had lower sedentary time, and had the highest activity intensity (mean SPM in QI). The Sedentary subgroup took fewer steps per day compared to the Active subgroup, had high sedentary time, and showed the highest resting heart rate. The AEHR subgroup took fewer steps per day compared to the Active subgroup and had high sedentary time. The AEHR subgroup also spent a higher percentage of time with an atypically high heart rate response to low levels of activity compared to the other subgroups. Our findings suggest that data from wearable devices can identify subgroups of adolescents with mTBI with distinct physiologic/physical activity profiles, which may ultimately be used to inform personalized activity prescriptions. Future work should aim to understand how the identified subgroups relate to longitudinal outcomes.

The Female Athlete Triad, characterized by low energy availability, menstrual dysfunction, and impaired bone health, poses short- and long-term health risks for female athletes. Despite its prevalence, awareness and education surrounding the Triad remain limited, contributing to delayed recognition and care. This project assessed baseline knowledge and comfort discussing Female Athlete Triad-related topics among collegiate female athletes and evaluated the impact of a brief educational intervention on knowledge, attitudes, and help-seeking intentions. A community-based educational initiative was conducted among collegiate female athletes at a South Dakota university. Participants completed anonymous pre- and post-surveys surrounding a 30-minute educational session on the Female Athlete Triad. Surveys assessed prior education, knowledge of the Triad and its components, likelihood of seeking medical care for menstrual irregularities, and comfort discussing related concerns. Paired t-tests analyzed changes in Likert-scale items, and a chi-square test evaluated changes in comfort discussing health concerns. A total of 79 female athletes completed both surveys. While most participants reported prior education on nutrition (72), fewer had received education on bone (31) or menstrual health (37). Following the intervention, mean knowledge scores improved for understanding of the Female Athlete Triad (3.00 to 4.27), the role of nutrition (3.95 to 4.35), and factors affecting bone health (2.46 to 4.22) (all p < 0.001). The likelihood of seeking care for irregular menses increased (3.19 to 4.10, p < 0.001). Comfort discussing Triad-related concerns also improved, with more participants selecting "yes" and fewer selecting "unsure" (p = 0.002). A brief educational session significantly improved collegiate female athletes' knowledge of the Female Athlete Triad and enhanced comfort with help-seeking behaviors. These findings support the feasibility and impact of concise educational interventions as a preventive strategy and highlight opportunities to integrate Triad education into athletic programs and pre-participation sports physicals.

Melanocytic matricoma is a rare biphasic cutaneous adnexal neoplasm composed of matrical epithelial cells admixed with dendritic melanocytes. First described in 1999, fewer than several dozen cases have been reported in the literature. These lesions most commonly arise on chronically sun-exposed skin of older adults and typically present as small, pigmented papules or nodules that may clinically mimic melanoma. Histopathologic evaluation is required for diagnosis and characteristically demonstrates matrical differentiation with shadow cell formation and admixed melanocytes. Atypical variants with increased cytologic atypia or mitotic activity can further complicate distinction from malignant melanocytic proliferations. An 83-year-old Caucasian male presented for a general skin evaluation with concerns of an irregular papule on the dorsal hand that had been present for over one year. Physical examination revealed a 7 mm verrucous crusted papule. A shave biopsy demonstrated a dermal proliferation of basaloid matrical cells with scattered shadow cells and numerous pigmented dendritic melanocytes. Cytologic atypia and increased mitotic activity were noted. Immunohistochemical staining supported a biphasic epithelial and melanocytic population and helped exclude melanoma. These findings were most consistent with atypical melanocytic matricoma. The lesion was subsequently treated with complete surgical excision, and histopathology confirmed clear margins without residual tumor. This case highlights the diagnostic challenges posed by atypical melanocytic matricoma, particularly its clinical and histologic overlap with melanoma and other pigmented adnexal tumors. Recognition of characteristic matrical differentiation and the use of immunohistochemical analysis are essential for accurate diagnosis. Complete surgical excision with negative margins appears to be curative in most cases, though the limited number of reported cases makes prognostic assessment difficult. This report adds to the growing literature describing the clinical and histopathologic features of this uncommon neoplasm and emphasizes the importance of clinicopathologic correlation in guiding management.

Incremental peritoneal dialysis (PD) is defined as prescribing a "less-than-standard" PD dose. High-certainty evidence to guide safe incremental PD prescription is lacking, resulting in substantial practice variability. We conducted a multi-national survey to evaluate current uptake, practice patterns and clinician perspectives on incremental PD. An online, unit-level survey, comprising 27 questions on incremental PD practice, was purposively disseminated to senior PD unit staff (physicians and/or nurses) from Australia, Canada and Thailand between June 2023 and September 2025. A total of 254 responses were received from 175 PD units (Australia: 55 (89%) of 62 units; Canada: 49 (60%) of 82 units; Thailand: 71 (34%) of 210 units). Incremental PD was reported as prescribed in fewer than 10% of patients in most units (56%, P=0.16). Incremental PD definitions varied substantially: CAPD with <4 daily exchanges (75%), APD or CAPD performed <7 days/week (65% and 61%), CAPD <8 L/day (50%), a single long overnight exchange (46%), or APD without a day dwell (44%), highlighting the absence of international consensus. Key reported advantages included increased patient satisfaction (81%), willingness to choose PD (75%) and preservation of residual kidney function (64%). Frequently cited disadvantages included patient or caregiver resistance to dose escalation (62%) and needing more frequent monitoring (31%). Quality of life was identified as the most important area for future research. Incremental PD is prescribed infrequently and variably. Concern about patient resistance to dose escalation is a barrier. High-quality data are needed to guide how incremental PD is defined, initiated and escalated.

Hypertension is a highly common cardiovascular risk factor, and a large proportion of patients with coronary heart disease (CHD) have uncontrolled hypertension. We report on the distribution and determinants of hypertension awareness, treatment, and control in CHD hypertensive patients. The EUROASPIRE V survey included 8261 CHD patients from 27 countries. Awareness was defined as patients reporting being told by a health professional to have raised blood pressure (BP), being aware of their BP target and latest measurement. Patients using antihypertensive medication to lower BP were considered treated. Controlled hypertension was defined as BP <140/90mmHg (<140/85mmHg in patients with diabetes). Factors associated with hypertension awareness, treatment and control were identified with logistic regression. A total of 6496 EUROASPIRE V patients were considered hypertensive, from which 60.4% were aware, 91.7% were on treatment, and 46.8% were controlled. Number of antihypertensive drugs and adherence were independently associated with awareness (OR 1.23, 95%CI 1.16-1.31, and 2.18, 1.74-2.74 respectively) and control (1.11, 1.05-1.17 and 1.93, 1.57-2.37 respectively). Secondary (1.32, 1.03-1.68) and tertiary (1.70, 1.32-2.17) education and undertaking lifestyle changes (1.60, 1.37-1.87) were associated with awareness. Controlled patients were more often aware (1.43, 1.23-1.65) and had a healthier risk factor profile (BMI >25kg/m2 0.73, 0.61-0.87, diabetes 0.67, 0.59-0.76, LDL &#x2265;1.8mmol/L 0.75, 0.65-0.86) than uncontrolled patients. Hypertension control remains poor in hypertensive CHD patients, despite high treatment and reasonable awareness levels. Communication with CHD hypertensive patients, especially those from vulnerable groups, needs to improve to facilitate change of health behaviours. Controlling blood pressure levels is very important in patients with cardiovascular disease, therefore, we investigated the awareness, treatment and control of hypertension among coronary heart disease and hypertension.Less than half of the patients had their blood pressure controlled, despite most being on medication.Patients who were aware of their hypertension, took their medication regularly, had fewer risk factors, and adopted healthy lifestyle changes were more likely to have controlled hypertension.

In CheckMate-9DW, the suboptimal early tumor control of nivolumab-ipilimumab resulted in higher early mortality compared with the sorafenib/lenvatinib arm during the first 12 months. We evaluated whether adding lenvatinib to nivolumab-ipilimumab (NIL) improves outcomes versus nivolumab-ipilimumab (NI). Patients with unresectable HCC treated with NI with or without lenvatinib were retrospectively analyzed. Responses were evaluated by RECIST v1.1, survival outcomes by Kaplan-Meier and inverse probability of treatment weighting (IPTW) adjustment, and multiple sensitivity analyses. Liver function changes were evaluated using the albumin-bilirubin (ALBI) score. Among 104 patients, 82 received NI and 22 received NIL. The NIL group demonstrated a higher disease control rate than the NI group (81.8% vs. 39.0%; p < 0.01), with similar duration of response (21.4 vs. 21.8 months). Median progression-free survival (PFS) was longer with NIL (10.2 vs. 3.2 months), but not for overall survival (OS). In the first-line setting, NIL showed a trend toward longer PFS and fewer early deaths within 12 months. After IPTW adjustment and sensitivity analyses, the NIL regimen consistently demonstrated improved PFS (HR 0.44; p < 0.01) without a statistically significant OS benefit. Hypertension, proteinuria and stomatitis were more frequent in the NIL group, while ALBI scores remained stable. Development of immune-related adverse events was associated with improved outcomes. This real-world study provides proof-of-concept evidence that incorporating a VEGF inhibitor into dual ICIs therapy is associated with improved tumor control and prolonged PFS, with a potential reduction in early mortality. Prospective studies are warranted to confirm these findings.

Translating artificial intelligence (AI) research in orthopedics from proof-of-concept studies into production-grade clinical systems requires the systematic satisfaction of four prerequisite domains: interdisciplinary team architecture, technical data management, ethical and regulatory governance and production-grade technology and deployment infrastructure. Despite a tenfold increase in orthopedic AI publications, fewer than 6% of studies reach routine clinical deployment, reflecting persistent gaps in each of these domains. This article provides a technically rigorous, evidence-based framework organized around these four pillars. The interdisciplinary team may be structured using a product-centric topology that decouples stream-aligned clinical teams from platform infrastructure teams, following Huffman et al.'s six-step AI project lifecycle: obtain/curate/label data; establish a reference standard; develop the model; evaluate performance; externally validate and iteratively reinforce until clinical implementation is viable. Data management requires data extraction protocols, integration for bulk exports and a multi-component de-identification pipeline. A multi-stage Institutional Review Board framework governs ethical oversight, scaling from Exempt review for retrospective de-identified studies to Full Board Review with prospective validation and mandatory human-override mechanisms for interventional deployment. Responsible clinical deployment requires a multi-layer Clinical Machine Learning Operations framework, implementing privacy-preserving deployment, clinical observability, compliance audit trails and human-in-the-loop governance. Model drift has to be monitored with a degradation threshold triggering mandatory human review. Level V.

In this hypothesis and theory paper, we propose a conceptual framework for identifying sports whose characteristics align with traits commonly associated with autism spectrum disorder (ASD). Inspired by reports in sports media about neurodiverse athletes who have excelled in various athletic activities, we hypothesized that some sports may especially suit individuals with ASD because they trigger fewer symptoms while also allowing them to play to their strengths. This article is not a review aimed at testing a hypothesis but instead presents our hypothesis, organizes relevant concepts, and discusses which sports may be best suited for athletes with ASD. To explore our hypothesis, we examined two recent reviews on sports-based interventions for individuals with ASD. Our examination revealed that most published studies have investigated symptom relief or the management of challenging behaviors, not participating in sports for enjoyment, to develop skills, or as a means of performance. Because few such studies have measured performance or the suitability of specific sports for individuals with ASD, we particularly considered whether some sports are especially suited for individuals with ASD for the purpose of not only competition but also performance. Following an overview of four sports categories, this article discusses how those categories are compatible with some common symptoms and features of ASD. Emphasizing the variability between and within the categories, we showcase certain sports in order to provide guidance for athletes and children with ASD, as well as their parents and therapists, in identifying appropriate sports for their particular forms of ASD.

Climate-linked heatwaves and dust storms can exacerbate non-communicable disease (NCD) morbidity, yet quantitative evidence from displacement settings remains limited. We assessed short-term impacts of heat and dust events on symptom burden among Syrian refugees with non-communicable diseases (NCDs) in Jordan's Zaatari Camp. We conducted a prospective study of 660 adults receiving care at King Salman Humanitarian Aid and Relief Clinics (KS-Relief) clinics in Zaatari across three periods aligned to seasonal heatwaves. Self-reported symptoms following heatwaves and dust storms were collected via structured interviews. Repeated measures were analyzed using generalized linear mixed-effects models and generalized estimating equations with prespecified covariates. Heatwaves and dust storms were associated with increased symptom burden among participants with NCDs. Symptom burden was highest in Phase 1, the hottest period of 2024 in the Mafraq region (mean daily max 37.8&#xb0;C; peak 43&#xb0;C; multiple heatwave events and dust storm days), with more dyspnea, fatigue, and hypertension symptoms, especially among those with asthma or hypertension. Phase 2 (moderate heat with intermittent dust; mean daily max 34.1&#xb0;C; peak 37&#xb0;C) had lower odds of heatwave- and dust storm-related impacts than Phase 1 (odds ratio 0.54 and 0.62, respectively) with similar symptom profiles. Phase 3 (moderate heat; fewer dust storms; mean daily max 32.6&#xb0;C) showed no significant change compared to Phase 2. Across phases, women, larger households, and asthma were associated with higher odds of adverse health impacts. In a displaced, low-resource setting, heatwaves and dust storms impose measurable, recurrent symptom burdens on adults living with NCDs, with heightened vulnerability among those with asthma and in larger households, and generally higher reported impacts among women. Camp-appropriate adaptation (improved cooling, shading, dust- mitigation) and targeted patient education and surveillance may reduce climate- sensitive NCD morbidity. This study looked at how very hot weather and dust storms affect the health of Syrian refugees with long&#x2010;term illnesses (such as asthma, high blood pressure, and diabetes) living in Zaatari Camp in Jordan. We followed 660 adults receiving care at KS&#x2010;Relief clinics during three time periods that matched the hot summer months. Refugees were asked about their symptoms after heatwaves and dust storms, and the information was analyzed using statistical models. The results showed that both heatwaves and dust storms caused more health problems for people with chronic illnesses. Heatwaves, especially in mid&#x2010;summer, were linked to increased breathing difficulties, tiredness, and worsening of asthma and high blood pressure. Dust storms mostly affected people with asthma, allergies, and breathing problems. Women and people living in bigger households reported more health impacts. Overall, the findings highlight that refugees with chronic diseases are at higher risk during extreme weather events. Practical solutions such as better shading and cooling, ways to reduce dust exposure, and special health education and follow&#x2010;up are needed to protect vulnerable patients.

More than 100,000 patients are on the U.S. transplant waitlist, with proportionally fewer organ donations coming from rural areas. Optimization of donation services in rural and frontier communities could address this discrepancy. We sought to better understand attitudes, knowledge, and concerns regarding organ donation and transplantation among frontier populations by surveying patients in the United States Great Plains region. A 15-item survey was distributed for voluntary completion to patients &#x2265;18 years at three rural clinics in the Great Plains from July 2025 to January 2026. The survey included questions on demographics, exposure to and knowledge of organ donation, and attitudes regarding organ donation and transplantation. A total knowledge score was created by scoring participants' accuracy in selecting which organs/tissues can be donated. Statistical analyses included Fisher exact and Mann Whitney U testing, as well as a multiple logistic regression. A p-value of &#x2264;0.05 was considered significant. Among 101 respondents (74.3% female, 77.2% registered donors), 90.1% were White and 7.9% were Native American/Alaska Native (NA/AN). Registered donors had significantly higher knowledge scores than non-donors (p=0.0012). Men were more likely to limit transplant acceptance to donations from friends/relatives (p=0.024), while NA/AN respondents showed higher willingness for unconditional living donation (p=0.039). Multivariable regression identified knowledge score as the sole independent predictor of donor status amongst variables surveyed (OR 1.48; 95% CI 1.13-1.99). The primary concern with donation reported was fear of health complications (37.5%) and the most requested intervention was more information on the donation process (18.1%). Medical literacy appears to be positively associated with organ donor status in this population. Sex-, race-, and education-specific differences in donation attitudes exist and may inform targeted interventions. Addressing knowledge gaps and specific concerns through education and outreach could provide a strategy to increase donation rates in rural populations.

The purpose of this study was to identify participation determinants among high-risk individuals in risk-stratified upper GI (UGI) cancer screening. This sequential mixed-methods study was conducted in a population-based UGI cancer screening program in Ningxia Province, China. It integrates quantitative and qualitative methods to comprehensively examine participation determinants. Between April and December 2023, quantitative data were collected from 2,571 high-risk individuals identified by validated diagnostic models. Subsequently, 42 high-risk individuals (median age: 63.0 years; 81.0% male) were interviewed by stratified purposive sampling from March to April 2024. Logistic regression explored factors associated with screening adherence. Thematic analysis of qualitative interviews integrated quantitative findings using the Capability, Opportunity, and Motivation-Behavior framework. Of the high-risk individuals, 52.8% declined endoscopy. Nonparticipation was significantly associated with older age (adjusted odds ratio [aOR], 1.28 [1.06-1.54]), male sex (1.31 [1.01-1.70]), Hui ethnicity (1.35 [1.12-1.62]), nonsmoking (1.23 [1.01-1.50]), nondrinking (1.36 [1.09-1.71]), no family history of UGI cancer (1.48 [1.20-1.84]), fewer UGI symptoms (2.64 [2.19-3.18]), and no prior UGI examination (1.67 [1.37-2.05]). In the qualitative phase, seven key barriers were identified, including insufficient knowledge about UGI cancer and risk assessment, physical limitations, low perceived risk, gastroscopy-related fears, cost concerns, time constraints, and inadequate information. Addressing limited knowledge and program accessibility may improve participation and real-world implementation of risk-stratified UGI cancer screening.

In-vitro embryo production (IVP) in cattle is limited by the suboptimal competence of oocytes matured outside the follicular environment. While maturation is often achieved, incomplete cytoplasmic maturation may impair embryo development and survival. This study evaluated the influence of follicle size on oocyte cytoplasmic maturation, lipid metabolism, cumulus cell function, and embryo cryosurvival. Oocytes were collected from small (<&#x2009;6&#x2009;mm), medium (6-9&#x2009;mm), and large (10-20&#x2009;mm) follicles and evaluated at 0, 12, and 24&#x2009;h of in-vitro maturation (IVM). Organelle distribution, lipid and mitochondrial content and distribution, cortical granule distribution, and transzonal projections (TZPs) were evaluated. Gene expression was assessed in surrounding cumulus cells, and embryo development and cryotolerance were evaluated following fertilization and culture. While organelle patterns did not differ among follicle sizes for mitochondria, lipids, or cortical granules, oocytes from large follicles had lower lipid accumulation by 24&#x2009;h IVM, and fewer TZPs throughout maturation. Gene expression in cumulus cells from large follicles also had a greater abundance of transcripts involved in steroidogenesis, growth factor signaling, and glucose metabolism midway through maturation. Although cleavage and blastocyst development rates were similar across groups, embryos from large follicle oocytes had higher post-thaw survival and lower lipid content than those from small follicles. These findings demonstrate that follicle size affects key metabolic and structural aspects of oocyte maturation, ultimately influencing embryo quality. Selecting oocytes from larger follicles may improve embryo cryosurvival by promoting more complete cytoplasmic maturation and more efficient lipid regulation during IVM.

Sleep disorders can severely impact adolescents' physical and mental well-being, with self-compassion potentially serving as a key factor in promoting sleep quality. To explore the association, this study recruited 1281 adolescents (Mage&#x2009;=&#x2009;14.78&#x2009;years) who completed questionnaires on self-compassion and sleep problems. Data were analyzed using latent profile analysis and network analysis. Results showed that participants could be divided into four groups: uncompassionate group, low self-relating group, self-compassionate group, and a high self-relating group. There were significant differences between the low self-relating group and the self-compassionate group in network structures. This suggests that adolescents with higher self-compassion experience fewer sleep problems. Additionally, SD8 (morning fatigue) was identified as the most effective intervention target for alleviating all types of sleep problems in both the uncompassionate group and the high self-relating group. This study provides new insights for developing sleep problem prevention strategies tailored to different patterns of self-compassion among adolescents.

Developing drugs to treat rhinovirus (RV) infections remains a serious and unresolved problem. Pleconaril is the most widely studied broad-spectrum RV inhibitor. Fewer than 10&#x202f;% of circulating RV types are naturally resistant to pleconaril, which is why researchers continue to study it as a basis for creating new, more active molecules. We conducted a comprehensive study on modifying the pleconaril molecule and demonstrated that the isoxazole ring is crucial for determining anti-RV activity. Based on these findings, we aimed to further study the pleconaril core to discover new therapeutic candidates. We synthesized a large series of new pleconaril derivatives with mono- or di-substituted central phenyl rings, modified linkers, and substitutions on the isoxazole or 1,2,4-oxadiazole moieties. We evaluated the cytotoxicity and inhibitory activity of the obtained compounds using RV-A2 and RV-B14 strains in HeLa cells. To explain the differences in inhibitory profiles, we performed molecular dynamics simulations. Results from the structure-activity relationship analysis revealed that the substituents on the isoxazole and 1,2,4-oxadiazole rings, as well as the linker, play a decisive role in the anti-RV activity profile of monomethylated pleconaril derivatives. We demonstrated that the movement of two loops at the entrance of the VP1 binding pocket of the capsid protein and the inhibitor molecules correlates with the stability of the complex, and therefore, with efficacy against RV. Compounds 1q, 1gg, 2g, and 4c were identified as potent new RV inhibitors from this series of compounds. These compounds are promising new candidates for lead optimization and preclinical studies in the development of antiviral drugs against RV.

This study aims to present a simplified and resource-efficient computational model for predicting activity-dependent conduction velocity changes in unmyelinated axons, serving as a complementary tool to Hodgkin-Huxley models. Our approach is based on the concept of 'memory', where the speed of action potentials is modulated by prior activity. We utilized microneurography data from 95 mechano-insensitive C-fibres of healthy human participants, including both sexes, across various stimulation protocols to optimize model parameters. The model incorporates linear long-term and non-linear short-term memory components, effectively predicting propagation speed by convolving the history of recorded action potentials with the memory function. The proposed one-dimensional and two-dimensional memory functions yielded low mean squared errors in predicting the propagation speed of subsequent action potentials. This computational framework provides insights into dynamics of unmyelinated axons under varying conditions, enhancing our understanding of signal processing along the axon and its short-term memory capabilities. Additionally our model demonstrates rapid computation times suitable for real-time applications in electrophysiological experiments. This study introduces a novel model that simulates activity-dependent conduction velocity changes in unmyelinated axons, which is crucial for effective signal processing during conduction. Unlike Hodgkin-Huxley models that are computationally intensive and complex, our approach leverages fibre 'memory' to capture how prior activity influences conduction. With fewer parameters required to fit diverse datasets, including patient data, our highly efficient model enables faster simulations than Hodgkin-Huxley models and facilitates the analysis of spike train propagation over long distances, and it is therefore suitable for modelling peripheral axons that extend up to 1&#xa0;m. KEY POINTS: Unmyelinated axons, which are present in the peripheral and central nervous system, exhibit conduction velocity changes influenced by previous fibre activity, creating a form of fibre 'memory'. This study presents a novel computational model that predicts conduction velocity changes in unmyelinated axons based on prior activity, providing a faster and more efficient addition to complex Hodgkin-Huxley models. The new model incorporates both linear long-term and non-linear short-term memory components, demonstrating rapid computation times suitable for real-time applications. The model effectively captures the dynamics of nerve fibres, enhancing our understanding of axonal signal processing. This work offers insights into how previous activity influences axonal behaviour, informing future research on neurological disorders associated with altered nerve function.

Waning immunity and recurring COVID-19 waves point to the importance of sustained booster vaccination strategies. With repeated boosters needed to sustain population-level immunity, evaluating public preferences for COVID-19 booster vaccination is important for informing future vaccination strategies, as changing perceptions of urgency, threat, and motivation may alter willingness to receive vaccine boosters compared with initial uptake. This study aimed to explore the public's stated preferences and implicit willingness to pay for COVID-19 vaccine boosters in Singapore and to identify the sociodemographic factors and health-risk acceptance profiles associated with these outcomes. A discrete choice experiment survey was conducted among the general population in Singapore, recruited from an online panel in June 2022. Discrete choice experiment scenarios presented hypothetical scenarios varying by booster characteristics, including effectiveness, protection duration, and cost, and risks of COVID-19 infection, hospitalization, and death. A 2-stage discrete choice design was used: participants first selected between 2 hypothetical scenarios and then reported real-life booster acceptance of their chosen option. A mixed logit model was used for analyses. We also estimated implicit willingness to pay for vaccine boosters, as well as assessed the associations of sociodemographic factors and health-risk profiles with booster acceptance or hesitancy. A total of 1567 participants were included in the analysis. Overall, respondents preferred boosters that offered a longer duration of protection, particularly under higher risks of COVID-19 infection and death. Respondents were willing to pay S$1.43 for every percentage-point increase in booster effectiveness, S$4.95 (S$1=US $0.77 as of July 10, 2026) per additional month of protection, and an additional S$55.23 for a vaccine booster under the hypothetical worst-case scenario of COVID-19. Younger adults, women, individuals of non-Chinese ethnicity, those without children, people with higher socioeconomic status, individuals who had received 2 or fewer COVID-19 vaccine doses, and those with chronic conditions or on chronic disease medication were more likely to receive a booster. On the other hand, older adults, individuals with lower education or socioeconomic status, those with prior COVID-19 infection, and those exhibiting higher health-risk acceptance were less likely to accept booster vaccination. Our findings demonstrate how vaccine attributes, sociodemographic factors, and health-risk attitudes influence booster acceptance. These insights can guide policymakers in tailoring strategies and communication efforts that address population needs and behavioral drivers to improve booster uptake, address hesitancy, and support sustainable long-term immunization coverage, contributing to adaptive vaccination planning in the ongoing management of COVID-19.