Search Results (8,510)

Oral minoxidil, including low-dose regimens, is increasingly used off-label for alopecia, but cardiovascular safety remains a clinical concern. We compared cardiovascular adverse event reporting patterns for oral versus topical minoxidil using a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS). FAERS data (2004Q1–2025Q3) were imported and deduplicated; minoxidil reports were restricted to primary/secondary suspect (PS/SS) drugs and eligible reports from 2012 to 2025. Exposure was classified as ORAL, TOPICAL, BOTH, or UNKNOWN using a standardized route/dose-form dictionary. Signals for Core and Expanded cardiovascular MedDRA Preferred Terms (PTs) were assessed using reporting odds ratios (RORs) with 95% confidence intervals; sensitivity analyses included alopecia-restricted cohorts excluding hypertension indications. In the primary ORAL-versus-TOPICAL cohort (559 oral; 56,947 topical), 23 Core-list PTs and 31 Expanded-list PTs met the signal definition. Strongest primary signals included pericardial effusion (ROR 307; 95% CI 158–597), hypertensive crisis (ROR 1037; 95% CI 133–8117), pulmonary hypertension (ROR 932; 95% CI 118–7368), and pulmonary edema (ROR 1965; 95% CI 114–33,813). In an alopecia-restricted sensitivity cohort excluding hypertension/blood-pressure indications (146 oral; 24,367 topical), hemodynamic and effusion-related PTs (e.g., tachycardia, palpitations, orthostatic hypotension, syncope, and pericardial effusion) remained disproportionately reported, although event counts were smaller and confidence intervals were wider. Oral minoxidil PS/SS reports in FAERS showed disproportionate reporting of several cardiovascular PTs relative to topical minoxidil reports. However, because FAERS is a spontaneous reporting system without exposed-patient denominators and with important limitations including under-reporting, stimulated reporting, incomplete clinical information, and residual confounding, these findings should be interpreted strictly as hypothesis-generating reporting signals rather than evidence of incidence, relative risk, or definitive comparative clinical safety. Full article

Background: Ultra-hypofractionated whole-breast irradiation (WBI) delivering 26 Gy in five fractions has been established as a standard of care following the FAST-Forward trial. However, real-world data addressing advanced delivery techniques and the feasibility of incorporating a simultaneous integrated boost (SIB) remain limited. Methods: We retrospectively analyzed 40 patients with early-stage breast cancer (pT1–2N0M0) treated with breast-conserving surgery, followed by ultra-hypofractionated WBI using helical tomotherapy. Patients received either WBI alone (26 Gy in five fractions) or WBI with an SIB to the tumor bed (29–30 Gy in five fractions). Dosimetric parameters for planning target volumes (PTVs) and organs at risk (OARs) were evaluated. Acute skin toxicity was assessed using CTCAE version 5.0. Results: The median patient age was 55.7 years. The mean PTV V95% was 97.8%, with excellent hotspot control (PTV V105% < 5% and V107% < 2%). For left-sided tumors, the mean heart dose was 1.67 Gy, and the ipsilateral lung V8Gy remained below 15% in all patients. Acute radiation dermatitis was limited to Grade 0–1 in all cases. At a median follow-up of 14.8 months, both local control and overall survival were 100%. Conclusions: Ultra-hypofractionated WBI delivered using helical tomotherapy, with or without SIB, demonstrates robust dosimetric quality, minimal acute toxicity, and favorable early clinical outcomes in routine clinical practice. Full article

Background/Objectives: Youths with cerebral palsy (CP) have reduced levels of physical activity (PA) due to motor impairments and functional difficulties. Few studies have observed its link with various factors and none in young adults with CP. This study aimed to investigate the relationships between PA and various factors in young adults with CP, such as gait function, endurance, participation, and personal/environmental influences. Methods: Participants over 15 years old with CP who underwent Clinical Gait Analysis (CGA), the 6 min walk test, and wore an actimeter (ActiGraph GT3X+) for seven days were included. PA was assessed by daily step count (NbSteps/day). Explanatory factors included the Gait Profile Score (GPS), walking speed, subjective walking perception, joint pain, fatigue, 6 min walk distance, SF-36 questionnaire scores, and lifestyle habits. Correlations, univariate, and multivariate regression models were used for the analysis. Results: Forty-seven CP patients (28 males, 19 females, mean age 23.6 years) were included, with 82% classified as GMFCS I and 18% as GMFCS II. The average NbSteps/day was 5685. Significant correlations were found between NbSteps/day and subjective perception, pain, GMFCS level, and walking speed. Multivariate regression identified walking speed and physiotherapy (PT) sessions as significant predictors of PA. Conclusions: PA in young adults with CP is linked to walking speed, GMFCS level, joint pain, fatigue, and PT. No differences have been observed between patient unilateral or bilateral CP. However, individual behaviors vary and are not fully explained by linear regression analysis. Full article

Catalysis has entered everyday life through a range of technological processes that rely on different catalytic systems. The increasing demand for such systems requires rationalization of the use of their expensive components, such as noble-metal catalysts. As such, a catalyst with low noble-metal concentration, in which each one of the noble atoms is active, would reach the lowest price possible. Nevertheless, no clear reactivity descriptors have been outlined for this type of low-coordinated supported atom. Using DFT calculations, we consider three diverse systems as models of single-atom catalysts. We investigate monomers and bimetallic dimers of Ru, Rh, Pd, Ir, and Pt on MgO(001), Cu adatom on thin Mo(001)-supported films (NaF, MgO, and ScN), and single Pt adatoms on oxidized graphene surfaces. The reactivity of these metal atoms was probed by CO. In each case, we see the interaction through the donation–backdonation mechanism. In some cases, CO adsorption energies can be linked to the position of the d-band center and the adatom’s charge. A higher-lying d-band center and less-charged, supported single atoms bind CO more weakly. Also, in some cases, metal atoms that are less strongly bound to the substrate bind CO more strongly. The results suggest that the identification of common activity descriptor(s) for single metal atoms on foreign supports is a difficult task with no unique solution. However, it is also suggested that the stability of adatoms and strong anchoring to the support are prerequisites for the application of descriptor-based search to novel single-atom catalysts. Full article

Background: The CONSTANS, CONSTANS-like, and TIMING OF CAB EXPRESSION 1 (CCT) domain proteins are key regulators of flowering time and circadian rhythms in annual plants, but their diversity and temporal expression patterns in perennial trees remain poorly understood. Methods: Here, we performed a genome-wide characterization of CCT family genes and analyzed their seasonal and circadian expression dynamics in Populus. Using an HMM-based search, we identified 49 putative CCT genes (PtCCTs) in the Populus genome and classified them into five subfamilies (COL, CMF, PRR, ALSM and ZIM) based on domain composition and phylogeny. Results: Synteny and duplication analyses showed that most PtCCTs arose from segmental duplication and have predominantly evolved under purifying selection. Promoter analyses revealed a rich repertoire of cis-regulatory elements, with a marked enrichment of light- and hormone-responsive motifs, particularly G-box and ABRE elements, in PtPRR and a subset of PtCOL promoters. Transcriptome data indicated that many PtCCTs display distinct tissue-specific expression patterns, with PtPRRs and PtZIMs being strongly enriched in dormant buds. Seasonal transcriptomes from leaves and shoot apices revealed discrete expression profiles associated with growth, bud set, and winter dormancy, and most PtPRRs showed increasing transcript levels from September to December. Diurnal time-series data further identified 19 PtCCTs with significant rhythmic expression, separating COL and PRR members into night- and day-phased groups. Network analysis using STRING indicated that PtPRRs interact with photoperiodic pathway components such as PtGI, and re-analysis of diurnal data from wild-type and lhy-RNAi hybrid aspen showed that several PtPRRs exhibit phase and amplitude changes when LHY expression is reduced. Conclusions: Together, these results provide a comprehensive overview of the CCT gene family in Populus and highlight PtPRRs and specific PtCOLs as promising candidates that link the circadian clock and light signaling to seasonal growth cessation and bud dormancy in perennial trees. Full article

Public bus systems are vital to achieving sustainable urban mobility in developing countries; yet, the quality of bus stops, a critical interface between users and transit services, remains widely overlooked. This study evaluates bus stop quality in Sulaymaniyah, Iraq, from bus users’ perspectives by integrating importance–performance analysis (IPA) and the customer satisfaction index (CSI) with level of conformity analysis (CR) using extensive, real-world survey data. The objective was to identify priority areas to help improve the quality of public bus stop provision in the city and ensure the most efficient allocation of resources by focusing on the quality attributes that matter most to bus users. The results highlight six critical service quality attributes that require immediate improvement due to their high importance to users and low service quality performance: (i) safety barriers to prevent traffic accidents while waiting at bus stops; (ii) accessibility of bus stops for elderly and disabled users; (iii) availability of signage and timetables/maps; (iv) overall bus stop quality; (v) narrow bus stop platforms; and (vi) waiting time at bus stops. Addressing these gaps is essential to enhance user satisfaction and ensure that users have a safer, more inclusive, and reliable PT experience. This study offers evidence-based recommendations to enhance bus stop design and service quality, thus contributing to improved user satisfaction and increased ridership. More broadly, the results can be applied to other rapidly urbanizing developing cities seeking to provide equitable, safe, and user-centered bus transit systems. Full article

Background/Objectives: Stroke is a leading cause of mortality and disability in Saudi Arabia; however, national estimates of stroke-related rehabilitation needs remain limited. This study quantified temporal trends in stroke incidence, prevalence, premature mortality, and disability from 1990 to 2021. It also examined disparities in stroke-related disability by subtype, sex, and age in 2021 and projected rehabilitation demand to 2030 to inform health system planning under Vision 2030. Methods: We conducted a secondary analysis of Global Burden of Disease (GBD) 2021 estimates for Saudi Arabia. Age-standardized rates for incidence, prevalence, years of life lost (YLLs), and years lived with disability (YLDs) were extracted for overall stroke and three subtypes: ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Temporal trends were evaluated using log-linear regression to estimate the average annual percentage change (AAPC). YLDs were mapped to severity levels and four rehabilitation modalities, physiotherapy (PT), occupational therapy (OT), speech–language therapy (SLT), and multidisciplinary comprehensive rehabilitation (MCR), using utilization probabilities informed by the literature. Projections to 2030 incorporated national population forecasts and included 95% prediction intervals and sensitivity analyses. Results: From 1990 to 2021, age-standardized stroke incidence declined from 166.3 to 130.7 per 100,000 (−21.4%; AAPC, −0.86%, p = 0.004), prevalence from 982.4 to 965.2 per 100,000 (−1.8%; AAPC, −0.10%, p = 0.056), and YLL rates from 3209.0 to 1893.4 per 100,000 (−41.0%; AAPC, −1.76%, p < 0.001). In contrast, YLD rates declined modestly from 133.5 to 129.9 per 100,000 (−2.7%; AAPC, −0.13%; p = 0.032). Despite these reductions in age-standardized rates, absolute stroke-related YLDs more than tripled, increasing from approximately 10,900 (95% UI: 8100–13,900) in 1990 to 36,245 (95% UI: 26,600–46,100) in 2021, largely driven by population growth and aging. In 2021, ischemic stroke accounted for 71.1% of total YLDs, followed by ICH (20.3%) and SAH (8.5%). Among adults aged 15–49 years, females had higher hemorrhagic YLD rates than males, with particularly pronounced differences for SAH (female-to-male ratio, 1.5–1.7). By 2030, the projected YLD-equivalent workload, a standardized proxy measure of relative service demand rather than a direct headcount of required therapists, is expected to increase to 29,758 for PT, 21,809 for OT, 14,879 for SLT, and 15,083 for MCR. Sensitivity analyses showed that rehabilitation demand estimates were sensitive to assumptions regarding severity distribution, with a hemorrhagic-weighted scenario increasing projected MCR demand by 6.8%. Conclusions: The increasing absolute burden of stroke-related disability in Saudi Arabia, despite declining age-standardized rates and substantial reductions in premature mortality, highlights the necessity to expand rehabilitation capacity. Scaling community-based, outpatient, and telerehabilitation services in alignment with the Health Sector Transformation Program and integrating disability-informed planning into Vision 2030 should be prioritized. Full article

Inflammatory bowel disease (IBD) requires sustained patient engagement in complex therapeutic and self-management processes, making health literacy (HL) a key determinant of effective care. This cross-sectional study assessed HL levels among adults with IBD attending a public day-hospital service in Lisbon, Portugal, and examined associations with sociodemographic, lifestyle, and selected clinical variables. A convenience sample of 280 participants completed a self-administered questionnaire, including the Portuguese version of the European Health Literacy Survey Questionnaire (HLS-EU-PT-Q16). Descriptive statistics, bivariate analyses, and multiple linear regression were used. HL indices were computed and categorized into proficiency levels; domain- and competency-specific indices were also analyzed. Overall, 48.3% of participants had inadequate or problematic HL, whereas 42.5% had sufficient HL. Healthcare-related HL showed the most favourable profile, whereas health promotion emerged as the weakest domain, with domain-specific mean indices ranging from 31.8 ± 8.3 to 34.4 ± 7.4 on a 0–50 scale. Competency-specific indices indicated that appraisal and, particularly in disease prevention, application were the lowest, and item-level analyses highlighted difficulties with mental health information-seeking and evaluating or acting on media-based health information. In multivariable linear regression analysis, higher educational attainment was positively associated with HL (B = 0.89; 95% CI: 0.05 to 1.73; p = 0.039), whereas female sex was independently associated with slightly lower HL scores (B = −1.72; 95% CI: −3.33 to −0.11; p = 0.036). These findings indicate that nearly half of patients with IBD in a day-hospital setting experience HL-related vulnerabilities, especially beyond clinician-mediated care. Targeted, HL-sensitive interventions focusing on critical appraisal and decision-to-action support may enhance self-management and equity in IBD care. Full article

Chromophobe RCC (chRCC) represents 5–10% of all RCC; however, data regarding outcomes and predictors of recurrence and survival in localized disease are limited. The Canadian Kidney Cancer Information System (CKCis) is a multi-institutional prospective cohort. Patients who had surgical resection for clinically localized chRCC between January 2011 and July 2024 were included. Descriptive statistics were used, and cancer recurrence and time to death were estimated using Kaplan–Meier curves. Associations between baseline and tumour characteristics and recurrence and survival were assessed using Cox proportional hazards models. The study cohort included 790 patients. Median follow-up was 4.9 years, mean age was 57.8 years and 57.5% were male. Partial nephrectomy occurred in 52.7% and radical in 47.3%. Recurrence-free survival was 93.6% at 5 years and 90.2% at 10 years. In the 45 patients who recurred, 40 had metastatic disease, 3 had local recurrences, and 2 had new contralateral disease. Predictors of recurrence included a higher pT stage, sarcomatoid features, positive margins, and tumour necrosis. Overall survival was 94.5% at 5 years and 83.7% at 10 years. Predictors of death included high pT stage, increase in pathological size, and increasing age at diagnosis. In this large Canadian cohort, patients with surgically resected, localized chRCC had favourable 5- and 10-year oncologic outcomes. These favourable outcomes are a reminder that not all RCC patients with non-clear cell histologies should be pooled together as a single entity. There is, however, a subgroup of patients with less favourable outcomes who should be the focus of future research that aims to prevent recurrence and RCC death. Full article

In the pathological cascade of cerebral ischemia, the pyroptosis axis mediated by the NLRP3 inflammasome in activated microglia is a core link driving neuroinflammation and secondary brain injury. Quercetin has been proven to possess multi-target neuroprotective activity, and its anti-inflammatory effect has attracted particular attention. However, direct molecular evidence is lacking regarding how quercetin precisely regulates the NLRP3/Caspase-1/GSDMD core pyroptosis axis in microglia in cerebral ischemia models and whether it can directly target NLRP3 to inhibit this axis, thereby alleviating cerebral ischemic injury. This study aimed to investigate the molecular mechanism by which quercetin alleviates cerebral ischemic injury through inhibiting the pyroptosis axis, combining cellular and animal models with molecular docking and molecular dynamics simulations. The oxygen-glucose deprivation (OGD) model of BV2 microglia and the photothrombotic (PT) model of focal cortical ischemia in male C57BL/6 mice were used to detect the ameliorative effect of quercetin on cerebral ischemia-related injury through cellular and animal experiments. AutoDock Vina 1.5.7 and GROMACS 2025.3 software were employed for molecular docking and molecular dynamics simulations, respectively, to analyze the binding mode and complex stability between quercetin and the NLRP3 protein. The results showed that quercetin could significantly ameliorate OGD-induced injury in BV2 cells and downregulate the expression of pyroptosis and inflammation-related proteins and factors. Meanwhile, it relieved motor dysfunction in PT mice, attenuated cortical neuronal injury, and inhibited the activation of the cerebral pyroptosis axis. At the molecular level, molecular simulation predictions indicated that quercetin might specifically bind to the NACHT domain of the NLRP3 protein, forming a complex with a stable conformation, and van der Waals interactions served as the main driving force for binding. This study confirmed that quercetin can directly bind to the NLRP3 protein and alleviate cerebral ischemia-induced inflammatory injury by inhibiting the activation of the NLRP3/Caspase-1/GSDMD pyroptosis axis and the release of downstream inflammatory factors. Combined with the molecular simulation results, a predictive hypothesis is proposed: direct binding of quercetin to the NLRP3 protein is one of its core mechanisms of action. These findings provide direct experimental evidence for the development of NLRP3-based drugs against ischemic brain injury. Full article

Background/Objectives: This study aimed to clinically investigate how variations in foot morphology influence spinal and lower limb alignment, based on the concept of an ascending kinetic chain. Methods: We analyzed the medical records of 100 patients who met the inclusion criteria. The X-ray image data used in the analysis included weight-bearing lateral views of both feet, whole-spine anteroposterior (AP) and lateral views, and full-length standing AP scanograms of the lower legs. In the obtained X-ray images, Calcaneal Inclination Angle (CIA), Tibiotalar Tilt Angle (TTA), Tibiotalar Angle (TA), Quadriceps Angle (Q-angle), Pelvic Incidence (PI), Pelvic Tilt (PT), Sacral Slope (SS), and L1–S1 Lordosis (LL) were measured. Participants were categorized into subgroups based on their CIA values: Pes Planus, Normal, and Pes Cavus. These subgroups were analyzed by foot orientation (right and left) using one-way analysis of variance (ANOVA) and Pearson correlation coefficient analysis. Results: The one-way ANOVA identified significant differences in mean right foot PT values among subgroups. Correlation analysis shows moderate associations between foot CIA and Q-angle of the knee, as well as pelvic parameters including PI, PT, SS, and LL. Conclusions: Analysis of the correlation between foot parameters and body alignment, in the context of diagnostic and evaluative aspects of Chuna manual medicine (CMM), revealed moderate correlations among the foot, ankle, knee, pelvis, and lumbosacral regions. These findings suggest that foot morphology may play a clinically relevant role in posture-related disorders and could contribute to preventive and corrective strategies for musculoskeletal alignment. Full article

Objective: This study aimed to determine the relationship between sigmoid sinus dehiscence (SSD), sigmoid sinus topography, mastoid pneumatization, and adjacent temporal bone structures in patients with pulsatile tinnitus (PT). Methods: A retrospective analysis was performed on 344 temporal bone cone-beam computed tomography (CBCT) scans (172 PT patients and 172 age- and sex-matched controls). The degree of mastoid pneumatization, presence and size of SSD, sinus topography, and distances between the sigmoid sinus and key landmarks—the lateral semicircular canal (LSCC), jugular bulb (HJB), and external auditory canal (EAC)—were measured. Quantitative and qualitative characteristics were compared between groups, and independent predictors of PT were identified using multivariate logistic regression. Results: Compared to controls, SSD was substantially more common in the PT group (115/172 vs. 44/172, p < 0.001). Patients with PT had significantly larger anteroposterior and vertical sigmoid sinus dehiscence diameters (4.61 ± 0.99 mm vs. 3.87 ± 0.25 mm and 3.37 ± 0.47 mm vs. 2.92 ± 0.14 mm, respectively; both p < 0.01). Additionally, in the PT group, the sigmoid sinus was situated closer to the lateral semicircular canal, jugular bulb (JB), and external auditory canal (all p < 0.01). Conclusions: Venous pulsatile tinnitus was substantially correlated with sigmoid sinus dehiscence, sinus topography, and decreased sinus–EAC distance. Quantitative CBCT evaluation of these anatomical relationships could help with surgical planning and enhance diagnostic evaluation. Full article

Because of concentrated connection damage, the impact of sequential hazards on CLT shear wall systems is much more severe than that on traditional concrete and steel structures considering ductile component behaviors. The present paper evaluated the dynamic response of CLT wall structures in wind-only and sequential seismic–wind scenarios and compared the structural dynamic responses and damage levels of different CLT wall systems. The structural models were established separately based on an SOM benchmark structure, a SOFIE project three-story CLT shear wall structure, and a PT CLT wall platform structure from the NHERI Tall Wood project. The equivalent fluctuating wind load was calculated with the ASCE 7 average wind speed, the reference ESDU wind profile, calibrated wind pressure distribution, and simulated fluctuation from the NatHaz Online Wind Simulator. The sequential load was applied to the structural models in the order of seismic excitation, resting time, and then dynamic wind load. The dynamic responses of different CLT wall structures were compared among loading scenarios with increasing seismic and wind intensities. The wind-excited peak story displacement and acceleration for both CLT structures were significantly magnified in the sequential seismic–wind scenarios compared with the wind-only scenarios. The simulation results indicated that the sequential seismic–wind scenarios caused significant acceleration in damaged connections for the conventional CLT shear wall structure. The PT CLT wall structure had minor displacement and acceleration, which were linear to the wind loading factors. For the conventional CLT shear wall structure, the magnification of the acceleration was found to have a strong correlation with the natural frequencies of the damaged structure. This study demonstrated that the wind responses of the PT wall structures were in a safe range after the seismic event, and conventional CLT wall structures need to be re-evaluated under sequential scenarios for structural resilience assessment. Full article

The study evaluated the drinking water quality of Rouxville (RX) in Mohokare Local Municipality in the Free State, using chemical, physical, and microbiological parameters in comparison with South African National Standard 241 (SANS 241:2015). Drinking water samples were collected monthly from five sample sites, including the water treatment plant (WTP) and four end-user points, over a period of three years (2021–2023). Microbiological parameters revealed persistent non-compliance, with total coliforms and Escherichia coli (E. coli) frequently exceeding recommended limits by SANS 241 at multiple sites. The highest total coliform concentration of 201 CFU was recorded at the Rouxville Water Treatment Plant during the third year (2023) of sampling, while E. coli reached a maximum of 11 CFU at an end-user point, indicating the presence of possible pathogens in the water system. Colour exceeded the recommended limit (15 Pt-Co mg/L) at all sampling sites, with the highest value of 133 Pt-Co mg/L recorded at Rolelethunya Library. Chemical parameters mostly complied with SANS 241 limits, elevated values of total alkalinity and aluminium were observed at certain sites, particularly during the third year (2023) of sampling. The Canadian Council of Ministers of the Environment Water Quality Index (CCME-WQI) was also used to determine the overall water quality of the sample sites. The findings revealed that several sample sites had non-compliant parameters. The CCME-WQI revealed that the drinking water quality of Rouxville was either in the marginal or fair category, indicating that the water quality may be occasionally or frequently threatened, posing public health risks. These findings highlight the urgent need to ensure regular maintenance of WTP and ensuring continuous microbial monitoring. Full article

Glioblastoma is the most aggressive primary malignant tumor of the central nervous system in adults, with a poor prognosis and high resistance to conventional therapies. Platinum drugs like cisplatin are effective but limited by systemic toxicity, poor blood–brain barrier penetration, and resistance. Natural compounds are increasingly studied for their anticancer potential and ability to enhance existing therapies. Based on this rationale, we designed Pt(IV)Ac-GA, a novel platinum(IV) complex obtained by conjugating cisplatin with ganoderic acid A, a triterpenoid from Ganoderma lucidum known for anticancer and immunomodulatory effects. The compound was synthesized, structurally characterized, and showed high stability and favorable pharmacokinetics. In vitro, Pt(IV)Ac-GA strongly reduced the viability of U251 and T98G glioblastoma cells while sparing normal astrocytes. It triggered apoptosis, cell cycle arrest, impaired migration, and increased sensitivity to ferroptosis and mitochondrial dysfunction. These results highlight Pt(IV)Ac-GA as a promising candidate to overcome current limitations in glioblastoma treatment. Full article