Doxorubicin (DOX) is a highly effective anthracycline chemotherapeutic agent whose clinical utility is limited by dose-dependent cardiotoxicity. Although oxidative stress and mitochondrial injury are established mechanisms, the contribution of regulated metal-dependent cell death (MCD) pathways remains incompletely defined. This study investigated the ferroptosis and cuproptosis role in doxorubicin-induced cardiotoxicity (DIC) and evaluated the protective effects of luteolin (LUT) and nanoliposomal LUT using an integrated network pharmacology and experimental validation approach in rats. Network pharmacology identified multitarget interactions linking LUT with oxidative stress, metal homeostasis, and cell death signaling pathways. In vivo, DOX administration induced marked cardiac dysfunction, elevated serum cardiac injury biomarkers, myocardial histopathological damage, and ultrastructural abnormalities. These changes were accompanied by significant cardiac iron and copper accumulation, increased malondialdehyde (MDA), depleted superoxide dismutase (SOD) and glutathione (GSH), reduced glutathione peroxidase-4 (GPX4) activity, and increased tumor protein p53 (TP53) expression. At the molecular level, DOX downregulated the ferroptosis-protective genes, SLC7A11 and SLC3A2, while upregulating the iron transport genes, transferrin receptor 1 (TFR1) and SLC39A14, together with the cuproptosis-related genes ferredoxin-1 (FDX1) and SLC31A1, while suppressing ATP7A. These changes were further supported by altered protein expression of SLC7A11, ATP7A, and TP53. LUT significantly ameliorated these functional, biochemical, molecular, and structural alterations, indicating suppression of both ferroptotic and cuproptotic signaling. Nanoliposomal LUT showed superior efficacy to free LUT across most assessed parameters. Collectively, these findings support the involvement of ferroptosis and cuproptosis related signaling in DIC and highlight LUT, particularly in nanoliposomal form, as a promising cardioprotective strategy against anthracycline toxicity.
Bacterial nanocellulose (BNC) nanocomposites functionalized with silver (BNC-AgNC) and zinc oxide (BNC-ZnONC) nanoparticles were developed and optimized using Box-Behnken design (BBD) for potential wound dressing applications. Quadratic models exhibited excellent predictability (R² = 0.9765 and 0.9811, respectively), identifying optimal loading conditions of 3% nanoparticle concentration, 4 h loading time, and 32.5 °C, yielding maximum inhibition zone diameters of 2.81 cm (BNC-AgNC) and 2.65 cm (BNC-ZnONC). Nanocomposite formation was confirmed by UV-Vis spectroscopy, XRD, FTIR, SEM-EDX, DLS, and TGA, collectively demonstrating successful nanoparticle incorporation without disruption of the cellulose crystalline backbone. Both composites exhibited pronounced antibacterial activity against Gram-positive (S. aureus, S. pyogenes) and Gram-negative (S. marcescens, P. aeruginosa) pathogens, with BNC-AgNC showing bactericidal potency (MIC: 8-32 µg/mL) compared to BNC-ZnONC (MIC: 32-128 µg/mL). Cytotoxicity assessment on human fibroblasts revealed that BNC-ZnONC maintained > 97% cell viability across all tested concentrations (IC₅₀ >125 µg/mL), whereas BNC-AgNC exhibited concentration-dependent toxicity (IC₅₀ =63 µg/mL). Scratch wound healing assays demonstrated that BNC-ZnONC promoted fibroblast migration comparable to pristine BNC (81.84% closure), while BNC-AgNC significantly impaired wound closure even at sub-lethal concentrations. DPPH radical scavenging and hydration studies further supported the biocompatibility profile of BNC-ZnONC. These findings establish a functional dichotomy: BNC-AgNC offers potent bactericidal activity with a narrow therapeutic window, while BNC-ZnONC represents a more favorable candidate combining antimicrobial efficacy, cytocompatibility, and pro-healing properties for biomedical wound management.
Globally, 85% of the population uses traditional medicine. Ethiopia is a country with various traditional medicinal practices. However, various studies also reported traditional medicine used in children by their parents has had adverse outcomes and hospitalized them with complications. Various studies had also reported that traditional medicine use was high during COVID-19. Despite the fact that, children are particularly vulnerable population, limited studies exists regarding the prevalence, types, and determinants of parental TM use during COVID-19. In addition the existing studies were also confined to quantitative methods. Therefore, this study uses a mixed study design to explore indigenous methods of traditional medicine knowledge acquisition, preservation, preparation, storage, and dosage of herbs; barriers of disclosure; and prevalence of concomitant use. A community-based concurrent mixed study design was conducted among 941 randomly selected parents from Dec 01/2023 to March 01/2024. The data was cleaned, coded, and entered in Epi-Data version 4.6 and transferred to Stata version 14.1 for analysis. Finally, an AOR with a 95% CI was computed, and variables with a p-value < 0.05 in the multivariable analysis were taken as significant factors. The qualitative data was collected from 16 selected key informants by in-depth face-to-face interviews and analyzed by using thematic analysis. The prevalence of parental TM use for children was 87.6%. Sibling relation to child (AOR: 0.45, 95% CI, 0.01-0.77), religion (AOR: 0.11, 95% CI, 0.04-0.29), parental TM use for themselves (AOR: 6.55, 95% CI, 1.67-25.69), easy accessibility (AOR: 2.72, 95% CI, 1.16-6.40), safety & efficacy (AOR: 4.53, 95% CI, 2.3-13.61), and TM skill in the family (AOR: 0.47, 95% CI, 0.19-0.84) were determinants of TM utilization. Lack of awareness, misperception of TM, lack of trust in HCP and negative judgment from HCP were the main-barriers for non-disclosure of TM use. This result indicated traditional medicine use was high; nearly 9 out of 10 parents had used TM for their children during COVID-19. There was high concomitant utilization (90.6%) and high non-disclosure rate (98.1%) of traditional medicine use to health workers. Hence, it is better to give priority to strengthening the implementation of TM policy and manage accordingly.
Hemodialysis (HD) is a life-sustaining but resource-intensive therapy, consuming large volumes of water and electricity and generating substantial waste. This hybrid modeling study quantified the environmental footprint of in-center HD in Türkiye using national registry data, published parameters, and measured facility-level data from two Turkish dialysis centers. A hybrid modeling approach combined published per-session resource parameters with measured facility-level data from two Turkish hemodialysis centers (4,000 sessions/month combined). Literature-derived parameters (493 L water/session at 42% RO recovery, 6.2-19.6 kWh electricity/session, 1.5-8.0 kg waste/session) were scaled nationally for 2023 (9.27 million sessions). Measured Turkish data (390 L water, 10.8 kWh electricity, 1.19 kg hazardous waste per session) provided empirical calibration. GHG emissions were calculated using Türkiye-specific (0.494 kg CO2e/kWh for electricity) and international conversion factors. Using literature parameters, annual national estimates include 4.57 million m³ water, 57.5-181.8 GWh electricity, and 13.9-74.2 kt waste, with total GHG emissions ranging from 45.3 to 171.1 kt CO2e/year. Measured Turkish facility data yielded lower per-session water consumption (~390 L vs. 493 L, a 21% reduction) and hazardous waste generation (1.19 vs. 1.5 kg/session under good segregation), while electricity consumption (mean 10.8 kWh/session) aligned with the moderate literature scenario. Electricity was the dominant emission source (63-72%), followed by waste incineration (up to 47% with poor segregation). In-center HD in Türkiye imposes a substantial yet modifiable environmental burden. Measured Turkish facility data demonstrated that actual water consumption is meaningfully lower than international estimates, highlighting the importance of locally validated parameters. Waste segregation and electricity decarbonization represent the highest-impact intervention points for reducing the sector's carbon footprint.
Two baseline 6-minute walk tests (6MWTs) have been recommended to mitigate a potential learning effect when assessing exercise performance, but the magnitude of any learning effect in heart failure with reduced ejection fraction (HFrEF) is uncertain. Using the Sildenafil in Heart Failure (SilHF) trial, in which two baseline 6MWTs were performed (screening and inclusion), we assessed a potential learning effect in this population. We also assessed whether choice of baseline test affected associations with longitudinal patient-reported outcomes and compared our findings to reports in the current literature. In SilHF, 69 patients with HFrEF and evidence of pulmonary hypertension performed 6MWTs at screening and again at study inclusion. Tests were performed no more than two weeks apart on unchanged optimal medical therapy. Only the inclusion 6MWT was used for efficacy evaluation of sildenafil. Screening and inclusion distances were compared using a paired t-test. Additionally, we assessed whether each baseline 6MWT (screening and inclusion) correlated with longitudinal patient-reported outcome measures. Outcomes included the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the EuroQoL-5D visual analogue scale (EQ-5D VAS), assessed at 24 weeks. Although the inclusion 6MWT distance was statistically significantly higher than the screening test (+11.3 m, 95% CI 2.6 to 20.1, p = 0.012), the two baseline tests demonstrated very similar correlation coefficients with longitudinal patient-reported outcomes. We observed a small increase in 6MWD between repeat baseline tests, consistent with a modest learning effect that is unlikely to be clinically meaningful. Both initial 6MWTs showed similar significant correlations with other longitudinal patient-reported outcome measures. In symptomatic HFrEF with pulmonary hypertension, a single baseline 6MWT may be sufficient to assess functional capacity.
Large language models (LLMs) are entering healthcare, but their ability to improve access depends on public willingness to use them. If acceptance is socially patterned, deployment may widen existing inequities. We quantified public acceptance of LLMs in healthcare and examined its bio-psycho-social correlates in China. We conducted a representative, multistage stratified survey of adults aged 18 years or older across 150 Chinese cities between June and September 2024. After a standardized description of LLM capabilities, participants rated acceptance of LLMs in healthcare on a 0-100 scale. Survey-weighted regression identified correlates of acceptance, and Classification and Regression Tree (CART) analysis identified profiles associated with non-acceptance. Among 35,861 respondents, weighted mean acceptance was 64.3/100 (95% CI 63.9-64.6). Acceptance was lower among respondents with chronic conditions than in the overall sample (62.4 vs 64.3) and declined with age. Higher acceptance was associated with greater perceived social status, prior digital health use, self-efficacy, stronger family-neighbour relationships, and higher eHealth literacy (β_std = 0.06 to 0.19), whereas lower acceptance was associated with older age, adverse social and developmental exposures, severe ADHD symptoms, social loneliness, and financial strain (β_std = -0.04 to -0.09). In CART analysis, lack of prior digital health use defined the largest non-acceptor group, comprising 62% of the sample. Among those with prior digital experience, lower social support and lower childhood socioeconomic status remained important markers of non-acceptance. In the test set, the tree showed modest discrimination (weighted AUC 0.62, 95% CI 0.61-0.64), with high specificity (0.94) and low sensitivity (0.19). Public acceptance of LLMs in healthcare in China was moderate but unequal. Lower acceptance among older adults, people with chronic conditions, and those with fewer social and digital resources suggests socially patterned uptake. Equity-oriented implementation strategies are needed so LLM integration does not preferentially benefit advantaged groups.
Declines in nicotinamide adenine dinucleotide (NAD+) are linked to metabolic stress accompanying aging and disease. While precursor-based approaches elevate systemic NAD, their clinical translation can be constrained by biosynthetic bottlenecks and first-pass metabolism. RENEWAL-NAD+ (ClinicalTrials.gov NCT07336836; retrospectively registered 01/04/2026) was a double-blind, randomized, placebo-controlled Phase 0/1b trial in healthy adults aged 45-75 years (60 randomized; primary analysis n = 50) evaluating 5 days of oral LathMized® NAD+ (LNAD+), a physicochemically modulated formulation that alters the supramolecular organization and solution behavior of NAD+ while preserving its native molecular structure. The primary endpoints were change in intracellular NAD (icNAD), measured in whole blood, and circulating NAD (cirNAD), measured in separated plasma, relative to baseline. LNAD+ produced a rapid and pronounced increase in icNAD, with a 53% elevation versus placebo at Day 6 (p = 5.48e-14; Hedges' g = 3.66), while cirNAD was unchanged (p = 0.60), demonstrating compartment-selective augmentation. Plasma NAD catabolites increased substantially (1-methyl-nicotinamide, MeNAM p = 5.39e-13; N1-methyl-2-pyridone-5-carboxamide, 2PY p = 2.95e-16), consistent with downstream engagement of NAD metabolic flux. Exploratory analyses identified non-overlapping correlates for the two compartments (cirNAD tracking inflammatory and metabolic markers, icNAD tracking red blood cell indices and NAM). Treatment was very well tolerated: symptom incidence was comparable between groups (p = 0.68), only one mild adverse event (nausea, Grade 1) occurred in the LNAD+ arm, and no secondary clinical, vital-sign, wellbeing, or wearable-derived endpoint survived multiplicity correction. These data demonstrate rapid intracellular NAD augmentation after oral LNAD+ dosing with pharmacodynamic evidence of downstream metabolism, compartment-specific physiological signatures, and a favorable short-term safety profile, with exploratory multi-omic analyses ongoing.
Metal-organic framework (MOF) membranes show immense promise for energy-efficient gas separations, yet their intrinsic brittleness has precluded their processing into practical membrane modules. Here, we report a symmetry-mismatch strategy that transforms brittle crystalline MOFs into amorphous membranes possessing an extraordinary combination of polymer-like flexibility and crystal-like ultra-microporosity. This is enabled by electrified co-assembly of two structurally related MOFs with identical metal nodes and connectivity yet distinct linkers and space groups. We demonstrate the incompatible crystal symmetries disrupt long-range periodicity while using preformed subunits for the assembly could preserve local structural order. The resulting membranes demonstrate remarkable mechanical properties, with a flexural modulus of 234 MPa and a curvature of 1000 m-1, alongside impressive gas separation performance. This work establishes a design principle for engineering mechanically resilient, high-performance amorphous materials, overcoming a critical barrier to the real-world application of advanced MOF membrane.
Endometriosis (EM) is a chronic, estrogen-dependent inflammatory disease affecting approximately 10% of women of reproductive age worldwide, causing debilitating pelvic pain, infertility, and substantially impaired quality of life. Conventional hormonal therapies and surgery are limited by systemic side effects, high recurrence rates, and failure to maintain adequate drug concentrations at ectopic lesion sites. Nanotechnology-based drug delivery has emerged as a promising strategy for directing therapeutic agents to ectopic lesion sites, potentially reducing the systemic toxicity that limits current pharmacological options. We systematically review three nanomaterial platforms-hydrogels, extracellular vesicles (EVs), and inorganic nanoparticles-with attention to their physicochemical properties, therapeutic rationale, and preclinical findings, as well as the specific strengths and unresolved limitations of each platform. We further compare how each platform addresses the core pathological processes of EM, namely, persistent inflammation, progressive fibrosis, and pathological angiogenesis. We hope that this review will assist researchers in comparing nanocarrier strategies and identifying more realistic pathways for clinical application in EM.
To determine the molecular genetic characteristics of the epithelial neoplasia of extrahepatic bile ducts (EHD) depending on the degree of epithelial dysplasia in order to identify mutations that facilitate their differential diagnosis. The study included 44 EHD biopsies containing epithelial neoplasms and cholangiocarcinoma. All samples underwent massive parallel sequencing of DNA isolated from 10-μm-thick histological sections. Mutations of categories I-III of clinical significance were considered. Statistical analysis of the obtained data utilized a two-tailed Pearson χ2 test with Holm's correction for multiple comparisons (p<0.045). The most frequent mutations in epithelial neoplasia of the EHD were identified: MYC, KRAS, PIK3CA, CDKN2A, ERBB2, KIT 6, TP53 6, FBXW7, POLE and TERT. The highest proportion of mutations was in biliary intraepithelial neoplasia and cholangiocarcinoma. Among epithelial neoplasia and cholangiocarcinoma, mutations in KRAS, POLE and TERT differed significantly. KRAS (p<0.045) - BilIN LG and BilIN HG, IPNB HG and cholangiocarcinoma; POLE (p<0.045) - BilIN LG and cholangiocarcinoma; TERT (p<0.045) - BilIN LG and cholangiocarcinoma. Specificity and sensitivity indicators for KRAS were 28 and 50%; POLE - 35 and 100%; TERT - 100 and 100%. Mutations have been identified that should be considered in the differential diagnosis of the degree of epithelial dysplasia and the types of epithelial neoplasia of the extrahepatic bile ducts. Определить молекулярно-генетические характеристики эпителиальных неоплазий внепеченочных желчных протоков (ВЖП) в зависимости от степени дисплазии эпителия с целью выявления мутаций, способствующих их дифференциальной диагностике. В исследование было включено 44 биоптата из ВЖП, содержащих структуры эпителиальных неоплазий и холангиоцеллюлярного рака (ХЦР). Все образцы подверглись массивному параллельному секвенированию ДНК, выделенной из гистологических срезов толщиной 10 мкм. При проведении исследования учитывали мутации I—III категории клинической значимости. При статистической обработке полученных данных использовали двусторонний критерий χ2 Пирсона с поправкой Холма на множественные сравнения (p<0,045). Были выявлены наиболее часто встречающиеся мутации при эпителиальных неоплазиях ВЖП: MYC, KRAS, PIK3CA, CDKN2A, ERBB2, KIT 6, TP53 6, FBXW7, POLE и TERT. Наибольшая доля мутаций приходилась на долю билиарной интраэпителиальной неоплазии и ХЦР. Среди эпителиальных неоплазий и ХЦР значимо отличались мутации KRAS, POLE и TERT. KRAS (p<0,045) — BilIN LG и BilIN HG, IPNB HG и ХЦР; POLE (p<0,045) — BilIN LG и ХЦР; TERT (p<0,045) — BilIN LG и ХЦР. Показатели специфичности и чувствительности для KRAS составили 28 и 50%; POLE — 35 и 100%; TERT — 100 и 100%. Выявлены мутации, которые стоит учитывать при дифференциальной диагностике степени дисплазии эпителия и типов эпителиальных неоплазий ВЖП.
BackgroundEye movement dysfunction plays an important role in understanding the pathology of neurodegenerative disorders. Fine particulate matter (PM2.5) exposures are associated with hallmark proteins diagnostic of Alzheimer's and Parkinson's diseases in Metropolitan Mexico City (MMC) ≤ 40-year-old residents.ObjectiveTo assess oculomotor function with neuroanatomical correlates using magnetic resonance imaging (MRI) region of interest analysis in young urbanites.MethodsVideo-based eye-tracking was used to explore oculomotor dysfunction and structural brain MRI changes in two highly exposed PM2.5 cohorts. We assessed fixation stability, smooth pursuit, pro-saccades, and anti-saccades using the Eyelink 1000-plus eye-tracker, in 80 volunteers' age 33 ± 11 years from MMC and Cuernavaca. Forty-five MMC subjects age 31.2 ± 14.7 years with oculomotor assessment had brain MRIs. Measurements of saccadic accuracy, latency, and smooth pursuit gain and square wave jerk frequency were collected.ResultsOculomotor variables did not reach statistically significant differences in MMC versusCuernavaca. Abnormal antisaccades, low gain pursuit, and square wave jerks were documented more often in MMC residents. Correlational analysis between oculomotor function and structural MRI data revealed statistical cortical and subcortical changes at frontal-temporal-parietal regions, hippocampus, thalamus, caudate, amygdala, habenula, nucleus accumbens, and cerebellum. Involved regions potentially reveal the location and severity of neurodegeneration processes via altered saccade parameters.ConclusionsOur findings suggest that simple oculomotor test batteries may provide a useful tool to monitor and/or measure the impact of pollution on neurodevelopment and early neurodegeneration. The integration of ocular movement parameters into the Continuum model of neurodegeneration offers a promising approach for neuroprotection decision-making and rigorous emissions control in polluted settings.
Diabetic wounds represent one of the most severe complications of diabetes, and their clinical management remains challenging. This study investigated the therapeutic potential of adipose-derived stem cell-derived exosomes (ADSCs-Exo) for diabetic wounds. We isolated ADSCs and their exosomes, and by using Transwell and CCK-8 assays, we found that ADSCs-Exo were associated with proliferation and migration of keratinocytes and fibroblasts, and that they also enhanced the angiogenic activity of endothelial cells in vitro. In contrast, these promotive effects were significantly attenuated when exosomes derived from ADSCs with DMBT1 knockdown via siRNA (ADSCssiDMBT1-Exo) were applied. In a diabetic mouse model, ADSCs-Exo treatment significantly accelerated wound healing, whereas the pro-healing capacity of ADSCssiDMBT1-Exo was markedly reduced. To further explore the underlying mechanism, we performed RNA sequencing, which suggested that ADSCs-Exo might exert their therapeutic effects by alleviating ferroptosis and promoting cell proliferation. Subsequent experiments, including TEM, ROS assays, JC-1 staining, and tissue immunofluorescence, provided further support for these mechanistic findings. In summary, this study demonstrates that DMBT1 in ADSCs-Exo participates in alleviating ferroptosis in diabetic wound tissue, which may contribute to creating a favorable microenvironment for cell proliferation and promoting wound healing. This discovery provides a novel potential therapeutic target and strategy for the clinical treatment of diabetic wounds.
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Single-cell RNA sequencing (scRNA-seq) enables genome-wide gene expression profiling at single-cell resolution but loses the spatial context essential for interpreting cell identity and tissue organization. In contrast, spatially resolved transcriptomics (SRT) preserves spatial information but typically lacks single-cell resolution or complete transcriptome coverage. To obtain a more comprehensive view of heterogeneous spatial domains and cellular gene expression, we present Cell2Map, an unsupervised deep learning method that integrates scRNA-seq and SRT data from the same tissue region. Cell2Map assigns individual cells to SRT spots using a graph attention autoencoder equipped with a specially designed multi-term objective function that jointly optimizes expression-based, density-based, and embedding-level similarity and distance constraints. On benchmark datasets from mouse cerebellum and hippocampus, Cell2Map achieves higher single-cell mapping precision and overall accuracy than three popular methods (Celloc, CytoSPACE, Tangram) across a range of noise levels and spot cell densities. In real cancer applications, Cell2Map resolves intratumoral heterogeneity by accurately localizing tumor subclones and separating normal epithelial cells from ductal carcinoma in situ regions, and more faithfully reconstructs tumor microenvironments and immune-cell localization than competing approaches. Across breast cancer and myocardial infarction datasets, Cell2Map consistently attains higher sensitivity with fewer false positives, in close agreement with histological and biological annotations.
Vascular cognitive impairment and dementia (VCID), a major contributor of dementia, remains underrecognized, owing to the absence of universally accepted diagnostic criteria. The VasCog Society and WSO recently released updated criteria (VasCog-2-WSO); however, their applicability is unknown yet. We aimed to evaluate these criteria in a dementia-free and stroke-free community cohort and determine their associations with vascular burden and long-term mortality. We conducted a community-based cohort study using data from the I-Lan Longitudinal Aging Study. Adults aged 50 years or older without prior stroke or dementia underwent standardized brain MRI and comprehensive neuropsychological assessment. VCID was classified according to the VasCog-2-WSO criteria using a neuroimaging-first approach. Participants were categorized as non-VCID, preclinical VCID (with or without objective cognitive impairment), or vascular mild cognitive impairment (vaMCI). Baseline 10-year Framingham cardiovascular disease risk was assessed. The primary outcome was all-cause mortality over a mean follow-up of 9.4 years, analyzed using multivariable Cox proportional hazards and Poisson regression models. A total of 1,236 participants (62.7 ± 8.8 years; 52.9% female) were included. Neuroimaging evidence of cerebrovascular disease was present in 19.6% of participants; 19.2% met criteria for preclinical VCID and 0.4% for vaMCI. Compared with non-VCID participants, neuroimaging-positive groups had worse cognitive performance and higher 10-year cardiovascular risk. Mortality increased across the VCID spectrum (7.4 [95% CI 5.7-9.4], 24.9 [16.0-37.1], 27.4 [18.2-39.6], and 137.9 [37.6-353.2] per 1,000 person-years). In adjusted Cox models, preclinical VCID was associated with a 1.5-1.7-fold higher mortality risk, and vaMCI with a hazard ratio of 7.2 (95% CI 2.4-21.1), with a significant graded association across the spectrum (p for trend <0.001). The VasCog-2-WSO criteria identify a spectrum of MRI-defined vascular cognitive vulnerability associated with increased cardiovascular risk and mortality, with excess mortality risk detectable at a neuroimaging-defined preclinical stage before overt cognitive impairment. These findings support their utility for early detection and risk stratification in community settings. A key limitation is the inability to assess mixed etiologies due to the absence of genetic data and Alzheimer disease biomarkers, which limits the ability to thoroughly evaluate the VasCog-2-WSO VCID diagnostic framework.
A drug-coated balloon (DCB)-based "leave-nothing-behind" strategy has become a predominant approach for femoropopliteal artery (FPA) lesions in contemporary clinical practice. However, despite the intention to complete procedures with DCB alone, stent implantation is frequently required because of severe dissection, elastic recoil, or suboptimal lesion preparation. Whether DCB angioplasty combined with selective stent implantation compromises 1-year primary patency compared with DCB monotherapy remains uncertain. In this prospective multicenter registry, 310 limbs in 277 patients undergoing endovascular therapy for FPA lesions between September 2021 and December 2022 were enrolled. Thirty-seven limbs were excluded if they had isolated common femoral artery lesions (n = 8), were treated with bare nitinol stents or stent grafts (n = 25), or were treated with plain old balloon angioplasty alone (n = 4). A total of 273 limbs in 254 cases were included in the primary outcome analysis. Patients were categorized into three groups: the DCB group (balloon angioplasty with DCB alone), the drug-eluting stent (DES) group (implantation of Eluvia™ or Zilver PTX™), and the Combination group (DCB angioplasty combined with DES). The primary endpoint was 1-year primary patency. Secondary endpoints included freedom from clinically driven target lesion revascularization (CD-TLR) and clinically driven target vessel revascularization (CD-TVR), which were assessed using Kaplan-Meier analysis. Factors associated with loss of primary patency were evaluated using Cox regression analysis. DCB monotherapy was performed in 78.3% of cases, DESs in 10.9%, and combination therapy in 10.6%. The overall 1-year primary patency rate was 84.0%, with no significant differences among strategies (DCB: 84.1%, DES: 84.6%, Combination: 82.8%; log-rank p value = 0.91). Freedom from CD-TLR and CD-TVR at 1 year was 88.7% and 93.8%, respectively. Chronic limb-threatening ischemia and history of revascularization were independently associated with loss of primary patency. Combination therapy was not associated with an increased risk of loss of primary patency. A DCB-based strategy with selective scaffolding may achieve acceptable patency outcomes.
This study aimed to evaluate the preparedness of diabetes educators (DEs) to support the use of MiniMed™ 780G in clinical practice, identifying knowledge gaps, onboarding barriers, success factors, and regional variations to inform a standardized training pathway for type 1 diabetes mellitus (T1DM) care. A cross-sectional, multiregional survey was conducted among 82 DEs from Africa, the Arabian Peninsula (Gulf States), Central and Eastern Europe, Türkiye, and Central Asia (June-July 2025). The questionnaire, adapted from a validated Delphi-derived tool, assessed knowledge and confidence, training challenges, success factors, educational needs, and professional development. Responses were collected using Likert scales, multiple-choice, and free-text fields. Quantitative data were analyzed descriptively, with graphics generated in Excel. Item-level missing data were handled by listwise deletion; all 82 participants completed the survey (100% response rate). A 23-question survey was shared with 82 DEs from four regions to assess their knowledge and confidence with MiniMed™ 780G, training challenges, success factors, educational needs, and educational pathways. Most DEs reported high confidence in key MiniMed™ 780G topics; however, confidence in managing high-fat/protein meals was lower (56.1%), highlighting the need for targeted education. Key professional development drivers included mentorship (24.9%) and strong educator networks (21.0%), with accreditation priorities emphasizing international certification bodies (25.6%) and continuing education (20.3%). Common challenges included managing patient expectations (33.6%), explaining SmartGuard™ (20.4%), lack of structured materials (17.1%), troubleshooting alarms (12.5%), and teaching device settings (11.8%). Specialist healthcare professionals are competent in the use of advanced diabetes technologies; however, standardized, personalized, and patient-centered educational programs are essential to fully realize their potential and ensure high-quality care for individuals with T1DM.
Continuous vital sign monitoring ensures early detection, prevents intensive care unit (ICU) admissions, and improves patient outcomes. Continuous heart rate (HR) monitoring methods often require direct skin contact, which can lead to patient discomfort. The rising popularity of ballistocardiography (BCG) offers a promising, noncontact solution for continuous vital sign monitoring with improved patient comfort. This study aims to develop and validate a novel HR measurement algorithm leveraging convolutional neural networks (CNNs) and BCG signals for accurate, noncontact, and continuous HR monitoring. By integrating time-domain peak detection with short-time Fourier transform and CNN models, the proposed approach seeks to enhance HR measurement accuracy across diverse health care settings. The study follows the Food and Drug Administration (FDA)'s Good Machine Learning Practice guidelines and evaluates the algorithm's robustness, generalizability, and clinical applicability through extensive testing on a diverse dataset, ensuring improved patient comfort and early detection of clinical deterioration. The proposed algorithm combines time-domain peak detection with short-time Fourier transform and CNNs to enhance HR measurement from BCG signals. The CNN model developed was trained on 129,976 data points from 373 participants (HR range: 36-230 bpm), including ICU patients, and was tuned on 75,970 data points from 192 participants (HR range: 46-169 bpm), with HR obtained from clinical-grade electrocardiography devices to improve generalizability. The algorithm was tested on 70,211 data points from 205 participants, including ICU patients, across 5 independent studies to demonstrate robust performance against diverse settings, demographics, and comorbidities. The methodology is in compliance with the FDA's Good Machine Learning Practice for Medical Device Development: Guiding Principles. The algorithm achieved a mean absolute error of under 3 bpm and a detection rate exceeding 80%, underscoring its robustness. The Bland-Altman analysis indicates high accuracy with a minimal bias of 0.25 and limits of agreement within 8.59 bpm. Additionally, the Pearson correlation coefficient of 0.97 from the Deming regression further demonstrates strong alignment with reference HR measurements, reinforcing its precision and reliability for clinical applications. This CNN-based algorithm presents a robust solution for contactless HR monitoring, addressing the limitations of prior methods in noise management and adaptability. Its demonstrated accuracy, particularly in real-world, noisy clinical environments, highlights its potential for broad application in patient monitoring and improved comfort.
Cigarette smoking, maintained predominantly by nicotine dependence, is a long-term and relapsing behavior that continues to be a leading cause of preventable death and disease worldwide. E-cigarettes with nicotine are less harmful than cigarettes and have been shown to be more effective for smoking cessation than US Food and Drug Administration-approved nicotine replacement therapies. However, misperceptions of the harms of e-cigarettes are common, even among clinicians. This Special Communication is a position manuscript developed by a working group within the Treatment Research Network of the international Society for Research on Nicotine and Tobacco. The aims of the manuscript were to summarize the evidence on the use of e-cigarettes for smoking cessation and to provide recommendations for clinicians on how to engage in conversations with adult patients who currently smoke cigarettes. Specifically, advice is provided on (1) integration of e-cigarettes into patient-centered shared decision-making conversations on the risks and benefits of various pharmacologic smoking cessation treatments; and (2) practical guidance on the use of e-cigarettes for smoking cessation. This Special Communication includes one overarching recommendation: integrate e-cigarettes into conversations on the risks and benefits of all evidence-based pharmacologic treatments for smoking cessation. In support of this recommendation, specific guidance is provided regarding how to discuss potential misperceptions and suggests questions to guide patient conversations. Finally, evidence-based best practices are provided for using e-cigarettes to quit smoking, which can be shared with patients. The significant burden of cigarette smoking, coupled with scientific evidence supporting e-cigarettes for smoking cessation, clearly indicates that it is appropriate to include e-cigarettes in discussions of evidence-based pharmacologic treatment for smoking cessation to reduce the harms of cigarette smoking. These recommendations are intended to provide evidence-informed guidance to clinicians regarding use of e-cigarettes for smoking cessation.
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