Search Results (34,528)

Objectives: This study aimed to evaluate auditory cortical maturation in pediatric cochlear implant (CI) users using speech-evoked cortical auditory evoked potentials (CAEPs) and to compare P1 latency responses with age-matched normal-hearing (NH) peers. Secondary objectives included examining the relationship between P1 latency, age, and duration of implant use to assess experience-dependent cortical plasticity. Materials and Methods: Seventy children were enrolled, including 40 prelingually deaf CI users and 30 NH controls matched for age and sex. CAEPs were recorded using the HEARLab system with three speech tokens representing low (/m/), mid (/g/), and high (/t/) frequencies, presented at 55 dB SPL in a free-field setup. The P1 component was identified as the first positive deflection between 50 and 150 ms after stimulus onset. Group comparisons were performed using Student’s t-test, and correlations between P1 latency, age, and implant-use duration were analyzed using the Pearson correlation test (p < 0.05). Results: Mean P1 latencies were significantly longer in CI users than in NH peers for the /m/ and /t/ stimuli (p = 0.036 and p = 0.045, respectively), while no significant difference was found for /g/ (p = 0.542). In NH children, P1 latency negatively correlated with age (r = −0.44, p < 0.05), indicating maturation-related shortening. Among CI users, longer implant-use duration was associated with shorter P1 latencies across all speech tokens (/m/: r = −0.37; /g/: r = −0.49; /t/: r = −0.43; p < 0.05 for all). Conclusions: Speech-evoked CAEPs provide a sensitive and objective measure of auditory cortical development in children with cochlear implants. P1 latency reflects both chronological and hearing-age-related maturation, supporting its clinical use as a biomarker for cortical plasticity and rehabilitation progress in pediatric CI care. Full article

Background/Objectives: Non-invasive samples offer an attractive alternative to logistically challenging invasive approaches in wildlife genetic studies but often contain low-quality host DNA that limits downstream analyses. Here, we assessed the applicability of moulted Eurasian goshawk feathers as a DNA source for whole-genome re-sequencing. Methods: We analysed 75 moulted feathers collected opportunistically from breeding territories. Each feather was measured from tip to tip, and its condition was visually assessed. Whole-genome re-sequencing was performed with a target coverage of 13× using 150 bp paired-end reads. Results: Feathers yielded an average of 7.19 ± 10.93 ng/μL DNA. DNA yield was positively correlated with feather size and the presence of blood traces in the calamus. On average, feather samples performed well, producing 208.7 ± 59.82 million reads, of which 82.69 ± 27.15% aligned to the reference genome, resulting in 83.58 ± 19.02% of the genome being covered at least once. After quality filtering, 10.34 ± 3.11 million biallelic single-nucleotide variants remained, of which 457,745 were common variants (MAF > 0.05). Larger feathers in good condition, with higher DNA yields and blood traces in the calamus, tended to perform better throughout the re-sequencing workflow. Nevertheless, approximately 22.7% of samples failed due to high missing data or poor genotype quality. Conclusions: Performance varied substantially even among samples with similar characteristics, indicating that improved sample selection incorporating direct measures of host DNA quality may be beneficial. Despite these challenges, moulted feathers represent a readily available DNA source for genome-wide re-sequencing of medium- to large-sized raptor species. Full article

Background/Objectives: The stability of metabolites and lipids in feces varies depending on the storage temperature and duration. Methods: We examined the stability of various metabolites and lipids in human feces under 10 different storage conditions (room temperature for 2, 6, 24, and 48 h, 4 °C for 6, 24, and 48 h, −20 °C for 1 week, 2 weeks and 1 month) and explored markers useful for quality control of fecal samples, using metabolites and lipids that vary depending on temperature and time. Results: There was generally more variation at 4 °C than at −20 °C, and more at room temperature than at 4 °C, and variation also increased as the storage duration was extended under each temperature condition. Some metabolites and lipids were found to be unstable, even over short periods (2 or 6 h) at room temperature or 4 °C storage. However, storage at −20 °C generally maintained the stability of most of them for up to two weeks. Our results suggest that the following ratios can serve as useful quality control markers: methionine to S-methyl-5-thioadenosine, xanthine to inosine and N-linoleoyl leucine to 1,2-dilinoleoyl-sn-glycerol. Conclusions: For comprehensive metabolite and lipid analysis, we recommend promptly transferring samples to −80 °C storage, except when stored at −20 °C for no longer than two weeks, with checks on markers for quality control. When measuring specific metabolites or lipids, our catalog data can be consulted to determine acceptable storage conditions. Full article

Background and Objectives: Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening vascular disease with limited effective diagnostic and therapeutic strategies. Although endothelial barrier dysfunction represents an early event in TAAD pathogenesis, the role of endothelial tight junction proteins remains largely undefined. In this study, we systematically explored the function of claudin-5 (CLDN5), an endothelial-specific tight junction sealing protein, in TAAD through integrated bioinformatic, clinical, and experimental approaches. Materials and Methods: In the study, we combined bioinformatic analysis of the CLDN5 gene with clinical and cellular investigations. The clinical cohort included 44 patients with thoracic aortic dissection (TAAD) and 41 healthy controls. Plasma CLDN5 levels were measured by ELISA. Cellular studies involved treating human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-α (TNF-α) and performing CLDN5 knockdown, with barrier function assessed using transendothelial electrical resistance and permeability assays. Results: Plasma CLDN5 was significantly elevated in TAAD patients (14.20 ± 1.394 ng/mL) compared to controls (6.061 ± 0.8208 ng/mL, p < 0.05) and showed strong diagnostic potential with an area under the receiver operating characteristic curve (AUC) of 0.7877 (95% CI: 0.6897–0.8857). In cellular experiments, TNF-α treatment induced the release of CLDN5 fragments into the supernatant and reduced membrane CLDN5. Furthermore, CLDN5 knockdown directly impaired endothelial barrier function. Conclusions: Our findings identify CLDN5 as a promising circulating biomarker for TAAD diagnosis and provide new insights into TAAD pathogenesis, offering potential diagnostic strategies. Full article

Background: In recent years, virtual consultations have emerged as a crucial approach for continuity of chronic care provision, indicating a promising avenue for the future of smart healthcare systems. However, reversions to in-person care highlight persistent limitations, despite notable advantages of remote modalities. In parallel, recent developments in artificial intelligence (AI) indicate the potential to enhance remote chronic care, but user perceptions of such assistance and the corresponding human factors remain underexplored. Objective: This mixed methods study aims to better understand the virtual consultation experiences and attitudes toward AI-assisted tools in remote care among patients with noncommunicable chronic conditions and their healthcare professionals (HCPs). It conducts an in-depth examination of the associated human–computer interaction and usability elements of virtual consultations and of potential AI assistance. Methods: Public and Patient Involvement was integrated to run pilots and refine documentations. Semi-structured interviews with patients (n = 10), focus groups with HCPs (n = 15), and an online survey (n = 83) were conducted. Qualitative data was analysed through a reflexive thematic approach. The survey comprised the Telehealth Usability Questionnaire (TUQ) and bespoke items on user AI views, and the data was used to triangulate the qualitative findings. Nonparametric Kruskal–Wallis tests and ε² effect sizes compared TUQ and AI views scores between current and former virtual consultation user groups. Results: Seven themes emerged from the qualitative data, which were supported by the quantitative findings. The statistical analyses resulted in a mean TUQ total score of 90.6 (SD = 15.0), which indicates high usability and user satisfaction; however, they failed to detect a difference between groups (p > 0.05; ε² = 0.002–0.032). There was a clear preference for hybrid models, while a lack of empathy was identified during remote interactions. While a notable proportion of users indicated a literacy gap towards AI use in healthcare settings, they expressed cautious openness towards AI assistance, contingent upon transparency, human oversight, and data integrity; indicating a potential gap between competence to judge the technology and willingness to use it. Significant differences in views on AI assistance across groups failed to be detected (p > 0.05; ε² = 0.005–0.065). Conclusions: Virtual consultations for chronic conditions are widely usable and acceptable, particularly through hybrid approaches. Addressing empathic engagement, holistic patient status, and transparent AI integration can enhance clinical quality and user experiences during remote interactions. However, the low statistical power and failure to detect a difference between groups (likely due to the small sample size) indicate the need for caution when interpreting the quantitative findings. There is also the implicit need to address potential AI literacy gap among users, indicating the need for robust safeguard measures. This study has also identified evidence-based assistive AI features that can potentially enhance virtual consultations. These insights can inform the co-design of evidence-based virtual care platforms, policies and supportive AI tools to sustain remote chronic care delivery. Full article

Background/Objectives: After fermentation, yogurt is often supplemented with probiotics, yet sweetened with added sugars that can negatively impact cardiometabolic health. Honey provides rare sugars, oligosaccharides and phenolics that may promote gut and cardiometabolic health. We aimed to determine the impact of yogurt sweetened with commercial clover blossom honey on pro-inflammatory Th17 cytokines and microbial-derived metabolites in healthy postmenopausal women. Methods: In a randomized controlled crossover dietary intervention trial, postmenopausal women (45–65 years of age) consumed two 150 g servings of yogurt for breakfast for 4 weeks, with each serving sweetened with a tablespoon of clover blossom honey or an isocaloric amount of sugar. Blood samples were collected for the measurement of plasma lipids, bile acids (BA) and Th17 cytokines, along with fecal short-chain fatty acids (SCFA). The primary outcome was plasma interleukin (IL)-23. Results: Neither dietary intervention significantly changed IL-23, plasma lipids, fecal SCFA or plasma BA. Compared to sugar-sweetened yogurt, IL-33 was significantly lower after 4 weeks of honey-sweetened yogurt intake. Conclusions: In a healthy population of postmenopausal women, the daily intake for 4 weeks of honey-sweetened yogurt did not significantly impact our primary outcome of IL-23. Instead, lower plasma levels of IL-33 were observed with honey compared to sugar-sweetened yogurt intake. The impact of the intervention on this cytokine was independent of changes in fecal SCFA and plasma BA. Confirmatory studies, in a larger population with levels of honey intake within dietary recommendations for added sugar, are warranted. Full article

Background/Objectives: Background: The International Agency for Research on Cancer has classified arsenic as a group 1 carcinogen of the lung, skin and bladder. Arsenic has been implicated in the pathogenesis of breast, prostate, and colorectal cancers; however, existing evidence is limited and inconsistent. Prospective studies, particularly those employing blood-based quantification of arsenic, remain scarce. This study aimed to address this gap by investigating the association between serum arsenic levels and breast, prostate, and colorectal cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC) Heidelberg case–cohort. Methods: Serum arsenic levels were measured using inductively coupled mass spectrometry in 5360 participants aged 35–65 years, recruited between 1994 and 1998. Over a median follow-up of 18 years (IQR: 17–19), 685 incident cases of breast, 597 of prostate, and 284 of colorectal cancer occurred. Prentice-weighted Cox proportional hazards regression models with age as the underlying time scale were used to estimate hazard ratios and confidence intervals for associations between serum arsenic levels and cancer risk. Results: No statistically significant association was found between serum arsenic levels and breast cancer, either overall with HR 1.04 (95% Cl: 0.96–1.35) or in subgroups based on pre- and post-menopausal status, estrogen/progesterone status, or BMI. Similarly, serum arsenic levels were not statistically associated with prostate cancer of HR 0.91 (95% Cl: 0.72–1.14). In contrast, a significant association with colon cancer emerged in the second quartile with HR 0.12 (95% Cl: 0.02–0.61) and third quartile with HR 0.19 (95% Cl: 0.05–0.73) compared to the first quartile but not in rectal cancer. Conclusions: More comparative studies on the different arsenic media and arsenic speciation should be conducted to determine the impact of arsenic on these cancers. Full article

Background/Objectives: Vitamin D deficiency and obesity are prevalent public health concerns among older adults, with potential impacts on metabolic health. Despite high deficiency rates reported globally, data on their relationship in Chilean older populations remain limited. This study investigates the relationship between 25(OH)D status, obesity, and metabolic parameters in Chilean older adults using data from the 2016–2017 National Health Survey (ENS). Methods: A cross-sectional analysis was conducted in 1252 individuals aged ≥ 65 years with complete 25(OH)D and anthropometric measurements. Plasma levels of 25(OH)D were classified as optimal ≥ 30 ng/mL, insufficiency 20–29.9 ng/mL, deficiency 12–19.9 ng/mL, and severe deficiency < 12 ng/mL. Logistic regression models adjusted for age, sex, education, comorbidities, and environmental factors were used to assess associations. Results: The results demonstrated that 88.3% of older adults had 25(OH)D ≤ 30 ng/mL, with 58.3% presenting deficiency. Obesity was an independent risk factor for vitamin D deficiency across all models. Geographic location, female sex, and smoking also influenced deficiency risk, while no significant associations emerged with type 2 diabetes or hypertension. Conclusions: These findings highlight the need for targeted strategies addressing vitamin D insufficiency in older adults, considering regional and lifestyle factors, to improve health outcomes in this vulnerable population. Full article

Background/Objectives: Prediction models are implemented frequently, yet, compared with other study designs, their incorporation of clinical measurements (CMs; i.e., vital signs and laboratory results) is rather underdeveloped. The purpose is to describe methods used and illustrate clinical utility in parameters systematically derived from CMs; as a case study, we use the risk of all-cause mortality following coronavirus disease 2019 (COVID-19) as the basis for prognosis. Methods: We identified cases through the Department of Veterans Affairs COVID-19 Shared Data Resource, utilizing data from the first visit until 14 days before testing positive. Thirteen parameters were derived from each of the 11 CMs, capturing departures from normality considering variability and time. The 143 candidate predictors were used to generate the main logistic regression model. The area under the receiver operating characteristic curve (AUROC) analysis was performed to assess discrimination between those who lived and died for subset and main regressions; for comparison, this was performed for an age-only model and the Charlson Comorbidity and Elixhauser Indices. Results: There were 329,491 patients. The main model’s AUROC (0.785 ± 0.002) was similar to the age-only model (0.783 ± 0.002; p > 0.05) and significantly greater than the comorbidity indices’ (range: 0.675 ± 0.002 to 0.729 ± 0.002; p < 0.001 each). Conclusions: The study found several parameters were significant determinants of mortality following COVID-19, highlighting the importance of a systematic approach for multivariate modeling to obtain informative insights into underlying pathophysiology. The main model outperforms common comorbidity indices as a summary metric for pre-existing conditions in this case study. If validated, this approach could revolutionize the way CMs are handled in multivariate models. Full article

Background/Objectives: This study aimed to investigate plasma duloxetine concentrations, factors influencing these concentrations, and the relationship between plasma levels and clinical response in patients diagnosed with generalized anxiety disorder who were treated with duloxetine. Additionally, the study evaluated whether dose escalation resulted in proportional increases in plasma concentration and assessed the clinical utility of therapeutic drug monitoring (TDM) for duloxetine. Methods: In this study, plasma duloxetine levels were analyzed in 68 patients with generalized anxiety disorder who had been receiving duloxetine treatment for at least three months. A review of digital medical files revealed that duloxetine was initiated at 30 mg/day in all patients, and doses were increased to 60 or 90 mg/day in those with insufficient symptom improvement. Digital medical files indicated that participants had been on the final prescribed duloxetine dose for at least four weeks at the time of plasma level measurement. Baseline Hamilton Anxiety Rating Scale (HAM-A) and Generalized Anxiety Disorder-7 (GAD-7) scores were compared with scores obtained on the day of blood sampling. Plasma duloxetine concentrations were quantified using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Associations between dose, plasma concentration, and clinical response were statistically analyzed. Results: Plasma duloxetine concentrations increased significantly following dose escalation. However, no significant correlation was observed between plasma concentrations and percentage change in HAM-A scores. Although patients receiving 60 or 90 mg/day had higher plasma levels than those maintained on 30 mg/day, clinical improvement did not differ significantly between dose groups. In addition to dose, increasing age and non-smoking status were associated with higher plasma duloxetine concentrations. Conclusions: Duloxetine demonstrates a predictable dose–concentration relationship; however, in this response-guided titration setting, plasma concentrations were not consistently associated with clinical improvement. Accordingly, these findings suggest that routine therapeutic drug monitoring may not consistently predict clinical response to duloxetine in generalized anxiety disorder; nevertheless, considering the study’s limitations, it could still offer clinically relevant insights in selected pharmacokinetically sensitive or treatment-resistant cases. Full article

Determining the concentration of fatty acid ethyl esters (FAEEs), ethyl sulfate (EtS), and ethyl glucuronide (EtG) is crucial for establishing the true scale of prenatal alcohol exposure (PAE) and enabling early diagnosis of fetal alcohol spectrum disorders. This study primarily aimed to compare two detection methods: retrospective maternal alcohol consumption surveys and chromatographic analysis of newborn meconium. Among 478 mothers, parallel survey data and meconium samples were collected. Nine FAEEs were measured by gas chromatography–mass spectrometry, and EtG and EtS by liquid chromatography–tandem mass spectrometry. The study also aimed to establish marker cut-offs and evaluate their clinical utility. While only 4% (approximately) of mothers reported alcohol consumption during pregnancy, the biomarker analysis suggested a significant underestimation of the actual PAE scale, highlighting the limitations of self-reported data. Analysis using the cumulative biomarker index for two biomarkers with a threshold of ≥5 indicated that alcohol consumption affected approximately 3% of the studied population, further demonstrating the low reliability of maternal self-reports. Ultimately, this study confirms that the combined EtG and EtS measurements provide the most reliable diagnostic information for PAE and underscores the necessity of objective meconium screening in clinical practice. Full article

Background: Botulinum toxin type A (BoNT-A) is an established preventive therapy for chronic migraine (CM), yet the accompanying neurochemical changes remain incompletely characterized. Objective: To evaluate the effects of BoNT-A on plasma substance P (SP), γ-aminobutyric acid (GABA), glutamate, glutamine, and 5-hydroxytryptamine (5-HT), and on urinary 5-HT, and to explore relationships with clinical outcomes. Methods: In this prospective study, plasma neurotransmitters were analyzed in CM patients (n = 31) at baseline and one month after BoNT-A (155 U; PREEMPT protocol) and in healthy controls (n = 30). Plasma SP was measured using enzyme-linked immunosorbent assay (ELISA); plasma GABA, glutamate, and glutamine were quantified via liquid chromatography–tandem mass spectrometry (LC–MS/MS) with isotopically labeled internal standards; plasma and urinary 5-HT were determined by high-performance liquid chromatography (HPLC). Clinical outcomes included monthly headache frequency, Visual Analog Scale (VAS), and Migraine Disability Assessment (MIDAS). Statistical analyses applied appropriate parametric or non-parametric tests with p < 0.05 considered significant. Results: One month post-BoNT-A, headache frequency, MIDAS, and VAS were significantly reduced (all p < 0.001). SP levels were significantly higher after BoNT-A than at baseline and versus controls. Plasma 5-HT increased post-BoNT-A, while urinary 5-HT decreased. Plasma GABA was elevated in patients versus controls without statistical significance. Glutamine was significantly higher before treatment, whereas the Glu/Gln ratio increased after BoNT-A. Correlations revealed that higher GABA was associated with lower VAS and attack frequency post-treatment. Conclusions: BoNT-A provided short-term clinical improvement with distinct neurochemical changes, including increased plasma SP and 5-HT, decreased urinary 5-HT, reduced glutamine, and a higher Glu/Gln ratio. These biomarkers, particularly Glu/Gln, may serve as indicators of cortical excitability and therapeutic response in CM. Full article

Background/Objectives: Porcine epidemic diarrhea virus (PEDV), particularly the emerging GII genotype, poses a severe threat to the swine industry in affected regions, primarily in Asia. Current vaccines based on classical strains often provide limited cross-protection against these heterogeneous variants, though it should be noted that these vaccines are primarily designed to induce maternal immunity in sows. The objective of this study was to develop a novel inactivated vaccine using an emerging PEDV GIIc variant and evaluate its immunogenicity and cross-protective efficacy against heterologous strains. Methods: A novel PEDV strain, designated PEDV-HeN2024, was isolated from clinical samples and identified through cell culture, immunofluorescence assay (IFA), genetic sequencing, and phylogenetic analysis. An inactivated vaccine was prepared by emulsifying the purified virus with ISA 201 VG adjuvant (1:1, v/v). Immunogenicity was assessed in piglets by measuring virus-neutralizing antibody titers and PEDV-specific IgG levels. Cross-protective efficacy was evaluated through in vitro neutralization assays and in vivo challenge studies with homologous GIIc and heterologous GIIa and GIIb strains. Results: The isolated PEDV-HeN2024 strain demonstrated pathogenicity, causing severe diarrhea and 100% mortality in PEDV-naïve neonatal piglets. Sera from vaccinated animals showed potent cross-neutralizing activity against homologous GIIc, as well as heterologous GIIa and GIIb strains. In challenge studies, vaccinated piglets were significantly protected against clinical disease, showing no diarrhea or viral shedding, and maintained normal intestinal architecture. Conclusions: The inactivated vaccine developed from the emerging PEDV GIIc variant elicits robust humoral immunity and provides cross-protection against prevalent heterologous GII strains. These findings highlight its potential as a promising spectrum vaccine candidate for controlling PEDV outbreaks. This study underscores the importance of using recently circulating strains for vaccine development to overcome the limitations of current vaccines. Full article

The objective of this research is to enable the engineered manufacturing of sewn and embroidered e-textiles. It is achieved by conducting sewability assessments of commercially available conductive yarns and providing optimal sewing parameters to ensure electrical performance and mechanical suitability. Our approach includes yarn sampling, measurements, sewing experiments, statistical modeling, and performance tests of sewn sensors. We have scrutinized a range of conductive yarns with different formation mechanisms and electrical conductivities. Highly conductive, flexible, and fine count yarns are of particular interest in this proposed research. The physical properties of selected conductive yarns have been characterized and sewing experiments have been followed to evaluate the machine sewability of these conductive yarns under diverse sewing conditions. Using multiple logistic regressions and machine learning, these empirical observations are generalized and sewability models are established. Full article

Background and Objectives: Controlled breathing can influence autonomic regulation and haemodynamics; however, the role of its timing relative to exercise remains unclear. Materials and Methods: Fourteen healthy, physically active men (mean age 21.8 ± 0.7 years; body mass index within the normal range) participated in this randomised crossover study. Each session consisted of five 5 min cycling bouts at 50% of heart-rate reserve, interspersed with 3 min passive recovery periods. The three conditions were: control (no structured breathing), 30 s hyperventilation (approximately 30 breaths·min⁻¹) performed before each bout, and the same hyperventilation performed after each bout. Resting heart rate variability spectra (low-frequency [LF], high-frequency [HF]) were assessed pre- and post-session; arterial blood pressure was measured stage-wise; quadriceps muscle oxygen saturation (StO₂) was monitored using near-infrared spectroscopy; and a discriminant co-integration index (Dsk) was calculated to integrate multisystem responses. Results: Compared with baseline, LF power increased and HF power decreased after exercise in the control and post-exercise hyperventilation conditions (p < 0.05), whereas pre-exercise hyperventilation attenuated these shifts. Post-exercise hyperventilation blunted the rise in systolic blood pressure and reduced diastolic blood pressure compared with control (p < 0.05). Both breathing interventions accelerated StO₂ recovery, with higher early recovery StO₂ following pre-exercise hyperventilation and sustained advantages after post-exercise hyperventilation (moderate-to-extensive effects). Dsk values were consistently highest after exercise, indicating stronger and more coherent multisystem coupling. Conclusions: In this acute crossover study of healthy young men, hyperventilation performed before or after exercise induced distinct short-term cardiovascular and muscular responses, reflecting respiratory-driven modulation of haemodynamic and autonomic processes. The timing of hyperventilation influenced these responses, suggesting that deliberate hyperventilation may acutely modify exercise-related regulatory mechanisms. Full article