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Bone-conducted ultrasonic auditory brainstem response thresholds in a mouse model of cisplatin-induced hearing loss
Cisplatin is widely used in cancer treatment but can cause hearing loss, predominantly at high frequencies. Auditory responses to bone-conducted ultrasonic stimulation have been proposed as a potential indicator of cochlear function, but it remains unclear how such responses are affected by cochlear damage. In this study, we measured auditory brainstem response (ABR) thresholds within and beyond the conventional hearing range in a mouse model of cisplatin-induced hearing loss. Of 32 mice initially examined, 9 were excluded at baseline because of pre-existing high-frequency hearing impairment. The remaining animals received either saline or cisplatin, and post-treatment analysis in the cisplatin group was based on 16 surviving mice. Cisplatin administration increased ABR thresholds within the conventional hearing range. In contrast, threshold shifts evoked by bone-conducted ultrasonic stimulation were often smaller. Paired comparison of mean threshold shifts showed that changes evoked by bone-conducted ultrasonic stimulation were significantly smaller than those within the conventional hearing range. These findings show that ABR threshold shifts evoked by bone-conducted ultrasonic stimulation do not necessarily parallel those within the conventional hearing range in cisplatin-treated mice.
Interplay of ELF5, GATA-3 and FLI-1 regulate malignant transformation of keratinocytes
Abstract Cutaneous squamous cell carcinoma (cSCC) arises from epidermal keratinocytes and is the second most common epithelial malignancy. E74-like factor 5 (ELF5) is a member of the epithelium specific ETS subfamily of transcription factors and is essential for epithelial development, homeostasis and prevention of epithelial tumourigenesis. Transformation of keratinocytes involves the disruption of the progenitor differentiation program causing keratinocytes to fail to complete the process. This can lead to dysplastic epithelium and precancerous cells in skin. However, the precise mechanisms that causes the failure of keratinocytes to differentiate completely is not well understood. In our study, we discovered that ELF5 is abundantly expressed in healthy human skin (both basal and suprabasal layers), while its expression is lost in cSCC tissue biopsies. Using CRISPR-Cas9 knockout technology, functional studies along with transcript and protein analysis, loss of ELF5 in immortalised healthy keratinocytes leads to decreased ability of cells to differentiation and increased migration and tumourigenicity, in vitro. Overexpression of ELF5 leads to inhibition of cell migration and proliferation in keratinocytes and in cancer cell lines (A431 and SCC-9), in vitro. Further analysis using RNA transcriptomics has uncovered that GATA-3 and FLI-1 are potentially key molecular targets of ELF5 in keratinocytes. ELF5 regulation of both GATA-3 and FLI-1 is required to maintain the balance between healthy keratinocytes (proliferation/differentiation) and to inhibit precancerous cell formation (tumourigenicity). Our data indicates that ELF5 plays an important role in potentially preventing transformation of keratinocytes and could suppresses skin tumourigenesis. However, additional studies are required to determine this, which could lead the targeting of ELF5 for future drug treatments in cSCC. Better understanding of the underlying mechanisms by which ELF5 regulates gene expression and consequently cell activity will provide new knowledge that can be translated into long-term benefits for patients with precancerous lesions to cSCC.
Rising dust pollution across Europe in a changing climate
Abstract Mineral desert dust is a major contributor to total atmospheric particulate matter 1 . Desert dust outbreaks degrade air quality and can pose adverse health effects 2 , including asthma exacerbation 3 and increased mortality 4 . At some European locations, there has been a rise in the intensity and frequency of transported dust outbreaks from deserts in recent decades 5–9 . However, it remains unclear whether this increase is consistent across Europe and whether desertification and aridity or shifts in atmospheric circulation are the main drivers behind this rise. Here we compile a database of daily dust metal concentrations from European sites, establishing robust elemental ratios for transported dust. Using this database, we develop a machine learning model to estimate daily PM 10 (particulate matter smaller than 10 μm) dust concentrations from 2012 to 2021, ranging from 2.09 ± 1.05 μg m −3 across northern and central Europe to 5.28 ± 2.65 μg m −3 across the south. In southern Europe, residents are exposed to transported dust events averaging 9.68 ± 4.85 μg m −3 , linked to a 0.67 ± 0.02% rise in daily mortality. Intensified dust intrusions over the past decade are linked to shifts in atmospheric circulation. Data from an Alpine ice core record shows a 110% increase in dust concentrations since pre-industrial times, mostly associated with North African desertification. As climate change accelerates land degradation and affects weather patterns, worsening dust pollution may pose increasing risks to public health and air quality goals.
Respiratory pattern change in female and male runners by respiratory tract restriction using a respirator
Respiratory protective equipment, particularly filtering facepiece respirators (FFRs), are increasingly used during physical activity, yet their influence on breathing mechanics remains unclear. This randomized, crossover trial investigated the impact of N95 FFRs on thoracoabdominal breathing patterns during graded treadmill exercise. Twenty competitive runners (10 male, 10 female; 18.9 ± 2.3 years) performed Bruce protocol tests with and without FFRs, while optoelectronic plethysmography quantified the contributions of pulmonary ribcage (RCp), abdominal ribcage (RCa), and abdomen (Ab) to tidal volume. Global ventilatory parameters (tidal volume, breathing frequency, minute ventilation) were unaffected by FFR use. However, compartmental analysis revealed significant alterations in breathing patterns at higher intensities. At 12 and 15 minutes, FFRs reduced RCp contribution (−7.85 ± 2.49%, P = 0.002; −8.41 ± 3.35%, P = 0.012) and increased Ab contribution (+5.97 ± 2.08%, P = 0.004; + 6.51 ± 2.80%, P = 0.020). Across all phases, females demonstrated moderate, but variable RCp dominance (P = 0.052). These findings indicate that while FFRs do not impair overall ventilation in trained runners, they substantially modify the biomechanics of breathing under load, reflecting compensatory adjustments that likely help preserve ventilatory efficiency. The results suggest that well-trained athletes may tolerate acute respiratory stress more effectively than the general population, which has implications for athletic training, rehabilitation, and occupational health where respirator use is required. Trial registration ClinicalTrials.gov NCT07032740
Growth and yield response of sorghum to omission of nutrients under contrasting landscape positions in the semi-arid tropical environment
Quality improvement intervention for school-based support teams for adolescents’ mental health in selected secondary schools in Gauteng: A study protocol
The prevalence of mental health disorders among adolescents poses a significant global health challenge, with approximately one in seven individuals aged 10–19 affected. The limited access to effective mental health services worsens this issue, particularly within schools, which are critical settings for early intervention. The study aims to develop and implement a school-based support team improvement intervention to enhance the mental health of adolescent learners in secondary schools. This study will employ a sequential explanatory mixed-methods approach design. The research will be conducted at selected secondary schools, and the participants for the study will be adolescents aged 13–19 and members of the school-based support team (SBST). Questionnaires will be administered to learners to determine the prevalence of common mental health challenges among adolescents and to determine the factors associated with mental health challenges among adolescents. A scoping review will also be conducted to examine existing interventions aimed at supporting learners with mental health challenges. Following the quantitative phase, interviews will be conducted with SBST members to explore the challenges and successes in supporting learners with mental health problems. The second phase will involve the development and implementation of the SBST quality-improvement intervention to support adolescents experiencing mental health challenges in secondary schools. The researcher will use Statistical Package for the Social Sciences (SPSS, 30.0.0) for quantitative data analysis and statistical interpretation. In addition, ANOVA will be employed to compare, identify, and understand specific factors that significantly impact adolescents’ mental health. The qualitative data will be analysed using Colaizzi’s seven-step framework and will be facilitated with NVIVO 15.
Generative AI tools receptivity promotes designer self perceived creativity through dual cognitive paths moderated by technophobia
Photo-Stitching of Nitroalkanes via Cross-Denitrative Olefination
Clustering recovered 18650 lithium-ion cells to improve homogeneity in second-life battery pack construction
Second-life use of lithium-ion batteries depends on assembling packs from recovered cells that behave as consistently as possible; however, recovered cells are often heterogeneous because of mixed models and different aging histories. This study aimed to improve pack-level homogeneity by clustering recovered cylindrical 18650 cells using laboratory-measured electrical variables and validating the approach through the construction and testing of a second-life pack. Cells were extracted from discarded laptop batteries, screened using safety and basic performance criteria, and characterized under a standardized charge–discharge protocol. For each retained cell, discharged capacity and internal resistance were measured, and health indicators were computed from nominal specifications and experimental results. Correlation analysis was used to identify the most informative variables associated with health status and to avoid redundant predictors prior to clustering. Clustering performance was evaluated across different numbers of groups using a cohesion–separation index, and two iterative selection algorithms were applied to select non-overlapping, highly homogeneous subsets of cells for series–parallel pack assembly. Using the same pack topology, the refined algorithm produced a second-life pack with higher usable capacity (8.98 Ah versus 8.72 Ah), lower equivalent internal resistance (76.38 mΩ versus 78.90 mΩ), and higher estimated maximum power (716.97 W versus 694.08 W) compared with the baseline algorithm. Overall, the results show that clustering guided by discharged capacity and internal resistance, combined with iterative refinement, enables the construction of more homogeneous and electrically consistent second-life packs from heterogeneous recovered cells.
misoTar: a novel approach for predicting miRNA and isomiR targets
Analysis of vapor cloud explosion behavior in LPG spherical tanks using multi-energy modeling and machine-learning-based factor assessment
Vapor cloud explosions (VCEs) associated with liquefied petroleum gas (LPG) storage systems represent a significant hazard in refinery operations. Accurate estimation of explosion distance is essential for safety setback design and quantitative risk assessment. This study developed an integrated framework that combines physics-based and data-driven techniques to study VCE behavior resulting from LPG releases from a 20,000-barrel pressurized spherical tank under realistic refinery conditions. A total of 336 leakage scenarios were simulated using DNV PHAST 2022 and the Multi-Energy method. Seven influencing parameters were considered, including leak diameter, LPG composition (propane–butane ratio), leak location, atmospheric category, seasonal period, day/night conditions, and three overpressure thresholds (0.02, 0.14, and 0.21 bar). The results revealed a wide dispersion in explosion distance across scenarios, with maximum distances exceeding 2,100 m for catastrophic full-bore ruptures. Feature-importance analysis using a Random Forest regression model showed that leak diameter was the dominant controlling parameter, accounting for approximately 74% of the predictive importance, while LPG composition contributed an additional 24–25%. Operational and atmospheric parameters had comparatively minor effects. The three investigated overpressure thresholds produced nearly identical explosion distances across the evaluated scenarios, indicating that within the low-pressure range, explosion extent is primarily governed by the released fuel mass and flammable cloud geometry rather than the threshold value. A classical power-law correlation was used to describe the geometric scaling between leak diameter and explosion distance; however, its predictive capability was limited (RMSE ≈ 337 m) due to its single-variable formulation. In contrast, the Random Forest model captured multi-factor interactions within the PHAST-generated dataset with very high predictive accuracy (R² ≈ 0.9997, RMSE ≈ 9 m). This hybrid framework provides a transparent approach for analyzing LPG vapor cloud explosions and offers practical insights for safety-distance determination, refinery layout optimization, and risk-based inspection planning.
Broadband achromatic metalens for the short-wave infrared
Abstract The 1.8-2.3 $$\upmu$$ m band lies within the short-wavelength infrared (SWIR) region and serves as a key operational window for a wide range of applications, including quantum sensing, molecular spectroscopy, and free-space quantum and classical optical communication. Despite its significance, optical devices operating in this band still face two major challenges: chromatic aberration across the wide spectral range and the difficulty of integration due to bulky optical elements. Metalenses are composed of subwavelength nanostructures that locally control the phase and group delay of light, enabling precise wavefront shaping and broadband dispersion compensation. These capabilities make them highly promising for use in infrared optical systems, particularly in applications such as focusing and imaging for compact integrated devices. In this study, we propose a metalens design based on a CaF $$_2$$ substrate, where each nanocell consists of a single-bar silicon structure. These nanocells are periodically arranged with a 900 nm period, enabling precise control of dispersion and phase. By systematically fine-tuning the bar length and width, the design enables simultaneous dispersion compensation and phase modulation, achieving stable focusing performance over a broad spectral range. Finite-Difference Time-Domain (FDTD) simulations demonstrate effective suppression of chromatic aberration across 1800–2300 nm, with simulated focal-length variation within 6% of the target value. We further analyze the polarization distribution across the focal spot and find a weak wavelength dependence of the degree of polarization (DoP), which we attribute to the spatially varying polarization state in the high-NA focal region together with the wavelength-dependent anisotropic response of the nanostructures. Meanwhile, this design offers a compact, broadband, and high-performance approach for beam collimation and wavefront shaping in the SWIR band, showing promising potential for applications in quantum communication and sensing systems.
Pharmacist-led educational intervention to improve knowledge, medication adherence, and asthma control among asthma patients at Ayder Comprehensive Specialized Hospital: A protocol for randomized controlled trial
Objective To evaluate the effect of a pharmacist‑led educational intervention on medication knowledge, adherence, and asthma control among adult asthma patients at Ayder Comprehensive Specialized Hospital, Ethiopia. Methods A single‑blind, parallel‑group randomized controlled trial will be conducted. All eligible adult asthma patients on active follow‑up at the chest clinic of Ayder Comprehensive Specialized Hospital will be included. Participants will be randomly assigned via a computer‑generated sequence to an intervention group (structured pharmacist‑led education using teach‑back, illustrated pamphlets, a follow‑up phone call and SMS) or a control group (routine care). Outcome assessors will be blinded to group allocation. Outcomes will be measured at baseline and after three months, including medication adherence (GMAS), asthma control (ACT), medication knowledge, correct inhaler technique, and domain‑specific adherence barriers. Data will be analyzed using intention‑to‑treat with multivariable binary logistic regression, chi‑square tests, independent T-test, McNemar test, Mann‑Whitney U test, and Fisher’s exact test where appropriate. Subgroup analyses will be performed to explore whether the intervention effect differs across patient characteristics. A p‑value < 0.05 will be considered statistically significant, with 95% confidence intervals reported. Trial registry Pan African Clinical Trials Registry (PACTR202508565637179).
Intelligent identification of dolphin whistle in acoustic signals via deep learning
Waist circumference versus BMI: A cross-sectional study comparing Cardiometabolic Risk association in the Nepalese Population
Background Obesity is a major cardiometabolic risk factor. Although body mass index (BMI) and waist circumference (WC) are established predictors of cardiometabolic risk, their predictive value may vary across ethnic groups. South Asians, including Nepalese individuals, exhibit a distinctive “thin-fat” phenotype characterized by increased central adiposity and higher body fat despite relatively normal BMI levels. Therefore, internationally validated anthropometric cutoffs may not accurately reflect cardiometabolic risk in the Nepalese population. Whether WC better predicts cardiometabolic risk than BMI in Nepalese individuals remains unclear. We conducted a comparative analysis of WC and BMI to evaluate their predictive ability for clinically relevant cardiometabolic outcomes. Methods In this cross-sectional study of 678 adults, BMI and waist circumference (WC) were evaluated as anthropometric indicators of cardiometabolic risk in the Nepalese population. Their associations were examined across six clinically relevant outcomes: hypertension, diabetes mellitus, thyroid disease, fatty liver disease (FLD), non-alcoholic fatty liver disease (NAFLD), and dyslipidemia. Comparative performance of BMI and WC was assessed using correlation analysis with biochemical markers, multivariable logistic regression adjusting for key covariates, and receiver operating characteristic (ROC) curve analysis to evaluate their relative predictive and discriminatory ability in this setting. Results BMI and waist circumference (WC) were strongly correlated (ρ = 0.75) but demonstrated distinct patterns in cardiometabolic associations. WC showed stronger correlation with triglycerides (ρ = 0.35 vs 0.24 for BMI) and was the only measure significantly associated with hypertension. Both BMI and WC were significantly associated with fatty liver disease (FLD), non-alcoholic fatty liver disease (NAFLD), and dyslipidemia; however, BMI generally showed higher odds ratios per unit increase compared to WC. Predictive performance was comparable between BMI and WC, with similar AUC values in the fair-to-acceptable range (0.6–0.7) across most outcomes. Notably, discrimination improved substantially (>0.8) when BMI and WC were combined with age and sex, yielding good predictive accuracy. Conclusion BMI and WC provide complementary information for cardiometabolic risk in the Nepalese population. Combined assessment with age and sex improves risk stratification, indicating that integrating both measures with calibrated thresholds enhances clinical prediction compared with using either alone.
Distinct site-specific bacterial microbiota within and between skin physiologic types in healthy Koreans: a pilot study
Factors associated with procedural difficulty and major adverse events during transcatheter closure of the patent ductus arteriosus
Transcatheter closure of the patent ductus arteriosus (PDA) is widely accepted as an alternative to surgical ligation. However, major complications are uncommon. Therefore, procedural difficulty, including device repositioning or change, may provide additional insight into technical challenges encountered during PDA closure. We aimed to identify the clinical and anatomical risk factors associated with procedural difficulty or major adverse events during transcatheter PDA closure and to document the prevalence and types of complications encountered in a single tertiary center. This retrospective cohort study included 341 patients who underwent a transcatheter PDA closure between 2010 and 2023. A composite primary outcome, defined as procedural difficulty or major adverse events, included device malposition requiring reposition or change, unsuccessful device deployment, device embolization, hemodynamic instability requiring intervention, or unplanned surgical conversion. Demographic, anatomical, and hemodynamic variables were analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent predictors. Procedural difficulty or major adverse events occurred in 49 patients (14.3%). There was no procedure-related mortality. Device embolization occurred in three patients (0.8%), all requiring surgical ligation. Multivariate analysis revealed that a minimum PDA diameter >5 mm (odds ratio [OR] = 2.75, P = 0.013), PDA length >8 mm (OR = 2.81, P = 0.009), and non-type A (non-conical) duct morphology (OR = 2.88, P = 0.025) were independently associated with the composite outcome. In conclusion, larger PDA diameter, longer ductal length, and non-conical morphology were significantly associated with increased procedural difficulty or major adverse events during transcatheter PDA closure. These findings highlight the importance of detailed anatomical assessment in patients undergoing transcatheter PDA closure.
AGFR-Net: anatomy-guided feature refinement for robust multi-label thoracic disease classification from chest X-rays
Real-world implementation and cost impact analysis of Oncotype DX testing in early-stage breast cancer
Background The decision on appropriate adjuvant treatment for patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2 -negative (HER2-) early breast cancer (eBC) is sometimes challenging. Genomic assays have improved individualized treatment decisions by providing information on the genomic risk of tumors. The Oncotype DX assay (ODX) is both prognostic and predictive of chemotherapy benefit. This study aimed to evaluate the implementation process of the ODX into clinical practice, the impact of ODX on adjuvant chemotherapy treatment decisions and conduct a cost impact analysis. Patients and methods A retrospective study at Tampere University Hospital included 129 patients with HR + , HER2- eBC tested with ODX between September 2021 and September 2023. Treatment decisions as well as adjuvant chemotherapy (CT) costs, associated health provider costs, and societal costs were projected. Results ODX testing significantly altered CT recommendations by reducing unnecessary CT for 73% of the study patients. With ODX testing, the cost impact analysis revealed partial cost savings for the health care provider due to reduced CT administration. From a societal perspective, the use of ODX resulted in substantial savings largely attributed to the maintenance of work productivity among working-aged and employed patients. Conclusion This study highlights the importance of streamlined testing processes and the need for clinician training in interpreting test results in a real-world setting. In addition, the findings underscore the role of ODX in enhancing personalized treatment in HR + , HER2- eBC while reducing overtreatment. The cost analysis indicates substantial cost savings with ODX testing.