Browse Articles

Association between lactate-to-albumin ratio and 28-day ICU mortality in pediatric severe pneumonia patients

Introduction The lactate-to-albumin ratio (LAR) has emerged as a promising prognostic biomarker in critical care, reflecting both metabolic dysfunction and inflammatory status. However, its prognostic value in pediatric severe pneumonia remains underexplored. This study aimed to investigate the association between LAR and 28-day ICU mortality in pediatric severe pneumonia patients using data from the Paediatric Intensive Care database. Methods A retrospective cohort study was conducted involving 617 pediatric severe pneumonia patients admitted to the ICU between 2010 and 2018. LAR was calculated as the ratio of lactate (mmol/L) to albumin (g/dL). The primary outcome was 28-day ICU mortality. Cox proportional hazards regression models were used to assess the relationship between LAR and mortality, with restricted cubic splines (RCS) employed to explore potential nonlinear associations. Subgroup analyses were performed based on age, sex, and oxygenation status. Results A significant linear relationship was observed between LAR and 28-day ICU mortality. Each unit increase in log (LAR) was associated with a 2.51-fold higher mortality risk (HR 2.51, 95% CI: 1.73, 3.65; P < 0.001). Kaplan-Meier analysis confirmed that patients in the highest LAR tertile had significantly lower survival probabilities compared to those in the lowest tertile (log-rank P < 0.001). Subgroup analyses revealed consistent associations across age, sex, and oxygenation status, with no significant interactions (all P for interaction>0.05). Conclusions Higher LAR levels are independently associated with increased 28-day ICU mortality in pediatric severe pneumonia patients, demonstrating a linear relationship. These findings highlight LAR as a valuable prognostic tool for early risk stratification and clinical decision-making in this population. Further multicenter studies are needed to validate these results and explore interventions targeting LAR reduction to improve outcomes. Trial registration Not applicable.

Study on the pathogenesis of varicocele induced by the ferroptosis of cremaster satellite cells with the m6A modification of TFRC mRNA

Background Varicocele (VC) is a leading cause of male infertility. Insufficient growth and development of the cremaster muscle may contribute to VC, but the underlying mechanism remains unclear. Cremaster muscle dysfunction may impair venous valve support, contributing to VC. The cremaster relies on satellite cells (SCs) for postnatal growth and damage repair. This study aimed to explore the mechanism of the cremaster muscle in the process of VC. Methods Ten male Sprague-Dawley (SD) rats were divided into two groups: the VC model group (5 rats) and the sham-control group (5 rats). After four weeks of observation, the cremaster muscles were collected. The diameters of the left and right spermatic veins were measured, and the left testis was isolated for morphological examination via H&E staining. SCs isolated from the left cremaster muscle were analyzed using multiple methods, including qPCR and Western blot. Data were analyzed using SPSS v.22.0. Results Compared to the control group, the model group showed decreased TFRC mRNA stability, decreased mitochondrial membrane potential, and decreased GSH and GSSG contents, as well as increased m6A modification levels and increased ROS, MDA, and Fe2+ contents. In addition, the model group also showed downregulation of transferrin receptor (TFRC, a key iron uptake protein involved in ferroptosis) expression and upregulated m6A methyltransferase and recognition proteins. Multiple biochemical test results indicated increased ferroptosis, characterized by changes such as decreased mitochondrial membrane potential and GSH and increased ROS, MDA, and Fe2+. Conclusion This study suggests that SCs in the cremaster muscle is associated with impaired cremaster muscle repair and VC pathogenesis through m6A modification of TFRC mRNA. Our findings offer fresh insights into the role of cremaster SCs in VC and provide a foundation for future research on the potential therapeutic target of VC. Strengths and limitations of this study This study is the first to investigate the pathogenesis of varicocele from the perspective of the cremaster muscle, and some clues have been discovered from it. The causal relationship between m6A-TFRC axis and ferroptosis requires further validation using functional rescue experiments (e.g., METTL3 knockdown or ferroptosis inhibitors). The small sample size may limit statistical power; future studies with larger cohorts are warranted.

Tulp3 deficiency results in ciliopathy phenotypes during zebrafish embryogenesis

Abstract Ciliopathies, caused by defective cilia biogenesis or function, comprise a genetically and clinically diverse group of diseases. Primary cilia play pivotal roles in the regulation of a multitude of signalling pathways during development and tissue homeostasis. Cilia assembly, maintenance and signalling depend on intraflagellar transport (IFT). Tubby-like protein 3 (TULP3) functions as an adapter protein for the ciliary trafficking of diverse membrane cargos via an interaction with the IFT-A complex. Recently, we and others have shown that individuals carrying pathogenic TULP3 variants suffer from progressive liver, kidney and heart disease. In line with these findings, adult Tulp3 knockout zebrafish displayed liver fibrosis and kidney cyst phenotypes. In the present study, we analysed the functional consequences of Tulp3 deficiency during zebrafish embryogenesis. Tulp3 deficiency resulted in well-known ciliopathy-associated phenotypes including pronephric cysts, body curvature and altered left-right asymmetry. Our analysis of urotensin 2-related peptide (Urp) signalling, which is required for proper spine morphogenesis, revealed reduced expression of urp1 in Tulp3 knockout embryos. We also observed scoliosis in a significant number of adult Tulp3 knockout zebrafish. Analysis of ciliogenesis revealed a reduced cilia number and ciliary length in Tulp3 deficient embryos. In addition, Tulp3 deficiency resulted in upregulation of cilia-dependent profibrotic Wnt and Jak/Stat signalling components. Furthermore, we demonstrate that loss of Tulp3 causes upregulation of genes related to liver fibrosis. In conclusion, our data highlights a role of Tulp3 in proper cilia formation and function to maintain healthy tissue architecture during zebrafish embryogenesis, and provides further insight into the spectrum of cilia-related phenotypes in adult zebrafish depleted for Tulp3 functions.

Shade provision and its influence on water intake and drinking behaviour of Nellore cattle in feedlot in a tropical environment

Heat stress is a significant challenge in tropical beef production systems, affecting feed intake, water intake, and overall animal welfare. This study aimed to evaluate the impact of shade provision on the water intake and drinking behaviour of Nellore steers (Bos indicus) in a tropical feedlot environment. A total of 47 steers (~450 kg body weight) were allocated into two groups: one with access to shade (+S) and another without (-S). Individual water intake, drinking behaviour (e.g., frequency, daily patters), and animal performance were monitored over 83 days using automated recording systems. Results showed that -S steers consumed 8% more water per day (p < 0.001), made more frequent visits to the water trough (p < 0.001), but drank less per visit (p < 0.001) and overall spend 39% more time per day drinking (p < 0.001) compared to the + S steers. Despite these differences in drinking behaviour, average daily gain and feed intake did not differ between groups (p > 0.05). Environmental factors like temperature, humidity, and solar radiation affected water intake in both groups. Higher air temperatures increased water intake by boosting drinking frequency, while higher relative humidity reduced water intake by decreasing visit frequency. Shade provision reduced water demand per unit of body weight gain, improving water-use efficiency. These findings suggest that while shade may not directly enhance body weight gain, it can optimise drinking behaviour, reduce water intake, and improve animal welfare in tropical beef production systems.

Urinary bisphenol levels and blood pressure after soda consumption from cans, PET and glass bottles

Abstract Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) that has been associated with various human disorders. Human exposure is ubiquitous. The primary route of exposure is ingestion, as BPA can leach from plastic food packaging and the epoxy resin lining of cans into food. Restrictions on the use of BPA in consumer products due to its health concerns have resulted in the development and introduction of new BPA alternatives. These compounds are likely to have health effects comparable to those of BPA. However, data on the type and amount of substitutes used in consumer products are difficult to obtain, and studies on their prevalence of use and impact on health in human populations are sparse. The aim of the present study was to evaluate the urinary concentrations of BPA and its analogues after the consumption of soda from cans compared to polyethylene terephthalate (PET) bottles and glass bottles. Additionally, we investigated blood pressure levels before and after soda consumption from cans, PET bottles, and glass bottles. We conducted a randomized crossover trial with 103 female participants between 30 and 65 years of age. The participants were assigned to drink soda (Coca-Cola light) from cans, PET bottles and glass bottles on two days of an intervention week. Urine samples were collected two to three hours after the intervention. Blood pressure levels were measured before and two to three hours after the intervention. Urinary bisphenol concentrations were measured via GC-AEI-MS/MS. The associations between the intervention and log10-transformed bisphenol concentrations and blood pressure levels were evaluated via a mixed models approach. For comparisons of the interventions, we used Tukey tests. We found significantly higher BPA concentrations in the urine samples of our study participants after soda consumption from cans than after soda consumption from PET bottles (+ 22.3%, 95% CI 3.37;44.64, P value 0.014). There was no difference compared to glass bottles. In addition to BPA, we detected BPF, BPS and BPE in some of the urine samples, but to a lesser extent, and independent of beverage packaging. Systolic and diastolic blood pressure increased across all interventions independent of whether soda was consumed from cans, PET bottles, or glass bottles. This study suggests that canned soda may increase the amount of BPA excreted in the urine of humans. The increase in blood pressure, independent of beverage packaging, may be due to the caffeine content of the consumed beverage. Given the potential of bisphenol exposure from canned food and beverage consumption, as well as the availability of alternatives in the epoxy resin lining of cans, complete removal of BPA from cans is an attractive option for mitigating human exposure to bisphenols. Universal Trial Number/ DRKS-ID: U1111-1244-7033/ DRKS00019922 (Registration Date 29/11/2019).

Applying the advocacy coalition framework to wildlife management: Explaining policy change for damage mitigation in Japan

Case studies in wildlife management and its policy often lack a unified analytical framework, there are few studies that have systematically investigated policy processes and pathways of policy change. This paper examines Japan’s ungulate (deer, wild boar) management policy as a case study, applying the Advocacy Coalition Framework (ACF) to the study of wildlife management to elucidate the mechanisms driving policy changes in ungulate management while evaluating the framework’s effectiveness. Insights into policy subsystems, policy beliefs, policy-oriented learning, and both external and internal perturbations in the advocacy coalition framework may be useful in understanding the policy change in wildlife management. Data were collected through diet records, official documents, newspaper articles, and semi-structured interviews with stakeholders. Using this data, discourse network analysis was employed to identify coalition structures, resources and policy-oriented learning of two advocacy coalitions—the Hunting Coalition and the Protection Coalition—and events leading to policy change were identified. The analysis revealed that between the 1990s, when ungulate damage became severe, and 2014, the core attributes of Japan’s government program transitioned from a centralized protection-focused policy to a decentralized policy promoting hunting. This shift was driven by four pathways proposed in the ACF’s bottom-up policy change hypothesis: policy-oriented learning, internal perturbations, external perturbations, and negotiated agreements. These findings highlight the utility of the ACF as an analytical framework. This study suggests that the ACF is a valuable tool for understanding the complex dynamics of wildlife management.

Optimal maximum power point tracking strategy based on greater cane rat algorithm for wind energy conversion system

Abstract With the rapidly increasing usage of renewable sources, especially wind power, maximizing the power produced from wind energy conversion system (WECS) has become a major concern. Various methods are utilized in the domain of wind turbine performance enhancement for tracking the maximum power point (MPP). Among them, the perturb and observe (P&O) approach is widely applied because of its straightforward implementation. Nevertheless, the primary drawback of this approach is the imprecision caused by variations at the peak power point. Consequently, due to wind’s arbitrary and complicated characteristics, using an intelligent optimization technique is compulsory as it can give effective tracking performance. In this study, a recently developed nature-inspired metaheuristic, termed the Greater Cane Rat Algorithm (GCRA), which emulates the cognitive foraging behavior of greater cane rats during and after the breeding season. The GCRA approach seeks to regulate the boost converter by computing the duty cycle value using the voltage and current variables. The Wind Energy Conversion System (WECS) incorporates a wind turbine, a Permanent Magnet Synchronous Generator (PMSG), a rectifier, and a DC/DC boost converter that is linked to a load. The wind system can track the maximum power via a mechanical sensorless tracker system without the need to connect an additional mechanical sensor. The suggested strategy is compared to various tracking methodologies, including the classical Perturb & Observe (P&O), Particle Swarm Optimization (PSO), and Gray Wolf Optimization (GWO). The obtained results, which have been executed in the environment of MATLAB/SIMULINK R2022b, illustrate that the proposed approach improves the performance of the tracking system under different wind profiles step, realistic, and ramp variation of the wind velocity. The proposed strategy outperforms a tracking efficiency that exceeds 99%, surpassing other considered tracking approaches, which are at 95.5%, 94.7%, and 91.4% with the least error ratio and the best tracking for the power coefficient ratio.

A Model to guide force-based manipulation research and practice

Introduction Manual therapies are forms of force-based manipulations (FBM) and involve the application of mechanical force to the outside of the body with therapeutic intent. The United States National Institutes of Health (NIH) U24 FBM Taxonomy and Terminology Committee (FBM-TTC) was formed to better understand why responses to FBM differ between individuals. One objective for this multi-disciplinary working group was to develop a framework outlining factors that should be considered, measured, and reported when developing and performing studies on FBM. Methods The workgroup collaborated to develop a model outlining elements to consider during FBM research and practice. Three different models were proposed by members of the group who voted on a preferred model using a rank-ordered process and refined the selected model based on consensus and published literature. Results A 3-dimensional (3D) matrix model was chosen that includes three elements: contextual factors influencing FBM outcomes, structure and function levels focusing on biological and physiological aspects, and force parameters. Each element expands into different components and sub-levels. The model is designed to be interactive, integrative, and dynamic. Discussion The model provides a framework to guide protocol development for FBM mechanistic research and clinical outcome studies. For example, researchers can design more robust studies systematically varying force parameters by considering other matrix components, while clinicians may develop more personalized treatment plans. The model supports the complexity of mechanistic responses to FBM by integrating the multitude of intrinsic and extrinsic factors that impact responses. Detailed discussion of each element is beyond the scope of this paper; however, content experts are encouraged to expand on this dynamic model. Conclusions An innovative 3D model was developed to guide FBM research. The framework integrates foundational elements and accommodates new insights, making it a valuable tool to advance FBM science and practice.

Love, laugh, life—the effect of empathy on the processing of emotion-label, emotion-laden and neutral abstract words

Abstract While there is accumulating evidence that emotional words are processed faster than neutral words, findings regarding processing differences between emotion-label and emotion-laden words are inconsistent, potentially due to uncontrolled word- or participant-specific characteristics. We therefore analyzed lexical decision reaction times for emotion-label, emotion-laden, and neutral abstract words, while controlling for subjective differences in word valence, arousal, concreteness, and interoception, as well as considering inter-individual differences in empathy. We neither replicated the facilitatory emotionality effect for emotion-label or emotion-laden compared to neutral word processing nor found evidence for a reaction time difference between emotion-label and -laden words. Notably, however, results showed a word type-specific effect of empathy: Participants reacted faster to specifically emotion-label words, the higher their empathy. Additional exploratory analyses confirmed a word-type-specific gradual pattern, with stronger association of emotion-label than emotion-laden than neutral words with absolute valence, arousal and interoception. These analyses yet again revealed a word-type-specific modulation by empathy, wherein emotion-label words’ ratings were significantly enhanced by empathy. Individual differences in empathy thus seem to affect specifically the processing of emotion-label words and the evaluation of their affective properties. Our findings underline the importance to consider word- and participant-specific characteristics in research on the semantic processing of emotional abstract words.

Broad-spectrum bioactivities and therapeutic potential of essential oils of certain aromatic and medicinal plants and their combination

Abstract This research investigates the bioactive properties of essential oils obtained from three medicinal and aromatic species: Mentha canadensis, Corymbia citriodora, and Plectranthus amboinicus. The essential oils were evaluated for antiviral, antioxidant, anticancer, and antidiabetic activities. The gas chromatography-mass spectrometry (GC–MS) examination identified a variety of phytochemical constituents, including thymol, citronellol, and levomenthol. Cytopathic impact studies indicated that M. canadensis and C. citriodora oils attained a maximum of 35.34% suppression of Adeno 7 virus replication. The oils exhibited minimal cytotoxicity in Vero cells, with viability exceeding 97% at concentrations of ≤ 312 µg/mL. P. amboinicus oil had the highest cytotoxicity against H1299 lung cancer cells (IC50 = 11 µg/mL), indicating significant anticancer efficacy. The antidiabetic effects were evidenced by α-glucosidase inhibition, with P. amboinicus oil displaying the greatest activity (IC50 = 248.1 µg/mL). The DPPH experiment demonstrated that P. amboinicus exhibited the highest antioxidant activity (IC50 = 5923 µg/mL). The results highlight the medicinal potential of these essential oils, including P. amboinicus for anticancer, antioxidant and antidiabetic applications, and C. citriodora and M. canadensisfor antiviral purposes. The current work serves about four goals of the sustainable development goals (SDG) as follow: SDG 3: Good Health and Well-being, SDG 12: Responsible Consumption and Production, SDG 9: Industry, Innovation, and Infrastructure and SDG 15: Life on Land.

Label-free volumetric imaging of porcine kidney tissue over extended areas using dynamic MHz-OCT

Abstract Dynamic optical coherence tomography (dOCT) enables high-resolution, label-free 3D tissue imaging with functional contrast, offering a potential advancement in kidney transplant viability assessment. Currently, no widely accepted non-invasive method provides an objective evaluation of transplant viability, as conventional imaging lacks the resolution to assess microvascular integrity and cellular dynamics. However, the clinical use of available dOCT systems is limited by prolonged imaging times that hinder clear visualization of tissue dynamics. To address these challenges, this paper presents a swept-source 3.2 MHz-OCT system for dynamic, high-speed, extended-area imaging. The system integrates an optimized inter-volume scan protocol and a micrometer-precision linear robot, enabling extended‑scale tissue imaging over an area of about 2.6 × 2.6 mm2. Using freshly excised porcine kidney tissue, we demonstrate recent advancements and challenges in MHz-dOCT for kidney imaging. Identified anatomical features are thoroughly examined, compared across resolutions, and validated through histology to assess the system’s clinical potential.

Impact of titanium nanoparticles on germination and early growth of faba bean (Vicia faba L.)

Abstract This study explores the potential of biosynthesized titanium dioxide nanoparticles (TiO2NPs), capped with phytochemicals from Zygophyllum simplex extract, in enhancing seed germination and related indices of faba bean (Vicia faba L.), aiming to support sustainable and biocompatible approaches in nano-agriculture. Specifically, the study assessed the impact of biogenic TiO2NPs (average size ≈ 12.8 nm) on seed germination, early plant growth parameters such as root and shoot length, and germination percentage, as well as the activity of selected antioxidant and hydrolytic enzymes in faba bean. Seeds were soaked for 6 h in an aerated solution containing six concentrations of TiO2NPs (1, 5, 10, 25, 50, and 100 µM), alongside a control group. Germination was conducted in dark at 25 ± 0.5 °C for six days. The results demonstrated that TiO2NPs at concentrations up to 25 µM significantly enhanced germination percentage, seedling growth parameters, and increased the activities of antioxidant enzymes; catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD), as well as α-amylase and protease enzymes, total soluble sugar and protein content, in comparison with non-treated seeds. However, TiO2NPs at a concentration of 50, and 100 µM significantly reduced germination rates, inhibited seedling growth, and decreased enzyme activities relative to the control. These findings suggest that nano-titanium, particularly at a concentration of 10 µM, effectively enhances germination potential, subsequent seedling growth, and enzyme activity in Faba beans. Further research on the impact of these nanoparticles on vegetative growth and yield could provide valuable insights based on the positive effects observed during germination and early seedling development.

Lab-on-PCB with integrated DNA amplification and electroanalytical detection for point-of-care diagnostics

Abstract Nucleic acid amplification tests (NAATs) are powerful medical diagnostic tools for point-of-care (POC) and other field applications. However, traditional methods like quantitative PCR (qPCR) require complex, expensive equipment and trained operators, limiting their use to centralized labs. Isothermal alternatives, like Loop-mediated Isothermal Amplification (LAMP), are better adapted for POC devices. Lab-on-PCB systems have the potential to overcome the challenges faced by conventional microfabrication-based systems. This study presents a novel lab-on-PCB device for nucleic acid amplification and electrochemical detection using reverse transcription LAMP (RT-LAMP) of SARS-CoV-2. The system consists of two disposable PCB-based chips making it close to zero cost. One PCB is for heating and nucleic acid amplification, while the other is for electrochemical detection using Cyclic Voltammetry (CV) with a redox-active intercalator. The PCB slides are connected to a compact electronic device (< 10 USD) for controlling the heating and electroanalytical readout. Using this device, we achieved successful rapid (< 1.5 h) nucleic acid amplification and detection at a target concentration of 10 copies/reaction. This work represents a notable step toward developing integrated, portable NAAT devices for POC diagnostics.

Sustainable Edamame production in an artificial light plant factory with improved yield and quality

Abstract A plant factory utilizing artificial light is an innovative agricultural model that enables efficient and sustainable crop production. However, its application to a diverse range of crops remains limited. Edamame, a highly nutritious legume, has gained global popularity, yet its long-term storage is challenging due to quality deterioration, restricting its market distribution to seasonal availability. In this study, we successfully cultivated edamame using three hydroponic systems—nutrient film technique (NFT), rockwool, and aeroponics (mist culture)—within an LED plant factory. Among these, NFT demonstrated the highest fresh seed yield, which was comparable to or exceeded that of conventional field cultivation. The high yield was attributed to enhanced pod formation and biomass production under controlled conditions. Furthermore, although free amino acid content was lower in NFT cultivation, NFT-grown edamame exhibited significantly higher total sugar and isoflavone contents than field-grown counterparts, suggesting superior sensory quality and nutritional benefits. These results indicate that NFT hydroponics is a promising method for stable, high-yield edamame production with enhanced nutritional properties. This study provides a foundation for expanding edamame cultivation in controlled environments, contributing to year-round supply and its potential application in urban and space agriculture.

Application of 4-CPA or ethanol enhances plant growth and fruit quality of phyA mutant under heat stress

Abstract As the phytochromes play a key role in plant light perception, they also modulate stress responses. The tomato mutant c.v. Moneymaker lacking PHYTOCHROME A (PHYA) exhibits tolerance to heat stress during the vegetative growth phase; however, this response does not continue into the reproductive stage. In this study, the response of phyA at the reproductive stage was improved through the exogenous application of 4-chlorophenoxy acetic acid (4-CPA) and ethanol under heat stress, either at 37 °C in controlled culture room or fluctuating high temperatures (approximately 50 °C and 30 °C in midday and night, respectively) during the summer in greenhouse. 4-CPA, a synthesized plant growth regulator with functions similar to that of auxins, induced growth and flower formation at the flowering stage when sprayed on phyA compared to that in the non-treated plants. Similarly, 4-CPA application improved fruit setting and fruit characteristics, and the quantity or quality of the phyA mutant. The expression of numerous heat-related genes, such as heat shock factors (HSFs), heat shock proteins (HSPs), and reactive oxygen species (ROS) scavengers, was upregulated in phyA as a result of 4-CPA application. Ethanol application showed better growth when sprayed on phyA than non-treated plants, and HSFA1a and HSP70 expression was significantly stimulated by this treatment. On the other hand, applying either 4-CPA or ethanol-induced auxin and gibberellin production by stimulating the expression of genes involved in hormone production. Finally, electrolyte leakage (EL) and malondialdehyde (MDA) levels were inhibited after both treatments. In contrast, proline production increased. Therefore, applying 4-CPA or ethanol improved phyA mutant tolerance, allowing the mutant to tolerate heat stress during all growth stages. Furthermore, the quality of tomato fruits is improved by the application of these chemicals.

Correction: Advancing forensic accuracy: mitigating methemoglobin interference in postmortem carbon monoxide analysis using sodium dithionite reduction

Characterizing the time of day and year of falls in people with probable Parkinson’s disease

Abstract Temporal aspects of falls are not well characterized in people with Parkinson’s disease (PD), particularly those later in life. The purpose of the current study is to characterize the timing (across day and year) of falls in people with probable PD compared to non-PD peers. Swedish registries were used to identify 441 people (mean age, 83.7 years, range = [59.0–100.0]) with one or more prospectively registered falls over the course of approximately 2.5 years. Of these participants, 40 were prescribed drugs of the class N04 “Anti-Parkinson Drugs”. Of these 40, 30 were prescribed dopamine or dopamine derivatives, suggesting presence of PD, and 10 were prescribed “other PD-related medications”. Given the unclear nature of these 10 participants, they were excluded from all analyses. Chi-squared tests and Generalized Estimating Equations were used to assess the time of day and year of falls in people with probable PD (n = 30) and non-PD (n = 401) accounting for covariates (age, gender, number of prescription medications). There was a statistically-significant effect of PD-group on fall time of day (accounting for gender, age, & number of prescription medications), such that Swedish residents with probable PD fell less often in the evening than the day (p = 0.015, OR = 0.61). Across the whole sample, female participants fell less frequently at night than the day (p = 0.032, OR = 0.73). People with probable PD fell more frequently in the spring months than other seasons (×2 = 32.1, p < 0.001). The finding that people with probable PD exhibit more falls during the day than night is consistent with previous work and extends knowledge to show a similar result in older, more frail people with PD. Characterizing the temporal nature of falls in people with PD can provide additional context to other fall circumstances, thus improving our ability to treat and predict falls in this group.

Epidemiological and microbiological characterization of Candidozyma auris (Candida auris) isolates from a tertiary hospital in Cairo, Egypt: an 18-month study

Abstract Candidozyma auris (formerly Candida auris) has emerged as a significant multidrug-resistant pathogen. Among 140 antifungal-resistant Candida spp. isolates, 120 were identified as C. auris using chromogenic agar, VITEK 2, and MALDI-TOF. Most cases (60%) were males, and 59% were aged ≥ 60 years. Bloodstream infections were predominant (60.8%), followed by respiratory (20.8%), urinary tract (15%), and other sites. Liver transplantation (35.8%) was the most common underlying risk factor, followed by post-COVID-19 (30.8%) and cancer (25%). All isolates exhibited thermotolerance, halotolerance, anaerobic blood hemolysis, and biofilm formation. Significant association was observed between virulence enzymes activity and both specimen source and clinical conditions (P < 0.001), with strong activity linked to blood isolates, liver transplant, post-COVID-19, and lung cancer. Among antifungal agents, voriconazole (MIC50/90: 0.125/0.5 µg/mL), posaconazole (0.03/0.125 µg/mL), and amphotericin B (0.5/1 µg/mL) showed consistently low MICs. Caspofungin (0.25/1 µg/mL) and micafungin (0.125/0.5 µg/mL) demonstrated favorable activity, with resistance rates of 3.3% and 4.2%, respectively. Fluconazole resistance was observed among all isolates (MIC50/90: 32/32 µg/mL). Itraconazole and ketoconazole showed elevated MICs (MIC50/90: 1/4 and 16/64 µg/mL, respectively) and was inactive against all isolates. Flucytosine (MIC50/90: 64/128 µg/mL) was inactive against 96.7%. Agreement between VITEK 2 and CLSI BMD was strong for fluconazole, voriconazole, amphotericin B, caspofungin, and micafungin (Cohen’s kappa ≥ 0.8), but poor for flucytosine (0.35), indicating limited reliability. This report provides crucial local data on antifungal susceptibility and virulence traits of C. auris, supporting infection control and treatment strategies in Egypt.

Honeybee associated Aspergillus niger AW17 as a source of selective anticancer compounds with cytotoxicity evaluation in human cancer cell lines

Abstract Cancer remains a leading cause of death worldwide, necessitating the discovery of novel therapeutic agents with improved efficacy and selectivity. This study investigated the anticancer potential of Aspergillus niger strain AW17 isolated from honeybees, a previously unexplored ecological niche for anticancer drug discovery. The fungal isolate was characterized through morphological, microscopic, and molecular methods, confirming its identity as Aspergillus niger. Chemical profiling using GC-MS and UPLC-MS/MS revealed a complex composition including high oleic acid content (28.88%) and unique compounds like pachymic acid (18.93%), rarely associated with A. niger. The extract’s anticancer activity was evaluated against colorectal (Caco-2), liver (HepG2), breast (MCF-7), and lung (A549) cancer cell lines using MTT assay, confocal microscopy with AO/PI staining, cell cycle analysis, and apoptosis detection. Results demonstrated remarkable selective cytotoxicity of the Aspergillus niger extract against cancer cell lines, following the sensitivity hierarchy HepG2 (IC50 = 5.22 µg/ml) > Caco-2 (26.78 µg/ml) > A549 (34.18 µg/ml) > MCF-7 (55.91 µg/ml), while sparing normal cell lines significantly, with IC50 values of 1454.7 µg/ml for WI-38 and 668.3 µg/ml for HFB-4, indicating high cancer cell selectivity. Confocal microscopy confirmed membrane integrity loss as a primary cytotoxic mechanism. Cell cycle analysis revealed cell-type specific arrest patterns, with Caco-2 and HepG2 exhibiting G1 arrest, while MCF-7 and A549 showed S phase accumulation. Flow cytometry indicated distinct death mechanisms, with Caco-2 undergoing early apoptosis and substantial necrosis, HepG2 showing predominant late apoptosis, and A549 displaying primary necrotic death. These findings highlight the potential of honeybee-associated fungi as sources of novel anticancer compounds with remarkable selectivity, providing new avenues for targeted cancer therapy development and demonstrating the value of exploring specialized ecological niches in natural product discovery.

Feasibility of high-resolution DWI of the healthy dental pulp in human using a hybrid TGSE BLADE sequence

Abstract Clinical evaluation of the human dental pulp is limited to imprecise, subjective methods, necessitating the development of an accurate and objective diagnostic parameter. Diffusion-weighted imaging (DWI) could address this gap; however, no in vivo data are available. To illustrate the feasibility of DWI imaging of the human pulp and to investigate physiological patterns. A turbo gradient spin echo (TGSE) BLADE diffusion MRI sequence was optimized for dental pulp imaging in three volunteers, defining an optimal b-value range and assessing intraindividual fluctuations at 3 T. Apparent diffusion coefficient (ADC) values were calculated in 18 participants using the 2-point and 7-point methods in 329 healthy teeth, analyzing data according to tooth and jaw type. Statistical analysis was performed using Kruskal-Wallis, Wilcoxon signed-rank-test, and one-way ANOVA. Mean pulp ADCs (± SD) for the 2-/7-point methods were 1.219 ± 0.340 / 1.242 ± 0.297 × 10−9 m2/s (p ≤ 0.0001), with intraindividual variations of 0.159 × 10−9 m2/s. Minor but significant differences were observed between tooth types for maxillary premolars vs. maxillary incisors/canines, mandibular canines, and maxillary incisors vs. molars (ADC difference range: 0.209–0.272 × 10−9 m2/s; p-values: 0.0017–0.0473). In vivo assessment of the dental pulp by DWI is feasible and reliable using the TGSE BLADE sequence. Reference ADC values were established, with no substantial differences between jaw and tooth types, indicating that the ADC is a stable intraindividual parameter here. These findings may substantially improve the diagnostic evaluation of pulp diseases to minimize over- and undertreatment.