Search Results (2,112)

Alagille syndrome (ALGS) is a multisystem disorder characterized by a paucity of intrahepatic bile ducts and cholestasis, often requiring liver transplantation before adulthood. Due to the lack of genotype–phenotype correlation, case series are essential to understand disease presentation and prognosis. Data on Mexican ALGS patients are limited. Therefore, we aimed to characterize a large series of Mexican patients by consolidating cases from major institutions and independent geneticists, with the goal of generating one of the most comprehensive cohorts in Latin America. We retrospectively analyzed clinical records of pediatric ALGS patients, focusing on demographics, clinical features, laboratory and imaging results, biopsy findings, and transplant status. Genetic testing was performed for all cases without prior molecular confirmation. We identified 52 ALGS cases over 13 years; 22 had available clinical records. Of these, only 6 had molecular confirmation at study onset, prompting genetic testing in the remaining 16. We identified six novel JAG1 variants and several previously unreported phenotypic features. A liver transplantation rate of 13% was observed in the cohort. This study represents the largest molecularly confirmed ALGS cohort in Mexico to date. Novel genetic and clinical findings expand the known spectrum of ALGS and emphasize the need for improved therapies, such as IBAT inhibitors, which may alleviate symptoms and reduce the need for transplantation. Full article

Background: While a few studies suggest that depigmentation tends to develop more frequently in patients with malignant melanoma (MM), the association between vitiligo and MM has been sparsely investigated in the setting of controlled studies. Methods: A population-based case–control study compared 14,632 patients with vitiligo with 71,580 control subjects matched by age, sex, and ethnicity regarding the prevalence of preexisting MM. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CIs) of developing vitiligo both in univariate and multivariate models, adjusting for demographic variables and comorbidities. The OR was also stratified by age, sex, ethnicity, and ultraorthodox status. Results: The prevalence of preexisting MM was statistically comparable between individuals with vitiligo and controls (0.30% vs. 0.35%, respectively). In the general study population, a history of MM was not significantly associated with an elevated likelihood of developing vitiligo (multivariate OR, 1.03; CI 95%, 0.76–1.40). Among the Arab population, however, preexisting MM was associated with a sixfold-increased likelihood of subsequent vitiligo (univariate OR, 6.55; 95% CI, 1.46–29.27). Patients with vitiligo and comorbid MM were older at the onset of vitiligo, had a higher burden of comorbid conditions, and showed an overrepresentation of Jewish ancestry. Conclusions: A history of MM does not increase the probability of vitiligo in the general Israeli population, except among the Arab minority, who show a sixfold-elevated odds of vitiligo after MM. Further investigation is essential to gain deeper insights into this relationship. Full article

Piezo1 is a mechanosensitive non-selective cation channel. Genetic alterations of the channel result in a hematologic phenotype named Hereditary Xerocytosis. With Yoda1 and, more recently, Yoda2, compounds to increase the activity of Piezo1 have become available. However, their concrete effect depends on the nano environment of the channel and hence on the cell type. Here we compare the potency of Yoda1 and Yoda2 in red blood cells (RBCs). We investigate the effect of the compounds on direct channel activity using automated patch clamp, as well as the secondary effects of channel activation on signalling molecules and cellular response. In terms of signalling, we investigate the temporal response of the second messenger Ca²⁺, and in terms of cellular response, the activity of the Gárdos channel. The opening of the Gárdos channel leads to a hyperpolarisation of the RBCs, which is measured by the Macey–Bennekou–Egée (MBE) method. Although the interpretation of the data is not straightforward, we discuss the results in a physiological context and provide recommendations for the use of Yoda1 and Yoda2 to investigate RBCs. Full article

Titanium alloys are frequently subjected to surface treatments to enhance their biocompatibility and corrosion resistance in biological environments. Plasma electrolytic oxidation (PEO) is an environmentally friendly electrochemical technique capable of forming oxide layers characterized by high corrosion resistance, biocompatibility, and strong adhesion to the substrate. In this study, the PEO process was performed using a low-melting-point ternary eutectic electrolyte composed of Ca(NO₃)₂–NaNO₃–KNO₃ (41–17–42 wt.%) with the addition of ammonium dihydrogen phosphate (ADP). The use of this electrolyte system enables a reduction in the operating temperature from 280 to 160 °C. The effects of applied voltage from 200 to 400V, current frequency from 50 to 1000 Hz, and ADP concentrations of 0.1, 0.5, 1, 2, and 5 wt.% on the growth of titanium oxide composite coatings on a Ti-6Al-4V substrate were investigated. The incorporation of Ca and P was confirmed by phase and chemical composition analysis, while scanning electron microscopy (SEM) revealed a porous surface morphology typical of PEO coatings. Corrosion resistance in Hank’s solution, evaluated via Tafel plot fitting of potentiodynamic polarization curves, demonstrated a substantial improvement in electrochemical performance of the PEO-treated samples. The corrosion current decreased from 552 to 219 nA/cm², and the corrosion potential shifted from −102 to 793 mV vs. the Reference Hydrogen Electrode (RHE) compared to the uncoated alloy. These findings indicate optimal PEO processing parameters for producing composite oxide coatings on Ti-6Al-4V alloy surfaces with enhanced corrosion resistance and potential bioactivity, which are attributed to the incorporation of Ca and P into the coating structure. Full article

Evaluating risk in complex systems relies heavily on human auditors whose subjective assessments can be compromised by knowledge gaps and varying interpretations. This subjectivity often results in inconsistent risk evaluations, even among auditors examining identical systems, owing to differing pattern recognition processes. In this study, we propose a causality model that can improve the comprehension of risk levels by breaking down the risk factors and creating a layout of risk events and consequences in the system. To do so, the initial step is to define the risk event blocks, each comprising two distinct components: the agent and transfer mechanism. Next, we construct a causal map that outlines all risk event blocks and their logical connections, leading to the final consequential risk. Finally, we assess the overall risk based on the cause-and-effect structure. We conducted real-world illustrative examples comparing risk-level assessments with traditional experience-based auditor judgments to evaluate our proposed model. This new methodology offers several key benefits: it clarifies complex risk factors, reduces reliance on subjective judgment, and helps bridge the gap between subjective and objective uncertainty. The illustrative examples demonstrate the potential value of the model by revealing discrepancies in risk levels compared to traditional assessments. Full article

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymatic disorder, affects over 500 million people worldwide and is often linked to exercise intolerance due to oxidative stress, but its true impact on physical performance remains unclear. This study aimed to evaluate the physiological and metabolic effects of G6PD deficiency on endurance capacity. Using humanized mice carrying the African G6PD variant [V68M; N126D] (hG6PD_A−), we show that despite reduced pentose phosphate pathway activity, these mice exhibit a 10.8% increase in treadmill critical speed (CS)—suggesting enhanced endurance capacity. Multi-omics profiling across red blood cells, plasma, skeletal muscle, spleen, kidney, and liver reveals metabolic adaptations, including elevated glycolysis, fatty acid oxidation, and increased mitochondrial activity, alongside heightened oxidative phosphorylation in muscle and accelerated red blood cell turnover in the spleen and liver. These findings indicate that systemic metabolic reprogramming may offset antioxidant deficiencies, potentially conferring a performance advantage. Given that G6PD deficiency affects up to 13% of African Americans and is associated with cardiovascular health disparities, our results challenge conventional exercise restrictions and highlight the need for personalized exercise guidelines for affected individuals. Full article

Background/Objectives: Accurate assessment of speech intelligibility is necessary for individuals with motor speech disorders. Transcription or scaled rating methods by naïve listeners are the most reliable tasks for these purposes; however, they are often resource-intensive and time-consuming within clinical contexts. Automatic speech recognition (ASR) systems, which transcribe speech into text, have been increasingly utilized for assessing speech intelligibility. This study investigates the feasibility of using an open-source ASR system to assess speech intelligibility in Hebrew and English speakers with Down syndrome (DS). Methods: Recordings from 65 Hebrew- and English-speaking participants were included: 33 speakers with DS and 32 typically developing (TD) peers. Speech samples (words, sentences) were transcribed using Whisper (OpenAI) and by naïve listeners. The proportion of agreement between ASR transcriptions and those of naïve listeners was compared across speaker groups (TD, DS) and languages (Hebrew, English) for word-level data. Further comparisons for Hebrew speakers were conducted across speaker groups and stimuli (words, sentences). Results: The strength of the correlation between listener and ASR transcription scores varied across languages, and was higher for English (r = 0.98) than for Hebrew (r = 0.81) for speakers with DS. A higher proportion of listener–ASR agreement was demonstrated for TD speakers, as compared to those with DS (0.94 vs. 0.74, respectively), and for English, in comparison to Hebrew speakers (0.91 for English DS speakers vs. 0.74 for Hebrew DS speakers). Listener–ASR agreement for single words was consistently higher than for sentences among Hebrew speakers. Speakers’ intelligibility influenced word-level agreement among Hebrew- but not English-speaking participants with DS. Conclusions: ASR performance for English closely approximated that of naïve listeners, suggesting potential near-future clinical applicability within single-word intelligibility assessment. In contrast, a lower proportion of agreement between human listeners and ASR for Hebrew speech indicates that broader clinical implementation may require further training of ASR models in this language. Full article

There has been a growing trend of young people coming out as Lesbian, Gay, Bisexual, Transgender, Queer (LGBTQ) in recent years. Research on the relationship between LGBTQ grandchildren and their grandparents is limited and primarily focuses on the grandchildren’s perspective. This pilot study seeks to understand the relationship between grandparents and their LGBT grandchildren, from the grandparents’ perspective. Six Israeli grandparents were interviewed using a qualitative methodology, guided by a semi-structured interview protocol. Analysis of the interviews revealed three main themes: grandparents’ exposure to the grandchildren’s sexual orientation and their gender identity; the shattering of the grandparents’ dream and concern for the grandchild; and the relations between the grandparents and their LGBT grandchildren. The research findings in this pilot study indicate that the relations remained close and did not change following disclosure of the sexual orientation. However, some grandparents needed time to resume their regular relationship. The insights learned from the research findings regarding the process undergone by the grandparents upon discovering their grandchildren’s sexual orientation can help professionals treat and counsel family members, when necessary, how to bridge the gaps, and rebuild the relations between the grandparent and the grandchild, as these relations are important for the well-being of both. Full article

Hydrazine, a highly toxic and reactive compound widely used as rocket fuel, poses significant environmental and health risks, particularly in long-term space missions. This study investigates the cometabolic capacity of Chlorella vulgaris and seven extremophilic Bacillus spp. strains—isolated from the arid Dead Sea region—to tolerate and degrade hydrazine at concentrations up to 25 ppm. The microalga C. vulgaris reduced hydrazine levels by 81% within 24 h at 20 ppm, while the Bacillus isolates achieved an average reduction of 45% over 120 h. Identified strains included B. licheniformis, B. cereus, and B. atrophaeus. Co-culture experiments demonstrated that C. vulgaris and B. cereus (isolate ISO-36) stably coexisted without antagonistic effects, suggesting a synergistic detoxification interaction. Flow cytometry revealed that most bacteria transitioned into spores under stress, highlighting a survival adaptation. Titanium, representing a biocompatible material common in aerospace hardware, did not inhibit microbial growth or hydrazine degradation. These findings underscore the potential of Dead Sea-derived microbial consortia for cometabolic hydrazine detoxification and support the feasibility of converting spacecraft components into functional photobioreactors. This approach offers dual-use benefits for space missions and industrial wastewater treatment. Future studies should investigate degradation pathways, stress resilience, and bioreactor scale-up. Full article

Background/Objectives: Laboratory tests conducted in community settings are occasionally repeated within hours of presentation to pediatric emergency departments (PEDs). Reducing unnecessary repetitions can ease child discomfort and alleviate the healthcare burden without compromising the diagnostic process or quality of care. The aim of this study was to develop a decision tree (DT) model to guide physicians in minimizing unnecessary repeat blood tests in PEDs. The minimal decision tree (MDT) algorithm was selected for its interpretability and capacity to generate optimally pruned classification trees. Methods: Children aged 3 months to 18 years with community-based complete blood count (CBC), electrolyte (ELE), and C-reactive protein (CRP) measurements obtained between 2016 and 2023 were included. Repeat tests performed in the pediatric emergency department within 12 h were evaluated by comparing paired measurements, with tests considered justified when values transitioned from normal to abnormal ranges or changed by ≥20%. Additionally, sensitivity analyses were conducted for absolute change thresholds of 10% and 30% and for repeat intervals of 6, 18, and 24 h. Results: Among 7813 children visits in this study, 6044, 1941, and 2771 underwent repeated CBC, ELE, and CRP tests, respectively. The mean ages of patients undergoing CRP, ELE, and CBC testing were 6.33 ± 5.38, 7.91 ± 5.71, and 5.08 ± 5.28 years, respectively. The majority were of middle socio-economic class, with 66.61–71.24% living in urban areas. Pain was the predominant presented complaint (83.69–85.99%), and in most cases (83.69–85.99%), the examination was conducted by a pediatrician. The DT model was developed and evaluated on training and validation cohorts, and it demonstrated high accuracy in predicting the need for repeat CBC and ELE tests but not CRP. Performance of the DT model significantly exceeded that of the logistic regression model. Conclusions: The data-driven guide derived from the DT model provides clinicians with a practical, interpretable tool to minimize unnecessary repeat laboratory testing, thereby enhancing patient care and optimizing healthcare resource utilization. Full article

The general framework of Entropic Dynamics (ED) is used to construct non-relativistic models of relational Quantum Mechanics from well-known inference principles—probability, entropy and information geometry. Although only partially relational—the absolute structures of simultaneity and Euclidean geometry are still retained—these models provide a useful testing ground for ideas that will prove useful in the context of more realistic relativistic theories. The fact that in ED the positions of particles have definite values, just as in classical mechanics, has allowed us to adapt to the quantum case some intuitions from Barbour and Bertotti’s classical framework. Here, however, we propose a new measure of the mismatch between successive states that is adapted to the information metric and the symplectic structures of the quantum phase space. We make explicit that ED is temporally relational and we construct non-relativistic quantum models that are spatially relational with respect to rigid translations and rotations. The ED approach settles the longstanding question of what form the constraints of a classical theory should take after quantization: the quantum constraints that express relationality are to be imposed on expectation values. To highlight the potential impact of these developments, the non-relativistic quantum model is parametrized into a generally covariant form and we show that the ED approach evades the analogue of what in quantum gravity has been called the problem of time. Full article

Accurate characterization of oleosome particle size distribution is needed for understanding their functionality in various applications. Traditionally, high-cost methods such as static laser diffraction and confocal or electron microscopy have been used. The current study presents a cost-effective alternative by combining optical microscopy (OM) with image analysis and dynamic light scattering (DLS) to evaluate particle size distribution in safflower (Carthamus tinctorius) oleosomes. Monodisperse and polydisperse standards (2 µm and 1–10 µm, respectively) were selected to validate instrument performance. The use of a smaller cuvette with a shorter path length in DLS extended its detection capabilities by minimizing multiple scattering and thermal effects. DLS and OM produced relatively consistent results, accurate particles’ diameters and distribution widths that agreed well with the standards. In contrast, static light scattering (SLS) showed strong sensitivity to the weighting method used (by number vs. by volume). In the case of polydisperse standard, volume-weighted SLS overestimated the particle size and yielded a broader distribution with a span of 2.2 compared to a span value of 0.8 as reported by the supplier. These findings highlight the importance of method selection and demonstrate the potential of combining DLS and OM as a practical and reliable approach for oleosome characterization. Full article

This paper reviews the variability of passenger service time (PST) at the platform–train interface (PTI), a critical performance indicator in metro systems shaped by the infrastructure design, affecting passenger behavior and accessibility. Despite its operational importance, PST remains underexplored in relation to crowd management strategies. This review synthesizes findings from empirical and experimental research to clarify the main factors influencing PST and their implications for platform-level interventions. Key contributors to PST variability include door width, gap dimensions, crowd density, and user characteristics such as mobility impairments. Design elements—such as platform edge doors, yellow safety lines, and vertical handrails—affect flow efficiency and spatial dynamics during boarding and alighting. Advanced tracking and simulation tools (e.g., PeTrack and YOLO-based systems) are identified as essential for evaluating pedestrian behavior and supporting Level of Service (LOS) analysis. To complement traditional LOS metrics, the paper introduces Level of Interaction (LOI) and a multidimensional LOS framework that captures spatial conflicts and user interaction zones. Control strategies such as platform signage, seating arrangements, and visual cues are also reviewed, with experimental evidence showing that targeted design interventions can reduce PST by up to 35%. The review highlights a persistent gap between academic knowledge and practical implementation. It calls for greater integration of empirical evidence into policy, infrastructure standards, and operational contracts. Ultimately, it advocates for human-centered, data-informed approaches to PTI planning that enhance efficiency, inclusivity, and resilience in high-demand transit environments. Full article

A reduced representation of a dynamical system helps us to understand what the true degrees of freedom of that system are and thus what the possible instabilities are. Here we extend previous work on barotropic flows to the more general non-barotropic flow case and study the implications for variational analysis and conserved quantities of topological significance such as circulation and helicity. In particular we introduce a four-function Eulerian variational principle of non-barotropic flows, which has not been described before. Also new conserved quantities of non-barotropic flows related to the topological velocity field, topological circulation and topological helicity, including a local version of topological helicity, are introduced. The variational formalism given in terms of a Lagrangian density allows us to introduce canonical momenta and hence a Hamiltonian formalism. Full article

The DFT method was used to evaluate the adsorption of methyl radicals and the evolution of ethane on the M(111) (M = Co, Ni, Pd, Pt) surfaces, eight metal atoms, in aqueous medium. A maximum of five and four radicals can be adsorbed on Co(111) and Ni(111), respectively, and six on Pd(111) and Pt(111) (top site). The ethane evolution occurs via the Langmuir–Hinshelwood (LH) or Eley–Rideal (ER) mechanisms. The production of ethane through the interaction of two adsorbed radicals is thermodynamically feasible for high coverage ratios on the four surfaces; however, kinetically, it is feasible at room temperature only on Co(111) at a coverage of (5/5) and on Pd(111) at a coverage ratio of 4/6, 5/6, and 6/6. Ethane production occurs via the ER mechanism: a collision with solvated methyl radical produces either C₂H₆ or ${\mathrm{C}\mathrm{H}}_2^{\ast }+{\mathrm{C}\mathrm{H}}_{4\left(\mathrm{a}\mathrm{q}\right)}$. On Pd(111) the product is only C₂H₆, on Pt(111), both products (C₂H₆ or ${\mathrm{C}\mathrm{H}}_2^{\ast }$) are plausible, and on Co(111) and Ni(111), only ${\mathrm{C}\mathrm{H}}_2^{\ast }+{\mathrm{C}\mathrm{H}}_{4\left(\mathrm{a}\mathrm{q}\right)}$ is produced. Further reactions of ${\mathrm{C}\mathrm{H}}_2^{\ast }$ with ${\mathrm{C}\mathrm{H}}_2^{\ast }$ or ${\mathrm{C}\mathrm{H}}_3^{\ast }$ to give ${\mathrm{C}}_2{\mathrm{H}}_4^{\ast }$ or ${\mathrm{C}}_2{\mathrm{H}}_5^{\ast }$ are thermodynamically plausible only on Pt(111); however, they are very slow due to high energy barriers, 1.48 and 1.36 eV, respectively. Full article