Search Results (230)

Background: RASopathies represent a clinically and genetically diverse group of syndromes resulting from germline mutations in genes regulating the RAS/mitogen-activated protein kinase (MAPK) signaling cascade. Methods: The aim of this study was to describe the clinical features and genetic variants identified in patients with genetically confirmed Noonan syndrome (NS) in a limited cohort from Romania. A total of 25 patients with positive genetic testing for NS-associated genes were included. Genetic testing was performed primarily using next-generation sequencing. Results: A total of twenty-six variants were identified in twenty-five patients, as one patient carried two pathogenic variants in the PTPN11 gene (c.188A>G and c.922A>G). Of these variants, twenty-four (92.31%) were classified as pathogenic and two (7.69%) as variants of uncertain significance (VUS). Pathogenic variants were found in different genes, including PTPN11, LZTR1, SOS1, and RAF1, with PTPN11 being the most frequently affected gene. Males predominated (17/25), with a male-to-female ratio of approximately 2:1. Two patients inherited the pathogenic variant from an affected parent. Cardiovascular involvement was present in 21 patients (84%), with pulmonary valve stenosis (PVS) being the most common finding (48%), followed by hypertrophic cardiomyopathy (16%). Additional cardiac anomalies included atrial septal defect, valvular regurgitation, dysplastic valves, coarctation of the aorta, and sinotubular junction narrowing. Short stature was observed in 64% of patients, and craniofacial dysmorphism was present in 96%. Cutaneous, ectodermal, dental, ophthalmologic, and auditory manifestations were variably observed. Conclusions: Although based on a limited cohort from Romania, this study provides insights into clinical features suggestive of NS. Our findings highlight the genetic heterogeneity of NS and emphasize the importance of comprehensive genetic testing for confirming diagnosis, guiding clinical management, and supporting family counseling. Full article

Most state-of-the-art machine learning techniques revolve around the optimization of loss functions, making the choice of an objective critical to model performance and reliability. Although recent reviews discuss loss functions in specific domains or in deep learning settings, there is still no single reference that presents widely used losses across major task families within a unified formal setting and with consistent optimization-relevant property annotations. In this survey, we compile and systematize the most widely adopted loss functions for regression, classification, generative modeling, ranking, energy-based modeling, and relational learning. Our selection procedure combines seeding from foundational textbooks and prior surveys with cross-checking of highly cited literature and common implementations in mainstream machine learning frameworks. We introduce 52 loss functions and organize them into an intuitive taxonomy, summarizing their theoretical motivation, key mathematical properties, and typical application contexts, with compact appendix tables for quick lookup. This survey is intended as a resource for undergraduate, graduate, and Ph.D. students, as well as researchers seeking a structured reference for selecting and comparing loss functions. Full article

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that severely affects cognitive, behavioral, and functional abilities, creating a substantial burden for family members who provide continuous care. Caregivers often experience role changes, occupational imbalance, emotional distress, and reduced quality of life, although some report personal growth. These experiences extend beyond active caregiving and include anticipatory grief during disease progression and grief after the relative’s death. Despite this continuum, few studies have examined caregiving, loss, and bereavement from an integrative perspective. This protocol describes a mixed-methods study aimed at exploring the lived experiences of family caregivers of individuals with AD, focusing on how evolving relational, occupational, and identity-related losses influence their well-being and adaptation. Methods: A parallel convergent mixed-methods design will be used. The quantitative component consists of a cross-sectional observational study including 66 caregivers recruited through purposive sampling across kinship categories (spouse/partner, adult child, grandchild) and care settings (home care with day-center attendance vs. institutionalized care). Data will be collected using the Zarit Burden Interview, Role Checklist, Short Form-36 Health Survey, and Occupational Balance Questionnaire. Descriptive and subgroup analyses will be conducted using SPSS (version 27). The qualitative component comprises a multiple-case study with approximately 36 participants across three groups: caregivers living with individuals with AD, caregivers of institutionalized relatives, and bereaved family members. Semi-structured interviews (45–80 min) will be conducted online or in person, transcribed verbatim, and analyzed thematically using MAXQDA (version 26). Integration will follow a concurrent approach, combining quantitative and qualitative results through joint narratives and displays to produce a comprehensive interpretation. Discussion: This study aims to deepen understanding of the caregiving–grief continuum in families affected by AD by integrating quantitative indicators of burden, health status, and occupational balance with qualitative accounts of adaptation and meaning-making. Findings are expected to support the development of holistic, evidence-based interventions that promote caregiver well-being throughout the care trajectory and during bereavement. Ethics and Dissemination: Ethical approval was granted by the Research Ethics Committee of Universidad Rey Juan Carlos (Code: 041220246522024; 15 October 2025). ClinicalTrials.gov Identifier: NCT07251738. Registered November 2025. Protocol version: Version 2. Full article

Background: This study aims to explore the potential factors that can support Ph.D. students in completing their theses in a timely manner while maintaining their mental well-being. Theory: Based on the JD-R model, we discriminate between two independent processes: (1) Job demands are a health impairment process that may lead to exhaustion and burnout. (2) Job resources are a motivational process that may lead to job satisfaction and engagement. In this study, we also wanted to explore grit as a potential mediator variable and how it could impact exhaustion at work and work engagement among Ph.D. students. Methods: A cross-sectional web-based survey design was used, from a sample of 194 Ph.D. students in Norway. Data were analyzed through structural equation modeling. Results: Our results indicated that demands at work, not resources, had a positive significant effect on Ph.D. students’ grit, which acted as a mediator variable for exhaustion at work and work engagement. Conclusions: This study improves our understanding of the factors affecting Ph.D. students’ mental well-being and sheds light on how institutions can optimize resources and demands to promote timely thesis completion while minimizing the risk of severe mental health challenges. Full article

Facial profile esthetics play a pivotal role in orthodontic diagnoses, treatment planning, and patient satisfaction; however, the perception of facial attractiveness is inherently subjective and varies according to professional expertise and sociocultural background. This study aimed to compare the perceived attractiveness of standardized sagittal facial profiles across skeletal Class I, II, and III patterns and to investigate the influence of professional training and sociodemographic variables on facial profile evaluations. It was hypothesized that straight facial profiles would be perceived as the most attractive across all observer groups, while deviations from the orthognathic profile would be rated as less attractive, with significant differences based on professional training and sociodemographic variables. This cross-sectional descriptive study included 509 participants, comprising orthodontists, orthodontic Ph.D. students, general dentists, specialist dentists, first- and fifth-year dental students, and laypersons. Seven standardized sagittal facial profile silhouettes (S1–S7) were digitally generated from a standardized lateral facial photograph and evaluated using a seven-point visual analog scale. Participants were also asked to identify the sagittal facial profile range (S8) they ideally preferred to possess. Intergroup comparisons were performed using non-parametric statistical tests (Mann–Whitney U and Kruskal–Wallis). The straight profile (S3) emerged as the most attractive and most frequently preferred across all participant groups, confirming its role as the dominant esthetic reference. Retrusive profiles, particularly bimaxillary retrusion (S2), mandibular retrognathism (S5), and maxillary retrusion (S6), were consistently rated as the least attractive. Significant differences in esthetic perceptions were observed according to the professional expertise, educational level, age, and nationality, whereas gender had no clinically meaningful effect. Orthodontic training was associated with increasingly critical evaluations, especially for protrusive and convex profiles, while laypersons demonstrated greater esthetic tolerance. Both anatomical characteristics and sociocultural experience shape the perception of facial profile esthetics. While the straight profile represents a widely shared aesthetic ideal, increasing orthodontic expertise accentuates discrepancies between professional standards and public preferences. These findings underscore the necessity of integrating patient-centered and culturally sensitive considerations into contemporary orthodontic treatment planning. Full article

Firm requirements on electromagnetic compatibility (EMC) of electronic devices demand low electromagnetic emissions (EMI) of high-speed circuits, especially in the automotive industry. To be able to apply cost-effective anti-perturbative measures that reduce noise emission, critical signal integrity and power integrity (SI/PI) tools are needed for developing high-speed printed circuit board (PCB) designs. This paper presents an efficient method for modeling and analyzing the current drawn by digital ICs based on SPICE modeling data. The profile of the current drawn by the ICs from the power supply is composed of the static supply current and the dynamic supply current. This method enables power integrity engineers, in particular, PhD students and researchers who aim to develop an intuitive understanding of PI phenomena during the pre-layout phase, to see the hidden impact of the supply current on the power rail noise through time domain simulations, using a complex simulation model that integrates the Finite-Difference Time-Domain (FDTD) method of modeling the power and ground plane, with Voltage Regulator Modules (VRMs) and decoupling capacitors. A comparison of simulation results between the proposed models and SPICE IC models is also included to validate the proposed model. Full article

In recent decades, the burden of TB has been gradually declining; however, with the emergence of COVID-19 and ongoing political conflicts, including the war in Ukraine, the proper functioning of healthcare services and TB control programs has been jeopardized. Recently, research has emphasized the importance of hematological parameters associated with inflammation, which can be easily analyzed through routine blood tests. Combining these parameters may have predictive value for various diseases, including pulmonary tuberculosis and even help monitor the effectiveness of treatment. Since there is no single hematological or inflammatory biomarker that provides precise and dynamic information about the success or failure of treatment, identifying individual markers or sets of biomarkers with higher sensitivity and specificity is essential. This is particularly important since sputum culture conversion at two months remains insufficiently sensitive and microscopy conversion has limited sensitivity and specificity in detecting treatment failure. Also, the analysis of the impact of the standard directly observed treatment, short-course regimen on pathogenic mechanisms also focuses on how it influences the interaction between inflammation and oxidative tissue degradation, by measuring plasma levels of glutathione. Utilizing a combination of hematological, inflammatory, and antioxidant biomarkers offers significant insights into systemic inflammatory responses in pulmonary tuberculosis patients, both before commencing treatment and during the entire duration of antituberculosis therapy. Combining different inflammatory parameters into a multiple biomarker can significantly enhance the accuracy of predicting prognosis and response to antibiotic chemotherapy. Identifying an optimal combination of biomarkers with predictive value is crucial for assessing treatment response and evaluating the effectiveness of anti-TB medication. Rather than developing or testing a composite prediction model, this review summarizes reported performance metrics from individual studies and highlights priorities for future prospective validation of integrated biomarker panels. Full article

Background: Post-COVID-19 syndrome (PCS) is defined as the persistence or development of new symptoms 3 months after the initial infection with the SARS-CoV-2 virus, these clinical aspects being most often associated with functional respiratory changes, as well as imagistic modifications. This study aimed to evaluate longitudinal changes in pulmonary function among patients with PCS, in relation to the severity of the acute COVID-19 episode and the time elapsed since infection. Methods: A retrospective, observational study was conducted at the Clinical Hospital of Pulmonary Diseases Iași, Romania, between January 2021 and December 2022, including 97 adult patients with confirmed PCS. Demographic, clinical, and functional data were collected from medical records. Pulmonary function tests (PFTs) were performed according to ATS/ERS standards, assessing Forced Vital Capacity (FVC), Forced Expiratory Volume in the First Second (FEV₁), FEV₁/FVC ratio (Tiffeneau Index), Maximal Expiratory Flow at 50% and 25% of FVC (MEF50, MEF25), Diffusing Capacity of the Lung for Carbon Monoxide (adjusted for haemoglobin) (DLCO), Carbon Monoxide Transfer Coefficient (KCO), Alveolar Volume (AV), Total Lung Capacity (TLC) and Residual Volume (RV). Patients were grouped by time elapsed since infection (1–3, 4–7, 9–12, and up to 22 months). Statistical analyses included the Mann–Whitney U test, Spearman’s correlation, ROC curve analysis, and Principal Component Analysis (PCA). Results: A progressive improvement in FVC was observed up to 9–18 months post-infection (p < 0.05), while FEV₁ remained stable, suggesting a predominantly restrictive ventilatory pattern. Patients with moderate acute COVID-19 presented significantly lower FVC%, FEV₁%, DLCO%, and KCO% values compared with those with mild disease (p < 0.05). Diffusion abnormalities (DLCO and KCO) persisted beyond 12 months, indicating lasting alveolar-capillary impairment. ROC analysis identified TLC (AUC = 0.857), AV (AUC = 0.855), and KCO (AUC = 0.805) as the most discriminative parameters for residual dysfunction. PCA revealed three major functional domains—airflow limitation, diffusion capacity, and lung volume—explaining up to 70% of total variance. Conclusions: We are facing the emergence of a new phenomenon, namely a secondary post-COVID-19 pandemic of patients confronting with persistent post-COVID-19 symptoms who present with functional respiratory changes and who require careful monitoring in dynamics, personalized treatments and a multidisciplinary approach. Full article

This paper presents a hybrid knowledge-based expert system (KBES) designed to predict crack incubation and fatigue life in gear design, serving as both a research tool and an educational resource. While crack growth and initiation are well understood, crack incubation remains a challenging area. The presented expert system (KBES) integrates a novel mathematical model for crack incubation based on analogy and defect analysis principles with an optimization algorithm for gear design. The system uses genetic algorithms to optimize gear parameters, demonstrating a 5–10% deviation from experimental values in a specific gear design problem case study. Based on this KBES and a hybrid approach, we developed a learning environment based on an intelligent tutoring system (ITS) which serves older students (MSc and PhD) as a learning environment for the acquisition of knowledge and, above all, for the development of an in-depth understanding of the phenomena that occur both during incubation and initialization and during the further propagation of cracks in the root of the gear tooth, which is the basis for determining the lifespan of gear transmissions. Full article

Background/Objectives: Differentiating benign, premalignant, and early malignant vocal fold lesions is challenging. Perpendicular vascular changes (PVCs) per the European Laryngological Society (ELS) are key malignancy indicators. Enhanced contact endoscopy with narrow-band imaging (NBI-CE) visualizes intrapapillary capillary loops (IPCLs) at high magnification, independent of gross morphology. However, defining malignancy as any PVC increases sensitivity but lowers specificity—particularly in papillomas—whereas limiting malignancy to narrow-angle PVC improves specificity but risks false negatives and reduced reproducibility. Methods: We intraoperatively evaluated 146 histology-proven vocal fold lesions using NBI-CE. Six raters (three experienced otolaryngologists, three PhD students) classified vascular patterns. Two approaches were tested: (1) malignancy = narrow-angle PVC; (2) malignancy = any PVC. Outcomes were accuracy, sensitivity, specificity, and interrater agreement. Results: Approach (1) had higher specificity but lower sensitivity than (2) (~85% vs. ~70% specificity; ~50% vs. ~80% sensitivity). Accuracy did not differ significantly. Experienced raters showed higher interrater agreement and a more favorable sensitivity–specificity balance. Common errors were false positives in papillomas and false negatives in dysplasia/early carcinoma. Conclusions: PVC assessment with NBI-CE is feasible and informative. Choosing between “any PVC” and “narrow-angle only” entails a sensitivity–specificity trade-off and depends on lesion type and experience. Refined ELS descriptors and automated analysis may improve reproducibility and accuracy. Full article

Objectives: This study aims to evaluate teachers’ lifestyle habits and to investigate their knowledge and behaviors related to cancer screening. Methods: This cross-sectional survey was performed among teachers randomly selected from schools located in the Campania region, Italy. Results: Only 17% of the teachers were current smokers, while 72.1% consumed alcohol. Female teachers, those who were married/cohabitant, and those who discussed with students about alcohol consumption were more likely to have never smoked or drunk alcohol. Female and older teachers, those with a university or a master/PhD degree, and those who had a moderate/high level of physical activity (PA) were more likely to sufficiently consume fruits and vegetables. Only 20.9% of teachers had a moderate/high level of PA. Those who had at least one child, who taught humanistic and support disciplines, and who needed additional information on healthy lifestyle habits were less likely to have a moderate/high level of PA. Among participants, 42.3% had ever undergone mammography for screening and 37.5% a Pap test and a fecal occult blood test. Conclusions: This survey describes a worrying prevalence of unhealthy behaviors and low adherence to screening programs among Italian teachers, suggesting the need for education and screening campaigns to improve preventive strategies in this population. Full article

Action bias, the cognitive tendency to favor action over inaction regardless of its necessity, has been extensively studied across domains such as behavioral economics, organizational behavior, and policy development. However, its manifestation in educational contexts remains critically underexplored. In the digital age, with an abundance of both factual and misleading information, the persistence of action bias within education jeopardizes the cultivation of initial critical thinking capable of addressing multifaceted global challenges. The analysis indicates how institutional norms may foster a performative academic identity that conflates speed and compliance with intellectual competence. Through workshops conducted with university students ranging from undergraduate to PhD levels, participants were tasked with solving a practical yet ambiguous problem to highlight potential cognitive differences across educational stages. Despite prior training in critical thinking, participants consistently defaulted to immediate ideation, bypassing fundamental inquiries into the problem’s legitimacy or broader implications. Using a sensemaking approach, this study demonstrates that reflexive actions are not interpreted as merely cognitive shortcuts but behaviors shaped by educational systems prioritizing visible outputs over critical inquiry. The findings reveal how institutional norms foster a performative academic identity, conflating speed and compliance with intellectual competence. This research challenges traditional pedagogical models, advocating for educational reforms that emphasize assessing the process of learning. By situating action bias within the broader framework of active learning, this study offers actionable insights for educators, policy makers and researchers to foster critical innovative thinking, essential in an increasingly digital future. Full article

Norovirus (NoV) is a symptomatic virus that is the leading cause of gastrointestinal disease. It spreads easily through the fecal–oral route and contact with contaminated food or surfaces. Maintaining a high level of hygiene in food industry settings and refocusing food production on isolating and testing natural compounds that exhibit antimicrobial and antioxidant properties are important elements in preventing NoVs infection. This study evaluated plant extracts prepared by cold brew and cold concentrate techniques for their antioxidant and antiviral activity. The extracts obtained demonstrated high antioxidant activity, with notable variation depending on the plant material, ranging from moderate to very strong levels. Correspondingly, high antiviral potential was observed, reaching the nearly complete inactivation of the virus. Remarkably, the highest virucidal effects were already achieved at relatively elevated, but not maximal, antioxidant activity levels. The results of the study indicate that cold water extraction techniques allow for the obtention of plant extracts showing strong virus-inactivating activity and favorable antioxidant activity. Full article

Hyperpolarization (HP) techniques, such as Parahydrogen-Induced Polarization (PHIP), Signal Amplification by Reversible Exchange (SABRE), and dissolution Dynamic Nuclear Polarization (d-DNP), significantly enhance the sensitivity of nuclear magnetic resonance (NMR) spectroscopy for chemical analysis and metabolic imaging. However, the high cost of equipment, ranging from tens of thousands to millions of dollars, limits accessibility of hyperpolarization for the broad scientific community. In this work, we aim to mitigate some of the challenges by developing a cost-effective solution for parahydrogen (pH₂)-based PHIP and SABRE HP methods. A custom coil-winding machine was designed to fabricate solenoid magnet coils, which were then evaluated for their magnetic field profiles, demonstrating a high degree of magnetic field homogeneity. A model ¹H SABRE experiment successfully implemented the constructed solenoid, achieving efficient hyperpolarization. Additionally, the solenoid magnet can be utilized for in situ detection of hyperpolarization when integrated with a low-field NMR spectrometer, reducing the total setup cost to a few thousand dollars. These findings suggest that our approach makes HP technology more affordable and accessible, potentially broadening its applications in chemical and biomedical research, as well as educational settings involving undergraduate student researchers. This work provides a practical pathway to lower the financial barriers associated with pH₂ HP setups. Full article

This study compared the yield, percentage solids, electrophoretic profile, gelatinolytic activity, and brine shrimp lethality of Bitis arietans venom prepared using freeze-drying and desiccator drying. Bitis arietans venom was collected from snakes at Bioken snake farm, Kenya, whereafter it was pooled and divided into two parts. Part 1 was desiccator dried venom (DDV) while part 2 was freeze-dried venom (FDV). The yield and percentage solids in DDV and FDV were compared using Welch’s Student’s t-test and the dried venoms were subsequently subjected to sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), 2D electrophoresis, gelatin in-gel zymography, and brine shrimp lethality assays. Mean venom yield and percentage solids did not differ between DDV and FDV (p = 0.5647 and p = 0.4676, respectively). SDS-PAGE and two-dimensional (2D) electrophoresis revealed similar protein profiles for DDV and FDV, showing bands and spot clusters within molecular weight ranges of ~16 kDa to >150 kDa and pH ranging from 3.5 to 9.5. Enzyme zymography revealed comparable gelatinolytic activity between DDV and FDV. However, the brine shrimp lethality assay indicated significantly higher toxicity in DDV (LC₅₀: 86.57 μg/mL) compared to FDV (LC₅₀: 460.37 μg/mL). DDV also showed greater lethality than FDV at 100 μg/mL (p = 0.0416) and 1000 μg/mL (p = 0.0008) but not at 10 μg/mL (p = 0.2465). These findings suggest that DDV exhibits higher toxicity in brine shrimp larvae than FDV, although both drying methods result in similar yields, percentage solids, venom profile, and gelatinolytic activity. Further research is necessary to investigate the mechanism behind this difference and its implications for antivenom production and long-term stability of venom. Full article