Search Results (366)

Protein-based APIs represent a big group of modern therapeutics. Their characterization involves complex analytical protocols which require special methods, especially in the case when the protein drug is included into tablet dosage forms. Although the fluorescence polarization assay (FPA) is not currently regulated by many national Pharmacopeias, it represents a promising approach for protein drug standardization, considering their rapid, sensitive, and automatable detection suitable for high-throughput analysis and real-time quality control. To evaluate the applicability of FPA for the analysis of protein drugs in tablets, the quantifying of lysozyme in tablet dosage forms was studied by this method with the use of a fluorescently labeled synthetic chitooligosaccharide tracer. It was shown that this approach overcomes the limitations of the conventional turbidimetric assay of lysozyme determination, which is labor-intensive and relies on unstable reagents. Measurements were performed with both portable and stationary fluorescence polarization readers. Commercial tablets from five manufacturers containing lysozyme (20 mg) and pyridoxine hydrochloride (10 mg) together with other excipients were analyzed. The FPIA method showed a linear range of 5.0–70 µg/mL, with specificity confirmed by the absence of interference from excipients. Accuracy, evaluated by standard addition (10–20 mg), yielded recoveries of 100.2–106.0%. Placebo spiked with lysozyme at 80–120% of nominal content demonstrated recoveries of 98.0–100.1%, with RSD (n = 6) not exceeding 13.7%, indicating good precision. The developed method enables reliable lysozyme quantification in tablets, offering speed, simplicity, and robustness, and shows its suitability for the routine quality control of protein-containing dosage forms including the enzyme ones. Full article

Background: Effective shared decision-making (SDM) for life-sustaining treatment (LST) requires alignment between physicians and surrogates. However, discrepancies in perceptions and communication may hinder ethically sound decisions. This study aimed to compare the perceptions and attitudes of physicians and surrogates toward SDM for LST in a Chinese hospital setting. Methods: This pre-planned secondary analysis included data from two cross-sectional surveys administered to physicians and surrogates. Participants were 325 surrogates of critically ill adult patients admitted to the Emergency Intensive Care Unit (EICU) of a tertiary teaching hospital and 351 physicians from hospitals in Beijing. Survey items assessed triggers and preferred models of decision-making, disclosure practices, perceived decisional capacity, and factors influencing LST decisions. Statistical comparisons were performed using appropriate tests for categorical data. Results: Although a majority in both groups nominally preferred SDM (physicians: 52.7%; surrogates: 44.3%; p = 0.155), significant discrepancies emerged across other domains. Physicians were more likely than surrogates to initiate LST discussions earlier (88.0% vs. 75.3%; p < 0.001). Perceived understanding differed markedly: 87.7% of surrogates rated their comprehension as “good” or “excellent”, whereas 73.8% of physicians rated surrogate understanding as “fair” or “poor” (p < 0.001). Surrogates expressed a stronger preference for receiving quantitative prognostic information and decision-support tools. Most physicians (94.9%) reported directing consent discussions primarily to families, with limited patient involvement. Priorities for LST decisions diverged: physicians emphasized clinical indicators such as prognosis (96.0%) and comorbidities (91.7%), whereas surrogates emphasized patient age (72.0%). Conclusions: Marked discordances exist between physicians and surrogates in their perceptions and practices regarding SDM for LST in China. Differences in communication strategies, informational expectations, and decision-making priorities underscore the need for contextually adapted interventions, such as structured communication tools and culturally sensitive clinician training, to bridge these gaps and support ethically aligned decision-making. Full article

Background/Objectives: The burden of nursing care is defined as the relation between the care needs of hospitalized individuals and the time available for nursing staff to perform direct, indirect, and educational care activities. This study aimed to design an instrument to measure the burden of nursing care and to assess its face and content validity. Methods: This methodological study was conducted in three phases: (1) operationalization of the concept, (2) instrument design, and (3) face and content validity assessment. Expert panels using the nominal group technique were employed in phases one and two. In phase three, item evaluations regarding clarity, coherence, and relevance were conducted by experts. Results: Face validity was assessed by six expert researchers, while content validity was evaluated by 55 nurses with graduate-level education. The results demonstrated content validity index (CVI) values ranging from 0.89 to 0.95; Aiken’s V values between 0.84 and 0.94; and Kendall’s W concordance coefficients between 0.54 and 0.73, all statistically significant (p < 0.001). Conclusions: The Care Load Scale, designed to measure the burden of nursing care based on hospitalized patients’ needs, demonstrated strong face and content validity. The instrument shows potential for use in clinical settings to guide nursing care planning, allocate resources effectively, and inform institutional policies. The inclusion of expert judgment and rigorous validation procedures ensures the instrument’s relevance and applicability. This scale represents a significant contribution to nursing research and practice by offering a standardized tool aligned with patient-centered care principles. Full article

Risk identification is a foundational process in construction project management, yet the selection of appropriate identification techniques often lacks empirical guidance. To address this gap, this study adopts a case study design and conducts a comparative evaluation of four established but underutilized methods—Delphi, Nominal Group Technique (NGT), Hazard and Operability Study (HAZOP), and Preliminary Hazard Analysis (PHA)—within the context of a large-scale infrastructure project in Türkiye. The Delphi panel consisted of five senior experts. The NGT session involved six site-level practitioners, and the HAZOP team was composed of four multidisciplinary professionals. Two project-level managers conducted the PHA. Each technique was assessed against seven evaluative criteria: methodological structure, stakeholder engagement, analytical depth, resource intensity, flexibility, decision-support value, and contextual fit. The findings reveal that HAZOP achieved the highest analytical depth and decision-support capacity, while NGT demonstrated the strongest stakeholder engagement and contextual adaptability. Delphi provided robust systemic insights but required substantial time and expert availability, whereas PHA offered rapid screening capacity with limited depth. Drawing on these findings, the study proposes a Contextual Decision Support Model that helps practitioners select the most suitable technique based on project complexity, available resources, and stakeholder conditions. This practical framework enables construction professionals to balance methodological rigor with contextual feasibility, ensuring that risk identification processes are both systematic and adaptable to real-world constraints. Beyond its methodological contribution, the study advances risk management in construction by providing a structured and transparent decision-support approach that bridges academic rigor with on-site practice. By aligning method selection with project-specific attributes and stakeholder dynamics, the model strengthens the integration of analytical precision and practical decision-making across the project lifecycle, thereby contributing to more proactive, evidence-based, and resilient risk management in construction projects. Full article

Black-identifying patients face many barriers to the receipt of equitable breast cancer care; however, little is currently known about the unique needs of this patient population, particularly in Canada. To address this gap, we identified and thematically grouped constructs from the published literature reporting on the needs of Black-identifying patients with breast cancer and compared these findings to a list generated through a virtual nominal consensus group (NG) attended by Canadian patients with breast cancer who self-identified as Black (n = 3). A scoping review was undertaken, and relevant citations published from database inception until January 2025 were identified from MEDLINE, Embase, and CINAHL. The literature review yielded 34 articles from the United States and identified 15 constructs consistent with the NG, which spanned the cancer continuum from screening to survivorship. The NG identified four additional constructs that were not found in the literature: advocacy and outreach, communication and health literacy, comorbidities and personalized care, and end-of-life care. The final set of constructs was then validated and prioritized by an expert panel consisting of patients with lived experience and relevant community partner organizations (n = 9) to drive future research, advocacy, and policy work. Patient navigation was identified as the top need, with financial support, access to culturally tailored information and resources, culturally relevant care, racialized data for treatment decision-making, and emotional support identified as high-priority needs. Full article

Given world immigration patterns, understanding immigrant children’s social inclusion is crucial, especially the role of school characteristics. The current study examines how individual- and school-level factors shape immigrant children’s peer relationship In Ireland, a context that has experienced rapid demographic change by remains underexplored in the literature. Drawing on social network theory, we analyse data from 2244 primary school children across 98 schools, using measures of peer group size, friendship nominations, and network centrality to capture social inclusion. Multilevel regression models show that immigrant children report smaller peer groups compared to non-immigrant peers, while minority language use is consistently associated with lower levels of social centrality. Contrary to expectations, school size and urbanicity had limited effects, and classrooms with a higher proportion of immigrant students were associated with reduced inclusion overall, although immigrant children themselves benefitted somewhat from greater classroom diversity. Family affluence was positively associated with all measures of inclusion, highlighting the role of socioeconomic inequalities alongside migration background. The findings underscore the complex and multifaceted nature of social inclusion, showing that both structural and interpersonal dynamics shape immigrant children’s experiences in Irish schools, and pointing to the need for targeted strategies to address linguistic and socioeconomic barriers. Full article

Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with dysfunction, with or without a structural substrate. They are frequently genetically determined. The dysfunction may be mechanical, both of the systole and diastole, or electrical, including arrhythmias or conduction disorders. Originally, only dilated, hypertrophic, restrictive–obliterative and arrhythmogenic dysfunctions were considered cardiomyopathies. Nowadays, since dysfunction can also be electric, disorders affected by electrical dysfunction without a structural substrate can be regarded as cardiomyopathies as well. This is the case of channellopathies and ryanodine receptors. This paper is a review of the history of cardiomyopathies, including the issues of their classification and nomination, genetic background and gene therapy. Full article

Immunogenic cell death (ICD) is a specialized form of cell death that triggers antitumor immune responses. In tumors, ICD promotes the release of tumor-associated and tumor-specific antigens, thereby reshaping the immune microenvironment, restoring antitumor immunity, and facilitating tumor eradication. However, the regulatory mechanisms of ICD and its immunological effects vary across tumor types, and a comprehensive understanding remains limited. We systematically analyzed the expression of 34 ICD-related regulatory genes across 33 tumor types. Differential expression at the RNA, copy number variation (CNV), and DNA methylation levels was assessed in relation to clinical features. Associations between patient survival and RNA expression, CNVs, single-nucleotide variations (SNVs), and methylation were evaluated. Patients were stratified into immunological subtypes and further divided into high- and low-risk groups based on optimal prognostic models built using a machine learning framework. We explored the relationships between ICD-related genes and immune cell infiltration, stemness, heterogeneity, immune scores, immune checkpoint and regulatory genes, and subtype-specific expression patterns. Moreover, we examined the influence of immunotherapy and anticancer immune responses, applied three machine learning algorithms to identify prognostic biomarkers, and performed drug prediction and molecular docking analyses to nominate therapeutic targets. ICD-related genes were predominantly overexpressed in ESCA, GBM, KIRC, LGG, PAAD, and STAD. RNA expression of most ICD-related genes was associated with poor prognosis, while DNA methylation of these genes showed significant survival correlations in LGG and UVM. Prognostic models were successfully established for 18 cancer types, revealing intrinsic immune regulatory mechanisms of ICD-related genes. Machine learning identified several key prognostic biomarkers across cancers, among which NT5E emerged as a predictive biomarker in head and neck squamous cell carcinoma (HNSC), mediating tumor–immune interactions through multiple ligand–receptor pairs. This study provides a comprehensive view of ICD-related genes across cancers, identifies NT5E as a potential biomarker in HNSC, and highlights novel targets for predicting immunotherapy response and improving clinical outcomes in cancer patients. Full article

Background: Chronic wrist pain is becoming increasingly recognized among athletes engaging in wrist-loading activities such as handstands. However, its prevalence and associated risk factors in handstand practitioners have not been systematically studied. This study aimed to investigate the prevalence of chronic wrist pain and to explore associated factors such as discipline, training habits, and pain management strategies. Methods: This cross-sectional study aimed to investigate the prevalence and associated factors of chronic wrist pain among handstand practitioners. Eligible participants were individuals aged 18 years or older, of any gender, who practiced handstands regularly (defined as at least once per week). Participants were recruited via a combination of open invitations on social media (Facebook, WhatsApp, Instagram) and direct outreach to movement studios and training communities. The survey was administered online using Google Forms and remained open for two months. Participation was voluntary and anonymous. Descriptive statistics were used to present sociodemographic characteristics, including age group, gender, sport discipline, and weekly training hours. Participants reported training habits, equipment use, pain history, and management strategies via a self-developed questionnaire designed for this study. Chronic pain was defined as recurring or persistent wrist pain. Descriptive statistics were used to summarize responses. Associations between chronic wrist pain and survey variables were analyzed using Chi-square or Fisher’s exact tests for nominal data, and Chi-square test for trend for ordinal data. A p-value < 0.05 was considered statistically significant. Results: A total of 321 participants were included in the study. The most represented age group was 25–34 years, comprising 123 (38.3%) of the participants. Gender distribution was 174 (54.2%) males and 147 (45.8%) females. The most common sport disciplines were Yoga (88, 27.4%), Capoeira (60, 18.7%), and Movement (52, 16.2%). Chronic wrist pain was reported by 182 (56.7%) of participants. Younger age was significantly associated with higher pain prevalence (p = 0.042). No significant associations were observed between chronic pain and weekly training hours, warm-up routines, brace use, or grip device use. Female participants demonstrated more proactive pain management behaviors (p = 0.016). Sport discipline and training practices showed non-significant trends toward pain differences. Conclusions: Chronic wrist pain is common among handstand practitioners, particularly among younger athletes. These findings suggest that injury risk may relate more to training intensity and biomechanics than to simple training volume. Further research incorporating objective diagnostics and standardized intervention protocols is warranted. Full article

Polypharmacy is prevalent in older people residing in care homes. Deprescribing, reducing or stopping harmful or unnecessary medicines, leads to improvements in patient- and health-system-orientated outcomes. This study identified the barriers and enablers to pharmacists proactively deprescribing in United Kingdon care homes. It draws on methods from behavioural science. Twenty-nine participants who had previously taken part in a deprescribing randomised control trial (sixteen pharmacists, six primary care doctors, and seven care home managers) were interviewed. Data were mapped to the Theoretical Domains Framework to understand pharmacists’ deprescribing behaviour. Barriers were deprescribing seen as risky and perceived resistance to deprescribing by residents, their families, and care home staff. Enablers were seeing benefits from deprescribing, part of a pharmacists’ role, and endorsement from a doctor. Ways to change pharmacist behaviour were identified from a suite of behaviour change techniques (BCT). Using a modified Nominal Group Technique, 15 staff (six pharmacists, five primary care doctors, and four care home managers) naïve to deprescribing interventions completed an online survey to assess the feasibility and acceptability of implementing the 27 BCTs. Seven BCTs achieved a more that 80% consensus on all implementation criteria. In a consensus workshop, the staff group discussed practical ways the BCTs might work in primary care practice. Fourteen UK policy and practice leaders worked with the researchers to develop recommendations from the consensus workshop into a policy briefing. In conclusion, this study provides detail on using a theory-informed approach to translate research into policy to inform deprescribing practices. Full article

Emerging evidence suggests a potential role of gut dysbiosis in neurodegenerative disorders and, in particular, Alzheimer’s disease (AD) pathology and cognitive decline. However, the role of gut microbiome in the early prodromal stages of AD and particularly in mild cognitive impairment (MCI) remains understudied and has been mostly explored in Asian populations with no representation of European populations. To address this research gap in the literature and to suggest novel microbiome features associated with MCI, we conducted a cross-sectional study in a European population sample and profiled gut microbiota in 99 individuals without dementia through 16s ribosomal RNA (rRNA) sequencing. Individuals were categorized by cognitive status based on standard clinical criteria to cognitively normal (n = 49) or individuals with MCI (n = 50). Differential abundance through Microbiome Multivariable Associations with Linear model (MaAsLin2) and elastic net logistic regression analyses were used to identify gut microbiome features associated with MCI. MCI group was older than the CN group and age was used as covariate in the differential abundance analysis. No differences in alpha and beta diversity were found between the two groups (p > 0.05). At false discovery rate (FDR) < 0.05, we identified specific genera associated with MCI, mostly linked to short chain fatty acids (SCFAs) production (e.g., Candidatus_Soleaferrea q = 0.027, MaAsLin2 coefficient = 1.65, Sellimonas q = 0.017, MaAsLin2 coefficient = −4.45), while we highlight nominal (p < 0.05, q > 0.05) correlations of genera (e.g., Hydrogenoanaerobacterium, Subdoligranulum) with metrics of cognitive assessment. Microbiota was shown to have a fairly good discriminative capacity for MCI status (area under the curve AUC = 0.77), with Rothia genus found as the top predictor for MCI (beta coefficient [95% confidence intervals] = 0.224 [0.216–0.233]). Overall, our findings add to current knowledge reporting gut microbiome alterations in MCI by suggesting novel associated microbiome features; however, larger scale longitudinal studies are needed to further elucidate the underlying biological pathways linked to the disease. Full article

Background: Borderline Personality Disorder (BPD) is a complex psychiatric condition with multifactorial origins, with a high proportion of patients reporting early trauma. Stressors such as adverse childhood experiences (ACEs) can shape the epigenetic landscape including DNA methylation (DNAm) and act on gene expression. DNAm is increasingly being investigated as a molecular link between environmental exposures such as ACE and psychiatric outcomes. Differential DNAm of the gene PR domain zinc finger protein 8 (PRDM8), a histone methyltransferase, has recently been reported to be sensitive to early life trauma. Its role in BPD, especially in the context of ACE, remains to be elucidated. Methods: This study investigated DNAm patterns of PRDM8 in peripheral blood and saliva obtained from BPD patients undergoing Dialectic Behavioral Therapy (DBT) compared to healthy control (HC) participants. Associations with ACE and BPD symptom severity were assessed, and therapy-related changes in DNAm were examined. Results: At baseline, BPD patients demonstrated significant hypomethylation of PRDM8 in blood relative to the HC group. Following DBT, a nominally significant increase in DNAm was observed, aligning with inversely correlated symptom severity. No significant differences in saliva were detected. ACE was not associated with PRDM8 DNAm. Conclusions: Our findings suggest that PRDM8 DNAm might be associated with BPD and therapeutic intervention but not with ACE. Together with prior research, the results underscore the importance of future investigation of gene–environment interactions and the functional significance of PRDM8 regulation in the pathophysiology of BPD. Full article

In this paper, I will discuss a topic concerning part–whole structures in the nominal and verbal domain. Specifically, I will address the question of whether there is a universal mechanism for the individuation of entities and events by exploring parallels between singulatives and semelfactives in Slavic. Singulatives are derived unit nouns, whereas semelfactives are punctual verbs that describe a brief event which culminates by returning to the initial state. Cross-linguistically, singulative morphology often alternates with collective marking, whereas semelfactives alternate with iteratives. Collectives and iteratives describe homogenous groupings of entities and events, respectively. From a conceptual perspective, both singulatives and semelfactives individuate to the effect of singular bounded unit reference and in the literature, the parallel between the mass count/distinction and aspect has often been drawn. In Slavic, singulative and semelfactive morphologies share a component; specifically, both markers involve a nasal -n and a vocalic component, e.g., compare Russian gorox ‘peas (as a mass)’ ∼goroš-in-a ‘a pea’ and prygať ‘to jump (repeatedly)’ ∼ pryg-nu-ť ‘to jump once’. I will argue that the singulative -in and semelfactive -nu are complex and both involve the very same -n, which denotes a declustering atomizer modeled in mereotopological terms. Full article

This systematic review aims to provide a comprehensive and up-to-date overview of the most effective identification protocols used to detect giftedness in primary school students, intended to be used by teachers, parents, and diagnostic professionals. This review, registered in PROSPERO (CRD420251064093), analyzed studies published between 2019 and 2024 in the PsycINFO, Web of Science, and Scopus databases. It included articles published in English or Spanish and focused on multidisciplinary fields. A total of 17 studies were selected and evaluated for quality using the Newcastle–Ottawa Scale. The findings highlight the effectiveness of using multiple tools in the identification process, grouped into teacher nominations, family nominations, and tools for diagnostic professionals. This multidimensional approach helps reduce false negatives and supports the identification of underrepresented and twice-exceptional students. In conclusion, the identification of giftedness should be grounded in methods that prioritize general cognitive abilities over IQ scores and academic achievements. Full article

Background: In recent years, comprehensive analyses using a genome-wide association study (GWAS) have been conducted to identify genetic factors related to athletic performance. In this study, we investigated the association between genetic variants and elite wrestling status across multiple ethnic groups using a genome-wide genotyping approach. Methods: This study included 168 elite wrestlers (64 Japanese, 67 Turkish, and 36 Russian), all of whom had competed in international tournaments, including the Olympic Games. Control groups consisted of 306 Japanese, 137 Turkish, and 173 Russian individuals without elite athletic backgrounds. We performed a GWAS comparing allele frequencies of single-nucleotide polymorphisms (SNPs) between elite wrestlers and controls in each ethnic cohort. Cross-population analysis comprised (1) identifying SNPs with nominal significance (p < 0.05) in all three groups, then (2) meta-analyzing overlapped SNPs to assess effect consistency and combined significance. Finally, we investigated whether the most significant SNPs were associated with gene expression in skeletal muscle in 23 physically active men. Results: The GWAS identified 328,388 (Japanese), 23,932 (Turkish), and 30,385 (Russian) SNPs reaching nominal significance. Meta-analysis revealed that the ATP2A3 rs6502758 and UNC5C rs265061 polymorphisms were associated (p < 0.0001) with elite wrestling status across all three populations. Both variants are located in intronic regions and influence the expression of their respective genes in skeletal muscle. Conclusions: This is the first study to investigate gene polymorphisms associated with elite wrestling status in a multi-ethnic cohort. ATP2A3 rs6502758 and UNC5C rs265061 polymorphisms may represent important genetic factors associated with achieving an elite status in wrestling, irrespective of ethnicity. Full article