Search Results (2,907)

A widely used repository of violent death records is the U.S. Centers for Disease Control National Violent Death Reporting System (NVDRS). The NVDRS includes narrative data, which researchers frequently utilize to go beyond its structured variables. Prior work has shown that NVDRS narratives vary in length depending on decedent and incident characteristics, including race/ethnicity. Whether these length differences reflect differences in narrative information potential is unclear. We use the 2003–2021 NVDRS to investigate narrative length and complexity measures among 300,323 suicides varying in decedent and incident characteristics. To do so, we operationalized narrative complexity using three manifest measures: word count, sentence count, and dependency tree depth. We then employed regression methods to predict word counts and narrative complexity scores from decedent and incident characteristics. Both were consistently lower for black non-Hispanic decedents compared to white, non-Hispanic decedents. Although narrative complexity is just one aspect of narrative information potential, these findings suggest that the information in NVDRS narratives is more limited for some racial/ethnic minorities. Future studies, possibly leveraging large language models, are needed to develop robust measures to aid in determining whether narratives in the NVDRS have achieved their stated goal of fully describing the circumstances of suicide. Full article

Background: Pyruvate kinase deficiency (PKD) is the most prevalent enzymatic defect of the glycolytic pathway, causing chronic congenital non-spherocytic hemolytic anemia. Clinical severity ranges from mild anemia to transfusion-dependent diseases. Severe neonatal presentations, including liver failure, have rarely been reported. Case presentation: We report a preterm female neonate with PKD who developed early-onset hemolytic anemia, conjugated hyperbilirubinemia, hepatosplenomegaly, coagulopathy, and progressive transaminitis. Imaging demonstrated hepatomegaly with diffuse parenchymal involvement. Whole-genome sequencing identified compound heterozygous pathogenic mutations in the PKLR gene, confirming the diagnosis of PKD. The patient required continuous transfusion support and was discharged following clinical stabilization. Discussion: Although PKD most often manifests as isolated hemolytic anemia, this case illustrates a rare neonatal phenotype with concurrent liver dysfunction. We investigated the potential underlying mechanism. Recognition of hepatic involvement in PKD is essential because liver failure is associated with considerable morbidity and mortality, and it may necessitate interventions such as liver transplantation. Conclusions: This case highlights the importance of considering PKD in neonates presenting with hemolysis and liver failure. Early genetic confirmation enables timely management, including transfusion support, iron overload surveillance, and anticipatory guidance for potential hepatic complications. Full article

Sepsis poses a significant global health burden, with millions of cases and high mortality rates annually, largely due to challenges in early diagnosis and monitoring. Traditional methods, reliant on nonspecific clinical manifestations and limited biomarkers like C-reactive protein and procalcitonin, often fail to distinguish infection from non-infectious inflammation or capture disease heterogeneity. This review synthesizes recent progress in omics technologies—genomics, transcriptomics, proteomics, and metabolomics—for advancing sepsis management. Genomics, via metagenomic next-generation sequencing, enables rapid pathogen identification and genetic variant analysis for susceptibility and prognosis. Transcriptomics reveals molecular subtypes and immune dynamics through RNA sequencing and single-cell approaches. Proteomics and metabolomics uncover protein and metabolite profiles linked to immune imbalance, organ damage, and metabolic disorders. Multi-omics integration, enhanced by artificial intelligence and machine learning, facilitates biomarker discovery, patient stratification, and predictive modeling, bridging laboratory findings to bedside applications like rapid diagnostic tools and clinical decision support systems. Despite advancements, challenges including data heterogeneity, high costs, and ethical concerns persist. Future directions emphasize single-cell and spatial omics, AI-driven personalization, and ethical frameworks to transform sepsis care from reactive to proactive, ultimately improving outcomes. Full article

Bronze materials are indispensable across numerous industries for enhancing the durability and performance of components, primarily due to their excellent tribological properties, corrosion resistance, and machinability. This study investigates the impact of different atmospheric conditions on the properties of WAAM (wire arc additive manufacturing) cladded bronze coatings on 09G2S steel substrate. Specifically, the research examines how varying atmospheres—including ambient air (N₂/O₂, no shielding gas), pure argon (Ar), carbon dioxide (CO₂), and 82% Ar + 18% CO₂ (Ar/CO₂) mixture—influence coating defectiveness (porosity, cracks, non-uniformity), wettability (manifested as uniform layer formation and strong adhesion), and the extent of intergranular penetration (IGP), leading to the formation of characteristic infiltrated cracks or “bronze whiskers”. Modern investigative techniques such as optical microscopy (OM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD) were employed for comprehensive material characterization. Microhardness testing was also carried out to evaluate and confirm the homogeneity of the coating structure. The findings revealed that the bronze coatings primarily consisted of a dominant, highly textured FCC α-Cu phase and a minor BCC α-Fe phase, with Rietveld refinement quantifying a α-Fe volume fraction of ~5%, lattice parameters of a = 0.3616 nm for α-Cu and a = 0.2869 nm for α-Fe, and a modest microstrain of 0.001. The bronze coating deposited under a pure Ar atmosphere exhibited superior performance, characterized by excellent wettability, a uniform, near-defect-free structure with minimal porosity and cracks, and significantly suppressed formation of bronze whiskers, both in quantity and size. Conversely, the coating deposited without a protective atmosphere demonstrated the highest degree of defectiveness, including agglomerated pores and cracks, leading to an uneven interface and extensive whisker growth of varied morphologies. Microhardness tests confirmed that while the Ar-atmosphere coating displayed the lowest hardness (~130 HV_0.1), it maintained consistent values across the entire analyzed area, indicating structural homogeneity. These results underscore the critical role of atmosphere selection in WAAM processing for achieving high-quality bronze coatings with enhanced interfacial integrity and functional performance. Full article

Leishmaniasis and Chagas disease, caused by Leishmania spp. and Trypanosoma cruzi, are neglected tropical diseases with significant global health burden, particularly in resource-limited regions. Despite their impact, diagnosis and treatment remain challenging due to limited diagnostic tools and the toxicity of available therapies. Our objective is to propose the incorporation of markers for the diagnosis of leishmaniasis and Chagas disease using ncRNA. This narrative review evaluates studies published between 2010 and 2024 (PubMed, Scopus, Google Scholar) using the SANRA scale to assess the potential of non-coding RNAs (ncRNAs) as biomarkers for these infections. Both parasites release small RNAs via extracellular vesicles that modulate host–pathogen interactions and gene expression. Although RNA interference machinery is absent in T. cruzi and most Leishmania species, it persists in early-diverging lineages. In leishmaniasis, distinct miRNA expression profiles—including miR-155-5p, miR-5011-5p, miR-6785-5p, and miR-361-3p—demonstrate high diagnostic accuracy for detecting infection (AUC up to 1.0). Serum long ncRNAs such as MALAT1 and NUTM2A-AS1 show potential diagnostic value, though clinical validation remains pending. For Chagas disease, the available evidence on ncRNAs primarily addresses the diagnosis of clinical manifestations rather than initial infection. Host miRNAs, including miR-21, miR-145, miR-146a/b, and miR-19a-3p, correlate with cardiac involvement, immune dysregulation, and inflammation during chronic T. cruzi infection. Circulating miRNAs exhibit modest sensitivity (57–67%) and specificity (57–80%) for diagnosing chronic Chagas cardiomyopathy, indicating their utility in assessing disease progression and organ damage rather than detecting early infection. This review distinguishes between ncRNAs that diagnose infection and those that evaluate disease severity or organ involvement. Altered ncRNA expression profiles represent promising biomarkers for species differentiation, treatment monitoring, and assessing cardiac complications in Chagas disease, with broader diagnostic applications emerging for leishmaniasis. Full article

In this study, the stress–strain constitutive models of Cu-Cu joints in hybrid bonding after primary and secondary annealing were determined using nanoindentation experiments and finite element inverse analysis, and the correlation mechanism between the microstructure and macroscopic mechanical properties in hybrid bonding Cu-Cu joints during secondary annealing was revealed. The 350–400 °C secondary annealing facilitates recrystallization–grain growth, increasing grain size from 0.62 μm after primary annealing to 0.71 μm, accompanied by a 12% reduction in kernel average misorientation (KAM) values. This process enhances interface non-planarization and optimizes bonding quality. Concurrently, the secondary annealed Cu-Cu joints exhibit a softening effect, manifested by decreasing trends in elastic modulus (131.02 → 118.98 GPa), hardness (1.78 → 1.51 GPa), and yield strength (70.52 → 56.12 MPa), primarily attributed to the Hall–Petch effect and residual stress release. Notably, the yield strength of secondary annealed Cu-Cu joints demonstrates 31.0% and 68.5% enhancements compared to TSV-Cu (42.83 MPa) and bulk Cu (33.3 MPa), respectively. Full article

Radiotherapy (RT) remains a cornerstone of cancer treatment, offering spatially precise cytotoxicity against malignant cells. However, emerging evidence reveals that ionizing radiation (IR) exerts biological effects beyond the targeted tumor volume, manifesting as radiation bystander effects (BEs) and other non-targeted effects (NTEs). These phenomena challenge the traditional paradigm of RT as a localized intervention, highlighting systemic and long-term consequences in non-irradiated tissues. This comprehensive review synthesizes molecular, cellular, and clinical insights about BEs, elucidating the complex intercellular signaling networks gap junctions, cytokines, extracellular vesicles, and oxidative stress that propagate damage, genomic instability, and inflammation. We explore the role of mitochondrial dysfunction, epigenetic reprogramming, immune modulation, and stem cell niche disruption in shaping BEs outcomes. Clinically, BEs contribute to neurocognitive decline, cardiovascular disease, pulmonary fibrosis, gastrointestinal toxicity, and secondary malignancies, particularly in pediatric and long-term cancer survivors. The review also evaluates countermeasures including antioxidants, COX-2 inhibitors, exosome blockers, and FLASH RT, alongside emerging strategies targeting cfCh, inflammasomes, and senescence-associated secretory phenotypes. We discuss the dual nature of BEs: their potential to both harm and heal, underscoring adaptive responses and immune priming in specific contexts. By integrating mechanistic depth with translational relevance, this work posits that radiation BEs are a modifiable axis of RT biology. Recognizing and mitigating BEs is imperative for optimizing therapeutic efficacy, minimizing collateral damage, and enhancing survivorship outcomes. This review advocates for a paradigm shift in RT planning and post-treatment care, emphasizing precision, personalization, and systemic awareness in modern oncology. Full article

Colonoscopy remains the gold standard for colorectal cancer (CRC) screening, but its invasiveness, cost, and limited availability in resource-constrained settings pose major barriers. Stool-based methylated DNA biomarkers, such as vimentin, offer sensitive, non-invasive alternatives. Given the high burden of HIV and helminth co-infections in sub-Saharan Africa and their potential contribution to cancer susceptibility, this study investigated whether stool-derived vimentin methylation could detect early oncogenic changes in these high-risk groups. In this retrospective cross-sectional study, archived stool samples from 62 South African adults were stratified into five groups: uninfected controls, HIV-infected only, helminth-infected only, HIV-helminth co-infected, and CRC-confirmed patients. DNA was extracted, bisulfite-converted, and analyzed for vimentin methylation using a high-resolution melt assay. Fecal occult blood testing (FOBT) was also performed. Vimentin methylation differed significantly across groups (p < 0.0001). CRC cases showed 90% methylation, confirming its role as a CRC biomarker. Interestingly, vimentin methylation frequencies were also observed in HIV-only (92.9%, p < 0.0001 vs. controls), helminth-only (93.3%, p < 0.0001), and HIV-helminth co-infected (77.9%, p < 0.0001) individuals without diagnosed cancer, compared to 10% in controls. Methylation levels in infected groups were not significantly different from CRC patients (all p > 0.05), suggesting infection-induced epigenetic changes of comparable magnitude to malignancy. To support these results, DNMT1–RG108 molecular docking (PDB 4WXX, Maestro 2025-3) demonstrated stable binding (GlideScore −6.285 kcal/mol; ΔG_bind −49.61 kcal/mol) via hydrogen bonding with Glu1266 and Asn1578 and π–π stacking with Phe1145, providing a mechanistic explanation for infection-driven vimentin methylation. No significant differences were found between infected groups. FOBT was positive in 83.3% of CRC cases, with only sporadic positives in infected groups. These findings provide novel evidence that chronic HIV and helminth infections are associated with vimentin promoter methylation at levels indistinguishable from CRC. This supports the hypothesis that persistent infection-driven inflammation promotes early epigenetic reprogramming toward oncogenesis. In high-burden African settings, stool-based methylation assays could serve as early diagnostic tools to identify at-risk individuals long before clinical disease manifests, enabling targeted surveillance and prevention. Full article

Human Immunodeficiency Virus (HIV) infection is associated with a wide spectrum of urological manifestations, reflecting both the direct effects of viral infection and the indirect consequences of immunosuppression, opportunistic infections, malignancies and long-term combined antiretroviral therapy (cART). This narrative review provides a contemporary, multifaceted overview of the clinical and pathological presentations of urological conditions in people living with HIV (PLWHIV), based on articles published between 1989 and 2025. Conditions discussed include HIV-associated nephropathy (HIVAN), opportunistic genitourinary infections, malignancies such as Kaposi sarcoma and lymphoma, as well as non-infectious complications such as HIV-associated nephropathy and erectile dysfunction (ED). The review highlights the evolving epidemiology of these conditions in the cART era, with a noted decline in opportunistic infections but a rising burden of chronic kidney disease and malignancies, largely due to improved survival and ageing of the HIV-positive population. Pathological insights are explored and discussed, including mechanisms of HIV-associated renal injury, such as direct viral infection of renal epithelial cells and genetic predispositions linked to Apolipoprotein L1 (APOL1) variants. In addition, psychosocial factors, including anxiety, stress, stigma, and alcohol use, are discussed, as they may contribute to late presentation to clinical urology services. The review also considers the challenges faced in low and middle-income countries, the impact of HIV on urological services, and the important role of palliative care in advanced disease. Ultimately, this review underscores the need for early recognition, comprehensive diagnostic and surgical evaluation, and integrated social, psychological, and palliative management strategies tailored to the unique needs of PLWHIV. A deeper understanding of the interplay between HIV, cART, psychosocial determinants, and urological health is essential for improving patient outcomes and guiding future research in this evolving field. Full article

Background: Anxiety disorders, including panic disorder, agoraphobia, specific phobias, and generalized anxiety disorder, are among the most frequent psychiatric conditions in primary care. They often present with somatic symptoms such as dyspnea, palpitations, chest or gastrointestinal discomfort, sweating, or flushing. Adaptol^® is a non-benzodiazepine anxiolytic with nootropic properties that modulates the limbic-reticular system, hypothalamic emotional centers, and multiple neurotransmitter systems. This study aimed to assess the association between Adaptol^® use and changes in anxiety symptoms, including somatic manifestations, in routine practice. Methods: A noninterventional observational study was conducted in 100 adults diagnosed with anxiety disorders in primary care. All received Adaptol^® 500 mg as prescribed. Patients had to have mild-to-moderate anxiety (5–14 points according GAD-7) to be enrolled. Exclusion criteria ruled out individuals with concomitant psychiatric or severe somatic conditions and those with use of other medications or any interventions that could affect the symptoms. Anxiety severity and somatic symptom burden were assessed at baseline and after treatment. Results: Adaptol^® treatment was associated with reduction in anxiety and somatic complaints. Improvements were reported in palpitations, chest discomfort, gastrointestinal disturbances, and autonomic symptoms. Greater benefit was observed in male patients, though without significance testing, and in those with severe baseline anxiety, as demonstrated by correlation between GAD-7 scores at baseline and changes after the treatment (r = 0.5). No unexpected adverse events occurred. Conclusions: In this real-world study, Adaptol^® showed anxiolytic efficacy and good tolerability, improving both psychological and somatic manifestations of anxiety disorders. These findings support its use in primary care, especially in severe cases of anxiety. Controlled trials are needed to support these results. Full article

Myelodysplastic neoplasms (MDS) are characterized by remarkable heterogeneity in clinical manifestations, posing significant management challenges arising due to genetic plasticity. While the Revised International Prognostic Scoring System (IPSS-R) has traditionally stratified MDS into higher-risk (HR) and lower-risk (LR) categories, the recently developed Molecular International Prognostic Scoring System (IPSS-M) integrates molecular signatures and has further enhanced prognostic stratification. In LR-MDS, current therapeutic interventions remain non-curative and the goal of treatment is centered along three critical axes: reducing transfusion dependence, improving quality of life, and reducing the risk of progression to acute myeloid leukemia (AML). This review examines recent progress made in the therapeutic landscape of LR-MDS, with particular emphasis on the molecular basis of these novel agents that may have disease-modifying potential. We evaluate the clinical trials and targeted agents in the pipeline for treating LR-MDS, providing a comprehensive perspective where these treatment modalities are placed in the current standard of care and how these novel targets can shape future therapeutic innovations. Full article

The present study evaluates the effectiveness of a non-invasive wearable sensor system, combining accelerometers, surface electromyography, and artificial intelligence, to objectively characterize swallowing in elderly individuals affected by Parkinson’s Disease, without clinically manifested dysphagia. A cohort of patients and healthy control subjects performed the same swallowing test protocol, including tasks with different viscosity boluses, positioning a commercial adhesive grid of High-Density surface Electromyography (HD-sEMG) electrodes on the submental muscle and a triaxial accelerometer over the thyroid cartilage. Relevant temporal and spectral features were extracted from electromyography data. Proper filtering and processing by machine learning and Principal Component Analysis allowed identification of two distinct clusters of subjects, one predominantly composed of controls with just a few patients, the other mostly crowded by patients. Excellent classification performances were achieved (accuracy = 83.3%, precision = 79.0%, recall = 90.7%, F1-score = 84.5%, Cohen’s kappa = 0.67), revealing consistent differences in muscle activation patterns among subjects, even in the absence of clinically diagnosed dysphagia. These results support the feasibility of wearable sensor-based assessment as a reliable and non-invasive tool for the early detection of subclinical swallowing dysfunction in Parkinson’s Disease. Full article

This study describes the effect of electron radiation on the macro- and micro-mechanical and tribological properties of composite polypropylene filled with 25% glass fiber. Micro-mechanical and tribological properties were investigated both on the sample surface and at various depths below the surface. Polypropylene was irradiated with radiation doses of 15, 33, 45, 66 and 99 kGy. As the results show, electron radiation has an influence on the change in PP’s structure, in which due to the electron radiation, a crosslinked phase and an increase in crystallinity are formed. These changes in morphology are reflected in an enhancement of micro-mechanical and tribological properties both at the surface and in deeper layers below the surface. More crosslinking and recrystallization occur across the sample’s cross-section up to a depth of 2 mm, where greater micro-mechanical and tribological properties are also measured. The difference between the surface and the center of the material can be up to 32%. The optimum radiation dose appears to be 45 kGy, where the maximum crosslinking, highest crystallinity and best micro-mechanical and tribological properties are found. The difference between non-irradiated and irradiated filled PP is 52% in indentation hardness. In terms of macro-mechanical properties, the tensile modulus increased by 44% (45 kGy). This translates into higher surface wear resistance and the overall stiffness of the part. Higher doses of radiation cause the beginning of degradation processes, which are manifested by a decrease in the degree of embedding, crystallinity and thus micro-mechanical and tribological properties. Full article

Arrhythmogenic cardiomyopathy (ACM) is a cardiac disorder manifesting through electrical and contractile dysfunction of the ventricles, characterized by fibro-fatty substitution of the myocardium. Cardiac mesenchymal stromal cells (CMSCs) are key contributors to this remodeling. In clinical management, several pharmacological approaches address ACM arrhythmias and heart failure, but, to date, none specifically target fibro-adipose replacement. Despite genetic origin, several studies have reported that non-genetic aspects influence ACM phenotype, including epigenetic factors. Little is known about their mechanisms in ACM and their potential therapeutic applications. In this work, we aimed to test whether, by perturbing the epigenetic landscape of ACM CMSCs, we could influence their propensity to fibro-fatty differentiation. We conducted a hypothesis-free screening of 157 epigenetic drugs on CMSCs, isolated from ACM patients. Through fluorescence assays, we evaluated lipid droplet accumulation, collagen deposition, and cell viability. Of the 157 drugs screened, five (splitomicin, suberohydroxamic acid, CPTH6, BVT-948, and PBIT) attenuated adipogenic differentiation of ACM CMSCs, with BVT-948 and CPTH6 also reducing collagen production. Overall, this study identified specific epigenetic drugs that were effective in reducing the fibro-fatty phenotype of ACM stromal cells, thus offering potential for adjunctive therapies in the clinical management of ACM patients. Full article

Anorexia nervosa (AN) is a severe psychiatric disorder with the highest mortality rate among mental illnesses, characterized by an intense fear of weight gain, persistent restriction of energy intake, and a distorted perception of body image. Despite decades of investigation, the pathogenesis of AN is only partially understood and is recognized as multifactorial, involving genetic, sociocultural, and neurobiological determinants. Beyond its core psychopathological features, AN leads to a wide spectrum of systemic complications, including cardiovascular, renal, skeletal, and endocrine dysfunctions. Increasing evidence implicates autophagy and oxidative stress as key molecular mechanisms underpinning its pathophysiology, while growing attention has been directed toward immune dysregulation and alterations in the gut–brain axis as potential mediators of disease onset and progression. Therapeutic advances, however, remain limited. Current management relies primarily on nutritional rehabilitation and psychotherapeutic interventions, while treatment outcomes are constrained by high relapse rates and the lack of pharmacological agents with proven efficacy. In this context, a more comprehensive understanding of the clinical spectrum and molecular substrates of AN is essential to improving prognosis and guiding the development of novel therapeutic strategies. This narrative review synthesizes current evidence on the non-psychopathological dimensions of AN, encompassing its clinical manifestations, systemic complications, and implicated molecular pathways. It also appraises existing treatment modalities and examines emerging interventions with translational potential. Overall, this review aims to provide clinicians and researchers with an updated and integrative overview of AN, shedding light on novel directions in ongoing research. Full article