Search Results (30,173)

Background/Objectives: The ErbB protein family plays a critical role in the progression of various solid tumors, and HER3 has been implicated in resistance mechanisms to multiple cancer therapies due to its ability to form heterodimers with other ErbB receptors, thereby activating pathways that promote tumor growth and survival. This study aimed to generate and characterize humanized monoclonal antibodies against HER3 to inhibit its function and evaluate their potential as therapeutic agents. Methods: Murine monoclonal antibodies TK-A3 and TK-A4 were humanized and tested for binding to ErbB3 and competition with neuregulin-1β (NRG). Specificity was assessed by ELISA, and epitope identified by X-ray crystallography. Downstream signaling was analyzed by western blot for phosphorylated ErbB3, Akt, and MAPK. Antitumor activity was evaluated in vitro and in a pancreatic cancer xenograft model. A toxicology study was also conducted. Results: TK-hu A3 and TK-hu A4 bound specifically to ErbB3 without cross-reactivity to other ErbB receptors. The ErbB3-TK-hu A3 Fab structure revealed the binding epitope. Both antibodies competed with NRG, inhibiting ErbB3, Akt, and MAPK phosphorylation in a dose-dependent manner. They suppressed cancer cell survival in vitro, and TK-hu A3 significantly delayed tumor growth in vivo. The toxicology study indicated good tolerability. Conclusions: TK-hu A3 emerged as the lead candidate, showing specific HER3 targeting, strong pathway inhibition, and antitumor efficacy in vivo. Beyond standalone use, it could support novel strategies such as T-cell engagers, ADCs, CAR-T, and bispecific antibodies. These findings highlight TK-hu A3 as a promising therapy for HER3-positive, treatment-resistant cancers, meriting further development. Full article

Background: Granulomatous mastitis (GM) is a rare, chronic inflammatory breast condition with poorly understood etiology and variable clinical presentation. The efficacy of corticosteroid therapy in reducing recurrence remains controversial, particularly in Middle Eastern populations where the condition appears more prevalent. This study aimed to describe the demographic and clinical characteristics of patients with GM, evaluate the efficacy of corticosteroid therapy in reducing recurrence rates, and identify risk factors associated with disease recurrence. Methods: A retrospective cohort analysis was conducted on 56 patients diagnosed with GM between 2003 and 2020 at a single tertiary referral center. Patients were stratified into two groups based on steroid use (n = 14 with steroids and n = 42 without steroids). Results: The mean age of the cohort was 46.3 ± 13.2 years, with no significant differences in baseline characteristics between the steroid and non-steroid groups. The most common presentation was a breast mass (32.69%), often associated with abscess formation (25%). Core biopsy was the primary diagnostic tool used (51.79%). Recurrence of GM occurred in 10 patients (18%) overall: 7 patients (17%) in the non-steroid group and 3 patients (21%) in the steroid group. The difference in recurrence rates between the treatment groups was not statistically significant (HR = 1.40, 95% CI:0.30–6.52, p = 0.671). A history of infection (HR = 5.85, 95% CI: 1.60–21.44, p = 0.008) and hormonal disorders (hyperprolactinemia in one patient) (HR = 13.90, 95% CI: 1.43–135.52, p = 0.024) were significantly associated with recurrence. Conclusions: GM remains diagnostically challenging with an 18% recurrence rate in our cohort. We observed no statistically significant reduction in recurrence with corticosteroids, though our analysis was limited by sample size. These findings suggest that targeted management of these conditions may be beneficial in GM patients, though larger multicenter studies are needed to confirm these associations and establish standardized treatment protocols. Full article

Serological testing for SARS-CoV-2-specific antibodies, particularly those targeting the nucleocapsid protein, plays a key role in assessing past infection and estimating population-level seroprevalence. The seroprevalence of nucleocapsid antibodies against SARS-CoV-2 was evaluated in 1048 blood donors using the Elecsys Anti-SARS-CoV-2 electrochemiluminescence immunoassay. Participants completed a questionnaire to assess risk factors, symptoms during SARS-CoV-2 infection and vaccination status. The overall SARS-CoV-2 seroprevalence was 89.69%. Seroprevalence was not significantly associated with gender or age. In multivariate logistic regression, most investigated risk factors showed no significant association with seroprevalence. However, residence area and vaccination status were independently associated with SARS-CoV-2 seropositivity. Donors from rural areas had significantly higher odds of seropositivity (aOR = 1.68; 95% CI: 1.01–2.79; p = 0.045) compared to those from urban areas. Unvaccinated individuals were more likely to test positive for SARS-CoV-2 compared to vaccinated participants (aOR: 2.59; 95% CI: 1.35–4.99; p = 0.004). After three years of the COVID-19 pandemic, the prevalence of SARS-CoV-2 among blood donors was remarkably high, indicating that the vast majority of this population group had been exposed to the virus. This study highlights the risk factors for SARS-CoV-2 infection and the differences in antibody prevalence between vaccinated and unvaccinated individuals. Our findings underscore the pivotal role of vaccination in controlling the pandemic and provide valuable insights for policymakers in designing targeted strategies to curb future SARS-CoV-2 transmission. Full article

Light quality is a recognized driver of plant growth and secondary metabolism in Coleus blumei, a valuable source of rosmarinic acid (RA) and quercetin (QU), whereas its combination with salinity stress represents a potential strategy that still requires further investigation. We evaluated four LED spectra, red–blue (RB) (6:1, control), blue (B), red (R), and RB + Far-Red, under both control (0 mM NaCl) and moderate salt stress (120 mM NaCl), measuring biomass (dry weight) and RA/QU in leaves and roots after three (T1) and five weeks (T2). Blue light produced the greatest root biomass, while the leaf dry weight under B did not differ significantly from RB or RBfr. RA peaked at T2 under B in leaves and under R in roots; QU was maximal under B in leaves and under RB in roots. Extending exposure from T1 to T2 markedly increased both metabolites’ yield. Salinity had little effect on biomass, increased the total QU yield, and did not enhance the total RA yield. These results indicate that targeted LED regimes and longer exposure can raise the yields of bioactive compounds, and that combining specific spectra with moderate salinity is an effective strategy for selectively increasing quercetin accumulation in indoor-grown C. blumei. Full article

Use of anticholinergic and sedative medications is potentially inappropriate in older adults due to associated adverse effects, including impaired cognitive and physical function. This study evaluated anticholinergic and sedative burden in Croatian community-dwelling older adults using the Drug Burden Index (DBI) and examined its association with self-reported health and healthcare utilization over 12 months. This observational, cross-sectional study, part of the EuroAgeism H2020 ESR 7 project, included conveniently sampled adults ≥ 65 years from community pharmacies in three Croatian regions. Data were collected using a standardized research questionnaire. DBI was used to quantify exposure to anticholinergic and sedative medications. Multivariate regression analyses examined associations between DBI and health outcomes, using logistic regression for binary outcomes and linear regression for self-reported health. Among 388 participants (63.7% female, median age 73), most had multimorbidity (median five diagnoses) and polypharmacy (63.9%), while 57% used at least one DBI medication—most commonly diazepam (15.5%) and tramadol (14.7%). High DBI (≥1) independently predicted more emergency department (ED) visits (OR = 2.45) and worse self-rated health (B = −0.26), but not hospitalization. High DBI in older adults was associated with more ED visits and poorer self-rated health, highlighting the need for targeted interventions to reduce anticholinergic and sedative use in this vulnerable population. Full article

Background/Objectives: This cross-sectional study aimed to identify predictors of parent-reported health-related quality of life (HRQOL) in young children with early brain damage and severe motor dysfunction. It used baseline data from the PIH Multi Study, a randomized controlled trial evaluating an intensive, family-centered habilitation program for preschool children and their parents. Methods: Parent-reported HRQOL were measured using the CPCHILD questionnaire. Potential predictors included adaptive function (PEDI-CAT), gross motor function (GMFM-66), postural control and balance (ECAB), and communication function (FOCUS). These were selected to reflect the domains of the ICF-CY framework. Data were collected by professionals and by parents. Linear regression analyses were conducted to identify significant predictors. Results: Analyses included 65 children. Better adaptive skills, gross motor function, postural control, and communication all predicted higher parent-reported HRQOL. Adaptive skills—particularly in self-care and mobility—and gross motor function emerged as the strongest predictors. Conclusions: The study highlights the importance of targeting basic functional skills in early habilitation efforts for children with severe disabilities. The findings support a multidimensional understanding of health in line with the ICF-CY framework and underline the value of early, individualized, and family-centered interventions. Future research should investigate these predictors longitudinally and explore ways to integrate children’s own perspectives in assessment of HRQOL. Full article

Background: Colorectal cancer (CRC) is significantly associated with multiple metabolic diseases, with plasma metabolites potentially mediating this relationship. This large-scale metabolomics study aims to (1) quantify the genetic correlations and causal effects between 10 metabolic disease-related phenotypes and CRC risk; (2) identify the plasma metabolites mediating these effects; and (3) explore downstream regulatory genes and druggable targets. Methods: Using linkage disequilibrium score regression and two-sample Mendelian randomization, we assessed the causal relationships between each metabolic trait and CRC. A total of 1091 plasma metabolites and 309 metabolite ratios were identified and analyzed for mediating effects by a two-step MR approach. Colocalization analyses evaluated shared genetic loci. The findings were validated in the UK Biobank for metabolite-trait associations. The expression of candidate genes was explored using data from TCGA, GTEx, and GEO. A FADS1-centered protein–protein interaction (PPI) network was constructed via STRING. Results: BMI, waist circumference, basal metabolic rate, insulin resistance and metabolic syndrome exhibited both genetic correlation and causal effects on CRC. Five plasma metabolites—mannonate, the glucose/mannose ratio, plasma free asparagine, 1-linolenoyl-2-linolenoyl-GPC (18:2/18:3), and the mannose/trans-4-hydroxyproline ratio—were identified as shared central mediators. A colocalization analysis showed rs174546 linked CRC and 1-linolenoyl-2-linoleoyl-GPC. Validation in the UK Biobank confirmed the associations between phosphatidylcholine (the lipid class of this metabolite), adiposity measures, and CRC risk. An integrative analysis of TCGA, GTEx, and GEO revealed consistent upregulation of FADS1/2/3 and FEN1 in CRC, with high FADS1 expression predicting a poorer prognosis and showing the distinct cell-type expression in adipose and colon tissue. The PPI network mapping uncovered nine FADS1 interacting proteins targeted by supplements such as α-linolenic acid and eicosapentaenoic acid. Conclusions: This study systematically reveals, for the first time, the shared intermediary plasma metabolites and their regulatory genes in the causal pathway from metabolic diseases to CRC. These findings provide candidate targets for subsequent functional validation and biomarker development. Full article

Background/Objectives: Therapeutic exercises during hospitalization may provide important benefits for onco-hematological patients. However, the most effective protocols and outcomes for evaluation remain unclear. The objective of this study was to evaluate the effects of a structured exercise program during hospitalization. Methods: We conducted a randomized clinical trial with hospitalized onco-hematological patients. The control group performed conventional exercises, while the intervention group received a combined program of aerobic and resistance training. Outcomes included functional capacity, muscle strength, quality of life, and fatigue, assessed at admission and discharge. The sample size was calculated for a moderate effect size (Cohen’s d = 0.50; α = 0.05; power = 80%), yielding a target of 35 participants per group. Data were analyzed using repeated measures analysis of variance, followed by Bonferroni post hoc tests. The significance level was set at 5%. Results: The intervention group showed significant improvements in dyspnea (p = 0.017) and pain (p = 0.024) compared with the control group. In addition, reductions in insomnia (p = 0.021) and improvements in emotional functioning (p = 0.024) were observed. No significant between-group differences were found for fatigue, muscle strength, or functional capacity. Conclusions: A short-term program of aerobic and resistance exercises was safe and improved pain and dyspnea in hospitalized onco-hematological patients, with additional favorable effects on insomnia and emotional function. However, no significant effects were detected in fatigue, muscle strength, or functional capacity, likely due to the short hospitalization period and limited number of sessions. Future studies should consider longer interventions and post-discharge follow-up to clarify the sustainability of these benefits. Full article

This study integrates the price-to-income ratio (PIR) with Pareto distribution characteristics to provide a novel approach for evaluating home affordability across U.S. counties. The methodology offers a new lens for the analysis of home affordability by capturing both the extreme values and central tendencies of PIR. The study normalizes the resulting Pareto parameters to a common scale and integrates data from the Zillow Home Value Index and the U.S. Department of Commerce’s SAIPE program to create a single affordability index. The findings point to significant regional differences: coastal and urban regions, such as California and New York, face significant affordability challenges, whereas the Midwest, especially Kansas, has higher affordability. The results highlight the significance of targeted policy interventions and are consistent with the body of research on systemic risk and housing market dynamics. This study also opens new avenues for future research, including the impact of economic factors on affordability and cross-regional comparative studies. The suggested approach encourages more equitable access to housing by providing policymakers with a useful tool to track and manage challenges related to housing affordability. Full article

Background: Vascular calcification has been highlighted as a prognostic factor for perioperative thrombosis but a protective factor for late restenosis in lower limb peripheral artery disease (LLPAD). The aim of this study was to investigate the association between calcification and twelve-month primary patency in patients with stenting of the common femoral artery (CFA) and its bifurcation for atheromatous stenosis. Materials/Methods: This single-center retrospective study analyzed consecutive limbs (n = 90) that underwent CFA stenting for symptomatic lesions between January 2018 and January 2023. Calcification was assessed using dedicated computed tomography angiography analysis software (EndoSize; Therenva), with blinded evaluation of volume (mm³) and density (Hounsfield Units) across three anatomically distinct zones: proximal CFA (Zone 1); distal CFA (Zone 2); and bifurcation segments (Zone 3). The primary endpoint was twelve-month primary patency, defined as a peak systolic velocity ratio (PSVR) < 2.4 on duplex ultrasound without target lesion revascularization. Secondary endpoints included predictors of restenosis using multivariable logistic regression. Results: Ninety cases of CFA stenting for LLPAD (lower limb peripheral artery disease) were analyzed. A total of 78.9% of CFA lesions were treated for claudication and 21.1% for critical limb-threatening ischemia (CLTI). Lesions were distributed as Azema types I (1%), II (43%), and III (56%). At twelve-month follow-up, primary patency (PSVR < 2.4) was achieved in 77.4% of limbs. Patent CFA stenting demonstrated significantly higher median calcification density in Zone 2 compared to those with restenosis (1122 [IQR: 903–1248] vs. 858 [788–987] HU; p = 0.006; q = 0.021 after false discovery rate correction). ROC curve analysis identified a density threshold of 800 HU with a 76% reduction in restenosis risk (OR 0.24; 95% CI: 0.08–0.72; p = 0.011). Bootstrap validation (1000 replications) confirmed threshold stability at 821 HU (95% CI: 656–990 HU). Conclusions: In this exploratory study, dense calcification (≥800 HU) in the distal CFA appears to be protective against twelve-month restenosis following stenting. These findings suggest that calcification density may serve as a valuable predictor for patient selection and procedural planning in CFA interventions. Full article

Sepsis is a life-threatening condition driven by a dysregulated host response to infection, with high mortality and few treatment options. Decades of failed drug development underscore the urgent need for therapies with novel mechanisms of action. Vimentin, an intermediate filament protein, acts as a network hub that senses and integrates cellular signals. Its involvement in key sepsis pathologies, including infection, hyperinflammation, immunosuppression, coagulopathy and metabolic dysregulation, positions it as a potential therapeutic target. This study evaluated the efficacy of ALD-R491, a novel small-molecule vimentin modulator, in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Mice received ALD-R491 prophylactically or therapeutically, alone or with ceftriaxone. The treatment significantly reduced serum levels of key biomarkers of sepsis, including C-reactive protein (CRP), lactate (Lac), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and dose-dependently improved the survival of septic mice. Organ-specific analysis confirmed the effects of ALD-R491 in mitigating hyperinflammation and multi-organ injury. The treatment reduced pulmonary edema and inflammation; preserved liver tissue architecture and improved hepatic function with lowered alanine aminotransferase/aspartate aminotransferase (ALT/AST); decreased kidney tubular damage; and improved renal function with lowered creatinine/blood urea nitrogen (BUN). These preclinical findings indicate that the vimentin-targeting agent ALD-R491 represents a promising therapeutic candidate for sepsis and merits further clinical investigation. Full article

In recent years, Meteorin-like protein (Metrnl/IL-41) and Follistatin-like 1 (FSTL1) have emerged as multifunctional molecules that play roles in immunity, metabolism and tissue remodeling. Although they demonstrate pleiotropic effects, they are promising candidates for biomarkers and possible therapeutic targets. The development of new, disease-specific biomarkers will enable clinicians to more effectively monitor inflammatory activity, more accurately assess disease severity, better predict survival, and select appropriate medical treatments. In this review, we present the role of Meteorin-Like Protein (Metrnl) and Follistatin-like 1 (FSTL1) in inflammation in autoimmune rheumatic diseases, as well as in other autoimmune pathologies, cardiovascular diseases, and metabolic diseases. Metrnl, widely expressed in different tissues and organs, is very important for inflammation, immune responses and metabolic disorders. FSTL1 also shows dynamic changes in its expression through various diseases, including cardiovascular conditions, cancer, asthma, and arthritis. Both proteins participate in multiple important signaling pathways, and understanding their diagnostic and therapeutic potential holds great scientific interest. Their complex nature requires careful evaluation of safety concerns and translation to clinical practice. Full article

Urban traffic noise has become an increasingly significant environmental and public health issue, with many cities—particularly those experiencing rapid urban growth, such as Kuwait—recording levels that often exceed recommended limits. In this study, we present a detailed, data-driven approach for assessing and predicting equivalent continuous noise levels (LAeq) in residential neighborhoods. The analysis draws on measurements taken at 12 carefully chosen sites covering different road types and urban settings, resulting in 21,720 matched observations. A range of predictors was considered, including road classification, traffic composition, meteorological variables, spatial context, and time of day. Four predictive models—Linear Regression, Support Vector Machine (SVM), Gaussian Process Regression, and Bagged Trees—were evaluated through 5-fold cross-validation. Among these, the Bagged Trees model achieved the strongest performance (R² = 0.91, RMSE = 2.13 dB(A)). To better understand how the model made its predictions, we used SHAP (SHapley Additive Explanations) analysis, which showed that road classification, location, heavy vehicle volume, and time of day had the greatest influence on noise levels. The results identify the main determinants of traffic noise in Kuwait’s urban areas and emphasize the role of targeted design and planning in its mitigation. Full article

Background/objectives: Alcohol use during pregnancy can result in adverse outcomes for the offspring, including Fetal Alcohol Spectrum Disorders (FASD). Psychosocial and contextual factors may influence gestational alcohol intake and women’s risk perception. This systematic review aimed to assess pregnant women’s and women of childbearing age’s perceived risk of alcohol use during pregnancy and to evaluate their knowledge of its potential effects on children. Methods: Following the PRISMA guidelines, a systematic search was conducted in Web of Science, PubMed and PsycArticles databases for studies published up to May 2025. Eligible studies examined gestational alcohol use, risk perception, or knowledge of fetal consequences among pregnant women or women of reproductive age. Methodological quality was assessed with the Critical Appraisal of Qualitative Studies tool from the Centre for Evidence-Based Medicine (CEBM). Results: Twenty-nine studies were included. Reported prevalence of alcohol consumption during pregnancy varied considerably across settings. A substantial proportion of women perceived alcohol use during pregnancy as acceptable, often depending on quantity, frequency, type of beverage, or stage of gestation. Knowledge of FASDs was generally limited and frequently restricted to physical malformations. Misconceptions were more common among women with prior alcohol use. The findings highlight persistent gaps in risk perception and knowledge about FASDs. Conclusions: Prevention strategies should not be limited to pregnant women but should also target women of childbearing age, especially those with active drinking patterns, as well as their immediate sociocultural environment. Strengthening professional training, community-based interventions, and consistent public health messaging are essential to reduce gestational alcohol exposure. Full article

In this study, inter-brand variations in volatile flavor compound profiles of four lager beers were systematically investigated by integrating sensory evaluation with GC-MS, GC×GC-TOF-MS, and GC-O-MS. A total of 594 volatile compounds were identified, of which 71 with odor activity values (OAV) ≥ 1 were found to contribute directly to aroma expression. Additionally, 59 compounds with taste activity values (TAV) ≥ 1 were identified and may also contribute to taste perception. Furthermore, 53 aroma-active compounds were confirmed through GC-O-MS, providing additional evidence for their sensory contribution. Partial least squares discriminant analysis (PLS-DA), correlation analysis, and flavor addition experiments revealed brand-specific differential flavor compounds. Ultimately, twenty key differential flavor compounds, encompassing esters, alcohols, aromatic compounds, acids, lactones, and others, were confirmed to contribute to fruity, floral, burnt, and sweet notes. Phenethyl alcohol, with concentrations varying from 1377.1 mg/L in QD to 3297.5 mg/L in HR, showed a more than 2.4-fold difference across brands and was strongly associated with fruity (r = 0.553) and floral (r = 0.564) aroma. These compounds acted in combination to shape distinct aroma profiles. This study provides a molecular-level basis for understanding lager beer flavor and offers practical guidance for targeted flavor modulation in brewing. Full article