Search Results (2,641)

Introduction: Major Depressive Disorder (MDD) has been increasingly associated with inflammatory dysregulation, particularly involving tumor necrosis factor-alpha (TNF-α). Genetic polymorphisms within the TNFA promoter region have been investigated as potential modulators of depressive susceptibility, symptom expression, treatment response, and inflammatory comorbidity. However, findings remain inconsistent across populations and clinical contexts. Methods: This systematic review adhered to PRISMA 2020 guidelines and was registered in PROSPERO (CRD420251242724). Observational and interventional studies evaluating associations between TNFA polymorphisms—specifically rs1800629 (−308 G/A), rs1799724 (−857 C/T), and rs1799964 (−1031 T/C)—and MDD-related outcomes in adults were included. Data extraction and methodological quality assessment were performed independently using an adapted GRIPS framework. Results: Eleven studies met the inclusion criteria, with eight investigating MDD without cardiovascular comorbidity and three assessing cardiovascular populations. Across diverse cohorts, rs1800629 and rs1799724 did not demonstrate consistent associations with MDD susceptibility. Although isolated population-specific findings were reported, genotype and allele distributions were generally comparable between cases and controls. Rs1799724 was associated with symptom dimensions and altered TNF-α expression in two cohorts. Rs1799964 was not linked to disease occurrence but showed potential association with antidepressant response and adverse cardiovascular outcomes in patients with chronic heart failure and comorbid depression. Overall, findings were heterogeneous and influenced by population characteristics, sample size, and clinical context. Conclusions: Current evidence does not support a robust etiological role for TNFA promoter polymorphisms in major depressive disorder. These variants may exert context-dependent modulatory effects on symptom expression, treatment response, or inflammatory-cardiovascular interactions rather than serving as primary susceptibility determinants. Larger, ethnically diverse studies integrating genetic, inflammatory, and clinical data are required to clarify the contribution of inflammatory genetic variability in depressive disorders. Full article

Under intensifying climate change and increasingly frequent extreme heat events, improving outdoor thermal environments has become critical for sustainable human settlements. While prior studies have mainly focused on urban contexts, systematic investigations of rural microclimates—particularly regarding the regulatory mechanisms of landscape configurations—remain limited. This study examines a mountain-adjacent village in the Loess Tableland region of China, integrating field measurements with ENVI-met simulations to analyze thermal characteristics of rural road spaces and the effects of vegetation and paving materials on human thermal comfort. The results show that village boundary areas experience the largest fluctuations in air temperature and relative humidity during midday and evening, indicating higher thermal sensitivity. Model validation demonstrates satisfactory accuracy, with RMSE values of 0.39–3.62 °C for air temperature, 1.32–3.22% for relative humidity, and 1.35–2.24 m/s for wind speed, and MAPE ranging from 0.80% to 9.05%. Furthermore, Basalt Brick and Populus alba show the best cooling performance, but when considering multiple factors such as temperature, humidity, and wind speed, Ligustrum lucidum has the most significant effects in improving thermal comfort and increasing humidity. Analysis based on Physiological Equivalent Temperature (PET) further indicates that vegetation configurations play a more substantial role in thermal comfort regulation than paving materials, and that different landscape elements exhibit synergistic and trade-off relationships in terms of cooling, humidification, and ventilation. This study provides quantitative reference for vegetation configuration and material selection in rural roads within the Loess Tableland region and similar semi-arid areas, enriches the research scope of rural microclimate studies, and offers scientific support for climate-adaptive rural planning and optimization of rural living environments. Full article

Background/Objectives: The guideline targets for blood pressure (BP), hemoglobin A1c (HbA1c), and low-density lipoprotein cholesterol (LDL-C) are frequently unmet, and physicians often misjudge control. This study aimed to characterize the real-world control of BP, HbA1c, and LDL-C in patients with type 2 diabetes (T2D) and hypertension, herein called cardiometabolic multimorbidity (CMM), and to compare guideline-based versus physician-perceived disease control. Methods: We conducted SNAPSHOT–Brazil, a nationwide, multicenter, cross-sectional study to gather real-world data on patients with CMM. The ESC guidelines defined the cardiovascular (CV) risk and control targets. Results: We included 451 patients with hypertension and T2D (median age 65 years; 60% female; 54% White). Most patients (98%) were on pharmacotherapy and reported high adherence (according to the Hill–Bone Medication Adherence Scale). A very high CV risk predominated (78%); 22% of the patients were at a high risk. The guideline-defined control was achieved in 27% for BP, 34% for HbA1c, 13% for LDL-C, and 6% for both BP and LDL-C; only 3% met all three targets simultaneously. The physicians accurately stratified the CV risk in 49% of patients, while 50% had their CV risk underestimated. They systematically overestimated control in 29% of cases for BP, 35% for LDL-C, and 25% for both. The sensitivity ranged from 0.88 to 0.98; the positive predictive values ranged from 0.19 to 0.48, and the positive likelihood ratios ranged from 2.16 to 3.65. Conclusions: The SNAPSHOT–Brazil study revealed a low attainment of BP, HbA1c, and LDL-C targets, despite the widespread pharmacotherapy and the high self-reported adherence. The physicians consistently overestimated disease control and underestimated the CV risk. Full article

Background. Cardiometabolic diseases (CMDs) have become a major health concern among adults living with HIV (ALWH) as antiretroviral therapy (ART) extends life expectancy. Metabolic syndrome (MetS)—a cluster of abdominal obesity, hypertension, hyperglycemia, hypertriglyceridemia, and hypoalphalipoproteinemia—is a key predictor of CMD risk. Despite high HIV prevalence in Panama, data on MetS among ALWH are scarce. Thus, the Colón C3 Study aimed to estimate the prevalence of MetS and its criteria in a large cohort of ALWH in Colón, Panama. Methods. Between April–December 2024, 659 ALWH aged ≥18 years were enrolled at the province’s sole ART Clinic (78.1% of active patients). Participants completed a computer-assisted survey on demographics and social determinants of health (SDoH), underwent anthropometry and body composition assessment, and provided ≥8 h fasting blood samples for glucose, lipid profiles, HbA1c, and high-sensitivity C-reactive protein (hsCRP). MetS was defined using NCEP-R ATP-III criteria, and analyses were stratified by sex. Results. Mean age was 43.9 (range 18–79) years; 55% were female, and 51% identified as Black/Afro-Caribbean. The overall prevalence of MetS was 38.6% (binomial 95% CI 34.5%, 42.9%), exceeding pooled estimates for ALWH in the Americas (30.4%). Among individual criteria, hypoalphalipoproteinemia (59.6%) and hypertension (52.6%) were most prevalent, followed by abdominal obesity (45.2%), hyperglycemia (33.5%), and hypertriglyceridemia (22.5%). Women exhibited significantly higher body fat mass and BMI than men. Mean hsCRP was 7.2 mg/L, indicating persistent inflammation despite virologic suppression. Socioeconomic vulnerabilities, food insecurity (30%), and housing instability (>40%) were common. Conclusions. Findings reveal a substantial cardiometabolic burden among ALWH in Colón and underscore the need for integrated HIV–CMD care models, earlier screening, and natal sex–responsive interventions. The results provide foundational evidence for improving long-term, equitable cardiometabolic outcomes in HIV care across Panama and the broader Latin American region. Full article

Background: Bikram yoga, a form of hot yoga practiced in heated environments, has been associated with improvements in flexibility, body composition, and overall well-being. However, longitudinal evidence on its effects in adult women remains limited. Obesity/metabolic syndrome (MetS) is highly prevalent among adult women worldwide, with estimates exceeding 40% in middle-aged populations, underscoring the need for low-impact interventions targeting adiposity and age-related metabolic risks. This study evaluated the effects of 6-month Bikram yoga on body fat percentage (%BF) in adult women, with age-stratified analyses. Methods: Twenty-two women (20–65 years) participated in a structured Bikram yoga program consisting of three weekly sessions (90 min, 26 postures + 2 breathing exercises, 40 °C, 40% humidity) over six months. Anthropometric assessments (8 skinfolds, 5 body circumferences, weight, and height) were conducted at T0, T1 (~45 days), T2 (~90 days), and T3 (6 months). %BF was estimated using multiple validated prediction equations integrated into the Exercise Science Toolkit. Results: A significant and progressive reduction in %BF was observed across the sample: −3.71% at T1 (p < 0.0001) and −6.07 at T3 (p < 0.0001) compared to the baseline. Positive outcomes were consistent across all age subgroups: subgroup A (20–35 years, T3 −6.62%), subgroup B (36–50 years, T3 −5.96%), and subgroup C (51–65 years, T3 −5.39%). Decreased inter-subject variability (SD) suggests a similar direction of change among participants. Conclusions: Regular Bikram yoga practice (three sessions per week for six months) was associated with significantly and consistently reduced %BF among adult women aged 20–65, exceeding the clinical threshold (>5%) for metabolic benefits. Effects were evident after six weeks and remained across all age subgroups, suggesting that Bikram yoga may represent an effective, low-impact intervention for health promotion and active aging. Full article

Background/Objectives: Cardiovasc{Citation}ular disease accounts for 50% of chronic kidney disease (CKD) mortality, yet fewer than 40% of patients achieve guideline LDL-cholesterol (LDL-C) targets on statins. Injectable lipid-lowering therapies (ILLTs)—PCSK9 inhibitors and inclisiran—offer 50–70% LDL-C reductions but lack comprehensive CKD-specific evidence synthesis. This systematic review evaluated ILLT efficacy, safety, and implementation across kidney function stages including dialysis. Methods: Following PROSPERO registration (CRD42024612594), we searched MEDLINE, Embase, Cochrane Library, CINAHL, and Google Scholar (1995–August 2025). Two reviewers independently screened studies using PICOS criteria: adults with CKD stages G3-G5, dialysis, or transplant recipients receiving injectable lipid therapies. Primary outcomes were LDL-C percentage change and major adverse cardiovascular events. Quality was assessed using NIH tools. Given heterogeneity, we performed narrative synthesis following SWiM guidance. Results: Eight studies (n = 28,013) met the criteria. The FOURIER trial demonstrated that evolocumab achieved 58–59% LDL-C reductions across kidney function strata (interaction p = 0.77) with preserved cardiovascular benefit (HR 0.82–0.89). Absolute risk reduction was greater in advanced CKD (2.5% vs. 1.7%), reflecting higher baseline rates. Pharmacokinetic studies showed no eGFR-exposure correlation requiring dose adjustment; evolocumab was not removed by haemodialysis. Inclisiran achieved a 67–80% PCSK9 reduction and a 35–58% LDL-C reduction across renal groups, with twice-yearly maintenance dosing. Both classes reduced non-HDL-C (45–50%), apoB (40–45%), and lipoprotein(a) (20–25%). Safety was favourable, with mild injection-site reactions (< 5%); no renal decline signals emerged. Conclusions: Evidence for injectable lipid-lowering therapies in CKD are driven largely by a single large post hoc subgroup analysis (FOURIER) and small phase 1–2 PK/PD studies, with minimal dialysis representation and no transplant data. These agents appear to provide substantial LDL-C reductions across CKD stages G3–G5 without dose adjustment, but cardiovascular and renal outcome data in advanced CKD and dialysis remain limited and should be interpreted cautiously. Full article

Background and Objectives: Autologous stem cell transplantation (ASCT) remains the standard of care for relapsed or refractory Hodgkin lymphoma (R/R HL), and an increasing proportion of patients receive programmed cell death protein 1 (PD-1) inhibitors prior to transplantation. Engraftment syndrome (ES) is a noninfectious inflammatory complication classically associated with neutrophil recovery; however, early peri-transplant inflammatory manifestations remain poorly characterized and may mimic infectious complications. We aimed to evaluate peri-transplant inflammatory events after ASCT, with particular emphasis on ES-compatible manifestations occurring before neutrophil engraftment and their association with prior PD-1 inhibitor exposure. Materials and Methods: In this single-center retrospective cohort study, 64 consecutive adult patients with HL undergoing ASCT between 2018 and 2025 were analyzed. ES was defined according to Spitzer and Maiolino criteria. Inflammatory manifestations fulfilling these criteria but occurring prior to neutrophil recovery were classified as pre-engraftment syndrome (pre-ES). Clinically significant events were defined by the requirement for systemic corticosteroid therapy. Clinical and laboratory parameters were compared using non-parametric statistical analyses. Results: No cases fulfilled the Spitzer criteria for classical ES, while three patients (4.7%) met the Maiolino criteria, none requiring corticosteroid therapy. Using the broader Maiolino definition, pre-ES was observed in 34 patients (53.1%) when the conventional engraftment time window was disregarded; however, only three patients required systemic corticosteroid therapy. Importantly, all three cases also fulfilled the Spitzer criteria outside the conventional time window, whereas the remaining Maiolino-defined pre-ES cases were self-limiting. All steroid-requiring pre-ES cases occurred exclusively in PD-1-exposed patients, and prior PD-1 therapy was significantly associated with severe pre-ES (p = 0.0007), although this finding is based on a very small number of events. These patients also demonstrated significantly higher early C-reactive protein (CRP) levels. Conclusions: While classical ES after ASCT was uncommon, clinically significant pre-ES occurred exclusively in PD-1-exposed patients. These early inflammatory events may represent a distinct phenotype and require prompt recognition and timely corticosteroid therapy after exclusion of infection. Prospective studies are warranted to validate these findings and refine risk stratification and monitoring strategies. Full article

Background/Objectives: Infantile cardiomyopathy is a rare but often life-threatening condition in which monogenic causes are particularly relevant, especially when cardiac disease is preceded by hypotonia or multisystem involvement. Among sarcomeric genes, MYL2, encoding the ventricular regulatory myosin light chain, plays a critical role in myocardial contractility. However, biallelic MYL2-associated disease remains exceptionally rare, and its clinical spectrum is not fully defined. This study aims to describe a novel case and further delineate the phenotype of recessive MYL2-related cardiomyopathy. Methods: We report a male infant with congenital hypotonia and delayed motor development who underwent extensive metabolic, neuromuscular, and neuroimaging evaluation. Trio-based whole-exome sequencing was performed to identify a potential genetic etiology, followed by variant interpretation using standard bioinformatic and ACMG/AMP criteria. Results: The patient developed acute decompensated heart failure at approximately 10 months of age, with severe left ventricular systolic dysfunction and multiorgan failure, and died at 12 months despite maximal intensive care support. Whole-exome sequencing identified a homozygous MYL2 c.413T>A (p.Met138Lys) missense variant. The variant is absent or extremely rare in population databases, affects a highly conserved residue, is predicted to be deleterious by multiple in silico tools, and is compatible with autosomal recessive inheritance, with both parents confirmed as heterozygous carriers. In the context of a phenotype consistent with recessive MYL2-associated disease, these findings support a likely pathogenic interpretation. Conclusions: This case expands the allelic and phenotypic spectrum of recessive MYL2-associated cardiomyopathy and highlights the value of early genomic testing in infants with unexplained hypotonia and rapidly progressive cardiac dysfunction. Molecular diagnosis may aid in prognosis, clinical decision-making, and genetic counseling. Full article

Background: Normal-weight obesity (NWO) is a nutritional status in which individuals have a normal body mass index (BMI) with a high percentage of body fat (%BF). However, the impact of elevated %BF on cardiometabolic risk remains unclear. This study aimed to evaluate whether NWO is associated with worse cardiometabolic risk markers and scores. Methods: We conducted a cross-sectional study using a convenience sample of employees from a public hospital. Participants aged ≥18 years with a BMI between 18.5–24.9 kg/m² were included in the study. %BF was categorized according to sex and age (InBody720). Normal weight and normal %BF (NWNB) and NWO were defined using cutoff points. Body composition, serum biochemical and inflammatory markers, hemodynamics, and autonomic function were considered cardiometabolic risk markers. The visceral fat area (VFA), atherogenic coefficient (AC), atherogenic index of plasma (AIP), body shape index (ABSI), and Framingham Risk (FR) score were considered cardiometabolic risk scores. Statistical significance was set at p < 0.05. Results: Of the 228 eligible participants, 52 met the inclusion criteria (NWNB, N = 29 and NWO, N = 23). Participants with NWO presented worse values of lipid profiles, anthropometric measurements, hemodynamic parameters, and autonomic function indices. After adjustment for age and sex, NWO remained associated with selected cardiometabolic markers, particularly LDL-c, triglycerides, and autonomic indices, whereas body composition findings should be interpreted as confirmatory of the phenotype. Conclusions: In this cross-sectional secondary analysis, NWO was associated with worse cardiometabolic markers and selected risk scores compared with NWNB. These findings support an unfavorable cardiometabolic profile in individuals with NWO, but do not allow inferences about future cardiometabolic events or causal relationships. Longitudinal studies are needed to clarify its prognostic significance. Full article

Unbiased stereology represents the most accurate approach for estimating the total number of neurons of specific brain regions; however, its reliability critically depends on the use of rigorously defined and anatomically appropriate sampling parameters. The brain nucleus Locus Coeruleus (LC) plays a key role in several brain functions. LC impairment has been associated with a range of disorders affecting individuals across the lifespan, from infancy to adulthood. In animal models of these conditions, precise estimation of LC neuronal number is essential. The LC analysis poses specific methodological challenges due to its small size, indistinct anatomical boundaries, and age-dependent changes in neuronal density. In this study, we present a detailed and reproducible stereological workflow for the quantification of LC neurons in the mouse brain across the lifespan. Using C57BL/6J mice at postnatal, adult, and aged stages, we optimized all key components of the Optical Fractionator method, LC neurons were identified by immunoperoxidase staining for tyrosine hydroxylase (TH) and quantified using systematic-random sampling implemented in Stereo Investigator^® software. We show that age-specific adjustment of stereological parameters is necessary to obtain reliable estimates, particularly at early postnatal stages characterized by high neuronal packing density. With the optimized protocols described here, TH+ LC neuron counts consistently met accepted precision criteria, as assessed by the Gundersen coefficient of error. Full article

This study systematically investigated the combined effects of drying method (mid- and short-wave infrared drying, MSID; hot air drying, HAD; radio frequency-hot air combined drying, RF-HAD), drying temperature (35, 45, 55, 60 °C), and initial wet-basis moisture content (20%, 25%, 30%) on drying characteristics, nutritional quality, texture, and oxidative stability of peanuts. RF-HAD achieved the shortest drying time, followed by MSID and HAD. Protein content remained stable across all treatments. Fat, oleic acid, and total amino acids were significantly affected by all three factors with significant two-way interactions; linoleic acid exhibited significant method × moisture and three-way interactions. Hardness, adhesiveness, springiness, gumminess, and chewiness showed significant three-way interactions, indicating interdependent effects. All samples met national standards for acid value and peroxide value. MSID yielded the lowest acid value and peroxide value immediately after drying, suggesting better initial oxidative quality. Acid value was primarily influenced by method and temperature, with significant two-way interactions, whereas peroxide value showed significant main effects and a highly significant three-way interaction. No single drying condition optimized all quality attributes. RF-HAD excels in drying efficiency and texture enhancement but requires temperature control to limit oxidation; MSID offers superior initial oxidative stability and amino acid retention. Initial moisture content acts as an active variable that modulates the effects of drying method and temperature. Full article

Background: Occult lymph node metastasis (LNM) occurs in 30–80% of patients with clinically node-negative papillary thyroid carcinoma (cN0-PTC), partly owing to the limited sensitivity of current preoperative nodal assessment, and may contribute to postoperative recurrence. Conventional sentinel lymph node (SLN) biopsy, typically performed with a single tracer, has limited reliability for detecting occult metastatic nodes, which can result in either overtreatment or undertreatment with lymph node dissection. We aimed to develop a highly accurate multimodal prediction framework to accurately identify second-echelon lymph node metastasis (SeLNM) and non-sentinel lymph node metastasis (NsLNM). Methods: We prospectively enrolled 301 patients with cN0-PTC between April and October 2024, of whom 131 met the inclusion criteria. Intraoperatively, a dual-tracer technique combining carbon nanoparticles and indocyanine green was applied, and near-infrared imaging was used to record the entire SLN visualization process in real time. For each case, a 3 min video clip (150 frames) was captured. Two senior surgeons delineated regions of interest to generate 19,650 mask images. A total of 2048 spatial features and 20 temporal features were extracted, combined with 32 clinical variables, including demographics, ultrasound characteristics, and gene mutation status. Nine deep learning models were developed and evaluated using 10-fold cross-validation. Model performance was quantified using receiver operating characteristic curves, decision curve analysis curves, calibration curves, precision–recall curves, learning curves, and 12 metrics. Statistical comparisons were performed using the DeLong test, and models were further evaluated using a probability-based ranking approach. Shapley Additive Explanations (SHAP) analysis was applied to interpret key predictive features. The primary outcomes were SeLNM and NsLNM, defined based on postoperative histopathology. Results: The Long Short-Term Memory (LSTM) + Transformer model showed the best performance for both prediction tasks, with stable AUCs across training and testing (SeLNM: 0.980/0.982; NsLNM: 0.986/0.983). In the testing set, the model reached the same accuracy for both outcomes (94.7%) and showed strong sensitivity/specificity for SeLNM (94.7%/94.6%) and NsLNM (96.4%/91.5%). SHAP analysis indicated that time-series fluorescence flow features were the most influential predictors, followed by spatial structural features and SLN status. Conclusions: Dual-tracer SLN mapping with deep learning demonstrated encouraging intraoperative prediction of lymph node metastasis with interpretable features in this single-center cohort. Independent multicenter validation and prospective outcome studies are needed before considering clinical adoption. Full article

Non-O1/non-O139 Vibrio cholerae strains are widely distributed in aquatic environments worldwide and are increasingly recognized as potential reservoirs of antimicrobial resistance and virulence-associated determinants. In this study, we performed an integrated phenotypic and genomic analysis of 116 V. cholerae isolates collected in 2024 from environmental and clinical sources in Jiaxing, China, including 106 non-O1/non-O139 isolates, 9 O1 isolates, and 1 O139 isolate. Antimicrobial susceptibility testing showed that most isolates remained susceptible to β-lactam/β-lactamase inhibitor combinations, third-generation cephalosporins, carbapenems, and tigecycline, whereas resistance was more frequently observed for ampicillin, streptomycin, nalidixic acid, and ciprofloxacin. Based on the non-susceptibility criteria of Maitrakas et al., 19 of 116 isolates (16.4%) were classified as multidrug-resistant, whereas none met the definition of extensively drug-resistant. Genomic analysis identified diverse resistance determinants, including plasmid-mediated quinolone resistance genes (qnrVC variants) and quinolone resistance-determining region mutations in gyrA and parC. Virulence-associated genes showed heterogeneous distributions: core regulatory and hemolysis-related genes were highly prevalent, whereas classical cholera toxin genes were largely absent. Several accessory virulence factors, including the RTX toxin operon, chxA, ninth, and makA, were detected in subsets of isolates. Core genome multilocus sequence typing revealed substantial genetic diversity, with environmental and clinical isolates distributed across multiple lineages and showing no clear clustering by isolation source. Overall, these data demonstrate the diverse antimicrobial resistance, virulence-associated gene repertoires, and population structure of the Jiaxing V. cholerae collection, with particular relevance to the predominant non-O1/non-O139 population. Full article

Background: Autologous serum eye drops (ASEDs) are produced without preservatives and need to be stored at 2–8 °C while in use. This study aims to analyze the behavior of specific bacteria and fungi in the case of contamination during the usage of single-day use ophtioles containing ASED. Methods: This is a prospective experimental study conducted at the Department of Ophthalmology, University Hospital of Zurich (USZ), and a regulatory-licensed, independent, external laboratory. The laboratory performed microbial testing on the ASEDs with 11 microorganisms in 100% concentration or 50% diluted using the original 2.5 mL ASED ophtioles provided by the Eye Bank of the Department of Ophthalmology, USZ. Storage took place at 2–8 °C and 20–25 °C. The acceptance criterion was the absence of microbial growth between opening (T0), 24 h afterwards (T24), and 48 h afterwards (T48). Results: The acceptance criteria were met for all microorganisms for 2–8 °C. For seven microorganisms, the acceptance criteria were met for 2–8 °C and 20–25 °C. For four microorganisms, the acceptance criteria were only met for 2–8 °C. Conclusions: No relevant growth was observed in any of the test strains from T0 to T24 and T48 at 2–8 °C, demonstrating the microbiological safety of reclosable single-day use ophtioles containing unpreserved ASEDs when stored at 2–8 °C. Full article

Background: This study aimed to investigate, from a scientific and formulation perspective, an oral semaglutide tablet incorporating sodium caprate (C10) as an intestinal absorption enhancer and to optimize its formulation performance using a Quality by Design (QbD)-based approach. Semaglutide—a peptide-based therapeutic—provides effective glycemic control and weight reduction; however, its extremely low oral bioavailability has limited administration to subcutaneous injection. Although various attempts have been made to improve peptide absorption, achieving consistent delivery through oral routes remains a significant challenge due to enzymatic degradation and poor membrane permeability. Methods: To overcome these limitations, an absorption enhancer (sodium caprate) was incorporated to enhance oral absorption, and a Quality by Design (QbD)-based approach was applied to systematically guide formulation development. Following the definition of the Quality Target Product Profile and critical quality attributes, risk assessments (Preliminary Hazard Analysis and Failure Mode and Effects Analysis) were conducted to identify key formulation factors. A design of experiments approach was then employed to determine the optimal tablet composition. Results: Consequently, the resulting formulation met all predefined quality criteria, including hardness, disintegration, friability, and content uniformity. In addition, the in vitro dissolution profile demonstrated a release pattern comparable to that of the reference product, with similarity factor values of 74.4, 74.7, and 71.3 at pH 1.2, 4.0, and 6.8, respectively. Conclusions: These findings indicate that the formulation can achieve consistent and reproducible quality performance as an oral semaglutide dosage form. The QbD-based formulation design strategy presented in this study provides a robust and broadly applicable approach for developing oral delivery systems for peptide drugs, including semaglutide, and ultimately provides useful formulation insight for future peptide-based oral delivery research. Full article