Search Results (20,237)

Background and Objective: This study presents a combined osteometric and biomechanical analysis of a Korean female cadaver exhibiting bilateral lower limb bone asymmetry with abnormal curvature and callus formation on the left femoral midshaft. Methods: To investigate bilateral bone length differences, osteometric measurements were conducted at standardized landmarks. Additionally, we developed three gait models using Meta Motivo, an open-source reinforcement learning platform, to analyze how skeletal asymmetry influences stride dynamics and directional control. Results: Detailed measurements revealed that the left lower limb bones were consistently shorter and narrower than their right counterparts. The calculated lower limb lengths showed a bilateral discrepancy ranging from 39 mm to 42 mm—specifically a 6 mm difference in the femur, 33 mm in the tibia, and 36 mm in the fibula. In the gait pattern analysis, the normal model exhibited a straight-line gait without lateral deviation. In contrast, the unbalanced, non-learned model demonstrated compensatory overuse and increased stride length of the left lower limb and a tendency to veer leftward. The unbalanced, learned model showed partial gait normalization, characterized by reduced limb dominance and improved right stride, although directional control remained compromised. Conclusions: This integrative approach highlights the biomechanical consequences of lower limb bone discrepancy and demonstrates the utility of virtual agent-based modeling in elucidating compensatory gait adaptations. Full article

Background/Objectives. Efficient nucleic acid delivery into target cells remains a critical challenge in gene therapy. Due to its advantages in biocompatibility and safety, recent research has increasingly focused on non-viral gene delivery. Methods. A series of copolymers—synthesized by integrating thermally sensitive poly(N-isopropylacrylamide) (PNIPAm), hydrophilic poly(ethylene glycol) (PEG) grafts, and a polycationic poly(L-lysine) (PLL) block of varying lengths ((PNIPAm)₇₇-graft-(PEG)₉-block-(PLL)_z, z = 10–65)—were investigated. Plasmid DNA complexation with the copolymers was achieved through temperature-modulated methods. The resulting polyplexes were characterized by evaluating complex strength, particle size, zeta potential, plasmid DNA loading capacity, resistance to anionic stress, stability in serum, and lysosomal membrane destabilization assay. The copolymers’ potential for plasmid DNA delivery was assessed through cytotoxicity and transfection studies in cancer cell lines. Results. Across all complexation methods, the copolymers effectively condensed plasmid DNA into stable polyplexes. Particle sizes (60–90 nm) ranged with no apparent correlation to copolymer type, complexation method, or N/P ratio, whereas zeta potentials (+10–+20 mV) and resistance to polyanionic stress were dependent on the PLL length and N/P ratio. Cytotoxicity analysis revealed a direct correlation between PLL chain length and cell viability, with all copolymers demonstrating minimal cytotoxicity at concentrations required for efficient transfection. PNL-20 ((PNIPAm)₇₇-graft-(PEG)₉-block-(PLL)₂₀) exhibited the highest transfection efficiency among the tested formulations while maintaining low cytotoxicity. Conclusions. The study highlights the promising potential of (PNIPAm)₇₇-graft-(PEG)₉-block-(PLL)_z copolymers for effective plasmid DNA delivery to cancer cells. It reveals the importance of attaining the right balance between polyplex tightness and plasmid release to achieve improved biocompatibility and transfection efficiency. Full article

Johannes Althusius (1563–1638) was a pioneer of early modern federalism. Opposing Jean Bodin’s theory of absolute sovereignty, his theory, centered on association and symbiosis, laid the groundwork for later concepts such as associationalism, consociationalism, and the principle of subsidiarity. While his ideas have been rediscovered and reinterpreted by scholars since the 20th century, systematic research on his federalist framework, especially contrasting it with rival theories of that time, remains insufficient. This article addresses this research gap by systematically exploring Althusius’s federalism. It argues that Althusius’s covenant-based, multi-level associational/federal framework provided a counter-theory to the concept of absolute sovereignty. Systematically studying his federalism not only helps to restore his federalist ideas to their rightful place in the history of federalist thought, but also provides insights for contemporary governance paradigms struggling with modern pluralism. Full article

Background/Objectives: Malnutrition is an imbalance of nutrients required for growth, development, and organ function. Its impact on bone development is known, but its effects on cartilage remain unclear. This study aimed to evaluate the femoral cartilage thickness in children with primary malnutrition. Methods: In this cross-sectional observational study, 83 children with primary malnutrition and 62 age- and sex-matched healthy controls were included. Patients with primary malnutrition were classified as mild, moderate and severe. Femoral cartilage thickness measurements of all children were taken by ultrasound from the femoral lateral condyle, femoral medial condyle and intercondylar area for both knees with the patient in a supine position with the knees flexed 90 degrees. Results: The right lateral, right medial, left lateral, and left medial femoral cartilages were significantly thicker in patients with malnutrition compared to those without malnutrition (p = 0.002, 0.004, <0.001, and 0.001, respectively). A significant negative correlation was found between age, weight Z-score, and height Z-score and triceps skinfold thickness. Conclusions: Distal femoral cartilage thickness is significantly greater in children with primary malnutrition. This demonstrates the effect of nutritional factors on cartilage tissue and suggests that children with chronic malnutrition are at risk for both knee joint problems and short stature later in life. Full article

Background: The influence of the initial ablation modality on pulmonary vein (PV) reconnection and substrate characteristics in redo procedures for recurrent atrial fibrillation (AF) remains unclear. We assessed how different thermal strategies—ablation index (AI)-guided radiofrequency (RF) versus cryoballoon (CB) ablation—affect remapping findings during redo pulmonary vein isolation (PVI). Methods: We included patients undergoing redo ablation between 2015 and 2024 with high-density electroanatomic mapping. Initial PVI modalities were retrospectively classified as low-power, long-duration (LPLD) RF; high-power, short-duration (HPSD) RF; or second-/third-generation CB. Reconnection sites were mapped using multielectrode catheters. Redo PVI was performed using AI-guided RF. Segments showing PV reconnection were reisolated; if all PVs remained isolated and AF persisted, posterior wall isolation was performed. Results: Among 195 patients (LPLD: 63; HPSD: 30; CB: 102), complete PVI at redo was observed in 0% (LPLD), 23.3% (HPSD), and 10.1% (CB) (p < 0.01 for LPLD vs. HPSD). Reconnection patterns varied by technique; LPLD primarily affected the right carina, while HPSD and CB showed reconnections at the LSPV ridge. Organized atrial tachycardia was least frequent after CB (12.7%, p < 0.002). Conclusion: Initial ablation strategy significantly influences PV reconnection and post-PVI arrhythmia patterns, with implications for redo procedure planning. Full article

Background/Objectives: Iron deficiency (ID) is a common and prognostically relevant comorbidity in heart failure with reduced ejection fraction (HFrEF). It contributes to reduced functional status, exercise capacity, and survival. Intravenous ferric carboxymaltose (FCM) improves symptoms, but its effect on cardiac structure and function remains incompletely understood. The aim of this study was to assess the impact of intravenous FCM on echocardiographic indices of left ventricular (LV), left atrial (LA), and right ventricular (RV) morphology and function in HFrEF patients with ID and determine whether these changes correlate with improvements in exercise capacity. Methods: This sub-analysis of the RESAFE-HF registry (NCT04974021) included 86 HFrEF patients with ID (median age 71.8 years, 83% male). Transthoracic echocardiography was performed at baseline and 12 months post-FCM. Parameters assessed included LV ejection fraction (LVEF), LV global longitudinal strain (GLS), LV diastolic function grade, LAVi, LA strain, TAPSE, and RV free wall strain (FWS). Peak VO₂ was measured to assess exercise capacity. Results: LVEF improved from 29.3 ± 7.8% to 32.5 ± 10.6% (p < 0.001), LV GLS from −7.89% to −8.62%, and the LV diastolic dysfunction grade improved (p < 0.001). LAVi, peak LA strain, TAPSE, and RV FWS also showed significant improvement. Peak VO₂ increased from 11.3 ± 3.2 to 12.1 ± 4.1 mL/min/kg (p < 0.001). Improvements in LVEF, RV FWS, and LV GLS were independent predictors of VO₂ increase (p < 0.001, p < 0.001, and p = 0.01, respectively), explaining 42% of the variance. Conclusions: FCM therapy improves biventricular and atrial function, with echocardiographic gains correlating with an enhanced exercise capacity in HFrEF patients with ID. Full article

Background/Objectives: Despite legal frameworks acknowledging the need to protect the rights of female prisoners, penitentiary systems often neglect gender-specific needs, particularly for foreign women. Among them, Muslim women face distinct challenges linked to cultural and religious practices, which are frequently unmet in prison contexts. This review aims to explore the academic literature on the experiences of Muslim women in detention. Methods: A systematic review was conducted using three major bibliographic databases—Scopus, PubMed, and Web of Science—covering the period from 2010 to 2024. Inclusion criteria focused on peer-reviewed studies examining the condition of Muslim women in prison. Of the initial pool, only four articles met the criteria and were included in the final analysis. Results: The review reveals a marked scarcity of research on Muslim women in prison at both national and international levels. This gap may be due to their limited representation or cultural factors that hinder open discourse. The selected studies highlight key issues, including restricted access to services, limited ability to practice religion, and language and cultural barriers. These challenges contribute to increased psychological vulnerability, which is often underestimated in prison settings. Conclusions: There is an urgent need for targeted research and culturally competent training for prison staff to adequately support Muslim women in detention. Greater academic and institutional attention is essential to develop inclusive policies that consider the intersection of gender, religion, and migration, particularly in the post-release reintegration process. Full article

Change point models are widely used in medical and epidemiological studies to capture the threshold effects of continuous covariates on health outcomes. These threshold effects represent critical points at which the relationship between biomarkers or risk factors and disease risk shifts, often reflecting underlying biological mechanisms or clinically relevant intervention points. While most existing methods focus on right-censored data, interval censoring is common in large-scale clinical trials and follow-up studies, where the exact event times are not observed but are known to fall within time intervals. In this paper, we propose a semiparametric transformation model with an unknown change point for interval-censored data. The model allows flexible transformation functions, including the proportional hazards and proportional odds models, and it accommodates both main effects and their interactions with the threshold variable. Model parameters are estimated via the EM algorithm, with the change point identified through a profile likelihood approach using grid search. We establish the asymptotic properties of the proposed estimators and evaluate their finite-sample performance through extensive simulations, showing good accuracy and coverage properties. The method is further illustrated through an application to the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial data. Full article

Background/Objectives: Preoperative strategies for hepatocellular carcinoma (HCC) requiring major hepatectomy remain controversial, particularly in “borderline resectable” cases. This study aimed to evaluate the oncological benefit and perioperative safety of Yttrium-90 transarterial radioembolization (TARE) in patients undergoing right or extended right hepatectomy for HCC. Material and Methods: All consecutive patients who underwent right or extended right hepatectomy for HCC at a single tertiary center between January 2013 and December 2023 were retrospectively reviewed. Patients were grouped based on whether they received preoperative TARE or underwent upfront resection. Outcomes analyzed included perioperative morbidity and long-term oncological endpoints. Results: A total of 39 patients were included, of whom 18 received preoperative TARE and 21 underwent upfront surgery. Patients in the TARE group showed significantly greater tumor necrosis at pathology (70% vs. 10%, p = 0.002) and more frequent extended resections. Five-year cancer-specific survival (80.4% vs. 33.5%, p = 0.011), recurrence-free survival (33.8% vs. 14.0%, p = 0.047), and curative-intent disease-free survival (69.3% vs. 18.9%, p = 0.0037) were significantly higher in the TARE group. Overall survival showed a favorable trend. Intraoperative outcomes, postoperative morbidity, and 90-day mortality were comparable between groups. Conclusions: Preoperative TARE is a safe and effective neoadjuvant strategy in selected patients with HCC undergoing major hepatectomy. It may enhance long-term oncological outcomes without increasing surgical risk, supporting its potential role in the management of borderline resectable HCC. Full article

Large, high-quality patient datasets are essential for applications like economic modeling and patient simulation. However, real-world data is often inaccessible or incomplete. Synthetic patient data offers an alternative, and current methods often fail to preserve clinical plausibility, real-world correlations, and logical consistency. This study presents a patient cohort generator designed to produce realistic, statistically valid synthetic datasets. The generator uses predefined probability distributions and Cholesky decomposition to reflect real-world correlations. A dependency matrix handles variable relationships in the right order. Hard limits block unrealistic values, and binary variables are set using percentiles to match expected rates. Validation used two datasets, NHANES (2021–2023) and the Framingham Heart Study, evaluating cohort diversity (general, cardiac, low-dimensional), data sparsity (five correlation scenarios), and model performance (MSE, RMSE, R², SSE, correlation plots). Results demonstrated strong alignment with real-world data in central tendency, dispersion, and correlation structures. Scenario A (empirical correlations) performed best (R² = 86.8–99.6%, lowest SSE and MAE). Scenario B (physician-estimated correlations) also performed well, especially in a low-dimensions population (R² = 80.7%). Scenario E (no correlation) performed worst. Overall, the proposed model provides a scalable, customizable solution for generating synthetic patient cohorts, supporting reliable simulations and research when real-world data is limited. While deep learning approaches have been proposed for this task, they require access to large-scale real datasets and offer limited control over statistical dependencies or clinical logic. Our approach addresses this gap. Full article

Background: Comorbid personality disorders (PDs) in patients with anorexia nervosa (AN) are associated with increased psychopathology, higher suicide risk, and poorer treatment response and outcomes. This study aimed to examine associations between gray matter (GM) volume and PDs in female adolescents with AN before and after short-term psychotherapeutic and nutritional therapy. Methods: Eighteen female adolescents with acute AN, mean age 15.9 years, underwent 3T magnetic resonance imaging before and after weight restoration. The average interval between scans was 2.6 months. Structural brain changes were analyzed using voxel-based morphometry. PDs were assessed using the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID II) and the Assessment of Identity Development Questionnaire. Results: SCID-II total scores showed significant positive associations with GM volume in the mid-cingulate cortex at both time points and in the left superior parietal–occipital lobule at baseline. The histrionic subscale correlated with GM volume in the thalamus bilaterally and the left superior parietal–occipital lobule in both assessments, as well as with the mid-cingulate cortex at follow-up. Borderline and antisocial subscales were associated with GM volume in the thalamus bilaterally at baseline and in the right mid-cingulate cortex at follow-up. Conclusions: PDs in female adolescent patients with AN may be specifically related to GM alterations in the thalamus, cingulate, and parieto-occipital regions, which are present during acute illness and persist after weight restoration therapy. Full article

Arrhythmogenic cardiomyopathies (ACMs) are a phenotypically and etiologically heterogeneous group of myocardial disorders characterized by fibrotic or fibro-fatty replacement of ventricular myocardium, electrical instability, and an elevated risk of sudden cardiac death. Initially identified as a right ventricular disease, ACMs are now recognized to include biventricular and left-dominant forms. Genetic causes account for a substantial proportion of cases and include desmosomal variants, non-desmosomal variants, and familial gene-elusive forms with no identifiable pathogenic mutation. Nongenetic etiologies, including post-inflammatory, autoimmune, and infiltrative mechanisms, may mimic the phenotype. In many patients, the disease remains idiopathic despite comprehensive evaluation. Cardiac magnetic resonance imaging has emerged as a key tool for identifying non-ischemic scar patterns and for distinguishing arrhythmogenic phenotypes from other cardiomyopathies. Emerging classifications propose the unifying concept of scarring cardiomyopathies based on shared structural substrates, although global consensus is evolving. Risk stratification remains challenging, particularly in patients without overt systolic dysfunction or identifiable genetic markers. Advances in tissue phenotyping, multi-omics, and artificial intelligence hold promise for improved prognostic assessment and individualized therapy. Full article

This study describes and validates a novel method for assessing anterior crystalline lens curvature along vertical and horizontal meridians using radial measurements derived from Scheimpflug imaging. The aim was to evaluate whether pupil diameter (PD), anterior lens curvature, and anterior chamber depth (ACD) change during accommodation and whether these changes are age-dependent. A cross-sectional study was conducted on 104 right eyes from healthy participants aged 21–62 years. Sixteen radial images per eye were acquired using the Galilei Dual Scheimpflug Placido Disk Topographer under four accommodative demands (0, 1, 3, and 5 dioptres (D)). Custom software analysed lens curvature by calculating eccentricity in both meridians. Participants were analysed as a total group and by age subgroups. Accommodative amplitude and monocular accommodative facility were inversely correlated with age. Both PD and ACD significantly decreased with higher accommodative demands and age. Relative eccentricity decreased under accommodation, indicating increased lens curvature, especially in younger participants. Significant curvature changes were detected in the horizontal meridian only, although no statistically significant differences between meridians were found overall. The vertical meridian showed slightly higher eccentricity values, suggesting that it remained less curved. By enabling detailed, meridionally stratified in vivo assessment of anterior lens curvature, this novel method provides a valuable non-invasive approach for characterizing age-related biomechanical changes during accommodation. The resulting insights enhance our understanding of presbyopia progression, particularly regarding the spatial remodelling of the anterior lens surface. Full article

Background: Right ventricular (RV) dysfunction is associated with poor clinical outcomes in critically ill sepsis patients, but its pathophysiology and predictors are incompletely characterized. We aimed to investigate the predictors of RV dysfunction and its outcomes in sepsis patients admitted to the intensive care unit (ICU). Methods: This is a single-center retrospective cohort study of adult patients admitted to the ICU for sepsis who had echocardiography within 72 h of diagnosis. Patients with acute coronary syndrome, acute decompensated heart failure, or significant valvular dysfunction were excluded. RV dysfunction was defined as the presence of RV dilation, hypokinesis, or both. Demographics and clinical outcomes were obtained from electronic medical records. Results: A total of 361 patients were included in our study—47 with and 314 without RV dysfunction. The mean age of the population was 66.8 years and 54.6% were females. Compared to those without RV dysfunction, patients with RV dysfunction were more likely to require mechanical ventilation (63.8% vs. 43.9%, p = 0.01) and vasopressor support (61.7% vs. 36.6%, p < 0.01). On multivariate logistic regression analysis, increasing age (OR 1.03, 95% C.I. 1.00–1.06), a history of HIV infection (OR 5.88, 95% C.I. 1.57–22.11) and atrial fibrillation (OR 4.34, 95% C.I. 1.83–10.29), and presence of LV systolic dysfunction (OR 14.40, 95% C.I. 5.63–36.84) were independently associated with RV dysfunction. Patients with RV dysfunction had significantly worse 30-day survival (Log-Rank p = 0.023). On multivariate Cox regression analysis, older age (HR 1.02, 95% C.I. 1.00–1.04) and peak lactate (HR 1.16, 95% C.I. 1.11–1.21) were independent predictors of 30-day mortality. Conclusions: Among other findings, our data suggests a possible association between a history of HIV infection and RV dysfunction in critically ill sepsis patients, and this should be investigated further in future studies. Patients with evidence of RV dysfunction had poorer survival in this population; however this was not an independent predictor of mortality in the multivariate analysis. A larger cohort with a longer follow-up period may provide further insights. Full article

Endometriosis is a benign and often underdiagnosed condition that affects women of reproductive age, typically between 18 and 45 years. It can cause infertility and pain, including radicular pain and low back pain (LBP). The aim of this case report is to emphasize the importance of making a differential diagnosis when facing LBP and radicular symptoms. We report the case of a 17-year-old female patient, R.A., presented with a significant LBP (NPRS 8/10) radiating from her lumbar spine to her right buttock and occasionally to both legs, accompanied by weakness. She revealed exacerbation of pain during menstruation, despite being under hormonal contraceptive treatment. After three physiotherapy sessions that included education, manual therapy and exercise, the patient’s pain persisted so her physiotherapist recommended an evaluation in the emergency department, where standard radiography did not reveal any significant findings. Physiotherapy continued until the fifth session, when the patient agreed to undergo evaluation at a specialized endometriosis centre. Further investigations revealed endometriotic tissue on the uterosacral ligament, leading to hormonal therapy adjustment, with which pain gradually decreased to a manageable level (NPRS 2/10). This case report highlights the importance of an early differential diagnosis in patients with LBP, as endometriosis can present not only in older women but also in younger patients, including those already on oral contraceptives. Therefore, to mitigate the risk of pattern recognition bias, clinicians must maintain a high index of suspicion for endometriosis, even in atypical or unlikely clinical presentations. Full article