Abstract: Introduction Malocclusions are often treated with appliances made of metal alloys. These alloys biodegrade in oral cavity and release toxic metals such as nickel and chromium. This study aimed to assess nickel and chromium content in the saliva of patients wearing fixed orthodontic appliances. Materials and methods This was a cross-cutting study aiming at assessing nickel and chromium content in saliva. A survey was conducted to record socio-demographic characteristics and clinical signs due to the wearing of orthodontic appliances. A 10ml saliva sample was used to measure salivary pH and assess nickel and chromium concentrations using atomic emission spectrophotometry. A Student's T-test compared saliva metal levels in non-wearers and wearers of metal orthodontic appliances. Results On the whole, 92 participants, among whom 46 without appliance and 46 wearing appliance were received during the study period. Their mean age was 17.05±6.46 years. Patients’ mean saliva pH was 6.97±0.44. Mean nickel concentration was 4.39±4.01g/l in the saliva of non-appliance wearers and 20.41±18.56g/l in the saliva of appliance wearers, respectively. Chromium mean concentration was 1.3±1.33g/l for non-appliance wearers and 9.38±19.49g/l and for appliance wearers. Conclusions Metal orthodontic appliances release nickel and chromium in saliva. It is necessary to monitor the risk of intolerance and optimize treatment duration.

Abstract: Background and Clinical Significance: Synchronous gastrointestinal tumors are ex-ceptionally rare, particularly when combining histologically distinct benign and ma-lignant components. Schwannomas represent uncommon mesenchymal tumors of the gastrointestinal tract, most frequently arising in the stomach, while rectal localization is exceedingly unusual. Papillary adenocarcinoma of the gallbladder is an aggressive malignant entity derived from intracholecystic papillary-tubular neoplasms (ICPNs). The coexistence of these two unrelated neoplasms has not been previously reported, making this case of dual tumor pathogenesis clinically and academically significant. Case Presentation: A 68-year-old female was admitted for surgical management of grade IV uterovaginal prolapse. Preoperative imaging incidentally revealed a well-circumscribed rectal wall mass and gallstones. A combined abdominopelvic op-eration was performed, including total hysterectomy with bilateral adnexectomy (Wiart procedure), rectosigmoid resection with colorectal anastomosis, and bipolar cholecystectomy. Intraoperatively, a firm intramural rectal lesion and a friable papil-lary mass in the gallbladder fundus were identified. Histopathologic examination con-firmed a benign rectal schwannoma (S-100 positive, CD117/DOG-1 negative) and a papillary adenocarcinoma of the gallbladder, pT3N0M0, with clear resection margins and no lymphovascular or perineural invasion. The postoperative course was une-ventful, and the patient remained disease-free at six-month follow-up. Conclusions: This case represents an exceedingly rare benign–malignant synchronous tumor association. The simultaneous occurrence of rectal schwannoma and gallblad-der papillary adenocarcinoma underscores the importance of thorough intraoperative exploration and histopathologic evaluation. Complete resection with negative margins and multidisciplinary follow-up remains crucial for optimal outcomes and contributes to understanding dual tumor pathogenesis within the gastrointestinal tract.

Abstract: Breast cancer diagnosis from MRI is challenging, hampered by complex image interpretation and scarce annotated medical datasets, which limits deep learning efficacy. To address these challenges, we propose the Hierarchical Attention Medical Transformer (HAMT), a novel Vision Transformer for enhanced breast cancer MRI classification, especially in data-limited scenarios. HAMT integrates a medical domain-specific self-supervised pre-training strategy to learn relevant features and a hierarchical attention aggregation mechanism to synthesize information from multiple MRI slices into a robust patient-level representation. Evaluated on the Duke Breast Cancer Dataset, HAMT consistently outperformed state-of-the-art Vision Transformer baselines across various data scales. Notably, even with limited training data, HAMT demonstrated strong diagnostic performance, significantly surpassing the best baseline ensemble model. Ablation studies further confirmed the significant contributions of both proposed components. HAMT demonstrates superior generalization in data-scarce scenarios, offering a promising AI-powered tool to augment breast cancer diagnostic workflows.

Abstract: Background: Pressure overload-induced heart failure is marked by pathological ventricular remodeling and myocardial fibrosis, contributing to impaired cardiac function and adverse clinical outcomes. Vericiguat, a soluble guanylate cyclase stimulator, has shown therapeutic promise in heart failure with reduced ejection fraction. However, its anti-fibrotic and metabolic effects in pressure overload models remain underexplored. Aim: This study aimed to investigate the anti-fibrotic and metabolic effects of Vericiguat in a murine model of pressure overload-induced cardiac remodeling. Material Method: Male mice (~25 g) underwent transverse aortic constriction (TAC) to induce pressure overload and received oral Vericiguat (10 mg/kg/day) for 14 days. Myocardial fibrosis was evaluated using Masson’s trichrome and Picrosirius red staining. Collagen deposition and wall stress indices were quantified. Proteomic profiling was performed on fibroblast- and myocyte-enriched cardiac tissue to identify differentially expressed proteins (DEPs) across metabolic, structural, mitochondrial, and signaling pathways. Results: Vericiguat treatment significantly reduced myocardial fibrosis and collagen accumulation compared to untreated TAC controls (p< 0.001). Improvements in wall stress indices were observed. Proteomic analysis revealed consistent modulation of DEPs, including reversal of TAC-induced downregulation of mitochondrial and energy-related proteins, indicating enhanced bioenergetic support. Conclusion: Vericiguat mitigates pressure overload-induced cardiac remodeling through anti-fibrotic and metabolic reprogramming mechanisms. These findings support its potential as a therapeutic strategy for heart failure and warrant further clinical investigation.

Abstract: The CXC chemokine receptor 2 (CXCR2) is a member of the G-protein-coupled receptor superfamily and regulates a diverse range of immune responses and tumor progression. CXCR2 is expressed on immune cells, especially neutrophils, and is involved in various immune responses by interacting with its chemokine ligands. Therefore, the development of sensitive monoclonal antibodies (mAbs) for CXCR2 has been desired for treatment and diagnosis. This study established a novel sensitive anti-mouse CXCR2 (mCXCR2) mAb; Cx2Mab-5 (rat IgG2a, kappa), using the mCXCR2 synthetic N-terminus peptide immunization method. In flow cytometry, Cx2Mab-5 recognized mCXCR2-overexpressed Chinese hamster ovary-K1 cells (CHO/mCXCR2) and WEHI-3B (murine myelomonocytic leukemia cell) cells, which express endogenous mCXCR2. Cx2Mab-5 did not cross-react with other mouse CC, CXC, CX3C, and XC chemokine receptors. Cx2Mab-5 showed a moderate binding affinity for both CHO/mCXCR2 and WEHI-3B. Further-more, Cx2Mab-5 detected mCXCR2 in western blot and immunohistochemistry in CHO/mCXCR2 cells. Hence, Cx2Mab-5 can be a valuable tool for analyzing mCXCR2-expressing cells, such as immune cells and tumors.

Abstract: Background/Objectives Oral health-related quality of life (OHRQoL) may influence mental health outcomes, yet longitudinal evidence on its association with depression remains limited. This study aimed to examine whether oral health status and OHRQoL are associated with the development of depression among adults in Japan. Methods We analyzed data from the Japan COVID-19 and Society Internet Survey (JACSIS), conducted in 2022 and 2023. A total of 15,068 participants aged ≥20 years without depression at baseline were included. Depression onset was identified by self-reported measures between the two survey waves. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for depression development in relation to OHRQoL and oral health status, adjusting for sociodemographic and behavioral factors. Results During follow-up, 218 participants (1.45%) developed depression. Poorer OHRQoL was significantly associated with development of depression (OR: 1.018; 95% CI: 1.001–1.036; p = 0.039). Additional risk factors included younger age (OR: 0.974; 95% CI: 0.964–0.985), participation in hobbies and cultural activities (OR: 2.224; 95% CI: 1.498–3.302), habitual use of sleeping pills or anxiolytics (current use OR: 3.512; 95% CI: 2.267–5.442), increased loneliness (OR: 1.217; 95% CI: 1.140–1.299), lower life satisfaction (OR: 0.900; 95% CI: 0.836–0.969), and poor self-rated health (OR: 2.921; 95% CI: 1.810–4.715). Conclusions Impaired OHRQoL was associated with depression development, potentially through psychosocial mechanisms. Maintaining good oral health and OHRQoL may help prevent depression, highlighting the need for integrated oral and mental health strategies in clinical practice.

Abstract: Breast cancer screening, while vital for reducing mortality, faces significant limitations in sensitivity and specificity, particularly in dense breasts. Current modalities primarily detect anatomical changes, often missing biologically aggressive tumors at their earliest stages. The altered metabolism of cancer cells establishes a characteristic inverted pH gradient that drives tumor invasion, metastasis, and treatment resistance. This makes tumor acidity a compelling, functional biomarker for early detection. This review synthesizes the emerging role of pH as a diagnostic biomarker and provides a critical evaluation of advanced imaging techniques for its non-invasive measurement. We detail the biological underpinnings of tumor acidosis, emphasizing its regulation through glycolytic reprogramming and dysregulated proton transport. Our analysis encompasses a broad spectrum of pH-sensitive imaging modalities, including magnetic resonance methods such as Chemical Exchange Saturation Transfer (CEST) MRI for ex-tracellular pH mapping and multi-nuclear Magnetic Resonance Spectroscopy (MRS) using ¹H, ³¹P, and ¹⁹F nuclei to probe various cellular compartments. Furthermore, we examine hyperpolarized ¹³C MRI for real-time metabolic flux imaging, where metrics like the lactate-to-pyruvate ratio show significant predictive value for treatment response. The review also assesses optical and photoacoustic imaging techniques, which offer high sensitivity but are often constrained to superficial tumors. Imaging tumor pH provides a powerful functional window into the earliest metabolic shifts in breast cancer, far preceding macroscopic anatomical changes. The ongoing de-velopment and clinical validation of these pH-sensitive imaging techniques hold im-mense promise for revolutionizing breast cancer screening by enabling earlier, more specific detection and personalized risk stratification, ultimately aiming to improve pa-tient outcomes.

Abstract: Ephrin type-B receptor 3 (EphB3) binds to transmembrane ephrin-B ligands to regulate cell mi-gration, adhesion, and proliferation. EphB3 exhibits a gradient expression pattern in the normal intestine, with the highest levels at the crypt base, and plays a crucial role in the maintenance of normal intestinal epithelium. Therefore, anti-EphB3 monoclonal antibodies (mAbs) are required for basic research and diagnosis. In this study, we developed novel anti-human EphB3, Eb3Mab-5 (IgG1, κ) and Eb3Mab-11 (IgG1, κ), using the Cell-Based Immunization and Screening (CBIS) method. Eb3Mab-5 and Eb3Mab-11 reacted with EphB3-overexpressed Chinese hamster ova-ry-K1 (CHO/EphB3) and endogenous EphB3-positive colorectal cancer LS174T in flow cytometry. The KD values of Eb3Mab-5 for CHO/EphB3 and LS174T were 7.6 ×10-9 M and 1.7 ×10-8 M, re-spectively. Eb3Mab-11 could detect EphB3 in western blot analysis and immunohistochemistry. Eb3Mab-5 and Eb3Mab-11 may contribute to the diagnosis and therapy of EphB3-positive tu-mors.

Abstract: Background: Survivors of sudden cardiac arrest frequently experience long-lasting problems with fatigue, cognition and mood. European Resuscitation Council (ERC) guidelines recommend functional assessment of physical/non-physical issues prior to discharge, and systematic review within three months covering at least cognition, mood, fatigue, and support for patients and their families1. How these recommendations are implemented and what barriers are encountered in routine care remains unknown. Methods: We conducted a multicentric, prospective 6-month audit across four tertiary cardiac-arrest centres in England where temporarily funded follow-up pathways were in place. Five operational criteria were developed based on ERC guidelines. Adherence was quantified, and reasons for non-completion were collected and mapped onto the Theoretical Domains Framework (TDF) to identify behavioural and contextual factors influencing implementation. Results: 143 OHCA survivors were discharged alive. Pre-discharge assessments were offered to 116/143 patients (81%) but only completed in 81 (57%). Reasons for non-completion included early discharge, severe cognitive impairment and, less frequently, patient refusal. Of 132 survivors eligible for follow-up, 108 (82%) were contacted and 87 (66%) attended. Only 25% of follow-ups occurred within the recommended 3-month period (median 185 days, IQR 81–225). Among those seen, assessments were completed for cognition (44%), mood (52%), and fatigue (51%). Reasons for omission included patient refusal, clinical discretion, and time constraints. Survivors’ family members were invited in all cases, but only 45% attended. Conclusions: Adherence to guideline-recommended assessments was variable and dependent on local practices, resource limitations, and patient/clinician-related factors. The most common barriers mapped to the TDF domains of ‘Environmental context and resources’ ‘Beliefs about consequences’ and ‘Social Influences’. Local care pathways (e.g. exclusion of out-of-area/non-ICU patients), clinician judgement, and engagement by patients/relatives were key influences on implementation. These findings can support targeted service development and contribute to sustainable models of post-resuscitation care.

Abstract: Background/Objectives: Precise identification of epileptic seizure onset zones (SOZs) and their propagation pathways is essential for effective epilepsy surgery and other interventional therapies, typically achieved through invasive electrophysiological recordings such as intracranial electroencephalography (EEG). Previous research has shown that analyzing information flow patterns, particularly in high-frequency oscillations (>80 Hz) using parametric and Wilson-algorithm (WL) based nonparametric Granger Causality (GC), is valuable for identifying SOZs. In this study, we analyzed scalp EEG recordings from epilepsy patients using an alternative nonparametric GC, which relies on spectral density matrix factorization based on the Janashia-Lagvilava algorithm (JLA). The aim of this study is to assess the effectiveness of JLA-based matrix factorization in nonparametric Granger causality for noninvasively identifying seizure onset zones from ictal EEG recordings in drug-resistant epilepsy patients. Methods: Two regions of interest in pairs across different time epochs were isolated in six people referred for presurgical evaluation. To apply the nonparametric Granger causality (GC) estimation approach to the EEG recordings from these regions, the cross-power spectral density matrix was first constructed by the multitaper method and then subsequently factorized by the JLA algorithm. The factorization gave a transfer function and noise covariance matrix needed for GC estimations. The GC estimates were obtained at different prediction time steps (measured in milliseconds). These estimates were used to confirm the visually suspected seizure onset regions and its propagation pathway. Results: JLA-based spectral factorization in Granger causality applied to scalp EEGs successfully identified seizure onset zones (SOZs) and their propagation patterns, aligning with positive outcomes (Engel I) in six epilepsy surgery cases. Conclusions: The JLA-based spectral factorization in Granger causality has the potential not only for accurately localizing SOZs to aid in diagnosis and treatment but also for broader applications in uncovering information flow patterns in neuroimaging and computational neuroscience.

Abstract: Background: This study was designed to assess the anatomical and functional responses in patients with refractory diabetic macular edema (DME), refractory retinal vein occlusion edema (RVO), and refractory neovascular age-related macular degeneration (nAMD) with suboptimal response to anti-VEGF treatments, specifically Bevacizumab or Aflibercept. Method: This prospective study includes 45 eyes of 35 patients with refractory (DME), (RVO) and (nAMD) previously treated with intravitreal Bevacizumab or/ and Aflibercept. Among the reasons for switching persistent retinal fluid, lack of improvement in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Patients received 3 monthly loading doses of Faricimab. Over 12 months, this study encompassed all essential stages, including patient recruitment, baseline evaluations, treatment administration, follow-up assessments, data analysis. Results: Switching to Faricimab show a significant improvement in the visual acuity (median VA decreased from 0.6 to 0.3) and a significant decrease in central retinal thickness (median central retinal thickness reduced from 411.0 to 289.0), subretinal fluid (proportion of eyes with SRF decreased from 53.33% to 6.66%), and intraretinal fluid (proportion of eyes with IRF decreased from 77.77% to 35.55%) after starting Faricimab treatment for all eyes. While Intraocular pressure remained stable over the course of the study. Conclusion: switching to Faricimab showed statistically significant improvements in both morphological and functional characteristics showing that Faricimab is a promising treatment option, particularly for patients with persistent or refractory macular edema.

Abstract: Artificial Intelligence (AI) and Precision Medicine represent foundational pillars for transforming pediatric healthcare, as children exhibit age-specific pharmacokinetic variations requiring highly personalized therapeutic approaches that make AI an indispensable tool for optimizing pharmacological safety and efficacy. This review analyzes current AI applications in pediatric precision pharmacotherapy, examining clinical opportunities and implementation challenges. AI demonstrates tangible clinical impact across multiple domains: pharmacogenomics with predictive models achieving R² = 0.95 for drug exposure; adverse drug reaction prediction with 81.5% sensitivity and 79.5% specificity; clinical decision support systems with 93.4% accuracy in pediatric epilepsy diagnosis. AI implementation has reduced prescription distribution errors by 75% and improved adverse drug reaction detection by 65%. However, significant gaps persist as only 0.38% of pediatric AI models reach clinical testing level, and 77% of studies show high risk of bias. AI transforms pediatric pharmacotherapy from empirical approaches to evidence-based predictive strategies, converting pediatric vulnerability into an innovation catalyst. The technology shifts understanding from correlation to causality, enabling personalized dosing and transforming pharmacovigilance into proactive safety mechanisms. Successful implementation requires overcoming current limitations including algorithmic bias, data quality issues, ethical considerations, and validation through rigorous clinical studies specifically designed for pediatric populations. Future development of sophisticated AI models promises enhanced precision, but real-world validation through interdisciplinary collaboration remains imperative for building robust pediatric AI ecosystems that opti-mize therapeutic outcomes for this vulnerable population.

Abstract: Background/Objectives: Acute heart failure (AHF) is a heterogeneous clinical syndrome, and prognosis varies depending on the ejection fraction phenotype. Although the N-terminal pro–B-type natriuretic peptide (NT-proBNP) remains the benchmark biomarker, conventional echocardiographic measures such as the tricuspid annular plane systolic excursion (TAPSE), the right ventricular to right atrial pressure gradient (RV–RA gradient), and the left ventricular outflow tract velocity–time integral (LVOT VTI) provide only partial prognostic information.We previously proposed the Virtue Index, defined as the ratio between the RV–RA gradient and the product of TAPSE and LVOT VTI, reflecting the interaction between right and left ventricular performance. The present study aimed to assess the clinical and prognostic behavior of the index in a cohort of patients with AHF and to determine whether its performance differs between reduced and preserved ejection fraction phenotypes. Methods: We retrospectively analyzed 222 patients admitted with a diagnosis of AHF. Complete echocardiographic data for Virtue Index calculation were available in 168 patients (99 [59%] with heart failure with reduced ejection fraction [HFrEF] and 69 [41%] with heart failure with preserved ejection fraction [HFpEF]). Patients with mid-range ejection fraction (40–49%) or incomplete echocardiographic parameters were excluded from subgroup analyses but retained for descriptive statistics where applicable. Correlation with NT-proBNP was evaluated using Spearman rank testing with bootstrap confidence intervals. Prognostic performance for in-hospital mortality was analyzed using ROC curves, area under the curve (AUC) with bootstrap intervals, and pairwise DeLong comparisons. Results: In the HFpEF subgroup, the index correlated moderately with NT-proBNP (ρ = 0.38, 95% CI 0.13–0.58, p = 0.002) and demonstrated fair prognostic discrimination (AUC 0.704, 95% CI 0.53–0.85), comparable to the RV–RA gradient (AUC 0.724) and higher than TAPSE (AUC 0.637) or LVOT VTI (AUC 0.669). In contrast, in HFrEF, the index showed a weak, non-significant correlation with NT-proBNP (ρ = 0.19, p = 0.06) and modest predictive accuracy (AUC 0.584, 95% CI 0.36–0.79), while LVOT VTI achieved the best discrimination (AUC 0.700). NT-proBNP remained superior in both subgroups (AUC 0.744 in HFrEF, 0.838 in HFpEF). Conclusions: The Virtue Index reflects integrated haemodynamic function and may demonstrate a phenotype-dependent prognostic role in AHF. In our study, its value was more evident in HFpEF, whereas in HFrEF traditional parameters, especially LVOT VTI, remained stronger predictors. Although NT-proBNP consistently outperformed Virtue, the index may complement biomarker assessment by providing rapid, bedside risk stratification of short-term mortality.

Abstract: Efgartigimod is a novel neonatal Fc receptor (FcRn) antagonist that reduces pathogenic IgG autoantibodies, offering a targeted therapeutic approach for generalized myasthenia gravis (gMG) and other antibody-mediated autoimmune diseases. This narrative review synthesizes clinical trial data, pharmacological insights, and real-world evidence to evaluate efgartigimod's efficacy, safety, and emerging applications. Phase 3 randomized controlled trials and extension studies demonstrate rapid and sustained improvements in muscle strength and patient-reported outcomes with a favorable safety profile, including reduced reliance on corticosteroids and intravenous immunoglobulin. Additionally, observational studies highlight its expanding utility in diverse IgG-mediated disorders such as immune thrombocytopenia and autoimmune encephalitis. Efgartigimod thus represents a paradigm shift in autoimmune disease management, enabling precision immunomodulation with the potential for broad clinical impact and improved patient quality of life (QOL).

Abstract: Introduction: Chronic Obstructive Pulmonary Disease (COPD), a respiratory pathology primarily linked to smoking, appears to exacerbate oral health problems through systemic and local mechanisms. This study evaluates the impact of COPD on the oral health of smoking patients in an Algerian context.​Methods: A descriptive cross-sectional study was conducted from January to June 2023 at the University Hospital Center of Sidi Bel Abbès, Algeria. A total of 138 male smoking patients were included. Each participant answered a standardized questionnaire, underwent a thorough clinical oral examination, and spirometry to confirm the diagnosis of COPD (FEV/FVC < 0.7 post-bronchodilator).​Results: Out of 138 patients, 62 (44.9%) had confirmed COPD. Tooth loss was significantly more frequent among COPD patients (88.7%) than among non-COPD patients (77.6%, p = 0.03). Dental caries were also more prevalent in the COPD group (85.5%) compared to the non-COPD group (70.1%, p = 0.02). Gum disease (93.5% vs. 91.3%, p = 0.65) and bad breath (79.0% vs. 76.0%, p = 0.70) showed similar prevalences in both groups.​Conclusion: COPD is associated with a significant deterioration of oral health, particularly regarding tooth loss and dental caries. A multidisciplinary management approach involving pulmonologists and dentists is crucial to improve clinical outcomes and patient quality of life.

Abstract: Background/Objectives: Colombia harbors exceptional plant diversity, comprising over 31,000 formally identified species, of which approximately 6,000 are classified as useful plants. Among these, 2,567 species possess documented food and medicinal applications, with several traditionally utilized for managing febrile illnesses. Despite the global burden of dengue virus infection affecting millions annually, no specific antiviral therapy has been established. This study aimed to identify potential anti-dengue compounds from Colombian medicinal flora through machine learning-based quantitative struc-ture-activity relationship (QSAR) modeling. Methods: An optimized XGBoost algorithm was implemented through Bayesian hyperparameter optimization (Optuna, 50 trials) to develop a QSAR model trained on 2,034 ChEMBL-derived activity records with experi-mentally validated anti-dengue activity (IC₅₀/EC₅₀). The model incorporated 887 molecular descriptors, comprising 43 physicochemical properties and 844 ECFP4 fingerprint bits, selected via variance-based feature selection. Bayesian hyperparameter optimization us-ing Optuna (50 trials) was performed to maximize model performance. Through system-atic literature review, 2,567 Colombian plant species were evaluated, identifying 358 with documented antiviral properties. Phytochemical analysis of 184 species generated 3,267 unique compounds for subsequent virtual screening. Compounds were prioritized based on predicted activity, drug-likeness, and applicability domain assessment for future ex-perimental validation. A dual-endpoint classification strategy was employed to simulta-neously evaluate both IC50 and EC50 activities, with compounds categorized into nine activity classes based on combined potency thresholds (Low: pActivity ≤ 5.0, Medium: 5.0 < pActivity ≤ 6.0, High: pActivity > 6.0). Results: The optimized XGBoost model achieved robust performance with a Matthews correlation coefficient of 0.583 and area under the receiver operating characteristic curve of 0.896. Virtual screening of 3,267 Colombian phytochemicals identified 276 compounds (8.4%) with high predicted potency (pActivity > 6) for both IC₅₀ and EC₅₀ endpoints (classified as "High-High"). Comprehensive struc-ture-activity relationship (SAR) analysis revealed that 239 of these compounds (86.6%) represented structurally novel chemotypes with low similarity (Tanimoto < 0.5) to the training dataset. Application of drug-likeness filters (QED ≥ 0.5) identified 20 priority can-didates (7.2% of high-potency hits), with 12 compounds showing exceptional profiles. In-cartine (pIC50: 6.84, pEC50: 6.13, QED: 0.83), Bilobalide (pIC50: 6.78, pEC50: 6.07, QED: 0.56), and Indican (pIC50: 6.73, pEC50: 6.11, QED: 0.51) exhibited the highest predicted potencies. Descriptor-activity correlation analysis identified QED (ρ = 0.14 with EC50), TPSA (ρ = -0.15), and aromatic rings as key modulators of antiviral activity. Conclusions: This pioneering systematic computational screening of Colombian flora for anti-dengue activity demonstrates the untapped potential of regional biodiversity in pharmaceutical discovery. The identified lead compounds represent prioritized candidates for experi-mental validation and subsequent development of dengue therapeutics, with all compu-tational resources made publicly available to facilitate future research.

Abstract: The pharmaceutics world today is rapidly transforming with the evolution of next-generation drug delivery systems. The current article discusses the history, mechanism of action, application, and limitations of liposomal and surfactant-based drug delivery systems. Liposomes have evolved from simple bilayer vesicles to advanced PEGylated nanocarriers that are common today in wide use for site-specific chemotherapeutic and biologic delivery. Surfactant-based products such as micelles and emulsions increase drug solubility and bioavailability and bring definitive benefits to drug resistance management.The review gives a critical appraisal of FDA-approved pharmaceuticals like Doxil®, illustrated with clinical effectiveness and regulatory impact. Challenges in immune responses, stability, and scalability issues are well-explored with focus on keeping commercialization as a concern. Comparative views postulate complementary strengths of surfactant carriers and liposomes in which the former possesses ease in formulation and facilitation of permeability and the latter possesses targeting and biocompatibility advantage.Based on integration of 25 key primary source pieces of information, the article provides birds-eye view of current capability and constraint, and direction in the future as hybrid delivery systems and novel nanocarrier design. The aim of this article is to raise awareness among researchers, clinicians, and regulators of translational and therapeutic potential of such systems and highlight the necessity of interdisciplinary solutions towards bridging contemporary constraints to clinical take-up.

Abstract: The skin-to-transverse process distance (st) correlates with the skin-to-dural sac depth (d) and may be used to estimate optimal angles for perpendicular needle insertion using the formula: inverse cosine d/√(1 + d²), as outlined in free visual guides. Objective: To analyze the relationship between the transverse process and dural sac depth at lumbar levels relevant to spinal anesthesia, and to determine the range of planes where a perpendicular paramedian needle insertion is feasible when midline access is not viable. Methods: Ten ex vivo trunks were flexed using an abdominal support, and CT scans were performed. Correlations between the transverse process and dural sac depth were evaluated from L3 to S1. Perpendicular planes at the level of needle paths were examined at L3-L4 and L4-L5. Median path viability was assessed. Results: The transverse process aligned with the dorsal dural sac at L3, the posterior third at L4, and the middle zone at L5-S1. Median needle insertion was not viable in 20–30% of L4-L5 and L3-L4 levels, respectively. However, paramedian access was possible. The vertical range of viable paramedian planes was 8.7 ± 2.9 mm (L4–L5) and 7.9 ± 1.9 mm (L3–L4). Coronal reconstructions showed that the upper level of the transverse process correlates with the skin-perpendicular planes where insertion is likely to succeed. Conclusion: Many elderly spines lack viable midline paths. The superior aspect of the transverse process serves as a useful landmark for estimating dural sac depth, calculating paramedian angles, and identifying the plane for successful perpendicular needle insertion.

Abstract: Introduction: Immune dysfunction plays a significant role in metabolic syndrome, contributing to both IR and chronic low-grade inflammation. This immune dysfunc-tion is characterized by overproduction of inflammatory cytokines among which of primary importance are tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and MCP-1, whereas others such as IFN-γ, IL-17А, and the anti-inflammatory IL-10 appear to be of secondary importance. Cytokines also play a significant role in post-COVID disorders contributing to prolonged immune dysregulation and persistent subclinical inflammation. However, their role in the newly emerging metabolic disorders follow-ing infection remains poorly defined. Methods and materials: In the current study 78 patients (26 men and 52 women) were included, divided into two groups - group 1 (individuals with newly diagnosed car-bohydrate disorders after proven COVID-19 or post-COVID group; n=35) and group 2 (COVID-19 negative persons with Metabolic Syndrome; n=33). They were further di-vided into several subgroups according to type of metabolic disorder present. Standard biochemical, hormonal and immunological parameters were measured using ELISA and ECLIA methods, as wells as some indices for assessment of insulin resistance were calculated using the corresponding formula. Results: Patients from both groups demonstrate similar (P>0.05) metabolic parameters including BMI, lipid profile, uric acid, whereas those from the Post-COVID group demonstrated poor glycaemic parameters (Fasting plasma glucose and HbA1c) (P< 0.05). Patients from both Post-COVID and COVID-negative group demonstrated high levels of IR, the latter having higher mean values of both indices. Higher TNF-α and IL-10 values were registered in the Post-COVID group (P>0.05) whereas higher levels of INF-γ (P< 0.001) and IL-17A we registered in the COVID-negative group (P>0.05). A lot of correlations were found between the immunological parameters evaluated and the metabolic ones. Conclusion: The observed changes in both metabolic and immune parameters studied among the two groups show many similarities, but some significant differences have also been identified. What can be asserted is that cytokines definitely have an im-portant role in Post-COVID newly-emerging metabolic disorders contributing to both adipose tissue dysfunction, IR, dysglycaemia and dyslipidemia observed.

Abstract: Background: Ultra-weak photon emission (UPE) from living systems has been reported and linked to oxidative reactions. Whether photons mediate communication—particularly at the level of DNA—remains unresolved. Objective: To review biochemical and quantum-biological bases of UPE, summarize measurement approaches, and evaluate whether DNA-related emission could support signalling; we also present pilot data on embryo UPE. Methods: We synthesise literature on sources (reactive oxygen species, lipid peroxidation, protein/DNA oxidation) and detectors (photomultiplier tubes, cooled CCD cameras, Complementary Metal-Oxide Semiconductor CMOS). We measured UPE from mouse embryos in a dark incubator using an ORCA-Quest CMOS system. Results: UPE is modulated by cellular state; mitochondria, membranes and peroxisomes are key contributors. Models posit DNA as a storage/emitter and potential resonator. In embryos, degenerated two-cell–stage embryos exhibited lower UPE than well-developed embryos. These findings motivate a Photon Emission Embryo Control System (PEECS) for non-invasive assessment. Conclusions: Ultra-weak cellular photon emission—especially the proposed DNA-linked mechanisms—remains a challenging yet promising field. Evidence does not convincingly show DNA acts as a biophotonic communication system, but the hypotheses suggest new ways to view biological information processing and cellular funcion.