Biology and Life Sciences

Abstract: This work builds AAV-CapNet, a deep learning model integrating Fourier frequency enhancement and cross-attention fusion, to predict infectivity of 20 AAV capsid variants across 52 cancer cell lines with a self-built multi-omics dataset of 392 validated measurements. Validated via stratified splitting and repeated five-fold cross-validation, it extracts dual-domain capsid features fused with host transcriptomics for joint classification and regression. Surpassing mainstream ML/DL baselines in key metrics, it performs far better at low FPR for high-throughput screening. Attention mapping and ablation tests validate core modules’ necessity. Despite poor generalization to unseen serotypes, this interpretable tool facilitates intraserotype capsid screening and rational engineering.

Abstract: Adequate polymerization is essential for the mechanical performance and longevity of resin-based composites; however, recently introduced chemically cured bulk-fill composites remains insufficiently investigated. This in vitro study compared the degree of conversion (DC) and surface microhardness (SMH) of a chemically cured bulk-fill composite (Stela, SDI) with those of a nano-hybrid light-cured composite (Filtek™ Z250, 3M). Sixty standardized disc shaped specimens (5 mm x 2 mm; n= 30 per material) were prepared according to the manufacturers instructions. The DC was measured using Fourier-transform infrared spectroscopy (FTIR) immediately after polymerization and after 5, 10, 20 minutes and 24 h. SMH was evaluated using Vickers microhardness tester before and after artificial aging by thermocycling (5,000 cycles). The light-cured composite exhibited significantly greater SMH then the chemical cured composite (95.01 ± 0.59 HV vs. 51.21 ± 0.50 HV, p < 0.001). Both materials demonstrated progressive increase in DC over time. However, the light-cured consistently achieved higher conversion values, reaching 62.39 ± 4.23% after 24 h compared with 47.58 ± 3.04% for the chemically cured composite (p < 0.001). These findings indicate that the DC and SMH alone should not be considered a predictor of composite performance.

Abstract: Finswimming is a high-intensity aquatic sport in which performance is determined by the interaction between biomechanical efficiency and physiological constraints, par-ticularly during underwater apnea sprint events. This study compared performance, kinematic characteristics, cardiovascular responses, metabolic stress, and perceived exertion during a maximal 50-m monofin sprint performed under three conditions: underwater apnea swimming (UW), surface swimming without snorkel (SN), and sur-face swimming with a closed snorkel (SC). Ten male elite national-level finswimmers completed a randomized repeated-measures protocol. Performance time, dolphin kick number and frequency, heart rate (HR), blood lactate, blood glucose, and rating of perceived exertion (RPE) were assessed. UW swimming resulted in significantly faster performance (17.38 ± 1.32 s) compared with both SN (19.20 ± 1.64 s) and SC (19.39 ± 1.53 s; p < 0.001), accompanied by a reduced number of dolphin kicks (40 ± 5 vs. 44 ± 6 and 44 ± 5 kicks, respectively), while kick frequency remained unchanged (~137–140 kicks·min⁻¹). Heart rate responses demonstrated a reproducible biphasic recovery pat-tern across all conditions, with HR declining rapidly from peak exercise values (HRpeak: ~169–171 bpm) to HRlow (~141–147 bpm), before increasing again to HRhigh (~160–162 bpm) during the first minute of recovery (p < 0.05). Post-exercise blood lactate increased significantly in all conditions from ~1.3–1.5 to ~10.7–11.9 mmol·L⁻¹ (p < 0.001), with no between-condition differences. Blood glucose (~5.2–5.8 mmol·L⁻¹) and RPE (7–8 AU) remained unchanged across conditions. In conclusion, underwater apnea swimming enhances sprint performance in elite male finswimmers primarily through biomechanical and hydrodynamic advantages without increasing acute metabolic or perceptual stress. The novel identification of a biphasic heart rate recovery response highlights complex autonomic regulation following maximal apnea exercise and may provide a relevant physiological marker for recovery dynamics in high-performance aquatic athletes.

Abstract: One of the most important adverse consequences of antibiotic use is the development of bacterial resistance. This study investigated the prevalence and antimicrobial resistance patterns of multidrug-resistant (MDR) Escherichia coli in a tertiary care hospital during 2013–2015 and 2024, together with trends in antibiotic consumption and the molecular characteristics of resistance genes in 2024 isolates. Identification and susceptibility testing were performed using the Vitek® 2 system, antibiotic consumption was assessed according to WHO ATC/DDD methodology, and resistance genes were detected by PCR. No significant differences were observed in the total number of isolates, patients, or the proportion of E. coli isolates during 2013–2015. However, the isolation rate of MDR E. coli significantly declined from 36.9% to 30%. Total antibiotic consumption remained stable, with no correlation between consumption and MDR isolation rates, although ampicillin resistance increased significantly. In 2024, MDR E. coli accounted for 24.3% of isolates despite lower antibiotic consumption. Compared with 2015, resistance significantly increased to amoxicillin-clavulanic acid, cefotaxime, cefepime, ceftazidime, ciprofloxacin, and levofloxacin, while ceftriaxone resistance decreased. The blaCTX-M gene was detected in 53% of bloodstream isolates, indicating widespread dissemination of ESBL-producing E. coli and highlighting the need for continuous surveillance and antimicrobial stewardship.

Abstract: Somatostatin receptors are being investigated as therapeutic targets for high‑risk neuroblastoma stage 4 (NBS4) due to their overexpression on chromosome 17q. This study explores the design of potential somatostatin receptor agonists that activate SSTR2 signalling pathways. It evaluates their ability to bind two additional overexpressed GPCRs located on chromosome 17: galanin receptor type 2 (GALR2) and corticotropin‑releasing hormone receptor 1 (CRHR1). Using a multi‑platform computer‑aided drug design workflow—including OpenEye Scientific Suite, Samson Suite, Flare Suite, and Discovery Studio Visualizer—eight candidate compounds were identified and assessed for docking performance, pose reliability, and structure–activity relationship (SAR). Their absorption, distribution, metabolism, excretion, and toxicity profiles were evaluated using T.E.S.T., DEEP‑PK, and SwissADME. Retrosynthetic analysis using ChemAIRS and Spaya confirmed synthetic feasibility, with compound 8 achieving an RScore of 1.0. Compound 8 demonstrated strong and consistent predicted binding to SSTR2, CRHR1, and GALR2, with interaction patterns consistent with those reported for known SSTR2 agonists. These findings suggest that compound 8 is a promising multitarget GPCR ligand candidate for high-risk NBS4 and warrants further experimental evaluation of its pharmacological activity.

Abstract: The Phaistos Disc is an undeciphered Minoan-era artifact bearing 242 stamped occurrences of 45 distinct signs. We test whether it encodes one or more protein sequences, with each sign representing an amino acid or post-translationally modified amino acid and the 45 signs mapping many-to-one onto the 20 canonical residues. We treat this as a substitution cipher using a pre-specified battery of methods. Map-invariant statistics disfavor the hypothesis: the disc is more repetitive than length-matched proteins, with a 15-sign exact repeat on Side A, and one sign occurs nineteen times, always in group-initial position, a confinement not observed for any amino acid. A Shannon unicity-distance calculation on Swiss-Prot shows that 242 signs are too few to identify a unique map from k-mer statistics. Simulated annealing fails to make the disc more protein-like than optimizer-matched nulls, and a known-plaintext attack against Swiss-Prot finds no decoding that beats a shuffled-disc null in any reading direction. Short stretches can be read as fragments of real proteins, from a woolly mammoth enzyme to a human topoisomerase, but the null predicts such matches by chance. We claim no decipherment and report effect sizes and p-values against matched nulls; the protein hypothesis is not supported.

Abstract: The presence of circulating microplastics (MPs) in human blood represents an emerging concern with potential cardiovascular implications. This pilot study evaluated a digestion-filtration protocol using confocal Raman microscopy to screen circulating MPs in healthy controls (N=8) and acute myocardial infarction (AMI) patients (N=6). The protocol effectively removed biogenic matter from blood filters, enabling reliable Raman measurements. MPs were detected in both groups, showing a descriptive prevalence of 50.0% (3/6) in AMI patients compared to 37.5% (3/8) in controls (Odds Ratio [OR] = 1.67, p = 1.000). At the particle level, positive particles accounted for 8.3% (5/60) in AMI patients and 10.0% (6/60) in controls (OR = 0.82, p = 1.000). Active smoking was associated with a significant qualitative polymer shift: active smokers exclusively carried polystyrene and ethylene-vinyl acetate—key components of cigarette packaging and filters—while non-active subjects carried baseline polyethylene and polypropylene (Fisher's p = 0.002; Chi-Square p = 0.012). No significant associations were found with age or sex. These findings support the viability of this methodology for larger clinical cohorts investigating circulating microplastics in cardiovascular health.

Abstract: Liver transplantation remains a technically demanding procedure despite continued surgical advances. Successful outcomes depend on balancing donor selection with perioperative complexity, where each decision shapes graft and patient survival. Conventional scoring systems such as MELD-based prioritisation only partially explain differences in patient outcomes across transplant centres worldwide. Advances in artificial intelligence (AI) and machine learning (ML)—including longitudinal modelling of electronic health records, deep learning for imaging, and multimodal data integration—offer new opportunities to individualise risk stratification for graft selection, predict allograft dysfunction and rejection, and improve long-term survival. Clinically developed AI models may strengthen organ matching decisions and acceptance, while identifying candidates who require intensified immunosuppressant monitoring or targeted diagnostic testing in the postoperative period, without increasing rejection risk. However, the introduction of AI/ML systems demands thorough validation, careful calibration, and ongoing clinical audit to reduce bias, detect technical errors, and ensure reproducible performance. This review summarises current and emerging clinical applications of AI in liver transplantation and explores near-future directions. These include AI-driven graft evaluation during organ retrieval and normothermic machine perfusion, along with emerging evidence for the safety, reliability, and clinical utility of AI in transplantation practice.

Abstract: Triple-negative Breast cancer is a highly heterogeneous tumor subtype lacking universal therapeutic targets, a factor that frequently renders standard pharmacological approaches ineffective. To address the urgent clinical need for precision strategies, we developed a computational framework centered on personalization. Utilizing specific gene expression data, we initially constructed and calibrated 41 individualized regulatory networks, thereby capturing the precise molecular signature of each patient. Then, we applied a hybrid approach to these models—integrating Boolean logical determinism with the exploratory optimization of the combinatorial search space via a Genetic Algorithm—and identified the minimal sets of driver nodes capable of irreversibly driving the tumor cell toward apoptosis. Subsequently, a rigorous optimization process translated these targets into actionable clinical options by mapping them to optimal combinations of oncological drugs under stringent therapeutic constraints. The apoptotic transition was successfully achieved in 92.7% of the samples. Results indicate that effective tumor reprogramming relies on manipulating critical nodes that orchestrate the network's logical dynamics. By minimizing unnecessary perturbations to the overall signaling architecture, this methodology demonstrates the computational feasibility of identifying robust, non-obvious therapeutic targets through Boolean modeling. Ultimately, it offers an adaptive and scalable platform for the rational design of minimally disruptive, patient-specific combinatorial therapies.

Abstract: The hierarchical organization of topological associating domains (TADs) is a funda-mental feature of three-dimensional genome architecture, yet its systematic character-ization remains challenging due to the scale-dependent nature of conventional detection methods. Here, we apply hyperbolic embedding into a Poincaré disc to analyze TAD hierarchies from Hi-C data. In this framework, genomic loci are projected onto the disc such that the radial coordinate encodes hierarchical depth: subTADs localize near the center, while metaTADs shift toward the periphery. The method was validated on ten cell lines, including the isogenic MCF10A/MCF7 pair, and does not require manual pa-rameter tuning across resolutions. In the MCF10A/MCF7 isogenic system, neoplastic transformation was associated with a redistribution of the hierarchy: the number of small TADs (levels 1–3) decreased by 6.7%, whereas large TADs (levels 4–6) increased by 4.7%, with the largest domains (level 6) showing a 33.9% increase. Comparison with standard approaches — Insulation Score (IS) and Directionality Index (DI) — yielded an average Jaccard index of 0.568 and F1 score of 0.718 against DI. Unlike IS and DI, which operate at fixed scales, the proposed approach recovers the full TAD hierarchy from a single embedding, enabling cross-resolution and cross-cell-line comparisons without parameter reoptimization. These results demonstrate that the Poincaré disc method provides a robust, interpretable, and scale-invariant framework for detecting hierar-chical chromatin rearrangements associated with cancer.

Abstract: Background: East African runners, particularly from Kenya, have long dominated long-distance running. This study compared structural and modifiable body composition traits between professional Kenyan and European long-distance runners, and explored associations between local muscularity and skeletal robustness. Methods: A total of 52 male marathon runners (32 Kenyan and 20 European) were assessed according to the International Society for the Advancement of Kinanthropometry (ISAK) protocol. Participants were 27.2±5.2 years with a BMI of 18.4±1.1 kg·m⁻² and a marathon time of 02:09:26 in the Kenyan group, and 30.9±4.9 years, BMI 21.1±2.1 kg·m⁻², and marathon time of 02:18:31 in the European group. Corrected girths were calculated to explore associations between skeletal breadths and muscularity. Results: European runners exhibited significantly greater body mass, sitting height, girths, skeletal breadths, and muscle mass compared to Kenyan runners (p<0.05), with large to very large effect sizes. In contrast, Kenyan runners showed lower adiposity and more linear body proportions, including a lower Cormic index and higher intermembral index. Differences in segment lengths were generally limited. Principal component analysis showed clearer group separation for modifiable than structural traits. Significant positive associations were observed between humeral breadth and corrected arm girth (r=0.41, p=0.002), femur breadth and corrected thigh girth (r=0.66, p<0.001), and bimalleolar breadth and corrected calf girth (r=0.72, p<0.001). Conclusions: These findings indicate that Kenyan long-distance runners are characterized by a lighter and more linear morphology, whereas European runners display greater structural robustness and musculoskeletal development. Differences in muscularity may also be associated with skeletal robustness.

Abstract: Substance use disorders (SUDs) are increasingly associated with systemic inflammatory, neuroendocrine, and cardiometabolic dysregulation; however, the biological signatures underlying distinct substance-use patterns remain incompletely characterized. This study compared biomarker profiles among healthy controls and clinical groups comprising alcohol-associated polysubstance users (A+PS), non-alcohol substance users (PS-A), and alcohol-associated polysubstance users with comorbid post-traumatic stress disorder (PTSD+). Plasma levels of interleukin-6 (IL-6), C-reactive protein (CRP), cortisol, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were evaluated through comparative, multivariate, dose–response, and receiver operating characteristic (ROC) curve analyses. All clinical groups exhibited significantly increased IL-6, CRP, cortisol, and NT-proBNP levels compared with controls, indicating systemic physiological dysregulation associated with substance exposure. Among the evaluated biomarkers, IL-6 demonstrated the most robust and consistent performance across all analytical approaches. Multivariate regression identified alcohol consumption as an independent predictor of IL-6 elevation (p = 0.0003), while dose–response analysis revealed progressive increases in IL-6 according to alcohol consumption severity. ROC analysis further demonstrated that IL-6 exhibited the highest discriminatory performance (AUC = 0.844), outperforming CRP, cortisol, and NT-proBNP in distinguishing substance-using individuals from controls. Collectively, these findings were able to identify IL-6 as a central biomarker associated with substance-related systemic inflammatory dysregulation and support its translational potential as a sensitive indicator of physiological burden associated with chronic alcohol and substance exposure.

Abstract: Maintaining skin elasticity, skin barrier function, and general skin health all depend on sufficient hydration. The current study's goal was to use non-invasive instrumental techniques to assess how three commercially available Helia-D topical cosmetic formulations affected skin hydration. The study involved thirty healthy adult volunteers, ten of whom were allocated to each product group. The MoistureMeterSC equipment was used to test skin hydration both before and one hour after the Sleeping gel-cream, SPF50 Sunscreen Fluid, and Hydrating Toner were applied. Untreated skin patches were used as controls, and measurements were made in a controlled atmosphere. After application, all evaluated formulations resulted in quantifiable improvements in skin moisture. The Hydrating Toner (+56.6%) showed the biggest rise, followed by the Sleeping gel-cream (+42.5%) and the SPF50 Sunscreen Fluid (+25.68%). Baseline and post-application measurements differed significantly in sleeping mask (p < 0.01) and hydrating toner (p<0.05), according to statistical analysis. These results show that within an hour of application, the evaluated cosmetic formulas significantly increased skin moisture. Additionally, the findings support the use of non-invasive skin diagnostic techniques in cosmetic research and product development and show their value for the objective evaluation of cosmetic product efficacy.

Abstract: Muscle strength and bilateral asymmetry of the lower limbs are central determinants of injury risk and performance in football, yet their age-related development in adolescent players outside elite Western European cohorts remains insufficiently described. This study determined age-related differences in lower-limb muscle strength and muscular balance in Bulgarian male football players. A total of 122 players aged 13 to over 19 years from three clubs were assessed at the end of the competitive season. Maximal concentric knee extension and flexion strength of both legs were measured at 60°/s using a system with electronically controlled resistance (Kineo). Relative strength, bilateral asymmetry, hamstring-to-quadriceps (H/Q) ratios and a knee muscle balance index were calculated. Age differences were analysed using one-way ANOVA with Tukey post-hoc tests (extension) and the Kruskal–Wallis test with DSCF comparisons (flexion). Strength increased by 132–149% in extension and 186–191% in flexion, with the largest gains at 13–14 years and a second peak around 16 years; the effect of age was large (η²p = 0.59–0.61; ε² = 0.58). The balance index ranged from 0.48 to 0.62. These findings have direct implications for individualised strength and injury-prevention programming in youth football.

Abstract: Potato (Solanum tuberosum) is a key staple crop in Kenya, where plant-parasitic nematodes are among the most damaging yield constraints for smallholder farmers. This study evaluated fluopyram-treated banana fibre paper, a biodegradable carrier for targeted delivery of ultra-low nematicide doses, under on-farm conditions in Nyandarua County over three consecutive cropping seasons across properly and poorly managed fields. Seventeen nematode genera were identified, with Helicotylenchus and Globodera (potato cyst nematode, PCN) recording the highest population densities. Fluopyram-treated banana paper significantly suppressed Globodera juvenile densities and reduced total nematode reproductive factors by ≥26% and PCN cyst multiplication factors, effects most pronounced under poor management. No significant nematode suppression was observed under good management. Potato yield and quality responded positively to fluopyram treatment: total yield approximately doubled in well-managed plots and increased by ~50% in poorly managed plots relative to untreated controls. Fluopyram-treated plots also produced a higher proportion of large-grade tubers under proper management, improving marketable yield. These findings demonstrate that banana fibre technology can effectively manage nematode pests under variable real-world smallholder conditions, with yield benefits amplified by good agronomic practices. The technology offers a practical, climate-smart and sustainable nematode management tool, with potential for wide adoption across sub-Saharan Africa.

Abstract:

In this paper, a dual Lorentzian closed strip $\{\tilde{X}(s), N(s)\}$ is considered within the context of Lorentzian $3$-space, with a real parameter \(s\), a timelike moving frame $\{A(s),G(s),N(s)\}$ is defined, which moves along the curve of this dual Lorentzian closed strip. A timelike vector \(D\), which is fixed in this frame, is investigated alongside the dual integral invariants (dual angles of pitch, dual pitch) and dralls of the dual Lorentzian closed strip corresponding to the dual Lorentzian closed curve traced by vectors $A,G,N$ and \(D\). Some fundamental relations among these integral invariants of the dual Lorentzian closed strip are studied. Furthermore, these dual results are mapped to the line-space \(R_{1}^{3}\) and several theorems are presented regarding the dual Lorentzian geodesic curvature \(K_{g}\), dual Lorentzian normal curvature \(K_{n}\) and dual Lorentzian geodesic torsion \(T_{g}\) of the strip, accounting for the causal characters (timelike) inherent in Lorentzian geometry.

Abstract: Polydeoxyribonucleotide (PDRN) is a DNA-derived biological therapy gaining prominence in the treatment of musculoskeletal disorders. It functions as an adenosine A2A receptor (A2AR) agonist and serves as a substrate in the nucleotide salvage pathway. These mechanisms drive anti-inflammatory effects, stimulate angiogenesis via vascular endothelial growth factor, and promote collagen synthesis. In osteoarthritis, PDRN reduces cartilage degradation and promotes the chondrogenic differentiation of stem cells. It effectively treats tendinopathies, including Achilles and rotator cuff injuries, by accelerating tissue repair. PDRN also facilitates early bone formation and supports the reconstruction of damaged ligament fibers. It serves as a safe non-steroidal option for treating spinal radiculopathy, especially when corticosteroids are contraindicated. Preclinical and clinical evidence indicate significant pain reduction and functional recovery across various soft tissue diseases. The agent maintained an excellent safety profile, with no reported systemic toxicity or allergic reactions. Future large-scale trials are needed to standardize the dosing protocols for integrated orthopedic rehabilitation.

Abstract: Leg-spring hysteresis quantifies the mechanical energy dissipated within the force–length loop during ground contact and serves as a proxy for stretch-shortening cycle (SSC) efficiency. Whether international-level track-and-field athletes and club-level multi-sport athletes differ in their hysteresis responses to increasing drop height, and whether hysteresis predicts jump height, remains unclear. Forty athletes (15 international-level, 25 club-level) performed bilateral (BLJ), dominant-leg (DOM), and non-dominant-leg (NDOM) drop jumps from 0.26 m and 0.42 m. Three-dimensional kinematics (500 Hz) and ground reaction forces were used to compute leg-spring stiffness, hysteresis, and jump height. Significant group × drop-height interactions emerged for hysteresis in all three conditions (η²p = 0.647, 0.507, 0.466; p < .001): international-level athletes became increasingly negative (greater SSC enhancement) at 0.42 m, whereas club-level athletes showed positive hysteresis (net dissipation). Between-group hysteresis differences at 0.42 m were large (DOM d = −1.73; NDOM d = −1.95), and jump height was consistently higher in international-level athletes (d = 1.14–1.77). Pooled across groups, hysteresis was associated with jump height (R² = 0.44–0.60), although this estimate is inflated by caliber differences and within-group associations were moderate and condition-dependent. Leg-spring hysteresis is a mechanically meaningful and practically relevant discriminator of reactive-jumping capacity.

Abstract: Socio-ecological systems (SES) in island territories are characterised by strong interdependence between human activities and fragile ecosystems, where governance constraints and sector-based management regularly hinder effective biodiversity conservation. This study intends to identify scientific advances that have been most effective in reconciling these dynamics between 2015 and 2025. A systematic review was conducted following the PRISMA 2020 framework, analysing research methods, socio-ecological interactions, governance arrangements, and thematic research trends across the literature. The results show a clear shift from predominantly ecological and sectoral-specific approaches toward more integrative and participatory SES frameworks, with mixed-methods designs, co-management strategies, and the incorporation of local knowledge emerging as the most effective advances. However, important gaps continue, particularly in the operationalisation of SES frameworks, the assimilation of climate change, and the strengthening of science–policy interfaces. Overall, the findings show that successful reconciliation between human activities and biodiversity conservation in island contexts depends on participatory and adaptive governance, institutional resilience, and the integration of diverse social and ecological values, highlighting the need for more transdisciplinary and practice-driven research.

Abstract: All reports containing original data in JAMA journals must include a statement that at least one author "had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis." Similar attestations are required by many other journals. Over the past several years, a rapidly increasing number of articles have been published, including many (up to 100) in the JAMA family of journals [1], for which this statement is false (yet still made). These studies use the TriNetX platform, a point-and-click dashboard on which users can create cohorts and run a limited selection of analyses.