Browse Articles

Genome-targeted enrichment and sequencing of human-infecting Cryptosporidium spp.

Integrated in silico assessment of the regulatory and structural consequences of pulmonary tuberculosis-associated SP110 polymorphisms

Abstract The molecular mechanisms underlying conflicting findings of association of SP110 single nucleotide polymorphisms (SNPs) with susceptibility to pulmonary tuberculosis (PTB) remain unclear. We selected ten SP110 SNPs from publicly available genomic databases, based on prior PTB association and minor allele frequencies exceeding 1% in African populations and identified in a Ugandan cohort with PTB. We then applied in silico multi-tool framework, incorporating deep-learning splice predictors including SpliceAI, Pangolin, and AlphaGenome, to evaluate the regulatory and functional consequences of the SNPs on transcription factor binding, RNA splicing, RNA secondary structure, and protein-level effects. The model captured population-relevant SP110 variations rather than a directly genotyped Ugandan cohort. Our analysis revealed allele-specific gains and losses involving transcription factors TFAP2A, TFAP2C, TP63, Zfx, and IRF1, suggesting modulation of regulatory potential through altered transcription factor binding motifs. However, SpliceAI and Pangolin uniformly predicted low splice-disruptive effects across both exonic and intronic variants, while multiple protein pathogenicity tools consistently classified missense and stop-gained variants as benign or tolerated. RNA secondary structure analysis predicted that most variants preserved global thermodynamic stability. From our findings, SP110 variants are unlikely to exert major effects through splicing disruption or protein destabilization but may contribute to functional diversity through subtle regulatory mechanisms, including transcription factor binding modulation and RNA structural reorganization.

The influence of Lucilia sericata larval secretions on fibroblast lineage: an in vitro cell culture study

National trends in mortality involving acute pyelonephritis and obstructiveand reflux uropathy in the United States, 1999–2023

Crashworthiness enhancement of three-wheel vehicle structures under rear-end collision: a computational modelling approach

Abstract Worldwide, Three-wheeled vehicles (TWV) are becoming more and more ubiquitous for use in daily transportation. These vehicles are similar to motorcycles and scooters in that they have a steering wheel on the front, and they have a suspension system and differential on the back two wheels, just like a car. They typically consist of one front wheel and two rear wheels, with an open frame or sheet metal body. Their frontal design consists of an upright body and windscreen, a small cabin, a canvas roof, and a mudguard with an attached headlamp. These cars have a top speed of about 55 km/h. The front cabin houses the driver, while the back section is occupied by the passengers. It weighs about 650 kg, including the occupants. TWV are viewed as unsafe for two reasons: Auto rickshaws are thought to be dangerous for two reasons: first, the vehicle body and internal structure have no proper safety features, and second, the drivers are thought to be incompetent motorists who are ready to overload their cars and make numerous trips in a short amount of time. The driver’s seat and the back passenger bench are the only soft surfaces in the sparse, hard metal interior of auto-rickshaws, which are thought to be unstable and prone to turning turtle due to shunts from other vehicles, bumps in the road, or drivers who drive too fast. Because there are no doors, even at slow speeds, the occupants could be thrown onto the road and suffer serious injuries. Because of its materials’ and structures’ inadequate impact energy absorption, it also seriously jeopardizes pedestrian safety. The goal of this article was to reduce crash injuries by modifying the current three-wheeled vehicle to increase its crashworthiness during rear-end collisions. Accidents that happen to the rear ends of vehicles are the third most frequent type. Rear-impact collisions are frequent but rarely fatal. They do, however, cause a variety of injuries, the most frequent being whiplash trauma to the neck. In this study, the Federal Motor Vehicle Safety Standard (FMVSS)-301-inspired approach was followed when performing the Finite element analysis (FEA) rear-impact test on the TWV. Enhancing the crashworthiness of the car and the gasoline tank is another goal of the rear-impact test. Consequently, to see how occupants respond to a crash, human dummies are incorporated. Thus, modeling and analysis of the current three-wheeled vehicle structure with human dummies was the first task completed in this research. Following that, the outcome will be interpreted, and based on those findings, a new model will be developed to address the drawbacks of the three now in use. The outcomes of the original and modified models were then contrasted. Livermore Software Dynamic Nonlinear Analysis (LS-DYNA) was utilized for Finite element method (FEM) analysis, and CATIA was used for 3D modeling to accomplish this. From the result, the modified model is fitted with a rear bumper, so it reduces intrusion into the rear compartment of the vehicle. It deformed less, and as a result, 30% more protection was obtained for rear parts such as the fuel tank and engine. The rear bumper is made up of composite material, and this led to a greater absorption of energy with less deformation. The energy absorption of TWV was increased by 1.6 kJ. As a result, less energy is transferred to the occupants with the use of the modified model. With the use of the modified model, the force of impact was reduced by 22%; consequently, the occupants inside the modified model experienced fewer injuries. It can be observed that with little modification, the safety of the current TWV can be improved so that the owners and manufacturers can implement some of the safety development concepts discussed in this paper to improve the crashworthiness of the TWV.

Combining AI interpretation of cholangiograms and clinical data for postoperative risk stratification after ERCP in cholodocholithiasis

Spatiotemporal evolution of rain-spell characteristics and multivariate extremes

Coupling ecosystem services with machine learning to construct ecological security patterns: a case study of Jiangxi Province, China

Mechanochemical synthesis of silver-integrated biogenic CaCO₃ nanocomposite for Cu(II) removal from aqueous solutions

Minimum adjacent vertebral hounsfield unit value and paraspinal muscle fat infiltration are associated with adjacent vertebral fracture after thoracic vertebroplasty

A transformer-based ensemble algorithm for fake review detection in e-commerce systems

Metformin is associated with reduced rejection and improved graft survival in kidney transplant recipients with post-transplant diabetes mellitus

Abstract Metformin is widely used as an initial therapy for type 2 diabetes mellitus and often adopted for glycemic control in kidney transplant recipients (KTRs) with post-transplantation diabetes mellitus (PTDM). Despite its increasing use, evidence regarding how metformin interacts with immunosuppressive agents, particularly calcineurin inhibitors, and whether it modifies the risk of allograft rejection, remains limited. We conducted a multicenter retrospective cohort study of 555 KTRs diagnosed with PTDM between 2000 and 2018. Patients were grouped according to calcineurin inhibitor (CNI), tacrolimus, or cyclosporine use and further stratified according to metformin use. Propensity score matching was performed to minimize confounding factors. Among tacrolimus-treated recipients, metformin use was associated with a significantly reduced risk of acute T cell-mediated rejection (TCMR) (HR 0.40, 95% CI 0.18–0.90) and graft failure (HR 0.32, 95% CI 0.14–0.72). A longer duration of metformin use (> 3.8 years) was associated with greater protective effects. Although these associations did not reach statistical significance in cyclosporine-treated recipients, the direction of the effect was similar across both CNI groups. Furthermore, interaction analysis demonstrated no significant interaction between metformin use and CNI type with respect to acute TCMR risk. In KTRs with PTDM, metformin use was associated with a reduced rejection risk and improved graft outcomes. This association appeared consistent across CNI groups, although statistical significance was observed only among tacrolimus-treated recipients. These findings support a potential immunomodulatory role of metformin in KTRs and warrant further investigation.

Machine learning-based prediction and SHAP interpretation of mechanical properties in Kenaf/PALF/flax reinforced vinyl ester hybrid composites

Intelligent malware detection on Android smartphones via a hybrid approach using gradient boosting and convolutional neural network

Development and characterization of a sustainable bacterial cellulose/collagen composite membrane for enhanced wound healing and tissue regeneration applications

Abstract This study aimed to develop a bacterial cellulose/collagen composite membrane (BC/COL) for its wound-healing ability using collagen extracted from the scales of golden grouper ( Epinephelus coioides ), thus providing a sustainable derived source. BC was produced by Acetobacter pasteurianus PV549389 under static fermentation, and culture conditions were optimized using response surface methodology. ANOVA analysis confirmed the significance of the model (F = 5.09, p  = 0.044), identifying optimal conditions of 21.3 g/L glucose, 4.9 g/L peptone, and pH 6.7, yielding a maximum BC of 3.99 g/L. The developed BC/COL membrane exhibited a uniform morphology, enhanced thermal stability, and clear functional group interactions, confirming the successful integration of the polymer. The biological performance of BC/COL membrane was evaluated through in vitro scratch assays and in vivo excisional wound-healing studies in rats. The BC/COL membrane exhibited a safe profile toward dermal fibroblasts, significantly enhancing cell migration (91%) and accelerating wound-healing rates (3.03%/h and 1.91%/h after 24 and 48 h, respectively) compared with the control and collagen-treated groups. Histological and histomorphometric analyses revealed enhanced tissue regeneration in BC/COL-treated wounds, characterized by increased epidermal thickness (97.5 μm), elevated collagen deposition (59.4%), improved epidermal organization, and reduced inflammatory cell infiltration compared with the untreated control group. This study shows that BC/COL membrane effectively provides a sustainable and biocompatible wound dressing material, with strong potential for clinical application.

Hyperspectral imaging for objective microcirculatory assessment in trauma patients

Abstract Hyperspectral imaging (HSI) is a non-invasive technology capable of assessing microcirculatory impairment. This study evaluated whether HSI can detect early microcirculatory alterations in trauma patients and differentiate between those with hemodynamic instability or stability during initial trauma resuscitation. In this prospective single-center observational study at a German level I trauma center (01/2023–10/2024), patients underwent HSI (TIVITA ® 2.0) at three time points: during the primary survey, after resuscitation room care, and 24 h after admission. HSI approximates four microcirculatory parameters: tissue oxygenation saturation (StO₂), tissue water index (TWI), tissue hemoglobin index (THI), and near-infrared perfusion index (NIR). Hemodynamic instability was defined as systolic blood pressure < 90 mmHg for > 10 min, catecholamine use > 10 min, or pronounced clinical signs of hypoperfusion. The primary outcome was the difference in StO₂ between patients with and without hemodynamic instability at the initial HSI measurement. Secondary outcomes included comparison of all HSI parameters between groups, correlations with Injury Severity Score (ISS), biomarkers (lactate, bicarbonate, base excess), and mortality. Statistical analyses comprised t-tests, receiver operator curve (ROC) analyses, diagnostic accuracy, and DeLong’s test. A total of 163 patients were analyzed (18 hemodynamic instability, 145 hemodynamic stability). No significant difference in initial StO₂ was observed between groups (hemodynamic instability: 56.50 (SD 17.08) vs. hemodynamic stability: 59.48 (SD 10.92); p  = 0.311). Likewise, TWI, THI, and NIR showed no significant differences. Initial elevated lactate levels (≥ 2 mmol/L) were associated with significantly lower StO 2 levels ( p  = 0.002). ROC analysis of StO₂ for predicting in-hospital mortality showed an area under the curve of 0.677 (95% CI 0.529–0.825). The optimal mortality cut-off (StO₂ ≤ 54%) demonstrated a sensitivity of 0.70, specificity of 0.66, positive predictive value of 0.22, and negative predictive value (NPV) of 0.94. AUCs of StO₂, lactate, bicarbonate, and base excess overlapped, with no significant pairwise differences. HSI did not discriminate between hemodynamically unstable and stable patients at initial trauma assessment but correlated well with high lactate levels. However, its high NPV for mortality suggests potential value as an objective, non-invasive tool for early trauma team downgrading. Trial registration: German Clinical Trials Register (DRKS ID DRKS00030986) on 27th December 2022.

Spatial mismatch between heat exposure and cooling accessibility in the Middle Yangtze River Urban Agglomeration

Abstract Urban heat risk is shaped not only by thermal intensity but also by whether cooling resources are spatially aligned with populations experiencing greater heat exposure. This study developed a spatial diagnostic framework to identify heat exposure–cooling accessibility mismatch across the built-up areas of 30 cities in the Middle Yangtze River Urban Agglomeration, China. Potential heat exposure was characterized using land surface temperature and population density, while potential cooling accessibility was quantified using a two-step floating catchment area method based on urban parks and water bodies. The results revealed pronounced spatial mismatch between heat exposure and cooling accessibility. High-exposure and low-accessibility areas were concentrated mainly in dense urban cores and transitional development zones, whereas higher cooling accessibility occurred more frequently near peripheral or waterfront blue–green resources. Cities with greater mean cooling accessibility did not necessarily exhibit more equitable spatial distributions, demonstrating that spatial configuration and proximity were as important as resource quantity. A leakage-controlled Random Forest (RF) model achieved an AUC of 0.747, while city-group cross-validation yielded a mean AUC of 0.744, indicating moderate and relatively stable cross-city discrimination. SHAP analysis identified impervious surface ratio, building density, and green-space ratio as the principal environmental predictors associated with mismatch probability. Priority screening further identified Level I and II zones covering 19.03% of the built-up analytical area, where high mismatch probability, limited cooling accessibility, and age-related vulnerability jointly occurred. The framework provides a potentially transferable approach for diagnosing exposure–cooling service mismatch and supporting context-specific urban climate adaptation planning.

Study on the macroscopic deformation characteristics and failure mechanisms of rock bridge specimens under compressive shear stress state

Abstract Rock bridges play a critical role in the initiation and evolution of tectonic earthquakes and locked-type landslides. However, existing laboratory methods have limitations in reproducing compressive-shear stress conditions and capturing the deformation evolution of rock bridges, restricting a comprehensive understanding of their failure mechanisms. To address these issues, this study proposes a uniaxial compression testing method for rock bridge specimens containing discontinuous cracks. Specimens with different rock bridge angles were designed to induce compressive-shear-dominated stress states within the rock bridge region under uniaxial loading. The deformation and failure processes were investigated by integrating mechanical response analysis, acoustic emission monitoring, and digital image correlation measurements. The results demonstrate that the proposed testing method effectively reproduces the macroscopic deformation characteristics and failure modes of rock bridges under compressive-shear conditions. Specimens with different rock bridge angles exhibited a characteristic valley-shaped evolution of AE activity, while the distributions of average frequency and rise angle parameters indicated that failure was predominantly governed by shear cracking. In addition, DIC measurements revealed the development of a nearly circular vertical displacement field immediately before failure, providing experimental evidence for the formation of circular slip surfaces in homogeneous three-stage locked-type landslides. These findings improve the experimental characterization of rock bridge shear failure and provide new insights into the mechanisms governing circular slip surface formation, offering a useful experimental basis for investigating rock bridge failure and related geological hazards.

Phenotype-specific white matter microstructural alterations and their clinical correlates in Wilson disease

Abstract Wilson disease (WD) is a genetic disorder of copper metabolism that leads to progressive brain damage, yet the microstructural mechanisms underlying white matter alterations remain insufficiently understood. Diffusion tensor imaging provides limited biological specificity and is sensitive to free water contamination. Therefore, we applied neurite orientation dispersion and density imaging to characterize white matter microstructure and its clinical relevance in 30 patients with WD, including neurological and hepatic phenotypes, and 30 matched healthy controls. We demonstrate widespread, phenotype-specific microstructural alterations, with reductions in neurite density and orientation dispersion accompanied by increased extracellular volume fraction and diffusivity metrics (mean, axial, and radial diffusivity) in neurological WD and isolated increased isotropic volume fraction without abnormalities in conventional diffusion metrics in hepatic WD across major white matter tracts. These patterns provide a coherent explanation for previously inconsistent fractional anisotropy findings. Reduced neurite density was associated with greater neurological impairment and lower cognitive performance, particularly in processing speed and visual attention. Together, these findings highlight neurite density as a potential marker of clinically relevant white matter disruption and reveal distinct microstructural signatures across WD phenotypes, consistent with differential underlying mechanisms and a potential progression from free water-related alterations to axonal degeneration. Advanced diffusion imaging thus enables a more specific characterization of white matter pathology and supports linking microstructural alterations to clinical outcomes in neurological disorders.

Assessment of c-Kit immunohistochemical expression in cutaneous basal and squamous cell carcinomas

Abstract Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most prevalent cutaneous malignancies. C-Kit plays a role in tumor initiation, progress, recurrence, and metastasis. Several medicinal treatments target the c-Kit pathway. The aim of the study was to assess the expression of c-Kit in BCC and cSCC. Furthermore, the study aimed to correlate c-Kit expression with available pathological data of the tumor and clinical data of the patients. A total of 62 excision specimens from patients with BCC (n =  41) and cSCC (n =  21) were histopathologically and immunohistochemically evaluated using anti-c-Kit, a rabbit monoclonal antibody clone IHC526. More than half of BCC cases (63.4%) showed positive c-Kit expression. C-Kit expression was significantly correlated with age (p-value = 0.011). The intensity of positive c-Kit staining was statistically related to tumor size (p-value = 0.028). All cSCC cases (100%) showed negative c-Kit expression. Receiver operating characteristic (ROC) curve analysis demonstrated an area under the curve (AUC) of 0.817 (95% confidence interval: 0.714–0.920, p-value < 0.001), with a sensitivity of 63.4% and a specificity of 100% in differentiating BCC from cSCC. Assessment of c-Kit expression may be beneficial in the diagnosis of BCC and in distinguishing it from cSCC. Its high specificity supports its diagnostic utility; however, due to its moderate sensitivity, it should be interpreted in conjunction with routine histopathological findings. While this study was a diagnostic, it suggested that c-Kit inhibitors may have therapeutic effects in BCC cases that express c-Kit; however, more research is needed to validate this.