Advancing Open Science

The fungus Penicillium digitatum causes citrus green mold, a major postharvest disease. Understanding the molecular mechanisms underlying its development is crucial for devising effective control strategies. In this study, we performed a comprehensive transcriptomic analysis of P. digitatum across three key developmental stages: spores, germinated spores, and mycelia. A total of 2175 novel mRNAs, 3957 novel long non-coding RNAs (lncRNAs), and 144 circular RNAs (circRNAs) were identified in P. digitatum. Genetic variation analysis revealed 12,396 Insertion-Ddeletion and 23,264 single nucleotide polymorphisms, with their prevalence decreasing as development progressed. The expression levels, temporal expression patterns and significant differences in mRNAs and lncRNAs across different developmental stages were also observed. Functional enrichment analysis of differentially expressed mRNAs and differentially expressed lncRNA target genes highlighted key biological processes and pathways associated with macromolecular metabolism, signal transduction, DNA replication, and reactive oxygen species scavenging. Additionally, differential expression analysis explored the potential interactions between differentially expressed lncRNAs and their target genes, as well as those between lncRNAs and circRNAs. Our findings provide valuable insights into the complex regulatory networks underpinning the development and pathogenicity of P. digitatum, offering a foundation for future research aimed at controlling green mold.

Visceral leishmaniasis (VL) is a severe zoonotic disease characterized by high mortality and a pronounced systemic inflammatory response. Although Pentraxin 3 (PTX3) has been implicated in infectious and inflammatory disorders, its role in human VL remains poorly defined, and host-derived indicators that simultaneously reflect inflammatory and parasitic activity are limited. This study investigated the association between plasma PTX3 levels, parasite load, and PTX3 gene polymorphisms (rs1840680 and rs2305619) in patients with VL. An observational study was conducted between 2017 and 2021, including 36 patients with confirmed VL and 45 healthy controls matched by age and sex. Plasma PTX3 concentrations were determined by ELISA, parasite load by quantitative PCR (qPCR), and cytokines (IL-2, IL-6, IL-10, IL-17A, IFN-γ and TNF-α) by flow cytometry. PTX3 levels were significantly higher in VL patients than in controls (23.2 ng/mL vs. 0.80 ng/mL; p < 0.0001) and correlated positively with parasite load (r = 0.39; p = 0.02) and cytokines IL-6, IL-10 and IFN-γ. No associations were observed between PTX3 polymorphisms and disease susceptibility. These findings suggest that PTX3 reflects both inflammatory responses and parasitic burden in VL and may serve as a potential indicator of disease activity.

Background and Objectives: Acute type A aortic dissection (ATAAD) remains a life-threatening condition requiring prompt surgical management. Over the last decades, improvements in diagnosis, surgical techniques, and perioperative care have influenced patient characteristics and outcomes. This study analyzes temporal trends in the clinical profiles and results of patients surgically treated for acute type A aortic dissection (ATAAD) in a Northern Italian region over a fifteen-year period. Materials and Methods: All consecutive patients undergoing emergency surgery for acute Stanford type A aortic dissection or acute intramural hematoma (IMH) between January 2010 and December 2024 were retrospectively reviewed. Patients with chronic penetrating atherosclerotic ulcer or traumatic etiology were excluded. Demographic, clinical, and perioperative variables were analyzed to assess temporal changes. Trends were evaluated using linear regression and Cochran–Armitage tests for trend. Results: A total of 427 patients underwent surgery for AAD during the study period. The proportion of patients presenting with preoperative intubation significantly decreased over time (p for trend < 0.05), as did the incidence of preoperative shock (p for trend < 0.001). Conversely, the mean EuroSCORE showed a non-significant increase over the years. No significant differences were observed in age or other baseline parameters. A non-significant but progressive increase in female representation was observed over time (p = 0.064). Given this observation, a sex-based subanalysis was performed: women were significantly older (p < 0.001) and presented with higher EuroSCORE values (p < 0.001) compared to men, yet postoperative mortality was similar between sexes. This finding contrasts with recent reports suggesting worse outcomes among female patients. Conclusions: Over fifteen years, patients undergoing surgery for acute type A aortic dissection have shown decreasing rates of preoperative critical conditions, reflecting earlier diagnosis and improved management. Despite higher operative risk scores, women demonstrated comparable short-term survival to men within our regional program. Multivariable analysis showed that sex was dependently associated with in-hospital mortality.

The new species Euphorbia peruviandina (Euphorbiaceae) is described and illustrated with photos and line drawings. It belongs to subgenus Chamaesyce section Anisophyllum and is restricted to the puna vegetation of central and southern Peru at elevations of 3300 to 4200 m. It is proposed to be endangered following IUCN criteria. A comparison is made with two other Andean species of the section, E. jamesonii of Ecuador and E. orbiculata of Colombia and Venezuela. For all three taxa, type specimens are cited, and morphological descriptions, habitat information, exsiccate, and synonymy are given. An identification key to these taxa is provided. Euphorbia melanocarpa is proposed to be a synonym of E. jamesonii, and E. meridensis is treated as a synonym of E. orbiculata.

Guidance information plays an important role in influencing metro passengers’ travel choices and enhancing their travel experience during unplanned service disruptions. However, limited research has examined passengers’ behavioral responses to personalized guidance information in such contexts. This study aims to fill the gap and explore the impact of personalized guidance information on passengers’ travel choice behavior during unplanned metro service disruptions. First, we reconstruct the decision-making process of metro passengers under disruption scenarios and design personalized guidance strategies, followed by a stated preference survey to collect preference data. Using data from Beijing, China, a hybrid utility–regret model is developed to analyze how the content and frequency of personalized guidance information affect passengers’ travel choice preferences. The results show that recommended plans with explanatory information are more likely to be adopted, particularly when explanations are framed from the passenger’s perspective. A single notification serves as a timely reminder, whereas overly frequent messages may trigger annoyance and reduce effectiveness. These findings provide practical implications for the design of personalized guidance strategies, thereby mitigating the impacts of metro service disruptions.

Recognizing handwritten Arabic characters written by children via scanned or camera-captured images is a challenging task due to variations in writing style, stroke irregularity, and diacritical marks. Although deep learning has advanced this field, building reliable systems remains challenging. This study introduces a stacking ensemble framework for sensor-acquired handwriting data, enhanced with a dynamic confidence-thresholding mechanism designed to improve prediction reliability. The framework integrates three high-performing convolutional neural networks (ConvNeXtBase, DenseNet201, and VGG16) through a fully connected meta-learner. A key feature is the use of an optimized threshold that filters out uncertain predictions by maximizing the macro ${\mathrm{F}}_1$ score on validation data. The framework is evaluated on two benchmark datasets for children’s Arabic handwriting: Hijja and Dhad. The results demonstrate state-of-the-art performance, with an accuracy of $95.13\%$ and ${\mathrm{F}}_1$ score of $94.62\%$ on Hijja and an accuracy of $96.14\%$ and ${\mathrm{F}}_1$ score of $95.59\%$ on Dhad. Compared to existing methods, the proposed approach achieves more than a $3\%$ improvement in Hijja accuracy while maintaining robust performance across diverse character classes. These findings highlight the effectiveness of confidence-based stacking ensembles in enhancing reliability for Arabic handwriting recognition and suggest strong potential for automated educational assessment tools and intelligent tutoring systems.

The proteasome β5 subunit plays a central role in protein degradation and is an established therapeutic target in glioblastoma. Marizomib (MZB), a natural β5 inhibitor, has shown promising anticancer activity, yet suboptimal pharmacological properties limit its clinical translation. Using a comprehensive computational approach, this study aimed to identify and characterize novel MZB analogs with improved binding affinity, stability, and drug-like profiles. An integrative in silico study was performed, including molecular docking, frontier molecular orbital (FMO) analysis, pharmacophore modeling, molecular dynamics (MD) simulations over 200 ns, MM/PBSA binding free energy calculations, and per-residue energy decomposition. ADMET profiling evaluated the pharmacokinetic and safety properties of MZB and top-performing analogs. Docking and pharmacophore modeling revealed strong complementarity between MZB analogs and the β5 catalytic pocket. MD simulations showed that MZBMOD-77 and MZBMOD-79 exhibited exceptional structural stability with low RMSD values (0.40–0.42 nm), persistent binding within the active site cavity, and significant disruption of hydrogen-bond networks in the active loop regions Ala19–Lys33 and Val87–Gly98. MM/PBSA analysis confirmed their superior binding free energies (−19.99 and −18.79 kcal/mol, respectively), surpassing native MZB (−6.26 kcal/mol). Per-residue decomposition highlighted strong contributions from Arg19, Ala20, Lys33, and Ala50. ADMET predictions indicated improved oral absorption, reduced toxicity, and favorable pharmacokinetics compared to native MZB. This integrative computational study identifies MZBMOD-77 and MZBMOD-79 as promising next-generation proteasome β5 inhibitors. These analogs mimic and enhance the inhibitory mechanism of native MZB, offering potential candidates for further optimization and preclinical development in glioblastoma therapy.

Background and Objectives: Osteoarthritis (OA) is a common cause of chronic pain. In refractory cases, cooled radiofrequency (CRF) of the genicular nerves is indicated. However, recent studies suggest that traditional targets may be insufficient, proposing the inclusion of the recurrent fibular nerve and the infrapatellar branch of the saphenous nerve. This study reports a prospective four-case series evaluating short-term outcomes of CRF at five revised targets in elderly Brazilian patients. Case Report: The study (CAAE No.: 55647722.5.0000.5142) included four patients (three women, one man; mean age 73.8 years) with moderate to severe refractory knee pain underwent diagnostic nerve block followed by ultrasound-guided CRF. After 30 days, three patients reported pain reduction, including two who experienced substantial improvement. One patient maintained severe pain. Improvements in physical performance, knee flexion, and extension were observed in patients who responded clinically, while individuals with coexisting myofascial pain showed limited functional gains. One patient experienced mild transient pruritus. In this prospective case series, CRF applied to five revised targets appeared feasible and well tolerated, with short-term improvement in pain and function in some patients. These preliminary descriptive findings support further investigation in larger controlled studies.