Objective: To determine whether loss of Mblac1, a gene implicated in copper metabolism and Alzheimer’s disease, causes systemic mitochondrial redox imbalance and whether treatment with the copper chaperone elesclomol (ES) can restore this balance. Methods: We employed 3D cryo-fluorescence imaging to quantify RR in kidneys and livers of Mblac1 KO mice and their wildtype (WT) littermates. Adult mice of both sexes were administered either vehicle control (C) or ES (10 mg/kg, i.p.). Results: KO tissues exhibited reduced RR values, indicating an oxidized metabolic state. ES treatment recovered 77 % of the RR deficit in kidneys and 48 % in livers, restoring RR to WT levels. Conclusion: Mblac1 deletion disrupts mitochondrial redox homeostasis in peripheral tissues, while ES partially reverses this imbalance by restoring Cu(I)-dependent metabolism. Significance: Optical metabolic imaging reveals Mblac1 as a key regulator of systemic redox balance and supports ES as a potential therapy for Cu-linked metabolic dysfunctions.

Exosomes, as critical biomarkers for cancer diagnosis and metastasis monitoring, are limited by current detection techniques due to low sensitivity and refractive index (RI) detection ranges. To address this, this study proposes a germanium-doped photonic crystal fiber (PCF) biosensor integrated with surface plasmon resonance (SPR) technology. The sensor features a D-shaped structure with three layers of periodic air holes, germanium-doped core capillaries, and a gold film coating, which expands the effective RI detection range to 1.00-1.45 RIU and achieves a maximum wavelength sensitivity of 30,000 nm/RIU at 1500 nm. Simulation and optimization results demonstrate its ability to distinguish normal exosomes (1.35-1.38 RIU), tumor exosomes (1.39-1.42 RIU), and pro-metastatic exosomes (PMEs, 1.43-1.45 RIU) by monitoring resonance wavelength shifts, with significantly enhanced sensitivity in the high RI range (RI > 1.42). This sensor provides a label-free, high-performance tool for early warning of postoperative micrometastasis and improves the efficiency of cancer management.

A fast mid-infrared spectral probe was used to record infrared (IR) spectra of fresh skin tissue removed from patients with biopsy-proven Keratinocytic cancer (KC) during Mohs surgery. A 150-patient library of IR spectral data was obtained to see if KC can be differentiated from adjacent nonmalignant tissue and normal skin. A linear Support Vector Machine model was found to minimize overtraining and predict the contributions to decisions at each step in the spectrum. Training demonstrated a KC Sensitivity of 93±5% and Specificity 84±6% (3-fold Testing esd) on the full library using equal cost for KC and nontumor cases. Success in this test problem warrants future studies to see if differentiation of melanoma from benign melanocytic as well as other skin lesions is possible. This study was approved by the Advarra Institutional Review Board, #PRO00053468.

Virtual Machine (VM) hardening is essential for mission-critical cloud infrastructures, where any security breach can result in cascading failures and operational disruption. Existing solutions remain constrained by fragmented defense strategies, limited cost awareness, and insufficient analytical guarantees. To overcome these limitations, we present VirtSec+, an entropy-aware framework that jointly models threat probability, impact severity, entropy-based exposure, and defense cost within a unified optimization formulation. VirtSec+ uses information-theoretic entropy to quantify and minimize adversarial uncertainty while dynamically allocating hardening controls to achieve risk-aware cost efficiency. The framework employs entropy-gradient updates with budget-aware activation and a convex optimization routine that ensures provable convergence with bounded runtime overhead. Extensive evaluations across representative cloud data center scenarios show that VirtSec+ reduces residual risk by up to 52%, accelerates adaptation latency by 28%, and improves resource efficiency by 2.3× over state-of-the-art baselines. All improvements are statistically significant at p<0 .01 . VirtSec+ establishes a resilient, adaptive, and mathematically grounded foundation for VM hardening in mission-critical cloud environments by integrating entropy minimization with rigorously validated cost–security optimization.

IntroductionChronic inducible urticaria (CIndU) is a heterogeneous disorder characterized by the development of transient wheals or angioedema in response to specific environmental or physical stimuli[1]. Among the various subtypes, touch-induced urticaria is defined by the appearance of erythematous, pruritic wheals after minimal mechanical stimulation, such as stroking the skin, friction from clothing, or pressure from surfaces[1]. These lesions typically arise within minutes and resolve spontaneously within a few hours[1]; however, recurrent episodes can significantly impair quality of life and disrupt daily activities, particularly in young adults and students[2].Management of CIndU is challenging due to its variable response to standard therapy[3]. Non-sedating H1 antihistamines constitute the first-line treatment, with doses escalated up to fourfold in refractory cases[4]. H2 blockers or short courses of systemic corticosteroids may be added when antihistamines fail to control symptoms[1]. Despite these interventions, a subset of patients continues to experience severe disease manifestations, underscoring the need for alternative treatment strategies, including biologic therapy[1]Omalizumab, a monoclonal antibody targeting IgE, has demonstrated efficacy in chronic spontaneous urticaria (CSU) and select cases of CIndU that are refractory to antihistamines[5]. While elevated serum IgE is often considered a predictor of response, evidence suggests that some patients with normal or fluctuating IgE levels may still benefit from anti-IgE therapy[6]. This raises important questions about the pathophysiological role of IgE in CIndU and the mechanisms underlying omalizumab’s clinical effects, which may extend beyond IgE neutralization to include mast cell stabilization and modulation of autoreactive immune pathways[7].In this report, we describe a 20-year-old male with touch-induced CIndU and a history of childhood atopy, whose serum IgE levels fluctuated over time and whose disease severity remained consistently high. The case illustrates the limitations of relying solely on IgE to guide therapy and emphasizes the importance of phenotype-driven management strategies in refractory urticaria.

A document by Na Li. Click on the document to view its contents.

Title:Pneumatosis Intestinalis Mimicking Perforated Viscus in an Ankylosing Spondylitis Patient Undergoing Adalimumab Therapy: A Case ReportAuthors:Ali Soltaniyan¹, Armin Tajik²*, Alireza Shakerpour³, Pegah Azarimanesh⁴, Sarah Mohabbi²¹ Department of Surgery, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran² Student Research Committee, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran³ Department of General Surgery, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran⁴ Department of Obstetrics and Gynecology, School of Medicine, Alborz University of Medical Sciences, Karaj, IranCorresponding author:Armin Tajik,Student Research Committee, School of Medicine, Alborz University of Medical Sciences, Karaj, IranEmail: armintajik.srgn@gmail.com

Biodiversity hotspots are often found in areas with high precipitation or diverse microhabitats. For plants, geographic areas with high soil variability tend to have high species richness or functional trait diversity. Serpentine soil is thought to have driven the diversification of numerous plant lineages, and many plant taxa show phenotypic variability across soil types. Precipitation can increase the effects of soil type on trait differences across soil types, such that trait differences are greater in wetter geographic areas. However, this has been examined only for growth and vegetative traits. We used a greenhouse common garden to characterize variation in reproductive phenology for a serpentine tolerator along a strong moisture gradient. We then evaluated if trait divergence changes with precipitation, and if the divergence in reproductive traits across soil types varies with precipitation. Furthermore, we conducted a water-limitation experiment and examined if water-limitation changes trait expression or divergence in trait expression. Finally, through a set of field observations we assessed if reproductive phenology and divergence in reproductive phenology differed between wetter and drier areas. We found strong effects of native precipitation regime on flowering phenology, and some support for the hypothesis that precipitation enhances divergence between plants growing on serpentine and non-serpentine soils both in the greenhouse common garden and in the field. Experimental water limitation in the greenhouse common garden resulted in reduced floral displays, phenological delays, and an increase in divergence across soil types for some traits. These results highlight the possibility that gene flow across soil types may be lower in wetter areas. In addition, they suggest that future drought may decrease the likelihood of gene flow across soil types, as well as plant reproductive potential via smaller floral displays.

We present a ‘scissorable’ piezoelectric nanogenerator (SCIPENG) platform comprising flexible micrograting electrodes laterally interconnected by piezoelectric nanowires, whose scalable and homogenous architecture uniquely allows easy cut into the desired size simply by using a scissors. On each sidewall of the microgratings formed by UV nanoimprint lithography, Ag and Au are sequentially deposited via glancing angle deposition (GLAD), followed by another GLAD of Cr on top of the microgratings. Through the metal-mediated seedless hydrothermal synthesis, the ZnO nanowires (ZNWs) can be laterally grown preferentially from each Au sidewall to interconnect each neighboring Ag sidewall while a catalytic-inactive Cr capping layer securely suppresses unnecessary ZNW growth outside the micrograting scaffold. The resulting SCIPENG structure, consisting of multiple stacks of laterally aligned ZNW-interconnected, Au- and Ag-deposited asymmetric micrograting electrodes, exhibits excellent piezoelectric performance under repeated mechanical bending without external bias, with the maximum peak-to-peak voltage of ~140 V. Scissoring into the controlled sizes ( e.g., half-length. half-stack) demonstrates well-predictable scaling behavior; output voltage increases with decreased micrograting length; current scales linearly with the stacking number of microelectrodes. This platform offers highly scalable fabrication and extremely easy scaling, particularly promising for sustainable high-mix, low-volume production of flexible devices requiring diverse sizes upon diverse uses.

A document by Jahin Ahmed. Click on the document to view its contents.

As survival improves for individuals with cystic fibrosis (CF) worldwide, the number of adolescents requiring transition from pediatric to adult care is rapidly growing. In addition to limited resources, lack of uniform access to medical care, access to traditional and advanced therapies, the increasing number of transitioning young adults in low- and middle-income countries (LMICs) face barriers and challenges to safe transition from pediatric to adult healthcare that are both universal and unique. This shift in demographics presents distinct challenges due to underdeveloped and under-resourced adult CF care infrastructure, sociopolitical variation, and cultural complexities. This manuscript focuses on healthcare transition (HCT) of people with CF (pwCF) in LMICs, identifies key barriers, and explores cultural, religious, and health system factors. Additionally, we emphasize the practical need to transition adolescents to adult care to maintain pediatric hospital capacity for younger children, as well as the developmental and educational needs of young adults entering a medical system that is challenging for adults without chronic disease. With much of the transition literature reflecting health systems in high-income countries (HIC), this integrated socio-ecological and socio-cultural overview underscores the urgent need for context-specific, culturally sensitive transition frameworks focused on reproductive and mental health, the integration of adolescent-responsive, family-inclusive, and even faith-informed care models in LMICs.

INTRODUCTIONNeuroendocrine tumors (NETs) of the head and neck are rare and aggressive neoplasms, accounting for less than 1% of all tumors in this anatomical region (1,2). The estimated 5-year survival rate is below 20%. These tumors most predominantly affect males in the 5th-6th decades of life and are most commonly located in the larynx and sinonasal tract.(1,3,4) NETs typically exhibit immunohistochemical positivity for synaptophysin and chromogranin and are characterized by a markedly elevated proliferative index. (3,5-8)Neuroendocrine carcinomas are a more aggressive known histological subtype. According to the World Health Organization, these tumors are currently classified into two major histological subtypes: small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC). (4,6,9) Both subtyped are considered highly aggressive tumors, with poor prognosis and frequent regional and/or distant metastasis. (3,4,6, 9-11).Management of head and neck neuroendocrine carcinomas is challenging and requires a multimodal approach (1,2,5,9). Achieving locoregional control is essential due to high risk of metastatic spread.Neuroendocrine tumors of the tongue are exceptionally rare, with very few cases documented in literature. They account for less than 1% of all tongue malignancies. (1,3,12) These tumors are associated with a poor prognosis, high recurrence rated and a significant risk of metastasis.

Software process metrics often rely on declarative data sources such as self-reported progress at daily meetings or manual inputs in project management tools. These approaches introduce subjectivity and limited traceability. In contrast, GitHub repositories contain rich, automatically generated traces offering more concrete and reproducible data for empirical analysis that can mitigate subjectivity. This paper introduces RepoInsights, a system designed to extract, store, and visualize key repository-based software process metrics derived from GitHub traces. We begin with a systematic literature review to compile existing process metrics, which are then operationalized using elements such as commits, pull requests, and issues as proxies. The metrics include, among others, Bus Factor, Time to First Response, and Pull Request Closure Rate. The tool provides dashboards tailored for project managers and researchers, enabling data-driven decision-making. The system’s effectiveness was validated through structured user testing involving two target profiles: software researchers and project managers. Results demonstrate the tool’s utility in teams’ assessment, comparison, and monitoring, offering a replicable, trace-based alternative to traditional metric gathering in software process improvement efforts.

Germline MRAS variant in an infant with bilateral adrenal neuroblastomaGorkem Oztosun, MD1; Eric Hawley, MD, PhD2; Sue L. Jaspersen, PhD, MGC, CGC3; Amy E. Armstrong, MD21: Division of Medical Oncology, Washington University in St. Louis, MO, USA2: Division of Pediatric Hematology/Oncology, Washington University in St. Louis, MO, USA3: Division of Genetic Counseling, Washington University in St. Louis, MO, USACorresponding author:Amy E. Armstrongarmstrongae@wustl.eduChildren’s Hospital, 1 Children’s PlaceSt. Louis, MO 63110314-454-6018Word count - Main text: 850Number of figures: 1Running title: germline MRAS mutation in metastatic bilateral adrenal neuroblastomaKeywords: bilateral adrenal neuroblastoma, germline MRAS, intermediate-risk neuroblastomaAbbreviation Key

The healthcare system in the Gaza Strip has been severely compromised by prolonged conflict, infrastructure degradation, and resource limitations. Interdependent systems—water, sanitation, energy, and transport—are critical for effective healthcare delivery, yet their collapse has amplified public health crises. This study evaluates optimal strategies for rebuilding Gaza’s healthcare system and related infrastructure to improve population health outcomes. A retrospective quantitative approach was employed using data from the World Health Organization (WHO), verified local sources, and media reports. Hospital functionality, health workforce availability, medical supply continuity, and infrastructure status were assessed. Infectious disease incidence was analyzed relative to system disruptions using Spearman’s rank correlation. Healthcare system recovery was modeled with Success Tree Analysis (STA), and potential interventions were evaluated via Multi-Criteria Decision Analysis (MCDA). Of 38 hospitals assessed, only 23.7% were fully functional, with North Gaza experiencing 50% non-functional facilities. Physicians per 10,000 population declined by 45%, and only 48% of facilities had essential medicines. Electricity and water system functionality were 27% and 35%, respectively, contributing to high diarrheal disease (72.4/10,000) and respiratory infection (96.5/10,000) rates. Strong correlations were observed between infrastructure and health outcomes, including electricity vs. hospital functionality (ρ = 0.82) and water supply vs. diarrheal disease (ρ = –0.76). STA modeling indicated that integrated recovery of energy, water, and workforce could restore up to 89% of hospital functionality within five months. MCDA ranked rapid infrastructure repair, renewable energy integration, and water network rehabilitation as top strategies. The findings highlight that Gaza’s healthcare system requires coordinated, multi-sectoral interventions and spatially targeted strategies to ensure equitable access, strengthen resilience, and improve population health in conflict-affected settings.

To advance the automation of timber harvesting, this paper addresses the challenges of high nonlinearity and uncertainty inherent in a harvester’s hydraulic manipulator by developing and validating a complete, high-performance trajectory control scheme. A kinematic model is established using the Denavit-Hartenberg (D-H) method, and an S-curve planning method generates smooth reference trajectories. A model-free Fuzzy PID adaptive controller is designed to achieve precise tracking. To validate its performance, a high-fidelity co-simulation platform was established. Simulation results demonstrate that, compared to a conventional PID controller’s 5% overshoot and 2.5s settling time, the proposed fuzzy PID controller eliminated overshoot and reduced settling time by 40% to 1.5s. However, in a more complex five-axis coordinated tracking task, a rigorous forward kinematics analysis revealed that while the controller ensures stable path following, the maximum end-effector tracking error reached approximately 1400 mm. This result highlights the significant challenge of kinematic error amplification in large-scale manipulators. It underscores that achieving high-precision positioning requires advanced control strategies beyond robust feedback alone.

Invasive alien plant species have garnered increasing global attention due to their profound environmental impacts,ecological disruptions,and significant economic consequences.Henan Province,located in the middle and lower reaches of the Yellow River,serves as a critical ecological barrier in central China.In recent years,invasive plants have adversely affected local biodiversity and the integrity of native ecosystems in the region.Moreover,future climate change is expected to reduce the climatic suitability of many invasive species.In this study,we identified 34 malicious invasive alien plant species in Henan Province,spanning 12 families and 25 genera.We used the Maximum Entropy modeling (MaxEnt) approach to predict the potential geographic distributions of 17 malicious invasive alien plant species.Our research results indicate that the potential geographical distribution areas suitable for malicious alien invasive plants are mainly concentrated in the western and southern regions of Henan Province.Currently,the potential distribution area of all 17 malicious alien invasive plant species accounts for 18.42% of the province’s total area.By 2050,this area is projected to decrease to between 17.27% and 15.99%,with the greatest reduction of 13.17% expected under the highest greenhouse gas emission scenario.In addition,malignant alien invasive plants are expected to expand from low to high altitudes in the future,and the centroid of suitable habitats is projected to shift southwestward.This study provides a scientific basis for assessing the risk of introduction and spread of invasive alien species in Henan.It also offers valuable guidance for biodiversity conservation,ecosystem protection,and sustainable development in the face of ongoing environmental change.

The future of sustainable industrial biotechnology relies on microbial hosts that can thrive where conventional strains fail. Although Saccharomyces cerevisiae remains the workhorse of industrial production, its intrinsic metabolic constraints and susceptibility to multiple stresses underscore the need for alternative yeast chassis. Here, we present a comprehensive characterization of 79 yeast isolates from the Brazilian Yeast Collection (BRYC), sourced from diverse ecosystems across six Brazilian biomes. Strains were evaluated for growth under industrially relevant conditions, including alternative carbon sources, inhibitory compounds from biomass pretreatment, elevated temperatures, and high ethanol concentrations. Phenotyping was carried out in both solid and liquid media, allowing comparison of trait analyses across cultivation conditions, and revealing how growth environment influences phenotypic expression. Performance was further assessed in raw and hydrolyzed sugarcane and agave biomass. This high-throughput approach identified multiple non- Saccharomyces yeasts with superior traits compared to S. cerevisiae controls. Pichia kudriavzevii (BRYC98) exhibited exceptional multi-stress tolerance, including thermotolerance and resistance to aldehydes, ethanol, and acetic acid. Candida flosculorum (BRYC21), a poorly characterized native yeast species, exhibited remarkable versatility in substrate utilization. Debaryomyces hansenii strains showed the best growth in saponin-rich agave leaf juice - the most challenging substrate tested-, while Wickerhamomyces anomalus strains consistently outperformed controls in sugarcane molasses and hydrolysate. Overall, around 68% of the non-conventional strains exhibited higher robustness across the 15 tested conditions for both maximum biomass and specific growth rate compared to S. cerevisiae. These findings expand the portfolio of stress-resilient, metabolically versatile yeasts and provide a foundation for their development as alternative industrial chassis.