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Hierarchical modeling of tumor subtypes in cell lines using large-scale genomic datasets.

Cancer cell lines (CLs) are widely used to study tumor biology and drug response, yet their translational relevance is often limited by inaccurate subtype annotations. Existing CL-tumor matching approaches are frequently constrained by flat classification schemes, weak subtype definitions, and the exclusion of normal tissue references, leading to potential confounding of tumor-specific and tissue-of-origin signals. To address these limitations, a hierarchical classification (HC) framework is presented in which CLs are aligned with patient tumors across biological resolutions, from organ to molecular subtype. Gene expression profiles from 802 CLs, 5,612 tumors from The Cancer Genome Atlas (TCGA) , and 8,939 non-cancerous tissues were integrated to separate oncogenic signals from tissue-specific signals. Node-specific features were selected using maximum relevance minimum redundancy, and balanced accuracies of 89% in cross-validation and 75%, and 80% on external datasets were achieved. Through the framework, 43 CLs were reassigned, and clinically relevant underrepresented subtypes were identified.

cancer cell lines

Innovation-related perception as a key driver of alternative protein acceptance: evidence from an early-stage model for cultivated meat and algae-/microalgae-based alternative protein products in Italy.

Alternative proteins are increasingly considered part of the transition toward more sustainable food systems, yet their diffusion depends critically on consumer acceptance. This study investigates the early-stage acceptance of two alternative protein categories in Italy-cultivated meat and algae-/microalgae-based alternative protein products. Focusing on the first three phases of acceptance, the analysis examines how innovation-related perception (IRP) shapes consumer perceived value (CPV), consumer perceived risk (CPR), and subsequent affective (AFF), cognitive (COG), and conative (CON) responses. Data were collected through an online survey administered to 238 Italian respondents and analysed using partial least squares structural equation modelling (PLS-SEM). The results show that IRP is the main upstream driver of early-stage acceptance in both product domains: more favourable perceptions strongly increase perceived value and reduce perceived risk. In turn, CPV exerts a much stronger influence than CPR on both affective and cognitive attitudes. A tentative cross-model comparison suggests only a descriptive variation in the final transition toward conative acceptance: affective and cognitive responses were both significant in the two models, with a relatively larger affective coefficient for cultivated meat and more balanced coefficients for algae-/microalgae-based products. Overall, the findings support a process-based interpretation of alternative protein acceptance and highlight the central role of innovation-related perception in shaping early consumer responses. These results provide relevant implications for communication strategies, product positioning, and policy actions aimed at improving the acceptability of alternative proteins in food cultures characterised by strong culinary traditions.

Italy

Optimized AAV5-RPGR ORF15 Gene Therapy Rescues Photoreceptor Structure and Function in X-Linked Retinitis Pigmentosa Mouse Model.

PURPOSE: To develop and evaluate an rAAV5-based gene therapy vector expressing an optimized human RPGR ORF15 transgene (rAAV5-RPGR) for the treatment of X-linked retinitis pigmentosa caused by RPGR mutations, addressing the challenges of cloning the unstable wild-type ORF15 sequence. DESIGN: This was a prospective experimental study. SUBJECTS: This was an animal study. METHODS: An optimized RPGR ORF15 sequence was designed to eliminate problematic secondary structures and cryptic splice sites. In vitro expression was validated in HEK 293T and photoreceptor-like 661 W cells. A complete Rpgr knockout mouse model (Rpgr-knockout [KO]) was generated and characterized phenotypically. Therapeutic efficacy was assessed in Rpgr-KO mice via subretinal injection of rAAV5-RPGR at low (1 &#xd7; 10&#x2079; vg/eye), medium (3 &#xd7; 10&#x2079; vg/eye), or high (1 &#xd7; 10&#xb9;&#x2070; vg/eye) doses. Structural and functional outcomes were evaluated at 12- and 14-month postinjection. Short-term safety was assessed in rabbits 1 month after subretinal injection. MAIN OUTCOME MEASURES: Level of RPGR protein expression and Protein isoform profile (elimination of truncated isoforms), Cellular localization of transgene expression and Dose-dependence of expression, outer nuclear layer thickness, and electroretinography parameters. RESULTS: (1) The optimized vector increased RPGR protein expression 3.3-fold in vitro compared to wild-type and eliminated truncated isoforms. (2) Subretinal delivery of rAAV5-RPGR in mice demonstrated dose-dependent transgene expression localized correctly to photoreceptor inner segments. (3) In Rpgr-KO mice, high-dose treatment significantly preserved outer nuclear layer thickness at the injection site (42% greater than controls at 14 months, P < .01) and central retina (P < .05), reduced aberrant rhodopsin mislocalization (P < .01), and partially restored retinal function. ERG showed significantly improved scotopic a-wave (&#x2265;100 vs <90 &#xb5;V in controls at 10 cd&#xb7;s/m&#xb2;) and photopic b-wave amplitudes (49-66 vs 31-46 &#xb5;V at 30 cd&#xb7;s/m&#xb2;) in treated mice. (4) No vector-related toxicity was observed in rabbits. CONCLUSIONS: rAAV5-RPGR mediated efficiently, targeted expression of optimized RPGR-ORF15, significantly preserved photoreceptor structure and function in a severe X-linked retinitis pigmentosa mouse model, and demonstrated a favorable safety profile. This study provides preclinical proof-of-concept for RPGR-targeted gene replacement therapy.

Animals

Urban stormwater infrastructure as a microplastic superhighway: a critical review of transport dynamics, modelling, and mitigation across pavements and drainage networks.

This review examines the transport, fate, modelling, and mitigation of Microplastics (MPs) in urban stormwater infrastructure, with emphasis on pavements, runoff pathways, micro-drainage, and macro-drainage systems. Following a systematic review approach, more than 1000 records were screened and approximately 50 core studies were retained when they addressed urban stormwater or drainage-related MP transport with adequate methodological reporting; marine-only studies and biological-effect studies without direct relevance to transport processes were excluded. The evidence shows that stormwater systems function not merely as passive conduits but as dynamic reactive transport systems with temporary storage, where particle mobilisation, sedimentation, resuspension, and temporary retention regulate MP export. Road surfaces, especially high-traffic areas, are major reservoirs of tyre wear, road-marking, atmospheric, and litter-derived particles that are rapidly mobilised during rainfall. Conventional grab sampling may underestimate MP loads, which in some cases exceed treated wastewater effluent loads by up to six-fold. Drainage structures such as manholes can immobilise up to 17.3% of near-neutrally buoyant particles, while biofouling and aggregation may shift buoyant polymers from wash-load to bedload. Mitigation systems, including permeable pavements, bioretention, wetlands, and technical inserts, can achieve high removal of coarse MPs, but performance declines for fine particles below 100&#xa0;&#xb5;m. The review highlights the need for standardised flow-proportional sampling, physically informed modelling, and treatment-train strategies targeting both surface sources and in-network storage.

Microplastics

De Novo 2.2&#x2009;Mb 19q13.42-q13.43 Microdeletion Encompassing U2AF2: Support for a Haploinsufficiency Model.

U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an essential pre-mRNA splicing factor involved in the early stages of pre-mRNA splicing. To date, multiple individuals have been reported with predominantly heterozygous missense variants presenting intellectual disability, speech and motor delays, seizures, hypotonia, and thin or hypoplastic corpus callosum. Here, we describe a patient with a de novo 2.2&#x2009;Mb interstitial deletion involving chromosome 19q13.42-q13.43, encompassing U2AF2, presenting with intellectual disability, epilepsy, corpus callosum hypoplasia, dysmorphic features, and congenital heart disease. The patient's clinical features overlap substantially with those reported in individuals harboring heterozygous U2AF2 variants, supporting haploinsufficiency as a plausible disease mechanism. To our knowledge, this represents the first postnatal report of complete U2AF2 gene deletion. In addition, this is the first detailed phenotypic characterization of a distal 19q chromosomal interstitial deletion, further delineating the clinical spectrum associated with this genomic region.

Humans

Ramu stunt virus genome reveals previously unreported segments and nucleocapsid domain duplication in Mechlorovirus.

Ramu stunt virus (RmSV), a member of the genus Mechlorovirus within the family Phenuiviridae, was previously described as a six-segmented RNA virus infecting sugarcane. In this study, we re-examined type material and additional isolates using high-throughput sequencing and RT-PCR validation, revealing that RmSV possesses a nine-segmented genome, making it the largest reported in the Phenuiviridae. This expanded architecture includes duplicated RNA segments (RNA 2a and RNA 2b) encoding nucleocapsid-like proteins and two novel segments (RNA 7 and RNA 8). Comparative analysis showed that RNA 2a and 2b share about 84% amino acid identity, while RNA 5 encodes a third nucleocapsid homolog, indicating unprecedented domain redundancy. Structural modeling confirmed that all three nucleocapsid proteins maintain a conserved fold despite low sequence identity, with electrostatic mapping suggesting differential RNA-binding potential. Additionally, RNA 6 encodes a hypothetical protein structurally similar to the rice stripe virus disease-specific S-protein, implicating a role in symptom development. Transcript abundance analysis revealed RNA 6 as the most highly expressed segment across isolates. These findings revise the genomic composition of RmSV, highlight mechanisms of genome plasticity and adaptive evolution in plant-infecting bunyaviruses, and underscore practical implications for diagnostic assay design, resistance breeding, and biosecurity surveillance.

Genome, Viral

Nipocalimab Phase 3 Dose Selection for Severe Hemolytic Disease of the Fetus and Newborn.

Nipocalimab, a neonatal Fc receptor (FcRn) blocker, is under evaluation for severe hemolytic disease of the fetus and newborn (HDFN). In the Phase 2 UNITY trial, weekly intravenous antenatal treatment with nipocalimab at dose regimens of 30 and 45 mg/kg prevented fetal anemia requiring intrauterine transfusion (IUT) in 54% of high-risk pregnancies and delayed the need for IUTs versus their previous pregnancies in the remaining 46% of pregnancies. This analysis aimed to select a weekly dose regimen of nipocalimab for the Phase 3 study in severe HDFN (NCT05912517) that maintains FcRn blockade throughout antenatal treatment, including with an unplanned dosing delay of up to 3 days. Observed pharmacokinetic/pharmacodynamic (PK/PD) data from UNITY (i.e., nipocalimab concentrations, FcRn occupancy, and serum IgG) were analyzed using a model-based approach. A PK/PD model originally developed in nonpregnant participants was updated to incorporate gestational weight gain. Nipocalimab PK and FcRn occupancy were described by a two-compartment model with nonlinear, dose-dependent PK, which captured longitudinal PK, FcRn occupancy, and IgG profiles during dosing and return toward baseline postpartum after discontinuation. Both 30 and 45 mg/kg achieved &#x223c;80%-85% reductions in maternal IgG; however, 30 mg/kg showed greater variability in predose trough concentrations, increasing the risk of falling below concentrations required for full FcRn occupancy across antenatal treatment. Simulations incorporating PK/PD variability indicated that 45 mg/kg weekly per current weight maintained full FcRn occupancy in >95% of pregnant individuals, even with dosing delays up to 3 days. Exploratory exposure-response analyses supported 45 mg/kg for the Phase 3 HDFN study.

Humans

Impacts of climate-driven yield changes on the affordability of healthy diets: a modelling study.

BACKGROUND: Food security is central to global nutrition improvement and public health goals, and healthy diets represent a higher-level aspiration beyond merely avoiding hunger. Climate change poses an increasing threat to food systems by affecting crop yields and food prices. Although climate change-driven risks to hunger have been widely studied, the extent to which climate change undermines the affordability of healthy diets while accounting for socioeconomic responses and regional inequalities remains insufficiently understood. This study aimed to quantify the effects of climate change on the future affordability of healthy diets under alternative socioeconomic and climate scenarios. METHODS: We developed an integrated modelling framework that explicitly couples multimodel crop-yield projections with an integrated assessment model (Global Change Analysis Model [GCAM]). Yield responses from six global gridded crop models driven by four climate models were integrated into GCAM, allowing endogenous socioeconomic adjustments such as land-use shifts, production reallocation, and price responses to emerge under shared socioeconomic pathways (SSPs). Diet affordability was then assessed using the Food and Agriculture Organization of the UN's Cost and Affordability of a Healthy Diet framework across three socioeconomic-climate scenarios (SSP1-2.6, SSP2-4.5, and SSP3-6.0). FINDINGS: Under a high-emissions pathway (ie, SSP3-6.0), climate change was projected to render healthy diets unaffordable for a model-mean of 119 million people globally by 2100, even when CO2 fertilisation effects are included, with the upper end of the model ensemble reaching about 1&#xb7;6 billion people. In contrast, climate-induced affordability losses were found to be negligible under both a low-emissions pathway (ie, SSP1-2.6; -0&#xb7;3 million) and a medium-emission pathway (SSP2-4.5; +0&#xb7;2 million). Under a high-emission pathway, model-mean projections indicated that diet costs could increase by up to 12% in the most affected regions by the end of the century. Under medium emissions, cost increases were projected to remain below 4%, whereas under low emissions, affordability changes were projected to be minimum across regions (within approximately 0&#xb7;5%). Substantial regional disparities emerged, with the largest and most consistent affordability losses concentrated in low-income regions that contributed least to historical greenhouse gas emissions. Under SSP3-6.0, these disparities persisted particularly in regions of Africa and Asia despite projected three-to-five-fold increases in income over the century, with climate-induced disruptions to food systems increasing the number of people unable to afford a healthy diet through mid-century. INTERPRETATION: Climate change is likely to exacerbate global nutritional inequalities by disproportionately increasing the affordability risks of healthy diets in regions that have contributed least to historical greenhouse gas emissions. Under high-warming scenarios, socioeconomic development alone is insufficient to fully offset these risks, highlighting the structural vulnerability of low-income food systems to climate-driven price shocks. These findings suggest that in the absence of targeted interventions, climate change could continue to undermine progress towards equitable and health-oriented nutrition outcomes. FUNDING: Ministry of Science and Technology of the People's Republic of China; National Natural Science Foundation of China; National Aeronautics and Space Administration Goddard Institute for Space Studies Climate Impacts Group; Future of Life Institute; and Global Alliance for Improved Nutrition.

Journal Article

An Assessment of Reliability Estimation Methods for Binomial Health Care Quality Measures.

We evaluated the performance of commonly used methods for estimating the reliability of binomial health care quality measures using simulated datasets spanning a range of performance score means and variances, numbers of entities, and patient sample sizes. For each simulation, reliability was estimated for all selected methods and compared with the known true reliability derived from the simulation parameters, with methods assessed on their accuracy and precision. Logistic regression with reliability estimated on the outcome scale demonstrated the highest accuracy and precision among all methods evaluated. The widely used Adams beta-binomial method performed poorly, although a modification recommended by Nieser and Harris substantially improved its performance. These approaches are applicable only to binomial measures. Among methods that can be applied to both binomial and continuous measures, permutation resampling of the Spearman rank correlation coefficient was the most accurate and precise, outperforming other commonly used approaches. Overall, for binomial quality measures, logistic regression on the outcome scale is the preferred method for reliability estimation, followed closely by the modified beta-binomial approach, while for non-binomial measures, permutation-based Spearman rank correlation appears to be the most suitable method.

Reproducibility of Results

Re-evaluating pediatric laryngoscope blade size recommendations: Comparable intubation performance across blade sizes in pediatric manikin models.

BACKGROUND: Pediatric airway management traditionally emphasizes strict adherence to age-based laryngoscope blade size recommendations, despite limited empirical validation. OBJECTIVES: To evaluate whether intubation performance varies across a range of blade sizes, and whether a Macintosh 2 blade performs comparably across multiple pediatric age groups in a simulation setting. METHODS: We conducted a randomized crossover simulation study using three pediatric airway manikins (neonate, infant, and child age groups). Emergency medicine residents and faculty physicians performed intubations using multiple laryngoscope blade types and sizes, including standard and nonstandard options. Primary outcomes were intubation time and first-attempt success. Secondary outcomes included complications and operator-rated ease of glottic view and tube passage. Between-blade differences were estimated with 95% confidence intervals. RESULTS: Across manikin sizes and blade types, intubation times were short and first-attempt success rates exceeded 98% in most conditions. Performance remained consistent even with blade sizes outside conventional age-based recommendations. Between-blade differences in intubation time were small, and complication rates were low across conditions. The Macintosh 2 blade performed comparably across all manikin sizes, with similar intubation times, high success rates, and favorable ease ratings. CONCLUSIONS: Intubation performance in pediatric manikin models was similar across a wide range of blade sizes. These hypothesis-generating findings warrant prospective clinical evaluation of simplified blade selection strategies for pediatric intubation.

Manikins

Cost-Effectiveness of Electronic Patient-Reported Outcome Measure Interventions in Cancer: Systematic Review and Parameter Extraction for Economic Modeling.

BACKGROUND: Complex digital interventions that integrate electronic patient-reported outcome measures (ePROM) into clinical practice in cancer have the potential to improve quality of life, increase survival, and reduce health resource use and costs. Such systems can help patients with cancer self-manage chemotherapy symptoms, reduce clinicians' workloads through automated decision support, and resolve problems earlier. However, more research on the cost-effectiveness of ePROM monitoring is needed. OBJECTIVE: This paper comprises two complementary components: (1) a systematic literature review summarizing and evaluating the quantitative and qualitative evidence related to the cost-effectiveness of ePROM monitoring and (2) a health economic model parameter extraction. We also conducted supplementary targeted searches and scoping to provide context to our findings. METHODS: We searched Ovid (including MEDLINE and Embase), Scopus, and the International Health Technology Assessment Database for original English-language papers published on or before March 2025 using search strings that combined terms related to ePROMs, health economics, and cancer/oncology. We included papers reporting health economic-related outcomes for ePROM interventions designed for adult cancer populations and excluded screening tools and conference abstracts. RESULTS: We included 34 publications from 27 unique studies and identified and analyzed 26 ePROM-integrated interventions within these. Most (23/26) of the included interventions explicitly described some form of alert handling and automated decision support based on remote ePROM monitoring. Of the 34 publications, 5 presented full cost-effectiveness analysis results, of which 3 were highly uncertain and lacked clear differences in costs and health outcomes between ePROMs and standard care; conversely, 2 presented strong evidence of cost-effectiveness due to quality-of-life improvements, reduced hospitalizations, and potentially more autonomy in health-related travel (eg, ePROM-monitored patients can drive or walk to the hospital instead of using taxis or ambulances). A further 5 publications reported partial health economic results (eg, cost-consequence and budget impact), of which 1 detected no difference in strategies; in contrast, 4 reported lower health resource use and costs of ePROMs, mainly due to hospitalization reductions. Overall, 12 of the 27 studies included a qualitative component but mostly focused on user experience and design-related themes; only 2 of these addressed economic-specific themes (eg, changes in workflow and resource use due to ePROM implementation and integration), indicating some potential for time saving due to ePROM monitoring. CONCLUSIONS: Some ePROM-integrated interventions demonstrated cost-effectiveness in cancer care, but the evidence base remains limited. Where evidence does exist, cost-effectiveness appears driven by reduced hospitalization and improved quality of life. Qualitative research within the included studies rarely addressed economic questions. We provide a detailed parameter extraction for use in future economic modeling and recommend research priorities, including quantitative mapping of ePROM symptom data onto health resource use patterns, and qualitative work exploring how ePROM implementation affects clinical workloads and patient-perspective costs.

Humans

The Impact of Chatbot Type and Normative Messaging on Chatbot Usage Intention Based on the Health Technology Acceptance Model: Randomized Controlled Trial.

BACKGROUND: Digital health tools, such as health chatbots, may improve access to scalable health support, but adoption remains inconsistent. Existing models do not fully integrate technology acceptance factors with health motivation factors relevant to digital health use. OBJECTIVE: This study proposed and tested the health technology acceptance model and examined whether normative message framing and chatbot type were associated with health motivation, technology acceptance, and intention to use a health chatbot. METHODS: In October 2025, we conducted a 4 &#xd7; 2 between-participants online experiment with 1000 US adults recruited from a nationally representative YouGov panel. Participants were randomized to 1 of 8 conditions varying norm message type (self-oriented, peer-oriented, expert-oriented, or family-oriented) and chatbot type (AI-powered or rule-based) in a cancer prevention and genetic risk information scenario. Outcomes included descriptive norms, injunctive norms, perceived susceptibility, perceived severity, perceived benefits, self-efficacy, perceived ease of use, trust, privacy concerns, and usage intention. Data were analyzed using a multivariate ANOVA with Bonferroni-adjusted post hoc tests and multiple linear regression. RESULTS: Peer-oriented and family-oriented messages produced higher usage intention than expert-oriented messages, and peer-oriented messages also increased descriptive norms, injunctive norms, self-efficacy, and trust. AI-powered chatbots were associated with higher usage intention (P=.02) and greater trust (P=.008) than rule-based chatbots. In regression analyses, the model explained 50.8% of the variance in usage intention. Usage intention was positively associated with descriptive norms (&#x3b2;=0.087; P=.003), injunctive norms (&#x3b2;=0.078; P=.009), perceived susceptibility (&#x3b2;=0.051; P=.03), perceived benefits (&#x3b2;=0.253; P<.001), and trust (&#x3b2;=0.33; P<.001), and negatively associated with perceived severity (&#x3b2;=-0.047; P=.049) and privacy concerns (&#x3b2;=-0.11; P<.001). Perceived ease of use and self-efficacy were not significant predictors. CONCLUSIONS: The health technology acceptance model was a useful framework for explaining the intention to use a health chatbot by combining technology acceptance and health motivation constructs. Both social design features and chatbot design features shaped adoption-related beliefs, with peer-oriented and family-oriented framing and AI-powered chatbots showing particular promise. Trust and privacy concerns remained central determinants of intended use.

Humans

Liver Cancer Risk and Incidence Attributable to Human Immunodeficiency Virus: A Meta-Analysis and Population-Attributable Modeling Study of Over 1.2 Million Individuals.

HIV-induced immune suppression and chronic inflammation elevate the risk of cancer progression. We conducted a systematic review and meta-analysis of studies published between January 1, 1984 and October 13, 2023 to assess the association between HIV infection and liver cancer. People living with HIV (PLHIV) had a higher risk (pooled relative risk&#x2009;=&#x2009;3.36, 95% CI: 2.72-4.15). The global PAF for HIV-attributed liver cancer was 1.43% in 2019, with a three-fold increase over the past 30&#x2009;years. The Asia-Pacific region recorded the second highest new cases of HIV-attributed liver cancer in 2019, and the highest age-standardized incidence rate (ASIR) in Eastern and Southern Africa. Particularly, the ASIR of HIV-attributed liver cancer increased rapidly in Eastern Europe and Central Asia, with the highest estimated annual percentage change reaching 22.98%. PLHIV have an increased risk and incidence of liver cancer. In regions with high burden of HIV-attributed liver cancer, it is essential to integrate prevention and effective treatment for HIV, viral hepatitis, alcoholic liver disease, nonalcoholic steatohepatitis, and liver cancer.

Humans

Spinal meningiomas: histopathological grading using a benchmark radiomics model with notes on disease control.

OBJECTIVE: Spinal meningiomas (SMs) are common primary spinal tumors for which surgery is considered the first-line treatment when safe and feasible. The ability to extrapolate the tumor grade from preoperative imaging may significantly inform early patient expectation-setting regarding recurrence. Building on radiomics studies in cranial meningiomas, the authors aimed to construct a benchmark radiomics model to preoperatively identify the histological grade of SMs. METHODS: Institutional surgical records from May 2012 to November 2025 were queried for pathology-confirmed meningiomas below the foramen magnum, with preoperative contrast-enhanced imaging available for segmentation. SMs were classified as low-grade (WHO grade 1) and high-grade (WHO grade 2 tumors and grade 1 tumors with atypia). Tumors were manually segmented, and features were extracted using the PyRadiomics software package. An ensemble model of k-nearest neighbors, random forest, and support vector machine classifiers was trained using nested cross-validation on a subset of 10 features to differentiate tumor grades. Clinical data for the cohort were also extracted, and disease control in an adjunctive clinical series was assessed. RESULTS: Seventy-four patients were included in radiomics analysis, with an area under the receiver operating characteristic curve of 0.879 and a mean F1 score of 0.748. The model's top 5 features were all texture features that differed significantly (p < 0.05) across low- and high-grade SMs. These included measures of tumor textural and contrast-enhancement heterogeneity, with overlap with features reported in radiomics models for histological grading of intracranial meningiomas. Fifty-five patients with a median radiographic follow-up of 22.2 (range 1.9-86.4) months remained for clinical analysis after exclusion of patients with less than 1 month of follow-up and syndromic meningiomas. Four recurrences occurred at a median of 20.8 (range 1.8-41.8) months. High-grade tumor pathology did not significantly impact progression-free survival (p = 0.682, log-rank test; Cox regression high vs low grade hazard ratio [HR] 0.62, 95% CI 0.06-6.11, p = 0.685). Subtotal resection was associated with poorer progression-free survival than gross-total resection (p = 0.004, log-rank test; Cox regression subtotal vs gross-total resection HR 10.62, 95% CI 1.46-77.05, p = 0.019). These findings remain contextualized within a relatively limited follow-up window and small recurrence event count, suggesting a need to characterize the interplay between tumor grade and extent of resection as drivers of local disease control in SMs. CONCLUSIONS: A preoperative radiomics model can stratify high-grade SMs using open-source tools applied to single-institution data.

Humans

Systematic evaluation of one-dimensional-to-two-dimensional near-infrared spectroscopy transformations with deep learning for quantifying coconut sap adulteration.

Near-infrared (NIR) spectroscopy have limitations when combined with deep learning (DL) algorithms because they rely on low-dimensional datasets. Therefore, we investigated the potential of transforming one-dimensional (1D) NIR spectra into two-dimensional (2D) spectrograms using synchronous and asynchronous techniques and the continuous wavelet transform (CWT) and their effectiveness by integrating with DL for detecting adulteration in coconut sap. NIR spectra (12,500-4000&#xa0;cm-1) were collected from binary mixtures (0%-100%;w/w). The performance of all DL (convolutional neural networks-CNN, AlexNet and ResNet) models was compared with that of partial least squares (PLS). The models were ranked in the mentioned order based on their performances: 2D-CWT&#xa0;>&#xa0;2D-asynchronous > 2D-synchronous > 1D/2D-PLS. The important features of the best model can be explained and visualized using gradient-weighted-class-activation-mapping. The findings highlight that the 1D-to-2D NIR data transformation combined with DL is a highly robust approach because it addresses the feature representation gap in NIR data and effectively captures the spatial-spectral correlations.

Spectroscopy, Near-Infrared

Differential contributions of mt-Tr and Cs variants to developmental cochlear defects and mitochondrial dysfunction in A/J mice.

A/J mice exhibit early-onset hearing loss linked to Cdh23, mitochondrial tRNA-Arg (mt-Tr), and citrate synthase (Cs) variants. Although developmental cochlear defects have been identified in juvenile A/J mice, the hierarchical contributions of mt-Tr versus Cs remain unclear. Using reciprocal intercross-derived strains to decouple mitochondrial haplotypes from nuclear factors, we demonstrate that the mitochondrial background is the primary determinant of auditory dysfunction. Mice with A/J mtDNA (AXB strains) displayed significantly higher ABR thresholds, accelerated hair cell attrition, and severe stereocilia dysmorphology compared to those with B6 mtDNA (BXA strains), occurring largely independently of the Cs genotype. While the Cs mutation exacerbated hearing loss, its impact was secondary to that of the dominant mitochondrial background. Systemic behavioral assessments and mitochondrial assays confirmed that A/J mitochondria exert a more profound metabolic impact than the Cs mutation. Our findings establish that the mitochondrial genomic background, with the mt-Tr locus as a prominent candidate variant, serves as the principal driver of developmental cochlear defects and early-onset hearing loss in A/J mice, while the nuclear Cs mutation acts as a synergistic modifier. This study underscores the critical role of mitonuclear crosstalk in inner ear maturation and provides new insights into the etiology of hereditary hearing loss.

Animals

Molecular mechanisms of neuroendocrine regulation of molting in the Chinese mitten crab (Eriocheir sinensis): A transcriptomic analysis based on eyestalk ablation model.

Molting disability severely restricts the sustainable aquaculture of the Chinese mitten crab, yet the neuroendocrine mechanisms coordinating physiological responses remain poorly understood. Using unilateral eyestalk ablation to remove the primary source of molt-inhibiting hormone (MIH), we performed time-resolved transcriptomic profiling of the thoracic ganglion at 24&#xa0;h (early premolt) and 48&#xa0;h (ecdysis) post-ablation. We identified 2825 differentially expressed genes and uncovered a biphasic molecular response. At 24&#xa0;h, the thoracic ganglion activates pathways associated with neuromuscular adaptation, oxidative stress, and cardiac muscle contraction. Notably, the arachidonic acid metabolism pathway is selectively rewired: cytochrome P450 &#x3c9;-hydroxylases (CYP2J2, CYP4V2) are upregulated, while competing branches (epoxide hydrolase, cyclooxygenase) are suppressed, promoting local synthesis of the potent vasoconstrictor 20-HETE within the thoracic ganglion. This enzymatic switch provides a mechanistic link between MIH withdrawal and the local generation of elevated hemolymph pressure required for molting. By 48&#xa0;h, the transcriptional program shifts toward chitin-based extracellular matrix remodeling, glycosphingolipid biosynthesis, and synaptic reorganization. Collectively, our findings redefine the thoracic ganglion as an active neuroendocrine integrator that translates reduced MIH signaling into phased physiological outputs, revealing a "neuro-endocrine-hemolymph pressure" regulatory axis. This study provides novel molecular targets (e.g., CYP2J2, CHS1, UGCG) for mitigating molting disability in E. sinensis aquaculture.

Animals

Genome-wide insights into the evolutionary and demographic history of the red alga Mazzaella laminarioides: Evidence for speciation with ancient migration along the southeast Pacific coast.

The mechanisms driving lineage divergence in red algae remain unexplored, despite the group's remarkable diversity and ancient evolutionary history. The red alga Mazzaella laminarioides, a Chilean intertidal species complex composed of three parapatric cryptic lineages (North, Center, South), offers a valuable system to evaluate these processes, as its life history combines severe dispersal limitation with a haploid-diploid cycle that may influence the emergence of reproductive barriers. We reconstructed its evolutionary history using whole-genome sequencing and nuclear genome assembly of representative individuals from each lineage. Phylogenomic analyses based on 1,507 single-copy orthologs recovered three deeply divergent lineages with limited nuclear discordance consistent with incomplete lineage sorting. For both splits, demographic modelling was most consistent with an Ancient Migration scenario, although support over strict isolation was moderate, suggesting that divergence may have begun with low asymmetric ancestral gene flow followed by subsequent loss of connectivity, demographic bottlenecks, and later population expansion. Coding sequence analyses revealed lineage-specific dN/dS heterogeneity; only one South-lineage locus passed FDR correction (metaxin-1, mitochondrial protein import), with two further South-lineage candidates in chlorophyll and heme biosynthesis falling below the FDR threshold. Together, these signals suggest that divergent selective pressures on energy acquisition may have contributed to divergence at the southern end of the distribution. These results add to the small but growing body of whole-genome data for red algae and, alongside recent macroalgal studies, suggest that ancestral connectivity could be a recurrent feature of lineage divergence even in marine organisms with extremely restricted dispersal.

Rhodophyta