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Effect of cognitive enhancement therapy for early course schizophrenia on gray matter volume: A confirmatory multisite randomized clinical trial.

BACKGROUND: Cognitive Enhancement Therapy (CET) is an evidence-based cognitive remediation intervention for early course schizophrenia with established benefits for cognition. CET may protect against broad temporolimbic gray matter volume loss associated with cognitive improvement, but this finding has yet to be replicated. This research reexamined if CET protects against temporolimbic gray matter volume loss in an independent and larger multisite early course sample, and if this neuroprotective effect predicts cognitive and social adjustment improvement. METHODS: Ninety-nine participants with early course schizophrenia completed MRI, cognitive, and social adjustment assessments at baseline, 9 (mid-treatment), and 18 (end of treatment) months. Linear mixed-effects models examined the differential impact of CET (n = 56) compared to Enriched Supportive Therapy (n = 43) on temporolimbic gray matter volume in regions-of-interest (ROIs) that previously demonstrated CET-related neuroprotection (primary ROIs), as well as frontotemporal ROIs outlined in the first trial (secondary ROIs). RESULTS: The right rostral anterior cingulate was the only primary ROI to demonstrate a significant group × time interaction, but was unrelated to cognitive and social adjustment change. No secondary ROIs exhibited a differential treatment effect. CONCLUSION: This confirmatory trial did not recapitulate the observed broad pattern of CET-related temporolimbic gray matter volume neuroprotection. Consistent with the larger literature demonstrating limited evidence of cognitive remediation effects on the brain in schizophrenia, these findings underscore the need for continued investigation of CET-related changes with other neuroimaging modalities, especially given its established cognitive benefits. Such information is critical for cognitive remediation optimization based on validated therapeutic mechanisms.

Humans

Changes in hippocampal functional connectivity and volume associated with cognitive improvement and decline in amnestic mild cognitive impairment following computerized cognitive training.

BACKGROUND: The hippocampus influences the outcomes of amnestic mild cognitive impairment (aMCI) and undergoes different changes during the cognitive decline or recovery of aMCI compared to elderly individuals with normal cognition, which may reveal disease-dependent neurodegeneration or plasticity. We first aimed to investigate the hippocampal changes associated with cognitive changes in aMCI using a combined case-control study design. METHODS: In total, 50&#x202f;aMCI individuals and 50 healthy controls (HCs) were recruited in Shenyang, China, and separately randomized into training and control groups: aMCI training group, aMCI no training group, HC training group, and HC no training group. The aMCI and HC training groups received computerized cognitive training (CCT) thrice weekly for 12 weeks. Cognitive assessments and MRI data were collected at baseline and follow-up. RESULTS: The primary outcome was significant CCT&#xd7;diagnosis interaction effect on the change in cognitive performance as measured by clock drawing test (CDT) scores (F&#x202f;=&#x202f;4.322, P&#x202f;=&#x202f;0.041); this interaction was driven by CCT specifically in aMCI (F&#x202f;=&#x202f;4.465, P&#x202f;=&#x202f;0.038). Significant CCT&#xd7;diagnosis interaction effects of right-hippocampal FC changes were observed in the bilateral precuneus/cuneus (Pvoxel<0.05) driven by CCT in aMCI (F&#x202f;=&#x202f;5.429, P&#x202f;=&#x202f;0.023), and in the left superior temporal gyrus/middle temporal gyrus (STG/MTG, Pvoxel<0.05), driven by CCT of only in HCs (F&#x202f;=&#x202f;6.587, P&#x202f;=&#x202f;0.013). A significant interaction effect of left-hippocampal FC changes were observed in the right triangular part of the inferior frontal gyrus (IFGtriang, Pvoxel<0.05), driven by CCT in aMCI and HCs (F&#x202f;=&#x202f;6.550, P&#x202f;=&#x202f;0.013; F&#x202f;=&#x202f;7.097, P&#x202f;=&#x202f;0.010). No significant interaction effect on the change in hippocampal GMV was noted (P&#x202f;>&#x202f;0.05). CONCLUSION: CCT can improve the visuospatial ability of aMCI, which is reflected by the CDT scores. CCT can alter hippocampal FC in the bilateral precuneus/cuneus, the right IFGtriang, and the left STG/MTG. The hippocampal GMV is difficult to change in both HCs and aMCI during the cognitive decline. REGISTRATION NUMBER: ChiCTR1900026849. DATE OF REGISTRATION: 24 October 2019 NAME OF TRIAL REGISTRY: Chinese Clinical Trial Registry (ChiCTR).

Humans

Effects of strength and balance training on the structure of the aging brain.

BACKGROUND: While it is established that motor training induces structural changes in the brains of young adults, structural adaptations in aging brains are less studied. METHODS: This randomized controlled study investigated the impact of long-term strength and balance training on the structural plasticity in 60 elderly adults (64 - 82 years old, 70.6 &#xb1; 4.7) using multi-modal neuroimaging. We compared the effects of three months of strength training to balance training of the same duration and to a passive control group. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to assess grey matter (GM) and white matter (WM) plasticity. White matter tract integrity (WMTI) modelling was employed to explore the microstructural underpinnings of white matter alterations. RESULTS: We found that strength training was associated with changes in diffusion metrics consistent with white matter microstructural remodeling, specifically increased extra-axonal axial diffusivity in the bilateral inferior fronto-occipital and longitudinal fasciculi. Additionally, both balance and strength training mitigated reductions in axonal water fraction in the splenium of the corpus callosum and the right posterior corona radiata observed in the control group. CONCLUSION: These results underscore the potential relevance of strength and balance training to induce beneficial neural plasticity by counteracting aging-related demyelination in the corpus callosum and highlight the specific role of strength training in facilitating white matter reorganization in key transmission fiber pathways.

Humans

Ultra-high-field 7T MRI reveals neural abnormalities of attention networks in relation to cognitive impairment in hypertension.

Hypertension is a significant risk factor for cognitive impairment (CI), yet the corresponding neural network abnormalities remain underexplored. In this study, we examined the associations among global and domain-specific cognitive dysfunction, neuroimaging measures, and blood pressure in a subgroup of hypertensive patients with CI (N&#xa0;=&#xa0;41) from a randomized controlled trial who underwent ultra-high-field 7&#xa0;T MRI. Structural atrophy related to CI was localized to regions overlapping the attention networks. Both whole-brain and within-network dysfunction of the attention networks were associated with worse global cognitive performance. Notably, hyperconnectivity within key attention network hubs, including the right anterior insula and posterior intraparietal sulcus, was associated with declined processing speed in hypertensive patients, mediating the association between pulse pressure and processing speed. These findings provide new insights into the neural pathophysiology of hypertension-related CI and suggest potential network-based targets for intervention.

Magnetic Resonance Imaging

Timing and Dose Matter: Late High-Speed Exposure and Higher High-Intensity Acceleration Volumes Reduce Hamstring Reinjury Risk in Elite Male Football (Soccer).

OBJECTIVES: The aims of this study were to (a) investigate whether the timing and magnitude of exposure to high-speed running (HSR), sprinting, and high-intensity accelerations during on-field rehabilitation after hamstring strain injury were associated with reinjury risk and (b) examine changes in match running performance upon return to play (RTP). DESIGN: Retrospective cohort study. METHODS: Data from 95 elite male football (soccer) players from five professional clubs competing in major European and Middle Eastern leagues were analyzed. Players with complete rehabilitation load profiles were included in the 2-month and 6-month reinjury analysis. Modified Poisson regression assessed associations between rehabilitation load characteristics and reinjury risk. Match running performance (HSR distance, sprint distance, and high-intensity accelerations per minute) during the five matches before injury and the first five matches after RTP was compared using paired t-tests for the entire cohort. RESULTS: Late introduction of HSR, sprinting, and high-intensity accelerations during rehabilitation (ie, &#x2265; 60% of rehabilitation progression) was associated with a significantly lower reinjury risk at 2 months (relative risk [RR] range = 0.948-0.969; P < .01) and 6 months (RR range = 0.964-0.979; P < .05). Higher daily exposure to high-intensity accelerations once introduced was protective (RR = 0.861 (0.778-0.951)). There were no meaningful associations between total volume of HSR or sprinting and reinjury. Match running performance metrics did not differ between pre-injury and post-RTP matches (all P > .05). Changes in performance were not correlated with rehabilitation load characteristics. CONCLUSION: The timing of high-intensity running exposure during on-field rehabilitation appeared associated with a lower hamstring reinjury risk. Delaying the introduction of HSR, sprinting, and accelerations, followed by a structured and progressive build-up, was associated with lower risk of reinjury without compromising the subsequent match performance of elite male football players. J Orthop Sports Phys Ther 2026;56(9):611-621. Epub 7 Jul 2026. doi:10.2519/jospt.2026.14077.

Humans

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n&#xa0;=&#xa0;15,765) consisted of UK Biobank participants (MDD only n&#xa0;=&#xa0;1230; T2DM only n&#xa0;=&#xa0;3644; comorbid T2DM&#xa0;+&#xa0;MDD n&#xa0;=&#xa0;721). Individuals with T2DM&#xa0;+&#xa0;MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR&#xa0;=&#xa0;4.44, 95% CI&#xa0;=&#xa0;[3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM&#xa0;+&#xa0;MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM&#xa0;+&#xa0;MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM&#xa0;+&#xa0;MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

Humans

Neurocorrelates of nocturnal enuresis in pre-adolescent children.

INTRODUCTION: Nocturnal enuresis (NE) is a common neurodevelopmental condition, yet its underlying neural mechanisms remain unclear. This study leverages the large-scale Adolescent Brain Cognitive Development (ABCD) dataset to identify structural and functional brain correlates associated with active symptoms and the resolution of bedwetting. METHODS: Using cross-sectional data from 3472 participants aged 9-10 years, children were categorized into three groups: active nocturnal enuresis (ANE, n = 225), history of nocturnal enuresis (HNE, n = 1171), and healthy control groups (CG, n = 2076). Multimodal neuroimaging protocol evaluated macrostructural properties via structural MRI (sMRI), microstructural white matter integrity via diffusion MRI (dMRI), and functional connectivity via resting-state fMRI (fMRI). Group differences were evaluated using linear models within an ANCOVA framework, adjusting for intracranial volume and handedness with False Discovery Rate (FDR) correction. RESULTS: Compared to controls, the ANE group exhibited a significant volume deficit in the right caudate, decreased sulcal depth in the left insula, and lower internal correlation within the Cingulo-Opercular Network (CON). Conversely, the dry HNE group demonstrated significant structural adaptations, including bilaterally larger putamen volumes and increased right caudate volume compared to the ANE group. The HNE group also showed increased microstructural density (decreased mean diffusivity) in the bilateral hippocampus and an increased cortical surface area in the left insula. Both NE groups demonstrated persistently reduced functional coupling within the CON. CONCLUSIONS: Nocturnal enuresis appears to be associated with a potential complex central signaling deficits. Reduced internal correlation within the CON across both active and former bedwetters indicates a potential for impairment in processing internal homeostatic bladder signals during sleep.

Humans

Quantitative susceptibility mapping in neurodegenerative diseases: An umbrella review of iron-related biomarkers and mechanisms.

Pathological iron accumulation is a common pathophysiological hallmark across multiple neurodegenerative diseases (NDDs), motivating the need for accurate, non-invasive quantification methods. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique that enables in vivo measurement of tissue magnetic susceptibility (&#x3c7;), providing a sensitive proxy for iron content. This umbrella review systematically evaluates the diagnostic accuracy, clinical correlations, and distinct iron distribution patterns of QSM in major NDDs, such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and atypical Parkinsonism. We included 15 (13/15 were rated Low or Critically Low on AMSTAR 2) systematic reviews and meta-analyses (through July 15, 2026); however, the findings should be interpreted cautiously because of heterogeneity and the low methodological quality. A Corrected Covered Area (CCA) analysis demonstrated only slight overlap of primary studies across the included reviews (CCA&#xa0;=&#xa0;5.42%). Collectively, the evidence indicates that QSM provides comparable or higher diagnostic sensitivity and reliability than conventional R2* and SWI techniques, particularly for deep gray matter structures. The findings support significant iron overload in the substantia nigra, particularly in the pars compacta, as a robust biomarker for PD that correlates with motor severity and disease duration. Furthermore, regional iron profiling in the basal ganglia is critical for differential diagnosis; specifically, elevated &#x3c7; in the putamen and globus pallidus effectively distinguishes multiple system atrophy and progressive supranuclear palsy from idiopathic PD. Distinctively, AD and ALS exhibit specific &#x3c7; alterations in the thalamus, motor cortex, and hippocampus, reflecting divergent iron-related pathophysiological mechanisms, which correlate with cognitive impairment and upper motor neuron signs. Overall, QSM shows diagnostic promise and offers mechanistic insights into iron-related neurodegenerative processes.

Humans

Exposure to size-specific particulate matter accelerates DNA methylation aging in people with HIV.

BACKGROUND: People with HIV (PWH) face accelerated aging and increased health risks, with DNA methylation age (DNAmAge) as a critical senescence biomarker. Particulate matter is linked to DNAmAge acceleration (DNAmAA) in general population, but its impact in PWH remains unstudied. METHODS: Thirty-two PWH from Wuhan, China, were enrolled in a prospective panel study with follow-up, and each participant underwent at least two repeated measurements during the study period. Portable air quality monitor measured PM 1 , PM 2.5 , and PM 10 exposures 72&#x200a;h preblood sampling. We analyzed genome-wide DNA methylation in peripheral blood and calculated six AA metrics. Linear mixed-effects and weighted quantile sum regression models evaluated associations between particulate matter exposure and DNAmAA. RESULTS: Significant associations between particulate matter exposure and DNAmAA were observed at various lag windows. For every 10&#x200a;&#x3bc;g/m 3 increase in 24-h average PM 2.5 , Hannum DNAmAA, Pheno DNAmAA, Grim DNAmAA, SkinBlood DNAmAA, and Elastic DNAmAA increased by 0.266&#x200a;years [95% confidence interval (CI): 0.035-0.480], 0.421&#x200a;years (95% CI: 0.032-0.701), 0.336&#x200a;years (95% CI: 0.073-0.546), 0.295&#x200a;years (95% CI: 0.021-0.495), and 0.254&#x200a;years (95% CI: 0.034-0.445), respectively. PM 10 contributed most substantially to the cumulative PM effect on epigenetic AA in the lag0-24&#x200a;h window. CONCLUSION: Short-term particulate matter exposure, particularly PM 10 , significantly accelerates epigenetic aging in PWH, highlighting the need to integrate air quality management into healthy aging strategies for this vulnerable population.

China

Coupling of spectroscopy and nitrogen-oxygen isotopes unveils the mechanisms of dissolved organic matter and nitrate pollution in lakes within the agro-pastoral transition zone.

Lakes in arid and semi-arid regions are subjected to severe ecological stress, such as organic pollution, eutrophication, and salinization, due to climate change and human activities. This study investigates Chagannur Lake, a typical arid-region lake that is representative and ecologically sensitive in Northern China's agro-pastoral ecotone, to uncover its pollution characteristics and mechanisms. We employed fluorescence spectroscopy and stable isotope analysis to trace dissolved organic matter (DOM) and nitrate sources. The DOM composition was dominated by microbial metabolic byproducts and protein-like substances, suggesting that microbial processes are key to organic matter transformation. Source apportionment revealed that pollutants primarily originated from livestock and poultry manure (37.6 %), agricultural fertilizers (35.6 %), and soil erosion (24.7 %), with agricultural fertilizers contributing most significantly in the Gogstai River (63.3 %). A structural equation model (SEM) coupling spectral and mass spectrometric data revealed that microbial transformation significantly impairs the lake's self-purification capacity, thereby promoting pollutant accumulation (path coefficient = 0.91,*p < 0.05). Moreover, microbial processes link endogenous and exogenous pollution, a mechanism effectively traced by isotopic and fluorescence indices (path coefficient = 0.55, &#x204e;&#x204e;p < 0.01). These findings enhance the understanding of pollution sources and transformation mechanisms in arid-region lakes and offer foundational theoretical support for policymakers engaged in pollution control strategies.

Lakes

Prenatal exposure to particulate matter (PM) and autism spectrum disorder (ASD) among children: a systematic review and meta-analysis.

The global surge in Autism Spectrum Disorder (ASD) cases, coupled with evidence linking prenatal Particulate Matter (PM) exposure to developmental disruption, demands a comprehensive review to design targeted health interventions. This systematic review and meta-analysis aim to evaluate the strength and consistency of evidence linking prenatal PM exposure to ASD across studies, quantifying this relation to identify actionable environmental risk thresholds. This study employed PRISMA protocols to systematically extract and evaluate evidence from PubMed, Web of Science, Scopus, and ScienceDirect (2010-2024), and screened 4,013 articles to identify qualified case-control and cohort studies (n=29). Data synthesis employed random-effects modeling, accompanied by comprehensive assessment through I2 statistics, Q-tests, funnel plots, Duval and Tweedie's trim-and-fill analysis, and Egger's regression, to ensure validity. A meta-analysis of 16&#xa0;case-control studies revealed a 34&#x202f;% increased risk of ASD associated with prenatal PM exposure (pooled OR=1.34; 95&#x202f;% CI: 1.13-1.54), despite substantial between-study heterogeneity (I2=94.02&#x202f;%, p<0.001). Publication bias was not significant (Egger's test p value=0.114). Critical trimester-specific analysis uncovered that third-trimester exposure significantly increased ASD risk (OR=1.17; 95&#x202f;% CI: 1.01-1.34), while first-trimester (OR=1.02; 95&#x202f;% CI: 0.92-1.11; I2=49.18&#x202f;%, p<0.10) and second-trimester exposures (OR=1.13; 95&#x202f;% CI: 0.88-1.38; I2=92.59&#x202f;%, p<0.001) showed non-significant associations. This review identified prenatal and early life exposure to PM as a risk factor for ASD, indicating a trimester-specific vulnerability. It highlighted the necessity of focused air quality interventions and targeted guidance to reduce prenatal PM exposure to alleviate ASD risk during the critical-window.

Child

A Letter Matters: ADRB2 rs1042713 c.46A Modulates Anti-osteogenic Effect of Epinephrine in Human Mesenchymal Stem Cells.

Osteoporosis (OP) is a systemic bone disease affecting millions worldwide, characterized by long-term asymptomatic development that manifests in low-energy fractures. Due to their high stability, genetic markers represent a promising strategy for early diagnostics. The ADRB2 rs1042713 polymorphism is one such marker, considered as a potential predictor for OP. Although the anti-osteogenic role of the &#x3b2;2-adrenergic receptor is well-established, debate continues on which allele (G or A) of this polymorphism drives bone deterioration. In this study, we examined the influence of the ADRB2 rs1042713 G/G and A/A variants on osteogenic differentiation in patient-derived mesenchymal stem cells (MSCs) under treatment with the endogenous agonist epinephrine. We show that epinephrine (whose levels are often elevated in comorbid conditions) drastically impairs osteogenic differentiation, specifically at the matrix mineralization stage in MSCs A/A. Epinephrine fails to activate the canonical &#x3b2;2-adrenergic receptor pathway and promotes receptor perinuclear and nuclear localization in MSCs A/A. Crucially, metformin, a common anti-diabetic drug, rescues this anti-osteogenic effect. These results open new perspectives for early diagnostics by identifying epinephrine sensitivity as a critical factor, while also suggesting a potential therapeutic strategy to counteract epinephrine detrimental effect in individuals carrying the ADRB2 rs1042713 A-allele.

Humans

Context matters: coordinated transcriptional regulation and root plasticity under multinutrient conditions.

Plants often encounter simultaneous imbalances in multiple nutrients, but the regulatory logic coordinating their responses remains poorly understood. We aimed to uncover shared transcriptional programs and regulatory nodes underpinning multinutrient adaptation in Arabidopsis thaliana roots. We analyzed publicly available RNA-seq datasets spanning 15 nutrient and beneficial element conditions using differential expression, co-expression network (WGCNA), and gene regulatory network analysis. Selected transcription factors (TFs) were validated via root phenotyping, suberin staining, and ionomic profiling under two-nutrient stress conditions. We identified a core set of 2050 genes responsive to multiple nutrient treatments, enriched for suberin biosynthesis, and structured into modular co-expression clusters. Eight prioritized candidate TFs (ARR10, GBF3, HHO5, NAC32, NF-YA3, NF-YB2, SARD1, and WRKY33) were&#xa0;shown to modulate root system architecture under specific nutrient combinations. WRKY33 and NF-YB2, in particular, regulated nutrient-responsive suberin deposition and ionomic plasticity. These findings reveal suberin remodeling as a shared downstream process in multinutrient responses and suggest that plasticity is not a fixed trait but a modular, polygenic, and context-dependent outcome. Repurposed TFs with pleiotropic functions coordinate structural and physiological traits, providing regulatory entry points for improving nutrient resilience.

Plant Roots

A novel neoadjuvant immunotherapy confers improved overall survival in oral cancer patients with low tumor PD-L1 expression The IT-MATTERS Clinical trial - Prognostic role of tumor PD-L1 expression.

OBJECTIVE: Five-year overall survival (OS) remains&#xa0;<&#xa0;50% for patients with resectable, locally advanced (LA) primary oral squamous cell carcinoma (OSCC) and soft palate, receiving current standard of care (SOC). The aim of our study was to examine neoadjuvant Leukocyte Interleukin Injection (LI) with CIZ (intravenous low dose cyclophosphamide, indomethacin and zinc multivitamins) effect on OS, in low-risk (LR) OSCC patients. PATIENTS AND METHODS: In a randomized, controlled Phase 3 trial, treatment-na&#xef;ve locally advanced patients, with stage III/IVa OSCC and soft-palate cancer, had surgical tumor samples assessed for pre-defined thresholds of PD-L1 tumor proportion score (TPS). OS was analyzed using proportional hazard models for LI&#xa0;+&#xa0;CIZ&#xa0;+&#xa0;SOC vs SOC, in the intention-to-treat (ITT) population. RESULTS: OS was superior in low risk (LR) patients receiving LI&#xa0;+&#xa0;CIZ&#xa0;+&#xa0;SOC compared to SOC; OS advantage hazard ratio (HR) 0.64, p&#xa0;=&#xa0;0.0569 (without selecting for N0, PD-L1 TPS&#xa0;<&#xa0;10%), and the Kaplan-Meier (K-M) lifetable achieved significance (log rank p&#xa0;=&#xa0;0.0340) favoring LI&#xa0;+&#xa0;CIZ&#xa0;+&#xa0;SOC vs SOC. Applying the selection criteria (cN0 and TPS&#xa0;<&#xa0;10%) to ITT, OS reached HR 0.34p&#xa0;=&#xa0;0.0012, Kaplan-Meier log rank p&#xa0;=&#xa0;0.0015. The ITT LR cohort (cN0 and TPS&#xa0;<&#xa0;10%) achieved a HR 0.26 (p&#xa0;=&#xa0;0.0023), Kaplan-Meier log rank p&#xa0;=&#xa0;0.0013, supported by progression free survival (PFS) HR 0.43, p&#xa0;=&#xa0;0.0178, Kaplan-Meier log rank p&#xa0;=&#xa0;0.0431, with 32% absolute survival advantage over control at 60&#xa0;months. CONCLUSIONS: Significant OS prolongation was observed in ITT population for LI&#xa0;+&#xa0;CIZ&#xa0;+&#xa0;SOC vs SOC, in LR and in ITT LR cN0, PD-L1TPS&#xa0;<&#xa0;10% cohort having locally advanced squamous cell carcinoma tumors in oral cavity/soft-palate. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01265849; EudraCT (Identifier: 2010-019952-35).

Humans

Degradation of a graphene-reinforced polyamide by fungi: When culture conditions matter.

The large-scale production, marketing and disposal of polymer-based graphene products can lead to the dispersal of graphene-enriched plastic particles into terrestrial ecosystems, where they might accumulate if not degraded by organisms. The objective of this work is to test the degradability and compatibility of one polyamide-6 polymer reinforced with reduced graphene-oxide (PA6-rGO) and its base constituents (polyamide-6, PA6; reduced graphene oxide, rGO) using mono- and co-cultures of two lignin-degrading fungi (Bjerkandera adusta and Morchella esculenta) grown under different nutrient conditions. Fungal (co-)cultures were exposed to pure rGO or abraded powders of PA6 and PA6-rGO in two different liquid media, and monitored over time for biomass growth, H2O2 production, and activity of two lignolytic enzymes (i.e., Laccase, Lac, and Lignin peroxidase, LiP). The changes in polyamide structure were evaluated by proton nuclear magnetic resonance and mass spectrometry, and changes in rGO were evaluated by Raman spectroscopy. The materials had no effect on fungal growth. PA6 increased Lac secretion only in low nutrient medium, while PA6-rGO slightly suppressed LiP activity. Only M. esculenta promoted polyamides oxidation when cultured in a low nutrient medium, as evidenced by a change in mass distribution values (m/z: 400-420) and the appearance of a new resonance peak (at 5.37 ppm). Lignolytic exudates in co-cultures low in nutrients caused a greater change in rGO, as shown by the increase in the ID/IG ratio. The degradation of rGO, PA6 and PA6-rGO depended on culture conditions.

Graphite

Identification Matters: How Data Sharing Affects Pupil Honesty and Engagement in Universal School Well-Being Assessments.

PURPOSE: Universal well-being assessments in schools may support early identification of pupils needing mental health support. However, little is known about how privacy and confidentiality concerns influence pupils' acceptability of assessments and willingness to engage authentically. This study examined how hypothetical identification, where responses are linked to pupils and shared with key stakeholders, affects pupils' anticipated honesty and engagement, and whether known help-seeking barriers predict negative responses. METHODS: Cross-sectional data were collected from 12,377 primary (ages 8-10) and secondary pupils (ages 11-17) across 55 schools in England. Pupils reported whether their responses would change if identifiable and shared with school staff, parents/guardians, or external professionals. Responses indicating reduced honesty or likelihood of disengagement were coded as negative. Predictors were examined using mixed-effects logistic regression models, including demographics, school connectedness, and mental well-being. RESULTS: Identification and data sharing influenced pupils' anticipated engagement, particularly in secondary schools. Identification by school staff elicited the highest proportion of negative responses in both phases, whereas external professionals elicited the fewest. Most primary pupils reported they would respond authentically, while a larger proportion of secondary pupils indicated they would respond less honestly or disengage when responses were identifiable and shared. Across primary and secondary samples, low well-being, low school connectedness, and being female were associated with greater likelihood of negative response. DISCUSSION: Pupils' anticipated engagement with well-being assessments is shaped by who accesses their data, with marked developmental differences. Strengthening trust, privacy, and connectedness, and supporting pupils' autonomy, may improve the acceptability and response accuracy.

Humans

Getting to the Core of the Matter-Assessing the Role of Replication in Metabarcoding-Based sedaDNA.

Replication is central to most experimental and sampling designs, increasing inferential power and capturing fine-scale data heterogeneity. However, its importance remains poorly evaluated in some ecological and evolutionary settings. This is the case of metabarcoding studies using DNA recovered from sedimentary archives, in which biological signals integrate ecological information through depositional and burial processes, yet are commonly inferred from a single sediment core per site. Here, we evaluated the effect of different types of replication using sedimentary DNA metabarcoding data from two genetic markers (mitochondrial COI and nuclear 18S) using a nested sampling design. The design included three intertidal sites, three spatially separated sediment cores per site (biological replicates), two sediment horizons per core, and eight PCR (technical) replicates per sediment sample. Variance partitioning showed that site identity and sediment age group together explained >&#x2009;70% of the variation in beta diversity, indicating that among-site spatial and stratigraphic differences were the dominant drivers of community composition. PERMANOVA likewise identified non-significant effects of biological replication. Among PCR replicates from the same sediment sample, richness varied substantially, whereas Shannon diversity was more consistent. Despite this variability, differences in community composition among technical replicates remained smaller than those associated with biological replication or site identity, indicating a limited influence on broader ecological patterns. Community composition was highly similar among replicate cores within sites, consistent with stratigraphic coherence. These results indicate limited within-site heterogeneity and suggest that, under stratigraphically coherent conditions, increasing biological replication may provide little additional information, whereas enhancing technical replication and stratigraphic resolution can improve ecological inference from sedimentary DNA metabarcoding datasets.

DNA Barcoding, Taxonomic

Oxidative potential of fresh vs. O&#x2083;-aged PM2.5 across urban and rural sources in China.

Fine particulate matter (PM2.5) is a major health risk, yet its impacts are still largely assessed using mass concentration, which does not capture toxicity. Recently, oxidative potential (OP) has emerged as a more relevant metric, reflecting the ability of particles to generate reactive oxygen species. A current challenge, especially in China, is understanding how emission sources and ozone (O3) aging affect PM2.5 toxicity, given that O3 is an increasingly important pollutant there. A work by Ma and co-workers published in J. Environ. Sci. (doi.org/10.1016/j.jes.2024.04.023) addressed this by evaluating the OP of fresh and O3-aged PM2.5 from multiple sources in China using the dithiothreitol (DTT) assay. Biomass burning particles exhibited the highest OP, up to 35 times greater than suburban PM2.5, driven by water-soluble organics and transition metals. While O3 aging generally reduced OP, it also induced complex chemical transformations. These findings highlight that PM2.5 toxicity is dynamic and source-dependent, underscoring the need to move beyond mass-based air quality metrics.

Particulate Matter