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PubMed2026

Optimal dose and exercise modality to improve HbA1c in older adults with type 2 diabetes mellitus: a systematic review with pairwise, network, and dose-response meta-analyses.

We aimed to compare exercise modalities and evaluate dose-response relationships with glycemic control including continuous aerobic exercise (CAE), resistance training (RT), combined exercise (CE), mind-body exercise (MBE), and high-intensity interval training (HIIT) in older adults with type 2 diabetes mellitus (T2DM). Three databases were searched for randomized controlled trials of exercise interventions in older adults with T2DM reporting glycated hemoglobin (HbA1c). Pairwise, Bayesian network, and dose-response meta-analyses were conducted. Compared with control, HIIT demonstrated the largest estimated reduction (MD = -0.95%; 95% CrI -1.45, -0.49), followed by CE (MD = -0.59%; 95% CrI -0.93, -0.25), CAE (MD = -0.46%; 95% CrI -0.69, -0.24), MBE (MD = -0.42%; 95% CrI -0.76, -0.10), and RT (MD = -0.29%; 95% CrI -0.51, -0.08). Dose-response network meta-analyses suggested a non-linear association between overall exercise dose and HbA1c reduction, with maximal estimated benefits at approximately 704 METs-min/week with the 95% CrI excluding zero between 241 and 920 METs-min/week. HIIT demonstrated the steepest estimated dose-response relationship, but with wider credible intervals. Other exercise modalities showed more gradual dose-response patterns across their estimated effective ranges. Our findings suggest that exercise prescription for older adults with T2DM should be individualized according to exercise modality, dose, and health status.

Humans↗

PubMed2026

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 > 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↗

PubMed2026

Littoral and wetland vegetation decrease carbon emissions from dry inland waters.

Lakes are recognized as active components of the inland water carbon (C) cycle, as organic matter is processed by microbial respiration, inducing large carbon dioxide (CO2) and methane (CH4) emissions. In the context of long-lasting drought periods, large uncertainties remain about: (1) the influence of wet-dry cycle on CO2 and CH4 fluxes in littoral zones and lacustrine wetlands; and (2) the contribution of emergent vegetation to C fluxes in dry inland waters. At the water-land interface of two shallow lakes, this study focuses on CO2 and CH4 fluxes from vegetated and bare dry inland waters in relation to hydrological fluctuations. Three seasonal campaigns were conducted to measure daytime CO2 and CH4 fluxes in pelagic, littoral and wetland surface waters, as well as in temporarily air-exposed sediments, using floating and static chambers, respectively. Our results reveal that wet-dry cycle in the littoral zone and wetlands strongly influence gaseous C fluxes through contrasting patterns, especially in late summer, when the biological processes are most active (primary production and respiration). In air-exposed littoral zones, organic-poor sandy sediments presented the lowest CO2 and CH4 emissions, whereas in air-exposed lacustrine wetlands, water-saturated sediments accumulated high amounts of plant-derived organic matter, promoting intense microbial activity and the highest C emissions. However, amphiphytes and helophytes vegetation in exposed littoral zones and wetlands reversed the direction of C fluxes, inducing the highest CO2 uptake due to high photosynthesis rates. This study underlines the relevance of considering vegetation in dry inland waters, particularly in lacustrine littoral zones and wetlands, to obtain comprehensive lake C budgets, especially under climate change scenarios.

Wetlands↗

PubMed2026

Diversity and population connectivity of members of the family Eunicidae inhabiting deep-water corals in the North Atlantic.

Eunicid polychaetes are often found in association with Cold Water Corals (CWCs), even establishing symbiotic relationships, such as those described between Desmophyllum pertusum and Eunice norvegica. While genetic connectivity of CWCs across the North Atlantic has been widely studied, little is known about their associated fauna in this regard. Here, we present a study combining a focused analysis of the genetic and genomic connectivity of E. norvegica with a regional assessment of the distribution and evolutionary relationships of three CWC-associated eunicid species from the Cantabrian Sea and the North of the United Kingdom (190-1,230 m depth). An integrative approach using genetic (16S, COI and 18S), morphological and ecological data allowed the identification of the eunicids studied, with new records of Eunice cf. nicidioformis and Leodice cf. antarctica in the Cantabrian Sea, as well as previously undocumented associations with CWC species. In addition, RADseq data contributed to the delimitation of the closely related species E. norvegica and Eunice philocorallia. Moreover, the genetic connectivity of E. norvegica was studied trough a RADseq (1,067 neutral SNPs) approach. Our results indicate a single panmictic population across approximately 2,000 km, suggesting that oceanographic currents facilitate passive dispersal of E. norvegica lecithotrophic larvae, aided by coral host stepping-stones. The connectivity patterns observed for E. norvegica mirror those of D. pertusum, on which the worm is ecologically dependent. Our study highlights the importance of using integrated genetic, morphological and ecological data to characterise and delineate understudied CWC-associated species and improve our understanding of their dispersal capabilities and genetic connectivity to inform future conservation recommendations.

Animals↗

PubMed2026

Dual-tasking reveals severity-dependent reorganization of cortical beta energy landscapes in Parkinson's disease.

Dual-task impairment is a hallmark of Parkinson's disease (PD), yet the large-scale neural mechanisms underlying postural-motor interference remain poorly understood. In particular, it is unclear how cortical network dynamics reorganize across disease severity when postural control competes with concurrent task demands. This study investigated EEG-derived beta-band cortical energy landscapes in healthy older adults, early-stage PD, and mid-stage PD during single- and dual-task conditions. Dual-task behavioral cost increased with disease severity for concurrent manual performance (p < 0.001), whereas a quadratic pattern was observed for postural performance. Energy landscape analysis revealed severity-dependent reconfiguration of cortical beta dynamics. Dual-task-related landscape changes in effective network flexibility (ΔNeff), landscape geometry (ΔEvar and ΔGmag), and dominant low-energy attractor organization (ΔLow mass and ΔLow area) showed significant monotonic trends (p < 0.05), reflecting progressive constrained cortical network dynamics with advancing PD severity. In addition, dual-task-related landscape alterations were associated with clinical severity, as indexed by Hoehn and Yahr stage (|r| = 0.353-0.423, p = 0.016-0.048), and showed associations with motor impairment, as measured by MDS-UPDRS part III scores (|r| = 0.333-0.455, p = 0.009-0.063). These findings demonstrate that dual-task demands induce severity-dependent reconfiguration of cortical beta energy landscapes in PD. Energy landscape geometry may capture systems-level neural constraints associated with dual-task susceptibility in PD, providing a physiologically grounded framework to characterize disease-related functional vulnerability.

Humans↗

PubMed2026

Antagonistic regulation by mango MiSPL9a and MiSPL9b regulates flowering time, drought and salt stress in Arabidopsis.

SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors, which are unique to plants, contain a highly conserved SBP domain that regulates gene expression by binding to downstream targets. They play critical roles in various biological processes, especially in the regulation of flowering in plants. In this study, two SPL-like genes (MiSPL9a and MiSPL9b) were identified from mango genomic and transcriptomic data, and their sequence, expression and function were further analyzed. Sequence analysis revealed that MiSPL9a and MiSPL9b have open reading frames of 1173 bp and 1158 bp, respectively, with slight differences in the number of cis-regulatory elements within their promoter regions. Expression analysis under stress conditions revealed distinct patterns: MiSPL9a expression significantly differed under drought stress but did not significantly differ under salt stress, whereas MiSPL9b expression responded significantly to salt stress but changed minimally under drought stress. Phenotypic analysis of the transgenic Arabidopsis lines revealed that MiSPL9a overexpression delayed flowering, whereas MiSPL9b overexpression promoted early flowering. Under stress conditions, compared with wild-type plants, MiSPL9a-overexpressing plants presented increased drought tolerance but did not significantly differ. In contrast, MiSPL9b-overexpressing plants were sensitive to salt stress, with no notable phenotypic differences observed under drought conditions. Physiological assays revealed that under drought stress, MiSPL9a transgenic plants presented significantly reduced levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) and increased proline (Pro) content and superoxide dismutase (SOD) activity. Under salt stress, MiSPL9b transgenic plants presented opposite trends in terms of these physiological markers. In summary, both MiSPL9a and MiSPL9b are involved in the regulation of plant flowering time and stress responses, but their functions differ.

Arabidopsis↗

PubMed2025

An integrated multiscale air quality modelling framework for industrial park pollution: Linking local emissions to regional transport.

Capturing the spatiotemporal distribution of pollutants in industrial parks remains challenging for regional air quality models because of their coarse resolution (3 km), resulting in uncertainties in local emission quantification. To address this, we developed the Integrated Multiscale Air Quality Modelling System for Industry (IAQMS-Industry), coupling the regional Nested Air Quality Prediction Modelling System (NAQPMS) with a city-scale chemical transport model. This framework integrates point-source locations and Gaussian plume dispersion to simulate particulate matter with a diameter smaller than 2.5 micrometres (PM2.5) at 100 m resolution. Applied to the Beijing Yi Zhuang and Tangshan industrial parks and evaluated against observations. The coupled model achieved a normalized mean bias (NMB) ranging from 3.1 % to 6.2 %, improving upon NAQPMS (-16.9 % to -7.7 %). Spatial analysis revealed that coarse regional grids underestimated the PM2.5 concentrations at industrial sites by smoothing gradients, whereas IAQMS-Industry successfully resolved spatial patterns. Industrial point emissions accounted for 22.9 %-26.4 % of PM2.5 in the coupled model, which was significantly greater than the regional model estimates of 1.6 %-13.7 %. These findings indicate that regional models overestimate pollutant dispersion processes in industrial parks while underestimating local industrial impacts. By explicitly resolving point-source dynamics and linking them to regional transport, IAQMS-Industry provides a robust tool for designing targeted emission controls in industrial cities and balancing local air quality improvements with minimized regional pollution outflow. This study underscores the necessity of multiscale modelling for accurate source apportionment and informed environmental governance in industrial zones.

Air Pollution↗

PubMed2026

The Effect of Breastfeeding on Cervical Dysplasias.

OBJECTIVE: This study aimed to investigate the relationship between breastfeeding and precancerous cervical lesions. MATERIALS AND METHODS: A case control study was conducted at a tertiary training and research hospital between September 1 and November 1, 2023. A total of 168 patients who attended the gynecology outpatient clinic and reported their breastfeeding experiences were included. Patients with abnormal cervical cytology formed the study group (n = 37), while patients with normal cytology formed the control group (n = 131). Breastfeeding duration and patterns were compared between groups. RESULTS: The control group had normal smear results. In the study group, 15 patients had high-grade squamous intraepithelial lesions, and 22 patients had low-grade squamous intraepithelial lesions. Human papillomavirus (HPV) was positive in 54.1% of the study group versus 9.2% of the control group. The mean breastfeeding duration was shorter in the study group (9.18 ± 3.43 months) than the control group (23.6 ± 3.35 months; p < 0.05). Most control group patients breastfed for 13-36 months (35.1%), while most study group patients breastfed for <6 months (48.6%; p < 0.05). Shorter breastfeeding (<6 months) and HPV positivity were the strongest predictors of abnormal cytology. Breastfeeding <6 months increased the risk 9.883-fold compared with >36 months, while HPV positivity increased the risk 27.612-fold. CONCLUSION: Breastfeeding and longer breastfeeding duration appear to be associated with a lower risk of cervical intraepithelial neoplasia. Given its multiple health benefits, including prevention of gynecological cancers, promoting breastfeeding through public health policies is strongly recommended. Early recognition and prevention of precancerous lesions remain essential to reducing the risk of cervical cancer.

Humans↗

PubMed2026

Is ophthalmology a pain-free career? A systematic review and meta-analysis of musculoskeletal pain among ophthalmologists.

OBJECTIVE: To estimate the pooled prevalence, anatomical distribution, and occupational impact of work-related musculoskeletal (MSK) pain among ophthalmologists, and to identify modifiable ergonomic risk factors. DESIGN: A systematic review and meta-analysis of published data. The protocol was preregistered (PROSPERO CRD42023422368) and reported in accordance with PRISMA. PARTICIPANTS: The participants were 6691 ophthalmologists from 21 studies. METHODS: Electronic databases (MEDLINE, Embase, Cochrane, and PubMed) were searched for peer-reviewed quantitative studies reporting MSK pain prevalence in ophthalmologists. Pooled estimates with 95% CI were calculated using random-effects models; heterogeneity was quantified using I². MAIN OUTCOME MEASURES: Prevalence of overall and site-specific MSK pain; effects on workload and productivity; prevalence of treatment or mitigation strategies. RESULTS: The pooled prevalence of any MSK pain was 70% (95% CI: 65%-75%; I² = 92%); neck (41%; 95% CI: 35%-47%; I² = 95%), lower back (36%; 95% CI: 32%-39%; I² = 87%), and shoulder pain (28%; 95% CI: 22%-35%; I² = 91%) were most common. Pain led to workload modification in up to 44% and contributed to reduced clinical volume, sick leave, or contemplation of early retirement. Forty-six percent (95% CI: 22%-71%) pursued no treatment; 39% (95% CI: 30%-49%) used medical therapy; and 29% (95% CI: 20%-41%) sought physiotherapy. Heterogeneity was high across studies, reflecting differing case definitions and self-reported measures. CONCLUSIONS: MSK pain affects most ophthalmologists, particularly in the cervical and lumbar regions and frequently alters practice patterns. These findings underscore the need for early ergonomic training, structured micro-breaks, and workspace redesign. Prospective intervention trials are required to establish causality and quantify benefit.

Humans↗

PubMed2026

Cerebrovascular involvement in Erdheim-Chester disease: a case report and systematic literature review.

BACKGROUND: Intracranial perivascular/vascular infiltrations and stenoses related to Erdheim-Chester disease (ECD), often associated with ischemic events, are rarely documented. This study aims to characterize intracranial perivascular/vascular infiltrations and stenoses. METHODS: We first report a new case of strokes revealing ECD with intracranial arterial involvement. We then searched all English- and French-language publications from database inception to November 2025 across 12 different search interfaces, including grey literature sources. Vascular involvement was defined by the presence of intracranial perivascular/vascular infiltrations and stenosis on imaging and/or histopathological evidence of small-vessel involvement. Cases with intracranial nodules or masses abutting vessels but without clear longitudinal perivascular infiltration were excluded. RESULTS: We present a case of recurrent strokes with intracranial vertebral and basilar artery wall stenosis, and aortitis. Initially diagnosed as giant cell arteritis, the patient was treated with corticosteroids, cyclophosphamide followed by methotrexate, but relapsed. The identification of tibial osteosclerosis led to the diagnosis of ECD, with a favorable response to anakinra. Twelve relevant articles were retrieved, in addition to our own case. Most patients exhibited focal cerebrovascular signs (11/13) and associated parenchymal involvement (11/13). Intracranial perivascular/vascular infiltrations and stenoses involved the carotid arteries (7/13), the vertebrobasilar arteries (1/13), or both territories (4/13). Aorta was involved in 8/12 cases. Among the nine patients with available follow-up data, five had poor overall or neurovascular outcomes. CONCLUSIONS: Intracranial perivascular/vascular infiltrations and stenoses, which leads to recurrent focal ischemic events, represents a likely underdiagnosed CNS pattern in ECD, referred to as "cerebrovascular ECD", which worsens overall prognosis. Vascular imaging should be included in brain MRI protocols for patients with ECD, given the overlap with parenchymal involvement.

Humans↗

PubMed2026

Polygenic risk scores in major depressive disorder: A systematic review across diagnostic, treatment, course/severity, and subtype domains.

BACKGROUND: Major depressive disorder (MDD) is heterogeneous across diagnostic, treatment-related, course/severity, and subtype domains. Polygenic risk score (PRS) studies have examined these domains, but differences in PRS sources, samples, methods, and endpoint definitions have fragmented the evidence. We synthesised findings and examined potential contributors to heterogeneity. METHODS: PubMed/MEDLINE, Embase, PsycINFO, and Web of Science were searched for studies published from January 2016 through 25 November 2025. Result records were synthesised using SWiM, and certainty was assessed with an adapted GRADE framework. RESULTS: Sixty studies contributed 493 retained records; 450 were descriptively classified as positive, null, or reverse, although records were not independent. Positive findings accounted for 44/56 diagnostic, 61/273 treatment-related, 64/100 course/severity, and 14/21 subtype records. For MDD/depression-derived PRSs and case-control MDD status, all 10 contributing studies showed higher liability in cases (exploratory exact sign test p = 0.002; FDR q = 0.004). The same PRS group showed positive findings for overall depressive symptom severity (14/18), although the study-level test was imprecise (5/5 studies; p = 0.063). Pharmacological response/remission findings for these PRSs were mostly null or directionally mixed (10 positive, 18 null, and 9 reverse). Treatment-resistant depression (TRD) findings differed by operational definition. Atypical and psychotic subtype signals arose mainly from single-study PRS and endpoint contrasts. CONCLUSIONS: PRS evidence was clearest for MDD diagnostic status and showed a tentative pattern for overall symptom burden. Treatment and subtype findings were less consistent or less replicated. Larger, ancestrally diverse studies with standardised endpoints and transparent PRS methods are needed.

Humans↗

PubMed2026

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 (χ), 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 = 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 χ in the putamen and globus pallidus effectively distinguishes multiple system atrophy and progressive supranuclear palsy from idiopathic PD. Distinctively, AD and ALS exhibit specific χ 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↗

PubMed2026

Evolutionary conservation of heat shock proteins in Blattodea and their roles in wing morphogenesis and ovarian development of Blattella germanica.

Heat shock proteins (Hsps) are essential molecular chaperones for protein homeostasis and stress responses. However, the Hsp repertoires and functions in Blattodea remain underexplored. Our genome-scale survey of nine Blattodea species revealed 37-46 conserved Hsp90, Hsp70, and DNAJ (Hsp40) genes, with DNAJ the most abundant and Hsp90 the least. Phylogenetic analysis confirmed the evolutionary conservation of three Hsp90, seven Hsp70, and 29 DNAJ subclades in Blattodea. Selection pressure analysis revealed predominant purifying selection (dN/dS ≪ 1) across lineages, strongest in DNAJ and highest in Hsp90 conservation. In Blattella germanica, expression of six representative BgHsp genes progressively increased during development, peaking in fifth-instar nymphs. Tissue expression profiling revealed that BgHspA1-2/3/4 were predominantly expressed in legs, BgDNAJB5 and BgHsp90AB1-2 were enriched in the fat body, and BgHsp90AB1 was highly expressed in the head. dsRNA injection targeting conserved Hsp gene regions achieved 61.9-94.1% knockdown of all six target genes. RNAi knockdown of six BgHsp genes disrupted wing morphogenesis, causing distinct phenotypes: wing whitening (56.7%, dsBgHspA1-4), unequal length (66.7%, dsBgHspA1-3; 76.7%, dsBgDNAJB5), and wing wrinkling (70%, dsBgHspA1-2; 63.3%, dsBgHsp90AB1; 76.7%, dsBgHsp90AB1-2). During ovarian formation, the developmental delay was most severe in the dsBgHsp90AB1 group, moderate in the dsBgHsp90AB1-2 and dsBgHspA1-2/3/4 groups, and weakest in the dsBgDNAJB5 group. Besides, knockdown significantly downregulated key developmental genes (apterous-a, nubbin, scalloped, ultrabithorax, wingless, and vitellogenin). These findings provide a reference for understanding the evolutionary patterns of Hsps in Blattodea, and offer mechanistic insights into the developmental regulation mediated by Hsps in this important public-health pest.

Animals↗

PubMed2026

Antennal transcriptome analysis of chemosensory proteins in the raspberry weevil, Aegorhinus superciliosus (Coleoptera: Curculionidae).

Aegorhinus superciliosus (Coleoptera: Curculionidae) is a polyphagous pest of economic importance in southern Chile, the chemical ecology of which remains poorly characterized. Across insect species, chemosensory proteins, including odorant receptors (ORs), gustatory receptors (GRs), ionotropic receptors (IRs), odorant-binding proteins (OBPs), chemosensory proteins (CSPs), and sensory neuron membrane proteins (SNMPs), mediate the detection of chemical cues involved in host selection, reproduction, and other ecologically relevant behaviors. In this study, the antennal transcriptome of adult A. superciliosus was sequenced and analyzed using a de novo RNA-seq approach. Three independent biological replicates per sex were used for RNA-seq, and the same number of independent biological replicates was used for RT-qPCR validation; sequencing yielded 147,409,936 high-quality reads after quality filtering. A total of 112 candidate chemosensory genes were identified, comprising 43 ORs, 34 OBPs, 10 CSPs, 18 IRs, 5 GRs, and 2 SNMPs. Phylogenetic analyses assigned these candidate proteins to established clades, providing a comparative framework for functional inference for ORs and OBPs. Sex- and tissue-biased expression analyses revealed that several ORs, including AsupOR4, AsupOR19, and AsupOBP13, exhibit antennal enrichment and sex-specific expression patterns. Notably, AsupOR19 and AsupOBP13 displayed strong female-biased expression. In addition, transcripts of selected ORs and OBPs were detected in non-antennal tissues, such as the rostrum and legs, suggesting potential functional versatility beyond canonical olfaction. Together, these findings represent the first molecular identification of the chemosensory repertoire of A. superciliosus. This study establishes a foundation for reverse chemical ecology approaches aimed at identifying behaviorally active volatile organic compounds (VOCs) toward environmentally sustainable strategies for integrated pest management.

Animals↗

PubMed2026

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↗

PubMed2026

Risk of adverse events in elotuzumab-treated patients with multiple myeloma: a systematic review and meta-analysis.

BACKGROUND: Elotuzumab, an anti-SLAMF7 monoclonal antibody for multiple myeloma (MM), lacks a comprehensive safety profile from meta-analysis. METHODS: We systematically searched PubMed, Web of Science, EMBASE and CENTRAL through February 13, 2025 for randomized controlled trials (RCTs) evaluating elotuzumab in MM. Pooled relative risks(RRs) of adverse events observed in elotuzumab-containing regimens versus control therapies. RESULTS: 6 RCTs (N=1,736) were included. Elotuzumabsignificantly reduced incidence of neutropenia (RR = 0.86, 95% CI: 0.76-0.98), but increased risks of cough (RR = 1.41, 95% CI: 0.96-2.09), pneumonia (RR = 1.30, 95% CI: 1.07-1.59), diarrhea (RR = 1.16, 95% CI: 1.05-1.30), pyrexia (RR = 1.47, 95% CI: 1.10-1.96) and infections (RR = 1.09, 95% CI: 1.03-1.15). No significant differences were observed for anemia, thrombocytopenia, respiratory infections, nausea, appetite loss, back pain, muscle spasms, peripheral edema, insomnia, rash, pruritus, fatigue, or hypokalemia. For grade 3-4 events, elotuzumab was associated with higher risks of lymphopenia (RR = 1.86, 95% CI: 1.31-2.64, p = 0.0005, I2 = 9%), diarrhea (RR = 1.47, 95% CI: 1.00-2.17), pneumonia (RR = 1.57, 95% CI: 1.11-2.23), cataracts (RR = 2.87, 95% CI: 1.15-7.21) and infections (RR = 1.30, 95% CI: 1.04-1.62). CONCLUSION: Elotuzumab in MM appears safe but with a specific adverse events pattern : lower neutropenia, but higher respiratory, gastrointestinal, metabolic, and infectious events. Differences may be influenced by longer treatment and corticosteroid use; therefore, interpretation of outcomes such as hyperglycemia and cataracts requires particular caution.

Humans↗

PubMed2026

Genome-Wide Impact of Human DBR1 Depletion on RNA Processing Networks Reveal a Connection Between Pre-mRNA Splicing, mRNA Surveillance and Stress Granule Dynamics.

The RNA lariat debranching enzyme DBR1 is essential for intron turnover and RNA metabolism, yet its broader impact on transcriptome regulation remains incompletely defined. To elucidate the consequences of DBR1 depletion, we performed transcriptome-wide RNA sequencing of DBR1-knockdown and wild-type HEK293 cells. Differential expression analysis revealed widespread perturbations in pathways linked to RNA splicing, mRNA surveillance, translational control, and stress-granule biology. Many of the most significantly altered transcripts encode splicing factors and RNA quality-control components, underscoring DBR1's influence on post-transcriptional regulation. Alternative splicing analysis showed changes across multiple event types, with exon skipping accounting for >50% of events, followed by mutually exclusive exons, alternative 5' and 3' splice sites, and retained introns, indicating that DBR1 depletion induces pervasive splicing defects. Direct spliceosome inhibition using isoginkgetin (blocks tri-snRNP recruitment) and pladienolide B (targets SF3B1) reproduced the DBR1-KD mis-splicing patterns of cell signaling genes and factors involved in RNA metabolism, supporting a functional link between DBR1 activity and alternative splicing. Notably, DBR1 knockdown revealed a subset of transcripts that are both NMD-sensitive and enriched within stress granules. Consistent with this observation, G3BP1 immunopurification and confocal microscopy further support a role for DBR1 and UPF1 in stress-granule dynamics, suggesting that these factors may participate at distinct stages to influence mRNA fate under stress conditions. Together, these findings indicate that DBR1 functions beyond lariat RNA turnover as a common regulator of RNA processing, transcriptome stability, and stress granule homeostasis, revealing intricate crosstalk between RNA splicing and RNA quality control pathways in human cells.

Humans↗

PubMed2026

Test-retest reliability of spatiotemporal, kinematic, and kinetic measures in marker-based 3D gait analysis: A systematic review.

BACKGROUND: Marker-based 3D gait analysis (3DGA) is widely used to quantify impairments and evaluate treatment effects. For longitudinal clinical interpretation, clinicians and researchers need reference values for inter-session measurement error. For this purpose, this systematic review synthesized Standard Error of Measurement (SEM) values for spatiotemporal, kinematic, and kinetic (moments) outcomes obtained from marker-based 3DGA studies. METHODS: PubMed and Scopus were searched (final search: 11 December 2025). Studies reporting inter-session test-retest SEM and/or MDC for steady-state overground or treadmill walking using marker-based motion capture were included. Two authors screened records and appraised methodological/reporting quality using a custom tool informed by COSMIN, GRRAS, and biomechanics-specific items. Due to heterogeneity, results were synthesized descriptively using study-level median SEM values, stratified by joint, plane, population (healthy, pathological, single subgroups), and walking condition. Minimal Detectable Change (MDC) values were computed for all available data. RESULTS: Thirty-four studies (762 participants, 44.2% females) were included, with substantially more evidence for overground than treadmill walking. Overground spatiotemporal outcomes showed low errors (walking speed SEM of 0.06 m/s; timing typically ≤0.03 s; spatial parameters generally ≤0.03 m). For joint kinematics during overground walking, median SEMs were 2.4° (sagittal), 1.9° (frontal), and 3.3° (transverse). The corresponding joint-kinetic SEMs were approximately 0.06, 0.04, and 0.03 Nm/kg, respectively. Treadmill data followed similar patterns. SIGNIFICANCE: Marker-based 3DGA allows for accurate assessment of spatiotemporal, kinematic, and kinetic gait features. We provided detailed SEM/MDC lookup tables to support clinical decision-making. Results further offer a benchmark for validating emerging gait assessment technologies (e.g., markerless systems) against realistic limits of marker-based 3DGA.

Humans↗