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PubMed2026

Exercise prehabilitation in head and neck cancer patients proposed for definitive chemoradiotherapy: The FIT4TREAT randomized controlled trial.

BACKGROUND: Patients with head and neck cancer (HNC) initially scheduled for definitive chemoradiotherapy (CRT) often experience early functional decline and deterioration in health-related quality of life (HRQoL) even before treatment initiation. Evidence for prehabilitation in this non-surgical setting remains limited. This study evaluated whether exercise prehabilitation (EP) initiated before CRT improves functional capacity compared with usual care (UC). METHODS: FIT4TREAT (ClinicalTrials.gov: NCT05418842) was a prospective, single-center, randomized clinical trial. Adults with HNC proposed for definitive CRT were randomly assigned (1:1) to EP or UC. EP consisted of supervised combined aerobic and resistance exercise performed three times per week from baseline until radiotherapy initiation. The primary outcome was the six-minute walk distance (6MWD) at the end of the pre-treatment period. Secondary outcomes included muscle strength, lower-limb functionality, body composition, and HRQoL assessed using the EORTC QLQ-C30 and QLQ-HN43. RESULTS: Between May 2021 and February 2025, 47 patients were enrolled; 40 were included in the primary analysis. After adjustment for baseline 6MWD and the randomization stratification variables, EP resulted in a significantly greater pre-treatment 6MWD than UC (adjusted between-group difference, 28.6 m; 95 % CI, 4.1-53.1; P = 0.023). EP also improved lower-limb functionality (P < 0.001) and was associated with better preservation in the QLQ-C30 summary score (P = 0.008), social functioning (P = 0.038) and body image (P = 0.011). CONCLUSION: EP before definitive CRT improves functional capacity and may help preserve HRQoL in patients with HNC, supporting its potential integration into routine oncology care.

Humans↗

PubMed2026

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↗

PubMed2026

From commensal to pathobiont: The emergence of virulence-enhanced Escherichia coli in China's food-animal systems - insights with future implications.

A fundamental shift in Escherichia coli epidemiology is being driven by convergence of virulence determinants and antimicrobial resistance within linked human-animal-environment systems. In China, the rapid growth of food-animal production, extensive antimicrobial use, and complex food networks are accelerating the emergence and dissemination of virulence-enhanced E. coli pathobionts. This review synthesizes recent epidemiological, genomics, and outbreak data to characterize China's evolving landscape of food-animal-associated E. coli. We highlight a significant shift from classical pathotypes to hybrid lineages that simultaneously carry virulence factors and last-resort antibiotic resistance determinants, including mcr-1, tet(X4), and blaNDM. These traits disseminate rapidly via plasmid-mediated horizontal gene transfer, facilitating rapid adaptation and enabling cross-sectoral One Health transmission. National surveillance, foodborne outbreak investigations, and whole-genome sequencing data show that food-animal reservoirs are active evolutionary niches that drive pathogen diversity and fitness, rather than serving merely as contamination sources. Whole-genome sequencing also pinpoints high-risk clones (e.g., ST394) and plasmid-mediated co-selection of virulence and AMR. The emergence of hybrid pathotypes (e.g., STEC/ETEC) and AMR-virulence co-selection challenges traditional classification and limits the effectiveness of conventional surveillance approaches. The 2017 colistin ban reduced mcr-1, yet ongoing resistance and emerging tet(X4) demand integrated surveillance. Collectively, these findings call for reconceptualizing E. coli as a dynamic genomic entity embedded within a unified ecological network. Addressing this threat requires an integrated One Health strategy including genomic surveillance, agricultural antimicrobial stewardship, and coordinated food-environment-clinical monitoring to prevent high-risk clone emergence and global spread.

Animals↗

PubMed2026

In Situ Hybridization and RT-PCR Detection of Nervous Necrosis Virus in Fourfinger Threadfin, Eleutheronema tetradactylum, in Taiwan.

Between April and July 2020, suspected outbreaks of nervous necrosis virus (NNV) infection were observed in fourfinger threadfin (Eleutheronema tetradactylum) fingerling hatcheries in Pingtung County, southern Taiwan. Affected fish exhibited spiral swimming behaviour and abdominal distension, resulting in mortality rates between 50% and 100%. Histopathological examination showed severe vacuolation in the brain and ocular tissues, with large oval and/or irregular basophilic cytoplasmic inclusion bodies in the brain. Phylogenetic analysis of the viral replicase (RNA1) and capsid protein (RNA2) genes revealed high nucleotide sequence identities among the isolates in this study, with sequence similarity rates of 96.9%-99% for RNA1 and 98.2%-99.0% for RNA2 compared to RGNNV reference strains available in the NCBI GenBank database. This is the first detection of betanodavirus in fourfinger threadfin in Taiwan, using RT-PCR and ISH. A positive correlation between elevated water temperatures and disease severity indicates the need for year-round surveillance and genomic analysis to clarify the epidemiology of FTNNV. The data suggest that infected eggs may facilitate the vertical transmission of Betanodavirus. Crucially, utilising virus-free broodstock, alongside routine health screening and environmental control, is essential for mitigating NNV risks in fourfinger threadfin aquaculture.

Animals↗

PubMed2026

Diverse structures of mcr-10-bearing plasmids and high colistin resistance in Enterobacter cloacae complex clinical isolates from South Korea.

BACKGROUND: The emergence of mcr-mediated colistin resistance in Enterobacter cloacae complex (ECC) poses a significant threat to antimicrobial therapy. Among mcr variants, mcr-10 has been identified in various environments, but its genetic diversity, structural context, and functional role in colistin resistance remain unclear. METHODS: We investigated 183 ECC isolates and identified 60 colistin-resistant strains through minimum inhibitory concentration (MIC) testing. The presence of mcr-10 was screened using reference genomes from NCBI, and whole plasmid sequencing was conducted on mcr-10-positive isolates. The genetic environment of mcr-10 was analyzed via synteny and structural annotation. RESULTS: Whole-plasmid sequencing of eight mcr-10-positive ECC isolates identified three replicon types among the mcr-10-harboring plasmids: IncFIB (n=3), IncFII (n=3), and IncFII/IncFIB (n=2). Although all plasmids shared the xerC-mcr-10 cassette, they lacked a conserved backbone and showed diverse genetic contexts with variable insertion sequences near mcr-10, indicating marked structural heterogeneity. No additional antimicrobial resistance genes were detected on these plasmids. When introduced into E. coli DH5α, the plasmids increased colistin MICs only modestly, whereas representative plasmids transferred into colistin-susceptible E. roggenkampii and E. kobei conferred high-level resistance comparable to that of the parental mcr-10-positive isolates. Consistently, qRT-PCR showed higher mcr-10 expression in ECC transformants than in E. coli under colistin exposure, supporting a hostdependent effect on mcr-10-mediated colistin resistance. CONCLUSION: These findings highlight the diversity of mcr-10-carrying plasmids and suggest that mcr-10-mediated colistin resistance is shaped by the host genetic background. Further studies are needed to clarify the mechanisms underlying mcr-10 expression.

Colistin↗

PubMed2026

Serotypic and Genomic Diversity of Vibrio anguillarum in Rainbow Trout Farms in Turkey: Implications for Vibriosis Control and Vaccine Candidate Selection.

Outbreaks of vibriosis caused by Vibrio anguillarum are a persistent constraint on rainbow trout (Oncorhynchus mykiss) aquaculture. However, information on the population structure of field strains in Turkey has been lacking. Here, we report the first systematic serotypic, proteomic, and genomic characterization of 23 V. anguillarum isolates collected over 10 years from rainbow trout farms located in six major aquaculture regions of Turkey. Serological analyses based on microagglutination, supported by ELISA characterization of hyperimmune sera, identified a clear predominance of serotype O1, whereas isolate V12 exhibited a non-agglutinating, atypical O-antigen profile. Protein profiling (SDS-PAGE) and immunoblotting showed largely conserved whole-cell protein patterns among the isolates, but distinct immunogenic bands at 14, 18, and 40 kDa were detected in isolates V18 and V21. Long-read whole-genome sequencing revealed that most Turkish isolates grouped within the global O1 clade, while V12, V25, and V28 isolates occupied more distant branches. Comparative genomics demonstrated a conserved core virulence gene set (RTX toxins, siderophore and iron-uptake systems, motility and adhesion factors, Type VI secretion system), with strain-dependent variation in accessory loci such as anguibactin and T6SS-I. Experimental infections of rainbow trout demonstrated significant differences in virulence among isolates (p < 0.05), with the V18 isolate showing high, the V15 intermediate, and the V12 low-mortality rates. By elucidating the relationship among the serotype, immunogenic protein profiles, virulence gene repertoires, and in vivo pathogenicity, this study provides a comprehensive overview of the antigenic and genomic diversity of Vibrio anguillarum isolates from Turkey. Notably, the identification of V18 and V21 as promising candidate strains for further vaccine evaluation, characterized by high virulence and unique immunogenic features, provides a scientific foundation for the development of serotype-specific vaccination strategies to mitigate vibriosis-associated losses in aquaculture.

Animals↗

PubMed2026

Novel Germline ELP1 Splice-Acceptor Variant in NF1-Negative Optic Pathway Glioma: Expanding the Clinical Spectrum Associated With ELP1 Variation.

We report a 7-year-old boy with NF1-negative optic pathway glioma harboring a novel germline ELP1 splice-acceptor variant (NM_003640.5:c.2205-2A>G) identified by whole-exome sequencing. The variant was likely pathogenic (ACMG/AMP: PVS1, PM2) and inherited from an asymptomatic father, consistent with incomplete penetrance, expanding the limited evidence linking germline ELP1 variation to gliomas.

Humans↗

PubMed2026

Obstructive sleep apnea and long-term risk of site-specific cancers: A population-based cohort study.

BACKGROUND: Obstructive sleep apnea is common, but its long-term association with site-specific cancers remains unclear. In this study, we examined 15-year risks of site-specific cancers in people with obstructive sleep apnea compared with the general population and to people with overweight or obesity. METHODS: We conducted a nationwide population-based cohort study using Danish registries, 1995-2021. People diagnosed with obstructive sleep apnea were compared with the general population and to people with overweight or obesity. Adjusted (weighted) 15-year risks, risk differences, and risk ratios (RRs) were estimated using the Aalen-Johansen estimator. Confounding was addressed using standardized morbidity ratio weighting. RESULTS: The study included 114,264 people with obstructive sleep apnea, 115,497 members of the general population, and 113,034 with overweight or obesity. After weighting, the distributions of sex (74% male), age (median 53 years), and comorbidities were comparable across the three cohorts. Obstructive sleep apnea was associated with an increased risk of cancers of the brain (adjusted 15-year risk: 5.78 vs. 3.61 per 1,000 persons; aRR 1.60 [95% CI 1.43-1.78]) and spinal cord (1.65 vs. 1.17 per 1,000 persons; aRR 1.41 [95% CI 1.16-1.72]) compared with the general population. Associations persisted when the obstructive sleep apnea cohort was compared with those with overweight or obesity. No associations were observed for other site-specific cancers. CONCLUSION: Obstructive sleep apnea was associated with an increased risk of brain and spinal cord cancers. These findings highlight the importance of effective prevention of obstructive sleep apnea and the need for further research on treatment.

Cohort Study↗

PubMed2026

Quantification of appetite-regulating hormones in children with hypothalamic and common obesity.

CONTEXT: The pathophysiology of hypothalamic obesity (HyOb) remains incompletely understood with no effective treatments. OBJECTIVE: We examined differences in appetite-regulating hormone concentrations between patients with HyOb, common obesity, and lean controls. DESIGN: Multiway cross-sectional case-control study of patients aged 2 through 19 years. SETTING: Two tertiary pediatric endocrinology centers. PATIENTS: Cases were obese (body mass index [BMI] > +2 SD score [SDS], "HyOb") and lean ("HyLean") patients with congenital (septo-optic dysplasia) or acquired (suprasellar brain tumor) hypothalamic disorders. Controls had common obesity ("Ob") or nonhypothalamic disorders and normal BMI ("Lean"). MAIN OUTCOME MEASURES: Relationships between the Dykens' Hyperphagia Questionnaire Score (DHQS), plasma or serum concentrations of leptin, insulin, α-melanocyte stimulating hormone (αMSH), brain-derived neurotrophic factor, oxytocin, acylated ghrelin, agouti-related peptide and copeptin, and BMI SDS. RESULTS: Dykens' Hyperphagia Questionnaire Score did not differ between HyOb and Ob patients (24 [17-34] vs 24 [18-31]) but correlated with BMI SDS in patients with hypothalamic disorders (P = 0.02). HyOb and Ob patients exhibited similarly increased anorexigens (insulin, leptin) and decreased orexigens (ghrelin, agouti-related peptide) compared to HyLean and Lean patients. The rate of BMI increase was independently associated with lower αMSH (β = -0.23 [-0.36 to -0.11], P = .0007) and ghrelin (β=-0.004 [-0.01 to 0.00], P = .001) concentrations, suggesting that αMSH replacement may be a therapeutic target for HyOb. HyLean patients demonstrated intermediate insulin responses to glucose compared to other subcohorts. CONCLUSION: In our cohort, patients with HyOb appeared indistinguishable from Ob in terms of their appetite and appetite-regulating neuroendocrine circuitry. Higher αMSH concentrations are associated with reduced weight gain and may be a target for therapeutic intervention.

alpha-MSH↗

PubMed2026

Navigated repetitive transcranial magnetic stimulation for post-stroke recovery: A systematic review and meta-analysis of randomized controlled trials.

Repetitive transcranial magnetic stimulation (rTMS) is a subcategory of non-invasive brain stimulation (NIBS), used to modulate brain plasticity and improve post-stroke recovery. Neuronavigation is used to improve the accuracy of stimulation with the aim of achieving a superior clinical outcome than with conventional targeting. The objective of this review is to evaluate the efficacy of navigated rTMS in subacute and chronic stroke patients in comparison to sham stimulation. We conducted a systematic-review and meta-analysis of randomized controlled trials (RCTs) identified from Pubmed, Scopus and Cochrane CENTRAL. Trials employing neuronavigated rTMS were included of these five types; high and low frequency rTMS, intermittent and continuous theta-burst stimulation (TBS) and Hebbian-type stimulation. 13 RCTs were included after a screening of 1900 studies. 606 patients receiving either active (n = 360) or sham stimulation (n = 246) were assessed. The pooled standardized mean difference (SMD) favored rTMS over sham SMD = 0.4 (95 %CI: 0.11-0.69), with moderate heterogeneity I2 = 55 %. Among stimulation modalities, continuous TBS showed the largest pooled effect. rTMS was also associated with significant improvements in disability-related outcomes, SMD = 0.61 (95 % CI 0.14-1.08). Navigated rTMS is associated with modest but significant improvements in motor and disability outcomes in subacute and chronic stroke. Large comparative trials are required to clarify the potential added value over conventional targeting approaches.

Humans↗

PubMed2026

Pathogenic Variants in HEPACAM Alter Protein Localization and Interactome in Astrocytes of the Developing Mouse Cortex.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare leukodystrophy characterized by early-onset macrocephaly, white matter edema, seizures, and motor and cognitive decline. Approximately 25% of MLC patients carry HEPACAM pathogenic variants, many of which are dominant missense variants causing remitting MLC Type 2b. HEPACAM encodes hepatic and glial cell adhesion molecule (hepaCAM), also known as GlialCAM, an astrocyte-enriched transmembrane protein with important roles in astrocyte territory establishment, gap junction coupling, branching organization, synaptic function, and development of the gliovascular unit. The molecular mechanisms through which pathogenic variants in HEPACAM alter hepaCAM protein function in vivo and facilitate MLC pathogenesis during brain development remain largely unknown. Here, we used new viral tools and proximity-based proteomics to examine how three different dominant pathogenic variants alter hepaCAM subcellular localization and protein interactome in astrocytes of the developing mouse cortex. We found dramatic changes in hepaCAM distribution throughout the astrocyte, which were common to all mutants tested. We also observed significant changes in protein interactome between wild type and mutant hepaCAM, including decreased association with previously described hepaCAM-interacting proteins Connexin 43 and CLC-2. Moreover, we identified the epilepsy-associate potassium channel KCNQ2 as a novel hepaCAM interaction partner and found reduced association between KCNQ2 and pathogenic variants. Collectively, our data provide new insights into hepaCAM protein function in astrocytes during brain development, reveal altered protein dynamics of pathogenic variants, and provide a new resource to explore the molecular underpinnings of MLC pathogenesis.

Animals↗

PubMed2026

Studies on functional differentiation of xpr1a and xpr1b genes in zebrafish.

Xenotropic and polytropic retrovirus receptor 1 (XPR1) is known to be involved in various biological processes, including phosphate homeostasis, cellular signaling, brain and vascular mineralization, whereas its specific contribution to bone development remains incompletely characterized. Due to genome duplication in teleosts, zebrafish Danio rerio possess two paralogous genes of XPR1 namely xpr1a and xpr1b, whose functional divergence remains unclear. The amino acid sequence similarity between zebrafish xpr1a and xpr1b was 83.26%. In situ hybridization demonstrated overlapping localization in the head and spinal cord at 24-48 hpf, while diverged by 72 hpf, with xpr1a becoming restricted to the head while xpr1b persisted in both regions. CRISPR/Cas9 was used to generate xpr1a and xpr1b mutants. The xpr1a mutants are comparatively healthy, viable but with mild growth reduction, whereas the xpr1b mutants display high mortality, reduced body length and severe vertebral deformities. Interestingly, all the double mutants died at the embryonic stage. Moreover, to further investigate the molecular and regulatory mechanisms, we conducted comparative transcriptome analysis on bone and brain tissues from xpr1b+/+ and xpr1b-/- zebrafish. In bone tissue, 6749 DEGs were identified, comprising 3846 upregulated and 2903 downregulated genes. These DEGs were mainly enriched in the MAPK signaling pathway, Wnt signaling pathway, cysteine and methionine metabolism, and ECM-receptor interaction. RT-qPCR validated results showed that seven osteogenesis-related genes (col1a1a, sp7, runx2b, col1a2, col1a1b, alp1 and entpd5), and two phosphate homeostasis related genes (slc20a2 and pdgfba), which are essential for skeletal mineralization and phosphate homeostasis, exhibited significantly downregulated expression in bone tissue of xpr1b mutant zebrafish. These results highlight the pivotal role of xpr1b in regulating skeletal mineralization and phosphate metabolism, thereby elucidating the functional specialization of XPR1 paralogs while providing a theoretical basis for understanding bone developmental mechanism in teleost vertebrates.

Animals↗

PubMed2026

Exercise for the mitigation of cancer therapy-related cardiac dysfunction in breast cancer patients treated with anthracyclines: a systematic review and meta-analysis.

PURPOSE: Cancer therapy-related cardiac dysfunction (CTRCD) is a significant concern for breast cancer patients undergoing anthracycline-based chemotherapy. Although exercise has been proposed as a cardioprotective strategy, existing reviews have largely examined heterogeneous cancer populations receiving varied treatments, leaving a gap in the evidence base focused exclusively on anthracycline-induced CTRCD. This systematic review and meta-analysis aimed to address that gap by evaluating the effects of long-term exercise on key CTRCD markers in breast cancer patients treated exclusively with anthracyclines. METHODS: A comprehensive search of PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science was conducted for randomized controlled trials including breast cancer patients undergoing anthracycline-based chemotherapy, receiving long-term exercise interventions (≥ 12 weeks, ≥ 1 session/week) compared to usual cancer care, and reporting at least one of the following outcomes: left ventricular ejection fraction, global longitudinal strain, cardiac troponin I, cardiac troponin T, or N-terminal prohormone of brain natriuretic peptide. RESULTS: Six randomized controlled trials involving 360 participants were included. Exercise significantly attenuated cardiac troponin I elevation compared to controls (SMD = -0.50; 95% CI, -0.93 to -0.06; p = 0.02). No statistically significant between-group differences were observed for left ventricular ejection fraction, global longitudinal strain, cardiac troponin T, or N-terminal prohormone of brain natriuretic peptide. CONCLUSION: The cardioprotective role of exercise during anthracycline treatment remains uncertain, though the attenuation of cardiac troponin I elevation suggests a potential protective signal warranting further investigation through larger, standardized trials employing advanced assessment modalities and longer follow-up periods.

Humans↗

PubMed2026

Micro- and nanoplastics-induced neurotoxicity: a CNS-centered, evidence-graded adverse outcome pathway framework based on systematic weight-of-evidence assessment.

Micro- and nanoplastics (MPs/NPs) are ubiquitous anthropogenic particulate pollutants posing emerging threats to human neurological health. Severe heterogeneity in particle physicochemical properties, environmental aging status, exposure paradigms and experimental platforms has created persistent mechanistic uncertainties in MP/NP neurotoxicology, hindering reliable hazard characterization and risk translation. Here, we systematically consolidate empirical toxicological evidence and construct a dedicated central nervous system (CNS)-targeted adverse outcome pathway (AOP) network integrated with rigorous weight-of-evidence (WoE) grading to elucidate the hierarchical, particle-specific toxic cascades underlying MP/NP-induced neural injury. Our synthesis overturns the conventional linear toxicity paradigm, demonstrating that MPs/NPs trigger neurotoxicity via a complex multi-input mechanistic network. We definitively establish oxidative stress as a robust early convergent key event-rather than a universal molecular initiating event-orchestrating ROS overproduction, lipid peroxidation, mitochondrial dysfunction, and neuroinflammation to propagate neuronal damage. This core module is driven by five distinct particulate upstream triggers: particle-biomolecule interfacial perturbation, corona-facilitated cellular internalization, plastic-associated chemical leaching, aging-derived free radical reactivity, and gut-borne systemic neurotoxic signaling. Downstream pathogenic outcomes encompass glial overactivation, neurotransmitter dyshomeostasis, autophagy-lysosome dysfunction, metabolic reprogramming, regulated neuronal cell death, and behavioral impairments. Tiered WoE analysis confirms strong validation for early oxidative/inflammatory cascades, moderate support for gut-brain axis crosstalk and intracellular trafficking disruption, and nascent evidence for synaptic dysfunction and neurodegeneration-linked proteostatic defects. Extrapolation to human health risk remains constrained by the frequent use of high-dose exposure paradigms, limited validated data on internal dosimetry in the human brain, discrepancies between effective concentrations in experimental models and environmentally relevant human tissue burdens, and insufficient causal validation of distal adverse outcomes. We highlight key research priorities including aged mixed-particle exposure systems, leachate-controlled assays, quantitative internal dose evaluation, and mechanistic intervention verification. This evidence-stratified AOP framework resolves longstanding mechanistic ambiguities in particulate neurotoxicity, providing a standardized, causality-based foundation for future mechanistic exploration and health risk assessment of global plastic pollution.

Adverse outcome pathway↗

PubMed2026

Multimodal alignment improves generalizability of genomic biomarker prediction in computational pathology.

Computational pathology models that use digitized histopathology whole-slide images have the potential to become a cost-effective and scalable alternative to molecular assays for the prediction of genomic biomarkers, a key task in precision oncology. However, as new genomic biomarkers are discovered or quantified, large, labeled datasets must be prospectively collected to train new models. To address this challenge, we developed multimodal alignment for biomarker learning and generalization (MARBLE), a multimodal contrastive pretraining strategy that integrates structured biomarker knowledge into representation learning of histopathology images. MARBLE aligns histopathology-derived representations with representations of genomic biomarkers generated by a large language model (LLM) and a protein language model (PLM). This biologically informed alignment enables data-efficient generalization to novel, out-of-distribution biomarkers. Using the MSK-IMPACT cohort of over 40,000 patients across multiple biomarker panel versions, we design experiments grounded in real-world data to demonstrate the value of our proposed approach.

CP: computational biology↗

PubMed2025

Impact of Chewing Behavior Change on Cognition and Cerebral Hemodynamics.

BACKGROUND: Impaired chewing ability is a recognized risk factor for cognitive decline in older adults, potentially due to reduced neural stimulation in cognition-related brain regions. While short-term studies have demonstrated transient increases in neural activity from chewing, the sustained cognitive and neurophysiological effects of encouraging thorough chewing habits in daily life remain unclear. OBJECTIVE: This randomized controlled trial investigated whether promoting thorough chewing during meals could improve cognitive function and cerebral hemodynamics in older adults. METHODS: Fifty participants aged 65 y or older were randomly assigned to either a 1-mo intervention group, which used a wearable device to monitor and increase chewing strokes during meals, or a control group that maintained usual chewing habits. Chewing behavior, cognitive performance (including memory and executive function via the color Stroop test), and cerebral hemodynamics in the dorsolateral prefrontal cortex (DLPFC) were measured at baseline and after 1 mo. Statistical analyses included t tests, chi-square tests, 2-way analysis of variance with post hoc tests, Pearson correlations, and generalized linear models to evaluate group differences and associations between chewing and cognitive outcomes. RESULTS: Significant time-by-group interactions were observed for memory, F(1, 48) = 6.24, P = 0.043, and hemodynamic responses in the left DLPFC, F(1, 48) = 6.19, P = 0.013. The intervention group showed increased chewing frequency (P = 0.017), improved memory performance, and reduced left DLPFC responses compared with controls. Chewing frequency was positively correlated with Stroop test scores (r = 0.53, P = 0.010) and negatively with hemodynamic changes in the left DLPFC (r = -0.30, P = 0.040). Although improvements in other cognitive outcomes and hemodynamic measures favored the intervention group, these differences did not reach statistical significance. CONCLUSIONS: Promoting intentional chewing habits for 1 mo may enhance memory-related cognitive performance and neural efficiency in the DLPFC during working memory tasks in older adults. This nonpharmacologic, low-burden strategy warrants further research with longer interventions to support cognitive health and dementia prevention. TRIAL REGISTRATION ID: UMIN000044280Knowledge Transfer Statement:This study demonstrates that promoting thorough chewing habits in older adults can improve memory and enhance neural efficiency in the brain. Encouraging intentional mastication is a simple, nonpharmacologic approach that may help maintain cognitive health and prevent dementia, providing a practical strategy for clinicians and policymakers to support healthy aging.

Humans↗

PubMed2026

Safe and Stable Germline Transmission of MSTN Mutations in Cattle.

With the global population expected to reach 10 billion by 2050, sustainable livestock production is critical. Gene editing of the myostatin (MSTN) gene represents a promising strategy to enhance muscle growth in cattle. In this study, MSTN-mutated founder (F0) cows were used to generate F1 offspring via ovum pick-up, in vitro fertilization, and embryo transfer. Four F1 calves were born, all confirmed to be heterozygous for the MSTN mutation. Long-term monitoring showed normal growth and no visible health abnormalities. Whole-genome sequencing identified SNPs, INDELs, and structural variants, most with minimal predicted functional effects. Proteomic profiling of Longissimus dorsi muscle quantified 2947 proteins, revealing only subtle expression differences between MSTN-mutated and wild-type cattle. These results demonstrate stable inheritance and confirm that MSTN editing does not disrupt genome integrity or protein expression. Overall, our findings support the safety and utility of MSTN gene editing to improve livestock productivity for future food security.

Animals↗

PubMed2026

Algae-to-host horizontal gene transfer in Paramecium bursaria is associated with host adaptation during endosymbiosis.

Paramecium bursaria maintains a stable endosymbiosis with green algae, yet the evolutionary consequences of this association remain unclear. Here, we screened the host genome for algal-derived horizontally transferred genes (HTGs) using a lineage-aware workflow designed to detect horizontal gene transfer (HGT) between two defined lineages. We identified 16 candidate HTGs, including four putative newly transferred genes and 12 homologous transferred genes, most of which were functionally associated with redox homeostasis and metabolism. Five HTGs showed symbiosis-dependent expression. RNAi knockdown of GH32s and SATs reduced host proliferation, total cell area, and motility, while GH32s knockdown also reduced endosymbiont load. Duplication patterns suggest that most transfers may have occurred after the P. bursaria lineage diverged from the sampled Paramecium species but before its lineage-specific whole-genome duplication (WGD). The HTGs also showed host-associated shifts in GC content and gene length, while representative HTGs retained conserved domains and functional motifs. Together, our results support algae-to-host HGT in P. bursaria and suggest that some transferred genes may contribute to metabolic integration during endosymbiosis.

Gene Transfer, Horizontal↗