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PubMed2026

Contrasting redox-related physiological responses associated with HaGATA23 and HaGATA36 during Orobanche cumana parasitism in sunflower (Helianthus annuus L.).

Helianthus annuus is an economically important Asteraceae species used for seed oil production and ornamental purposes, but its production is seriously affected by the root-parasitic plant Orobanche cumana. GATA transcription factors are zinc-finger DNA-binding regulators involved in plant development and stress adaptation. However, the molecular characteristics of GATA transcription factors in Helianthus annuus and their contribution to Helianthus annuus -Orobanche cumana interaction remain poorly understood. Here, 36 HaGATA members were retrieved from the Helianthus annuus genome and classified into four phylogenetic clades. Chromosomal placement, collinearity, gene structure, motif composition, and promoter elements varied among the 36 HaGATA members, indicating evolutionary conservation coupled with functional diversification. Expression analysis and RT-qPCR analyses revealed differential expression patterns among HaGATA genes under O. cumana stress, with HaGATA23 markedly downregulated and HaGATA36 strongly upregulated. Overexpression of HaGATA23 was associated with increased malondialdehyde (MDA) accumulation and unfavorable changes in antioxidant enzyme activities, whereas its silencing showed the opposite physiological tendency. In contrast, overexpression of HaGATA36 reduced malondialdehyde accumulation, increased peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD) activities, while its silencing showed the reverse tendency. These results indicate that HaGATA23 and HaGATA36 are candidate genes associated with contrasting redox-related physiological responses during O. cumana stress. This work provides evidence that GATA transcription factors are associated with redox-related physiological responses in sunflower under O. cumana treatment and identifies HaGATA23 and HaGATA36 as functionally divergent candidate genes for further validation.

Helianthus↗
PubMed2026

Neighborhood Deprivation and Screening Mammography Utilization: A Retrospective Cross-Sectional Study.

RATIONALE AND OBJECTIVES: Access to screening mammography reduces breast cancer mortality disparities. The Area Deprivation Index (ADI) is a validated measure of neighborhood socioeconomic disadvantage linked to adverse health outcomes. There is limited data evaluating mammography utilization among patients residing in areas of higher deprivation. This study evaluated the association between ADI and screening mammography utilization within an accountable care organization (ACO) affiliated with a multicenter academic medical center in the Upper Midwest. METHODS: This retrospective cross-sectional study included women aged 40-85 years attributed to the ACO in 2022, based on Wisconsin Collaborative for Healthcare Quality criteria. The primary outcome was receipt of screening mammography within two years. The primary exposure was ADI, analyzed by decile (ordinal) and as low (deciles 1-5) versus high (deciles 6-10) deprivation. The logistic regression models evaluated associations between ADI and screening, unadjusted and adjusted for age, race, ethnicity, and preferred language. RESULTS: Among 7463 participants with geographic data, 74.4% completed screening. Screening rates were 75.7% in low-deprivation areas versus 66.2% in high-deprivation areas. Increasing ADI decile was associated with reduced screening in unadjusted (OR 0.891, 95% CI 0.87-0.91, p<0.001) and adjusted analyses (OR 0.897, 95% CI 0.88-0.92, p<0.001). Black participants (OR 0.444, p<0.001) and individuals preferring non-English languages (OR 0.333, p<0.001) had lower screening odds after adjustment. CONCLUSION: Higher neighborhood deprivation is independently associated with lower screening mammography utilization. Targeted, equity-focused interventions addressing neighborhood, racial, and language-related barriers are needed to reduce screening disparities.

Area deprivation Index↗
PubMed2026

Functional Reading Activities to Motivate and Empower: Maintenance of Reading Outcomes for Young Adults With Intellectual and Developmental Disabilities Following a Randomized Controlled Trial.

PURPOSE: This study examined whether the effects of Functional Reading Activities to Motivate and Empower (FRAME), a functional, strategy-based reading comprehension intervention for young adults with intellectual and developmental disabilities (IDDs), were maintained 6 months following the completion of the intervention and explored participants' perceptions of the intervention's feasibility, relevance, and perceived impact. METHOD: Participants were 44 young adults with IDDs (ages 18-26 years) who participated in a previously reported randomized controlled trial (FRAME participants: n = 23; controls: n = 21). Trial outcomes were assessed via telepractice at pretest, posttest, and 6-month follow-up. Six-month maintenance analyses focused on outcomes that demonstrated significant posttest group differences: use of (a) reading comprehension strategies (proximal) and (b) reading comprehension questions (distal). Participant perceptions (social validity) were collected post-intervention from FRAME participants using a structured interview protocol with closed- and open-ended items. RESULTS: At the 6-month follow-up, FRAME participants demonstrated sustained but reduced improvements in strategy use relative to controls (p = .040). Between-groups differences were not maintained for reading comprehension questions (p = .091). Participants reported high acceptability and perceived relevance of FRAME, with qualitative themes reflecting perceived improvements in comprehension, self-improvement, and increased independence. CONCLUSION: Findings suggest that FRAME supports sustainable gains in reading comprehension strategy use and is perceived as meaningful and feasible for young adults with IDDs, although additional supports may be needed to promote sustained improvements in distal comprehension outcomes. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.33307218.

Humans↗
PubMed2026

Genetic regulation of CPEB3-mediated alternative polyadenylation associated with survival of patients with hepatocellular carcinoma.

BACKGROUND: Alternative polyadenylation (APA) is a key post-transcriptional mechanism that regulates gene expression by modulating 3'UTR length, its dysregulation has been implicated in carcinogenesis. How genetic variants influence APA to affect hepatocellular carcinoma (HCC) prognosis remains unclear. METHODS: Prognosis-APA quantitative trait loci (apaQTL) were performed using genotype and APA profiling from TCGA data. A two-stage survival analysis in 848 Chinese and 369 TCGA LIHC patients and functional validation were used to identify prognostic apaQTL in HCC progression. RESULTS: A total of 2,025 and 817 significant APA events were identified in Chinese and TCGA cohort, respectively. Besides, 859 events were associated with poor prognosis in HCC and enriched in RNA splicing / metabolism pathways. We detected 32,034 significant apaQTLs, predominantly enriched in 3'UTRs and RBP-binding regions. CPEB3 was prioritized as a key APA regulator RBP; its low expression correlated with poor patient survival and promoted proliferation, migration, and invasion in HCC cells. Notably, a functional apaQTL variant rs2037547, located in GSK3B and mediated by CPEB3, demonstrated a poor survival of HCC patients in both cohort (pooled HR=1.29, p=0.016). Mechanistically, rs2037547 promoted aberrant APA at proximal poly(A) sites of GSK3B through CPEB3, leading to increased expression of short 3'UTR isoform. This regulatory alteration enhanced HCC cell proliferation, invasion, and migration, and contributed to HCC progression. CONCLUSION: These findings elucidated the distinct role of apaQTL-mediated APA dysregulation in HCC prognosis, providing insights for prognostic stratification and potential targets for personalized therapy in HCC.

RNA-binding proteins↗
PubMed2026

The effect of hip abductor or external rotator strength on dynamic knee valgus in healthy subjects-a systematic review with partial meta-analysis.

BACKGROUND: Weak hip abductors and external rotators (ER) have long been suggested to cause increased dynamic knee valgus. Patients are often prescribed strengthening of these muscles with the expectation that it will reduce their risk of pain and injury. The validity of this claim remains unclear. METHOD: We conducted a systematic review and partial meta-analysis assessing the association between hip strength and knee valgus in healthy subjects. An online search was conducted in May 2026. Databases included Medline, EMBASE, CINAHL and Google Scholar. INCLUSION CRITERIA: English language, asymptomatic subjects, dynamometric hip strength, single or multi-camera kinematic analysis, and statistical tests of difference or correlations between hip abductor or ER strength and dynamic valgus. Data were extracted concerning study design, subject characteristics, relevant outcome measures and statistics. RESULTS: 22 papers qualified for inclusion. Hip abductor correlations: 12 papers found no significant correlation, 2 supported the hypothesis and 2 found evidence contrary. Hip ER correlations: 8 papers found no significant correlation, 2 supported the hypothesis and 2 were contrary. Group differences for hip abduction strength: 3 papers found no difference, 2 found significant differences in support of the hypothesis, 1 found significant difference to contrary. Group differences for ER strength: 1 paper found no significant difference. None of the partial meta-analyses achieved statistical significance. CONCLUSION: Weakness in hip abductors or external rotators may not result in increased dynamic knee valgus in healthy subjects. While continued research may further illuminate our understanding, we discuss alternative explanations.

Humans↗
PubMed2026

Pelvic lymph node dissection in prostate cancer: current evidence, controversies, and future directions.

BACKGROUND: Pelvic lymph node dissection (PLND) remains controversial in the management of prostate cancer. Although it provides the most accurate pathological staging, its therapeutic value beyond staging has long been debated due to conflicting evidence and concerns regarding procedure-related morbidity. OBJECTIVE: To critically evaluate the contemporary role of PLND, particularly extended pelvic lymph node dissection (ePLND), in prostate cancer management in the context of modern imaging, risk stratification tools, and evolving oncologic endpoints. EVIDENCE ACQUISITION: A narrative review of recent literature was conducted, focusing on high-level evidence including randomized trials, observational studies, and contemporary guideline recommendations addressing the indications, extent, oncologic outcomes, and complications of PLND. EVIDENCE SYNTHESIS: Recent randomized and observational studies suggest that ePLND improves nodal staging accuracy and may be associated with modest improvements in metastasis-free survival (MFS) in selected patients with intermediate- and high-risk prostate cancer, although the absolute benefit remains limited and causality is not definitively established. Advances in molecular imaging, particularly prostate-specific membrane antigen (PSMA) PET/CT, together with multiparametric MRI, validated nomograms, and emerging genomic classifiers, now allow more precise identification of patients most likely to benefit from ePLND. The integration of these tools supports a more individualized surgical strategy, including image-guided and sentinel lymph node approaches designed to maximize staging accuracy while minimizing unnecessary dissection. CONCLUSIONS: In the contemporary PSMA imaging era, ePLND continues to play an important role in nodal staging and may contribute to improved oncologic outcomes in carefully selected patients.

Humans↗
PubMed2026

Perinatal depression, maternal thyroid status and fetus/infant health and development: A systematic review.

BACKGROUND: Thyroid hormones are known to influence both maternal depression and child developmental outcomes, while maternal depression independently affects child outcomes. The potential interaction between thyroid dysfunction and depression in shaping child development remains insufficiently explored. The present study addresses such interplay. METHODS: Following PRISMA 2020 and JBI guidelines, three databases were searched through December 2025 for primary studies on maternal thyroid status, perinatal depression, and child development. Risk of bias (RoB) was assessed using validated tools. Due to clinical and methodological heterogeneity, data were synthesized narratively following SWiM guidelines. RESULTS: Eleven studies were included. Beyond independent risks for preterm birth and behavioral problems, limited evidence supports a synergistic model, while most studies likely reflect the simple co-occurrence of risks. Maternal thyroid peroxidase antibodies (TPO-Ab) were associated with child externalizing problems exclusively in the presence of clinical depression. High depressive symptoms also attenuated the cognitive benefits of prenatal iodine supplementation. Thyroid status appears to function as a risk moderator rather than a mediator. However, 50% of observational studies presented high RoB, primarily due to participant attrition. CONCLUSION: Findings are still scarce to support a synergistic risk model where specific maternal thyroid parameters (i.e. thyroid autoimmunity and iodine status) may moderate the impact of depressive symptoms on child development. Despite the high RoB in half of the studies, results highlight the need for integrated screening protocols. Simultaneously assessing mental health and thyroid status may optimize risk stratification for high-risk mother-infant dyads.

Female↗
PubMed2026

Integrative modeling of the genome structure and dynamics in fission yeast.

Genome organization in the nucleus is highly structured and dynamic. Recent advances in genomic technology have enabled the measurement of genome-wide architecture and locus-specific motion, yielding contact maps and live-cell trajectories. However, these outcomes are derived from different modalities and are not directly comparable, with their quantitative integration being a key challenge. Here we establish a genome-wide live-cell imaging platform in fission yeast Schizosaccharomyces pombe, tracking 131 chromosomal loci, along with the spindle pole body (SPB) and nucleolus, to construct a quantitative map of locus dynamics. By integrating these dynamics with contact data through polymer modeling of Hi-C data, we build a physics-based "digital twin" of the S. pombe genome consistent with the spatiotemporal dynamics of interphase chromatin. We validate it against genome-wide mobility patterns and known architectural features, including centromere and telomere clustering. The model also identifies distinct dynamical regimes: centromere- and telomere-proximal loci relax within [Formula: see text]150 s, whereas the remaining loci relax within [Formula: see text]70 s. We measure semiperiodic dynamics of SPB motion, including a characteristic peak near 225 s and [Formula: see text] fluctuations. We use the model with SPB-directed forcing to show how these low-frequency components propagate through the genome to drive genome-wide chromatin displacements. Together, this predictive physics-based modeling framework integrates genome structure and dynamics to reveal how nuclear mechanical driving forces shape chromosome motion, linking mechanically driven chromatin responses to genome maintenance and regulation.

Schizosaccharomyces↗
PubMed2026

Lactylation-related immune-metabolic dysregulation defines prognostic and therapeutic stratification in lung adenocarcinoma.

BACKGROUND: Lactylation links lactate metabolism with inflammatory signaling and immune regulation in tumors. However, its cellular distribution and translational value in lung adenocarcinoma (LUAD) remain unclear. METHODS: Single-cell RNA-sequencing datasets GSE189357 and GSE171145 were integrated to characterize lactylation-related activity, intercellular communication, and malignant epithelial cell states in LUAD. Single-cell-derived lactylation-related differentially expressed genes were mapped to TCGA-LUAD and multiple GEO cohorts. Univariate Cox regression and machine learning algorithms were used to construct a lactylation-related prognostic signature (LRPS). The associations of LRPS with prognosis, immunotherapy response, drug sensitivity, genomic alterations, immune infiltration, and inflammation- and metabolism-related pathways were evaluated. KRT7 was further validated using virtual knockout analysis, spatial transcriptomics, and in vitro and in vivo experiments. RESULTS: lactylation-related transcriptional activity showed heterogeneous distribution across LUAD cell populations and was associated with altered cell-cell communication. In malignant epithelial cells, LRTS-high and LRTS-low states exhibited distinct metabolic, inflammatory, and tumor-related pathway activities. LRPS showed stable prognostic performance in TCGA-LUAD and multiple GEO cohorts and remained an independent prognostic factor. Low LRPS was associated with greater potential benefit from immunotherapy, whereas different LRPS groups displayed distinct drug sensitivity, genomic alteration, and immune microenvironment patterns. KRT7 was highly expressed in LUAD and associated with poor prognosis. KRT7 knockdown suppressed LUAD cell proliferation, migration, invasion, colony formation, and tumor growth in vivo. CONCLUSIONS: This study identifies lactylation-related immune-metabolic dysregulation as a clinically relevant feature of LUAD and develops a single-cell-guided LRPS for prognosis and therapeutic stratification. KRT7 emerged as an LRPS-related functional candidate with experimentally supported roles in malignant LUAD phenotypes.

Immunotherapy↗
PubMed2026

A chromosomal gtrB homolog and dam differentially contribute to dry-heat and high hydrostatic pressure resistance in Salmonella enterica.

Salmonella enterica can persist in low-moisture foods and shows enhanced dry-heat resistance under low water activity, posing significant food safety challenges. However, the genetic basis of extreme dry-heat resistance and its relationship with other processing stresses remain unclear. In this study, twelve S. enterica strains were screened for dry-heat treatment at 60&#xa0;&#xb0;C and 80&#xa0;&#xb0;C, with S. Infantis CICC21649 identified as the most resistant strain. Comparative genomics and transcriptional analysis identified candidate genes related to envelope integrity and regulation, including gtrB and dam. Deletion of the chromosomal gtrB homolog reduced dry-heat resistance, producing an additional 0.91-log10 reduction relative to the parent strain at 80&#xa0;&#xb0;C. Deletion of dam caused broader stress sensitivity, reducing resistance to both dry heat and high hydrostatic pressure, with the stronger phenotype observed under high hydrostatic pressure. Proteomic analysis of the chromosomal gtrB homolog mutant revealed broad alterations in envelope-associated proteins, transport functions, oxidative stress pathways, and central metabolism under dry-heat stress. These findings indicate that the chromosomal gtrB homolog is an important contributor to extreme dry-heat resistance, whereas dam contributes to resistance against both dry-heat and high hydrostatic pressure, likely through a broader regulatory role in stress adaptation. These results reveal distinct structural and regulatory layers underlying stress adaptation in S. enterica and provide practical guidance for low-moisture food processing by highlighting the need to account for strain-dependent and stress-specific resistance during process validation.

Hydrostatic Pressure↗
PubMed2026

Protective association of the ELMO1 rs741301 variant against diabetes mellitus and diabetic nephropathy: a systematic meta-analysis of case-control studies.

CONTEXT: Diabetes mellitus (DM), an endocrine disorder, is characterised by persistently elevated blood glucose levels due to inadequate insulin production. Diabetic nephropathy (DN), is a critical complication associated with DM, often leading to end-stage renal failure and increased mortality. OBJECTIVE: This meta-analysis aimed to evaluate the association between the ELMO1 rs741301 polymorphism and susceptibility to DN among individuals with diabetes. METHOD: A systematic literature search was conducted for studies published between 2014 and 2024 using Embase, Google Scholar, and PubMed. Eligible case-control studies investigating the association between ELMO1 rs741301 and DN among individuals with DM were selected according to predefined inclusion criteria. Nine case-control studies comprising 880 individuals with DM and 1008 individuals with DN were included in the meta-analysis. RESULTS: The pooled analysis demonstrated a significant protective association between the ELMO1 rs741301 polymorphism and DN under the allelic model (OR = 0.77, 95% CI: 0.67-0.88), recessive model (OR = 0.74, 95% CI: 0.61-0.90), and dominant model (OR = 0.68, 95% CI: 0.53-0.88). In contrast, no statistically significant association was observed under the over-dominant model. CONCLUSION: The findings suggest that the ELMO1 rs741301 polymorphism may be associated with a reduced susceptibility to DN among individuals with DM. These findings provide evidence for a potential genetic contribution of ELMO1 to DN susceptibility and may help improve understanding of the genetic factors underlying diabetic complications. Further well-designed studies in diverse populations are warranted to validate this association.

Humans↗
PubMed2026

Investing in Canada's nursing workforce: a comprehensive review to inform policy innovations and directions.

BACKGROUND: Health systems worldwide face persistent health workers challenges including nursing shortages, workforce strain, and inequities. In Canada, these challenges have prompted renewed national and provincial reforms to strengthen recruitment, retention, leadership, and sustainability. This paper compares nursing workforce policy directions across Canada, and international jurisdictions to inform policy and planning. METHODS: A cross-country comparative analysis of policies building on a comprehensive national funded review that included an umbrella review of 69 systematic reviews, a comparative policy review of nursing workforce strategies in five jurisdictions, and validation through national horizon-scanning and policy dialogues (n >100). Evidence was analyzed across system, organizational, and individual levels. RESULTS: At the system level, international jurisdictions demonstrate comprehensive, legislated approaches integrating data, governance, and multi-year funding have advanced key nursing strategies. In Canada, the advances show the importance of strategies to have national and provincial/territorial alignment emphasizing leadership, flexibility, and inclusion as key levers. Organizational and individual-level reforms such as mentorship, leadership development, and wellness initiatives are expanding but remain variably evaluated. Experts identified national workforce data strategies and policy integration with embedded evaluation as key enablers to inform scalability and sustainability of implemented strategies. CONCLUSIONS: Canada's nursing workforce reforms are advancing toward coordinated, equity-driven, and evidence-informed strategies. Continued investment in evaluation, leadership, and national integrated data systems along with integrating nursing workforce planning within broader intersectoral planning will consolidate these gains and position Canada as an international leader in sustainable nursing workforce policy.

Canada↗
PubMed2026

Comparative transcriptome analysis reveals ncRNA-mediated regulatory networks associated with muscle crispiness in grass carp.

Non-coding RNAs (ncRNAs) have been demonstrated to be involved in muscle development and to function as key regulators. However, the molecular mechanism underlying muscle crispiness in grass carp (GC) remains poorly understood, and whether these ncRNAs are involved in its regulation is still unknown. In the current investigation, differentially expressed (DE) RNAs (including lncRNAs, circRNAs, miRNAs, and mRNAs) were identified; concomitantly, target genes prediction was conducted, and functional and signaling pathway enrichment analyses were performed. Pathways related to muscle crispiness were identified, and the competitive endogenous RNA (ceRNA) (lncRNA/circRNA-miRNA-mRNA) regulatory network was further constructed. The results showed that a total of 126 DE-lncRNAs, 17 DE-circRNAs, 329 DE-miRNAs, and 442 DE-mRNAs were identified in muscle tissues of both the GC and crisp grass carp (CGC). GO and KEGG enrichment analyses revealed that target genes of DE-ncRNAs were significantly enriched in signaling pathways, including structural constituents of muscle, apoptosis, oxidative phosphorylation, and regulation of actin cytoskeleton, suggesting that these pathways may be involved in muscle texture remodeling. Subsequently, DE-RNAs enriched in related pathways were identified, and a core ceRNA regulation network comprising 3 lncRNAs, 4 circRNAs, 3 miRNAs, and 17 mRNAs was constructed. Additionally, 10 DE-RNAs from randomly selected groups were validated by qRT-PCR. Our findings not only provide scientific evidence elucidating the molecular mechanisms underlying muscle crispiness in GC but also establish a foundation for studying changes in muscle textural qualities across other fish species.

Animals↗
PubMed2026

[Analysis of clinical phenotypes and pathogenicity of a c.4476+5G>T variant of SCN1A gene in a Chinese pedigree affected with Genetic epilepsy with febrile seizures plus].

OBJECTIVE: To explore the pathogenicity and characteristics of a heterozygous splicing variant of SCN1A gene in a Chinese pedigree affected with Genetic epilepsy with febrile seizures plus (GEFS+). METHODS: A retrospective analysis was carried out on the clinical data and results of genetic testing of a GEFS+ pedigree consisting of 5 members who had visited the First Affiliated Hospital of Zhengzhou University on July 1, 2024. Pathogenicity of the splicing variant of the SCN1A gene was validated with a minigene splicing assay. This study was approved by the Medical Ethics Committee of the the First Affiliated Hospital of Zhengzhou University (Ethics No.: KS-2018-KY-36). RESULTS: The proband, a 24-year-old female, presented with FS in conjunct with focal seizures, and both of her younger brothers had Dravet syndrome. All of the three patients had carried a c.4476+5G>T variant of the SCN1A gene, which was unreported previously. Minigene experiment verified that the variant could cause loss of the first 7 bps of exon 24 and 138 bps from exon 23 of the SCN1A gene, resulting in alteration p.V1447_1495delfs*6 and affecting splicing. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the variant was predicted as likely pathogenic (PVS1+PM2_Supporting). CONCLUSION: The c.4476+5G>T variant at an intronic site of the SCN1A gene probably underlay the pathogenesis of GEFS+ in this pedigree.

Adult↗
PubMed2026

Redefining the real problem in psychedelic trials: Why fighting the Lessebo matters more than blinding integrity.

Imperfect blinding is not specific to psychedelic trials. In randomized trials, treatment allocation is frequently correctly guessed, yet blinding integrity is rarely assessed outside of psychedelic research and is generally not considered a barrier in regulatory evaluation. The intense debate in psychedelics may reflect a broader double standard affecting mental health research, when uncertainties arising from imperfect blinding are confounded by those linked to patient-reported outcome measures. Indeed, people living with mental disorders are often viewed as unreliable reporters, despite well-documented limitations of clinician-rated scales and the absence of robust biological markers of symptomatic change. Importantly, it is the maintenance of reasonable doubt of treatment allocation that sustains internal validity and ethical feasibility of placebo-controlled designs, rather than perfect blinding. Concerns about expectancy bias in psychedelic trials are closely tied to blinding debates. When allocation is inferred, expectations may cluster in the arm perceived as active or in stereotyped experiences and influence outcomes differently in active and control arms, leading to a risk of lessebo, a negative placebo effect due to the negative expectation related to receiving a placebo. However, we argue that an underrecognized mechanism of lessebo is disappointment. This risk may reflect insufficient clinical management of disappointment rather than pre-treatment expectation alone. We therefore propose shifting the emphasis from preserving inevitably imperfect blinding towards mitigating disappointment in both arms. Establishing non-stereotyped expectations prior to treatment through structured psychoeducation, strengthened therapeutic alliance, and realistic preparation would help avoid lessebo effects. Such strategies would enhance ethical rigor, interpretability, and the clinical usefulness of psychedelic trials.

Humans↗
PubMed2026

Nanopore-based epigenomic profiling reveals the absence of widespread CpG methylation in the African swine fever virus genome.

DNA methylation is a critical epigenetic mechanism implicated in regulating replication and transcription in DNA viruses. However, the epigenetic landscape of African swine fever virus (ASFV), a large double-stranded DNA virus infecting pigs, remains controversial. Here, we systematically profiled the DNA methylome of the first ASFV strain isolated in Hong Kong (HK_NT_202103) using Oxford Nanopore Technologies (ONT) R10.4.1 sequencing. We employed a paired design: native whole-genome sequencing (WGS) against a methylation-free whole-genome amplification (WGA) control. Using conservative thresholds, we found no evidence of 5-methylcytosine (5mC), especially typical CpG methylation, across the viral genome. Importantly, clear CpG methylation signals were successfully detected in the host genome from WGS data, confirming the functionality of the workflow to detect 5mC at CG sites. While widespread 5mC seems absent, a small number of putative N6-methyladenine (6mA) loci were identified. A specific 6mA candidate exhibited raw ionic current disruptions and gene-level intersection with another ASFV isolate (CAS19-01/2019), although it lacked single-base consensus across different methylation callers or between the two isolates. Although our biological findings are restricted to a single isolate under specific experimental conditions, this study introduces a novel, highly rigorous ONT framework for viral epigenomics research. Furthermore, the absence of ASFV CpG methylation indicates that host CpG-depletion remains a viable strategy for viral metagenomic enrichment. Ultimately, our work offers a critical methodological baseline for ASFV surveillance and highlights the necessity of targeted experimental validation for rare viral modifications.

African Swine Fever Virus↗
PubMed2026

The gut microbiota-obesity axis in the pathogenesis and prognosis of breast cancer.

BACKGROUND: Breast cancer (BC) remains a major global health concern, accounting for 11.7% of all cancer cases and ranking as the second leading cause of female cancer-related deaths worldwide. Increasing evidence highlights the interplay between&#xa0;gut microbiota (GM) dysbiosis and obesity-associated metabolic dysfunction in BC progression. This review aims to elucidate&#xa0;the role of GM in obese patients with BC. METHODS: A systematic literature search was conducted in PubMed and Web of Science databases for publications from July 2015 to January 2025. Search terms combined BC, GM, obesity, dysbiosis, immunity, and microbiome. Article selection prioritized studies investigating microbial alterations in BC patients, mechanistic links between obesity and cancer progression, and GM-targeted interventions. Both original studies and authoritative reviews were included, supplemented by manual reference screening. DISCUSSION: Obesity may trigger systemic inflammation, altered adipokine secretion, and disrupted steroid hormone metabolism via gut-derived &#x3b2;-glucuronidase activity, thereby exacerbating BC occurrence and recurrence. GM dysbiosis-driven metabolites such as branched-chain amino acids (BCAAs) and short-chain fatty acids (SCFAs) can activate oncogenic signaling pathways and immunosuppressive myeloid-derived suppressor cells (MDSCs), fostering tumor immune evasion. Conversely, dietary interventions, probiotics, and fecal microbiota transplantation (FMT) can alleviate dysbiosis, strengthen gut barriers, and restore anti-tumor immunity, improving chemotherapy response and reducing recurrence. However, challenges persist in deciphering BC subtype-related microbial signatures and optimizing microbiota-targeted therapies. CONCLUSION: Future longitudinal studies are needed to clarify causal relationships, validate microbial biomarkers, and translate preclinical findings into clinical applications. Addressing the gut-breast axis may offer transformative potential for precision oncology in obesity-driven BC.

Humans↗
PubMed2026

Integrated single-cell and bulk transcriptomic analysis identifies a novel senescent fibroblast subtype associated with poor prognosis in acral melanoma.

BACKGROUND: Acral melanoma (AM) exhibits significant intratumoral heterogeneity, but its tumor microenvironment (TME) and immune regulation remain unclear. This study aims to dissect TME heterogeneity and establish a prognostic model based on key cell subpopulations. METHODS: We collected AM single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA). Unsupervised clustering, CellChat, and Scissor analysis were performed to characterize cellular heterogeneity, cell-cell communication, and prognosis-related cell subpopulations. Kaplan-Meier analysis was used to assess the prognostic value of key genes, which were further validated by multiplex immunohistochemistry (mIHC). RESULTS: In AM, Mel_C2, C7, and C9 with high SEMA6A and KIT expression were strongly linked to poor prognosis. We further identified a senescent fibroblast subpopulation (sCAF_CDKN2A) characterized by high fibroblast senescence signature (FSS) scores. Integrating Scissor analysis of fibroblast subtypes with bulk prognostic data, we identified COL3A1, VCAN, and KIT as prognosis-associated genes upregulated in poor-outcome-related fibroblast subsets. Cell-cell communication analysis revealed that sCAF_CDKN2A engages in an immunosuppressive network, interacting with regulatory T cells (Tregs) via MIF signaling and receiving signals from exhausted CD8+ T cells through PPIA-BSG interactions. Using transcription factor expression patterns from these fibroblast subtypes, we constructed a prognostic model that effectively stratified patients into distinct risk groups with significant differences in overall survival (OS). mIHC confirmed significantly higher protein levels of SEMA6A and COL3A1 in tumor tissues compared to matched normal tissues. CONCLUSIONS: We established a novel prognostic model for AM and identified sCAF_CDKN2A as an immunosuppressive senescent fibroblast subpopulation driving poor prognosis.

Acral melanoma↗