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Single-organ proteomics in Drosophila melanogaster larva.

The combination of genetic accessibility, organ complexity, evolutionary conservation, and cost-efficiency makes Drosophila melanogaster (Dm) a well-known model system for biomedical and fundamental biological research. Proteomic analysis of single organs enables the identification and quantification of proteins expressed in specific organs. This will help to uncover specific biological functions and unique protein profiles that are not detectable in whole-organism analyses. In this study we have isolated single organs form Dm larvae, and we have performed a deep proteomics mapping by following a minimal manipulation preparation procedure. The combined dataset across all organs comprised 9132 identified proteins. As anticipated, principal component analysis (PCA) revealed clear separation between the proteomes of most organs, confirming distinct protein profiles. These findings demonstrate the applicability of the sample preparation strategy for high-resolution proteomic characterization of individual organs in Drosophila. Given the extensive genetic tools available for this model organism, our approach has the potential to open new avenues for proteomic studies in Drosophila melanogaster and any other biological systems where the sample amount is limiting. SIGNIFICANCE STATEMENT: Drosophila melanogaster is a well-known model system for biomedical and fundamental biological research that serves as a valuable in vivo model organism due to its high degree of evolutionary conservation with higher vertebrates, tractable genetics, and logistical efficiency. However, the proteome of Drosophila at single organ level has been elusive to date, due to several factors like low sensitivity of previous generation mass spectrometers and sample preparation procedures, difficult isolation of some organs. In this study we have applied a compilation of advanced methods including minimal sample manipulation together with simple, straightforward and efficient protein extraction and digestion methods. Obtained peptides were minimally handled to be analyzed by applying specific and sensitive nLC methods coupled on-line to state-of-the-art MS/MS system. Altogether, the applied strategy allowed us to get the first single organ study to date for this animal. These datasets represent a significative resource for future genomic, transcriptomic and proteomic studies in Drosophila, as multi-omic integration requires deep proteomics to translate data into functional biochemistry, and serves as a critical bridge and an indispensable standalone resource across the genomic, transcriptomic, and proteomic landscapes.

Animals

Reduced FOXP3 expression and its association with genetic ancestry in neuromyelitis Optica spectrum disorder: a Colombian cohort.

BACKGROUND: Autoimmune disorders are characterized by impaired immune tolerance, largely mediated by CD4⁺ regulatory T cells (Tregs), whose function depends on the transcription factor FOXP3. OBJECTIVES: To compare FOXP3 expression levels between patients with neuromyelitis optica spectrum disorder (NMOSD) and healthy controls from Bogotá, Colombia, and to explore their association with genetic ancestry. METHODS: FOXP3 expression was quantified from peripheral blood mononuclear cells using RNA-based analysis. Genomic ancestry proportions were estimated using ancestry-informative markers. RESULTS: FOXP3 mRNA expression was significantly reduced in NMOSD patients compared with controls (∼2.4-fold decrease in median expression; p = 0.027). Lower FOXP3 mRNA expression was associated with optic neuritis (p = 0.0059), but not with historical or current AQP4-IgG seropositivity. In a sensitivity analysis restricted to patients with documented historical AQP4-IgG seropositivity, the direction of reduced FOXP3 mRNA expression was preserved but did not reach statistical significance. In pre-specified exploratory ancestry-related analyses, African (p = 0.035) and Amerindian ancestry (p = 0.012) were associated with FOXP3 mRNA expression levels. CONCLUSIONS: Reduced FOXP3 mRNA expression in Peripheral Blood Mononuclear Cells (PBMCs) suggests an altered immune regulatory profile in NMOSD, potentially involving mechanisms beyond antibody-mediated immunity. The association between genetic ancestry and FOXP3 mRNA expression suggests that population-specific genetic background may influence immune regulatory pathways. These findings should be interpreted as exploratory and require validation in larger, clinically homogeneous cohorts.

Adolescent

Extended Long-Term Effects of Cognitive and Aerobic Training on Cognitive Function in Patients With Stress-Related Exhaustion Disorder: A 4.5-Year Follow-Up of a Randomized Controlled Trial.

Stress-related conditions like clinical burnout and exhaustion disorder (ED) are associated with enduring cognitive problems. We have previously demonstrated that the addition of computerised cognitive training (CCT) and aerobic training (AT) to a multimodal rehabilitation programme (MMR) yielded greater improvements in cognitive function compared to MMR alone in patients with ED. These effects were maintained at the 1-year follow-up for CCT, but not for AT. Building on these findings, the present study examined the extended long-term effects of CCT and AT on cognitive function, psychological health, and work ability, 4.5 years after the interventions. Participants were recruited from a stress-rehabilitation clinic and 56 of the initial 132 participants returned for the 4.5-year follow-up. Assessments were conducted before (T1), immediately after (T2), 1-year after (T3) and 4.5-years after (T4) the interventions. Mixed model analyses assessed changes in the intervention groups relative to the control group from T1 to T4, with follow-up comparisons examining within-group stability of outcomes between T3 to T4. The primary outcome was cognitive performance on a global cognitive score. Secondary outcomes included domain-specific cognitive functioning, self-reported cognitive function, psychological health (burnout, depression, anxiety, and fatigue), and work ability. The analysis revealed sustained long-term effects on the global cognitive score, a trained updating task and episodic memory in the CCT group, with stable performance between one- and 4.5-year follow-up. The addition of AT did not yield any extended long-term effects on cognitive performance. Both groups showed extended long-term improvements in self-reported memory problems, although findings were mixed. Extended long-term improvements were observed on burnout for both groups, with additional effects on anxiety and work ability in the AT group. Notably, these effects were not present at the 1-year follow-up and are more plausibly explained by selective attrition rather than a delayed intervention effect. In conclusion, the result indicates that cognitive interventions such as CCT can have lasting positive effects on cognitive function in patients with ED, whereas the long-term psychological effects should be interpreted with caution. TRIAL REGISTRATION: ClinicalTrials.gov: NCT0073772.

Adult

Do adherence-focused interventions in low back pain have an impact on rehabilitation outcomes? A systematic review with meta-analysis.

BACKGROUND: Low back pain (LBP) is the leading cause of disability worldwide. Exercise-based interventions are effective, but adherence remains suboptimal. This systematic review and meta-analysis evaluated the effectiveness of strategies designed to enhance adherence to exercise-based interventions in individuals with LBP in terms of adherence as well as pain and functionality. METHODS: Randomized controlled trials including adults with non-specific LBP were eligible if they compared exercise-based interventions incorporating adherence-enhancing strategies versus exercise alone or usual care. Primary outcome was adherence; secondary outcomes were pain and functionality. Searches were conducted in PubMed, Embase, Web of Science, Cochrane Library, CINAHL, Scopus, and PEDro up to May 2026. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane RoB 2 tool. Random-effects meta-analyses were performed using standardized mean differences. Certainty of evidence was evaluated using the GRADE approach. RESULTS: Fourteen randomized controlled trials including 1233 participants were included. Risk of bias was low in six studies, with the remainder showing some concerns or high risk. For adherence outcomes, evidence showed no clear effect of adherence-enhancing strategies on either device-measured physical activity (SMD = 0.21, 95% CI -0.01 to 0.43; 3 trials, 320 participants; moderate-certainty evidence) or questionnaire-based adherence (SMD = 0.33, 95% CI -0.23 to 0.89; 4 trials, 377 participants; very low-certainty evidence). For pain and functionality, moderate certainty of evidence indicated small improvements favoring intervention groups in the medium term. CONCLUSIONS: Strategies to enhance adherence to exercise in LBP show uncertain effects on adherence but may provide small improvements in clinical outcomes in the medium term. Higher-quality trials are needed to strengthen the evidence base.

Adult

Applications of artificial intelligence in robot-assisted surgery: a systematic review.

To characterize applications of artificial intelligence (AI) in robot-assisted surgery, summarize technical and clinical performance, and assess the quality of the available evidence. PubMed, Web of Science Core Collection, and Scopus were searched for English-language journal articles published from 1 January 2020 through 31 October 2025. Randomized, observational, model-development, validation, and feasibility studies evaluating AI in robot-assisted surgery or closely related image-guided minimally invasive workflows were eligible. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment. Owing to heterogeneity in surgical procedures, AI tasks, analytical units, validation strategies, and outcomes, findings were synthesized descriptively without statistical pooling. The review was registered in the International Prospective Register of Systematic Reviews (CRD420251175699). Seventeen studies were included: seven clinical prediction or decision-support studies, eight intraoperative recognition, segmentation, or image-guided studies, and two training or workflow studies. Five prediction studies reported area-under-the-curve values of 0.74-0.95. Technical studies reported F1 or Dice scores of 0.525-0.995 and task-specific accuracies of 0.840-0.998. Two randomized studies suggested benefits for personalized suturing feedback and automated camera control, but neither established improved patient outcomes. Only one study had low overall risk of bias; the remaining studies were at high or unclear risk or raised some concerns. AI applications in robot-assisted surgery show promise for prediction, intraoperative perception, training, and workflow support. Evidence primarily demonstrates technical feasibility rather than established clinical effectiveness. Independent multicenter validation and prospective evaluation of patient, educational, and workflow outcomes are required before widespread implementation.

Robotic Surgical Procedures

Atopic dermatitis and the risk of osteoporosis and fractures: a meta-analysis of cohort studies.

BACKGROUND: This meta-analysis aims to evaluate the risk of osteoporosis and fractures in patients with atopic dermatitis (AD) by synthesizing data from cohort studies. We also provide a comprehensive analysis of fracture risks across different severities of AD and anatomical sites. METHODS: Following the PRISMA 2020 guidelines, a systematic search was conducted in PubMed, Embase, and the Cochrane Library up to May 30, 2025. Studies that investigated the relationship between AD and osteoporosis or fractures were included in the analysis. Data extraction and screening were performed independently by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was applied, alongside sensitivity and subgroup analyses. Publication bias was evaluated using funnel plots and Egger's test. RESULTS: Ten cohort studies, involving 368 to over 2 million AD patients, were included. NOS scores ranged from 7 to 8, indicating generally high study quality. The pooled analysis revealed a 56% increased risk of osteoporosis (OR = 1.56, 95% CI: 1.14-2.13; I2&#xa0;=&#xa0;99.9%, p&#x2009;<&#x2009;0.0001) and an 8% increased risk of all-cause fractures (OR = 1.08, 95% CI: 1.05-1.10; I2&#xa0;=&#xa0;82.1%, p&#x2009;<&#x2009;0.0001) in AD patients. Subgroup analyses demonstrated a progressive increase in fracture risk with the severity of AD. Specific risks were significantly higher for vertebral fractures (OR = 1.14, 95% CI: 1.08-1.20; I2&#xa0;=&#xa0;67.3%, p&#x2009;=&#x2009;0.009) and lower limb fractures (OR = 1.11, 95% CI: 1.08-1.13; I2&#xa0;=&#xa0;65.0%, p&#x2009;=&#x2009;0.014). Sensitivity analyses confirmed the robustness of these findings, and no significant publication bias was detected (p&#x2009;=&#x2009;0.316). CONCLUSION: AD is associated with an increased risk of osteoporosis and fractures, particularly among patients with severe AD and those experiencing vertebral or lower limb fractures. These findings highlight the importance of targeted bone health monitoring in the clinical management of AD patients.Registration: (PROSPERO: CRD420251066550).

Humans

Effects of CPAP on endothelial activation and fibrinolytic balance in coronary artery disease with obstructive sleep apnea: The RICCADSA randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) promotes endothelial activation and a prothrombotic milieu through intermittent hypoxia, oxidative stress, and systemic inflammation, mechanisms closely linked to atherosclerosis progression. The vascular effects of continuous positive airway pressure (CPAP) therapy in patients with established coronary artery disease (CAD) remain incompletely understood. OBJECTIVE: To evaluate the longitudinal effects of CPAP treatment on endothelial adhesion molecules and fibrinolytic balance in patients with CAD and OSA. METHODS: In this randomized controlled analysis from the RICCADSA trial, 210 revascularized CAD patients with moderate-to-severe OSA were assigned to CPAP (n&#xa0;=&#xa0;104) or no-CPAP (n&#xa0;=&#xa0;106) and had available biomarker measurements at baseline and 12&#xa0;months. Circulating intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and plasminogen activator inhibitor-1 (PAI-1) were assessed. Linear mixed-effects models were used to examine longitudinal changes and time-by-treatment interactions adjusted for cardiometabolic covariates. RESULTS: For ICAM-1, no significant time-by-treatment interaction was observed. For PAI-1, a borderline time-by-treatment interaction suggested a numerically smaller increase in the CPAP group compared with no-CPAP (p&#xa0;=&#xa0;0.09). CPAP treatment was associated with a significantly greater reduction in VCAM-1 over time compared with no-CPAP (time-by-treatment interaction p&#xa0;=&#xa0;0.045 in adjusted models). CONCLUSIONS: CPAP treatment was associated with selective modulation of vascular biomarkers in patients with CAD and OSA, characterized by attenuation of endothelial activation reflected by reduced VCAM-1 levels, while fibrinolytic imbalance appeared largely resistant to intervention. These findings support pathway-specific vascular responses to CPAP and provide mechanistic insight into residual atherosclerotic risk in this high-risk population.

Aged

Specialized pro-resolving mediator (SPM)-enriched supplementation modulates inflammatory biomarkers in patients with symptomatic knee osteoarthritis: Blood plasma analysis from the GAUDI study.

BACKGROUND: Osteoarthritis (OA) is a leading cause of chronic pain and functional impairment, associated with persistent inflammation, potentially due to impaired resolution. Specialized pro-resolving lipid mediators (SPMs) regulate inflammation resolution and restore homeostasis. The GAUDI study previously demonstrated that SPM supplementation reduces pain and improves quality of life (QoL) in patients with knee OA. This analysis assesses the impact of SPM supplementation on inflammatory biomarkers (IB) and SPM levels and their relationship with clinical outcomes. METHODS: This is a secondary analysis of the GAUDI trial, a randomized, multicenter, double-blind, placebo-controlled study conducted in Spain in adults with symptomatic knee OA who received daily supplementation with SPMs or placebo for 12 weeks. Endpoints included changes in plasma IB and SPM levels and their correlation with clinical outcomes. RESULTS: Changes in IL-1 (15.9 vs. -1.1 pg/ml, p-value: 0.051) and IL-18 (10.3 vs. -1.4 pg/ml, p-value: 0.29) showed a tendency toward reduction in the SPM group compared to the placebo group. Changes in IL-1 and IL-8 positively correlated (r = 0.707, p-value: 0.005 and r = 0.551, p-value: 0.04; respectively) with changes in WOMAC score and negatively correlated (r = -0.797, p-value <0.001 and r = -0.804, p-value <0.001; respectively) with changes in EuroQoL-5 VAS score. Changes in IL-1 (r = 0.554, p-value: 0.048) and IL-6 (r = 0.631, p-value: 0.014 and r = 0.572, p-value: 0.031) correlated with changes in OMERACT-OARSI pain score. No significant differences in IB levels were observed between groups during the intervention. Minor changes in SPM levels point to metabolic pathways at work with SPM supplementation. In patients with a BMI &#x2265;25 kg/m&#xb2;, most IB tended to decrease following SPM consumption. CONCLUSIONS: This analysis suggests a potential association between SPM supplementation, decreased inflammation, and improved pain and QoL in patients with knee OA. Subtle changes in blood plasma SPM levels were detected that indicate, through bioinformatics analysis, a pathway-specific metabolome activation induced by SPM supplementation. TRIAL REGISTRATION: NCT05633849. Registered December 1st, 2022. Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT05633849.

Humans

Thermal analysis techniques for microplastic mass quantification: Methodological challenges and standardization needs.

Microplastics (MPs, 1 &#x3bc;m-5 mm) and nanoplastics (NPs, <1&#x202f;&#x3bc;m) are ubiquitous contaminants requiring standardized quantification methods. This systematic review evaluates thermal analysis techniques for mass-based MP detection, including pyrolysis-gas chromatography-mass spectrometry (Py-GC-MS), thermogravimetry-MS (TGA-MS), thermal extraction desorption-GC-MS (TED-GC-MS), and differential scanning calorimetry (DSC). Database searches (Web of Science, from inception to December 1, 2025) following PRISMA guidelines identified studies across seven environmental matrices (water, soil/sediment, atmosphere, biota, human tissues). We identify critical standardization gaps: inconsistent marker ion selection, unvalidated conversion factors for tire and road wear particles (TRWPs), and the absence of certified reference materials for complex matrices. Py-GC-MS demonstrates versatility but suffers from lipid interference in biological samples; TED-GC-MS offers superior sensitivity (sample capacity &#x223c;200&#xd7; Py-GC-MS) but lacks real-time chromatographic monitoring. To advance data comparability, we propose: (i) harmonized ion selection hierarchies based on specificity-sensitivity balance, (ii) matrix-specific TRWP quantification protocols, and (iii) inter-laboratory validation using environmental reference materials. This review provides a methodological roadmap for standardizing thermal analysis in MP research.

Humans

Deciphering CD8+ T cell exhaustion in human cancers through single-cell and spatial transcriptomics.

Exhausted CD8+ T cells (Tex) within the tumor microenvironment (TME) represents a critical barrier limiting anti-tumor immune responses. Tex cells are characterized by upregulated inhibitory immune checkpoint receptors, reduced cytotoxicity, and functional heterogeneity. Their genomic features and regulatory networks remain poorly defined, and only a minority of patients respond to immune checkpoint blockade (ICB) therapy. Single-cell RNA sequencing (scRNA-seq), through high-resolution transcriptomic profiling, has revealed diverse Tex subpopulations, identified subpopulation-specific marker genes and regulatory pathways. Spatial transcriptomics has further mapped the spatial distribution of Tex and their interaction networks with immune cells, tumor cells, and stromal cells, elucidating the impact of spatial heterogeneity on Tex functionality. Current studies indicate that the exhausted state of Tex is dynamic and modifiable, with functional differences among subpopulations closely associated with tumor progression and therapeutic response. However, the genomic characteristics, epigenetic regulation, and spatial interaction mechanisms of Tex require further exploration. This review summarizes recent advances in high-resolution omics technologies for precisely dissecting Tex heterogeneity, functional features, and interactions with other cells. It emphasizes the central value of optimizing Tex-targeted tumor immunotherapy strategies, providing theoretical foundations and directional guidance for developing more effective anti-tumor immunotherapies.

Humans

Artificial Intelligence in Diagnosing Depression Through Behavioural Cues: A Diagnostic Accuracy Systematic Review and Meta-Analysis.

AIM: To synthesise existing evidence concerning the application of AI methods in detecting depression through behavioural cues among adults in healthcare and community settings. DESIGN: This is a diagnostic accuracy systematic review. METHODS: This review included studies examining different AI methods in detecting depression among adults. Two independent reviewers screened, appraised and extracted data. Data were analysed by meta-analysis, narrative synthesis and subgroup analysis. DATA SOURCES: Published studies and grey literature were sought in 11 electronic databases. Hand search was conducted on reference lists and two journals. RESULTS: In total, 30 studies were included in this review. Twenty of which demonstrated that AI models had the potential to detect depression. Speech and facial expression showed better sensitivity, reflecting the ability to detect people with depression. Text and movement had better specificity, indicating the ability to rule out non-depressed individuals. Heterogeneity was initially high. Less heterogeneity was observed within each modality subgroup. CONCLUSIONS: This is the first systematic review examining AI models in detecting depression using all four behavioural cues: speech, texts, movement and facial expressions. IMPLICATIONS: A collaborative effort among healthcare professionals can be initiated to develop an AI-assisted depression detection system in general healthcare or community settings. IMPACT: It is challenging for general healthcare professionals to detect depressive symptoms among people in non-psychiatric settings. Our findings suggested the need for objective screening tools, such as an AI-assisted system, for screening depression. Therefore, people could receive accurate diagnosis and proper treatments for depression. REPORTING METHOD: This review followed the PRISMA checklist. PATIENTS OR PUBLIC CONTRIBUTION: No patients or public contribution.

Humans

Serum Albumin on Admission: A Prognostic Marker of Morbidity and Mortality in Burns? A Systematic Review and Meta-Analysis.

Albumin is essential for maintaining oncotic pressure and vascular integrity. In burn injuries, increased capillary permeability leads to hypoalbuminemia, which is a recognized marker of poor outcomes in critical illness. However, its prognostic value in acute burn care remains underexplored. This study evaluated the prognostic value of admission serum albumin in predicting mortality, acute kidney injury (AKI), hospital and intensive care unit length of stay, ventilatory requirements, sepsis, and pulmonary infection in patients with burn injuries. A systematic search of PubMed, Scopus, Cochrane Library, Web of Science, MEDLINE, and Embase was conducted. Of 5587 studies screened, 19 were included in the systematic review and 9 in the meta-analysis. Statistical analysis was performed using RStudio, with pooled outcomes reported as odds ratios (ORs), standardized mean differences, and hierarchical summary receiver operating characteristic curves. Heterogeneity was assessed using Cochran's Q, I2, and tau2. Hypoalbuminemia on admission was significantly associated with increased mortality during admission (OR 9.51; 95% CI, 3.04-29.78; I2 49.3%). Admission hypoalbuminemia was also associated with an increased risk of AKI (OR 2.83; 95% CI, 2.49-3.22; I2 0%). Evidence for other outcomes was limited and heterogeneous. Admission serum albumin appears to be a valuable prognostic marker in patients with burn injuries, particularly for mortality and AKI. Further research is required to support its integration into burn-specific risk models, characterize albumin trends within the first 24&#xa0;h postinjury, and establish optimal cut-off values.

Humans

Vitamin D Supplementation Modulates Base Excision Repair (BER) Machinery in Systemic Sclerosis: A Prospective Longitudinal Study.

Systemic sclerosis (SSc) is a chronic, autoimmune, fibrotic disorder involving immune dysregulation, vascular abnormalities and progressive fibrosis. Although oxidative stress and defective DNA repair have been implicated in its pathogenesis, the impact of vitamin D on DNA repair pathways remains unclear. This study aimed to investigate the expression of DNA repair enzymes in SSc, explore their relationship with vitamin D status and assess the effects of vitamin D supplementation on the transcriptional expression of these enzymes. Peripheral blood samples were collected from 52 female patients with SSc and 31 age-matched healthy controls (HCs). Gene expression levels of base excision repair (BER) enzymes (APE1 and OGG1) and nucleotide excision repair (NER) enzymes (XPA and XPC) were analyzed. Serum vitamin D levels were measured and correlated with disease activity scores. In a prospective arm of the study, patients received six months of vitamin D supplementation and their DNA repair capacity was evaluated pre- and post-intervention. Baseline expression of APE1 and OGG1 was significantly lower in SSc patients than in HCs, whereas expression of the NER genes remained unchanged, indicating selective impairment of the BER pathway. Vitamin D deficiency was prevalent in SSc and inversely correlated with disease severity. Supplementation significantly increased serum vitamin D levels and up-regulated APE1 and OGG1 expression; while NER genes remained unaffected. These findings are consistent with evidence of elevated oxidative DNA lesions in SSc and support a mechanistic link between BER activity and the repair of oxidative DNA damage. SSc patients exhibit reduced transcription of BER-specific enzymes associated with vitamin D deficiency andrestoration of vitamin D levels partially rescues BER enzyme expression. These findingshighlight a potentially modifiable axis linking micronutrient status, genomic stability and disease activity and provide a rationale for investigating vitamin D optimization as an adjunctive strategy to enhance DNA repair and potentially attenuate inflammatory and fibrotic processes in SSc.

Humans

Mul-PheG2P: decoupled learning and prediction-space fusion enables robust and interpretable multi-phenotype genomic prediction.

Genomic prediction of multiple phenotypes is crucial in modern plant breeding; however, existing methods struggle with negative transfer and lack interpretability, particularly across high-dimensional small-sample data and diverse species. To address this, we propose Mul-PheG2P, a novel paradigm based on decoupled learning and predictive space fusion. It employs a two-stage design: first training phenotype-specific encoders using genetic data, then decoupling phenotype-specific learning from cross-phenotype aggregation via an interpretable prediction layer. Mul-PheG2P outperforms existing methods across diverse crop datasets, including maize (Zea mays), wheat (Triticum aestivum), and tomato (Solanum lycopersicum). It provides a multi-scale interpretability chain: at the macro level, it quantifies phenotypic contributions via attention-based weighting; at the micro level, Integrated Gradients reveal the genetic basis of predictions. Notably, the model successfully identified the CCT (CONSTANS, CO-like, and TOC) motif regulating photoperiodism and the SQUAMOSA (SQUAMOSA promoter binding protein) promoter for inflorescence development, confirming its ability to capture functional biological mechanisms. These results highlight the high performance and interpretability of Mul-PheG2P, showcasing its value for low-cost, large-scale screening to advance precision breeding.

Phenotype

Diagnosis, treatment and monitoring of pediatric Beh&#xe7;et's disease: Systematic literature review informing the ISSAID/PRES recommendations.

BACKGROUND: Pediatric-onset Beh&#xe7;et's disease (BD) accounts for up to 20% of cases and represents a distinct clinical entity characterized by evolving phenotypes and age-specific patterns of organ involvement. This systematic literature review synthesizes current evidence on pediatric BD, informing forthcoming recommendations by the International Society of Systemic Auto-Inflammatory Diseases (ISSAID) and the Pediatric Rheumatology European Society (PReS). METHODS: A systematic search was conducted according to PRISMA guidelines. Observational studies reporting clinical features, diagnostic criteria, management strategies, and outcomes in BD patients diagnosed before the age of 16&#xa0;years were included. Proportional meta-analysis was performed to give pooled estimates for organ system involvement. RESULTS: Fifty-two studies, encompassing 2929 patients, met inclusion criteria. Sex distribution was balanced, with a 1:1 male-to-female ratio. The age of onset differed, with 1&#xa0;year old being the lowest median age of onset and 2&#xa0;years the lowest median age of diagnosis. The pooled random-effects estimate demonstrated that 50% of patients were HLA-B51 positive (95% CI, 0.5-0.6). Mucocutaneous manifestations were nearly universal (97.8%) and frequently represented the initial feature (80.9%). Musculoskeletal (36%), ocular (35%), neurological (17.9%), gastrointestinal (20%), vascular (15.4%) manifestations showed substantial variability in prevalence. Therapeutic approaches varied widely and were extrapolated from adult practice, with treatment guided by organ involvement and severity. CONCLUSIONS: Pediatric BD encompasses a heterogeneous spectrum of phenotypes requiring harmonized diagnostic frameworks, structured phenotypic stratification, and standardized monitoring to improve long-term outcomes. The relative burden and combination of organ manifestations varied across cohorts, reflecting both biological heterogeneity and differences in study design.

Humans

Translational reprogramming of TGF-&#x3b2; signaling via TRMT61A-mediated tRNA m1A drives prostatic fibrosis and hyperplasia.

Dysregulation of the epitranscriptomic landscape is closely linked to pathological proliferation, but its specific role in benign prostatic hyperplasia (BPH) remains unclear. Here, we identify the tRNA methyltransferase TRMT61A as a critical driver of BPH progression. We found that TRMT61A and global N1-methyladenosine (m1A) levels are aberrantly upregulated in human BPH tissues. Functionally, TRMT61A knockdown potently suppresses prostate cell proliferation and reduces stromal fibrosis, inducing G1 cell cycle arrest and reversing pathological remodeling both in vitro and in vivo. By integrating ribosome profiling (Ribo-seq) and tRNA-seq, we observed that TRMT61A drives translational reprogramming. TRMT61A preserves the stability of specific tRNA isoacceptors (e.g., tRNA-Leu-CAA), which is required for the efficient decoding of mRNAs containing m1A-dependent codons. Consequently, TRMT61A selectively promotes the translational elongation of the key receptor TGF&#x3b2;R1. This amplifies downstream TGF-&#x3b2;/SMAD signaling and drives epithelial-mesenchymal transition (EMT) without affecting mRNA transcription. In summary, our study reveals how TRMT61A drives BPH progression through TGF&#x3b2;R1 translation, highlighting the therapeutic potential of targeting epitranscriptomic pathways to reverse prostatic hyperplasia and fibrosis.

Male

Plant cis-regulatory grammar: Decoding the multidimensional code of transcriptional regulation for programmable crop engineering.

Cis-regulatory elements (CREs) orchestrate the spatiotemporal precision of gene expression that underlies plant development, adaptation, and domestication. Decoding the cis-regulatory grammar of plant genomes remains a central challenge in modern biology, with profound implications for programmable crop engineering. Here, recent conceptual and technological advances are synthesized to reshape our understanding of plant CREs. This review first argues that CRE function is not only an intrinsic property of DNA sequence alone but also emerges from a multidimensional context, including chromatin accessibility, histone modifications, three-dimensional genome topology, and cell type-specific regulatory landscapes. Furthermore, the convergence of single-cell epigenomics, high-throughput functional assays, and CRISPR-based dissection has begun to unravel this contextual grammar, revealing the computational principles governing transcriptional regulation. Critically, we propose that artificial intelligence (AI) platforms are catalyzing an ongoing transition from descriptive discovery to predictive engineering, wherein these platforms outperform natural evolution in designing synthetic CREs. Finally, a roadmap is outlined toward a plant regulatory grammar foundation model, which will enable truly predictive engineering of gene expression when fine-tuned for specific tasks. Collectively, the integration of single-cell resolution maps, precise genome editing, AI-driven design, and regulatory-compliant delivery systems promises to transform our ability to reprogram plant gene regulation for next-generation agriculture, bridging the gap between foundational regulatory biology and tangible crop improvement.

artificial intelligence

Providing Feedback on Previous Pain Scores Did Not Affect Weekly Pain Variability: A Cohort-Nested Randomised Study.

BACKGROUND: Spinal pain is one of the leading causes of disability worldwide and repeated symptom monitoring is increasingly used to capture its fluctuating nature. However, repeated pain assessments may be influenced by prior responses, potentially affecting longitudinal patterns of pain reporting. This study examined whether providing feedback on prior pain scores influenced within-person variability in weekly pain intensity ratings and retention over 60&#x2009;weeks. METHODS: This randomised study evaluating a methodological feature of repeated pain assessment was embedded within a cohort of adults with spinal pain referred to an outpatient hospital clinic. Participants (n&#x2009;=&#x2009;2448) were randomised 1:1 to weekly pain intensity ratings (0-10 numerical rating scale) either with feedback ('You answered [X] last week') or without feedback. Analyses included participants with &#x2265;&#x2009;40% valid responses (n&#x2009;=&#x2009;1883), of whom 948 received feedback and 935 did not. The primary outcome was within-person variability in pain intensity, quantified using the root mean square of successive differences. Secondary outcomes included additional fluctuation metrics and the number of weeks with missing responses. RESULTS: No meaningful between-group differences were observed for the primary outcome (mean difference -0.04 points [95% confidence interval -0.08 to 0.01]) or secondary outcomes, including retention rates. Sensitivity analyses yielded consistent findings. CONCLUSIONS: Providing participants with feedback on their previous pain score did not meaningfully influence within-person pain variability or retention during 60&#x2009;weeks of weekly monitoring. These findings aid the interpretation of repeated longitudinal pain assessments by showing that the observed variability was robust to this specific study design. SIGNIFICANCE: This randomised study showed that providing participants with feedback on prior pain scores did not meaningfully alter weekly pain variability or retention during 60&#x2009;weeks of longitudinal monitoring. These findings contribute to the interpretation of repeated longitudinal pain assessments in spinal pain research and suggest that weekly pain reporting patterns are robust to prior-pain feedback during long-term symptom monitoring.

Humans