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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

Maternal obesity in rats results in male-specific increases in genome-wide DNA methylation in postnatal offspring liver.

Male-specific peripubertal DNA demethylation in the liver has been reported in mice. Here, we investigated whether it also occurs in rats, the influence of maternal obesity and whether DNA demethylation changes contribute to observed sex-specific effects of maternal obesity in offspring. Female rats were fed a high-fat, high-sugar 'cafeteria' (Caf) diet before mating with standard chow-fed males. The offspring liver methylome and transcriptome were examined. Body weight was higher in Caf-fed dams prior to mating, during gestation and at parturition. Male and female offspring from Caf-fed dams had lower birth weights but higher adult weights and adiposity than offspring from chow-fed dams. A comparison of DNA methylation in 3-week-old weaner males versus female siblings from chow-fed dams did not reveal the male-specific DNA demethylation that was previously reported in mice. However, strong maternal diet effects in male weaner offspring methylation were observed. A comparison of female weaners from chow- versus Caf-fed dams showed a range of differences, with 39% of differentially methylated regions (DMRs) having higher methylation in Caf offspring and 61% of DMRs having higher methylation in chow offspring. In stark contrast, 99% of maternal-diet-induced DMRs in male weaner offspring had higher methylation in offspring from Caf-fed dams. This suggests that maternal obesity induces widespread hypermethylation in the male offspring liver at weaning. However, a comparison with RNA sequencing data revealed limited transcriptional changes at this developmental stage or in adult offspring. While these data highlight how environmentally sensitive DNA methylation is in the male rodent perinatal period, these methylation changes may not be a major contributor to sex differences in developmentally programmed liver disease.

Animals↗

PubMed2026

Novel splice site variants in GBA1 are associated with Gaucher disease and genotype-phenotype correlations.

BACKGROUND: Variants in GBA1 are associated with neurodegenerative disease. This study aimed to explore pathogenic GBA1 variants. METHODS: Four patients with progressive myoclonic epilepsy (PME) and extremely low β-glucosidase levels were recruited. Whole-exome sequencing and long-range PCR were performed to identify GBA1 variants. Bioinformatic analyses were used to predict the impact of the identified variants. A literature review was performed to explore the genotype-phenotype correlations. GBA1 expression data across different brain regions and developmental stages were analyzed using the BrainSpan database. RT-PCR was performed to verify the splicing effects. RESULTS: Compound heterozygous GBA1 variants were identified in four patients. Five distinct variants were detected, including two novel splice site variants (c.308-2A>G and c.762-2A>C) and three previously reported variants. All identified variants were rare or absent in gnomAD. Splice site variants c.308-2A>G and c.762-2A>C were predicted to cause aberrant splicing. Minigene-based splicing assays coupled with RT-PCR and Sanger sequencing confirmed that both variants cause complete exon skipping (exon 4 and exon 7, respectively). All patients presented with PME onset in childhood/adolescence, intellectual regression, low β-glucosidase, and diffuse brain atrophy and were subsequently diagnosed with Gaucher disease type 3. GBA1 expression in the brain showed two distinct peaks: one in infancy and another after five years of age. The onset age of PME aligned with the second GBA1 expression peak (after five years of age). CONCLUSION: This study identified compound heterozygous GBA1 variants, including two novel candidate pathogenic splice site variants, in Gaucher disease type 3 patients, expanding the known mutational spectrum.

Humans↗

PubMed2026

Effect of urinary catheter securement band on meatal pressure injury in male intensive care patients: A randomized controlled trial.

OBJECTIVES: To investigate the effectiveness of a urinary catheter securement band in preventing meatal pressure injury (meatal-PI) in male ICU patients, and to identify associated risk factors and the timing of injury development. METHODS: A total of 248 adult male ICU patients were randomly allocated to an intervention group (n = 124) or a control group (n = 124) between December 2024 and April 2025. The intervention group received a catheter securement band in addition to standard care, while the control group received standard care alone. Meatal-PI was evaluated daily using a structured monitoring form and a validated staging system. RESULTS: The incidence of meatal-PI was significantly lower in the intervention group (6.5%) compared with the control group (16.1%) (p = 0.016). Multivariate analysis identified catheter securement, use of silicone catheters, higher Braden Scale scores, and shorter ICU length of stay as independent protective factors, while advanced age was associated with increased risk. Additional factors significantly associated with meatal-PI included comorbidities, higher device burden, latex catheter use, dry skin, lower Glasgow Coma Scale and Braden scores, sedation, and perineal oedema (p < 0.001). CONCLUSIONS: The use of a catheter securement band significantly reduces the incidence of meatal-PI in male ICU patients. Incorporating catheter securement devices into routine nursing care, prioritising silicone catheter use, and performing regular meatal assessments may enhance patient safety by reducing the risk of device-related pressure injuries. Further research comparing different catheter securement methods across diverse patient populations is warranted. IMPLICATIONS FOR CLINICAL PRACTICE: The use of catheter securement bands may reduce the incidence of meatal-PI in male ICU patients. Incorporating standardized catheter stabilization strategies into routine intensive care nursing practice may enhance patient safety and support pressure injury prevention efforts.

Humans↗

PubMed2026

Repetitive transcranial magnetic stimulation in substance use disorders is safe and tolerable: A Systematic review of 141 clinical trials including 4299 participants.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulation intervention investigated as a treatment for substance use disorder (SUD) and its co-occurring disorders. As the number of rTMS SUD clinical trials increase, the safety and tolerability profile should be assessed. In this systematic review, we investigate adverse events (AEs) of rTMS in individuals with SUD and factors that may influence their occurrence. METHODS: We performed a systematic PubMed search to identify all controlled trials of rTMS in SUD published up to January 2025. Eligible studies were assessed, and safety information was extracted for analysis. RESULTS: A total of 141 clinical trials with 4299 participants were included in their active arms. rTMS trials recruited participants who were engaged in active substance use, were in the pre-treatment phase, in early recovery, or in sustained recovery. Twenty-two studies explicitly reported no AEs. Sixty-nine studies reported only mild AEs, while only six studies reported moderate AEs. Thirty-five studies did not report safety-outcomes/AEs. As expected, participants reported mild and temporary AEs such as headaches, pain or discomfort under the coil, or dizziness. Only nine studies reported serious AEs (7 studies in active TMS and 2 in sham TMS). Importantly, no seizures attributable to active rTMS were reported in these SUD samples. CONCLUSION: Overall, rTMS in SUD samples is safe and well-tolerated regardless of recovery stage and substance. Most reported side effects were mild, self-limiting, and tolerable. However, AE reporting was incomplete, as 35 of 141 trials reported no safety data, limiting conclusions to reported outcomes. This evidence supports the safety of rTMS as a potential stand-alone or adjunctive treatment for SUD.

Humans↗

PubMed2026

The effects of mindfulness-based cognitive therapy in the psychological and physical health of cancer patients: A systematic review and meta-analysis.

PURPOSE: No prior systematic review has specifically evaluated the efficacy of mindfulness-based cognitive therapy (MBCT) in improving both psychological and physical outcomes among cancer populations. This study aims to assess MBCT's effects on cancer patients' mental and physical health. METHOD: Following PRISMA guidelines and with PROSPERO registration (CRD42023453581), we systematically searched PubMed, Cochrane CENTRAL, Embase, and Web of Science for randomized controlled trials (RCTs) were searched up to June 2026. Eligible trials enrolled adults (≥ 18 years) with any cancer type/stage, compared MBCT delivered per standard manual against non-MBCT controls, and reported at least one validated measure of distress, depression, or anxiety; secondary outcomes included fatigue, quality of life, and mindfulness skills. Two reviewers independently selected studies, extracted data, and assessed risk of bias using the Cochrane tool; random-effects meta-analyses were performed in Stata 16. RESULTS: 11 RCTs comprising 1122 participants (mean age 54.8 years; 91% female) were included. MBCT produced large, significant reductions in psychological distress (SMD = -0.81, 95% CI-1.27 to-0.40), depression (SMD = -0.95, 95% CI -1.40 to-0.49), and anxiety (SMD = -0.86, 95% CI -1.22 to-0.51). It also markedly decreased fatigue (SMD = -0.83, 95% CI-1.10 to-0.56), improved quality of life (SMD = 0.56, 95% CI 0.22-0.88), and enhanced mindfulness skills (SMD = 0.76, 95% CI 0.59-0.92). CONCLUSIONS: This meta-analysis is the first to exclusively synthesize RCT evidence of standardized MBCT in cancer care, demonstrating significant dual benefits for emotional and physical well-being while providing strong support for integrating MBCT into comprehensive oncology rehabilitation.

Humans↗

PubMed2026

Pretreatment EBV-DNA/TLG-Based Risk Stratification Is Associated With Survival Outcomes in Nonmetastatic Nasopharyngeal Carcinoma: An Exploratory Study.

Whether combining pretreatment plasma Epstein-Barr virus DNA (EBV-DNA) with 18F-FDG PET/CT-derived total lesion glycolysis (TLG) improves prognostic stratification in nonmetastatic nasopharyngeal carcinoma (NPC) is unclear, particularly in nonendemic populations. We retrospectively analyzed 86 eligible nonmetastatic NPC patients treated with definitive radiotherapy (2010-2024) at a single nonendemic-region institution. EBV-DNA (prespecified cutoff 3500 copies/mL) and TLG (cutoff 200, ROC-derived within this cohort) were dichotomized. Both were available in 59/86 patients (68.6%), who differed from the rest in nodal and overall stage and in RT technique. Baseline PET/CT was in-house in 57 of 86 patients, and a robustness analysis in that subgroup is reported. Given limited events (13 PFS, 9 OS), Cox analyses are exploratory and were supplemented with penalized regression and bootstrap validation. At a median follow-up of 75.5 months, 5-year PFS and OS for the whole cohort (n = 86) were 81.1% and 85.9%. The EBV-DNAhigh/TLGhigh subgroup remained associated with inferior PFS after adjustment in an exploratory model (adjusted HR = 3.97, 95% CI: 1.32-11.93) and, in a single-variable model, with inferior OS (HR = 4.13, 95% CI: 1.10-15.52). Discrimination was comparable to the individual-biomarker model for PFS and lower for OS. Five-year PFS fell monotonically across the four risk groups in the complete-case cohort (n = 59; 89.7%-58.3%). OS differed across groups (log-rank p = 0.044) but was not strictly monotonic, with wide, overlapping confidence intervals. This two-biomarker model is hypothesis-generating and needs prospective, multicenter validation before any consideration of risk-adapted treatment.

Epstein–Barr virus DNA↗

PubMed2026

Neuromodulation for Subjective Tinnitus: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVE: To evaluate the effectiveness and safety of neuromodulation and bimodal stimulation for chronic subjective tinnitus in randomized controlled trials (RCTs). DATA SOURCES: PubMed/MEDLINE, Web of Science, and EMBASE (January 2015-December 2025) searched per PRISMA 2020. REVIEW METHODS: Adult RCTs (≥ 18 years) with chronic subjective tinnitus (> 3 months) assessing validated outcomes (THI, TFI, TQ) for neuromodulation/bimodal interventions vs. sham/controls. Two-stage screening, Cochrane RoB-2 risk-of-bias assessment. Random-effects meta-analyses (REML) were performed when ≥ 3 comparable trials were available; effects reported as standardized mean differences (SMD) with 95% CIs. Main Outcomes and measures included change in tinnitus severity (THI/TFI/TQ) while secondary outcomes included loudness (VAS/NRS), durability, and adverse events. RESULTS: Twenty-six RCTs (n = 1576) met criteria: tES (11; n = 372), rTMS (8; n = 432), acoustic coordinated reset (1; n = 100), vagus nerve stimulation (2; n = 90), and bimodal stimulation (4; n = 582). Meta-analysis showed a nonsignificant pooled effect for tDCS (SMD -0.36; 95% CI -0.75 to 0.02; I 2 = 51%) and rTMS (SMD -0.15; 95% CI -0.37 to 0.07; I 2 = 0%). Single-trial evidence for coordinated reset showed no advantage over broadband noise. VNS demonstrated modest benefits with safety concerns limited to implanted approaches. Bimodal stimulation yielded consistent, clinically meaningful reductions (often ≥ 10-20 points on THI/TFI), with durability up to 12 months. Adverse events were mild/transient across noninvasive modalities. CONCLUSIONS: Noninvasive neuromodulation appears safe with average benefits; among modalities, bimodal stimulation shows the most consistent and durable clinical improvements. Standardized, adequately powered RCTs with harmonized protocols and long-term follow-up are needed to refine targets and dosing.

Humans↗

PubMed2026

Catecholaminergic Contributions to Inhibitory Control Following Physical Fatigue: Behavioral and Neurophysiological Findings.

Acute physical fatigue can impair cognitive control, yet its underlying neurochemical mechanisms remain unclear. This study investigated whether catecholaminergic modulation influences behavioral and neural markers of inhibitory control following physical fatigue. Eighteen healthy, recreationally active adults (9 males, 9 females; 23.4 ± 2.2 years) completed a randomized, triple-blind, placebo-controlled crossover study. On separate visits, participants received methylphenidate (MPH; 20 mg; a dopamine and noradrenaline reuptake inhibitor), reboxetine (REB; 8 mg; a noradrenaline reuptake inhibitor), or placebo. Physical fatigue was induced by repeated bilateral leg extensions to task failure. Cognitive performance was assessed before and after physical fatigue using a Go/No-Go task with electroencephalographic recording. Behavioral outcomes included reaction time and accuracy, while event-related potentials measured neural stages of response execution and inhibition (N2 and P3). Mixed-effects models were used for statistical analysis. For No-Go trials, a significant MPH × Time interaction was observed for accuracy (p = 0.008), with improved post-fatigue performance following MPH administration (p = 0.048). At the neural level, MPH was associated with shorter fronto-central No-Go N2 latency (p = 0.038) and altered fatigue-related changes in No-Go P3 latency (p = 0.047). REB did not produce comparable behavioral or neural effects. These findings provide pharmacological evidence that catecholaminergic mechanisms contribute to inhibitory control following physical fatigue. The differential effects of MPH and REB suggest that selective noradrenergic enhancement alone is insufficient to maintain inhibitory control following physical fatigue. Instead, the findings implicate broader dopaminergic and noradrenergic mechanisms, potentially involving alterations in the temporal dynamics of inhibitory processing. TRIAL REGISTRATION: (G095422N and identifier NCT05880342).

Adult↗

PubMed2026

Repeated scoring with the adult appendicitis score improves the sensitivity and the specificity of appendicitis diagnosis in patients with early equivocal signs of appendicitis: a secondary analysis.

PURPOSE: The utilization of computed tomography in the early stage of acute appendicitis may result in overdiagnosis and unnecessarily expose patients to ionising radiation. The Adult Appendicitis Score (AAS) can be used to select patients for imaging. Observation and re-scoring in the DIAMOND trial reduced the need for imaging. Now, we wanted to determine if the change in AAS (∆AAS) can serve as a diagnostic tool to select patients for imaging even more precisely. METHODS: Eighty-eight patients with early equivocal appendicitis participated in the observation arm of the DIAMOND trial. The data for these patients were reanalysed, and ∆AAS during the observation was calculated. The baseline AAS, final AAS, and the change in C-reactive protein (∆CRP) were selected as reference standards. RESULTS: Eighty-three patients with complete data were included in the analysis. The AUROC (Area Under the Receiver Operating Characteristic) values are as follows: ∆AAS, 0.932 (95% CI 0.868-0.996); baseline AAS, 0.629 (95% CI 0.498-0.760); final AAS, 0.936 (95% CI 0.886-0.987); and ∆CRP, 0.796 (95% CI 0.696-0.897). Using receiver operating characteristic curves, we established the thresholds for low (AAS ≤ -2), intermediate (AAS -1 to 0), and high (AAS ≥ 1) probability of appendicitis. The negative predictive value for the low-probability group and the positive predictive value for the high-probability group concerning acute appendicitis were 97% and 94%, respectively. CONCLUSION: Patients with equivocal signs of appendicitis may benefit from short observation and the calculation of ∆AAS to reduce overdiagnosis and exposure to excessive imaging. REGISTRATION: The DIAMOND trial was officially registered on ClinicalTrials.gov (NCT02742402) on April 13, 2016.

Adult↗

PubMed2026

Effectiveness and usability of artificial intelligence-powered assistive technologies in Supporting daily activities of children with cerebral palsy: a systematic review.

BACKGROUND: Cerebral Palsy (CP) is the main cause of motor disabilities in childhood, necessitating innovative approaches to rehabilitation and assistive technology (AT). Simultaneously, artificial intelligence (AI) is increasingly being integrated into devices to create more adaptive, personalized, and effective AT. This systematic review aimed to evaluate the effectiveness and usability of AI-powered assistive technologies designed to support daily activities and rehabilitation in children with CP. MATERIALS AND METHODS: Five databases, including Scopus, Web of Science, PubMed, Embase, and IEEE Xplore, were systematically searched, and 23 articles were included in the final analysis. Articles were identified, selected, and categorized into emerging thematic areas based on the primary function and application of the technology. RESULTS: Five key thematic topics were identified: 1) AI-driven motor rehabilitation and gait training for functional mobility; 2) intelligent assessment and monitoring systems for clinical decision support; 3) AI-supported communication, social interaction, and intention recognition tools; 4) gamified and virtual reality-based interventions to enhance engagement and usability; and 5) smart assistive systems supporting daily living and independent mobility. The findings demonstrate a strong trend toward the application of AI technologies in personalized, engaging, and data-driven interventions for children with CP. However, the field is predominantly in the proof-of-concept stage, with limitations including small sample sizes, lack of long-term clinical validation, challenges in user-centered design, and usability for children with CP. CONCLUSION: AI-powered assistive technologies hold significant potential for transforming the care of children with CP by enabling highly personalized and engaging interventions. To actualize this potential, future work must realize that practical application remains challenging owing to limited clinical validation, technological integration, and usability barriers for children with CP. Future research must prioritize user-centered design and multidisciplinary collaboration to ensure that AI and robotic advancements improve the usability and quality of life for children with CP.

Humans↗

PubMed2026

A framework for delivering real-time, instrument-relative navigation in transoral robotic surgery.

Transoral robotic surgery (TORS) is a minimally invasive, inside-out technique that, compared with traditional open approaches, provides fewer post-operative complications, shorter hospital stays, and improved survival for early-stage head and neck cancer. However, TORS is limited by its steep learning curve and poor visualization of deep tumor margins. This randomized crossover study evaluated a surgical navigation system's potential to enhance accuracy and user experience with real-time, instrument-relative feedback. Seven Teflon beads (d = 2.381 mm) were embedded at the tongue base of a porcine pharynx-and-larynx model. Tongue blade compression and retraction were applied to the model to mimic intraoperative tissue deformation, reproducing the anatomical shifts that occur relative to preoperative imaging. Eight participants used the da Vinci Surgical system to localize the beads by placing pins under two conditions: (a) preoperative computed tomography with no navigation; (b) model-based visual navigation with quantitative instrument-to-target metrics. Surgical accuracy was determined by calculating the target localization error (TLE, pin-to-bead Euclidean distance) and the angular error (AE, pin axis trajectory to bead). Accounting for training level and bead depth, surgical navigation reduced TLE by 5.44 mm (95% CI, 4.02-6.86 mm; p = 2.00e-11) and AE by 8.47 degrees (95% CI, 6.21-10.72 degrees; p = 5.17e-11). Impressions of the system were generally favorable using a 5-point Likert survey and task duration (p = 0.26) or cognitive workload via the NASA-Task Load Index (p = 0.22) were not significantly affected. The navigation system demonstrated translational promise, offering improved target localization accuracy and more consistent performance across experience levels, two critical determinants of surgical quality in TORS.

Robotic Surgical Procedures↗

PubMed2026

Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase IIb KEYNOTE-942 Study.

Intismeran autogene (intismeran; formerly V940 or mRNA-4157) is an mRNA-based individualized neoantigen therapy. We report 5-year outcomes of intismeran plus pembrolizumab from the phase IIb KEYNOTE-942 study (ClinicalTrials.gov identifier: NCT03897881). Eligible patients with resected stage IIIB to IV cutaneous melanoma were randomly assigned 2:1 to receive nine doses of intramuscular intismeran 1 mg once every 3 weeks plus 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks or 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks. The primary end point was recurrence-free survival (RFS); secondary end points included distant metastasis-free survival (DMFS) and safety. Five-year analyses were descriptive. Among 157 randomly assigned patients (intismeran plus pembrolizumab, n = 107; pembrolizumab, n = 50), the median planned follow-up at data cutoff (December 15, 2025) was 60.3 (range, 50.5-76.4) months. Intismeran plus pembrolizumab continued to prolong RFS (hazard ratio [HR], 0.510 [95% CI, 0.294 to 0.887) and DMFS (HR, 0.411 [95% CI, 0.200 to 0.843]), with a favorable trend in overall survival (HR, 0.471 [95% CI, 0.165 to 1.345]) versus pembrolizumab. Safety profile continued to be manageable, with no new safety signals. Intismeran plus pembrolizumab was associated with increased T-cell receptor clonality and novel clonotypes versus pembrolizumab; greater novel clone expansion was observed in patients without versus with recurrence in the combination arm. After a 5-year follow-up, intismeran plus pembrolizumab demonstrated sustained, durable treatment benefits versus pembrolizumab alone in resected high-risk melanoma.

Humans↗

PubMed2026

Integrated salivary proteomic and metabolomic analyses reveal molecular characterization and novel biomarker panels of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterized by chronic inflammation, oxidative stress, and metabolic dysregulation. The lack of convenient and easily-accessible non-invasive diagnostic approaches remains a major clinical challenge. This study applied an integrated saliva-based proteomic and untargeted metabolomic strategy to identify potential biomarkers for COPD classification. Comprehensive multi-omics analyses identified 225 differentially abundant proteins and 60 differentially abundant metabolites between patients with COPD and healthy controls, including 24 biologically relevant endogenous metabolites. Functional enrichment analyses revealed pronounced dysregulation of mitochondrial energy metabolism, redox homeostasis, lipid remodeling, and inflammatory-related pathways in COPD. By integrating salivary proteomic and metabolomic biomarkers, a stepwise feature selection combined with LASSO logistic regression was used to construct diagnostic models, yielding an optimized biomarker panel consisting of 11 proteins and 2 endogenous metabolites. This integrated model achieved excellent diagnostic performance, with an area under the ROC curve of 0.96. Collectively, these findings demonstrate that integrated salivary proteomic and metabolomic profiling provides a robust, non-invasive approach for COPD classification and offers a promising foundation for the development of biosensor-based diagnostic platforms and early disease detection. SIGNIFICANCE: Chronic obstructive pulmonary disease (COPD) remains a major global health burden. Current diagnostic approaches rely largely on spirometry and clinical assessment, which are limited in sensitivity for early-stage disease and unsuitable for large-scale screening. This study employs an integrated saliva-based proteomic and metabolomic strategy to identify non-invasive biomarkers for COPD classification. Our findings reveal coordinated dysregulation of mitochondrial energy metabolism, redox homeostasis, and lipid remodeling in COPD, highlighting the interconnected roles of metabolic reprogramming, oxidative stress, and inflammation in disease pathophysiology. Notably, a robust diagnostic panel comprising 11 proteins and 2 endogenous metabolites was established, achieving excellent classification performance (AUC of 0.96). To our knowledge, the integrated application of salivary proteomics and metabolomics for COPD diagnosis remains largely unexplored, underscoring the significance and translational potential of our findings.

Humans↗

PubMed2026

Patient and Public Involvement and Engagement in Pediatric Health Research: A Systematic Review.

BACKGROUND: Patient and public involvement and engagement (PPIE) can increase the relevance and efficiency of research projects. An overview of PPIE approaches and implementation in pediatric research studies is needed to facilitate learning from others' experiences. OBJECTIVE: We aimed to systematically review practices in PPIE across all pediatric health research disciplines regarding characteristics and recruitment of PPIE participants, timepoints and methods used for PPIE, levels of involvement, benefits and barriers of PPIE. SEARCH STRATEGY: We searched Pubmed, EMBASE, Cochrane and PsycInfo using a comprehensive set of terms based on the concepts 'Patient and Public Involvement,' 'Health Research' and 'Pediatrics.' INCLUSION CRITERIA: We included original research articles describing PPIE implementation in pediatric health research published in English or German between 01/2003-10/2024. DATA EXTRACTION AND SYNTHESIS: Data was extracted using predefined categories and synthesized by narrative summary and thematic synthesis. PPIE reporting quality was assessed using the GRIPP2 short form checklist. MAIN RESULTS: Out of 1910 references, we included 37 original research articles, representing 35 studies. PPIE participants were mostly children, adolescents or caregivers involved in all research stages, especially in study design (89%) and recruitment (51%). Key positive impacts of PPIE on research included enhanced recruitment and retention rates and personal benefits for PPIE participants. Barriers to PPIE were financial and time resources required and challenges in recruiting representative PPIE participants. The level of involvement and PPIE reporting quality varied highly between studies. DISCUSSION: Common benefits and barriers of PPIE exist across pediatric research disciplines. Reporting quality varied highly between studies. CONCLUSIONS: PPIE is valuable in pediatric health research. Adherence to guidelines for conducting and reporting PPIE is important to enhance mutual learning. PATIENT OR PUBLIC CONTRIBUTION: PPIE input contributed to the understandability of the lay summary. The findings of this review, together with parent and public input, will inform guidelines for future PPIE activities at the authors' institutions.

Humans↗

PubMed2026

Histopathologic, Genomic, and Clinical Characteristics of Primary Cutaneous Melanocytic Tumors With Concomitant NRAS Q61 and IDH1 R132C Mutations.

Cutaneous melanocytic tumors with concomitant NRAS Q61 and IDH1 R132C mutations have been described as intermediate-grade melanocytomas with characteristic biphasic morphology, but the malignant end of this genotype-defined spectrum remains poorly characterized. We assessed histopathologic, immunohistochemical, molecular, and clinical features of 16 primary cutaneous melanocytic tumors harboring both mutations. Following integrated review, 7 tumors were classified as melanocytoma and 9 as melanoma. Melanocytomas showed reproducible biphasic architecture with congenital nevus-like features, a biphasic HMB-45 pattern, low Ki-67, PRAME negativity, retained p16, and minimal copy number variations (CNVs). Melanomas retained partial morphologic overlap in a subset but were distinguished by higher-grade cytology, immunohistochemical features supportive of malignancy, and progression-associated genomic alterations, including TERT promoter mutation (9/9), 9p21/CDKN2A loss (4/7), and higher CNV burden. NRAS and IDH1 variant allele frequencies were strongly concordant (r = 0.83, P < 0.001), supporting their presence in the same dominant clone. Clinically, two patients presented with stage IIIB disease, but no distant metastasis or melanoma-related death occurred during a median melanoma follow-up of 3.9 years (IQR, 2.5-5.1). In exploratory analyses, moderate-to-severe atypia (RR, 6.2; 95% CI, 1.0-38.8; P = .009), Ki-67 ≥10% (RR, 4.4; 95% CI, 1.1-18.4; P = .003), lymphocytic infiltrate (RR, 2.4; 95% CI, 1.1-5.3; P = .03), absence of the typical biphasic pattern (RR, 2.4; 95% CI, 1.1-5.3; P = .03), and complete p16 loss (RR, 2.4; 95% CI, 1.1-5.3; P = .03) were associated with molecular or clinical progression to melanoma, defined as the presence of at least one of the following: TERT promoter mutation, pathogenic CDKN2A mutation, 9p21/CDKN2A loss, ≥3 genome-wide segmental CNVs, or any metastasis. These findings support the existence of NRAS/IDH1 co-mutated melanoma as the malignant counterpart of NRAS/IDH1-mutated melanocytoma within a single genotype-defined spectrum.

IDH1 mutations↗

PubMed2026

The clinical value of adding immune checkpoint inhibitors to radiotherapy for cancer: a systematic review and meta-analysis.

BACKGROUND: While several randomized clinical trials (RCTs) have explored the addition of immune checkpoint inhibitor (ICI) treatment for patients undergoing radiotherapy, studies systematically assessing the clinical value of such interventions are lacking. METHODS: PubMed, Embase, and Cochrane Library databases were searched for relevant RCTs of cancers that received ICIs plus radiotherapy or radiotherapy. Eligible studies were those published in English as of 14 April 2024. Two independent reviewers screened the included studies and extracted relevant data, then selected the random or fixed-effects model based on the I2 statistic. The main outcomes were hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS); Odds ratios (ORs) with 95% CIs for objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Stratified analysis was performed based on cancer type, ICI type, and the timing of ICI addition. The study was registered on PROSPERO (CRD42024551008). RESULTS: 15 RCTs with 7947 patients were included. Pooled HRs were 0.865 (95% CI, 0.730-1.000; I2 = 72.1%) for OS and 0.799 (0.677-0.922; I2 = 82.0%) for PFS in cancer patients. In cancer types, adding immunotherapy to radiotherapy significantly improved patients with non-small-cell lung cancer (OS: 0.544 [0.371-0.717]; PFS: 0.527 [0.438-0.617]) and cervical cancer (OS: 0.722 [0.578-0.867] and PFS: 0.754 [95%CI, 0.621-0.887]). Regarding the ICIs schedule, adjuvant ICI therapy with pooled HRs was 0.742 (0.649-0.834) for OS and 0.638 (0.579-0.697) for PFS. In addition, the pooled ORs for the incidence of grade 3 or higher treatment-related and immune-related adverse events were 1.227 (1.059-1.421; I2 = 71.9%) and 2.217 (1.743-2.821; I2 = 74.0%), respectively. CONCLUSION: Adding immunotherapy to radiotherapy can provide significant clinical benefits for patients with NSCLC and cervical cancer, and the addition of these ICIs in the adjuvant stage is supported.

Humans↗

PubMed2026

Adaptive proteomic remodeling and eNOS upregulation in luminal endothelium and perivascular adipose tissue of patent saphenous vein grafts after CABG.

OBJECTIVE: Long-term patency of saphenous vein grafts (SVGs) remains a significant challenge in coronary artery bypass grafting (CABG). The biological factors underlying successful human grafts are poorly understood. We aimed to characterize the structural and molecular features associated with successful graft function. METHODS: Patent and occluded SVG and internal thoracic artery (ITA) grafts were obtained from explanted hearts of CABG patients undergoing heart transplantation for end-stage heart failure not attributable to graft failure, along with freshly harvested ITA and SVG controls. Samples underwent histomorphological analysis, immunohistochemistry (IHC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomics. RESULTS: Patent ITA (ITA-P) showed minimal intimal hyperplasia with medial reinforcement, whereas patent SVGs (SVG-P) had organized, α-smooth muscle actin (αSMA)-positive myofibroblast-rich neointima. Endothelial nitric oxide synthase (eNOS) was markedly upregulated in patent grafts at two sites-the luminal endothelium and adventitial microvessels within perivascular adipose tissue (PVAT)-and lost at both sites in occluded SVG (SVG-O). Adventitial CD31-positive microvessels were significantly increased in patent grafts. Proteomically, ITA-P and SVG-P shared a largely common adaptive proteome enriched in translation, RNA processing, and extracellular matrix (ECM) organization, with shared upstream activation of NR4A3, EGFR, and STAT1, and conduit-specific signatures (IGF-1/RUNX2 in ITA-P; RETN/SRC/PTGES in SVG-P). PTGES was strongly expressed in the adventitia of SVG-P. CONCLUSIONS: Patent arterial and venous bypass grafts exhibited a shared adaptive phenotype characterized by dual-site upregulation of eNOS in both the luminal endothelium and the perivascular microvessels/PVAT. In SVG-P, PTGES was co-upregulated alongside eNOS, indicating a mechanistic link between the proteomic and IHC findings. These findings highlight the perivascular compartment as a site of adaptive, eNOS-associated changes in patent vein grafts.

Humans↗