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PubMed2026

Multicancer Detection Tests for Population-Wide Screening of Asymptomatic Individuals: A Systematic Review.

PURPOSE: Multicancer detection (MCD) tests aim to detect different cancer types using a single test. However, evidence on their potential for screening asymptomatic populations remains limited. We consolidated evidence from prospective cohort studies evaluating blood-based MCD tests in primarily asymptomatic adults to contextualize upcoming randomized controlled trial results. MATERIALS AND METHODS: We updated and extended a prior review (to September 2023), conducting comprehensive Medline/Embase searches to February 1, 2026. Key outcomes included cancers detected and not detected by MCD tests, false-positive MCD tests, and diagnostic investigation pathways. Risk of bias (RoB) was assessed using a modified Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS: From 2,723 screened records (244 previously shortlisted to 2023, 2,479 records for 2023-2026), we included 18 articles (12 studies, nine MCD tests); of these, 11 articles had not appeared in prior reviews. Cancer detection rates varied widely between studies, for example, new MCD-test-detected invasive cancers diagnosed ≤12 months post-test ranging from 18.8 (95% CI, 11.0 to 30.1) to 43.8 (95% CI, 29.4 to 62.8) per 10,000 tested, with MCD-test-detected invasive stage I to II cancers ranging from 9.0 (95% CI, 4.2 to 17.2) to 21.0 (95% CI, 11.6 to 35.5) per 10,000 tested. False-positives exceeded MCD-test-detected cancers (eg, approximately 1.6-fold in PATHFINDER, 1.5-fold K-DETEK, 4.2-fold DETECT-A, 8.1-fold SeekInCare studies). Diagnostic investigation pathways were prespecified/suggested in four of eight interventional studies. Where reported, the median time to diagnostic resolution varied from <0.1 months to 4 months for MCD-test-detected cancers, with substantially higher 75th percentiles (3.1-7 months), and similar patterns were observed for false-positive MCD tests. No study was judged to have overall low RoB. CONCLUSION: Substantial heterogeneity in cancer yield metrics likely reflects differences in MCD technologies, diagnostic pathways, follow-up duration, and background standard-of-care screening. Long-term follow-up, randomized trials, fully-paired test comparisons, and implementation research are essential to determine the potential of MCD tests for population screening.

Journal Article↗

PubMed2026

Mitochondrial genetic effects mediate the response to stress through development, but not adult metabolic rate in Drosophila.

Energy expenditure is fundamental to physiology, behaviour, ecology, and life history, yet the mechanisms that regulate metabolic rate remain poorly understood. At the cellular level, incompatibilities between the maternally inherited mitochondrial genome and the nuclear genome can impair energy production, signalling and gene expression, with potential to disrupt a wide range of physiological processes. However, how these often-subtle genomic mismatches influence whole-organism traits such as metabolic rate, activity, and fitness remains unclear. Here, we generated mitonuclear-mismatched fly lines to test how early-life dietary and metabolic stress affect larval and adult physiology. Our results revealed sex and line-specific physiological effects, with larval development, survival and female fertility strongly contingent on the haplotypes and treatment, while adult resting metabolic rate and activity were not influenced by mitochondrial haplotype, nor by developmental stress.

Drosophila melanogaster↗

PubMed2026

Efficacy and Safety of Celecoxib Combined With Jintiange Capsules for the Treatment of Knee Osteoarthritis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND Knee osteoarthritis (KOA) poses a substantial global health burden, and conventional nonsteroidal anti-inflammatory drug (NSAID) therapy with celecoxib is hindered by adverse effects. This study evaluated the efficacy and safety of combining celecoxib with Jintiange capsules, a synthetic tiger bone formulation used in traditional Chinese medicine (TCM), to manage symptomatic KOA. MATERIAL AND METHODS This 12-week, randomized, double-blind, placebo-controlled trial enrolled 120 patients with KOA (age 40 years; visual analog scale [VAS] score 4-7). Participants received celecoxib (200 mg/day tapered to 100 mg/day) combined with either Jintiange capsules (3.6 g/day) or placebo. The primary outcome was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score. Secondary outcomes included WOMAC subscale scores (pain, function, and stiffness), VAS scores, and adverse drug reaction reports. RESULTS The experimental group demonstrated a 23.5-point (37.8%) reduction in WOMAC total score from baseline (P<0.001); the control group showed a 13.2-point (21.6%) reduction (P<0.001). The experimental group achieved 51.6% improvement in the WOMAC pain subscale (P<0.001), whereas the control group showed 33.3% improvement (P<0.001). Relative to the control group, the experimental group demonstrated a greater reduction in VAS score (P<0.001). Combined TCM-NSAID therapy produced significantly greater pain relief and functional improvement than NSAID monotherapy. CONCLUSIONS Celecoxib combined with Jintiange capsules provided clinically meaningful improvements in pain relief and functional outcomes relative to celecoxib monotherapy in patients with KOA. These findings support integration of TCM with conventional pharmacotherapy for osteoarthritis management.

Humans↗

PubMed2026

Engineered Bacteriophages in Cancer Immunotherapy: Emerging Concepts and Potential Integration with CAR-T Cell Therapy.

Due to antigen heterogeneity, restricted immune cell trafficking and an immunosuppressive, nutrient-restricted tumour microenvironment, solid tumours remain resistant to modern immunotherapies. Engineered bacteriophages offer a modular framework to overcome these obstacles: programmable virus-like particles with scalable production. Through genome engineering, capsid decoration with mammalian cell-targeting ligands, or hybrid AAV/phage systems, engineered bacteriophages can display tumour-associated antigens, enhance receptor-mediated uptake and deliver therapeutic payloads such as cytokines, chemokines and suicide genes without naturally infecting mammalian cells. These features support their use as vaccine platforms, immunological adjuvants and targeted gene-delivery vehicles. These may enable more precise, tumour-localized therapeutic intervention. Phages can engage innate immune pathways, including TLR9, TLR3/7/8, cGAS-STING and AIM2, promoting dendritic cell maturation and inflammatory mediators that may convert immunologically "cold" tumours into inflamed microenvironments. Their multivalent antigen display enhances B- and T-cell priming, while cDC1-mediated cross-presentation supports cytotoxic CD8+ T-cell responses and immunological memory. In CAR-T therapy, engineered phages may improve tumour homing through chemokine modulation, support persistence through local cytokine delivery, reduce antigen escape by presenting multiple tumour epitopes, and limit T-cell exhaustion through dominant-negative receptor strategies or local checkpoint blockade. This review summarizes engineering approaches, delivery systems, manufacturing, biodistribution, dosing, and safety issues, including immunogenicity, pre-existing anti-phage antibodies and horizontal gene transfer. It also distinguishes therapeutic engineered phage particles from phage display technologies used for molecular discovery. Despite encouraging results integrating modified bacteriophages with CAR-T cell therapy, the evidence remains mostly preclinical, indicating both substantial translational prospects and crucial obstacles for future clinical development.

CAR-T cell therapy↗

PubMed2026

Digital and computational morphology in hematology: current platforms, clinical evidence, and future requirements.

INTRODUCTION: Morphologic examination of peripheral blood and bone marrow remains central to the diagnosis and classification of hematologic disorders. Conventional optical microscopy, however, is labor-intensive, dependent on operator expertise, and affected by interobserver variability. Digital morphology has developed from automated image acquisition and cell pre-classification into a broader field that includes whole-slide imaging, remote review, quantitative morphometry, and artificial intelligence-based analysis. CONTENT: This review examines current applications of digital morphology in peripheral blood, bone marrow aspirates, malaria detection, and body-fluid analysis. Commercial platforms are evaluated with particular attention to the distinction between raw automated pre-classification, expert digital post-classification, and comparison with independent optical microscopy. Digital systems generally perform well for common mature leukocyte populations but remain less reliable for rare or diagnostically critical cells, including blasts, abnormal lymphoid cells, plasma cells, and intermediate maturation stages. Research systems increasingly extend analysis from individual-cell classification to whole-slide, specimen-level, and patient-level assessment. SUMMARY: Digital morphology can improve standardization, image traceability, remote consultation, education, proficiency testing, quality assurance, and selected aspects of laboratory workflow. Its clinical value depends on appropriate validation, transparent reporting of reference methods, recognition of algorithm-specific failure modes, and clearly defined criteria for expert review and conventional microscopy. Human expertise remains essential not only for validating results but also for adapting cell taxonomies and interpretive rules to evolving classifications of hematologic diseases. OUTLOOK: Future progress will require representative multicenter datasets, harmonized morphologic terminology, external validation, interoperability with laboratory information systems, and continuous monitoring after software or hardware updates. Integration of morphology with quantitative hematology, flow cytometry, cytogenetics, genomics, and clinical data may support more comprehensive computational diagnosis. Digital platforms may also broaden access to specialist expertise, training, and quality programs in resource-limited institutions and regions, provided that infrastructure, governance, and professional competency are adequately supported.

artificial intelligence↗

PubMed2026

A bi-directional Mendelian randomization study of sarcopenia-related traits and renal function.

The association between sarcopenia and renal function has been reported in observational studies; however, the directionality and potential causal nature of these associations remain uncertain. We assessed whether genetically predicted sarcopenia-related traits are associated with renal function and vice versa using bidirectional Mendelian randomization (MR). We conducted a bidirectional two-sample MR analysis using publicly available European-ancestry GWAS summary statistics for appendicular lean mass (ALM), hand-grip strength (left and right), and walking pace, and for renal function (cystatin C-based estimated glomerular filtration rate [eGFRcystatin C] and urinary albumin excretion [UAE]). Causal estimates were primarily obtained using inverse-variance weighted (IVW) models, complemented by sensitivity analyses (MR-Egger intercept, weighted median/mode, MR-PRESSO, Radial MR, and leave-one-out). In forward MR, genetically predicted walking pace was positively associated with eGFRcystatin C. Genetically predicted ALM and grip strength (right and left) were inversely associated with UAE. In reverse MR, genetically predicted UAE was inversely associated with ALM and right-hand grip strength. Estimates were broadly consistent across sensitivity analyses, and outlier-robust analyses (MR-PRESSO/Radial MR) yielded similar results. These findings provide genetic evidence consistent with bidirectional relationships between sarcopenia-related traits and renal function (particularly UAE), under standard MR assumptions. Given potential limitations (e.g., heterogeneity, pleiotropy, and possible sample overlap), the results should be interpreted cautiously and complemented by other lines of evidence.

Humans↗

PubMed2026

Conflict-dependent gain control in area VIP during visual-vestibular self-motion processing.

Visual and vestibular signals are continuously integrated to estimate self-motion, yet these sensory cues are often inconsistent under natural conditions. How cortical circuits regulate multisensory interactions under cue conflict while preserving stable heading representations remains poorly understood. Here, we recorded neurons in male macaque ventral intraparietal area (VIP) during passive movement stimulation while systematically varying visual-vestibular heading offsets. VIP neurons exhibited strong conflict-sensitive gain modulation: congruent cues enhanced neuronal responses, whereas increasing cue offsets progressively suppressed response gain. This effect was observed not only in multisensory neurons but also in neurons classified as predominantly visual or vestibular, indicating widespread cross-modal interactions across the population. In contrast, preferred-heading shifts remain modest, suggesting that cue conflict primarily modulated response gain rather than altering heading tuning. Despite substantial suppression at the single-neuron level under large cue offsets, population Fisher information was largely preserved, indicating robust heading discriminability. Further analyses revealed flexible sensory weighting in VIP, with visual and vestibular contributions shifting as cue conflict increased. Finally, a feedforward-gated normalization model substantially improved the characterization of VIP responses by allowing cue conflict to dynamically regulate the effective normalization pool, thereby capturing both multisensory enhancement at small visual-vestibular heading offset and suppression under large cue conflict. Together, these findings show that VIP exhibits conflict-dependent regulation of multisensory gain, preserving robust self-motion representations under sensory conflict.Significance statement Visual and vestibular cues are often misaligned in natural environments, creating a challenge for accurate self-motion perception. We demonstrate that neurons in the macaque ventral intraparietal area (VIP) dynamically adjust multisensory gain according to the degree of visual-vestibular conflict. As the visual-vestibular heading offset increases, neuronal responses are progressively enhanced or suppressed, while population coding of heading direction remains largely preserved. A conflict-sensitive normalization model accounts for these response dynamics and outperforms traditional multisensory integration models, suggesting that VIP implements adaptive gain-control computations to regulate interactions between visual and vestibular signals. These results identify a cortical mechanism that links sensory conflict detection to robust perceptual coding, advancing our understanding of multisensory processing in the brain.

Journal Article↗

PubMed2026

In vivo CRISPR screening links NFKB1 to endocrine resistance in ER+ breast cancer.

Resistance to endocrine therapy (ET) remains a major clinical challenge in the treatment of estrogen receptor-positive (ER+) breast cancer, underscoring the need for novel therapeutic targets. To identify genetic drivers of ET resistance, we conducted an in vivo genome-wide CRISPR-Cas9 screen in MCF7 cells implanted into ovariectomized nude mice under estrogen-deprived conditions. Despite the bottlenecks inherent to in vivo pooled screening, recurrent enrichment analysis identified NFKB1 as a candidate regulator of estrogen-independent tumor progression. Functional studies confirmed that NFKB1 deficiency enhanced tumorigenicity and conferred resistance to tamoxifen and fulvestrant both in vitro and in vivo. Mechanistically, transcriptomic and biochemical analyses revealed that NFKB1 deficiency activated canonical NF-κB signaling, leading to inflammatory gene induction and enhanced ER signaling. Furthermore, pharmacologic inhibition of NF-κB signaling restored ET sensitivity in NFKB1-deficient cells. Analysis of TCGA breast cancer datasets revealed reduced NFKB1 expression in luminal breast tumors, whereas expression of other NF-κB family members was largely unchanged. Further analysis showed that low NFKB1 expression was associated with poorer clinical outcomes in patients with ER+ breast cancer. Collectively, these findings identify NFKB1 as a negative regulator of NF-κB signaling and endocrine resistance in ER+ breast cancer and provide mechanistic evidence linking NF-κB activation to ligand-independent ER signaling. Our results support further investigation of NFKB1 as a candidate biomarker and of NF-κB pathway inhibition as a potential therapeutic strategy in endocrine therapy-resistant breast cancer. These findings also illustrate the utility of in vivo CRISPR screening for identifying candidate regulators of endocrine resistance in breast cancer.

ER+ breast cancer↗

PubMed2026

Targeted ORF8-N Sanger Sequencing as a SARS-CoV-2 Surveillance Contingency During Supply Shortages.

BACKGROUND: Global shortages of next-generation sequencing (NGS) reagents threatened SARS-CoV-2 genomic surveillance in low- and middle-income countries during the COVID-19 pandemic. METHODS: During the 2021 NGS reagent shortages, we implemented targeted ORF8-N Sanger sequencing for SARS-CoV-2 variant surveillance in Brazilian public health laboratories. RESULTS: In silico analysis of whole-genome sequencing (WGS)-derived SARS-CoV-2 genomes from the Federal District, Brazil, showed that the ORF8-N target discriminated the major 2021 lineages (Gamma and Delta) and enabled analysis of ˃300 samples despite constrained NGS access. CONCLUSIONS: Targeted ORF8-N Sanger sequencing was a useful temporary contingency during NGS reagent shortages but offered lower phylogenetic resolution than WGS.

SARS-CoV-2↗

PubMed2026

Proteomic characterization of Tityus championi venom and recombinant expression of its major neurotoxin.

BACKGROUND: Tityus championi is a species endemic to the southern Talamanca Mountain Range, along the border region between Costa Rica and Panama, and has been associated with severe clinical cases. Despite its medical relevance, the composition of its venom remains poorly studied. The present study aimed to characterize the proteomic composition of T. championi venom, identify its main toxin families, and recombinantly produce one of its most abundant and lethal toxins for potential use in antivenom development. METHODS: Venom composition was analyzed by tandem mass spectrometry (MS/MS), enabling the identification of venom proteins. Subsequently, one of its primary lethal toxins (Tcham27) was identified and recombinantly expressed. RESULTS: Proteomic analysis revealed that the most abundant family in the venom corresponded to metalloproteases, with 43 protein groups (17% of the total identifications), which are associated with processes such as hemorrhage, edema, inflammation, hypotension, and necrosis. CIIMET family toxins comprised 27 protein groups (11%). Among ion channel-acting toxins, 18 protein groups (7%) corresponded to sodium channel toxins and 14 (6%) to potassium channel toxins, homologous to components from geographically proximate species such as Tityus discrepans, Tityus cf. asthenes, and Tityus jaimei. Other relevant families included cysteine-rich secretory proteins (CRISPs; 6 proteins, 3%), serine proteases (5 proteins, 2%), and lectins (5 proteins, 2%). In addition, low-abundance components such as insulin-like growth factors, nucleotide pyrophosphatases, hyaluronidase, α-amylase, lipolysis-activated toxins, and chitinase were detected, contributing to the functional diversity of the venom. CONCLUSIONS: Proteomic characterization of T. championi venom demonstrates that metalloproteases constitute a major protein family alongside neurotoxins. Recombinant production of its most abundant toxic peptide, which is identical to toxins in the venom of geographically proximate Tityus species, provides a key tool for developing specific antivenoms.

Protein↗

PubMed2026

Integrated single-cell transcriptomics, Mendelian randomization, and machine learning identify CEBPZ as an immune-related biomarker in oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a chronic, immune-mediated oral mucosal disease with complex pathophysiology and potential for malignant transformation. Understanding its molecular basis is critical for the development of precise diagnostic and therapeutic strategies. OBJECTIVES: We aimed to identify key immune-related biomarkers and characterize cellular dynamics in OLP, with a particular focus on the role of CEBPZ in disease pathogenesis. MATERIAL AND METHODS: We analyzed single-cell RNA sequencing (scRNA-seq) data from OLP lamina propria samples (GSE211630) to identify disease-specific T-cell subpopulations using high-dimensional weighted gene co-expression network analysis (hdWGCNA) for oxidative stress-related gene modules.-data-based Mendelian randomization (SMR) integrated FinnGen genome-wide association study (GWAS; 342,499 Europeans) data with Genotype-Tissue Expression (GTEx) expression quantitative trait loci (eQTL) data to identify causal genes. Machine learning (ML) models (least absolute shrinkage and selection operator (LASSO) and convolutional neural network (CNN)) were developed using bulk RNA-seq datasets (GSE52130 and GSE38616) for diagnostic purposes. RESULTS: We identified OLP-specific T-cell populations (clusters 0, 3, 5, 7, 13, and 15) with enhanced migration inhibition factor (MIF) pathway signaling toward B cells and monocytes. Two oxidative stress-associated modules contained hub genes, including CEBPZ. Summary-data-based Mendelian randomization analysis identified 231 OLP-associated genes, with CEBPZ uniquely intersecting LASSO-selected markers (odds ratio (OR) = 1.057, 95% confidence interval (95% CI) = 1.013-1.102, p = 0.010). Machine learning models achieved area under the curve (AUC) values ranging from 0.653 to 0.745, with the CNN model reaching a validation accuracy of 0.735. CEBPZ showed elevated expression in OLP T cells and correlated with enhanced MIF-(CD74+CXCR4) signaling. CONCLUSIONS: This integrative approach identifies CEBPZ as a pivotal biomarker linking genetic susceptibility, oxidative stress, and immune dysregulation in OLP. Our diagnostic models offer promising tools for OLP management.

CEBPZ↗

PubMed2026

Webcam-Based Real-Time Visual Feedback During Baduanjin Practice in Older Adults: 6-Week Pilot Randomized Study.

BACKGROUND: Baduanjin qigong is a traditional mind-body exercise used to support balance and physical health in older adults. Age-related changes in proprioception may make accurate self-directed performance difficult without external guidance. OBJECTIVE: The aim of this study is to explore whether webcam-based real-time visual feedback delivered during supervised laboratory sessions was associated with differences in webcam-derived 2D pose discrepancy and movement consistency during Baduanjin practice in older adults. METHODS: A total of 31 older adults were enrolled, and 28 participants with complete analyzable records were included in this complete-case dataset (feedback group, n=14; nonfeedback group, n=14). All sessions were conducted face-to-face in a supervised motion-analysis laboratory. Weekly 2D pose-discrepancy values were analyzed using a linear mixed-effects model with fixed effects for group, categorical week, and the group-by-week interaction and a participant-specific random intercept. Joint- and movement-specific participant-level 6-week means were analyzed exploratorily using Welch independent-samples t tests. Holm correction was applied across 24 exploratory contrasts (6 week-specific, 8 joint-specific, and 10 movement-specific comparisons), and Hedges g and 95% CIs were reported. Participant-specific weekly slopes and within-participant variability were additionally examined to directly assess longitudinal error drift. RESULTS: The linear mixed-effects model showed no significant group-by-week interaction (Wald χ25=1.09; P=.96) and no significant overall week effect (Wald χ25=6.40; P=.27). Averaged across 6 weeks, the feedback group had an estimated mean 2D pose discrepancy 1.20° lower than the nonfeedback group (95% CI -2.38° to -0.02°; P=.046), although this marginal pilot finding was sensitive to an analytic approach. No week-specific contrast remained significant after Holm adjustment. Nominal right elbow, right shoulder, and right knee differences did not survive global Holm correction. Form 3 showed a lower mean discrepancy in the feedback group (mean difference -3.70°, 95% CI -5.86° to -1.54°; Hedges g=-1.30; unadjusted P=.002; Holm-adjusted P=.04). Direct analyses of participant-specific slopes and within-participant SDs did not support a significant between-group difference in longitudinal error drift. CONCLUSIONS: In this small exploratory pilot study conducted under supervised laboratory conditions, the 6-week trajectories did not differ significantly between groups. A marginally lower average 2D pose discrepancy was observed in the feedback group across the 6 weeks, but no individual week- or joint-specific comparison remained significant after multiplicity adjustment. Form 3 was the only exploratory contrast that remained significant after global Holm correction. Direct longitudinal analyses did not demonstrate prevention of error drift. Larger studies using validated reference measurements, prespecified outcomes, and adequately powered longitudinal designs are required.

Humans↗

PubMed2026

Health Literacy and Capecitabine Adherence in a Remote Monitoring Pilot Trial for Breast Cancer: Post Hoc Exploratory Analysis.

BACKGROUND: Oral anticancer therapy enables convenient, home-based cancer care but can introduce adherence challenges, particularly with complex dosing schedules. Capecitabine is commonly used in breast cancer, often as adjuvant therapy or in advanced disease, and typically requires twice-daily dosing on cyclical schedules, increasing the risk of missed or incorrect doses. Low health literacy may exacerbate these difficulties, and emerging remote monitoring tools may help close this gap. OBJECTIVE: In this post hoc exploratory analysis, we evaluated whether health literacy (1) was associated with capecitabine adherence and (2) modified a remote monitoring intervention's effectiveness. METHODS: We conducted post hoc analyses of a 2-arm pilot trial that randomized women with breast cancer treated with capecitabine to enhanced usual care (EUC) or remote patient monitoring (RPM). Adherence was captured with a smart pill bottle, Nomi by SMRxT, that recorded dose timing and quantity. Participants in the RPM group received messages for missed or incorrect doses and weekly symptom assessments. Incorrect or missed doses and severe symptoms triggered alerts to the oncologist. Health literacy was assessed at enrollment. To evaluate moderation, we used linear regression with an interaction term (health literacy × intervention arm) predicting adherence (proportion of days). Marginal effects quantified differences in adherence by study arm and health literacy. RESULTS: Among 28 participants (EUC, n=15 and RPM, n=13), 9 (32.1%) had lower health literacy, 16 (57.1%) identified as Black, 10 (35.7%) identified as White, and 15 (53.6%) had income below 200% of the federal poverty level. In the regression model, the health literacy × randomized group interaction did not reach statistical significance (-16.3 percentage points, 95% CI -35.5 to 2.9; P=.09). Predicted adherence among lower health literacy participants was 87.5% in the RPM group and 65.5% in the EUC group (difference: +22.1 percentage points, 95% CI 6.2-37.9; P=.008). Among participants with higher health literacy, adherence was 89.9% in the RPM group and 84.1% in the EUC group (difference: +5.7 percentage points, 95% CI -5.2 to 16.7; P=.29). Within the EUC group, predicted adherence was 18.6 percentage points lower among those with lower versus higher health literacy (95% CI -32.4 to -4.9; P=.01); within the RPM group, this difference was 2.3 percentage points lower among those with lower versus higher health literacy (95% CI -15.8 to 11.1; P=.73). CONCLUSIONS: In this post hoc exploratory analysis, the estimated difference in capecitabine adherence between the RPM and EUC groups was larger among participants with lower health literacy. Although the formal interaction test was not statistically significant, the magnitude and direction of the observed difference support further investigation of RPM as a potential approach to improve adherence among patients facing health literacy-related adherence barriers. Larger, prospectively powered studies are needed to confirm these findings and evaluate downstream clinical outcomes.

Humans↗

PubMed2026

Adverse Experiences in Brief Meditation Practices: Randomized Controlled Trial.

BACKGROUND: Meditation has become increasingly popular in recent decades. However, relatively little remains known about the prevalence of and risk factors for adverse experiences related to a single meditation practice. OBJECTIVE: The objective of our study was to examine adverse experiences associated with 3 brief, digitally delivered meditation practices (mindfulness, self-compassion, and gratitude) relative to using the internet as usual, as well as to investigate whether preintervention characteristics could predict such outcomes. METHODS: In a secondary analysis of a randomized controlled trial using samples that were representative of the US and UK adult populations with regard to ethnicity, sex, and age, we examined adverse experiences associated with 3 brief (ie, 5 or 10 minutes) meditation practices (ie, mindfulness, self-compassion, and gratitude) relative to using the internet as usual. We also investigated the potential of using preintervention characteristics to predict such outcomes. RESULTS: A total of 5049 participants completed all preintervention measures and were randomly assigned to meditation or control conditions. Across the sample, 4.1% (204/4925) of participants reported having a distressing experience during the intervention, and 7.1% (348/4908) of participants experienced an increase in negative affect from before to after the intervention. The results showed that participants who were randomized to a brief meditation intervention were no more likely to report a distressing experience than those who were randomized to use the internet as usual (odds ratio [OR] 1.05, 95% CI 0.76-1.47; P=.76). The results also showed that participants who were randomized to a brief meditation intervention were less likely to report clinically relevant increases in negative affect relative to using the internet as usual (OR 0.63, 95% CI 0.50-0.80; P<.001). Notably, participants in the 10-minute condition had a significantly higher likelihood of reporting a distressing experience than those in the 5-minute condition (OR 1.42, 95% CI 1.07-1.89; P=.02). Preintervention characteristics showed acceptable discrimination ability to predict a distressing experience (area under the curve=0.73) and slightly lower ability to predict increased negative affect (area under the curve=0.67). CONCLUSIONS: Taken together, we found that the brief, digitally delivered meditation practices tested in this study carry risks of adverse experiences that are comparable to or lower than those of typical activities on the internet; 10-minute condition was more likely to result in distressing experiences than 5-minute condition; and adverse responses to a brief meditation practice can, at least to a certain degree, be predicted using preintervention characteristics. TRIAL REGISTRATION: Open Science Framework 94HKS; https://osf.io/94hks/overview.

Humans↗

PubMed2026

Home-Based Cardiac Rehabilitation Using a Smart Ring and Telephone Counselling: A Randomized Controlled Trial.

BACKGROUND: Home-based cardiac rehabilitation (HB-CR) is a promising alternative to center-based cardiac rehabilitation as it can address several barriers impeding CR implementation because of its enhanced accessibility. However, to date, HB-CR has not garnered adequate attention due to a lack of communication between patients and medical staff. In this study, we aimed to investigate the effectiveness of HB-CR by monitoring the pulse rate (PR) using a smart ring equipped with photoplethysmography. METHODS: Patients with cardiovascular disease were educated on structured HB-CR methods following a symptom-limited cardiopulmonary exercise test (CPET), and were instructed to wear the device during the exercise session. The recorded PR was uploaded to a website via a smartphone and monitored by medical staff. Patients were randomly assigned to one of two groups: intervention or control group. The intervention group received weekly telephone counselling and was encouraged to maintain optimal levels of physical activity. In contrast, the control group only recorded their exercise data without additional interventions. After 3 months of training, the CPET was performed. RESULTS: Among the 64 randomized patients (32 in each group), an intention-to-treat analysis showed that peak oxygen consumption increased over time in both the groups, with a significantly greater improvement in the intervention group. The group-by-time interaction for peak oxygen consumption was statistically significant (estimated mean difference, 2.0 mL/kg/min; 95% confidence interval, 0.7-3.3; P = 0.004). CONCLUSION: HB-CR using a smart device was effective in improving oxygen consumption. However, appropriate monitoring and timely counselling by medical professionals are important for improved outcomes. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0005893.

Humans↗

PubMed2026

Clonal stochasticity in early NK cell response to mouse cytomegalovirus is generated by mature subsets of varying proliferative ability.

Natural killer (NK) cells are classically defined as innate immune cells, but experiments show that mouse cytomegalovirus (MCMV) infection in C57BL/6 mice can cause NK cells to undergo antigen-specific proliferation and memory formation, similar to adaptive CD8+ T cells. One shared behavior between CD8+ T cells and NK cells is clonal expansion, where a single stimulated cell proliferates rapidly to form a diverse population of cells. For example, clones derived from single cells are most abundant during expansion when they are primarily CD27- for NK cells and CD62L- for T cells, phenotypes derived from precursor CD27+ and CD62L + cells, respectively. Here we determined the mechanistic rules involving proliferation, cell death, and differentiation of endogenous and adoptively transferred NK cells in the expansion phase of the response to MCMV infection. We found that the interplay between cell proliferation and cell death of mature CD27- NK cells and a highly proliferative CD27-Ly6C- mature subtype and intrinsic stochastic fluctuations in these processes play key roles in regulating the heterogeneity and population of the NK cell subtypes. Furthermore, we estimate rates for maturation of endogenous NK cells in homeostasis and in MCMV infection and found that only NK cell growth rates, and not differentiation rates, are appreciably increased by MCMV. Taken together, these results quantify the differences between the kinetics of NK cell antigen-specific expansion from that of CD8+T cells and unique mechanisms that give rise to the observed heterogeneity in NK cell clones generated from single NK cells in the expansion phase.

Animals↗

PubMed2026

Dual Aberrant Splicing Caused by an Apparently Missense CHD7 Variant, c.5273A>G (p.Asp1758Gly), in CHARGE Syndrome.

CHARGE syndrome is a rare congenital disorder primarily attributed to heterozygous pathogenic variants of the CHD7 gene. Most pathogenic CHD7 variants are loss-of-function (LoF) variants, whereas the interpretation of missense variants remains challenging in the absence of functional evidence for their pathogenicity. We report a female infant presenting with clinical features characteristic of CHARGE syndrome. Targeted sequencing identified a heterozygous CHD7 variant (NM_017780.4:c.5273A>G), initially annotated as a missense substitution p.Asp1758Gly. This variant has been previously reported and registered with conflicting pathogenicity classifications; however, its transcript-level consequences remain unclear. Long-PCR-based RNA sequencing of total RNA from peripheral blood mononuclear cells revealed two aberrant splicing patterns associated with the variant: a predominant transcript carrying a 28-bp deletion due to cryptic donor splice-site activation, and a minor transcript with partial intron 24 retention. Both transcripts were predicted to result in premature termination codons. These findings demonstrate that c.5273A>G functions as a LoF variant through dual aberrant splicing rather than a simple missense substitution. This case underscores the importance of RNA-level splicing analysis for the accurate interpretation and classification of CHD7 missense variants.

CHD7↗

PubMed2026

Reproduction on the Rocks: Life History of a Freshwater Macrobioeroding Bivalve.

Macrobioerosion, the excavation and removal of consolidated mineral substrates by macrofauna, is well established in marine systems, where macrobioeroders drive carbonate cycling, sediment production and habitat formation. In freshwater ecosystems, however, it has been documented in only a small number of invertebrate taxa and remains a poorly resolved ecological process. Among these, the teredinid shipworm Lithoredo abatanica represents a remarkable departure from the wood-boring ecology of its family, having evolved to excavate and ingest limestone in fresh water. Despite this remarkable ecological transition, its reproductive biology and life history remain unknown. Here, we investigate the reproductive mode and life history strategy of this species using population size structure, in situ observations of siphonal morphology, and sperm morphometrics. We show that L. abatanica reaches exceptional dimensions, with measured body lengths exceeding 100 mm, one intact empty burrow exceeding 200 mm and in-water observations indicating burrows possibly exceeding 500 mm, establishing it as the largest known freshwater macrobioeroder. Its large size and dense aggregations indicate considerable capacity for local rock breakdown and habitat modification within the Abatan River system (Bohol, Philippines). Recently settled juveniles (< 10 mm) alongside reproductively mature individuals indicate ongoing recruitment. The morphology of the siphons and calcareous tube appears to preclude direct sperm transfer via pseudocopulation, while sperm morphometrics are consistent with external fertilisation. Together, these findings indicate that L. abatanica reproduces via broadcast spawning with external fertilisation and likely possesses a planktotrophic larval phase. This raises a fundamental question: how does a broadcast-spawning species with planktotrophic larvae maintain populations up to 15 km upstream in a flowing freshwater river subject to persistent downstream advection? By resolving the life history of the largest known freshwater macrobioeroder, this study provides critical insight into the persistence, dispersal and ecological role of a globally unique riverine ecosystem engineer.

broadcast spawning↗