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PubMed2026

Transient acoustic stimulation induces time-dependent synaptic remodeling and enhancement of auditory nerve output after threshold recovery.

BACKGROUND: Acoustic stress can alter cochlear function even in the absence of permanent threshold elevation; however, synaptic consequences of transient acoustic stimulation remain incompletely understood. OBJECTIVE: This study aimed to investigate whether transient acoustic stimulation induces changes in the auditory nerve output and cochlear ribbon synapse morphology following hearing threshold recovery. METHODS: Young adult CBA/CaJ mice were exposed to band-limited acoustic stimulation (45-2,000 Hz, 95 dB SPL, 2 h). Auditory brainstem responses (ABRs), hair cell and spiral ganglion neuron survival, and synaptic morphology were evaluated before exposure and up to 2 weeks post-exposure. RESULTS: ABR thresholds were transiently elevated immediately after exposure but largely recovered by 1 day post-exposure. In contrast, ABR wave I amplitudes significantly increased after threshold recovery across multiple test frequencies. Ribbon-associated puncta in both inner and outer hair cell regions exhibited biphasic temporal changes, with an initial decrease immediately after exposure followed by an increase at 1 day post-exposure. The ribbon-associated punctal area also increased after exposure and remained elevated at later post-exposure time points. No significant loss of hair cells or spiral ganglion neurons was observed. Exploratory genomic analysis suggested enrichment of pathways related to metabolic defense and cellular stress responses. CONCLUSIONS: Transient acoustic stimulation induces time-dependent synaptic remodeling and enhancement of peripheral auditory nerve output without overt cellular degeneration. These findings support a model in which early cochlear responses to acoustic perturbation include adaptive synaptic plasticity and gain regulation, extending current concepts of noise-induced cochlear change beyond irreversible synaptic loss.

Animals↗
PubMed2026

Transvalvular Flow Rate is Associated With Mortality Rate and Lifetime Loss in Aortic Valve Stenosis: A Meta-Analysis of Reconstructed Time-to-Event Data.

Low-flow states are associated with adverse outcomes in aortic stenosis (AS), but the prognostic value of transvalvular flow rate (TFR) has not been consistently established across studies. This study is a systematic review and meta-analysis of reconstructed time-to-event data was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses. PubMed/MEDLINE, EMBASE, and Cochrane Library were searched for studies (published by November 14, 2025) comparing low versus normal TFR in AS. Data were collected from Kaplan-Meier curves. The primary endpoint was all-cause mortality. Survival was assessed using pooled Kaplan-Meier curves, Cox regression, flexible parametric survival models, and restricted mean survival time (RMST) analysis. A total of 9 studies including 6,494 patients were analyzed; 2,575 (39.7%) had low TFR. At 8 years of follow-up, estimated survival was 34.1% (95% confidence interval [CI] 24.7% to 47%) in the low-TFR group and 63% (95% CI 58.9% to 67.4%) in the normal-TFR group. Low TFR was associated with higher all-cause mortality (hazard ratio 1.59, 95% CI 1.45 to 1.74, p < 0.001). We observed a progressively greater hazard over time, with the hazard ratio approaching 1.9 by 8 years. At 8 years, RMST in the normal-TFR group was 7.37 years (95% CI 7.21 to 7.53 years) versus 5.07 years (95% CI 4.91 to 5.23 years) in the low-TFR group, representing a lifetime loss of 2.3 years in the low-TFR group (&#x394;RMST -2.30 years, 95% CI -2.53 to -2.07 years, p < 0.001). In patients with AS, low TFR is associated with significantly higher mortality and lifetime loss. These findings support TFR as a clinically meaningful marker for risk stratification in AS.

Aortic Valve Stenosis↗
PubMed2026

Rates, Timing, and Predictors of Retreatment Across Risk-Cohorts in Retinopathy of Prematurity: Intravitreal Bevacizumab Injection Versus Laser.

OBJECTIVE: To characterize rates, timing, and predictors of retinopathy of prematurity (ROP) retreatment among infants treated with primary laser or intravitreal bevacizumab injection. DESIGN: Retrospective consecutive, comparative clinical study. PARTICIPANTS: Infants who underwent initial treatment for treatment-warranted ROP (TW-ROP) with either intravitreal bevacizumab or laser photocoagulation between 2017 and 2023. METHODS: Patients were stratified into two treatment groups: primary laser group vs primary bevacizumab group. MAIN OUTCOME MEASURES: Retreatment within the first 3 months (0-90 days) was assessed and classified as early (&#x2264;30 days) or late (31-90 days). RESULTS: Two hundred and thirty eight eyes of 122 infants were treated for ROP; of those, 181 (76.1%) eyes of 93 (76.2%) patients were included. There were 116 (64.1%) eyes in the bevacizumab group, and 65 (35.9%) eyes in the laser group. Thirty-three (18.2%) eyes-all micro- or nano-premature (<27 weeks GA and/or <800 grams)-required retreatment for TW-ROP. Sixteen (8.8%) required early retreatment at a median postmenstrual age (PMA) of 40.4 weeks (IQR, 38.44-43.3). There were differences in the proportion of early retreated infants (21.5% for laser vs 1.7% for injection, P < .001). Seventeen (9.4%) eyes required late retreatment. The median PMA at late retreatment was 45.6 weeks (IQR, 43.7-47.4). Infants in the bevacizumab group had lower odds of retreatment within three months than those with laser (OR, 0.23; 95% CI, 0.06-0.82). Similarly, patients in the bevacizumab group had lower odds of requiring early retreatment compared to those with laser (OR, 0.08; 95% CI, 0.04-0.18). Within eyes with retreatment, infants in the bevacizumab group had a later PMA at retreatment than those in the laser group (B = 6.81; 95% CI: 4.68-8.93). AROP was associated with earlier PMA at retreatment (B = -7.72; 95% CI, -9.36 to -6.10). CONCLUSION: In this study, early retreatment was low (8.8%), with most eyes initially treated with laser (21.5%) rather than bevacizumab (1.7%). Aggressive ROP was associated with earlier retreatment, highlighting its role as a marker of more severe disease. Compared to laser, bevacizumab was associated with lower overall and early retreatment, and delayed need for additional intervention when necessary. All retreatments occurred in micro- or nano-premature infants, suggesting that medium-to-low risk infants may require less strict post-treatment monitoring.

Humans↗
PubMed2026

Time-varying hazard rates reveal patterns of progression in HR+/HER2- metastatic breast cancer: Towards risk-adapted monitoring.

BACKGROUND: optimal imaging intervals for patients with hormone receptor-positive/HER2-negative metastatic breast cancer (MBC) remains undefined. Aim of this study was to analyze the temporal patterns of disease progression to identify high risk subgroups that may benefit from intensified monitoring. METHODS: we analyzed 149 hormone receptor-positive/HER2-negative MBC patients prospectively enrolled in the MAGNETIC.1 trial (NCT05814224) and treated with first line endocrine therapy. Hazard rates (HR) for disease progression were determined according to clinico-pathological and liquid biopsy features. RESULTS: in the overall population, two distinct progression-risk peaks emerged at 2-3 months (32.9/1000 person-months) and at 24 months (28.0/1000). Higher risk of progression was observed in lobular carcinoma (61.1) [HR 61.12 per 1000 person month (pm)], progesterone receptor-negative status (HR 39.07), fulvestrant-based treatment (HR 46.88), liver metastases (HR 59.00), and presence of &#x2265; 3 metastatic sites (HR 40.10). CONCLUSIONS: Hazard distribution in hormone receptor-positive/HER2-negative MBC is biphasic and modulated by readily available clinical variables. High-risk subgroups may benefit from intensified radiologic and liquid-biopsy surveillance during the first three months and around two years after treatment start.

Breast cancer↗
PubMed2026

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↗
PubMed2026

Antagonistic regulation by mango MiSPL9a and MiSPL9b regulates flowering time, drought and salt stress in Arabidopsis.

SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors, which are unique to plants, contain a highly conserved SBP domain that regulates gene expression by binding to downstream targets. They play critical roles in various biological processes, especially in the regulation of flowering in plants. In this study, two SPL-like genes (MiSPL9a and MiSPL9b) were identified from mango genomic and transcriptomic data, and their sequence, expression and function were further analyzed. Sequence analysis revealed that MiSPL9a and MiSPL9b have open reading frames of 1173&#xa0;bp and 1158&#xa0;bp, respectively, with slight differences in the number of cis-regulatory elements within their promoter regions. Expression analysis under stress conditions revealed distinct patterns: MiSPL9a expression significantly differed under drought stress but did not significantly differ under salt stress, whereas MiSPL9b expression responded significantly to salt stress but changed minimally under drought stress. Phenotypic analysis of the transgenic Arabidopsis lines revealed that MiSPL9a overexpression delayed flowering, whereas MiSPL9b overexpression promoted early flowering. Under stress conditions, compared with wild-type plants, MiSPL9a-overexpressing plants presented increased drought tolerance but did not significantly differ. In contrast, MiSPL9b-overexpressing plants were sensitive to salt stress, with no notable phenotypic differences observed under drought conditions. Physiological assays revealed that under drought stress, MiSPL9a transgenic plants presented significantly reduced levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) and increased proline (Pro) content and superoxide dismutase (SOD) activity. Under salt stress, MiSPL9b transgenic plants presented opposite trends in terms of these physiological markers. In summary, both MiSPL9a and MiSPL9b are involved in the regulation of plant flowering time and stress responses, but their functions differ.

Arabidopsis↗
PubMed2026

Time Heals Some Wounds? Burnout but Not Secondary Traumatic Stress in Critical Care Nurses.

BACKGROUND: Burnout among new nurses has been widely documented. Less is known about how years of professional experience relate to distinct components of professional quality of life, including compassion satisfaction and secondary traumatic stress. Early-career nurses appear particularly vulnerable to occupational strain, warranting examination of how years of experience may influence perceptions of professional well-being. OBJECTIVE: To examine the relationship between years of nursing experience and professional quality of life among critical care nurses. METHODS: A quantitative, cross-sectional pilot study was conducted using the Professional Quality of Life scale. A convenience sample of 55 nurses were recruited and consented from a rural hospital in the western United States. Descriptive statistics and Pearson correlations were used to examine relationships between years of experience and scores on the instrument's subscales. RESULTS: Forty nurses provided complete survey responses. Years of nursing experience correlated positively with compassion satisfaction and negatively with burnout. No significant relationship was found between years of experience and secondary traumatic stress. CONCLUSIONS: Greater professional experience was associated with higher compassion satisfaction and lower burnout but not with secondary traumatic stress. These findings suggest that experience may buffer against cumulative occupational strain, whereas trauma-related stress responses may persist across career stages. Structured mentoring and transition support may help to mitigate burnout among early-career nurses, and trauma-informed leadership approaches may warrant consideration in high-acuity environments.

Humans↗
PubMed2025

Application of Perioperative Real-Time Fluorescence Imaging to Achieve High-Quality Debridement: A Randomized Control Trial.

OBJECTIVE: To investigate the effectiveness of real-time fluorescence imaging (RTFI)-assisted debridement in managing chronic wounds compared with standard surgical debridement. APPROACH: This study was a patient-blinded, randomized clinical trial conducted from February 17, 2021, to July 30, 2021, on patients with chronic wounds. Patients were randomized to an RTFI group (M group) or conventional group (C group). The primary outcomes were as follows: percentage of residual bacterial area (preoperative and postoperative), number of debridements, high-quality debridement ratio, operation duration, and wound healing duration. RESULTS: A total of 100 patients were enrolled in both groups. No significant difference in the percentage of preoperative residual bacterial area or high-quality debridement ratio was seen. The M group underwent debridement an average of 2.6 times and had a significantly longer duration of operation (33.5 &#xb1; 12.7 min) than the C group (29.9 &#xb1; 10.4 min; p = 0.031). The postoperative residual bacterial area was significantly lower in the M than in the C group (6.83% &#xb1; 1.39% vs. 30.0% &#xb1; 12.37%, respectively; p < 0.001). The M group required significantly fewer wound healing days (49.2 &#xb1; 25.3 vs. 63.0 &#xb1; 27.9, p < 0.001). Secondary outcomes also demonstrated statistically significant differences in total hospitalized days (17.5 &#xb1; 9.3 vs. 21.5 &#xb1; 12.5, p < 0.01), days of antibiotic use (15.5 &#xb1; 8.7 vs. 18.7 &#xb1; 6.7, p < 0.01), and reinfection rates (4 of 100 vs. 22 of 100, p < 0.001). INNOVATION: RTFI can detect signals from normal skin components and bacterial metabolites. Therefore, interpretation of RTFI results should be correlated with the clinical condition. RTFI is associated with high-quality debridement. This technique can also be applied in targeted biopsy and in training young staff to mature debridement procedures. CONCLUSION: RTFI in debridement is associated with favorable clinical outcomes and may have a positive influence on chronic wound healing.

Humans↗
PubMed2026

Temporal redistribution of control reveals age-related differences in task switching at the level of preparation.

Task-switching studies often report minimal age-related differences in switch costs, leading to the conclusion that switching-related control processes are relatively preserved in aging. However, this conclusion is based on paradigms that confound preparatory and execution processes. This study examined whether age-related differences in semantic task-set reconfiguration may be underestimated due to this confound. In Experiment 1 (36 young and 30 older adults), participants performed an externally paced task-switching paradigm without control over preparation. In Experiment 2 (28 young and 28 older adults), a self-paced paradigm allowed participants to initiate stimulus onset, enabling measurement of preparation time. Across both experiments, reaction time (RT) and error rate (ER) showed reliable age effects but no interactions between age and condition, whereas switching-related condition effects varied across measures and experiments. The expression of switching-related costs differed across measures and task structures. Local switch costs were expressed in ER in Experiment 1 but in RT in Experiment 2. Global switch costs (all-switch vs. all-repeat) were observed in execution measures only in Experiment 1. In Experiment 2, preparation time showed reliable mixing, local, and global switching effects, with age-related amplification emerging specifically for global switching. These findings indicate that switching-related costs are redistributed across processing stages and behavioral measures. The results suggest that age-related modulation of semantic task-set reconfiguration may emerge more clearly during preparation than task execution, particularly under continuous switching demands. Preparation time is interpreted cautiously as reflecting participant-regulated preparatory processes rather than a pure measure of preparation efficiency.

Humans↗
PubMed2026

Candidate biomarkers for early Giardia duodenalis infection revealed by time-resolved secretome proteomics.

Giardia duodenalis is a zoonotic protozoan parasite that causes giardiasis in humans and other mammals. Early diagnosis remains challenging because current diagnostic methods, including microscopy and enzyme-linked immunosorbent assays (ELISAs), primarily detect established infections. Consequently, a critical diagnostic gap exists during the early stage of infection within the first 2-48&#xa0;h following exposure. To address this limitation, we characterized the proteins released by in vitro-cultured G. duodenalis trophozoites under serum-free conditions and evaluated their potential as early diagnostic biomarkers. Proteomic analysis of culture supernatants collected during early trophozoite incubation identified 31,773 peptides corresponding to 2504 quantifiable proteins. Temporal profiling showed distinct secretion patterns, including proteins that peaked during the early stage, progressively accumulated over time, or remained persistently abundant throughout the incubation period. Based on their secretion characteristics and predicted immunogenic properties, five candidate biomarkers were selected for further evaluation. Polyclonal antibodies raised against selected candidates successfully detected the corresponding proteins in serum-free culture supernatants, providing preliminary evidence for their potential utility as early-stage diagnostic targets. These findings identify stage-associated candidate proteins that may serve as a resource for future early giardiasis diagnostic development, provide a valuable resource for investigating host-parasite interactions, and establish a foundation for future diagnostic assay development. However, further validation in clinical and biological samples is required to confirm their diagnostic applicability. SIGNIFICANCE: Giardiasis, caused by Giardia duodenalis, is a major diarrheal disease worldwide. Although enzyme-linked immunosorbent assays (ELISAs) provide rapid detection, their diagnostic utility is limited by the lack of biomarkers capable of identifying infection during its earliest stages, creating a critical gap in the detection of active infection within 2-48&#xa0;h following exposure. Using data-independent acquisition proteomics, this study provides a time-resolved characterization of proteins released by G. duodenalis trophozoites into serum-free culture supernatants. Our findings reveal temporal secretion dynamics of protein secretion and identify candidate biomarkers with potential utility for the development of early-stage diagnostic assays pending rigorous biological and clinical validation. In addition, this proteomic resource provides a foundation for investigating host-parasite interactions and may facilitate the development of future point-of-care diagnostic strategies.

Giardiasis↗
PubMed2026

Longitudinal associations between family factors and the neurodevelopmental and psychosocial outcomes of children with congenital heart disease: A systematic review.

Family factors have been gaining increased attention in understanding adverse neurodevelopmental and psychosocial outcomes for children with congenital heart disease (CHD). To clarify relevance, we undertook a systematic review of only longitudinal studies which assessed such associations. Comparisons with the contribution of disease/surgical factors were also made where included studies considered such. We included longitudinal studies which assessed dynamic family factors (e.g. parent mental health, attachment, family functioning) and later child outcomes. Searches were conducted across CINAHL, Medline-Pubmed, PsychInfo and SCOPUS Web of Science. The NIH Quality Assessment Tool was used to evaluate study quality and risk of bias. Eighteen studies, utilizing data from 11 study samples and 2109 participants, met inclusion criteria. These studies included samples from infancy, with follow-up periods stretching into young adulthood, and with various degrees of CHD severity. The quality of studies was "good" to "fair", with key limitations of attrition and limited sociocultural diversity in samples. Findings suggested that family factors predicted later child psychosocial outcomes and more consistently than severity of disease indicators. This contrasted with a much smaller number of studies examining family factors and child neurodevelopmental outcomes, where no reliable conclusions could be reached. Findings highlight the importance of screening and family focused interventions for this population.

Child↗
PubMed2026

Association between seminal and serum iron parameters and male infertility: a systematic review and meta-analysis.

BACKGROUND: Iron is an essential trace element for normal spermatogenesis, yet excessive iron accumulation may impair male fertility. Preliminary studies imply a link between elevated iron levels and male infertility, but evidence remains limited without systematic quantitative synthesis. This metaanalysis assessed the association between iron concentrations and male infertility. METHODS: We systematically searched PubMed, CBM, CNKI and Cochrane Library. RevMan, Stata and R were used for data analysis. Randomeffects models pooled effect sizes, with forest and funnel plots generated to evaluate seminal and serum iron levels in male infertility. RESULTS: After screening studies published up to April 2025, a total of ten eligible articles involving 985 participants were finally included in this meta-analysis. Pooled results revealed that seminal and serum iron concentrations were notably higher in infertile males compared with fertile controls. Specifically, infertile men presented higher seminal iron levels (SMD&#x2009;=&#x2009;0.44, 95% CI: 0.12-0.76, P&#x2009;<&#x2009;0.05), as well as elevated serum iron levels (SMD&#x2009;=&#x2009;3.77, 95% CI: 1.68-5.87, P&#x2009;<&#x2009;0.05). The present results suggest that increased seminal and serum iron concentrations may be potentially correlated with male infertility risk.

Humans↗
PubMed2026

A Multi-omics Regulated Cell Death Framework Defines Immune Phenotypes and Guides Precision Therapy in Colorectal Cancer.

Colorectal cancer (CRC) is molecularly and immunologically heterogeneous, contributing to variable treatment response. Because regulated cell death (RCD) intersects with tumor metabolism, immune regulation, and therapeutic susceptibility, we built an RCD-centered framework for CRC stratification. Multi-cohort transcriptomic data were used to infer RCD subtypes with non-negative matrix factorization (NMF) and non-negative least squares (NNLS). Genomic, bulk RNA-seq, single-cell RNA-seq, and spatial transcriptomic datasets were integrated to characterize subtype-associated biology. Machine-learning models were developed for immunotherapy response and survival-risk estimation. Candidate compounds were screened by GDSC2-based drug-sensitivity modeling and molecular docking, and FSTL3 was functionally assessed in vitro. The framework separated CRC samples into two RCD-related phenotypes resembling immune-hot and immune-cold states. RCD1 showed immune activation and higher mutational burden, whereas RCD2 showed immune-suppressed features, intratumoral heterogeneity, and aggressive biology. RCD-associated signatures showed potential for predicting immunotherapy response and survival risk. Dasatinib was prioritized for immune-cold, high-risk tumors, with preliminary evidence supporting its activity in CRC cells, while functional assays suggested a role for FSTL3 in growth, invasion, epithelial-mesenchymal transition, and apoptosis regulation. These findings suggest that RCD-based multi-omics analysis may refine CRC stratification and help generate therapeutic hypotheses.

Colorectal cancer↗
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&#x2009;=&#x2009;2.381&#xa0;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&#xa0;mm (95% CI, 4.02-6.86&#xa0;mm; p&#x2009;=&#x2009;2.00e-11) and AE by 8.47 degrees (95% CI, 6.21-10.72 degrees; p&#x2009;=&#x2009;5.17e-11). Impressions of the system were generally favorable using a 5-point Likert survey and task duration (p&#x2009;=&#x2009;0.26) or cognitive workload via the NASA-Task Load Index (p&#x2009;=&#x2009;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

Methods for defining equity-stratifying variables: a systematic review of validation studies.

BACKGROUND AND OBJECTIVE: Disease burden is often disproportionally higher among those who are socially disadvantaged by factors defined in the PROGRESS-Plus framework (ie, Place of residence, Race/ethnicity/culture/language, Occupation, Gender/sex, Religion, Education, Socioeconomic status, and Social capital, with "Plus" covering features like age and disability). The accuracy and applicability of case definitions to identify these variables from administrative and clinical health data are unknown. We conducted a systematic review to explore how equity-stratifying variables, as categorized by the PROGRESS-Plus framework, have been defined and validated in epidemiologic studies using administrative health, population-level, or electronic health record (EHR) data. METHODS: Medline, EMBASE, CINAHL, Web of Science, and Google Scholar were searched from the inception of the databases to 2024 for validation studies of equity-stratifying variables in adults using administrative health datasets, health registries, or EHR data. Titles and abstracts, followed by relevant full-text articles, were screened in duplicate by two reviewers for eligibility. The data sources utilized, algorithms employed, and their associated performance measures were extracted and synthesized from included studies. Given substantial heterogeneity in study design, equity-stratifying variable definition, and performance metrics, meta-analysis was not possible. RESULTS: Of the 9099 unique citations screened, 188 full texts were reviewed and 116 were included in this review. Most studies were published between 2019 and 2024 (n = 64, 55%) and were validation studies of race/ethnicity definitions that used race/ethnicity codes or surname list algorithms (n = 66, 57%). No studies examined religion. Regarding the reported performance measure estimates, the race/ethnicity/culture/language equity-stratifying variables category had the largest variability across sensitivity, positive predictive value (PPV), and Cohen's Kappa. Occupation validation studies had the lowest variation in sensitivity and PPV. CONCLUSION: Despite an increasing number of publications reporting on the validation of equity-stratifying variables relevant to the PROGRESS-Plus framework, performance measures varied widely across studies. The significant heterogeneity in equity-stratifying variable definitions and methods used to validate them support the need for further rigorous validation of equity-stratifying variables in administrative and clinical health data. PLAIN LANGUAGE SUMMARY: Disease burden is often higher in people who experience financial hardships, lower level of education, discrimination due to race/ethnicity, and unstable housing. These social factors can be considered health equity factors and are important for understanding health inequalities. Health researchers often use large datasets, such as hospital or electronic health records (EHRs), to study these health equity factors. However, it is not clear how accurately these data sources capture information about people's social circumstances and how these factors are defined. In this study, we reviewed existing research to understand how health equity factors have been defined across health data sources and how accurate they are at measuring aspects of health equity and social disadvantage. Of the more than 9000 studies we identified, we included 116 that met our criteria for this systematic review. Most included studies focused on identifying race and ethnicity, often using codes or surname-based methods. We found that the accuracy of these methods varied widely across studies, meaning results may not always be reliable or comparable. Overall, our findings show that there are inconsistencies in how social factors are defined and measured in health data. This makes it difficult to fully understand and address health inequalities using routinely collected health data. More work is needed to develop and validate better quality and more consistent methods for capturing these important social factors.

Humans↗
PubMed2026

Bergamottin, a bioactive component of bergamot: dual inhibition of Japanese encephalitis virus internalization and genome replication.

Japanese encephalitis virus (JEV) is associated with high mortality and severe neurological sequelae, and existing prevention and control strategies remain insufficient. Therefore, the development of novel antiviral agents is of critical public health importance. This study systematically evaluated the antiviral activity and underlying mechanism of bergamottin, a natural product. Bergamottin exhibited significant dose-dependent inhibitory effects against JEV in multiple cell lines, including BHK-21, HuH-7, and Vero cells, demonstrating potent antiviral efficacy. Mechanistic investigations revealed that bergamottin primarily targeted the internalization and replication stages of the JEV life cycle, thereby effectively suppressing viral proliferation. Additionally, adaptive mutation screening indicated that the D389G mutation in envelope protein E confers drug resistance by potentially changing E protein conformation or reducing endocytic efficiency. In vivo experiment, bergamottin significantly reduced viral loads in mouse brain tissue and effectively improved the survival rate of infected mice. Our findings indicated that bergamottin exerted antiviral activity by dual targeting of key steps in the viral life cycle, making it a highly promising candidate for anti-JEV therapy. Further exploration of the antiviral properties of bergamottin is expected to facilitate its clinical development as a treatment for JEV infection.

Animals↗
PubMed2026

Engineering bubble structures as Cas12a activators for highly sensitive monitoring of WRN helicase function.

The Werner syndrome helicase (WRN) is a critical synthetic lethal target in microsatellite instability cancers, essential for resolving complex genomic structures like replication bubbles and R-loops. However, strategies to simultaneously discriminate WRN activity on DNA versus DNA-RNA substrates in living cells are lacking. Here, we developed a structure-specific CRISPR/Cas12a biosensing strategy to visualize WRN functional activity by engineering bubble-structure probes. These probes were rationally designed to structurally mimic DNA replication bubbles and R-loop associated DNA-RNA hybrids. Upon specific unwinding by WRN, the probes release a sequestered activator strand that triggers Cas12a trans-cleavage, effectively converting the unwinding event into an amplified fluorescent signal. This assay achieves low picomolar sensitivity (LODs: 5.6-6.0 pM) and exceptional selectivity against homologous RecQ helicases. Uniquely, this strategy enables the parallel quantification of WRN activity on both substrate types, providing insights into distinct WRN-mediated pathways for resolving genomic stress. We further demonstrated the strategy's utility by visualizing endogenous WRN dynamics in living cells and profiling the efficacy of small-molecule inhibitors. This work offers a powerful molecular toolkit for dissecting WRN biology and facilitating high-throughput drug screening in targeted cancer therapy.

Werner Syndrome Helicase↗