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Photoplethysmography (PPG) is a non-invasive optical technique commonly used to measure heart rate and oxygen saturation, but its waveform contains additional physiological information that can be analyzed using artificial intelligence (AI). This narrative review summarizes the emerging applications of AI-based PPG in cardiovascular, respiratory, sleep, hemodynamic, pregnancy-related, and portal-hypertension assessment, with the aim of evaluating its potential beyond conventional monitoring and identifying barriers to clinical translation. The literature search was conducted using PubMed, Google Scholar, IEEE Xplore, ScienceDirect, and SpringerLink. Additional relevant studies were identified through screening the reference lists of included articles. Studies published between 2002 and 2026 were identified to capture the development of PPG from conventional monitoring to newer AI-based applications. Human studies were prioritized, while relevant computational, simulated, synthetic, ex vivo, and technical studies were also included. Studies unrelated to PPG, duplicates, and studies with limited relevance were excluded. A total of 96 references were included, covering AI approaches such as convolutional and deep neural networks, ensemble methods, transfer learning, U-Net, generative adversarial networks, and Transformer-based models. Overall, the reviewed evidence suggests that AI-based PPG may support blood pressure estimation, atrial fibrillation detection, sleep and respiratory monitoring, vascular aging assessment, pulmonary hypertension screening, preeclampsia assessment, volume-status and compensatory-reserve assessment, and exploratory assessment related to portal hypertension. However, clinical translation remains limited by motion artifacts, sensor and measurement-site variability, skin-pigmentation-related bias, physiological and environmental influences, heterogeneous methods, limited external validation, and inconsistent clinical and regulatory standards.

Transcranial magnetic stimulation can provide noninvasive measures of cortical excitability and plasticity, but relationships between these measures and clinically observable features of autism are not fully characterized. Nineteen autistic participants aged 15 to 40 years were included in the analysis of a left primary motor cortex continuous theta-burst stimulation (cTBS) biomarker protocol. Motor evoked potentials were measured at baseline and at seven assessments from 5 to 60 min after stimulation. Linear mixed-effects models evaluated whether clinical measures moderated the post-stimulation motor evoked potential log-response ratio over time. Aberrant Behavior Checklist (ABC) and Attenuated Behavior Questionnaire (ABQ) analyses were restricted to the same 15 participants with caregiver-informant assessments. Catatonia severity, social impairment, ABQ Motor Total, ABQ Total, and cognitive ability did not significantly moderate the post-stimulation response. ABC Inappropriate Speech was associated with progressively greater post-stimulation facilitation (standardized Time-by-Inappropriate Speech interaction: beta = +0.688, SE = 0.210, 95% CI +0.276 to +1.099; Holm-adjusted P = .008 across eight informant-rated models). Two individual speech-related items ("Talks excessively" and "Talks to self loudly") survived false-discovery-rate correction. An exploratory eight-item ABC phenotype showed a large descriptive in-sample association (beta = +0.904, SE = 0.200, P less than .001) and directionally positive held-out performance. However, full-pipeline permutation tests were nonsignificant for both Pearson (r = .357, two-sided empirical P = .360) and Spearman correlations (rho = .446, two-sided empirical P = .261). Caregiver-rated inappropriate speech may be associated with altered post-cTBS motor cortical facilitation in autism. The candidate phenotype remains hypothesis-generating and requires independent validation.

Age-related gastrointestinal dysfunction is common, but the mechanisms of aging-associated smooth muscle failure remain unclear. We show that aging in mice slows whole gut and colonic transit, increases regional stiffness, and reduces smooth muscle contractility. Inducible smooth muscle cell (SMC)– specific deletion of Piezo1 preserved youthful transit and force generation, whereas Piezo1 activation in young mice phenocopied aging-associated transit delay. Single-cell transcriptomics, RNA velocity, stiffness-controlled cell and tissue cultures, and pharmacologic studies revealed that Piezo1 couples increased stiffness to Ca 2+ –calcineurin–NFAT signaling, loss of contractile gene programs, leading to age- related contractile loss and contractile-to-synthetic SMC remodeling and gut wall stiffening. Human intestinal SMCs supported conservation of this pathway, and PIEZO1 gain-of-function carriers showed a trend toward delayed colonic transit. Thus, maladaptive SMC Piezo1 mechanotransduction is a targetable mechanism of aging-associated gut dysmotility. Aging alters organ structure, yet how these changes drive functional decline remains poorly defined. We show that progressive stiffening of the gut with age activates the mechanosensitive ion channel Piezo1 in smooth muscle cells, initiating a maladaptive response that impairs contractility and slows intestinal transit. On the other hand, deletion of smooth muscle Piezo1 prevents age-related gut dysmotility. These findings reveal that age-related physical shifts actively drive functional decline through mechanotransduction pathways. By identifying Piezo1 as a critical link between tissue mechanics and organ aging, this work provides a framework for understanding how mechanical cues contribute to age-related dysfunction in the gut and possibly other smooth muscle organs.

Importance Patients undergoing cardiac surgery with cardiopulmonary bypass often require platelet transfusions for bleeding. Platelets are routinely stored at room temperature (20-24 °C) for up to 5 to 7 days; however, cold storage (1-6 °C) may allow for increased storage duration without loss of hemostatic function. Objective To determine the maximum cold-storage duration, up to 21 days, for which cold-stored platelets (CSPs) are noninferior or superior in hemostatic efficacy to room-temperature platelets (RTPs) when transfused in actively bleeding patients undergoing cardiac surgery with cardiopulmonary bypass. Design, Setting, and Participants A phase 3, multicenter, randomized, partially blinded, adaptive, noninferiority, storage duration–ranging trial conducted in pediatric and adult patients undergoing cardiac surgery with planned cardiopulmonary bypass at 27 sites in the US and Australia from December 2021 to March 2025. Statistical analysis was conducted from September 9 to October 3, 2025. Intervention Patients were randomized 2:1 to receive CSPs with a maximum of 21 days of storage vs RTPs with a maximum of 7 days of storage. Main Outcomes and Measures The primary outcome was a hemostatic efficacy score with values ranging from 1 to 5 and higher values indicating greater bleeding. The noninferiority margin was 1 point. The success criterion was met if at least 1 cold-storage duration of 7 days or more had a posterior probability of noninferiority of at least 97.5%. The secondary outcome was 24-hour chest tube output. Results Of the 1000 patients who underwent platelet transfusion, 989 were included in the primary analysis (650 CSPs and 339 RTPs). The cohort had a mean (SD) age of 42.1 (30.1) years and 67.8% were male. CSPs were noninferior to RTPs for the primary outcome, with a probability of greater than 99.9% for all cold-storage durations. Pooled across storage durations, CSPs had a mean difference from RTPs of 0.09 (95% credible interval, −0.06 to 0.23). Median (IQR) chest tube output at 24 hours (8.9 mL/kg [5.2-15.4] for CSPs vs 8.4 mL/kg [5.5-15.9] for RTPs; difference in medians, 0.4 [95% CI, −1.0 to 1.5]) was not statistically different between study groups. In a post hoc analysis, as all storage durations were noninferior, considering the CSPs as a single group, the hemostatic efficacy score was similar between both groups: mean (SD) of 3.08 (1.15) CSPs vs 2.99 (1.10) RTPs. There were no differences in venous or arterial thrombotic events, transfusion-associated adverse events, acute respiratory distress syndrome, kidney failure, septic shock, and mortality between the study groups, except for increased reexploration rates in the CSP group. Conclusions and Relevance For patients undergoing cardiac surgery, CSPs stored up to 21 days are noninferior to RTPs for the control of active surgical bleeding. Use of CSPs may allow for increased availability of platelets by reducing wastage and shortages and may allow for incorporation of platelets into inventory at locations where platelets cannot be maintained due to the 5- to 7-day shelf life of RTPs. Trial Registration ClinicalTrials.gov Identifier: NCT04834414

ABSTRACT Background Radiotherapy is a cornerstone of treatment for pediatric central nervous system (CNS) tumors, but dose selection remains uniform despite interpatient variability in tumor radiosensitivity. This is consequential in children, for whom toxicity can have lifelong effects. Genomic-adjusted radiation dose (GARD) integrates tumor genomics with delivered radiation dose to quantify the biological effect of radiotherapy and has been validated across adult malignancies. Its relevance in pediatric CNS tumors is unknown. Methods We performed a cohort study using gene expression and data from 246 pediatric patients with high-grade glioma, medulloblastoma, or ependymoma from the Children’s Brain Tumor Network. GARD was calculated using a sequencing-adapted radiosensitivity index integrated with radiation dose through the linear–quadratic model. Associations of GARD and physical radiation dose with event-free and overall survival were evaluated using Cox proportional hazards models stratified by tumor type and anatomic location. Patients who did not receive radiotherapy comprised a negative control cohort (sham-GARD). Results Among patients receiving radiotherapy, physical dose was uniform, whereas GARD showed substantial interpatient variability in biological effect. Higher GARD was associated with improved event-free survival (hazard ratio [HR] 0·90, 95% CI 0·83–0·97; p=0·004) and overall survival (HR 0·90, 95% CI 0·83–0·99; p=0·018). Physical dose was not associated with either endpoint. Among patients who did not receive radiotherapy, sham-GARD was not associated with outcomes, supporting GARD as a treatment-specific predictor rather than a prognostic biomarker. Conclusions In pediatric CNS tumors, the biological effect of radiotherapy quantified by GARD was associated with outcomes, whereas physical dose was not. These findings challenge uniform radiotherapy dosing and support genomically informed dose individualization. Prospective evaluation of GARD-guided radiotherapy is warranted to optimize tumor control while minimizing long-term toxicity in children.

Background: Whether robot-assisted cholecystectomy reduces bile duct injury compared with laparoscopic cholecystectomy remains uncertain because prior studies have inadequately accounted for disease severity and have rarely classified injury severity using standardized criteria. This study compared perioperative outcomes after robot-assisted and laparoscopic cholecystectomy across a large healthcare system while adjusting for operative complexity. Study Design: Adults undergoing robot-assisted or laparoscopic cholecystectomy within the Mayo Clinic Enterprise (2014–2025) were retrospectively evaluated. Propensity score weighting adjusted for demographics, surgeon case volume, learning curve, and disease severity using the Tokyo Guidelines and Parkland grading system in patients with acute cholecystitis. The primary outcome was bile duct injury; secondary outcomes included general and procedure-specific complications. Results: Among 23,513 patients (19,998 laparoscopic; 3,515 robotic), robot-assisted cholecystectomy was used more frequently for Parkland grade ≥3 disease. Overall, 227 bile duct injuries occurred (204 laparoscopic; 23 robotic), corresponding to absolute risks of 1.02% and 0.65%, respectively (absolute risk difference −0.37%, 95% CI −0.72% to −0.02%; number needed to treat, 273). Robot-assisted cholecystectomy was associated with lower odds of conversion to open surgery, 30-day readmission, and mortality, shorter hospital stay (β −0.56, 95% CI −0.66 to −0.45; P<0.001), and a 5-minute longer median operative time. In acute cholecystitis, robot-assisted cholecystectomy was associated with lower adjusted odds of bile duct injury (aOR 0.29, 95% CI 0.07–0.78; P=0.011). Conclusions: After adjustment for disease severity and surgeon-related factors, robot-assisted cholecystectomy was associated with lower odds of bile duct injury in acute cholecystitis and improved perioperative outcomes, including shorter hospitalization and lower conversion rates, despite greater use in more complex cases.

Importance Elevated low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for cardiovascular disease, the leading cause of premature death worldwide. Assessing the LDL-C–related burden is critical for guiding prevention and treatment strategies. Objectives To estimate the global, regional, and national burden of ischemic heart disease and ischemic stroke attributable to elevated LDL-C (relative to 35-54 mg/dL) from 1990 to 2023 and to quantify the contributions of population growth, aging, risk-deleted burden, and exposure changes to burden trends. Design, Setting, and Population This comparative risk assessment, part of the Global Burden of Disease Study 2023, estimated population-level LDL-C exposure and associated health loss in 204 countries and territories. Mean LDL-C levels were estimated using spatiotemporal gaussian process regression based on 806 studies across 161 countries. Relative risks were derived from meta-analyses of 38 randomized clinical trials. Population-attributable fractions for deaths and disability-adjusted life-years (DALYs) were estimated by age and sex for adults aged 25 years or older from 1990 to 2023, with 95% uncertainty intervals. Exposure Population-level LDL-C concentrations. Main Outcomes and Measures Population-attributable fractions, counts, and rates (all ages and age standardized per 100 000) of LDL-C–attributable deaths and DALYs from ischemic heart disease and ischemic stroke, with uncertainty intervals. Results In 2023, elevated LDL-C accounted for 3.6 million deaths (95% uncertainty interval, 2.2-5.4 million; 6.0% of global mortality) and 90.7 million DALYs (95% uncertainty interval, 58.9-123.3 million; 3.2% of DALYs). Although global all-ages rates remained stable, age-standardized death and DALY rates decreased by 45.6% and 39.5%, respectively, since 1990. In 2023, age-standardized LDL-C–attributable DALY rates were highest in Eastern Europe and lowest in high-income Asia-Pacific. One-third of the global LDL-C burden occurred in India and China. Population growth and aging drove the increasing burden, with notable regional disparities in LDL-C exposure and risk-deleted DALY rates shifting toward middle-sociodemographic settings. Conclusions and Relevance Despite declining age-standardized rates, the absolute LDL-C burden has increased since 1990 due to demographic changes and has shifted toward middle-sociodemographic countries. Measurement and surveillance gaps persist. Strengthened prevention, diagnosis, and treatment access strategies are essential to mitigate the health burden of LDL-C.

Background Youth-onset diabetes mellitus (DM) is an increasing public health concern, especially among adolescents facing socioeconomic challenges. Food insecurity (FI), a key social determinant of health, has been linked to adverse metabolic outcomes, but its association with youth-onset DM and the role of preventive care remain unclear. Methods Using repeated cross-sectional data from the National Survey of Children’s Health (2016–2021), we examined the association between FI status (food secure, mild FI and moderate-to-severe FI) and youth-onset DM among adolescents aged 10–17 years. We also evaluated whether usual preventive care modified this association. Propensity score weighting (PSW) was used to reduce the imbalance of measured confounders across FI groups. These weights were applied in the least absolute shrinkage and selection operator logistic regression for variable selection and in the final multivariable logistic regression models. Results In the PSW analysis of 66 560 adolescents, 432 had youth-onset DM. Moderate-to-severe FI was associated with higher odds of DM than food-secure adolescents (OR 1.55, 95% CI 1.35 to 1.77; p<0.0001), whereas mild FI was not associated with youth-onset DM. Among adolescents with preventive care visits, both mild FI (OR 1.19, 95% CI 1.04 to 1.37; p=0.0126) and moderate-to-severe FI (OR 1.67, 95% CI 1.46 to 1.92; p<0.0001) were associated with higher odds of DM. Among those without preventive care visits, FI was associated with lower odds of having a reported DM diagnosis, especially in the moderate-to-severe FI group (OR 0.11, 95% CI 0.03 to 0.35; p=0.0002). Conclusions Moderate-to-severe FI was associated with youth-onset DM, and this relationship varied by access to preventive care. Adolescents with FI who lack regular preventive care may have fewer opportunities for DM diagnosis. Public health strategies should integrate FI screening, equitable access to preventive services and culturally responsive approaches to chronic disease prevention.

Black race and Hispanic ethnicity are associated with higher mortality in severe combined immunodeficiency (SCID) following hematopoietic cell transplantation (HCT), though mechanisms remain unclear. We evaluated 796 children with SCID who received nonsibling HCT between 1982 and 2020 using data from the Primary Immune Deficiency Treatment Consortium. Overall survival for Black (aHR 2.47, 95%CI 1.64, 3.71) and Asian/Pacific Islander patients (aHR 1.82, 95%CI 1.00, 3.30) was significantly lower compared with non-Hispanic White patients, while Hispanic patients had lower event-free survival (aHR 1.83, 95%CI 1.27, 2.63) compared with non-Hispanic White patients. Even after adjusting for age and infection, Black patients with SCID had more than twofold hazard of death compared with non-Hispanic White patients. NBS was associated with earlier diagnosis, reduced infection at HCT, and elimination of survival disparities between Black and non-Hispanic White patients. These findings suggest that universal, system-level interventions such as NBS can mitigate disparities in outcomes for children with SCID.