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Importance Cerebral hemodynamic impairment in patients with asymptomatic internal carotid artery (ICA) stenosis is associated with reduced cognition. It is uncertain whether revascularization might be an effective treatment for cognitive impairment in these patients. Objective To test whether any cognitive benefit from revascularization of high-grade, asymptomatic ICA stenosis varies based on the degree of baseline cerebral hemodynamic impairment. Design, Setting, and Participants This substudy was conducted within a multicenter phase 3 randomized clinical trial. Adults (aged 35-86 years) without dementia with eighth-grade education or higher and unilateral asymptomatic ICA stenosis greater than or equal to 70% were enrolled from January 2018 to July 2024 at 61 sites in North America (last follow-up in July 2025). Of 607 participants screened from 2485 in CREST-2, 392 were enrolled. Magnetic resonance or computed tomographic perfusion imaging tested for baseline hemodynamic impairment defined by delayed time-to-peak (TTP) arrival of intravenous contrast in the hemisphere ipsilateral minus contralateral to the stenotic artery. Intervention Carotid revascularization (endarterectomy or stenting) plus intensive medical management (IMM) vs IMM alone. Main Outcomes and Measures The primary outcome was the difference in composite cognitive z score over 1 year based on 5 cognitive tests. The primary analysis tested for an interaction between treatment group (revascularization vs IMM alone) and degree of baseline hemodynamic impairment among those with reduced baseline cognition (cognitive z score ≤−1.0 SD). Results Of 392 participants enrolled (mean age, 71 years; 125 [32%] females), 61 were excluded for missing baseline imaging and 40 for missing cognitive examinations or other covariates, leaving 291 with complete data. Fifty-one had reduced cognition at baseline (25 in the revascularization group and 26 in the IMM alone group). TTP ranged from no interhemispheric TTP delay to a more-than-2-second delay. Mean (SD) cognitive z scores were −1.36 (0.51) at baseline and −1.17 (0.47) at 1 year in the revascularization group and −1.34 (0.83) at baseline and −1.01 (0.97) at 1 year in the IMM alone group. The primary analysis showed no difference in cognition by treatment group over 1 year, adjusting for treatment group × hemodynamic status interaction and other covariates (adjusted difference in cognitive z score, −0.15 SD [95% CI, −0.54 to 0.24]). The interaction was not significant (β estimate = 0.018 [95% CI, −0.025 to 0.061]; P = .40). Conclusions and Relevance In this substudy of a randomized clinical trial, there was no differential effect of revascularization vs IMM alone on cognition over 1 year by cerebral hemodynamic status among those with baseline reduced cognition, suggesting that revascularization does not improve cognitive dysfunction by restoring flow to the brain in chronic asymptomatic carotid stenosis. Trial Registration ClinicalTrials.gov Identifier: NCT03121209

ABSTRACT Aim To systematically review and meta‐analyze cohort studies evaluating associations of gingival inflammation, periodontitis, and tooth loss with cognitive decline and incident mild cognitive impairment or dementia. Methods PROSPERO‐registered searches of MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library identified cohort studies from inception through October 10, 2025, with a PubMed update on June 24, 2026. Random‐effects meta‐analyses pooled adjusted hazard ratios (HRs) for dementia/MCI; cognitive function outcomes were summarized qualitatively. Risk of bias (RoB) was assessed using the Newcastle–Ottawa Scale. Results Fifty‐nine studies met inclusion criteria; 28 contributed to dementia/MCI meta‐analyses. Severe periodontitis (HR: 1.16; 95% CI: 1.06–1.27; I 2 = 0%; Q ‐test p = 0.49), periodontitis of unspecified severity (HR: 1.45; 95% CI: 1.21–1.73; I 2 = 98%; Q ‐test p < 0.001), edentulism (HR: 1.26; 95% CI: 1.19–1.33), and low tooth count (HR: 1.27; 95% CI: 1.14–1.42; I 2 = 94%; Q ‐test p < 0.001) were associated with elevated dementia/MCI risk. RoB was low in 31 studies (53%), moderate in 25 (42%), and high in 3 (5%); inadequate confounder adjustment was common. Meta‐regression showed stronger estimates for ICD‐code periodontitis definitions (fold change (FC) = 1.44 95% CI: 1.04–2.01), older cohorts (FC per year = 1.02 95% CI: 1.00, 1.05), and weaker estimates with lower RoB (FC per NOS star = 0.81 95% CI: 0.73–0.92). Follow‐up duration, cohort age, and RoB were not associated with tooth‐count estimates. Conclusion Periodontitis and tooth loss are associated with modestly higher dementia/MCI risk and poorer cognitive function, but heterogeneity, residual confounding, and bias temper causal interpretation. Longitudinal studies with rigorous baseline cognition assessment and intervention studies are needed.

Aberrant activation of the Hippo–YAP/TAZ–TEAD transcriptional axis is a recurrent feature of multiple solid tumors and contributes to tumor maintenance, lineage plasticity, and therapeutic resistance. Recent medicinal chemistry has shown that TEAD proteins are druggable, but the rate at which in silico screening nominates compounds that prove functionally active in cells remains poorly defined, and negative validation results are rarely reported. Here we describe an experimental assessment of a focused set of computationally nominated candidate compounds, selected from a structure-guided virtual screen of the YAP–TEAD interface across approximately 917,000 library compounds and three predicted binding sites. Candidates were evaluated using long-term (144 hour) CellTiter-Glo proliferation assays in three Hippo-altered malignant pleural mesothelioma cell lines (MSTO-211H, NCI-H2052, NCI-H226), with the validated TEAD inhibitor K-975 and cisplatin as positive controls, and an exploratory TEAD-responsive luciferase reporter in MCF7 cells. K-975 produced dose-dependent antiproliferative activity in MSTO-211H and NCI-H2052, with reduced sensitivity in NCI-H226, while cisplatin reduced viability in all lines. In contrast, the computationally nominated compounds, including AG-690/36549045, AN-655/40856217, and additional library members, did not produce measurable antiproliferative activity at the concentrations tested. In the exploratory reporter, apparent suppression of TEAD activity consistently co-occurred with loss of cell viability, a pattern consistent with cytotoxicity rather than selective transcriptional inhibition; no TEAD-active reference compound was co-tested within the reporter panel, and no direct YAP–TEAD biochemical or target-engagement assay was performed. These results describe a case in which computational nomination at the YAP–TEAD interface showed limited concordance with cell-based activity and provide a transparent account of negative findings to inform expectations for early-stage discovery targeting Hippo-dependent transcriptional programs.

Aims: To synthesise and critically appraise evidence on artificial intelligence (AI) and multimodal data approaches for diagnosis, prognosis, and treatment decision support in diffuse large B-cell lymphoma (DLBCL) and acute myeloid leukaemia (AML), and to compare how disease biology shapes model design and clinical readiness. Study Design: Systematic review with narrative synthesis. Place and Duration of Study: PubMed/MEDLINE, Embase, Scopus, Web of Science Core Collection, IEEE Xplore, and the Cochrane Library were searched from database inception to 29 July 2026. Methodology: English-language original studies involving human participants, clinical images, human-derived samples, or patient-derived datasets were eligible. Two reviewers independently screened records, assessed full texts, and extracted study characteristics, data modalities, analytical methods, validation approaches, and performance measures. PROBAST+AI domains were used to guide appraisal of eligible patient-level prediction models; exploratory multi-omics, molecular-subtyping, biomarker-discovery, and segmentation studies underwent structured descriptive appraisal. TRIPOD+AI informed assessment of reporting completeness. Owing to substantial clinical and methodological heterogeneity, findings were synthesised narratively. Results: Twenty-eight studies were included: 22 on DLBCL and six on AML. DLBCL research was dominated by PET/CT radiomics, deep imaging, digital pathology, and imaging-clinical-molecular fusion. Internally evaluated diagnostic models reported area under the curve values as high as 0.999, whereas externally validated prognostic models achieved values of 0.66-0.71 and showed inconsistent incremental improvement over the International Prognostic Index. AML studies mainly integrated genomic, transcriptomic, epigenomic, single-cell, proteomic, metabolic, and functional drug-response data. Prognostic models reported concordance indices of 0.72-0.81 and time-dependent area under the curve values of 0.795-0.899. The most frequent methodological concerns were retrospective sampling, high-dimensional modelling in modest cohorts, incomplete calibration reporting, and limited independent validation. Treatment-response models in both diseases remained retrospective or exploratory, and none demonstrated improved outcomes through AI-guided treatment allocation. Conclusion: AI and multimodal data approaches show greatest maturity for prognostic stratification, but diagnostic replacement and treatment selection remain unproven. Prospective, multicentre clinical-impact validation is the principal requirement for translation into routine care.

Purpose To compare lower extremity soft tissue injury and revision surgery rates for patients with anorexia nervosa (AN) and bulimia nervosa (BN) compared with matched controls. Methods This retrospective cohort study used a deidentified claims database. Patients were included if they carried an International Classification of Diseases code for AN or BN. Respective matched cohorts for AN and BN were created using propensity score matching. Primary and revision surgeries for anterior cruciate ligament (ACL) reconstruction, posterior cruciate ligament reconstruction, knee collateral ligament reconstruction, meniscus repair or meniscectomy, and any ankle ligament reconstruction were identified by their CPT codes. Patients over the age of 40 and without a minimum 2‐year follow‐up after primary surgery were excluded. Differences in prevalence and revision rates were analyzed. Results A total of 56,146 patients with AN and 42,630 patients with BN were included in this study with equal numbers in respective matched cohorts. Patients with BN showed an increased risk of ACL injury (relative risk = 1.32, P = .019), medial collateral ligament injury (1.17, 0.04), calcaneofibular sprain (1.92, <0.001), deltoid sprain (1.41, 0.004), and unspecified ankle sprain (1.44, <0.001). Patients with AN showed an increased risk for calcaneofibular sprain (1.25, 0.007), deltoid sprain (1.28, 0.015), and unspecified ankle sprain (1.17, <0.001). Patients with BN were more likely to have revision ACL repair (1.89, 0.02), partial meniscus revision (3.44, <0.001) and any meniscus revision (4.74, <0.001) while patients with AN were more likely to have an ACL revision (2.81, <0.001), partial meniscus (4.37, <0.001), and any meniscus (4.52, <0.001). Conclusions In this study, patients with AN and BN had a significantly increased risk for various knee and ankle injuries and revision surgeries compared with matched controls. Additionally, patients with AN and BN who sustained these injuries were more likely to undergo a revision surgical procedure within the first 5 years of the primary procedure. Level of Evidence Level III, retrospective comparative study.

Ear, nose, and throat (ENT) surgeons often perform multiple daily procedures requiring sustained postures while wearing headlights or loupes, increasing the risk of work-related musculoskeletal disorders (WMSDs). This in situ case study aimed to (1) evaluate ENT surgeon workload and (2) introduce ergonomic interventions through workflow changes, education, and personal protective equipment. Three trained ergonomists observed the intraoperative workflow of three ENT surgeons at a tertiary academic hospital, identifying awkward postures. Surgeons received education on surgical microbreaks and OR-Stretch before trialing passive exoskeletons. Exoskeleton effectiveness was evaluated using interviews and surveys. Workflow interventions improved neck posture. One surgeon reported reduced body-part discomfort but increased subjective workload when using the exoskeleton, while interviews identified aesthetic concerns. This exploratory case study identified workflow issues and introduced ergonomic interventions. Although one surgeon reported reduced discomfort with an exoskeleton, larger studies are needed to establish quantitative trends.

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.