Search

Neurocognitive functions (NCFs) might change after conventional whole-brain radiotherapy (WBRT). The technique of hippocampus sparing during WBRT (HS-WBRT) may substantially preserve NCFs. Therefore, the aim of this study was to examine whether trajectories of neuropsychological performances maintained or improved after HS-WBRT. A total of 125 cancer patients underwent the HS-WBRT course. Before HS-WBRT, all participants underwent multidomain neurocognitive assessment, mainly involving executive functions and hippocampus-related memory. After radiotherapy, the above assessment was administered at regular time points to monitor longitudinal neuropsychological performances. The delta values of post-radiotherapy and baseline NCF scores showed a sustained trend, signifying cognitive maintenance rather than deterioration. This trend was observed for hippocampus-related verbal memory and frontal-lobe-related executive functions, represented by the score of Word List-immediate memory and Modified Card Sorting Test - Complete Categories, respectively. The potential predictors of longitudinal multidomain neuropsychological performances included age at enrollment, baseline NCF scores, and the assessment time (months) elapsed since enrollment, signifying the trajectory of patients' neuropsychological performances after HS-WBRT. Among longitudinal neuropsychological outcomes, there was a considerable time trend toward maintenance in verbal learning immediate memory [odds ratio, 1.112, 95% confidence interval, 1.08 - 1.15], which persisted even after adjusting for the most independent predictor (baseline NCF scores). Functional preservation of longitudinal multidomain neuropsychological performances was evident after HS-WBRT. Such neurocognitive preservation, particularly hippocampus-related memory functions, was meaningfully sustained in our patients after undergoing the standardized course of hippocampus sparing during WBRT.

Objective: Alternative medical imaging techniques are necessary to address the limitations of magnetic resonance imaging (MRI). Therefore, this study aimed to develop an ultrasonographic method that integrates anterior and posterior approaches for measuring the entire length of the anterior cruciate ligament (ACL). We validated this method by identifying the middle ACL during arthroscopy and comparing the results to those of MRI. We hypothesized that the ACL length measurements obtained via ultrasonography and MRI would not differ significantly and that the posterior approach would provide a longer visual field of the ACL than the anterior approach., Methods: Thirty-six patients (21 males, 15 females) diagnosed with meniscal injury or internal knee derangement were included. During arthroscopy, the surgeon identified the middle ACL using Ti-Cron™ sutures. Ultrasonographic approaches from the anterior and posterior perspectives were used to identify the distal and proximal ACL, respectively. The ACL length was measured using both ultrasonography and MRI, and the visual fields from both approaches were compared., Results: One participant was excluded because of a torn ACL, and seven participants were excluded because of poor ultrasonographic image quality. The ACL length of the 28 included patients did not differ significantly between ultrasonography and MRI, with a moderate correlation between the two measurements. The visualized proportion of the ACL was greater through the posterior approach than through the anterior approach., Conclusions: This ultrasonographic method visualizes the entire ACL length by combining anterior and posterior approaches, with the posterior offering a more extensive and clinically significant visual field., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Type 2 diabetes mellitus (T2DM) is an independent risk factor of knee osteoarthritis (KOA). This study was mainly based on data from the Taiwan National Health Insurance Database. Using big data analysis, we showed that glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment is helpful for patients with T2DM who have a lower risk of KOA or total knee replacement (TKR). A total of 35,762 patients with T2DM were included in this study. We divided these patients into 988 patients with T2DM without KOA and 372 patients with T2DM with KOA who received GLP-1RA treatment and those who did not receive GLP-1RA treatment. The patients were matched for sex, age, and inclusion date by 1:1 propensity score, which was included in the control group. Cox proportional hazards analyses were performed to compare KOA risk and TKR rate during a maximum follow-up period of 5 years. There were 1976/744 patients with T2DM without/with KOA who received and did not receive GLP-1RA treatment, including 1052/322 men (53.24/43.28%) and 924/422 women (46.76/56.72%). At the end of follow-up, there were 46/39 (4.66/10.48%) patients with T2DM without/with KOA who received GLP-1RA treatment and underwent KOA/TKR were lower than those without GLP-1RA treatment 87/70 (8.81/18.82%). Cox proportional hazard regression analysis showed a lower rate of KOA/TKR among patients with GLP-1RA treatment (adjusted hazard ratio [HR] = .852; 95% confidence interval [CI] = .784-.930, P < .001/ adjusted HR = .913; 95% CI = .885-.977, P = .015, respectively). Kaplan-Meier analysis showed that the cumulative risk of KOA/TKR in patient with/without GLP-1RA was significantly different (log-rank test, P < .001/P < .001, respectively). This study aimed to provide clinicians with the option of GLP-1RA as a treatment for patients with T2DM with or without KOA to reduce the risk of KOA or TKR among such patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

Large-scale whole-genome sequencing (WGS) studies have improved our understanding of the contributions of coding and noncoding rare variants to complex human traits. Leveraging association effect sizes across multiple traits in WGS rare variant association analysis can improve statistical power over single-trait analysis, and also detect pleiotropic genes and regions. Existing multi-trait methods have limited ability to perform rare variant analysis of large-scale WGS data. We propose MultiSTAAR, a statistical framework and computationally scalable analytical pipeline for functionally informed multi-trait rare variant analysis in large-scale WGS studies. MultiSTAAR accounts for relatedness, population structure and correlation among phenotypes by jointly analyzing multiple traits, and further empowers rare variant association analysis by incorporating multiple functional annotations. We applied MultiSTAAR to jointly analyze three lipid traits in 61,838 multi-ethnic samples from the Trans-Omics for Precision Medicine (TOPMed) Program. We discovered and replicated new associations with lipid traits missed by single-trait analysis., Competing Interests: Competing interests: Z.R.M. and R.D. are employees of Insitro. S.M.G. is an employee of Regeneron Genetics Center. M.E.M. receives research funding from Regeneron Pharmaceutical Inc., unrelated to this project. B.M.P. serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. L.M.R. and S.S.R. are consultants for the TOPMed Administrative Coordinating Center (via Westat). P.N. reports research grants from Allelica, Amgen, Apple, Boston Scientific, Genentech/Roche and Novartis, personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Creative Education Concepts, CRISPR Therapeutics, Eli Lilly & Co, Esperion Therapeutics, Foresite Capital, Foresite Labs, Genentech/Roche, GV, HeartFlow, Magnet Biomedicine, Merck, Novartis, TenSixteen Bio and Tourmaline Bio, equity in Bolt, Candela, Mercury, MyOme, Parameter Health, Preciseli and TenSixteen Bio, and spousal employment at Vertex Pharmaceuticals, all unrelated to the present work. X. Lin is a consultant of AbbVie Pharmaceuticals and Verily Life Sciences. The other authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objectives: To examine if frailty is associated with cognitive status or depression in older adults following surgery for hip fracture., Design: A 2-year longitudinal correlational cohort study., Setting and Participants: Older adults (≥ 60 years) who had hip-fracture surgery were recruited from a 3,000-bed medical center in Taiwan., Methods: Participants were recruited between September 2012; follow-up was completed in March 2021. Measures for frailty, cognitive status, and depression were assessed at six points. Frailty changes were analyzed using generalized estimating equations., Results: Mean age was 78.51 ± 9.0 years. Compared to those without cognitive impairment or without depression, pre-fracture basic activities of daily living (BADLs), baseline walking ability and frailty were worse for participants with cognitive impairment or depression (P < .001). Frailty increased over time for those with cognitive impairment and depression after controlling for covariates (P < .001)., Conclusions: Assessing cognitive status and depression in older adults following hip fracture could guide interventions to reduce frailty., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Energy transfer catalysis (EnT) has had a profound impact on contemporary organic synthesis enabling the construction of higher in energy, complex molecules, via efficient access to the triplet excited state. Despite this, intermolecular reactivity, and the unique possibility to access several reaction pathways via a central triplet diradical has rendered control over reaction outcomes, an intractable challenge. Extended chromophores such as non-symmetrical dienes have the potential to undergo [2+2] cycloaddition, [4+2] cycloaddition or geometric isomerisation, which, in combination with other mechanistic considerations (site- and regioselectivity), results in chemical reactions that are challenging to regulate. Herein, we utilise boron as a tool to probe reactivity of non-symmetrical dienes under EnT catalysis, paying particular attention to the impact of boron hybridisation effects on the target reactivity. Through this, a highly site- and regioselective [2+2] cycloaddition was realised with the employed boron motif effecting reaction efficiency. Subtle modifications to the core scaffold enabled a [4+2] cycloaddition, while a counterintuitive regiodivergence was observed in geometric isomerisation versus [2+2] cycloaddition. The observed reactivity was validated via a mechanistic investigation, determining the origin of regiodivergence and reaction selectivity in competing EnT processes., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Objective: Burn injuries can be traumatic and lead to psychological sequelae, particularly acute stress disorder (ASD). Information regarding the prevalence and risk factors of ASD following DSM-5 criteria is relatively limited among survivors of burn and other traumas. This study aimed to investigate the prevalence of probable ASD post-burn according to DSM-5 criteria and explore the impact and interplay of pre- and peri-trauma psychological risk factors on DSM-5 ASD symptomatology., Methods: Between February 2017 and November 2020, 118 patients admitted to the largest burn center in Taiwan were enrolled, with 100 completing assessments within 30 days of injury during acute hospitalization. Most participants were men (73 %), with a mean age of 41.9±12.5 years. The average percentage of total body surface area (TBSA) burned was 15.1±11.5 %., Results: Around 9 % of the hospitalized burn patients had probable DSM-5 ASD. The most common ASD symptoms were intrusive memories, distress triggered by trauma reminders, and distressing dreams. Pre- and peri-trauma psychological risk factors uniquely accounted for 42.4 % of the variance in DSM-5 ASD symptomatology post-burn after adjusting for covariates. Both peritraumatic emotions and peritraumatic dissociation emerged as strong predictors with medium-to-large effect sizes (semi-partial r 2 =.13 and .09). Notably, prior depression severity significantly moderated the associations between peri-trauma psychological risk factors and ASD symptoms post-burn (incremental R 2 = 5.6-8.8 %)., Conclusion: The findings underscore the interplay of pre- and peri-trauma psychological processes in susceptibility to ASD symptomatology post-burn., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Background/aim: Gastric cancer (GC) is one of the most common cancers worldwide. Cisplatin is a key therapeutic agent for treating GC. Currently, the resistance of GC cells to cisplatin remains a major concern. Pterostilbene (PTS) is a natural phytochemical found in blueberry and grape. The anti-cisplatin-resistant GC effects and pharmacological mechanisms of PTS are unknown., Materials and Methods: We investigated the anticancer activity of PTS in cisplatin-resistant GC cells and explored its pharmacological mechanisms of action via cell viability assay, cell confluence assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, acridine orange (AO) staining, monodansylcadaverine (MDC) staining, caspase-9/-3 activity assay, and RNA sequencing (RNA-Seq) analysis., Results: Our results showed that PTS inhibited cell viability and cell confluence of cisplatin-resistant GC cells using the CCK-8 assay and the IncuCyte S3 ZOOM System. The TUNEL assay showed that PTS promoted apoptosis in cisplatin-resistant GC cells. PTS induced apoptosis by increasing caspase-9 and caspase-3 activity. PTS promoted cell autophagy by increasing vacuole formation and acidic vesicular organelles using MDC and AO staining. We also observed an increase in the expression of LC3B in PTS-treated cisplatin-resistant GC cells. RNA-Seq analysis demonstrated that PTS induced apoptosis and autophagy in cisplatin-resistant GC cells by decreasing the expression of ATM/ATR, HIF-1, PI3K, RB1CC, TBK1, and mitochondria-related genes., Conclusion: Our results suggested that PTS is a promising phytochemical for GC therapy, particularly against cisplatin resistance., (Copyright © 2025 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

With health equity growing as a priority within health care, health systems must transform that calling into action within their social, economic, and political environments. The current literature has not compared how different organizations manage the same health disparities intervention. This qualitative study aims to illustrate how different organizations navigated the implementation and sustainability of a hypertension disparities intervention by comparing experiences across Federally Qualified Health Centers (FQHCs), a private health system, and other non-clinical partnering organizations. As a study within a randomized controlled trial designed to reduce disparities in hypertension care, we conducted interviews with health care leaders before and after participation in the trial's multi-level intervention. Before participation, we interviewed five health care leaders representing five health systems. Following the intervention, we interviewed 14 leaders representing the five health systems and two partnering organizations. Discussions focused on intervention implementation and plans for sustainability. The primary considerations in implementation were appropriate staffing and multi-level organizational buy-in. When discussing long-term planning, health systems prioritized the structure of a stepped-care protocol incorporating community health workers (CHWs) and case managers. The sustainability of the CHW intervention at FQHCs was dependent on funding, whereas a private, non-FQHC physician practice network focused on expanding current resources for more patients. These findings serve as anticipatory guidance for organizations aiming to reduce hypertension disparities and provide support for policies that financially assist these interventions. Further investigation is warranted on the organizational factors that may influence the degree of success in eliminating health care disparities., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Osteoarthritis (OA) is a degenerative joint disease with a complex aetiology, which includes inflammation, cellular growth dysregulation and extracellular matrix (ECM) degradation. This study investigated the therapeutic potential of a small-molecule compound, 2-amino-4-(3,4,5-trimethoxyphenyl)-4H-benzo[h]chromene-3-carbonitrile (CN7:1h) in modulating these critical biochemical pathways in OA. Cellular models and rat models of OA were used to explore the impact of CN7:1h on the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and mechanistic target of rapamycin (mTOR) signalling pathways. Parameters such as autophagy, apoptosis and ECM preservation were evaluated. CN7:1h demonstrated a non-cytotoxic profile at a concentration as high as 140 μM as confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. At a concentration of 5 μM, CN7:1h was shown to inhibit the activation of NF-κB and mTOR pathways. CN7:1h was also shown to promote autophagy and reduce apoptosis in cellular models. In rat models, CN7:1h facilitated cartilage repair and demonstrating the therapeutic efficacy of this compound. In conclusion, CN7:1h is a promising bioactive compound for the modulation of key biochemical pathways with therapeutic benefits in degenerative conditions, such as OA. Its high bioavailability and lack of cytotoxicity make CN7:1h an excellent candidate for further research aimed at clinical applications., (© 2025 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Insulin resistance (IR) is the core for type 2 diabetes and metabolic syndrome. The homeostasis assessment model is a straightforward and practical tool for quantifying insulin resistance (HOMA-IR). Multiple adaptive regression spline (MARS) is a machine learning method used in many research fields but has yet to be applied to estimating HOMA-IR. This study uses MARS to build an equation to estimate HOMA-IR in pre-menopausal Chinese women based on a sample of 4,071 healthy women aged 20-50 with no major diseases and no medication use for blood pressure, blood glucose or blood lipids. Thirty variables were applied to build the HOMA-IR model, including demographic, laboratory, and lifestyle factors. MARS results in smaller prediction errors than traditional multiple linear regression (MLR) methods, and is thus more accurate. The model was established based on key impact factors including waist-hip ratio (WHR), C reactive protein (CRP), uric acid (UA), total bilirubin (TBIL), leukocyte (WBC), serum glutamic oxaloacetic transaminase (GOT), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), serum glutamic pyruvic transaminase (GPT), and triglycerides (TG). The equation is as following:HOMA-IR = 6.634 - 1.448MAX(0, 0.833 - WHR) + 10.152MAX(0, WHR - 0.833) - 1.351MAX(0, 0.7 - CRP) - 0.449MAX(0, CRP - 0.7) + 1.062MAX(0, UA - 8.5) + +1.047(MAX(0, 0.83 - TBIL) + 0.681MAX(0, WBC - 11.53) - 0.071MAX(0, 11.53 - WBC) + 0.043MAX(0, 24 - GOT) - 0.017MAX(0, GOT - 24) + 0.021MAX(0, 59 - HDL) - 0.005MAX(0, HDL - 59) - 0.013MAX(0, 141 - SBP) - 0.033MAX(0, 100 - GPT) + 0.013MAX(0, GPT - 100) - 0.004MAX(303 - TG)Results indicate that MARS is a more precise tool than fasting plasma insulin (FPI) levels, and could be used in the daily practice, and further longitudinal studies are warranted.

Elevated levels of uric acid (UA) in the body may not only lead to the formation of stones but also increase the risk of developing chronic kidney disease (CKD). This study presents a biosensor for detecting UA concentration in stones and a deep learning-based artificial neural network (ANN) system for analyzing CKD risk. The biosensor is a screen-printed electrode (SPE) chip, whose surface was modified using oxygen plasma, enabling the detection of UA concentration via cyclic voltammetry. Experimental results show a good linear relationship between UA concentration and anodic peak current within the range of 0.15-5 mM. The surface modification method for this biosensor is simple and cost-effective. The ANN system took age and creatinine values as inputs, utilizing the Chronic&#95;Kidney&#95;Disease dataset and supplementary data from literatures for training. After detecting the UA concentration in stones using the biosensor, the result was converted into serum uric acid concentration, allowing the estimation of creatinine level, which was then used by the ANN to assess the risk of developing CKD. This system can assist urologists in determining whether patients should seek consultation with nephrologists for early diagnosis and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Kidney transplant recipients have an increased risk of cytomegalovirus (CMV) infection and disease. A strategy for mitigating the risk of CMV infection in kidney transplant recipients has not yet been established in Taiwan. The Transplantation Society of Taiwan aimed to develop a consensus by expert opinion on the prevention and management of CMV infection. Based on the results of Consensus Conference, we suggested low-dose valganciclovir prophylaxis (450 mg once daily) for kidney transplant recipients. The prophylaxis duration was ≥6 months for high-risk (D+/R-) patients and 3 months for moderate-risk (R+) patients. Even for low-risk (D-/R-) patients, prophylaxis for at least 3 months is recommended because of the high seroprevalence of CMV in Taiwan. CMV prophylaxis was suggested after anti-thymocyte globulin treatment but not after methylprednisolone pulse therapy. Routine surveillance after prophylaxis, secondary prophylaxis after CMV disease treatment, and mTOR inhibitors for primary CMV prophylaxis were not recommended. Letermovir and marabavir are emerging CMV agents used for prophylaxis and refractory CMV disease. CMV immunoglobulins have been used to treat refractory CMV disease in Taiwan. We hope this consensus will help professionals manage patients with CMV in Taiwan to improve the quality of care., Competing Interests: Declaration of competing interest All authors declared no conflicts of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Dextran had been used in free flap reconstruction surgery to increase the patency of anastomotic vessels. This study aimed to evaluate the outcome of perioperative and postoperative dextran in free flap surgery., Methods: This was a single-center, retrospective study that enrolled 622 patients who received free flap surgery from 2016 to 2020. Propensity score matching was done to minimize the effect of covariance. The outcome included flap-related complications, hospital stay, and mortality. Differences in outcomes were compared between patients treated with dextran and those treated without dextran., Results: After propensity score matching, a total of 378 cases of free flap surgery were included. No difference in total flap failure rate, partial flap failure rate, take-back rate, or major and minor complications were found between the 2 groups. Dextran did not increase the overall complication rate of free flap surgery. Vascular thrombosis remains the most common cause of take-back re-exploration reasons in both the dextran and non-dextran groups., Conclusions: We found that the use of dextran perioperatively combined with postoperative treatment in microvascular free flap reconstruction showed no statistical difference in flap survival rate and complication rate., Competing Interests: Competing interests statement The authors declare no competing interests., (Copyright © 2025 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Patients with chronic kidney disease (CKD) have an elevated risk of both vitamin D deficiency (VDD) and depression. However, the relationship between VDD and the risk of depression in this population remains unclear., Methods: Using the TriNetX network database (2010-2019), we conducted a propensity score-matched cohort study of CKD patients aged ≥50 years. Patients were categorized into VDD (≤20 ng/mL) and control (≥30 ng/mL) groups based on measurements within 3 months of CKD diagnosis. The primary outcome was the incidence of major depression within 1 year of follow-up., Results: Among 17,955 matched pairs, VDD was associated with increased depression risk at 1 year (hazard ratio [HR]: 1.929; 95% confidence interval [CI]: 1.52-2.448; p  < 0.0001). This association persisted through 3 years of follow-up. The relationship remained consistent across CKD stages, with similar risks in early (HR:1.977; 95% CI: 1.382-2.829) and CKD stage 3-5 (HR:1.981; 95% CI: 1.533-2.559). Males with VDD showed higher depression risk (HR: 2.264; 95% CI: 1.498-3.421) compared to females (HR:1.761; 95% CI: 1.307-2.374). Even vitamin D insufficiency (20-30 ng/mL) increased depression risk compared to normal levels (HR:1.667; 95% CI: 1.318-2.11). In patients with VDD, cerebrovascular disease, malnutrition, and ischemic heart disease are risk factors for depression., Conclusion: VDD is independently associated with increased depression risk in patients with CKD, particularly in males. These findings suggest that maintaining adequate vitamin D levels might be important for mental health in patients with CKD, although randomized trials are needed to confirm whether supplementation can prevent depression in this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Chen, Wang, Lai, Chang, Lin and Hung.)

Parkinson's disease (PD) is characterized by motor and non-motor symptoms, including olfactory dysfunction. Prior studies have shown that olfaction deteriorates with disease progression, however fluctuations in olfaction and related PD symptoms have been less explored. This study aimed to investigate correlations between changes in odor identification ability and PD symptoms. PD patients recruited from Taichung Veterans General Hospital underwent at least two consecutive Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and University of Pennsylvania Smell Identification Test (UPSIT) evaluations. The patients were grouped based on changes in olfactory identification ability between evaluations, and fluctuations in PD symptoms were compared between groups. Ninety-seven PD patients with 114 complete sets of data were analyzed. Significant divergent results were observed between changes in five MDS-UPDRS non-motor subscores and the conversion status of five pleasant odors, including anxiety vs. bubble gum, apathy vs. banana, dizziness vs. coconut, urination vs. root beer, and dopamine dysregulation syndrome (DDS) vs. grape. Fluctuations in the ability to detect pleasant odors, may have a complex interaction with other non-motor symptoms, including in the neurobehavioral and autonomic domains. Serial monitoring of olfactory function, particularly with pleasant odors, may provide valuable insights for tracking non-motor symptoms in PD and warrants further investigation into their therapeutic implications., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical Approval: The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of Taichung VeteransGeneral Hospital (Approval No.: CE22189B-1). Informed Consent: Informed consent was obtained from all subjects involved in the study., (© 2025. The Author(s).)

Ventricular arrhythmias (VAs) are major causes of sudden cardiac death in chronic kidney disease (CKD) patients. Indoxyl sulfate (IS) is one common uremic toxin found in CKD patients. This study investigated whether IS could induce VAs via increasing right ventricular outflow tract (RVOT) arrhythmogenesis. Using conventional microelectrodes and whole-cell patch clamps, we studied the action potentials (APs) and ionic currents of isolated rabbit RVOT tissue preparations and single cardiomyocytes before and after IS (0.1 and 1.0 μM). Calcium fluorescence imaging was performed in RVOT cardiomyocytes treated with and without IS (1.0 μM) to evaluate the calcium transient and the calcium leak. In rabbit RVOT tissues, IS (0.1 and 1.0 μM) attenuated the contractility and shortened the AP durations in a dose-dependent manner. In addition, IS (0.1 and 1.0 μM) enhanced the pro-arrhythmia effects of isoproterenol (ISO, 1.0 μM) and rapid ventricular pacing in RVOT (before versus after ISO, 25% versus 83%, N = 12). In RVOT cardiomyocytes, IS (1.0 μM) significantly decreased the L-type calcium currents but increased the sodium-calcium exchanger and sodium window currents. Cardiomyocytes treated with IS (1.0 μM) had lower calcium transients but higher diastolic calcium and calcium leak than those without IS treatment. Pretreatment with secretoneurin (SN, 30 nM, a potent neuropeptide, suppressing CaMKII) or KN-93 (0.1 μM, a CaMKII inhibitor) prevented IS-induced ionic current changes and arrhythmogenesis. In conclusion, IS modulates RVOT electrophysiology and arrhythmogenesis via enhanced CaMKII activity, which is attenuated by SN, leading to a novel therapeutic target for CKD arrhythmias., Competing Interests: Declarations. Competing Interests: All authors have no potential conflicts of interest relevant to this article to declare. The funders had no role in the study design, data analyses, or manuscript writing. Ethical Approval: The National Defense Medical Center Ethics Committee approved all procedures., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Disturbances in calcium and phosphorus homeostasis resulting from chronic kidney disease (CKD) may lead to atherosclerotic changes in blood vessels, potentially altering bone marrow perfusion. Our study aimed to investigate vertebral bone marrow perfusion using dynamic contrast-enhanced (DCE) MRI with a pharmacokinetic model. We also measured possible changes in water and fat content and bony trabeculae using T2* quantification, MR spectroscopy (MRS), and microcomputed tomography (μCT)., Methods: Twelve rats were randomly separated into a normal control group and a CKD (5/6 nephrectomy) group. Their lumbar spines were imaged, with monitoring of the L5 vertebral body conducted at 0, 8, 16, 30, and 43 weeks. After Week 43, all rats were sacrificed, and histologic changes were correlated with MRI and μCT results., Results: The CKD group demonstrated significantly lower A and k el values ( p  < 0.05), significantly increased T2* values ( p  < 0.05), significantly decreased fat content and trabeculation ( p  < 0.05), sinusoidal dilatation, and decreased adipocytes in the vertebral bone marrow., Conclusion: Using quantitative MRI and μCT to assess CKD-related arthropathy of the vertebral body is feasible. Lumbar spine bone marrow perfusion deficiency in experimental CKD may be associated with decreased fat content, increased water content, and sparse trabeculation., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Purpose: This systematic review examines the utility of deep learning algorithms in predicting pathological complete response (pCR) in rectal cancer patients undergoing neoadjuvant chemoradiotherapy (nCRT). The primary goal is to evaluate the performance of MRI-based artificial intelligence (AI) models and explore factors affecting their diagnostic accuracy., Methods: The review followed PRISMA guidelines and is registered with PROSPERO (CRD42024628017). Literature searches were conducted in PubMed, Embase, and Cochrane Library using keywords such as "artificial intelligence," "rectal cancer," "MRI," and "pathological complete response." Articles involving deep learning models applied to MRI for predicting pCR were included, excluding non-MRI data and studies without AI applications. Data on study characteristics, MRI sequences, AI model details, and performance metrics were extracted. Quality assessment was performed using the PROBAST tool., Results: Out of 512 initial records, 26 studies met the inclusion criteria. Most studies demonstrated promising diagnostic performance, with AUC values for external validation typically exceeding 0.8. The use of T2W and diffusion-weighted imaging (DWI) MRI phases enhanced model accuracy compared to T2W alone. Larger datasets generally correlated with improved model performance. However, heterogeneity in model designs, MRI protocols, and the limited integration of clinical data were noted as challenges., Conclusion: AI-enhanced MRI demonstrates significant potential in predicting pCR in rectal cancer, particularly with T2W + DWI sequences and larger datasets. While integrating clinical data remains controversial, standardizing methodologies and expanding datasets will further enhance model robustness and clinical utility., Competing Interests: Declarations. Ethics approval: This article does not contain any studies with human participants or animals performed by any of the authors. Consent to participate: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objectives: To assess hotspot micro-vessel flow velocity waveforms in human papillomavirus (HPV) cervical infections using transvaginal power Doppler ultrasound (TV-PDU) and explore associations with high-grade squamous intraepithelial lesions (HSIL, cervical intraepithelial neoplasia [CIN] II and III)., Methods: In all, 62 patients with confirmed HPV-HSIL (14 CIN II, 48 CIN III) and 65 age- and parity-matched women with neither HPV infection nor CIN were compared. Seven parameters by TV-PDU were used to assess vascular classification and micro-vessel flow velocity, including vascular grading (class I, II, III), lowest pulsatility index (PI), resistance index (RI), peak systolic velocity (PS), end-diastolic velocity (ED), time average maximum velocity (TAMV), and the vascular index (VI = PS/ED)., Results: HSIL was primarily associated with vascular class I (75.8%), followed by class II (14.5%) and class III (9.7%). PI, RI, and VI in HSIL were significantly lower than the control group (P < 0.0001). Mean PI, RI, and VI values decreased progressively from the normal cervix to CIN II-III. At a PI cutoff of 1.03, sensitivity was 88.7%, specificity was 83.8%, and area under the curve (AUC) was 95.0. At an RI cutoff of 0.68, sensitivity was 96.8%, specificity 61.5%, and AUC 84.0. At a VI cutoff of 2.84, sensitivity was 85.5%, specificity 78.5%, and AUC 85.0., Conclusion: Based on different patterns of hotspot vascular classification and micro-vessel flow velocity waveforms, particularly PI between HSIL and the normal cervix, TV-PDU may offer a potential role for aiding the planning for patients with suspicious HSIL. Further studies are needed to validate the findings., (© 2025 International Federation of Gynecology and Obstetrics.)

Background: Sacubitril/valsartan (S/V) reduces mortality and hospitalization rates in patients with heart failure with reduced ejection fraction (HFrEF), but low adherence remains a challenge. Early initiation of S/V is recommended, yet no practical tool currently exists to effectively communicate its benefits to outpatients or assess patient stability before S/V initiation during hospitalization., Methods: We collected data retrospectively from 527 HFrEF patients who started S/V between March 2017 and January 2020 at the National Taiwan University Hospital, with follow-up through September 2022. A modern stepwise variable selection approach was applied to fit the optimal Cox's proportional-hazards model to address nonlinear covariate effects and potential multicollinearity. Penalized smoothing splines were used to visualize nonlinear effects and identify cutoff values for continuous covariates. The model was then integrated into an interactive Streamlit dashboard for real-time simulation and risk prediction based on patient-specific covariates., Results: We identified 20 key variables - 12 associated with increased risk and 8 conferring protective effects. Some variables presented actionable cutoff values. The predictive model helped estimate individualized hazard ratios and covariate-adjusted survival curves, which serve as both a patient engagement platform in outpatient settings and a practical tool for physicians to assess inpatient stability before initiating S/V., Conclusion: Our interactive visualization dashboard can potentially improve medication adherence and clinical outcomes by involving patients in their treatment journey and facilitating more informed decision-making. A pragmatic clinical trial is currently underway to further evaluate the dashboard's clinical utility and effectiveness in both outpatient and inpatient environments., Competing Interests: Declaration of competing interest The authors affirm the absence of any known competing financial interests or personal relationships that might have been perceived to influence the work presented in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Study Design: Retrospective cohort study., Objective: To analyze the efficacy and safety of Halo-femoral traction (HFT) following spinal release, and preoperative Halo-gravity traction (HGT) in patients with severe spinal kyphoscoliosis and spinal cord risk classification (SCRC) type 3 at the apex., Methods: A total of 73 patients (24 males, 49 females, mean age 22.4 ± 6.4 years) and 56 patients (15 males, 41 females, mean age 22.9 ± 10.4 years) were included in the HFT and HGT group, respectively. Radiographic parameters were measured at the initial assessment, post-traction, post-final surgery, and during each follow-up. Neurologic function was assessed using the Frankel score system. IONM alerts and all complications were documented. Quality-of-life was evaluated using the SF-36 questionnaire., Results: In the HFT vs HGT group, the total correction rates were 39.9 ± 7.2% v.s. 41.3 ± 6.8% for the major Cobb and 36.6 ± 9.3% v.s. 44.4 ± 9.2% for global kyphosis (GK) after final surgery, respectively. The traction contributions were 57.6 ± 11.1% v.s. 52.3 ± 9.3% for major Cobb and 70.1 ± 10.5% v.s. 63.9 ± 11.1% for global kyphosis (GK), respectively. More than half of the total correction can be achieved gradually and safely through preoperative traction with patients in an awake state. No deterioration in neurological function was found post-final surgery. During the last follow-up, SF-36 questionnaire scores improved significantly in both groups ( P < .05)., Conclusions: Significant outcomes can be expected in patients with severe kyphoscoliosis, even with spinal cord risk classification (SCRC) type 3 at the apex undergoing HFT and HGT., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

In this study, Ta 2 O 5 was obliquely deposited on a polymer grating, resulting in a nanostructured thin film (NTF) with pronounced anisotropic optical properties. We measured and compared the principal indices and principal axes orientations of NTFs grown on both a grating and a smooth glass substrate. By adjusting the deposition angle, we observed a significant variation in the columnar angle and principal indices of the NTF on the grating, compared to the NTF on a smooth surface. Furthermore, the phase retardation and corresponding birefringence of the NTFs on the gratings were notably larger than those on a smooth substrate, highlighting the enhanced optical performance achieved through this method.

Invariant natural killer T (iNKT) cells are a subset of innate T cells displaying powerful immunomodulatory functions. Despite extensive preclinical research on the use of iNKT agonist and antagonist for various diseases, translating these findings into successful clinical applications has proven challenging, leaving no approved treatments to date. Efforts to optimize therapeutic outcomes by developing alternative glycolipids to α-galactosylceramide (α-GalCer or KRN7000), the prototypical iNKT antigen, have shown improved preclinical results. However, significant obstacles remain, including the relatively laborious synthesis of α-glycosides and their vulnerability to degradation by α-glycosidases. To overcome these limitations, we explored the use of sp 2 -iminosugars, a class of glycomimetics, to replace the carbohydrate moiety in α-GalCer-like glycolipids. This substitution offers enhanced biostability and precise control over α-selectivity in glycosylation reactions. The resulting sp 2 -iminoglycolipids (sp 2 -IGLs) were tested for their immunomodulatory effects, demonstrating the ability to bind the α-GalCer binding site on the CD1d protein in antigen-presenting cells (APCs), and functioning as iNKT antagonists in α-GalCer-stimulated splenocytes. Notably, analogs featuring a 4-alkyl-1,2,3-aminotriazol-1-yl segment in place of the C 25 N-acyl tail in α-GalCer additionally exhibited mild agonistic activity in the absence of α-GalCer stimulation. Computational studies support the formation of stable CD1d- sp 2 -IGL and CD1d - sp 2 -IGL - T-cell receptor complexes, with significant differences in the dynamics depending on the glycone nature and lipid tail length. These findings provide a molecular rationale for the observed experimental data. Furthermore, in vivo studies using murine models of asthma and autoimmune hepatitis have identified promising sp 2 -IGL candidates for further development in immunotherapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Carmen Ortiz Mellet reports financial support was provided by State Agency of Research. Jose M. Garcia Fernandez reports financial support was provided by State Agency of Research. Jesus Angulo reports financial support was provided by State Agency of Research. Carmen Ortiz Mellet reports financial support was provided by Spain Ministry of Science and Innovation. Jose M. Garcia Fernandez reports was provided by Spain Ministry of Science and Innovation. Jesus Angulo reports was provided by Spain Ministry of Science and Innovation. Carmen Ortiz Mellet reports financial support was provided by European Regional Development Fund. Jose M. Garcia Fernandez reports financial support was provided by European Regional Development Fund. Jesus Angulo reports financial support was provided by European Regional Development Fund. Ya-Jen Chang reports financial support was provided by National Science and Technology Council. Jose M. Garcia Fernandez reports financial support was provided by Government of Andalusia Department of University Research and Innovation. Reports a relationship with that includes:. Has patent pending to. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

In the present study, we deposited buffer solutions containing hydrophobic (GA) 15 fibrils onto highly oriented pyrolytic graphite (HOPG) and imaged the surfaces through atomic force microscopy (AFM). Within 3 h of applying ambient (nondegassed) buffers, we observed the formation of two-dimensional stripe-like domains on the HOPG surfaces surrounding the (GA) 15 fibrils. However, these stripe domains did not form under degassed buffers. Furthermore, the formation of stripe domains on HOPG occurred considerably faster in the presence of buffer solutions containing (GA) 15 fibrils than in the presence of pure buffer solutions. These stripe structures have recently been identified as nitrogen gas hydrate layers, which are formed through the self-assembly of nitrogen and water molecules on HOPG surfaces. Our findings suggest that gas enrichment occurs in the interfacial water surrounding hydrophobic macromolecules. The results have crucial implications for understanding hydrophobic interactions and the self-assembly of hydrophobic nano-objects in aqueous environments.

Tauopathies cover a range of neurodegenerative diseases in which natively unfolded tau protein aggregates and spreads in the brain during disease progression. To gain insights into the mechanism of tau structure and spreading, here, we examined the biochemical and cellular properties of human full-length wild-type and familial mutant tau, ΔK280, with a deletion at lysine 280. Our results showed that both wild-type and mutant tau are predominantly monomeric by analytical ultracentrifugation. The mutant tau may lose intramolecular contacts and is significantly destabilized assessed by cross-linking mass spectrometry and urea denaturation. Moreover, the mutant tau displayed accelerated fibril formation compared to the wild-type tau. Upon cross-seeding, the wild-type tau was seeded more easily by wild-type seeds than mutant seeds showing that homotypic seeding is more efficient. The wild-type tau was successfully converted to fibrils with mutant signatures by mutant seeds. Live cell cross-correlation fluorescence spectroscopy studies indicated that wild-type tau forms trimeric species and the mutant tau forms a larger assembly and processes higher cell-to-cell transmission. Overall, these findings shed light on the fundamental mechanisms of tau structure/stability, aggregation, and seeding to facilitate future therapeutic development for tauopathies., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Hydration plays a crucial role in regulating the dispersion behavior of biomolecules in water, particularly in how pH-sensitive hydration water network forms around proteins. This study explores the conformation and hydration structure of Type-I tropocollagen using small- and wide-angle X-ray scattering (SWAXS) and molecular dynamics (MD) simulations. The results reveal that tropocollagen exhibits a significant softening conformation in solution, transitioning from its rod-like structure in tissues to a worm-like conformation, characterized by a reduced radius of gyration of 50 nm and a persistent length of 34 nm. The SWAXS-supported MD calculations further establish a hydration water network characterized by a 2.8 Å free-water exclusion zone where water molecules are largely hydrogen-bonded to the densely distributed polar groups on the tropocollagen surfaces. These first-layer water molecules are bridged by outer water molecules extending up to 4 Å from the protein surfaces, forming a major hydration shell that encapsulates the protein.

Objectives : To evaluate the effectiveness of astigmatism correction between topographic- and manifest-based methods in individuals who underwent second-generation keratorefractive lenticule extraction (KLEx) surgery. Methods : This study was conducted with participants who underwent second-generation KLEx surgery. After exclusion, there were 46 and 43 participants in the manifest and topographic groups, respectively. The main outcomes were postoperative uncorrected distance visual acuity (UDVA), spherical equivalent (SE), and residual astigmatism. The independent T-test and generalized estimate equation were used to investigate differences between the two groups. Results : Three months postoperatively, UDVA was 0.02 ± 0.04 in the manifest group and 0.00 ± 0.06 in the topographic group which also revealed no significant difference ( p = 0.155). Also, the SE value in the two groups three months postoperatively was statistically similar (-0.57 ± 0.48D versus -0.63 ± 0.62D, p = 0.574). The final residual astigmatism was -0.26 ± 0.27 in the topographic group which was significantly lower than the -0.51 ± 0.40 in the manifest group ( p < 0.001). Moreover, the amplitude of astigmatism change was significantly lower in the topographic group ( p = 0.002). In the subgroup analysis, UDVA and residual astigmatism were significantly better in the topographic group than in the manifest group (both p < 0.05). Conclusions : The topographic-based method represents a better astigmatism correction than the manifest-based method in second-generation KLEx surgery, especially in the low astigmatism population.

Importance: Blood culture (BC) use benchmarks in US hospitals have not been defined., Objective: To characterize BC use in adult intensive care units (ICUs) and wards in US hospitals., Design, Setting, and Participants: A retrospective cross-sectional study of BC use in adult medical ICUs, medical-surgical ICUs, medical wards, and medical-surgical wards from acute care hospitals from the 4 US geographic regions was conducted. Critical access hospitals, less than 6 months of BC data, and non-US hospitals were excluded. The study included BC use data from September 1, 2019, to August 31, 2021. Data were analyzed from February 23 to July 14, 2024., Main Outcomes and Measures: The primary outcome was BC use per 1000 patient-days. Adjusted means with 95% CIs were calculated using mixed-effects negative binomial regression models adjusted for unit type, hospital bed size, geographic region, seasonality, and state COVID-19 case load, with random intercepts accounting for clustering at unit and hospital levels. Secondary outcomes included blood culture positivity, single BCs, BC contamination, and minimum threshold for BC use where blood culture positivity would be optimized., Results: A total of 362 327 blood cultures were analyzed from 27 medical ICUs, 35 medical-surgical ICUs, 121 medical wards, and 109 medical-surgical wards from 48 hospitals in 19 states and the District of Columbia. The adjusted mean BC use per 1000 patient-days was 273.1 (95% CI, 270.2-275.9) for medical ICUs, 146.0 (95% CI, 144.5-147.5) for medical-surgical ICUs, 80.3 (95% CI, 79.8-80.7) for medical wards, and 65.1 for medical-surgical wards. Blood culture use was significantly higher across all 4 unit types in hospitals with more than 500 beds compared with 500 or less beds and in the West-Midwest compared with other regions. Single blood culture and positive blood culture rates were below 10% across all 4 unit types. Of the 292 units, 97% had a mean BC contamination rate within 3% of the recommended threshold, and 51% were within 1%. The minimum BC use thresholds (ie, BC use below this number may represent undertesting) were 120 BCs per 1000 patient-days for medical ICUs, 80 BCs per 1000 patient-days for medical-surgical ICUs, and 30 BCs per 1000 patient-days for medical-surgical wards., Conclusions and Relevance: The findings of this study suggest that blood culture positivity may help determine appropriate BC use for individual unit types.

Background: To evaluate and compare the long-term efficacy of medical treatments for normal tension glaucoma (NTG) in controlling intraocular pressure (IOP), and establish a hierarchical ranking based on their effectiveness. 'Long-term' is defined as a treatment duration of over 12 weeks in randomised controlled trials (RCTs)., Methods: This systematic review and model-based network meta-analysis (MBNMA) collected data of 795 patients with 997 eyes from RCTs. Patients with NTG were selected based on strict inclusion/exclusion criteria, with randomsation procedures and masking as reported in the individual trials. Eight different medications were compared, including prostaglandin analogues, beta-blockers, brimonidine, unoprostone isopropyl, brovincamine, and palmitoylethanolamide (PEA). Notably, PEA is an oral medication, while other drugs are topical agents., Results: Primary outcome is the long-term efficacy of IOP control across medications with different follow-up durations. Among the eight medications, PEA demonstrates the highest efficacy (Surface under the cumulative ranking, SUCRA = 7.46%), followed by two prostaglandin analogues: travoprost (SUCRA = 6.86%) and latanoprost (SUCRA = 6.76%), then two beta-blockers: nipradilol (SUCRA = 4.90%) and timolol (SUCRA = 4.89%). Both brimonidine and unoprostone isopropyl have SUCRA scores below 4.0%, indicating modest but limited efficacy. Brovincamine has the lowest SUCRA score (1.32%), reflecting minimal effectiveness., Conclusions: This study revealed PEA as a promising agent for long-term IOP control in NTG patients, suggesting potential use as primary or adjunctive therapy. The outcomes call for PEA's consideration in clinical practice and highlight the need for further research into its long-term efficacy and safety for NTG., (© 2024 Royal Australian and New Zealand College of Ophthalmologists.)

Background: To explore the role of gut microbiota in preterm infants at high risk of developing retinopathy of prematurity (ROP)., Methods: Preterm infants with gestational age (GA) < 32 weeks and/or birth weight (BW) < 1500 g born between 2020 and 2021 were prospectively enrolled. Their faecal samples were collected and analysed at different postnatal ages of life using 16S rRNA gene sequencing on the Miseq platform. The main outcome measures were the microbial diversity, taxonomy, relative abundance, bacterial predicted functional analysis, and their associations with different ROP groups. Subgroup analyses were performed by matching their GA and BW across different ROP groups., Results: A total of 268 stool samples were collected from 110 preterm infants, including 13 with type 1 ROP, 44 with type 2 or mild ROP, and 53 without ROP. Type 1 ROP showed no significant difference in microbial diversity up to 8 postnatal weeks (p = 0.057), while type 2 and no ROP groups displayed increased diversity (p = 0.0015 and p = 0.049, respectively). Bifidobacterium genera was notably less abundant in type 1 ROP group at first postnatal week (p = 0.022) and remained low in subsequent weeks. Predicted functional analysis revealed enriched pathways in membrane transport, carbohydrate metabolism, amino acid metabolism, and replication and repair., Conclusions: Reduced gut microbial diversity may be associated with ROP development in high-risk preterm infants. Further research is needed to comprehend how early-life Bifidobacterium reduction affects metabolism and how targeting microbiome may help for ROP prevention and management., (© 2024 Royal Australian and New Zealand College of Ophthalmologists.)

Background:  Postoperative new-onset atrial fibrillation (AF) has been shown to be associated with increased surgical morbidity and mortality following cancer ablation surgery. However, evidence of new-onset AF's impact on surgical outcomes in head and neck cancer patients undergoing tumor ablation and microvascular free tissue transfer remains scarce. This study aims to evaluate the association between AF and surgical outcomes in these patients., Methods:  We enrolled head and neck cancer patients who underwent tumor ablation reconstructed with microvascular free tissue transfer from the National Health Insurance Research Database (NHIRD). Patients were grouped into the following: (1) without AF, (2) new-onset AF, and (3) preexisting AF. The groups were matched by propensity score based on age, gender, cancer stage, and comorbidities. The primary outcome was postoperative complications, whereas all-cause mortality was the secondary outcome., Results:  In total, 26,817 patients were included in this study. After matching, we identified 2,176 (79.24%) patients without AF, 285 (10.37%) with preexisting AF, and 285 (10.37%) with new-onset AF. Our results demonstrated that the free flap failure rate was twofold escalated in patients with new-onset AF (9.8%) compared to those without AF (5.4%) or preexisting AF (5.3%; p  = 0.01). However, we did not identify significant differences among other postoperative complications across groups. Additionally, we found that the risk of all-cause mortality was significantly elevated in patients with preexisting AF ( p  < 0.001) compared to those without AF or new-onset AF., Conclusion:  Our study demonstrated that new-onset AF is associated with an increased risk of flap failure and could serve as a predictor. On the other hand, all-cause mortality in patients with preexisting AF was significantly elevated. Close postoperative monitoring in patients with new-onset and preexisting AF is crucial to identify any potential adverse effects., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Approximately 10-15 % of endometrial cancer patients with tumors confined to the uterus (FIGO 2009 stage I) demonstrate recurrence and the oncologic outcomes are highly related to recurrence patterns. This study aimed to verify whether the FIGO 2023 staging system could discriminate outcomes., Materials and Methods: Between January 2010 and March 2019, 536 FIGO 2009 stage I patients were eligible for this retrospective cohort study. Patient characteristics and clinicopathological data were retrieved from electronic medical records. The patients were reclassified according to the FIGO 2023 staging criteria. Oncological outcomes included the recurrence rate, recurrence pattern, and overall survival., Results: Among the 536 eligible patients, the (sub)stage migration rate was 23.5 % from the FIGO 2009 to the FIGO 2023 stage system. FIGO 2023 staging system resulted in (sub)stage up-migration, mostly owing to aggressive histological types. A higher recurrence rate was detected in the FIGO 2023 stage II patients (12.3 %) compared to the stage I patients (6.9 %). In comparison to the FIGO 2023 stage I patients, the stage II patients had a higher distant recurrence rate (8.8 % vs. 2.6 %) and poorer overall survival (38.0 vs 69.0 months, p = 0.02)., Conclusion: Patients who are upstaged are prone to worse oncological outcomes, including distant recurrence and mortality. Therefore, comprehensive adjuvant treatment strategies based on each FIGO 2023 substage are imperative., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Round spermatid injection (ROSI) into oocytes offers men with nonobstructive azoospermia (NOA) the opportunity to have biological offspring in cases where mature spermatozoa are not detected. However, the clinical outcomes of ROSI remain poor. This study compared the outcomes of ROSI with intracytoplasmic sperm injection (ICSI) and investigated the effect of hormonal pretreatment., Methods: This retrospective cohort study enrolled infertile couples undergoing either ROSI or ICSI at the reproductive center in Taipei Veterans General Hospital. The administration of selective estrogen receptor modulators, gonadotropins, and aromatase inhibitors in male patients were recorded. Relevant hormonal markers and biochemical parameters were determined. The outcomes of ROSI and ICSI were assessed based on fertilization rate, implantation rate, and live birth rate., Results: A total of 36 couples were recruited in the ROSI group, whereas 39 couples were recruited in the ICSI group for the analysis. Patients in each group demonstrated similar characteristics, except for a higher proportion of male patients in the ROSI group who were pretreated with anastrozole. The fertilization rate and implantation rate were similar between ROSI and ICSI groups after adjusting for confounding variables. The live birth rate was significantly lower in the ROSI group (8.3%) than in the ICSI group (30.8%) before and after adjusting for confounding variables., Conclusion: ROSI demonstrated fertilization and implantation rates comparable to those of ICSI for male patient with NOA undergoing testicular sperm extraction surgery. Anastrozole may improve the outcomes of ROSI into oocytes. Further studies evaluating the effect of anastrozole administration on ROSI outcomes are warranted., Competing Interests: Conflicts of interest: Dr. William J. Huang Dr. Yi-Jen Chen, editorial board members at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Objective: With an estimated global frequency ranging from5 % to 21 %, polycystic ovary syndrome (PCOS) is one of the most prevalent hormonal disorders. There are many factors found to be related to PCOS. However, most of these researches used traditional methods such as multiple logistic regression (LR). Nowadays, machine learning (Mach-L) emerges as a new method and can be used in medical researches. In the present study, there were two goals: 1. Compare the accuracy of five alternative Mach-L techniques with that of conventional LR. 2. Use Mach-L to forecast PCOS and prioritize the risk factors., Materials and Methods: Totally, 170 PCOS patients and 950 control participants were included. We collected information on demographics, biochemistry, and lifestyle. PCOS was identified using Rotterdam criteria. Random Forest (RF), stochastic gradient boosting (SGB), multivariate adaptive regression splines (MARS), extreme gradient boosting (XGBoost), and gradient boosting with categorical features support (CatBoost) are five Mach-L algorithms that were used. Models with lower estimation errors were better., Results: By using t-test, we found subjects with PCOS were younger, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), γ-Glutamyl transferase (γ-GT), Triglyceride (TG), and educational levels were higher. All the five Mach-L methods had lower estimation errors compared to LR. The average of the AUC derived from Mach-L was mean AUC of 0.6669, higher than the that of LR (0.5908). Finally, age, TG, GPT, white blood cell count (WBC), uric acid (UA), and platelet (Plt) were the six most important risk factors selected by Mach-L., Conclusion: Mach-L methods overtook conventional LR and age was the most significant factor, followed by TG, GPT, WBC, UA, and Plt in a cohort of Chinese women., Competing Interests: Conflicts of interest The authors have no conflicts of interest relevant to this article., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: This retrospective study evaluates the effectiveness of pulsed dye laser (PDL) treatment in early versus late treatment groups for traumatic or postoperative scars. The study aims to determine the threshold between early and late treatment. Additionally, it investigates factors that may influence wound healing outcomes., Methods: The medical records of 147 patients who underwent PDL treatment at our institution between January 2018 and December 2022 were retrospectively reviewed. Inclusion criteria were patients receiving PDL treatment for traumatic or postoperative scars. Out of these patients, we selected those who were willing to receive telephone interviews or re-visit at a scheduled time. Eventually, 52 participants were included in our study. A standardized questionnaire was administered to all participants during telephone interviews, encompassing inquiries regarding their medical history, treatment experiences, and the patient component of the Patient and Observer Scar Assessment Scale. Among the enrolled patients, 38 were contacted and interviewed via telephone, while the remaining 14 patients attended follow-up visits where photographs of their current skin condition were captured. The pretreatment and latest follow-up photographs obtained from the clinical database were independently scored in a blinded manner by two dermatologist reviewers using both the Vancouver Scar Scale and the Manchester Scar Scale., Results: Among the 52 patients, 43 (82.7%) were successfully treated with good response. The correlation coefficients between week-to-treatment initiation and posttreatment MSS and VSS among patients with good response were 0.50 (p < 0.001) and 0.46 (p = 0.002), respectively. Given these findings, we established a treatment initiation threshold of 10 weeks, distinguishing patients into early and late treatment groups. The early treatment group showed borderline significantly lower posttreatment MSS and VSS scores than the late treatment group (MSS: 7.5 ± 2.1 vs. 9.3 ± 2.5, p = 0.011; VSS: 2.8 ± 2.0 vs. 4.5 ± 2.3, p = 0.011). Furthermore, both MSS and VSS of posttreatment showed significantly greater improvement in the early treatment group (4.4 ± 1.6 vs. 3.2 ± 1.9; p = 0.03 and 3.8 ± 1.8 vs. 2.8 ± 1.4; p = 0.04)., Conclusions: Early intervention using a PDL within 10 weeks post-injury achieved better outcomes in treating traumatic and postoperative scars based on both clinical and patient opinions., (© 2024 Wiley Periodicals LLC.)

Background: Postoperative radiotherapy (PORT) and concurrent chemoradiation (CCRT) are indicated for patients with advanced oral cancer. However, the benefits for pT1-2N1 disease without adverse pathological features are controversial., Methods: This retrospective study using the Taiwan Cancer Registry database included patients with pT1-2N1 oral cancer from January 1, 2011, to December 31, 2017. Overall survival was analyzed in patients receiving surgery alone, PORT, or CCRT., Results: Among the 862 patients, the five-year overall survival rate in patients receiving surgery alone, PORT, and CCRT was 62.2%, 58.7%, and 71.1% (P = 0.03), respectively. CCRT was associated with longer survival than PORT (P = 0.008). Survival in patients with pT2 disease was significantly higher with CCRT than PORT (P = 0.001), but no difference was observed in pT1 disease., Conclusion: CCRT demonstrated a favorable impact on survival outcomes in patients diagnosed with pT2N1 oral cancer when compared to PORT. However, no significant survival benefits were observed for patients with pT1 disease., Competing Interests: Declaration of competing interest Mu-Hung Tsai received research grants from Varian Medical Systems outside of the submitted work. The other authors declare no potential conflicts of interest., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Misfolding and accumulation of amyloid-β (Aβ) in the brains of patients with Alzheimer's disease (AD) lead to neuronal loss through various mechanisms, including the downregulation of eukaryotic elongation factor 2 (EEF2) protein synthesis signaling. This study investigated the neuroprotective effects of indole and coumarin derivatives on Aβ folding and EEF2 signaling using SH-SY5Y cells expressing Aβ-green fluorescent protein (GFP) folding reporter. Among the tested compounds, two indole (NC009-1, -6) and two coumarin (LM-021, -036) derivatives effectively reduced Aβ misfolding and associated reactive oxygen species (ROS) production. Additionally, these compounds decreased acetylcholinesterase and caspase-3/-6 activities while promoting neurite outgrowth. NC009-1 increased active phosphorylation of extracellular-signal regulated kinase (ERK) (T202/Y204), leading to an increase in inactive eukaryotic elongation factor 2 kinase (EEF2K) phosphorylation (S366). LM-021 decreased the active phosphorylation of AMP-activated protein kinase (AMPK) (T172) and EEF2K (S398), while LM-036 exhibited dual effects, increasing inactive phosphorylation and decreasing active phosphorylation of EEF2K. These changes in EEF2K phosphorylation led to decreased EEF2K activity and a subsequent reduction in inactive phosphorylation of EEF2 (T56). This cascade further promoted the phosphorylation of transcription factor cAMP-response-element binding protein (CREB) (S133) and the expression of brain-derived neurotrophic factor (BDNF), and reduced BCL-2 associated X-protein (BAX)/B-cell lymphoma 2 (BCL2) ratio. Knockdown of EEF2 abolished the effects of NC009-1, LM-021, and LM-036 on CREB phosphorylation, BDNF expression, caspase-3 activity, and neurite outgrowth. These findings demonstrate that NC009-1, LM-021, and LM-036 exert their neuroprotective effects through modulation of EEF2K signaling, highlighting their potentials as therapeutic candidates for AD., (© 2025 International Society for Neurochemistry.)

Objective: The association between gastroesophageal reflux disease (GERD) and laryngeal disorders remains debatable, although it has been the focus of extensive clinical and laboratory research. We conducted this study to obtain evidence on the association., Study Design: Population-based cohort study., Setting: Taiwan National Health Insurance Research Database (NHIRD)., Methods: Using data from Taiwan's NHIRD (January 2000 to December 2018), we performed a population-based analysis to estimate the risk of laryngeal disorders in patients with GERD and those without GERD., Results: The GERD and non-GERD cohorts comprised 176,319 and 705,276 patients, respectively. The cohorts were matched at a ratio of 1:4 based on sex, age, urbanization level, and income level. The risk of laryngeal disorders was higher in the GERD cohort than in the non-GERD cohort (adjusted hazard ratio: 1.64; 95% confidence interval: 1.61-1.67)., Conclusion: This study is the first to use population data for identifying the association between GERD and laryngeal disorders for real-world findings. Our population-based analysis indicates that patients with GERD have an elevated risk of laryngeal disorders., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

To entrap sparingly water-soluble drugs like CPT-11 (irinotecan), the poly(lactic-co-glycolic acid) (PLGA) nanoparticle (NP) is highly favored due to its low cytotoxicity and approval for clinical use. On the other hand, entrapping hydrophobic oleic acid-coated iron oxide magnetic nanoparticles (OMNP) in PLGA NP can provide a nanovehicle for magnetically targeted drug delivery. Our goal in this study is to develop a new dual-targeted magnetic lipid-polymer NP for the delivery of CPT-11. We first co-entrap OMNP and CPT-11 in self-assembled lipid-PLGA NP to prepare OLNP@CPT-11. The OLNP@CPT-11 surface was modified with an epidermal growth factor receptor (EGFR) antibody Cetuximab (CET), which can actively target the overexpressed EGFR on the U87 glioblastoma cell surface. The OLNP-CET@CPT-11 enables dual targeting through both external magnetic guidance and CET-mediated active targeting. The NP was characterized for physicochemical properties using various analytical techniques. In vitro study confirms ligand-receptor interaction results in enhanced endocytosis of OLNP-CET@CPT-11 by U87 cells, which offers increased cytotoxicity and elevated cell apoptosis rates. Furthermore, magnetic guidance of OLNP-CET@CPT-11 to U87 cells can induce cell death exclusively in the magnetically targeted zone. The dual-targeted strategy also provides the best therapeutic efficacy against subcutaneously implanted U87 tumors in nude mice with intravenously delivered OLNP-CET@CPT-11., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Jyh-Ping Chen reports financial support was provided by Chang Gung Memorial Hospital Linkou. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The effect of dispersing multiwalled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs) in the matrix on the low-velocity impact resistance and post-impact residual tensile strength of the carbon fiber reinforced epoxy composite laminates has been experimentally analyzed in this study. The composite specimens with the matrix reinforced by different nanoparticle types and various nanoparticle concentrations (0.1, 0.3, and 0.5 wt.%) were prepared and impacted. The post-impact tensile quasi-static and fatigue tests were performed on the specimens with different configurations to study the influence of aforementioned factors on the impact resistance and damage tolerance. Experimental results show that adding nanoparticles in the matrix increases the maximum impact force, reduces the damage area, and alleviates the dent depth of the laminates remarkedly. Moreover, the improvement in these impact resistances increases with the applied nanoparticle concentrations. The nano-modified composite laminates present higher post-impact static strength and longer fatigue life than the specimens with a neat epoxy matrix. Furthermore, both the post-impact static tensile strength and fatigue life increase with the applied nanoparticle concentrations. The damage areas measured using infrared thermography were found to increase linearly with the applied fatigue cycles for all the studied specimens with various configurations. The damage area growth rates of nano-modified composite laminates decrease significantly as the applied nanoparticle concentrations increase. The MWCNTs present better performance than GNPs in improving post-impact static strength and extending the residual fatigue life, however the effect of applied nanoparticle type on the fatigue damage growth rate is slight.

Delivering microRNA (miRNA) to treat cardiac disease is a significant challenge, and selecting an efficient delivery method to target the affected organ is critical for therapeutic success. Here, we present a protocol for delivering miRNA to the heart of rats with heart failure using adeno-associated virus (AAV9) coupled with a hydrodynamic transfusion strategy. We describe steps for inducing heart failure, echocardiography, and AAV9 application. Further, we provide a comprehensive procedure to detect miRNA expression in cardiac tissues using stem-loop RT-qPCR. For complete details on the use and execution of this protocol, please refer to Mushtaq et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Muscle loss after radiotherapy is associated with poorer survival in patients with oral cavity squamous cell carcinoma (OCSCC). However, the threshold of muscle loss remains unclear. This study aimed to utilize explainable artificial intelligence to identify the threshold of muscle loss associated with survival in OCSCC., Materials and Methods: We enrolled 1087 patients with OCSCC treated with surgery and adjuvant radiotherapy at two tertiary centers (660 in the derivation cohort and 427 in the external validation cohort). Skeletal muscle index (SMI) was measured using pre- and post-radiotherapy computed tomography (CT) at the C3 vertebral level. Random forest (RF), eXtreme Gradient Boosting (XGBoost), and Categorical Boosting (CatBoost) models were developed to predict all-cause mortality, and their performances were evaluated using the area under the curve (AUC). Muscle loss threshold was identified using the SHapley Additive exPlanations (SHAP) method and validated using Cox regression analysis., Results: In the external validation cohort, the RF, XGBoost, and CatBoost models achieved favorable performance in predicting all-cause mortality (AUC: 0.898, 0.859, and 0.842). The SHAP method demonstrated that SMI change after radiotherapy was the most important feature for predicting all-cause mortality and consistently identified SMI loss ≥ 4.2% as the threshold in all three models. In multivariable analysis, SMI loss ≥ 4.2% was independently associated with increased all-cause mortality risk in both cohorts (derivation cohort: hazard ratio: 6.66, p < 0.001; external validation cohort: hazard ratio: 8.46, p < 0.001)., Conclusion: This study can assist clinicians in identifying patients with considerable muscle loss after treatment and guide interventions to improve muscle mass., Key Points: Question Muscle loss after radiotherapy is associated with poorer survival in patients with oral cavity cancer; however, the threshold of muscle loss remains unclear. Findings Explainable artificial intelligence identified muscle loss ≥ 4.2% as the threshold of increased all-cause mortality risk in both derivation and external validation cohorts. Clinical Relevance Muscle loss ≥ 4.2% may be the optimal threshold for survival in patients who receive adjuvant radiotherapy for oral cavity cancer. This threshold can guide clinicians in improving muscle mass after radiotherapy., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Dr. Jie Lee. Conflict of interest: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: One of the authors (Dr. Jie Lee) has significant statistical expertise. Informed consent: Written informed consent was waived by the Institutional Review Board. Ethical approval: This study was approved by Institutional Review Board of MacKay Memorial Hospital (23MMHIS437e) and Changhua Christian Hospital (IRB No.180503). Study subjects or cohorts overlap: None. Methodology: Retrospective Observational Multicenter study, (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Introduction: Evidence of neuroprotective effects of glucosamine on Asian optic neuritis (ON) patients remains sparse. We aimed to examine the longitudinal association between glucosamine use and the incidence of first-ever ON to identify the factors contributing to reducing ON risk in older Asian populations., Methods: This nationwide cohort study from 2000 to 2015 evaluated 24,155 individuals. The International Classification of Diseases-9 Clinical Modification code 377 determined newly diagnosed ON. Outcomes include the annual trend of first-ever ON incidence, crude/adjusted hazard ratios (HRs) of incident ON stratified by sociodemographic characteristics, and comorbidities., Results: Glucosamine exposure has been significantly associated with reduced ON incidence (Log-rank p < 0.001) since the fifth year of clinical surveillance. The overall adjusted HR of ON among glucosamine users was 0.718 (CI = 0.524-0.901, p = 0.001), and in the glucosamine-exposed group, disease onset was approximately 129 days later than in nonusers (6.83 ± 4.27 vs. 6.47 ± 4.01 years to ON, p < 0.001). Moreover, glucosamine was associated with reduced ON risk in patients without diabetes mellitus, hypertension, tobacco use, and chronic heart failure. While administering glucosamine, the risk was reduced by more than half among individuals aged between 45 and 64 years (aHR = 0.433, CI = 0.316-0.544, p < 0.001) and patients from medical centers (aHR = 0.453, CI = 0.330-0.568, p < 0.001)., Conclusion: Taiwanese glucosamine users have a decreased risk of developing ON. Our work provides a theoretical basis for expanding glucosamine indications in regions with minimal prevalence of ON., (© 2024 S. Karger AG, Basel.)

Unbalance faults are among the common causes of interruptions and unexpected failures in rotary systems. Therefore, monitoring unbalance faults is essential for predictive maintenance. While conventional time-invariant mathematical models can assess the impact of these faults, they often rely on proper assumptions of system factors like bearing stiffness and damping characteristics. In reality, continuous high-speed operation and environmental factors like load variations cause these parameters to change. This work presents a novel architecture for unbalance fault monitoring and prognosis, in which the bearing parameters are treated as variables that change with operating conditions. This enables the development of a more reliable mathematical model for continuous monitoring and prognosis of unbalance faults in rotor systems. This Bayesian inference framework uses Markov Chain Monte Carlo (MCMC) sampling to identify dynamic bearing parameters. Specifically, the Metropolis algorithm is employed to systematically evaluate the range of acceptable parameter values within the framework. A novel dual-MCMC loops explore and assess the parameter space, resulting in more accurate and reliable bearing parameter estimations. These updated parameters improve the demonstrated turbine rotor-bearing system's unbalance assessment up to 74.48% of the residual error compared to models with fixed parameters. This validates the Bayesian framework for predictive monitoring and maintenance-oriented solutions.

Extracellular vesicles (EVs) derived from T cells have been proposed to mediate intercellular communication and orchestrate immune responses. The immunosuppressive drug, tacrolimus (TAC), suppresses T cell activity; however, the impact of TAC on T cell-derived EVs remains primarily unexplored. In this study, human primary T cells purified from healthy donors were used to investigate TAC-mediated regulation of EV secretion by T cells. Using size exclusion chromatography (SEC) to isolate EVs released by T cells, we found that the number of released EVs was increased upon anti-CD3/CD28 bead-mediated activation. Furthermore, pre-treatment with TAC before activation had a potentiating effect on EV release, as evidenced by western blot analysis of EV markers and small particle flow cytometry. In addition, we showed that EVs isolated from the plasma of TAC-treated kidney transplant patients were increased compared to those observed with pre-transplant plasma. Upon examining the mechanism underlying the action of TAC, we found that TAC impaired autophagy-lysosome-mediated degradation by inhibiting the nuclear translocation of transcription factor EB, a master regulator of lysosomal biogenesis. Notably, the addition of trehalose, an autophagy inducer, abrogated the TAC-induced EV release, indicating that TAC regulated EV secretion via the autophagy-lysosomal pathway. At the functional level, we demonstrated that EVs from TAC-treated T cells carried a decreased amount of CD40L, a protein critical for the activation of the adaptive immune response. Collectively, these findings demonstrate that an overall increase in EV production and decreased CD40L levels in EVs are characteristic responses of T cells to TAC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To develop and evaluate measures of patient work system factors in medication management that may be modifiable for improvement during the care transition from hospital to home among older adults., Design, Settings and Participants: Measures were developed and evaluated in a multisite prospective observational study of older adults (≥65 years) discharged home from medical units of two US hospitals from August 2018 to July 2019., Main Measures: Patient work system factors for managing medications were assessed during hospital stays using six capacity indicators, four task indicators and three medication management practice indicators. Main outcomes were assessed at participants' homes approximately a week after discharge for (1) Medication discrepancies between the medications taken at home and those listed in the medical record, and (2) Patient experiences with new medication regimens., Results: 274 of the 376 recruited participants completed home assessment (72.8%). Among capacity indicators, most older adults (80.6%) managed medications during transition without a caregiver, 41.2% expressed low self-efficacy in managing medications and 18.3% were not able to complete basic medication administration tasks. Among task indicators, more than half (57.7%) had more than 10 discharge medications and most (94.7%) had medication regimen changes. Having more than 10 discharge medications, more than two medication regimen changes and low self-efficacy in medication management increased the risk of feeling overwhelmed (OR 2.63, 95% CI 1.08 to 6.38, OR 3.16, 95% CI 1.29 to 7.74 and OR 2.56, 95% CI 1.25 to 5.26, respectively). Low transportation independence, not having a home caregiver, low medication administration skills and more than 10 discharge medications increased the risk of medication discrepancies (incidence rate ratio 1.39, 95% CI 1.01 to 1.91, incidence rate ratio 1.73, 95% CI 1.13 to 2.66, incidence rate ratio 1.99, 95% CI 1.37 to 2.89 and incidence rate ratio 1.91, 95% CI 1.24 to 2.93, respectively)., Conclusions: Patient work system factors could be assessed before discharge with indicators for increased risk of poor patient experience and medication discrepancies during older adults' care transition from hospital to home., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Over a 2-year period, we identified Transmission from Room Environment Events (TREE) across the Johns Hopkins Health System, where the subsequent room occupant developed the same organism with the same antimicrobial susceptibilities as the patient who had previously occupied that room. Overall, the TREE rate was 50/100,000 inpatient days.