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Lei Sun, Xin-Yu Kuang, Jing Zhang, Wen-Yan Huang Department of Nephrology and Rheumatology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaCorrespondence: Wen-Yan Huang, Email huangwenyan@sjtu.edu.cnPurpose: As a rare collagen type IV hereditary kidney disease, X-linked Alport syndrome (XLAS) is the most common form of Alport syndrome, the prevalence of which is estimated at 1:10,000 of the population, four times higher than the prevalence rate of autosomal recessive Alport syndrome. To describe a series of eight XLAS children with persistent hematuria and proteinuria and the clinical outcomes after hydroxychloroquine (HCQ) treatment to assess its efficacy as early intervention.Patients and Methods: The study retrospectively analysed 8 patients with persistent hematuria and proteinuria at different onset ages who were diagnosed with XLAS and been treated with HCQ. The urinary erythrocyte count, urinary albuminn were measured. Descriptive statistics were used to estimate the patients’ responses to HCQ treatment after one month, three months, and six months.Results: After the first month, the three months, and the six months of HCQ treatment, the urinary erythrocyte counts of four, seven, and eight children were significantly reduced; the decreasing proteinuria was found in two, four, and five children. Only one child with increasing proteinuria was found after 1-month HCQ treatment. This proteinuria was maintained after 3-month HCQ treatment but decreased to minor after 6-month HCQ treatment.Conclusion: We present the first potential efficacy of HCQ treatment in XLAS with hematuria and persistent proteinuria. It suggested that HCQ could be an effective treatment to ameliorate hematuria and proteinuria.Keywords: X-linked Alport syndrome, hematuria, proteinuria, hydroxychloroquine, therapy

Nalee Kim,1,* Jason Chia-Hsien Cheng,2,* Nitin Ohri,3 Wen-Yen Huang,4 Tomoki Kimura,5 Zhao Chong Zeng,6 Victor Ho Fun Lee,7 Chul Seung Kay,8 Jinsil Seong9 1Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan School of Medicine, Seoul, Republic of Korea; 2Division of Radiation Oncology, Department of Oncology, National Taiwan University Hospital, Taipei City, Taiwan; 3Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York; 4Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan; 5Department of Radiation Oncology, Hiroshima University Hospital, Hiroshima, Japan; 6Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 7Department of Radiation Oncology, The University of Hong Kong, Hong Kong; 8Department of Radiation Oncology, Jeju Halla Hospital, Jeju, Republic of Korea; 9Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Jinsil Seong, Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea, Tel +82-2-2228-8095, Fax +82-2-2227-7823, Email jsseong@yuhs.acBackground/Purpose: The Asian Liver Radiation Therapy Study Group has formed a large and detailed multinational database of outcomes following stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC). Here, we explored the potential impact of HCC etiology on SBRT efficacy. Tumor control probability (TCP) models were established to estimate the likelihood of local control (LC).Methods: Data from 415 patients who were treated with SBRT for HCC were reviewed. Cox proportional hazards models were used to identify key predictors of LC. TCP models accounting for biologic effective dose (BED) and tumor diameter were generated to quantify associations between etiology and LC.Results: Cox models demonstrated that hepatitis C virus (HCV) infection was associated with favorable LC following SBRT (HR=0.52, 95% CI 0.04– 0.96, p=0.036). The 2-year LC rate for patients with HCV etiology was 88%, compared to 78% for other patients. Small tumor and high BED were also associated with favorable LC. TCP models demonstrated a 10– 20% absolute increase in predicted LC across the range of SBRT doses and tumor sizes.Conclusion: We found a novel association between HCV status and LC after SBRT for HCC that warrants further exploration. If validated in other datasets, our findings could help clinicians tailor SBRT schedules.Graphical Abstract: Keywords: tumor control probability, hepatocellular carcinoma, stereotactic body radiation therapy, hepatitis C virus

Chih-Weim Hsiang,1 Wen-Yen Huang,2,3 Jen-Fu Yang,2 Po-Chien Shen,2 Yang-Hong Dai,2 Ying-Fu Wang,2 Chun-Shu Lin,2 Wei-Chou Chang,1 Cheng-Hsiang Lo2 1Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 3Institute of Clinical Medicine, National Yang-Ming University, Taipei, TaiwanCorrespondence: Cheng-Hsiang LoDepartment of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec 2, Cheng-Gong Road, Neihu, Taipei, 114, TaiwanTel +886-2-87927122Fax +886-2-66002357Email lsir183@yahoo.com.twPurpose: Immune response to antitumor therapies has been correlated with oncologic outcomes. This study aimed to determine whether dynamic changes in immune parameters could predict survival outcomes and assess their relationship with liver toxicity in hepatocellular carcinoma (HCC) patients treated with stereotactic body radiation therapy (SBRT).Methods: Data on pre- and post-SBRT (within 3 months) peripheral blood cell counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were retrospectively collected. Kinetic changes in these immune parameters and delta-NLR (dNLR) and delta-PLR (dPLR) in response to SBRT were evaluated. Overall survival (OS) and progression-free survival (PFS) were compared based on baseline NLR/PLR and dNLR/dPLR. Additionally, the association of these dynamic measures with liver toxicity was determined.Results: The study included 93 patients with a median 10.7-month follow-up. Significant increases in NLR (p< 0.001) and PLR (p=0.003) were observed after SBRT. In the multivariable analysis, elevated pre-SBRT NLR (p< 0.001) and dNLR (p=0.011) were predictive of worse OS. dNLR was not associated with PFS. Neither PLR nor dPLR was predictive of survival outcomes. Patients with Child–Turcotte–Pugh class B had higher dNLR and greater risk of liver toxicity than class A counterparts. Receiver operating characteristic curve analysis found that dNLR ≥ 1.9 was an optimal cut-off value for determining liver toxicity risk (35.1% vs 7.5%, p=0.002).Conclusion: Baseline NLR and dNLR can complementarily predict OS in HCC patients treated with SBRT. Elevated dNLR is associated with worse OS and development of liver toxicity, possibly through their relationship with baseline liver function. Dynamic changes in NLR should be monitored in HCC care.Keywords: hepatocellular carcinoma, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, stereotactic body radiotherapy, liver toxicity

Wei-Chou Chang,1 Hsian-He Hsu,1 Sung-Hua Chiu,1 Wen-Yen Huang,2 Cheng-Hsiang Lo,2 Hsuan-Hwai Lin,3 Pei-Ching Huang,4 Yu-Lueng Shih,3 Yung-Liang Wan4 1Department of Radiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan; 2Department of Radiation Oncology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan; 3Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan; 4Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, TaiwanCorrespondence: Yung-Liang WanDepartment of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, TaiwanEmail ylw0518@cgmh.org.twAbstract: Drug-eluting beads transarterial chemoembolization (DEB-TACE) is an alternative to conventional lipiodol-based TACE (cTACE) to treat hepatocellular carcinoma (HCC). With the advancement in pharmacology, small-caliber DEB-TACE (< 100 μm) has been introduced since 2016. For the treatment of hepatic neoplasms or HCC, there is a tendency to use smaller beads by DEB-TACE to achieve more extensive tumor necrosis and a significant reduction in liver toxicity in comparison with that caused by cTACE. However, the indications and potential complications of small-caliber DEB-TACE remain uncertain and have not been well established, due to lack of randomized phase III clinical trials. Instead of systematic or meta-analysis review, this narrative review article describes the suggested indications and contraindications of DEB-TACE with small DEBs, benefit of super-selective embolization of the feeding arteries and the recommended selection of small-caliber DEB. This review was approved by the institutional review board (File Number: 1-105-05-158).Keywords: chemoembolization, HCC, TACE, DEB-TACE, liver, review

Sung-Hua Chiu,1 Ping-Ying Chang,2 Yu-Lueng Shih,3 Wen-Yen Huang,4 Kai-Hsiung Ko,1 Wei-Chou Chang,1 Guo-Shu Huang1 1Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Division of Hematology/Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 3Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 4Department of Radiotherapy, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanCorrespondence: Wei-Chou ChangDepartment of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanTel +886-2- 8792-3311 ext. #16480Fax +886-2-8792-7245Email Weichou.chang@gmail.comPurpose: To evaluate the therapeutic efficacy and safety of supplement transarterial chemoembolization (TACE) with drug-eluting beads TACE (DEB-TACE) through extrahepatic collateral (EHC) arteries for the treatment of hepatocellular carcinoma (HCC).Patients and Methods: In this retrospective study, 61 unresectable HCC patients with treatment-naïve EHC blood supplies who received TACE from January 2016 to March 2019 were enrolled; of these patients, 42 (68.9%) received DEB-TACE, and 19 (31.1%) received cTACE. The hepatic tumor feeding arteries were treated in the same TACE session if it presented. The tumor response, time-to-progression (TTP), and overall survival (OS) were analyzed. Safety was assessed based on the occurrence of liver function deterioration and major complications within three months after TACE.Results: DEB-TACE showed better efficacy than cTACE in the disease control rate (p=0.001), overall response rate (p=0.005), the TTP (eight months vsthree months, p=0.002) and the OS (23.8 months vs nine months, p=0.045). Nine patients in the DEB-TACE group and one patient in the cTACE group were downstaged to resection or liver transplantation (21.4% vs 5.3%, p=0.151). DEB-TACE and cTACE have no difference in the acute and chronic liver toxicity. With regard to complications, there was no significant difference in the occurrence of both major (16.7% vs 21.1%, p=0.72) and minor (57.1% vs 47.4%, p=0.48) complications between DEB-TACE and cTACE.Conclusion: DEB-TACE through EHC arteries has a potential therapeutic effect in the treatment of unresectable HCC, with comparable safety compared with cTACE.Keywords: hepatocellular carcinoma, chemoembolization, therapeutic, collateral circulation, cone-beam computed tomography

PengMing Sun,1,* XiaoDan Mao,1,* Min Gao,2 MeiMei Huang,1 LiLi Chen,1 GuanYu Ruan,1 WeiYi Huang,1 Elena Ioana Braicu,3 Jalid Sehouli3 1Laboratory of Gynecologic Oncology, Fujian Provincial Maternity and Children’s Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, People’s Republic of China; 2Department of Gynecology Oncology, Beijing Cancer Hospital, Beijing 100142, People’s Republic of China; 3Department of Gynecology, Campus Virchow Clinic, Charité Medical University Berlin, Berlin, Germany *These authors contributed equally to this work Purpose: To explore the targeted therapy of estrogen-related receptor α (ERRα) in endometrial cancer (EC) cells and its potential mechanisms.Methods: The mRNA and protein expression levels of ERRα and estrogen receptor α (ERα) were detected by qPCR and Western blotting in RL-952, AN3-CA, HEC-1A, and HEC-1B EC cell lines. After treatment with the ERRα-specific antagonist XCT790 or infection with lentivirus-mediated small interfering RNA (siRNA) targeting the ERRα (siRNA-ERRα), cell proliferation and apoptosis were evaluated by MTS assay and flow cytometry. After treatment with siRNA-ERRα, the expression profiles of transcription factors (TFs) were analyzed by protein/DNA arrays in EC cells.Results: The relative mRNA levels of ERRa in RL-952 (1±0.0831) and AN3-CA (1.162±0.0325) were significantly higher than those in HEC-1A (0.3081±0.0339) and HEC-1B (0.1119±0.0091) (P

Lih-Rou Rau,1 Wan-Yu Huang,1 Jiunn-Woei Liaw,2–5 Shiao-Wen Tsai1,3,6 1Graduate Institute of Biochemical and Biomedical Engineering, 2Department of Mechanical Engineering, 3Center for Biomedical Engineering, Chang Gung University, 4Institute for Radiological Research, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, 5Center for Advanced Molecular Imaging and Translation, 6Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan, Republic of China Abstract: The specific properties of gold nanoparticles (AuNPs) make them a novel class of photothermal agents that can induce cancer cell damage and even death through the conversion of optical energy to thermal energy. Most relevant studies have focused on increasing the precision of cell targeting, improving the efficacy of energy transfer, and exploring additional functions. Nevertheless, most cells can uptake nanosized particles through nonspecific endocytosis; therefore, before hyperthermia via AuNPs can be applied for clinical use, it is important to understand the adverse optical–thermal effects of AuNPs on nontargeted cells. However, few studies have investigated the thermal effects induced by pulsed laser-activated AuNPs on nearby healthy cells due to nonspecific treatment. The aim of this study is to evaluate the photothermal effects induced by AuNPs plus a pulsed laser on MG63, an osteoblast-like cell line, specifically examining the effects on cell morphology, viability, death program, and differentiation. The cells were treated with media containing 50 nm AuNPs at a concentration of 5 ppm for 1 hour. Cultured cells were then exposed to irradiation at 60 mW/cm2 and 80 mW/cm2 by a Nd:YAG laser (532 nm wavelength). We observed that the cytoskeletons of MG63 cells treated with bare AuNPs followed by pulsed laser irradiation were damaged, and these cells had few bubbles on the cell membrane compared with those that were not treated (control) or were treated with AuNPs or the laser alone. There were no significant differences between the AuNPs plus laser treatment group and the other groups in terms of cell viability, death program analysis results, or alkaline phosphatase and calcium accumulation during culture for up to 21 days. However, the calcium deposit areas in the cells treated with AuNPs plus laser were larger than those in other groups during the early culture period. Keywords: pulsed laser, photothermal, gold nanoparticles, osteoblast, apoptosis, mineralization

Shen-Fu Lin,1 Ying-Chen Chen,2 Hsiu-O Ho,2 Wei-Yu Huang,2 Ming-Thau Sheu,2,3 Der-Zen Liu1,4 1Graduate Institute of Biomedical Materials and Tissue Engineering, College of Oral Medicine, 2School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; 3Clinical Research Center and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan; 4Center for General Education, Hsuan Chuang University, Hsinchu, Taiwan Abstract: The utilization of self-microemulsifying premicroemulsion systems (SMEPMS) as templates for preparing poorly water-soluble compounds in the nanosized range represents a promising strategy. Fenofibrate was formulated with n-butyl L-lactate, Tween 80, and a number of cosurfactants (ethanol, 1-propanol, and PEG 600), diluted with the water phase (either water or saccharide solution) and then subjected to a freeze-drying (FD) process to obtain SMEPMS nanosized particulates. Results demonstrated that the particle size after resuspension of these FD SMEPMS nanosized particulates in water was too large, so the addition of saccharide solutions (lactose, mannitol, glucose, sucrose, and trehalose) as the solid carrier to prevent particles from aggregating seemed to be necessary and workable due to steric hindrance and repulsion. However, instability of these resuspended FD nanosized particulates after 30–90 minutes still occurred, and the addition of 0.5% sodium lauryl sulfate in the resuspending medium was able to retard the aggregation and maintain the particle size within the nano-range. Evaluation by scanning electron microscopy and X-ray powder diffraction also confirmed the results. It was concluded that using an SMEPMS formulation with PEG 600 as the cosurfactant, and in the presence of a suitable saccharide as an anticaking agent and FD process were able to produce fenofibrate nanoparticles. Keywords: fenofibrate, saccharides, freeze-drying, nanoparticles

Objective To examine whether a history of sexually transmitted infections (STIs) or positive STI serology is associated with prevalent and incident benign prostatic hyperplasia (BPH)/lower urinary tract symptoms (LUTS)-related outcomes in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Methods Self-reported history of STIs (gonorrhoea, syphilis) was ascertained at baseline, and serological evidence of STIs (Chlamydia trachomatis, Trichomonas vaginalis, human papillomavirus (HPV)-16, HPV-18, herpes simplex virus type 2, human herpesvirus type 8 and cytomegalovirus) was detected in baseline serum specimens. We used data collected on the baseline questionnaire, as well as results from the baseline prostate-specific antigen (PSA) test and digital rectal examination (DRE), to define prevalent BPH/LUTS-related outcomes as evidence of LUTS (self-reported diagnosis of an enlarged prostate/BPH, BPH surgery or nocturia [waking ≥2 times/night to urinate]) and evidence of prostate enlargement (PSA > 1.4 ng/mL or prostate volume ≥30 mL) in men without prostate cancer. We created a similar definition of incident BPH using data from the follow-up questionnaire completed 5-13 years after enrolment (self-reported diagnosis of an enlarged prostate/BPH or nocturia), data on finasteride use during follow-up, and results from the follow-up PSA tests and DREs. We used Poisson regression with robust variance estimation to calculate prevalence ratios (PRs) in our cross-sectional analysis of self-reported (n = 32 900) and serologically detected STIs (n = 1 143) with prevalent BPH/LUTS, and risk ratios in our prospective analysis of self-reported STIs with incident BPH/LUTS (n = 5 226). Results Generally null results were observed for associations of a self-reported history of STIs and positive STI serologies with prevalent and incident BPH/LUTS-related outcomes, with the possible exception of T. vaginalis infection. This STI was positively associated with prevalent nocturia (PR 1.36, 95% confidence interval (CI) 1.18-1.65), prevalent large prostate volume (PR 1.21 95% CI 1.02-1.43), and any prevalent BPH/LUTS (PR 1.32 95% CI 1.09-1.61); too few men had information on both STI serologies and incident BPH/LUTS to investigate the associations between T. vaginalis infection and incident BPH/LUTS-related outcomes. Conclusions Our findings do not support associations of several known STIs with BPH/LUTS-related outcomes, although T. vaginalis infection may warrant further study.

Background: Clinical outcome of internal carotid artery (ICA) occlusion is highly variable and the reason is uncertain.Aim: To study the predictive factors of clinical outcome and stroke recurrence in patients with ischemic stroke associated with unilateral atherosclerosis-related ICA occlusion.Settings and Design: Prospective study in neurology department of a single hospital.Materials and Methods: We prospectively studied 66 patients who suffered from first-ever ischemic stroke associated with unilateral atherosclerosis-related ICA occlusion over a period of two years. The end point was death or stroke recurrence.Statistical Analysis: Chi-square or Fisher's exact test was used to analyze predictors of early functional outcome. Multivariate analysis was used to analyze predictors of death or stroke recurrence within two years.Result: Higher age (>or=70 years) predicted a worse functional outcome (P=0.049). Total anterior circulation syndrome (TACS) was associated with a poor functional outcome (P<0.001), but lacunar syndrome had a better outcome (P=0.001). Stroke in evolution predicted a poor outcome (P=0.001), while those with symptom improvement had a better outcome (P=0.016). Pneumonia predicted a poor outcome (P=0.021). Five patients expired and 22 patients suffered from recurrent stroke in the following 24 months. Previous transient ischemic attack (TIA) and anemia were associated with a higher risk of death or recurrent stroke within two years (P=0.036, P=0.012).Conclusion: High age, TACS, stroke in evolution and pneumonia were predictors for poor functional outcome. Previous TIA and anemia were predictors for death and recurrent stroke within two years. [ABSTRACT FROM AUTHOR]

Background: Patent foramen ovale (PFO) is a well-recognized risk factor for ischemic strokes. The true prevalence of PFO among stroke patients is still under debate. Transesophageal echocardiography (TEE) is the 'gold standard' in diagnosing PFO but the physiology requires right-to-left atrial shunting. In this report, we evaluate the prevalence of PFO in a diverse group of ischemic stroke patients studied by TEE. Methods: TEE of 1,663 ischemic stroke patients were reviewed for cardiac source of embolism, including PFO and atrial septal aneurysm (ASA). Agitated saline bubble injection was performed to look for right to left atrial shunting. Success of maneuvers to elevate right atrial pressure (RAP) was noted by looking at the atrial septal bulge. Results: Among 1,435 ischemic stroke patients analyzed, the presence or absence of PFO could not be determined in 32.1% because bulging of the septum could not be demonstrated in patients with negative contrast study despite aggressive maneuvers to elevate RAP. Of the remaining 974 patients, 294 patients (30.2%) had a PFO. The mean age was 61.5 years in both groups, with a bimodal distribution of PFO and the highest prevalence occurring in

Background: Sudden sensorineural hearing loss (SSNHL) is characterized by rapid, unexplained loss of hearing within a 72-hour period and exhibits a high incidence globally. Despite this, the outcomes of therapeutic interventions remain largely unpredictable, especially for those with profound hearing loss. Extracellular vesicles (EVs), nano-sized entities containing biological materials, are implicated in the development of numerous diseases. The specific relationship between EVs and both the severity and treatment effectiveness of SSNHL, however, is not well understood., Methods: This study involved the analysis of medical records from the Department of Otolaryngology (September 1, 2020 - December 31, 2022) of patients diagnosed with SSNHL according to the 2015 Guidelines for Diagnosis and Treatment of Sudden Deafness in China. Peripheral blood samples from patients with various types of SSNHL before and after treatment were collected, alongside samples from healthy volunteers serving as controls. Plasma EVs were isolated using gel rejection chromatography and analyzed for concentration, marker presence, and morphology using Nanosight, Western blot, and transmission electron microscopy (TEM), respectively. Proteomics and miRNA assessments were conducted to identify differentially expressed proteins and miRNAs in the plasma EVs of SSNHL patients and healthy volunteers. Key proteins were further validated through Western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was utilized to determine the levels of complement C3 in plasma EVs, and correlation analyses were performed with audiological data pre- and post-treatment., Results: Plasma from SSNHL patients of varying types was collected and their EVs were successfully isolated and characterized. Proteomic analysis revealed that complement C3 levels in the plasma EVs of patients with profound SSNHL were significantly higher compared to healthy controls. Differential expression of miRNAs in plasma EVs and their related functions were also identified. The study found that the level of complement C3 in plasma EVs, but not the total plasma complement C3, positively correlated with the severity of SSNHL in patients exhibiting positive therapeutic responses, particularly in those with initially lower levels of EV-associated complement C3. After treatment, complement C3 level was decreased in patients with initially higher levels of EV-associated complement C3. No significant correlation was observed between changes in plasma EV-derived complement C3 levels and the degree of hearing loss in either responders or non-responders among patients with profound SSNHL., Conclusion: Differential profiles of proteins and miRNAs were identified in patients with profound SSNHL. Notably, plasma EV-derived complement C3 was linked to both the severity and early treatment effectiveness of patients with profound SSNHL., 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.)

Background: To develop an enhanced epilepsy diagnosis system by integrating an expert-informed ontology with a custom generative pre-trained transformer (GPT), validated by inferring possible seizure lateralization and localization using retrospective textual data from the pre-surgical assessments of patients with pharmaco-resistant epilepsy (PRE)., Methods: We developed an AI system for epilepsy diagnosis using Protégé with OWL/SWRL, integrating a knowledge base with seizure semiology, seizure types EEG descriptors, expert insights, and literature to pinpoint seizure locations. A customized GPT model was then tailored for specific diagnostic needs. Validated through 16 surgical cases, the system's accuracy in seizure localization and the JSON (JavaScript Object Notation) Epilepsy Matcher's term matching capabilities were confirmed against a Protégé-based knowledge base., Results: A total of 117 patients with PRE underwent video-EEG monitoring at a single institution. However, only 16 of these patients received epilepsy surgery. The Protégé system achieved 75 % accuracy in diagnosing epilepsy from 16 cases using semiology, which increased to 87.5 % with EEG data. The Json Epilepsy Matcher further improved accuracy to 87.5 % with symptoms alone and 93.8 % when including EEG data, highlighting the benefits of applying GPT techniques., Conclusions: This study highlights the efficacy of the JSON Epilepsy Matcher in improving seizure diagnosis accuracy. When combined with EEG data, it achieves a 93.8 % accuracy rate, suggesting a potential improvement in the practicality and generalizability of the original ontology expert system, boosting physicians' confidence in confirming surgery and potentially sparing many children from prolonged suffering. This innovative approach not only improves diagnostic accuracy but also sets a precedent for future applications of AI in neurology., 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 Ltd. All rights reserved.)

Background/purpose: Effective prevention could protect the health of the workforce, save human capital loss, and maintain employee productivity as well as economic growth., Methods: Using real-world data of patients with end-stage kidney disease (ESKD) and lung cancer, we multiplied their lifetime survival functions with employment ratios and working salaries to estimate the lifetime employment durations and earnings. They were compared with corresponding age-, sex-, and calendar year-matched referents to assess the differences in loss of lifetime employment duration and earnings. From 2000 to 2017, 83,358 patients with end-stage kidney disease (ESKD) were associated with 32-66% lifetime productivity losses. Similarly, we collected 24,904 incident cases of lung adenocarcinoma during 2011-2018 and estimated the potential savings in human capital due to early detection. Based on the evolving trends of ESKD incidence rates in Taiwan, we calculated the lifetime human capital losses of ESKD patients in GDP (gross domestic product) percentages during 2000-2020., Results: The aggregate lifetime productivity losses of ESKD in terms of GDP% varied between 0.000398% and 0.01% for male patients and between 0.0001% and 0.009% for female patients. The younger the patients, the bigger the losses in GDP%. Similarly, early detection of lung adenocarcinoma saved lives and productivity to some extent., Conclusions: Successful prevention of catastrophic illnesses at early stages would save the lifetime employment duration and productivity of the workforce. Future reform on the NHI could consider closer coordination between public health and healthcare organizations, focusing on effective prevention of diseases and complications to save productivity loss., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist. No one received compensation or was offered incentive for participating in this study., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Importance: The oral microbiota may be involved in development of head and neck squamous cell cancer (HNSCC), yet current evidence is largely limited to bacterial 16S amplicon sequencing or small retrospective case-control studies., Objective: To test whether oral bacterial and fungal microbiomes are associated with subsequent risk of HNSCC development., Design, Setting, and Participants: Prospective nested case-control study among participants providing oral samples in 3 epidemiological cohorts, the American Cancer Society Cancer Prevention Study II Nutrition Cohort, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, and the Southern Community Cohort Study. Two hundred thirty-six patients who prospectively developed HNSCC were identified during a mean (SD) of 5.1 (3.6) years of follow-up. Control participants who remained HNSCC free were selected by 2:1 frequency matching on cohort, age, sex, race and ethnicity, and time since oral sample collection. Data analysis was conducted in 2023., Exposures: Characterization of the oral bacterial microbiome using whole-genome shotgun sequencing and the oral fungal microbiome using internal transcribed spacer sequencing. Association of bacterial and fungal taxa with HNSCC was assessed by analysis of compositions of microbiomes with bias correction. Association with red and orange oral pathogen complexes was tested by logistic regression. A microbial risk score for HNSCC risk was calculated from risk-associated microbiota., Main Outcomes and Measures: The primary outcome was HNSCC incidence., Results: The study included 236 HNSCC case participants with a mean (SD) age of 60.9 (9.5) years and 24.6% women during a mean of 5.1 (3.6) years of follow-up, and 485 matched control participants. Overall microbiome diversity at baseline was not related to subsequent HNSCC risk; however 13 oral bacterial species were found to be differentially associated with development of HNSCC. The species included the newly identified Prevotella salivae, Streptococcus sanguinis, and Leptotrichia species, as well as several species belonging to beta and gamma Proteobacteria. The red/orange periodontal pathogen complex was moderately associated with HNSCC risk (odds ratio, 1.06 per 1 SD; 95% CI, 1.00-1.12). A 1-SD increase in microbial risk score (created based on 22 bacteria) was associated with a 50% increase in HNSCC risk (multivariate odds ratio, 1.50; 95% CI, 1.21-1.85). No fungal taxa associated with HNSCC risk were identified., Conclusions and Relevance: This case-control study yielded compelling evidence that oral bacteria are a risk factor for HNSCC development. The identified bacteria and bacterial complexes hold promise, along with other risk factors, to identify high-risk individuals for personalized prevention of HNSCC.

Background: Thyroid surgery has undergone significant transformation with the introduction of minimally invasive techniques, particularly robotic and endoscopic thyroidectomy. These advancements offer improved precision and faster recovery but also present unique challenges. This study aims to compare the learning curves, operational efficiencies, and patient outcomes of robotic versus endoscopic thyroidectomy., Methods: A retrospective cohort study was conducted, analyzing 258 robotic (da Vinci) and 214 endoscopic thyroidectomy cases. Key metrics such as operation duration, drainage volume, lymph node dissection outcomes, and hypoparathyroidism incidence were assessed to understand surgical learning curves and efficiency., Results: Robotic thyroidectomy showed a longer learning curve with initially longer operation times and higher drainage volumes but superior lymph node dissection outcomes. Both techniques were safe, with no permanent hypoparathyroidism or recurrent laryngeal nerve damage reported. The study delineated four distinct stages in the robotic and endoscopic surgery learning curve, each marked by specific improvements in proficiency. Endoscopic thyroidectomy displayed a shorter learning curve, leading to quicker operational efficiency gains., Conclusion: Robotic and endoscopic thyroidectomies are viable minimally invasive approaches, each with its learning curves and efficiency metrics. Despite initial challenges and a longer learning period for robotic surgery, its benefits in complex dissections may justify specialized training. Structured training programs tailored to each technique are crucial for improving outcomes and efficiency. Future research should focus on optimizing training protocols and increasing accessibility to these technologies, enhancing patient care in thyroid surgery., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background/purpose: Curative technologies improve patient's survival and/or quality of life but increase financial burdens. Effective prevention benefits all three. We summarize estimation methods and provide examples of how much money is spent per quality-adjusted life year (QALY) or life year (LY) on treating a catastrophic illness under a lifetime horizon and how many QALYs/LYs and lifetime medical costs (LMC) could be potentially saved by prevention., Methods: We established cohorts by interlinkages of Taiwan's nation-wide databases including National Health Insurance. We developed methods to estimate lifetime survival functions, which were multiplied with the medical costs and/or quality of life and summed up to estimate LMC, quality-adjusted life expectancy (QALE) and lifetime average cost per QALY/LY for catastrophic illnesses. By comparing with the age-, sex-, and calendar year-matched referents simulated from vital statistics, we obtained the loss-of-QALE and loss-of-life expectancy (LE)., Results: The lifetime cost-effectiveness ratios of ventilator-dependent comatose patients, dialysis, spinal cord injury, major trauma, and cancers were US$ 96,800, 16,200-20,000, 5500-5,900, 3400-3,600, and 2900-11,900 per QALY or LY, respectively. The successful prevention of lung, liver, oral, esophagus, stomach, nasopharynx, or ovary cancer would potentially save US$ 28,000-97,000 and > 10 QALYs; whereas those for end-stage kidney disease, stroke, spinal injury, or major trauma would be US$ 55,000-300,000 and 10-14 QALYs. Loss-of-QALE and loss-of-LE were less confounded indicators for comparing the lifetime health benefits of different technologies estimated from real-world data., Conclusions: Integration of prevention with treatment for resources allocation seems feasible and would improve equity and efficiency., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jung-Der Wang reports was provided by National Science and Technology Council. 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 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Chronic endometritis (CE) refers to the persistent inflammation of endometrium and is closely associated with infertility. Recurrent pregnancy loss (RPL), which has complex etiological factors, is two or more pregnancy loss of a couple before 20 weeks. However, CE is found in approximately 30% RPL patients, indicating that the endometrial immune microenvironment disorder caused by CE may play important role in RPL. Therefore, we should pay high attention and give CE screening to the RPL patients. Due to the inconsistent diagnostic criteria of CE, the relationship between RPL and CE remains controversial. Antibiotic is the primary treatment of CE. Using the higher CE diagnosis value can ensure effective treatment to RPL patient, and avoid the abuse of antibiotic. The effective treatment of CE can improve the pregnant outcomes of RPL patient.

Background: PANoptosis plays an important role in many inflammatory diseases. However, there are no reports on the association between PANoptosis and CD., Materials and Methods: This study used five machine learning algorithms - least absolute shrinkage and selection operator, support vector machine, random forest, decision tree and Gaussian mixture models - to construct CD's PANoptosis signature. Unsupervised hierarchical clustering analysis was used to identify PANoptosis-associated subgroups of CD. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were conducted to compare the PANoptosis-associated subgroups of CD among the potential biological mechanisms. Single sample GSEA was used to assess immune microenvironmental differences among the subgroups. The potential role of PANoptosis in CD was further explored using single-cell RNA-Seq (scRNA-Seq) for PANoptosis scoring, differential analysis, pseudotime analysis, cellular communication analysis and weighted gene co-expression network analysis (WGCNA) analysis., Results: CD's PANoptosis signature consisted of seven genes: CEACAM6, CHP2, PIK3R1, CASP10, PSMB1, PSMB8 and UBC. The PANoptosis signature in multiple cohorts had a strong ability to recognise CD. The levels of immune cell infiltration and the vigour of the immune responses significantly varied between the two subpopulations of CD associated with PANoptosis. Multiple lines of evidence from the GO, KEGG, GSEA, GSVA, scRNA-Seq and WGCNA analyses suggested that I-kappaB kinase/NF- kappaB signalling, mitogen-activated protein kinase (MAPK), leukocyte activation and leukocyte migration were mechanisms closely associated with PANoptosis in CD., Conclusion: This study is the first to construct a PANoptosis signature with excellent efficacy in recognising CD. PANoptosis may mediate the process of CD through inflammatory and immune mechanisms, such as NF- kappaB, MAPK and leukocyte migration., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants that are detectable in the serum of most U.S. adults. Some studies of highly-exposed individuals have suggested positive associations between PFAS and B-cell non-Hodgkin lymphoma (B-NHL). To investigate whether associations exist at lower exposure levels, we conducted a nested case-control study investigating serum PFAS concentrations and B-NHL within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We measured pre-diagnostic serum concentrations of five PFAS among 706 cases (age at diagnosis = 55-93 years, median 73 years) and 706 controls individually matched on age at blood draw, sex, self-reported race and ethnicity, study center, and year of blood collection (the median follow-up years = 10). We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for PFAS concentrations in relation to B-NHL, both overall and for selected histologic subtypes [diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), and marginal zone lymphoma (MZL)] using conditional logistic regression. We found no evidence of a positive association with B-NHL for any of the five PFAS. In analyses of histologic subtypes, perfluorohexane sulfonate (PFHxS) was significantly associated with DLBCL in a model adjusting for all other PFAS (OR for highest vs. lowest quintile = 2.19, 95 % CI = 1.21, 3.95; P trend  = 0.02), but not in a model without mutual adjustment (OR = 1.37, 95 % CI = 0.82, 2.29; P trend  = 0.26). We also observed an inverse association between perfluorononanoate and DLBCL (mutually-adjusted OR = 0.83, 95 % CI = 0.69, 0.99 per doubling in concentration), although the association was null among participants with blood drawn prior to 1997 (OR <1997  = 1.00, 95 % CI = 0.82, 1.21; OR ≥1997  = 0.65, 95 % CI = 0.53, 0.79; P interaction  = 0.0003). In conclusion, our findings from a prospective cohort study with PFAS serum concentrations comparable to that of the general population do not support an association with increased risk of B-NHL overall. The suggestive evidence of a positive association between PFHxS and DLBCL warrants further investigation., 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., (Published by Elsevier Ltd.)

Prcis: Severe atopic dermatitis (AD) in patients with glaucoma heightens the risk of requiring surgical intervention, necessitating prompt specialist care and strict surveillance., Objective: The impact of AD on the prognosis of patients with glaucoma is rarely studied. This study aims to assess the risk of requiring glaucoma surgery among patients with glaucoma with and without AD., Materials and Methods: In this retrospective cohort analysis, we assessed patients with glaucoma initially diagnosed from December 5, 2003 to December 3, 2018 using the TriNetX database, dividing them into AD and non-AD cohorts. 1:1 propensity-score matching created balanced groups for baseline traits and comorbidities. We compared the cohorts' risk and cumulative incidence of needing glaucoma surgery (minimally invasive glaucoma surgery, trabeculectomy, aqueous shunt, or transscleral cyclophotocoagulation). A subgroup analysis was also conducted for patients with severe AD., Results: Out of 528,469 patients with glaucoma, 2624 were in the AD group. Among the AD group, 584 had severe AD. The AD group showed a comparable risk of requiring surgery to the non-AD group (hazard ratio: 1.03; 95% CI: 0.72, 1.47). In contrast, the severe AD group demonstrated a significantly greater risk and cumulative incidence of surgery (hazard ratio: 2.80; 95% CI: 1.37, 5.73; log-rank P = 0.003) compared with the non-AD group., Conclusion: Patients with glaucoma with severe AD are significantly more likely to need surgical intervention, with AD severity being a correlating factor for increased risk., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Renal tubular epithelial cell senescence plays a critical role in promoting and accelerating kidney aging and age-related renal fibrosis. Senescent cells not only lose their self-repair ability, but also can transform into senescence-associated secretory phenotype (SASP) to trigger inflammation and fibrogenesis. Recent studies show that mitochondrial dysfunction is critical for renal tubular cell senescence and kidney aging, and calcium overload and abnormal calcium-dependent kinase activities are involved in mitochondrial dysfunction-associated senescence. In this study we investigated the role of mitochondrial calcium overload and mitochondrial calcium uniporter (MCU) in kidney aging. By comparing the kidney of 2- and 24-month-old mice, we found calcium overload in renal tubular cells of aged kidney, accompanied by significantly elevated expression of MCU. In human proximal renal tubular cell line HK-2, pretreatment with MCU agonist spermine (10 μM) significantly increased mitochondrial calcium accumulation, and induced the production of reactive oxygen species (ROS), leading to renal tubular cell senescence and age-related kidney fibrosis. On the contrary, pretreatment with MCU antagonist RU360 (10 μM) or calcium chelator BAPTA-AM (10 μM) diminished D-gal-induced ROS generation, restored mitochondrial homeostasis, retarded cell senescence, and protected against kidney aging in HK-2 cells. In a D-gal-induced accelerated aging mice model, administration of BAPTA (100 μg/kg. i.p.) every other day for 8 weeks significantly alleviated renal tubuarl cell senescence and fibrosis. We conclude that MCU plays a key role in promoting renal tubular cell senescence and kidney aging. Targeting inhibition on MCU provides a new insight into the therapeutic strategy against kidney aging., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Introduction: Several studies have linked increased risk of osteosarcoma with tall stature, high birthweight, and early puberty, although evidence is inconsistent. We used genetic risk scores (GRS) based on established genetic loci for these traits and evaluated associations between genetically inferred birthweight, height, and puberty timing with osteosarcoma., Methods: Using genotype data from two genome-wide association studies, totaling 1039 cases and 2923 controls of European ancestry, association analyses were conducted using logistic regression for each study and meta-analyzed to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were conducted by case diagnosis age, metastasis status, tumor location, tumor histology, and presence of a known pathogenic variant in a cancer susceptibility gene., Results: Genetically inferred higher birthweight was associated with an increased risk of osteosarcoma (OR =1.59, 95% CI 1.07-2.38, P = 0.02). This association was strongest in cases without metastatic disease (OR =2.46, 95% CI 1.44-4.19, P = 9.5 ×10 -04 ). Although there was no overall association between osteosarcoma and genetically inferred taller stature (OR=1.06, 95% CI 0.96-1.17, P = 0.28), the GRS for taller stature was associated with an increased risk of osteosarcoma in 154 cases with a known pathogenic cancer susceptibility gene variant (OR=1.29, 95% CI 1.03-1.63, P = 0.03). There were no significant associations between the GRS for puberty timing and osteosarcoma., Conclusion: A genetic propensity to higher birthweight was associated with increased osteosarcoma risk, suggesting that shared genetic factors or biological pathways that affect birthweight may contribute to osteosarcoma pathogenesis., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Changes in alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT) levels in patients with primary liver cancer (PLC) after radiofrequency ablation (RFA). Hepatocellular carcinoma is a malignant tumor with high incidence worldwide. As a common local treatment, RFA has attracted much attention for its efficacy and influence on liver function., Aim: To investigate the effect of serum ALP and GGT levels on the prognosis of patients with PLC treated by RFA., Methods: The preoperative clinical data of 165 patients who were pathologically or clinically diagnosed with PLC and who received RFA in our hospital between October 2018 and June 2023 were collected. The chi-square test was used to compare the data between groups. The Kaplan-Meier method and Cox regression were used to analyze the associations between serum ALP and GGT levels and overall survival, progression-free survival (PFS) and clinical characteristics of patients before treatment., Results: The 1-year survival rates of patients with normal (≤ 135 U/L) and abnormal (> 135 U/L) serum ALP before treatment were 91% and 79%, respectively; the 2-year survival rates were 90% and 68%, respectively; and the 5-year survival rates were 35% and 18%, respectively. The difference between the two groups was statistically significant ( P = 0.01). Before treatment, the 1-year survival rates of patients with normal serum GGT levels (≤ 45 U/L) and abnormal serum GGT levels (> 45 U/L) were 95% and 87%, the 2-year survival rates were 85% and 71%, and the 5-year survival rates were 37% and 21%, respectively. The difference between the two groups was statistically significant ( P < 0.001). Serum ALP [hazard ratio (HR) = 1.766, 95% confidence interval (95%CI): 1.068-2.921, P = 0.027] and GGT (HR = 2. 312, 95%CI: 1.367-3.912, P = 0.002) is closely related to the overall survival of PLC patients after RF ablation and is an independent prognostic factor. The 1-year PFS rates were 72% and 50%, the 2-year PFS rates were 52% and 21%, and the 5-year PFS rates were 14% and 3%, respectively. The difference between the two groups was statistically significant ( P < 0001). The 1-year PFS rates were 81% and 56% in patients with normal and abnormal serum GGT levels before treatment, respectively; the 2-year PFS rates were 62% and 35%, respectively; and the 5-year PFS rates were 18% and 7%, respectively, with statistical significance between the two groups ( P < 0.001). The serum ALP concentration (HR = 1. 653, 95%CI: 1.001-2.729, P = 0.049) and GGT (HR = 1.949, 95%CI: 1.296-2.930, P = 0.001) was closely associated with PFS after RFA in patients with PLC. The proportion of male patients with abnormal ALP levels is high, the Child-Pugh grade of liver function is poor, and the incidence of ascites is high. Among GGT-abnormal patients, the Child-Pugh grade of liver function was poor, the tumor stage was late, the proportion of patients with tumors ≥ 5 cm was high, and the incidence of hepatic encephalopathy was high., Conclusion: Serum ALP and GGT levels before treatment can be used to predict the prognosis of patients with PLC after RFA, and they have certain guiding significance for the long-term survival of patients with PLC after radiofrequency therapy., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Considering the finite time within a 24-h day, the distribution of time spent on movement behaviours has been found to be associated with health outcomes., Objectives: This systematic review and meta-analysis aimed to summarise and evaluate the overflow effects of interventions targeting a single behaviour (physical activity, sedentary behaviour/screen time, or sleep) on other non-targeted behaviours among children and adolescents., Methods: Six databases (MEDLINE [Ovid], PsycINFO [ProQuest], EMBASE [Ovid], PubMed, Web of Science and SPORTDiscus [EBSCO]) were searched for relevant studies published before 13 May, 2024. Randomised controlled trials and clustered randomised controlled trials that targeted a single behaviour and also assessed the effects on non-targeted behaviours, comprised of healthy children under the age of 18 years, were included. Movement behaviours can be measured either objectively or subjectively. The revised Cochrane risk-of-bias tool for randomised trials was adopted to evaluate the risk of bias., Results: A total of 102 studies with 45,998 participants from 21 countries were identified, and 60 of them with 26,183 participants were incorporated into the meta-analysis. The meta-analysis demonstrated that physical activity interventions led to a reduction in the proportion of each day spent in sedentary behaviour (mean difference =  - 0.95% of wear time, 95% confidence interval - 1.44, - 0.45, I 2  = 39%). Sedentary behaviour interventions resulted in increased standing time (mean difference = 3.87%, 95% confidence interval 1.99, 5.75, I 2  = 0%). Interventions targeting screen time did not yield changes in physical activity or sleep. The findings on the effectiveness of sleep interventions on non-targeted behaviours and of physical activity interventions on sleep were inconclusive., Conclusions: Overall, the findings suggested that interventions aimed at increasing physical activity or reducing sedentary behaviour had overflow effects on non-targeted behaviours, but the effect sizes were small. Additional evidence is needed to reach definitive conclusions regarding the impact of behaviour change interventions on sleep and of the overflow effects of sleep interventions., (© 2024. The Author(s).)

Background: Coronary artery disease (CAD) is a major global cardiovascular health threat and the leading cause of death in many countries. The disease has a significant impact in China, where it has become the leading cause of death. There is an urgent need to develop non-invasive, rapid, cost-effective, and reliable techniques for the early detection of CAD using machine learning (ML)., Methods: Six hundred eight participants were divided into three groups: healthy, hypertensive, and CAD. The raw data of pulse wave from those participants was collected. The data were de-noised, normalized, and analyzed using several applications. Seven ML classifiers were used to model the processed data, including Decision Tree (DT), Random Forest (RF), Gradient Boosting Decision Tree (GBDT), Extra Trees (ET), Extreme Gradient Boosting (XGBoost), Light Gradient Boosting (LightGBM), and Unbiased Boosting with Categorical Features (CatBoost)., Results: The Extra Trees classifier demonstrated the best classification performance. After tunning, the results performance evaluation on test set are: 0.8579 accuracy, 0.9361 AUC, 0.8561 recall, 0.8581 precision, 0.8571 F1 score, 0.7859 kappa coefficient, and 0.7867 MCC. The top 10 feature importances of ET model are w/t 1 , t 3 /t max , t max , t 3 /t 1 , As, h f/3 , t f/3 /t max , t f/5 , w and t f/3 /t 1 ., Conclusion: Radial artery pulse wave can be used to identify healthy, hypertensive and CAD participants by using Extra Trees Classifier. This method provides a potential pathway to recognize CAD patients by using a simple, non-invasive, and cost-effective technique., (© 2024. The Author(s).)

Background: Interventions focusing on individual behaviours (physical activity, sedentary behaviour, sleep) of preschool-aged children have been widely studied. However, there is a lack of understanding about integrated interventions that target all three 24-hour movement behaviours. This is the first study to assess the effectiveness of an intervention aimed at improving all three 24-hour movement behaviours among preschoolers in Hong Kong., Methods: A 12-week randomised controlled trial with a 12-week follow-up was conducted. Parent-child pairs were randomised to integrated approach (targeting all three behaviours), dyadic approach (targeting physical activity and sedentary behaviour including screen time), or wait-list control group. Utilising the Internet-based delivery, this intervention consisted of education materials, workshops, and interactive questionnaires and reminders. Two intervention groups employed the same strategies, with the only difference being that the integrated approach targeted sleep in addition to physical activity and sedentary behaviour. The outcomes were preschoolers' overall 24-hour movement behaviours which were assessed by the Activity Sleep Index (ASI), movement behaviour composition, and absolute duration of movement behaviours. Generalised estimating equations were conducted to evaluate the intervention., Results: A total of 147 preschoolers (4.8 ± 0.9 years old, 56.5% boys) and their parents were included. Preschoolers in all groups had a lower ASI at follow-up compared with baseline. Preschoolers in the integrated approach had a smaller decline in ASI at follow-up, compared to that in the control group (3.41; 95% confidence interval [CI] = 0.07, 6.76). Preschoolers in both intervention groups had a smaller reduction of the composition of time spent in physical activity at follow-up, and a decreased screen time at postintervention and follow-up. No significant differences were found for the sleep subcomponent. Furthermore, preschoolers in the dyadic approach had a smaller increase in the sedentary behaviour subcomponent (vs., Control: - 0.21; 95% CI = - 0.37, - 0.05) at follow-up., Conclusions: Both intervention groups showed a decrease in screen time at postintervention, but there were no significant changes in other behaviours. The favourable changes observed at follow-up demonstrated the effectiveness of both intervention approaches on alleviating the decline in the composition of time spent in physical activity and reducing screen time and revealed the possible effectiveness of the integrated approach in promoting overall movement behaviours among preschoolers., Trial Registration: The study is prospectively registered at the Chinese Clinical Trial Registry (ChiCTR2200055958)., (© 2024. The Author(s).)

Introduction: Little is known about how frequently family medicine (FM) clerkship directors remediate faculty with student mistreatment concerns and their comfort level in performing the remediations. In this exploratory study, we investigated factors associated with the number of faculty remediated for student mistreatment concerns by FM clerkship directors and the comfort level of FM clerkship directors in remediating these faculty., Methods: Data were collected as part of the 2022 Council of Academic Family Medicine Educational Research Alliance (CERA) survey of FM clerkship directors. FM clerkship directors provided responses on how frequently they remediated faculty with mistreatment concerns and their comfort level in performing remediations., Results: Ninety-four of 159 FM clerkship directors (59.1%) responded to the survey. FM clerkship directors remediated more community faculty than employed faculty ( P <.001). FM clerkship directors at schools where a larger percentage of students spent at least half of their rotation with a community faculty ( P =.002) or where there were a higher percentage of paid community faculty ( P =.004) were more likely to have remediated community faculty. FM clerkship directors reported more comfort in remediating employed faculty compared to community faculty ( P =.048). FM clerkship directors with access to a formal mechanism for remediation ( P =.016) or having a better adequacy in number of precepting sites ( P =.041) reported higher comfort levels in remediating community faculty., Conclusions: Our study identified factors associated with remediating family medicine clerkship faculty with mistreatment concerns. Additional research is needed to determine the most effective strategies to remediate faculty with mistreatment concerns., (© 2024 by the Society of Teachers of Family Medicine.)

Background and Aims: The association between fiber or whole grain intakes and the risk of liver cancer remains unclear. We assessed the associations between fiber or whole grain intakes and liver cancer risk among 2 prospective studies, and systematically reviewed and meta-analyzed these results with published prospective studies., Approach and Results: A total of 111,396 participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and 26,085 men from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study were included. Intakes of total fiber and whole grains were estimated from validated food frequency questionnaires. Study-specific HRs and 95% CI with liver cancer risk were estimated using multivariable-adjusted Cox regression. We systematically reviewed existing literature, and studies were combined in a dose-response meta-analysis. A total of 277 (median follow-up = 15.6 y) and 165 (median follow-up = 16.0 y) cases of liver cancer were observed in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, respectively. Dietary fiber was inversely associated with liver cancer risk in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (HR 10g/day : 0.69; 95% CI: 0.55-0.86). No significant associations were observed between whole grain intakes and liver cancer risk in either study. Our meta-analysis included 2383 incident liver cancer cases (7 prospective cohorts) for fiber intake and 1523 cases (5 prospective cohorts) for whole grain intake; combined HRs for liver cancer risk were 0.83 (0.76-0.91) per 10 g/day of fiber and 0.92 (0.85-0.99) per 16 g/day (1 serving) of whole grains., Conclusions: Dietary fiber and whole grains were inversely associated with liver cancer risk. Further research exploring potential mechanisms and different fiber types is needed., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: Folate is involved in multiple genetic, epigenetic, and metabolic processes, and inadequate folate intake has been associated with an increased risk of cancer., Objective: We examined whether folate intake is differentially associated with colorectal cancer (CRC) risk according to somatic mutations in genes linked to CRC using targeted sequencing., Design: Participants within 2 large CRC consortia with available information on dietary folate, supplemental folic acid, and total folate intake were included. Colorectal tumor samples from cases were sequenced for the presence of nonsilent mutations in 105 genes and 6 signaling pathways (IGF2/PI3K, MMR, RTK/RAS, TGF-β, WNT, and TP53/ATM). Multinomial logistic regression models were analyzed comparing mutated/nonmutated CRC cases to controls to compute multivariable-adjusted odds ratios (ORs) with 95% confidence interval (CI). Heterogeneity of associations of mutated compared with nonmutated CRC cases was tested in case-only analyses using logistic regression. Analyses were performed separately in hypermutated and nonhypermutated tumors, because they exhibit different clinical behaviors., Results: We included 4339 CRC cases (702 hypermutated tumors, 16.2%) and 11,767 controls. Total folate intake was inversely associated with CRC risk (OR = 0.93; 95% CI: 0.90, 0.96). Among hypermutated tumors, 12 genes (AXIN2, B2M, BCOR, CHD1, DOCK3, FBLN2, MAP3K21, POLD1, RYR1, TET2, UTP20, and ZNF521) showed nominal statistical significance (P < 0.05) for heterogeneity by mutation status, but none remained significant after multiple testing correction. Among these genetic subtypes, the associations between folate variables and CRC were mostly inverse or toward the null, except for tumors mutated for DOCK3 (supplemental folic acid), CHD1 (total folate), and ZNF521 (dietary folate) that showed positive associations. We did not observe differential associations in analyses among nonhypermutated tumors, or according to the signaling pathways., Conclusions: Folate intake was not differentially associated with CRC risk according to mutations in the genes explored. The nominally significant differential mutation effects observed in a few genes warrants further investigation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Significance: Near-infrared autofluorescence (NIRAF) utilizes the natural autofluorescence of parathyroid glands (PGs) to improve their identification during thyroid surgeries, reducing the risk of inadvertent removal and subsequent complications such as hypoparathyroidism. This study evaluates NIRAF's effectiveness in real-world surgical settings, highlighting its potential to enhance surgical outcomes and patient safety., Aim: We evaluate the effectiveness of NIRAF in detecting PGs during thyroidectomy and central neck dissection and investigate autofluorescence characteristics in both fresh and paraffin-embedded tissues., Approach: We included 101 patients diagnosed with papillary thyroid cancer who underwent surgeries in 2022 and 2023. We assessed NIRAF's ability to locate PGs, confirmed via parathyroid hormone assays, and involved both junior and senior surgeons. We measured the accuracy, speed, and agreement levels of each method and analyzed autofluorescence persistence and variation over 10 years, alongside the expression of calcium-sensing receptor (CaSR) and vitamin D., Results: NIRAF demonstrated a sensitivity of 89.5% and a negative predictive value of 89.1%. However, its specificity and positive predictive value (PPV) were 61.2% and 62.3%, respectively, which are considered lower. The kappa statistic indicated moderate to substantial agreement (kappa = 0.478; P < 0.001 ). Senior surgeons achieved high specificity (86.2%) and PPV (85.3%), with substantial agreement (kappa = 0.847; P < 0.001 ). In contrast, junior surgeons displayed the lowest kappa statistic among the groups, indicating minimal agreement (kappa = 0.381; P < 0.001 ). Common errors in NIRAF included interference from brown fat and eschar. In addition, paraffin-embedded samples retained stable autofluorescence over 10 years, showing no significant correlation with CaSR and vitamin D levels., Conclusions: NIRAF is useful for PG identification in thyroid and neck surgeries, enhancing efficiency and reducing inadvertent PG removals. The stability of autofluorescence in paraffin samples suggests its long-term viability, with false positives providing insights for further improvements in NIRAF technology., (© 2024 The Authors.)