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Yi-Chun Hsiao,1,&ast; Pei-Yi Shen,1,&ast; Li-Ting Wong,2 Ming-Cheng Chan,3,4 Wen-Cheng Chao3– 6 1Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; 3Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 4Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; 5Big Data Center, Chung Hsing University, Taichung, Taiwan; 6Department of Automatic Control Engineering, Feng Chia University, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Wen-Cheng Chao, Department of Critical Care Medicine, Taichung Veterans General Hospital, No, 1650, Section 4, Taiwan Boulevard, Xitun District, Taichung City, 40705, Taiwan, Email cwc081@hotmail.comObjective: Absolute lymphocyte count (ALC) has been implicated with short-term outcomes in a number of diseases, and we aimed to investigate the association between week-one ALC and long-term mortality in patients who were admitted to the medical intensive care units (ICUs).Methods: We enrolled patients who were admitted to the medical ICUs at the Taichung Veterans General Hospital, a referral centre located in central Taiwan, between 2015 and 2020 to conduct this retrospective cohort study. The outcome of interest was long-term all-cause mortality, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to determine the association. Furthermore, we employed propensity score-matching (PSM) and weighting techniques, consisting of inverse probability of treatment weighting (IPTW) and covariate balancing propensity score (CBPS), to confirm the association between ALC and mortality.Results: A total of 5722 critically ill patients were enrolled, and the one-year mortality was 44.8%. The non-survivor group had a lower ALC (1549, 1027– 2388 vs 1948, 1373– 2743 counts/μL, p< 0.01) compared with those in the survivor group. Cox regression showed that low ALC was independently associated with mortality (adjHR 1.091, 95% CI 1.050– 1.134). Propensity score-based analyses demonstrated the robust association, with adjHRs in the original, PSM, IPTW, and CBPS populations of 1.327 (95% CI 1.224– 1.438), 1.301 (95% CI 1.188– 1.424), 1.292 (95% CI 1.186– 1.407), and 1.297 (95% CI 1.191– 1.412), respectively. Sensitivity analyses further showed that the association between low ALC and mortality existed in a dose-response manner.Conclusion: We found that low ALC was associated with long-term mortality in critically ill patients; further studies are warranted to validate and translate these findings into clinical utility.Keywords: absolute lymphocyte counts, critical illness, mortality, long-term outcome, propensity score

Chinmaya Mutalik,1,2 I-Hsin Lin,3 Dyah Ika Krisnawati,4 Siti Khaerunnisa,5 Muhamad Khafid,6 Widodo,7 Yu-Cheng Hsiao,1,8– 10 Tsung-Rong Kuo1,2 1International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 2Graduate Institute of Nanomedicine and Medical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 3School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 4Dharma Husada Nursing Academy, Kediri, Indonesia; 5Department of Physiology and Medical Biochemistry, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia; 6Department of Nursing, Faculty of Nursing and Midwifery, Universitas Nahdlatul Ulama Surabaya, East Java, Indonesia; 7College of Information System, Universitas Nusantara PGRI, Kediri, Indonesia; 8Graduate Institute of Biomedical Optomechatronics, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 9Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 10Stanford Byers Center for Biodesign, Stanford University, Stanford, CA, USACorrespondence: Yu-Cheng Hsiao; Tsung-Rong Kuo, Tel +886-2-66382736 ext. 1359 ; +886-2-27361661 ext. 7706, Email ychsiao@tmu.edu.tw; trkuo@tmu.edu.twAbstract: Across the planet, outbreaks of bacterial illnesses pose major health risks and raise concerns. Photodynamic, photothermal, and metal ion release effects of transition metal-based nanocomposites (TMNs) were recently shown to be highly effective in reducing bacterial resistance and upsurges in outbreaks. Surface plasmonic resonance, photonics, crystal structures, and optical properties of TMNs have been used to regulate metal ion release, produce oxidative stress, and generate heat for bactericidal applications. The superior properties of TMNs provide a chance to investigate and improve their antimicrobial actions, perhaps leading to therapeutic interventions. In this review, we discuss three alternative antibacterial strategies based on TMNs of photodynamic therapy, photothermal therapy, and metal ion release and their mechanistic actions. The scientific community has made significant efforts to address the safety, effectiveness, toxicity, and biocompatibility of these metallic nanostructures; significant achievements and trends have been highlighted in this review. The combination of therapies together has borne significant results to counter antimicrobial resistance (4-log reduction). These three antimicrobial pathways are separated into subcategories based on recent successes, highlighting potential needs and challenges in medical, environmental, and allied industries.Graphical Abstract: Keywords: transition metals, nanocomposites, photodynamic, photothermal, metal ion release, antibacterial mechanisms

Haw-Ming Huang,1,2 Ping-Han Wu,3 Po-Chien Chou,4 Wen-Tien Hsiao,5 Hsin-Ta Wang,4 Hsin-Pei Chiang,3 Chi-Ming Lee,6 Shwu-Huey Wang,6 Yu-Cheng Hsiao2,7 1School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan; 2Graduate Institute of Biomedical Optomechatronics, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 3Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 4School of Organic and Polymeric, National Taipei University of Technology, Taipei, Taiwan; 5Department of Medical Imaging and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu, Taiwan; 6Core Facility Center, Office of Research and Development, Taipei Medical University, Taipei, Taiwan; 7Cell Physiology and Molecular Image Research Center, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, TaiwanCorrespondence: Yu-Cheng Hsiao; Ping-Han WuTaipei Medical University, No. 250, Wu-Hsing Street, Taipei, 11031, TaiwanTel +886-291-937-9783Fax +886 2 27362295Email ychsiao@tmu.edu.tw; gahwclbjwph@gmail.comIntroduction: It has been reported that low-molecular-weight hyaluronic acid (LMWHA) exhibits a potentially beneficial effect on cancer therapy through targeting of CD44 receptors on tumor cell surfaces. However, its applicability towards tumor detection is still unclear. In this regard, LMWHA-conjugated iron (Fe3O4) nanoparticles (LMWHA-IONPs) were prepared in order to evaluate its application for enhancing the T2* weighted MRI imaging sensitivity for tumor detection.Methods: LMWHA and Fe3O4 NPs were produced using γ-ray irradiation and chemical co-precipitation methods, respectively. First, LMWHA-conjugated FITC was prepared to confirm the ability of LMWHA to target U87MG cells using fluorescence microscopy. The hydrodynamic size distribution and dispersion of the IONPs and prepared LMWHA-IONPs were analyzed using dynamic light scattering (DLS). In addition, cell viability assays were performed to examine the biocompatibility of LMWHA and LMWHA-IONPs toward U87MG human glioblastoma and NIH3T3 fibroblast cell lines. The ability of LMWHA-IONPs to target tumor cells was confirmed by detecting iron (Fe) ion content using the thiocyanate method. Finally, time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging and in vitro magnetic resonance imaging (MRI) were performed to confirm the contrast enhancement effect of LMWHA-IONPs.Results: Florescence analysis results showed that LMWHA-FITC successfully targeted the surfaces of both tested cell types. The ability of LMWHA to target U87MG cells was higher than for NIH3T3 cells. Cell viability experiments showed that the fabricated LMWHA-IONPs possessed good biocompatibility for both cell lines. After co-culturing test cells with the LMWHA-IONPs, detected Fe ion content in the U87MG cells was much higher than that of the NIH3T3 cells in both thiocyanate assays and TOF-SIMs images. Finally, the addition of LMWHA-IONPs to the U87MG cells resulted in an obvious improvement in T2* weighted MR image contrast compared to control NIH3T3 cells.Discussion: Overall, the present results suggest that LMWHA-IONPs fabricated in this study provide an effective MRI contrast agent for improving the diagnosis of early stage glioblastoma in MRI examinations.Keywords: hyaluronic acid, Fe3O4 nanoparticles, TOF-SIMS, MRI

Er-Yuan Chuang,1 Ping-Yuan Lin,1 Po-Feng Wang,1 Tsung-Rong Kuo,1 Chih-Hwa Chen,1– 4 Yankuba B Manga,1 Yu-Cheng Hsiao1,5 1Graduate Institute of Biomedical Optomechatronics; Graduate Institute of Nanomedicine and Medical Engineering; International PhD Program in Biomedical Engineering; Graduate Institute of Biomedical Materials and Tissue Engineering; School of Biomedical Engineering; College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; 2Department of Orthopedics, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan; 3School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4Research Center of Biomedical Device, Taipei Medical University, Taipei, Taiwan; 5Cell Physiology and Molecular Image Research Center, Taipei Medical University–Wan Fang Hospital, Taipei, TaiwanCorrespondence: Yu-Cheng HsiaoGraduate Institute of Biomedical Optomechatronics, College of Biomedical Engineering, Taipei Medical University, Taipei, 11031, TaiwanTel +886-2-27361661Email ychsioa@tmu.edu.twIntroduction: The sensitive interfacial interaction of liquid crystals (LC) holds potential for precision biosensors. In the past, the developments of LC biosensors were limited by the complicated manufacturing process, which hinders commercialization and wider applications of such devices. In this report, we demonstrate the first nano-structural polymeric stabilized-cholesteric LC (PSCLC) thin films to be a new label-free biosensing technology.Methods: The transmission spectra of PSCLC devices were measured by the fiber-optic spectrometer with high-resolution. In addition, a smartphone was set on the stage, and the camera of smartphone was placed and aligned with a set of lenses embedded in the designed stage. To decrease the chromatic and spherical aberrations, an achromatic lens set composition, consisting of both dual-convex lens and concave-plane lens, was applied for measuring and imaging the PSCLC texture. The average and the estimated standard deviation (SD) were used to present quantitative experimental results. The test BSA was immobilized and fulfilled by the ceramic silicon-constructed DMOAP-coated glass in aqueous BSA solutions at 1 mg/mL, 1 μg/mL, and 1 ng/mL.Results: The fabrication process of PSCLC is much simplified compared to previous LC biosensors. The color of PSCLC biosensor altered with the BSA concentration, making detection result easy to read. The detection limit of 1 ng/mL is achieved for label-free PSCLC biosensor. The PSCLC biosensor was able to successfully detect due to the albumin concentration’s alteration, with a linear range of 1 ng/mL– 2 mg/mL. Thus, the label-free-proposed design-integrated nanoscale PSCLCs smartphone-based biosensor could successfully detect BSA in a preclinical urine sample.Conclusion: Finally, we propose a design to integrate the PSCLC biosensor with a smartphone. The PSCLC owns potential for high performance, low cost for detecting various disease biomarkers in home use. Owing to its great potential for high performance and low cost, the PSCLC biosensors can be used as a label-free point-of-care for detecting various disease biomarkers for patients in care homes.Keywords: polymer-stabilized cholesteric liquid crystal, ceramic silicon compound, trimethoxysilyl, constructed DMOAP, label-free, biosensor, point-of-care, bovine serum albumin

Chinmaya Mutalik,1,* Yu-Cheng Hsiao,1,2,* Yi-Hsuan Chang,3 Dyah Ika Krisnawati,4 Moh Alimansur,4 Achmad Jazidie,5,6 Mohammad Nuh,7 Chia-Che Chang,8 Di-Yan Wang,8 Tsung-Rong Kuo1,3 1International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan; 2Graduate Institute of Biomedical Optomechatronics, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan; 3Graduate Institute of Nanomedicine and Medical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan; 4Dharma Husada Nursing Academy, Kediri, East Java 64114, Indonesia; 5Department of Electrical Engineering, Institut Teknologi Sepuluh Nopember, Surabaya 60111, Indonesia; 6Universitas Nahdlatul Ulama Surabaya, Surabaya 60111, Indonesia; 7Department of Biomedical Engineering, Institut Teknologi Sepuluh Nopember, Surabaya 60111, Indonesia; 8Department of Chemistry, Tunghai University, Taichung 40704, Taiwan*These authors contributed equally to this workCorrespondence: Di-Yan WangDepartment of Chemistry, Tunghai University, Taichung 40704, TaiwanTel +886-4-23590121Email diyanwang@thu.edu.twTsung-Rong KuoGraduate Institute of Nanomedicine and Medical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, TaiwanTel +886-2-27361661Email trkuo@tmu.edu.twPurpose: Antibiotic resistance issues associated with microbial pathogenesis are considered to be one of the most serious current threats to health. Fortunately, TiO2, a photoactive semiconductor, was proven to have antibacterial activity and is being widely utilized. However, its use is limited to the short range of absorption wavelength.Methods: In this work, heterostructured TiO2-FeS2 nanocomposites (NCs) were successfully prepared by a facile solution approach to enhance light-induced antibacterial activity over a broader absorption range.Results: In TiO2-FeS2 NCs, FeS2 NPs, as light harvesters, can effectively increase light absorption from the visible (Vis) to near-infrared (NIR). Results of light-induced antibacterial activities indicated that TiO2-FeS2 NCs had better antibacterial activity than that of only TiO2 nanoparticles (NPs) or only FeS2 NPs. Reactive oxygen species (ROS) measurements also showed that TiO2-FeS2 NCs produced the highest relative ROS levels. Unlike TiO2 NPs, TiO2-FeS2 NCs, under light irradiation with a 515-nm filter, could absorb light wavelengths longer than 515 nm to generate ROS. In the mechanistic study, we found that TiO2 NPs in TiO2-FeS2 NCs could absorb ultraviolet (UV) light to generate photoinduced electrons and holes for ROS generation, including ⋅O2− and ⋅OH; FeS2 NPs efficiently harvested Vis to NIR light to generate photoinduced electrons, which then were transferred to TiO2 NPs to facilitate ROS generation.Conclusion: TiO2-FeS2 NCs with superior light-induced antibacterial activity could be a promising antibacterial agent against bacterial infections.Keywords: antibacterial agent, antibacterial mechanism, reactive oxygen species, light harvester, light-induced antibacterial activity

Aim: To examine the usefulness of dual-phase 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) for the evaluation of thyroid incidentalomas. Materials and Methods: In this retrospective study, cases with focal thyroid lesions seen incidentally at FDG PET in which the histopathological diagnosis was available and in which dual-phase FDG PET imaging was performed at 1 and 2 h after FDG injection were reviewed. In the included cases, the 1 and 2 h maximal standard uptake value (1-hour maximal SUV and 2-hour maximal SUV, respectively) and retention index (RI) were calculated, and the differences between benign and malignant thyroid incidentalomas were analysed. Receiver operating characteristic (ROC) analysis was performed to evaluate the ability of 1-hour maximal SUV, 2-hour maximal SUV, and RI to discriminate benign from malignant lesions. Results: A total of 39 patients (25 females, 14 males) with 45 lesions (17 malignant, 28 benign) were included. In malignant thyroid incidentalomas, the average 1-hour maximal SUV, 2-hour maximal SUV, and RI were 5.20, 5.72, and 7.67%, respectively, and in benign thyroid incidentalomas the values were 4.67, 4.97, and 7.38%, respectively. There were no significant differences in 1-hour maximal SUV, 2-hour maximal SUV, and RI between benign and malignant lesions. The area under the ROC curve did not differ from 0.5. Conclusion: Dual-phase FDG PET is not useful for differentiating benign from malignant thyroid incidentalomas. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We performed a retrospective, longitudinal study to compare the prevalence of hyperkinetic laryngeal features before and after successful correction in patients with unilateral vocal cord paralysis (UVCP). METHODS: Eighty-six patients with UVCP who had a successful surgical correction were enrolled. Preoperative and post-operative videolaryngostroboscopy images were analyzed, and the muscle tension patterns (MTPs) were rated according to the Morrison-Rammage classification. A 4-item glottal closure index was used for each patient on study entry and for 40 normal subjects as the control group. RESULTS: There was no significant difference in MTP prevalence before (57%) and after (55%) surgical correction for UVCP. Although the glottal closure symptoms were tremendously improved through surgical medialization for UVCP, they persisted and were more prevalent than those in normal individuals. CONCLUSIONS: Persistence of MTPs after correction of UVCP may be due to intractable vocal habits or psychogenic factors. [ABSTRACT FROM AUTHOR]

The upregulation of BCL2 and BCL-XL, two proteins in the BCL2 family of proteins, leads to a disproportional expression of pro-death and pro-survival proteins in favor of leukemia survival, tumorigenesis, and chemoresistance. In different subsets of acute lymphoblastic leukemia (ALL), the proportion of these two proteins varies, and their potential as therapeutic targets needs detailed characterization. Here, we investigated BCL2 and BCL-XL, the genes that encode BCL2 and BCL-XL, and their expression differences between B-cell acute lymphoblastic leukemia (B-ALL) and T-cell ALL (T-ALL). We also evaluated the therapeutic potential of targeting these proteins with AZD0466, a novel drug-dendrimer conjugate of the BCL2/-XL inhibitor AZD4320, and with BCL2 inhibitor venetoclax (ABT-199). Gene expression and activity analyses supported by the protein expression patterns in ALL cell lines and primary samples demonstrated increased levels of BCL2 expression in B-ALL with high sensitivity to venetoclax or AZD4320. In contrast, strong BCL-XL expression and sensitivity to dual BCL2/-XL inhibition was observed specifically in T-ALL samples. This observation was confirmed by BH3 profiling, demonstrating BCL2/-XL co-dependence in T-ALL and BCL2 dependence in B-ALL. In a mouse model of T-ALL, AZD0466 but not venetoclax reduced leukemic burden and prolonged survival without significant toxicities. Our findings therefore suggest that the novel dual BCL2/-XL inhibitor AZD0466 outperforms single BCL2 inhibition by venetoclax in T-ALL. These findings facilitate the translation of dual BCL2/-XL inhibitors into ALL clinical trials, either alone or in combination with standard- of- care chemotherapy and immune therapies., (Copyright © 2024 American Society of Hematology.)

Background: Aesthetic standards vary and are subjective; artificial intelligence (AI), which is currently seeing a boom in interest, has the potential to provide objective assessment., Objectives: The aim of this study was to provide a relatively objective assessment of the aesthetic outcomes of lower blepharoplasty-related surgeries, thereby enhancing the decision-making process and understanding of the surgical results., Methods: This study included 150 patients who had undergone lower blepharoplasty-related surgeries. Analysis was performed with FaceAge software, created by the authors' research team, which included 4 publicly available age estimation convolution neural network (CNN) models: Amazon Rekognition (Seattle, WA), Microsoft Azure Face (Redmond, WA), Face++ Detect (Beijing, China), and Inferdo face detection (New York, NY). This application was used to compare the subjects' real age and their age as estimated by the 4 CNNs. In addition, this application was used to estimate patient age based on preoperative and postoperative images of all 150 patients and to evaluate the effect of lower blepharoplasty., Results: In terms of accuracy in age prediction, all CNN models exhibited a certain degree of accuracy. For all 150 patients undergoing lower blepharoplasty-related surgeries, these surgeries resulted in about 2 years of rejuvenation with a statistically significant difference; for the sex difference, men had more age reduction than women also with a statistically significant difference; quadrilateral blepharoplasty showed the most significant antiaging effect., Conclusions: By using deep-learning models, lower blepharoplasty-related surgeries actually had an effect on perceived age reduction. Deep learning models have the potential to provide quantitative evidence for the rejuvenating effects of blepharoplasty and other cosmetic surgeries., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Pseudohyperkalemia (falsely elevated serum potassium) must be distinguished from true hyperkalemia to avoid unnecessary treatment. Some case reports suggest that pneumatic tube transportation may increase the risk of pseudohyperkalemia, but comprehensive research on the topic is lacking. Here, we aimed to assess the association between WBC levels, pneumatic tube transport, and pseudohyperkalemia prevalence., Methods: We analyzed 1188 samples collected from 240 patients between 2019 and 2022. Samples with elevated WBC counts (≥ 100 × 10 3 /μL) and potassium levels were included in this study. The method of specimen transportation was documented., Results: Pseudohyperkalemia was observed (7/390) in specimens transported using pneumatic tubes. No pseudohyperkalemia was identified with manually transported specimens (0/132). Every increase in WBC count by 100 × 10 3 /μL in the specimens multiplied the odds ratio of pseudohyperkalemia by 3.75 when delivered with pneumatic tube. The prevalence of pseudohyperkalemia increased as WBC count increased, especially at WBC counts greater than 200 × 10 3 /μL., Conclusion: Pneumatic tube transport poses a risk for pseudohyperkalemia in patients with extreme leukocytosis. Physicians should anticipate odd potassium levels when interpreting blood test results. Redrawing of blood samples, manual specimen transportation, or point-of-care testing are suggested to prevent further misdiagnosis., (© 2024. Japanese Society of Hematology.)

Objective: This study aimd to assess recent trends in the control of low-density lipoprotein cholesterol (LDL-C) and the utilization of lipid-lowering drugs (LLD) among patients with atherosclerotic cardiovascular disease (ASCVD) in Taiwan., Methods: Patients with ASCVD and without a history of hemorrhagic stroke were identified from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. ASCVD patients were stratified into four categories: those who ever had acute coronary syndrome (ACS), those who underwent percutaneous coronary intervention or coronary artery bypass grafting (PCI/CABG) without ACS, those who ever had an ischemic stroke (IS) without ACS or PCI/CABG, and other ASCVD cases. We assessed their latest recorded LDL-C levels for the periods 2015-16, 2017-18, and 2019-20. LLD therapy patterns were presented as monotherapy, dual therapy, or combination therapy of three or more drugs, with statin use classified by intensity., Results: We identified 3831 ASCVD patients in 2015-16, 3531 in 2017-18, and 1231 in 2019-20. LLD utilization rose from 58.4% in 2015-16 to 73.2% in 2019-20. The proportions of patients achieving LDL-C goals in 2015-16, 2017-18, and 2019-20 were 21.5%, 25.8%, and 33.3% in the ACS cohort (goal <70 mg/dL); 20.4%, 26.1%, and 39.0% in the PCI/CABG cohort (goal <70 mg/dL); 54.4%, 58.5%, and 58.9% in the IS cohort (goal <100 mg/dL); and 60.0%, 65.5%, and 67.0% in the other ASCVD cohort (goal <100 mg/dL), respectively. Over half of the patients were prescribed moderate-intensity statins. Statin use, age, history of diabetes mellitus, and hypertension were important factors for attaining LDL-C goal in ACS patients., Conclusion: Despite improvements in LDL-C management observed over recent years, significant gaps remain in guideline adherence, especially for patients with ACS or PCI/CABG in Taiwan, with over 60% not meeting LDL-C targets. Intensifying efforts to align clinical practice with guidelines are imperative., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Non/low-caloric artificial sweeteners (NAS) are recognized as chemical additives substituting sugars to avoid caloric intake and subsequent sugar-derived diseases such as diabetes and hyperglycemia. Six NAS have been claimed safe and are authorized by the US Food and Drug Administration (FDA) for public use, with acceptable daily intake information available: aspartame, acesulfame-K, saccharin, sucralose, neotame, and advantame. However, the impacts of NAS on the gut microbiome have raised potential concerns, since sporadic research revealed NAS-induced microbial changes in the gastrointestinal tracts and alterations in the microbiome-host interactive metabolism., Methods: Given the fact that the gut microbiome influences kaleidoscopic physiological functions in host health, this review aimed to decipher the impacts of NAS on the gut microbiome by implementing a comprehensive two-stage literature analysis based on each NAS., Results: This review documented disturbed microbiomes due to NAS exposure to a maximal resolution of species level using taxonomic clustering analysis, and recorded metabolism alterations involved in gut microbiome-host interactions., Conclusions: The results elucidated that specific NAS exhibited discrepant impacts on the gut microbiome, even though overlapping on the genera and species were identified. Some NAS caused glucose tolerance impairment in the host, but the key metabolites and their underlying mechanisms were different. Furthermore, this review embodied the challenges and future directions of current NAS-gut microbiome research to inspire advanced examination of the NAS exposure-gut microbiome-host metabolism axis.

We describe a process for rapid antibody affinity optimization by repertoire mining to identify clones across B cell clonal lineages based on convergent immune responses where antigen-specific clones with the same heavy (V H ) and light chain germline segment pairs, or parallel lineages, bind a single epitope on the antigen. We use this convergence framework to mine unique and distinct V H lineages from rat anti-triggering receptor on myeloid cells 2 (TREM2) antibody repertoire datasets with high diversity in the third complementarity-determining loop region (CDR H3) to further affinity-optimize a high-affinity agonistic anti-TREM2 antibody while retaining critical functional properties. Structural analyses confirm a nearly identical binding mode of anti-TREM2 variants with subtle but significant structural differences in the binding interface. Parallel lineage repertoire mining is uniquely tailored to rationally explore the large CDR H3 sequence space in antibody repertoires and can be easily and generally applied to antibodies discovered in vivo., (© 2024. The Author(s).)

Objective: This pilot study aimed to assess the feasibility and effectiveness of an auricular acupressure intervention on sleep quality, mood state, and quality of life (QOL) among parents of children with cancer., Methods: Thirty-five parents were assigned to three-weeks intervention in an active auricular acupressure group (AAG) or a sham auricular acupressure group (SAG). Feasibility was assessed by adherence to the acupressure protocol. Outcomes were measured using the Pittsburgh Sleep Quality Index for sleep quality, the Profile of Mood States for mood, and the QOL short form for QOL. The data were analyzed using generalized estimating equations to identify changes over time within and between the groups., Results: Adherence to the protocol was 78%. There were no differences between the groups in overall sleep quality or mood state, but QOL in the Physical Component Summary was better in the AAG at time 1. Parents in the AAG exhibited significantly higher levels of vigor compared to those in the SAG group. Statistically significant differences were observed in the Physical Functioning and General Health subscales, with the AAG showing better outcomes than the SAG group at time 1 and time 2, respectively., Conclusions: Likely due to the small sample size, the AAG and SAG did not differ in overall sleep quality, mood state, or QOL, but there were significant subscale differences that support intervention effectiveness. A fully powered large-scale trial is needed to determine whether this intervention would be effective for parents of children with cancer. Reducing symptom distress and improving QOL in these parents are essential, and interventions to achieve this goal must be tested., Trial Registration: ClinicalTrials.gov NCT05654155., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors.)

Background: Acute kidney injury (AKI) is a severe complication of coronavirus disease 2019 (COVID-19) and is associated with a higher risk of mortality. Understanding the risk factors contributing to COVID-19-related AKI and mortality before vaccination is important for the initiation of preventative measures and early treatment strategies., Methods: This study included patients aged ≥18 years diagnosed with COVID-19 through polymerase chain reaction from May 2020 to July 2021, admitted in three local hospitals in Taiwan, with an extended follow-up until June 30, 2022. A median follow-up period of 250 days was used to assess AKI development and mortality. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. Multivarible Cox regression analysis of AKI and mortality-related risk factors were performed., Results: Of the 720 hospitalized patients with COVID-19, 90 (22%) developed AKI. Moreover, 80%, 10.1%, and 8.9% of the patients had stage 1, 2, and 3 AKI, respectively. Patients with stage 1 to 3 AKI had significantly lower survival rates than those without AKI ( p = 0.001). The mean duration of post-admission AKI occurrence was 9.50 ± 11.32 days. Older age, hypoalbuminemia, and higher D-dimer and ferritin levels were associated with COVID-19 mortality. In COVID-19 AKI, in addition to older age and high D-dimer and ferritin levels, chronic kidney disease emerged as an independent risk factor., Conclusion: COVID-19-related AKI develops early, exhibits a temporal association with respiratory failure, and is linked to an unfavorable prognosis. The mortality rate increased according to the AKI stage ( p = 0.001). Age, albumin, D-dimer, and ferritin levels, and the underlying chronic kidney disease status upon admission are crucial factors for predicting AKI development, which increases the mortality risk. Monitoring the renal function not only within 10 days of COVID-19 onset, but also within 1 month after the disease onset., Competing Interests: Conflicts of interest: The 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.)

Dynamic disease pathways are a combination of complex dynamical processes among bio-molecules in a cell that leads to diseases. Network modeling of disease pathways considers disease-related bio-molecules (e.g. DNA, RNA, transcription factors, enzymes, proteins, and metabolites) and their interaction (e.g. DNA methylation, histone modification, alternative splicing, and protein modification) to study disease progression and predict therapeutic responses. These bio-molecules and their interactions are the basic elements in the study of the misregulation in the disease-related gene expression that lead to abnormal cellular responses. Gene regulatory networks, cell signaling networks, and metabolic networks are the three major types of intracellular networks for the study of the cellular responses elicited from extracellular signals. The disease-related cellular responses can be prevented or regulated by designing control strategies to manipulate these extracellular or other intracellular signals. The paper reviews the regulatory mechanisms, the dynamic models, and the control strategies for each intracellular network. The applications, limitations and the prospective for modeling and control are also discussed.

Oral cancer, particularly oral squamous cell carcinoma (OSCC), is a significant global health challenge because of its high incidence and limited treatment options. Major risk factors, including tobacco use, alcohol consumption, and specific microbiota, contribute to the disease's prevalence. Recently, a compelling association between diabetes mellitus (DM) and oral cancer has been identified, with metformin, a widely used antidiabetic drug, emerging as a potential therapeutic agent across various cancers, including OSCC. This review explores both preclinical and clinical studies to understand the mechanisms by which metformin may exert its anticancer effects, such as inhibiting cancer cell proliferation, inducing apoptosis, and enhancing the efficacy of existing treatments. Preclinical studies demonstrate that metformin modulates crucial metabolic pathways, reduces inflammation, and impacts cellular proliferation, thereby potentially lowering cancer risk and improving patient outcomes. Additionally, metformin's ability to reverse epithelial-to-mesenchymal transition (EMT), regulate the LIN28/let-7 axis, and its therapeutic role in head and neck squamous cell carcinoma (HNSCC) are examined through experimental models. In clinical contexts, metformin shows promise in enhancing therapeutic outcomes and reducing recurrence rates, although challenges such as drug interactions, complex dosing regimens, and risks such as vitamin B12 deficiency remain. Future research should focus on optimizing metformin's application, investigating its synergistic effects with other therapies, and conducting rigorous clinical trials to validate its efficacy in OSCC treatment. This dual exploration underscores metformin's potential to play a transformative role in both diabetes management and cancer care, potentially revolutionizing oral cancer treatment strategies.

We present a practical scheme for the efficient preparation of laser-cooled 43 Ca + ions in an ion trap. Our approach integrates two well-established methods: isotope-selective photoionization and isotope-specific parametric excitation. Drawing inspiration from the individual merits of each method, we have successfully integrated these techniques to prepare extended chains of 43 Ca + ions, overcoming the challenge posed by their low natural abundance of 0.135% in a natural source. Furthermore, we explore the subtleties of our scheme, focusing on the influence of different factors on the purification process. Our investigation contributes to a broader understanding of the technique and highlights the adaptability of established methods in addressing specific isotopic challenges., (© 2024. The Author(s).)

The prevalence of different metabolic syndromes has grown globally, and the farnesoid X receptor (FXR), a metabolic homeostat for glucose, lipid, and bile acid metabolisms, may serve an important role in the progression of metabolic disorders. Glucose intolerance by FXR deficiency was previously reported and observed in our study, but the underlying biology remained unclear. To investigate the ambiguity, we collected the nontargeted profiles of the fecal metaproteome, serum metabolome, and liver proteome in Fxr -null ( Fxr -/- ) and wild-type (WT) mice with LC-HRMS. FXR deficiency showed a global impact on the different molecular levels we monitored, suggesting its serious disruption in the gut microbiota, hepatic metabolism, and circulating biomolecules. The network and enrichment analyses of the dysregulated metabolites and proteins suggested the perturbation of carbohydrate and lipid metabolism by FXR deficiency. Fxr -/- mice presented lower levels of hepatic proteins involved in glycogenesis. The impairment of glycogenesis by an FXR deficiency may leave glucose to accumulate in the circulation, which may deteriorate glucose tolerance. Lipid metabolism was dysregulated by FXR deficiency in a structural-dependent manner. Fatty acid β-oxidations were alleviated, but cholesterol metabolism was promoted by an FXR deficiency. Together, we explored the molecular events associated with glucose intolerance by impaired FXR with integrated novel multiomic data.

Objective: The efficacy of medical treatments and the changes in radiologic imaging before and after treatment have consistently remained pivotal factors. This is particularly critical for surgical procedures, where precise evaluation of disparities pre and postsurgery or the accuracy of implantation is paramount. Based on three-dimensional morphological interests, we provide an automatic quantification evaluation method that delivers an evident base for assessing the outcomes of a widely employed surgical technique, cervical laminoplasty., Methods: The sample study included patients who underwent cervical laminoplasty for cervical spondylotic myelopathy/ossification of the longitudinal ligament. We present a superimposition method that facilitates a unique and precise assessment between pre and postsurgery. The degree of expansion was evaluated by the canal volume increase and canal expansion rate after surgery., Results: There were 31 patients with 112 vertebral segments measured. The target cervical's pre and postoperative canal areas were 122.63 ± 30.34 and 196.50 ± 37.10 mm 2 , respectively (P < 0.001). The average cervical canal expansion rate was 64.42%. The expansion effect of C5 cervical laminoplasty was the maximum (71.01%), and the canal volume of other segments expanded by approximately 60%. The functional outcomes demonstrated significant improvements in symptoms., Conclusions: The quantification evaluation method can be utilized for any morphology changes before and after laminoplasty, as it does not lead to errors or variations from different inspection machines or human factors. The automatic method delivers an evident base for assessing the outcomes of a widely employed surgical technique., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest and sources of funding: none declared.

We report a catalyst family of high-entropy alloy (HEA) atomic layers having three elements from iron-group metals (IGMs) and two elements from platinum-group metals (PGMs). Ten distinct quinary compositions of IGM-PGM-HEA with precisely controlled square atomic arrangements are used to explore their impact on hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR). The PtRuFeCoNi atomic layers perform enhanced catalytic activity and durability toward HER and HOR when benchmarked against the other IGM-PGM-HEA and commercial Pt/C catalysts. Operando synchrotron x-ray absorption spectroscopy and density functional theory simulations confirm the cocktail effect arising from the multielement composition. This effect optimizes hydrogen-adsorption free energy and contributes to the remarkable catalytic activity observed in PtRuFeCoNi. In situ electron microscopy captures the phase transformation of metastable PtRuFeCoNi during the annealing process. They transform from random atomic mixing (25°C), to ordered L1 0 (300°C) and L1 2 (400°C) intermetallic, and finally phase-separated states (500°C).

Background: Erythema induratum (EI) is a tuberculid associated with Mycobacterium tuberculosis infection. Using polymerase chain reaction (PCR), M. tuberculosis has been identified in Taiwan with a high percentage of EI. However, this pathogen is now rarely detected in Taiwan., Objectives: To explore the association between EI, the annual incidence of tuberculosis (TB) in Taiwan and treatment outcomes over the last two decades., Methods: Patients diagnosed with EI between 2001 and 2020 were enrolled based on histopathology, tissue culture and positive M. tuberculosis PCR tests. Other cases of panniculitis with positive M. tuberculosis PCR results were used as controls. The clinical information of participants was obtained. The results were correlated with the annual incidence of TB and compared between groups., Results: Fifty-five biopsy specimens from patients with EI met the inclusion criteria; three (5%) had positive M. tuberculosis PCR results. One patient diagnosed with erythema nodosum in the control group had a positive M. tuberculosis PCR (n = 1/27; 4%). There was no significant relationship between M. tuberculosis and EI (odds ratio 1.5, 95% confidence interval -0.964 to 3.964). The correlation between the incidence of M. tuberculosis and the number of EI cases was not statistically significant (r = -0.185, P = 0.45). Only four patients received anti-TB treatment; they all showed clinical improvement without recurrence. One patient with M. tuberculosis PCR-positive EI was not treated with anti-TB therapy; however, the skin lesion improved after 3 months. No other patients in the EI group were diagnosed with M. tuberculosis infection over a follow-up period of 508 person-years., Conclusions: Most cases of EI in Taiwan are nodular vasculitis and not tuberculid, owing to well-controlled TB. This condition can be alleviated without anti-TB treatment., Competing Interests: Conflicts of interest The authors have no conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Human genetics and preclinical studies have identified key contributions of TREM2 to several neurodegenerative conditions, inspiring efforts to modulate TREM2 therapeutically. Here, we characterize the activities of three TREM2 agonist antibodies in multiple mixed-sex mouse models of Alzheimer's disease (AD) pathology and remyelination. Receptor activation and downstream signaling are explored in vitro, and active dose ranges are determined in vivo based on pharmacodynamic responses from microglia. For mice bearing amyloid-β (Aβ) pathology (PS2APP) or combined Aβ and tau pathology (TauPS2APP), chronic TREM2 agonist antibody treatment had limited impact on microglia engagement with pathology, overall pathology burden, or downstream neuronal damage. For mice with demyelinating injuries triggered acutely with lysolecithin, TREM2 agonist antibodies unexpectedly disrupted injury resolution. Likewise, TREM2 agonist antibodies limited myelin recovery for mice experiencing chronic demyelination from cuprizone. We highlight the contributions of dose timing and frequency across models. These results introduce important considerations for future TREM2-targeting approaches., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Gut microbiome is a group of microorganisms that plays important roles in contributing to health and diseases. These bacterial compositions have been demonstrated to impact bile acids (BAs) profiles, either by directly metabolizing primary BAs to secondary BAs or indirect ways through host metabolism by influencing BAs synthesis, transportation and conjugation in liver. It has been observed sexually dimorphic gut microbiome and bile acids composition, with variations in expression levels of bile acid metabolizing genes in the liver. However, associations between sex-specific differences in gut microbiome and BAs profiles are not well understood. This study aimed to investigate whether gut microbiome could influence BAs profiles in host in a sexspecific manner. We transplanted cecum feces of male and female C57BL/6 mice to male mice and measured BAs concentrations in feces, serum and liver samples 7 days after fecal transplantation. We found different BAs profiles between mice with male and female gut microbiome, including altering levels and proportions of secondary BAs. We also observed varied expression levels of genes related to bile acid metabolism in the liver and distal ileum. Our results highlight sex-specific effects of gut microbiome on shaping bile acid metabolism through gut bacteria and regulation of host genes., Competing Interests: Conflict of Interest 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.

Hormones and neurotransmitters are essential to homeostasis, and their disruptions are connected to diseases ranging from cancer to anxiety. The differential reactivation of endobiotic glucuronides by gut microbial β-glucuronidase (GUS) enzymes may influence interindividual differences in the onset and treatment of disease. Using multi-omic, in vitro, and in vivo approaches, we show that germ-free mice have reduced levels of active endobiotics and that distinct gut microbial Loop 1 and FMN GUS enzymes drive hormone and neurotransmitter reactivation. We demonstrate that a range of FDA-approved drugs prevent this reactivation by intercepting the catalytic cycle of the enzymes in a conserved fashion. Finally, we find that inhibiting GUS in conventional mice reduces free serotonin and increases its inactive glucuronide in the serum and intestines. Our results illuminate the indispensability of gut microbial enzymes in sustaining endobiotic homeostasis and indicate that therapeutic disruptions of this metabolism promote interindividual response variabilities., Competing Interests: Declaration of interests M.R.R. is a founder of Symberix, Inc., which is developing microbiome-targeted therapeutics. M.R.R. has also received research funding from Eli Lilly., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to evaluate the performance of a modified U.S. (MUS) model for risk prediction of cardiovascular (CV) events in Asian patients and compare it to European and Japanese models., Methods: The MUS model, based on the US ACC/AHA 2018 lipid treatment guideline, was employed to stratify patients under primary or secondary prevention. Two multi-center prospective observational registry cohorts, T-SPARCLE and T-PPARCLE, were used to validate the scoring system, and the primary outcome was the time to first occurrence/recurrence of major adverse cardiac events (MACEs). The MUS model's performance was compared to other models from Europe and Japan., Results: A total of 10,733 patients with the mean age of 64.2 (SD: 11.9) and 36.5% female were followed up for a median of 5.4 years. The MUS model was validated, with an AUC score of 0.73 (95% CI 0.68-0.78). The European and Japanese models had AUC scores ranging from 0.6 to 0.7. The MUS model categorized patients into four distinct CV risk groups, with hazard ratios (HRs) as follows: very high- vs. high-risk group (HR = 1.91, 95% CI 1.53-2.39), high- vs. moderate-risk group (HR = 2.08, 95% CI 1.60-2.69), and moderate- vs. low-risk group (HR = 3.14, 95% CI 1.63-6.03). After adjusting for the MUS model, a history of atherosclerotic vascular disease (ASCVD) was not a significant predictor of adverse cardiovascular outcomes within each risk group., Conclusion: The MUS model is an effective tool for risk stratification in Asian patients with and without ASCVD, accurately predicting MACEs and performing comparably or better than other established risk models. Our findings suggest that patient management should focus on background risk factors instead of solely on primary or secondary prevention., Competing Interests: Conflicts of interest The authors declared no conflicts of interest., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The psychological effects of staged nasal reconstruction with a forehead flap were prospectively investigated. Thirty-three patients underwent nasal reconstruction with forehead flaps between March 2017 and July 2020. Three questionnaires were used to assess psychosocial functioning before surgery (time 1), 1 week after forehead flap transfer (time 2), 1 week after forehead flap division (time 3), and after refinement procedures (time 4). The patients were categorized into three groups according to the severity of nasal defects. Between- and within-group comparisons were conducted. All patients reported increased satisfaction with their appearance during nasal reconstruction. For most patients, levels of distress and social avoidance were highest before reconstruction (time 1). Both levels decreased as reconstruction advanced, and were significantly improved by times 3 and 4. The stage of reconstruction had a greater effect on these levels than did severity of nasal defect. Nasal reconstruction with forehead flap is beneficial physically and psychologically. Psychological evaluation before and after surgery facilitates patient-surgeon interactions and further enhances outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2024 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Current treatment of snakebite relies on immunoglobulin-rich antivenoms. However, production of these antivenoms is complicated and costly. Aptamers - single-stranded DNAs or RNAs with specific folding structures that bind to specific target molecules - represent excellent alternatives or complements to antibody-based therapeutics. However, no studies have systematically assessed the feasibility of using aptamers to mitigate venom-induced toxicity in vivo. β-bungarotoxin is the predominant protein responsible for the toxicity of the venom of Bungarus multicinctus, a prominent venomous snake inhabiting Taiwan. In this study, we reported the screening and optimization of a DNA aptamer against β-bungarotoxin and tested its utility in a mouse model. After 14 rounds of directed evolution of ligands by exponential enrichment, an aptamer, called BB3, displaying remarkable binding affinity and specificity for β-bungarotoxin was obtained. Following structural prediction and point-modification experiments, BB3 underwent truncation and was modified with 2'-O-methylation and a 3'-inverted dT. This optimized aptamer showed sustained, high-affinity binding for β-bungarotoxin and exhibited remarkable nuclease resistance in plasma. Importantly, administration of this optimized aptamer extended the survival time of mice treated with a lethal dose of β-bungarotoxin. Collectively, our data provide a compelling illustration of the potential of aptamers as promising candidates for development of recombinant antivenom therapies., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: All the authors declare no conflict of interest.

DNA cross-links severely challenge replication and transcription in cells, promoting senescence and cell death. In this paper, we report a novel type of DNA interstrand cross-link (ICL) produced as a side product during the attempted repair of 1, N 6 -ethenoadenine (εA) by human α-ketoglutarate/Fe(II)-dependent enzyme ALKBH2. This stable/nonreversible ICL was characterized by denaturing polyacrylamide gel electrophoresis analysis and quantified by high-resolution LC-MS in well-matched and mismatched DNA duplexes, yielding 5.7% as the highest level for cross-link formation. The binary lesion is proposed to be generated through covalent bond formation between the epoxide intermediate of εA repair and the exocyclic N 6 -amino group of adenine or the N 4 -amino group of cytosine residues in the complementary strand under physiological conditions. The cross-links occur in diverse sequence contexts, and molecular dynamics simulations rationalize the context specificity of cross-link formation. In addition, the cross-link generated from attempted εA repair was detected in cells by highly sensitive LC-MS techniques, giving biological relevance to the cross-link adducts. Overall, a combination of biochemical, computational, and mass spectrometric methods was used to discover and characterize this new type of stable cross-link both in vitro and in human cells, thereby uniquely demonstrating the existence of a potentially harmful ICL during DNA repair by human ALKBH2.

Gluten is a well-known food allergen globally, and it can induce immune responses in celiac- and nonceliac gluten-sensitive patients. The gliadin proteins from gluten have a special amino acid sequence that make it hydrophobic. One way to deal with gluten allergies is to provide a gluten-free diet. The hydrophobic characteristic of gliadin makes gliadin detection more difficult. An analyst needs to use an organic solvent or multiple processes to denature gluten for extraction. Although organic solvents can rapidly extract gluten in a sample, organic solvent also denatures the antibody and induces false biotest results without buffer dilute, and the accuracy will reduce with buffer dilute. An ionic liquid (IL) is a highly modifiable green chemical organic salt. The imidazolium has a cationic structure and is modified with different lengths ( C = 0, 1, 3, 5, 7, 9, and 12) of carbon side chains with organic and inorganic anions [methanesulfonate (MSO), Cl - , F - , NO 3 - , HSO 4 - , and H 2 PO 4 - ] to make different kinds of ILs for testing the solubility of gliadin. Different IL/water ratios were used to test the solubility of gluten. We measured the solubility of gliadin in different imidazolium ILs, and the kinetic curve of gliadin dissolved in 1% [C5DMIM][MSO] aq was conducted. We also used circular dichroism spectroscopy and an enzyme-linked immunosorbent assay to measure the gliadin structure and the effect of binding with an antibody after 1% [C5DMIM][MSO] aq treatment. An 2,3-bis-(2-methoxy-4- nitro-5-sulfophenyl)-2 H -tetrazolium-5-carboxanilide (XTT) assay was used to test the toxicity of [C5DMIM][MSO] aq in N2a cells. In our research, 1% [C5DMIM][MSO] aq produced a good solubility of gluten, and it could dissolve more than 3000 ppm of gluten in 5 min. [C5DMIM][MSO] aq did not break down the gluten structure and did not restrict antibody binding to gluten, and more importantly, [C5DMIM][MSO] did not exhibit cell toxicity. In this report, we showed that [C5DMIM][MSO] could be a good extraction solution applied for gluten detection., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The study measured the levels of azoxystrobin (AZ) and thiabendazole (TBZ) in wallboards and metabolite levels of these fungicides in children. The paper covering of wallboard samples contained a higher concentration of AZ and TBZ than the gypsum core, and similar amounts (w/w) of these two fungicides were present in the samples. These data suggest that commercial products containing a 1:1 (w/w) amount of AZ and TBZ, such as Sporgard® WB or Azo Tech™, were applied to the wallboard paper. This is the first detection of TBZ in mold-and-mildew resistant wallboards. The TBZ metabolite, 5OH-TBZ, was detected in 48% of urine samples collected from children aged 40-84 months, and was co-detected with AZ-acid, a common AZ metabolite, in 37.5% of the urine samples. The detection frequency of 5OH-TBZ was positively associated with the detection frequency of AZ-acid. These findings suggest that certain types of wallboards used in homes and commercial buildings may be a potential source of co-exposure to AZ and TBZ in humans., Competing Interests: 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., (© 2024 The Authors.)

Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival. An unbiased CRISPR screen provides an aerial map of RAD18-interacting DNA damage response (DDR) pathways deployed by GBM to tolerate TMZ genotoxicity. Analysis of mutation signatures from TMZ-treated GBM reveals a role for RAD18 in error-free bypass of O 6 mG (the most toxic TMZ-induced lesion), and error-prone bypass of other TMZ-induced lesions. Our analyses of recurrent GBM patient samples establishes a correlation between low RAD18 expression and hypermutation. Taken together we define molecular underpinnings for the hallmark tumorigenic phenotypes of TMZ-treated GBM., (© 2024. The Author(s).)

Animal testing has been the primary approach to assess the neutralization potency of antivenom for decades. However, the necessity to sacrifice large numbers of experimental animals during this process has recently raised substantial welfare concerns. Furthermore, the laborious and expensive nature of animal testing highlights the critical need to develop alternative in vitro assays. Here, we developed an antibody-detection enzyme-linked immunosorbent assay (ELISA) technique as an alternative approach to evaluate the neutralization potency of hyperimmunized equine plasma against B. multicinctus, a medically important venomous snake in Taiwan. Firstly, five major protein components of B. multicinctus venom, specifically, α-BTX, β-BTX, γ-BTX, MTX, and NTL, were isolated. To rank their relative medical significance, a toxicity score system was utilized. Among the proteins tested, β-BTX presenting the highest score was regarded as the major toxic component. Subsequently, antibody-detection ELISA was established based on the five major proteins and used to evaluate 55 hyperimmunized equine plasma samples with known neutralization potency. ELISA based on β-BTX, the most lethal protein according to the toxicity score, exhibited the best sensitivity (75.6 %) and specificity (100 %) in discriminating between high-potency and low-potency plasma, supporting the hypothesis that highly toxic proteins offer better discriminatory power for potency evaluation. Additionally, a phospholipase A 2 (PLA 2 ) competition process was implemented to eliminate the antibodies targeting toxicologically irrelevant domains. This optimization greatly enhanced the performance of our assay, resulting in sensitivity of 97.6 % and specificity of 92.9 %. The newly developed antibody-detection ELISA presents a promising alternative to in vivo assays to determine the neutralization potency of antisera against B. multicinctus during the process of antivenom production., 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: Improving the philtrum morphology of patients with a secondary cleft lip deformity has been a challenge in cleft care. Combining fat grafting with percutaneous rigottomy has been advocated for treatment of volumetric deficiency associated with a scarred recipient site. This study assessed the outcome of synchronous fat grafting and rigottomy for improvement of cleft philtrum morphology., Methods: Consecutive young adult patients ( n = 13) with a repaired unilateral cleft lip who underwent fat grafting combined with rigottomy expansion technique for enhancement of philtrum morphology were included. Preoperative and postoperative three-dimensional facial models were used for three-dimensional morphometric analyses including philtrum height, projection, and volume parameters. Lip scar was qualitatively judged by a panel composed by two blinded external plastic surgeons using a 10-point visual analogue scale., Results: Three-dimensional morphometric analysis revealed a significant (all P < 0.05) postoperative increase of the lip height-related measurements for cleft philtrum height, noncleft philtrum height, and central lip length parameters, with no difference ( P > 0.05) between cleft and noncleft sides. The postoperative three-dimensional projection of the philtral ridges was significantly ( P < 0.001) larger in cleft (1.01 ± 0.43 mm) than in noncleft sides (0.51 ± 0.42 mm). The average philtrum volume change was 1.01 ± 0.68 cm 3 , with an average percentage fat graft retention of 43.36% ± 11.35%. The panel assessment revealed significant ( P < 0.001) postoperative scar enhancement for the qualitative rating scale, with mean preoperative and postoperative scores of 6.69 ± 0.93 and 7.88 ± 1.14, respectively., Conclusion: Synchronous fat grafting and rigottomy improved philtrum length, projection, and volume and lip scar in patients with repaired unilateral cleft lip., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Abstract: Preclinical studies suggest that Bcl-2 inhibition with venetoclax has antileukemic activity in acute lymphoblastic leukemia (ALL) and may synergize with conventional chemotherapy. We designed a phase 1/2 clinical trial to evaluate the safety and efficacy of low-intensity chemotherapy in combination with venetoclax in adults with relapsed or refractory ALL. Patients received the mini-hyper-CVD regimen (dose-attenuated hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with methotrexate and cytarabine) in combination with venetoclax (200 mg or 400 mg daily) on days 1 to 14 in cycle 1 and on days 1 to 7 in consolidation cycles. Twenty-two patients were treated. The median number of prior therapies was 2 (range, 1-6). Thirteen patients (59%) had undergone prior allogeneic stem cell transplant (allo-SCT), and 7 of 18 patients (39%) with B-cell ALL had previously received both inotuzumab ozogamicin and blinatumomab. The recommended phase 2 dose of venetoclax in the combination regimen was 400 mg daily. The composite complete remission (CR) and CR with incomplete hematologic recovery (CRi) rate was 57% (CR, 43%; CRi, 14%), and 45% of responders achieved measurable residual disease negativity by multiparameter flow cytometry. Four patients proceeded to allo-SCT. The median duration of response was 6.3 months. The median overall survival was 7.1 months, and the 1-year overall survival rate was 29%. The most common grade ≥3 nonhematologic adverse events were infection in 17 patients (77%) and febrile neutropenia in 4 patients (18%). Overall, the combination of mini-hyper-CVD plus venetoclax was active in heavily pretreated relapsed/refractory ALL. Further development of venetoclax-based combinations in ALL is warranted. This trial is registered at www.clinicaltrials.gov as #NCT03808610., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Targeted mass spectrometry is a powerful technique for quantifying specific proteins or metabolites in complex biological samples. Accurate peak picking is a critical step as it determines the absolute abundance of each analyte by integrating the area under the picked peaks. Although automated software exists for handling such complex tasks, manual intervention is often required to rectify potential errors like misclassification or mis-picking events, which can significantly affect quantification accuracy. Therefore, it is necessary to develop objective scoring functions to evaluate peak-picking results and to identify problematic cases for further inspection. In this study, we present targeted mass spectrometry quality encoder (TMSQE), a data-driven scoring function that summarizes peak quality in three types: transition level, peak group level, and consistency level across samples. Through unsupervised learning from large data sets containing 1,703,827 peak groups, TMSQE establishes a reliable standard for systematic and objective evaluations of chromatographic peak quality in targeted mass spectrometry. TMSQE shows a high degree of consistency with expert experiences and can efficiently capture problematic cases after the automated software. Furthermore, we demonstrate the generalizability of TMSQE by successfully applying it to various data sets, including both peptide and metabolite data sets. Our proposed scoring approach provides a reliable solution for consistent and accurate peak quality evaluation, facilitating peak quality control for targeted mass spectrometry.

Large-area metamorphic stretchable sensor networks are desirable in haptic sensing and next-generation electronics. Triboelectric nanogenerator-based self-powered tactile sensors in single-electrode mode constitute one of the best solutions with ideal attributes. However, their large-area multiplexing utilizations are restricted by severe misrecognition between sensing nodes and high-density internal circuits. Here, we provide an electrical signal shielding strategy delivering a large-area multiplexing self-powered untethered triboelectric electronic skin (UTE-skin) with an ultralow misrecognition rate (0.20%). An omnidirectionally stretchable carbon black-Ecoflex composite-based shielding layer is developed to effectively attenuate electrostatic interference from wirings, guaranteeing low-level noise in sensing matrices. UTE-skin operates reliably under 100% uniaxial, 100% biaxial, and 400% isotropic strains, achieving high-quality pressure imaging and multi-touch real-time visualization. Smart gloves for tactile recognition, intelligent insoles for gait analysis, and deformable human-machine interfaces are demonstrated. This work signifies a substantial breakthrough in haptic sensing, offering solutions for the previously challenging issue of large-area multiplexing sensing arrays., (© 2024. The Author(s).)

Summary: The crescentic alar groove serves as a topographic landmark that frames the ala and separates this convex structure from the surrounding cosmetic subunits. This aesthetic landmark can be attenuated or even obliterated during wound repair in this area. Flaps spanning the alar crease are often noticeably bulky with a pin-cushioned appearance in nasal reconstruction, and it is challenging to reproduce a natural-appearing alar groove. The authors proposed a novel technique with a modified, interrupted inverted horizontal mattress suture to create an alar groove. From March of 2016 to May of 2021, 22 consecutive patients with alar defects who underwent nasal reconstruction with the paramedian forehead flap were identified. All patients underwent the authors' novel technique for the creation of the alar groove. The mean follow-up time was 3 years 7 months (range, 14 months to 5 years). A total of 32 alar crease creation suture operations were performed. All uneven wounds healed uneventfully within 2 weeks. Two cases of postoperative fading alar grooves required alar crease creation sutures to be redone. The authors' novel alar crease creation suture is a safe, straightforward, and reliable technique to create an aesthetic alar groove in forehead flap nasal reconstruction. It can create a medially shallow and laterally deep alar crease without apparent complications., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2023 by the American Society of Plastic Surgeons.)

To find new molecular targets for triple negative breast cancer (TNBC), we analyzed a large-scale drug screening dataset based on breast cancer subtypes. We discovered that BDP-9066, a specific MRCK inhibitor (MRCKi), may be an effective drug against TNBC. After confirming the efficacy and specificity of BDP-9066 against TNBC in vitro and in vivo , we further analyzed the underlying mechanism of specific activity of BDP-9066 against TNBC. Comparing the transcriptome of BDP-9066-sensitive and -resistant cells, the activation of the focal adhesion and YAP/TAZ pathway were found to play an important role in the sensitive cells. Furthermore, YAP/TAZ is indeed repressed by BDP-9066 in the sensitive cells, and active form of YAP suppresses the effects of BDP-9066. YAP/TAZ expression and activity are high in TNBC, especially the Claudin-low subtype, consistent with the expression of focal adhesion-related genes. Interestingly, NF-κB functions downstream of YAP/TAZ in TNBC cells and is suppressed by BDP-9066. Furthermore, the PI3 kinase pathway adversely affected the effects of BDP-9066 and that alpelisib, a PI3 kinase inhibitor, synergistically increased the effects of BDP-9066, in PIK3CA mutant TNBC cells. Taken together, we have shown for the first time that MRCKi can be new drugs against TNBC, particularly the Claudin-low subtype., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Hemodialysis is the most common therapy for managing patients with end-stage renal disease. Depression is one of the most common psychological problems faced by dialysis patients, and there is limited research on the influences of religion and spirituality on dialysis patients., Purpose: This study was designed to compare religion and spiritual health status between hemodialysis patients with and without depressive symptoms., Methods: A cross-sectional survey was conducted on 137 hemodialysis patients living in Taiwan. The self-report instruments used included the Religious Beliefs Scale, Spiritual Health Scale-Short Form, and Beck Depression Inventory-II. Data were analyzed using t test, chi-square test, point-biserial correlation of variance, and logistic regression., Results: Most (63.5%) of the participants were classified with depression, of which most were male (70.1%), older (mean = 62.56 years), and unemployed (73.6%) and had less formal education. Fifty-two of the participants with depression had a 1- to 5-year duration of hemodialysis, whereas the nondepressed group had a higher mean score for number of religious activities, positive religious beliefs, and total score for spiritual health. Logistic regression showed an increased odds ratio ( OR ) of depression for participants with a duration of hemodialysis of 1-5 years ( OR = 3.64, 95% CI [1.01, 13.15]). Participants with higher scores for spiritual health had a lower risk of depression ( OR = 0.82, 95% CI [0.75, 0.90]), indicating a positive association between spiritual health and lower depression risk., Conclusions/implications for Practice: The prevalence rate of depression in hemodialysis patients is higher than that in the general population. Providing screenings for spiritual health and depression as part of routine medical care for hemodialysis patients is recommended to detect spiritual distress and depression early., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc.)

Glyphosate is a widely used active ingredient in agricultural herbicides, inhibiting the biosynthesis of aromatic amino acids in plants by targeting their shikimate pathway. Our gut microbiota also facilitates the shikimate pathway, making it a vulnerable target when encountering glyphosate. Dysbiosis in the gut microbiota may impair the gut-brain axis, bringing neurological outcomes. To evaluate the neurotoxicity and biochemical changes attributed to glyphosate, we exposed mice with the reference dose (RfD) set by the U.S. EPA (1.75 mg/Kg-BW/day) and its hundred-time-equivalence (175 mg/Kg-BW/day) chronically via drinking water, then compared a series of neurobehaviors and their fecal/serum metabolomic profile against the non-exposed vehicles (n = 10/dosing group). There was little alteration in the neurobehavior, including motor activities, social approach, and conditioned fear, under glyphosate exposure. Metabolomic differences attributed to glyphosate were observed in the feces, corresponding to 68 and 29 identified metabolites with dysregulation in the higher and lower dose groups, respectively, compared to the vehicle-control. There were less alterations observed in the serum metabolome. Under 175 mg/Kg-BW/day of glyphosate exposure, the aromatic amino acids (phenylalanine, tryptophan, and tyrosine) were reduced in the feces but not in the serum of mice. We further focused on how tryptophan metabolism was dysregulated based on the pathway analysis, and identified the indole-derivatives were more altered compared to the serotonin and kynurenine derivatives. Together, we obtained a three-dimensional data set that records neurobehavioral, fecal metabolic, and serum biomolecular dynamics caused by glyphosate exposure at two different doses. Our data showed that even under the high dose of glyphosate irrelevant to human exposure, there were little evidence that supported the impairment of the gut-brain axis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This paper presents an innovative method of producing a low-density, high-strength, thin cement sheet. A seaweed powder was mixed with Portland cement, a foaming agent, calcium sulfoaluminate (CSA), and a quantity of water to create an A4-sized thin sheet with a thickness of 7 mm, which can withstand 1.5 kg in weight. This sheet was then covered with ethylene vinyl acetate and a backsheet to create a sandwiched cement sheet. The advantages of this sandwiched cement sheet are two-fold. First, it can support up to 13 kg in a static mechanical loading test, without bending, for over eight hours. Second, it can be quickly recovered at the end of its life cycle. This was a preliminary experiment to produce a large cement sheet that could satisfy the loading requirements for a solar panel. The purpose of the large, thin cement sheet is to replace the glass in a conventional solar panel and create a lightweight solar panel of less than 10 kg, which would mean that the installation of solar panels would become a one-person operation rather than a two-person operation. It would also increase the efficiency of the solar panel installation process.

In this study, we analyze the influences of carbon nanotube (CNT) addition on the martensite transformation and internal friction of Cu-Al-Ni shape-memory alloys (SMAs). X-ray diffraction and differential scanning calorimetry results demonstrate that Cu-13.5Al-4Ni-xCNT (x = 0, 0.2, 0.4, 0.6, and 0.8 wt%) SMA/CNT composites exhibit a [Formula: see text] martensitic transformation. The martensitic transformation temperatures and transformation enthalpies of the martensitic transformation peaks for the Cu-13.5Al-4Ni-xCNT (x = 0-0.8 wt%) composites gradually decrease with the increase in the amount of CNT addition. Compared to the Cu-13.5Al-4Ni SMA, the Cu-13.5Al-4Ni-xCNT (x = 0.2-0.8 wt%) SMA/CNT composites exhibit significant improvements in the amount of dissipation of energy (storage modulus ([Formula: see text] and mechanical strength. However, the tan δ of the internal friction peak gradually decreases with the increase in the CNT content above 0.6 wt%. The reduction in tan δ is attributed to the decrease in the magnitude of the austenite-to-martensite transformation and precipitation of γ 2 (Cu 9 Al 4 ) phase particles, which impede the interface motion in between the parent/martensitic phase and martensitic phase., (© 2023. The Author(s).)

Background: The use of magnetic resonance linear accelerators (MR-LINACs) for clinical treatment has opened up new possibilities and challenges in the field of radiation oncology. However, annual quality assurance (QA) is relatively understudied due to practical considerations. Thus, to overcome the difficulty of measuring the dose with a small water phantom for TRS-398 or TG-51 in all external beam radiation treatment unit environments, such as MR compatibility, we designed a remote phantom with a three-axis changeable capacity for QA., Methods: The designed water phantom was tested under an MR environment. The water phantom system comprised of three parts: a phantom box, a dose measurement tool, and a PMD401 drive system. The UNIDOSE universal dosimeter was used to collect beam data. The manufacturer's developer tools were utilized to position the measurement. To ensure magnetic field homogeneity, a distortion phantom was prepared using sixty fish oil capsules aligned radially to distinguish the oil and free air. The phantom was scanned in both the MR simulator and computed tomography (CT), and the acquired images were analyzed to determine the position shift., Results: The dimensions of the device are 30 cm in the X-axis, 20 cm in the Y-axis, and 17 cm in the Z-axis. Total cost of materials was no more than $10,000 US dollars. Our results indicate that the device can function normally in a regular 1.5 T MR environment without interference from the magnetic field. The water phantom's traveling speed was found to be approximately 5 mm/s with a position difference confined within 6 cm intervals during normal use. The distortion test results showed that the prepared MR environment has uniform magnetic field homogeneity., Conclusions: In this study, we constructed a prototype water phantom device that can function in an MR simulator without interference between the magnetic field and electronic components. Compared to other commercially available MR-LINAC water phantoms, our device offers a more cost-effective solution for routine monthly QA. It can shorten the duration of QA tests and relieve the burden on medical physicists., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-189/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

We designed three new controllers: a sigmoid-based controller, a polynomial dynamic inversion-based controller, and a proportional-integral-derivative (PID) impulsive controller for cancer differentiation therapy. We compared these three controllers to existing control strategies to show the improvement in performance and compare their robustness. The sigmoid-based controller adds a sigmoid term associated with the error of the controlled state and a selected observed state. The sigmoid term is multiplied by a control gain, thereby decreasing the control effort for state transition. The polynomial dynamic inversion-based controller adds a cubic error term in the error dynamic aiming to achieve a shorter convergence time to the desired value of the controlled state. The PID impulsive controller considers the accumulated controlled state error and the rate of change of the controlled state error, thereby forcing the controlled state to converge to the desired value and alleviating the damping effect in the steady state. For the considered cancer network, the 3 new cancer control strategies exhibit superior and robust performance. The PID impulsive controller has a significant improvement in robustness compared to the impulsive controller and has greater potential for cancer differentiation therapy., 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 © 2023 Elsevier Inc. All rights reserved.)