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Hsiao-Ping Huang,1 Kee-Hsin Chen,2– 6 Chen-Liang Tsai,7 Wen-Pei Chang,8,9 Sherry Yueh-Hsia Chiu,10,11 Shin-Rou Lin,10,11 Yu-Huei Lin2 1Nursing Department, Center for Nursing and Healthcare Research in Clinical Practice Application, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 2Post-Baccalaureate Program in Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan; 3Cochrane Taiwan, Taipei Medical University, Taipei, Taiwan; 4Department of Nursing, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 5Center for Nursing and Healthcare Research in Clinical Practice Application, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 6Evidence-Based Knowledge Translation Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 8Department of Nursing, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; 9School of Nursing, College of Nursing, Taipei Medical University, Taipei, Taiwan; 10Department of Health Care Management, College of Management, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan; 11Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, TaiwanCorrespondence: Yu-Huei Lin, Tel +886 2 27361661 Ext 3620, Fax +886 2 23772842, Email gracelin@tmu.edu.twPurpose: This study aimed to evaluate the efficacy of high-frequency chest wall oscillation for sputum expectoration and hospital length of stay in patients with acute exacerbations of chronic obstructive pulmonary disease. The improvements in pulmonary function and oxygenation were also investigated.Patients and Methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. Automated literature database searches were conducted from the earliest records to March 31, 2022. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias tool (RoB 2.0), and meta-analysis software (RevMan 5.4) was used to analyze the data.Results: From 5439 identified articles, 13 studies (with 756 patients) were included in this meta-analysis. Compared to other airway clearance techniques, HFCWO significantly increased expectorated sputum volume by 6.18 mL (95% CI: 1.71 to 10.64; I2 = 87%), shortened hospital stay by 4.37 days (95% CI: − 7.70 to − 1.05; I2 = 84%). However, FEV1 (%), PaO2, and PaCO2 did not improve significantly.Conclusion: AECOPD patients may benefit from HFCWO therapy. HFCWO enables AECOPD patients to excrete more sputum and shorten their hospital stays. However, due to heterogeneity among the included research, these results should be interpreted with caution.Keywords: acute exacerbation of chronic obstructive pulmonary disease, AECOPD, high-frequency chest wall oscillation, HFCWO, sputum expectoration, length of hospital stay

Yu-Chin An,1 Chia-Lin Tsai,2 Chih-Sung Liang,3 Yu-Kai Lin,2 Guan-Yu Lin,2 Chia-Kuang Tsai,2 Yi Liu,2 Sy-Jou Chen,1 Shih-Hung Tsai,1 Kuo-Sheng Hung,4 Fu-Chi Yang2 1Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 2Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 3Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 4Center for Precision Medicine and Genomics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of ChinaCorrespondence: Fu-Chi Yang, Department of Neurology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China, Tel +886-2-87923311 # 88078, Fax +886-2-87927174, Email fuji-yang@yahoo.com.twPurpose: Although insomnia and migraine are often comorbid, the genetic association between insomnia and migraine remains unclear. This study aimed to identify susceptibility loci associated with insomnia and migraine comorbidity.Patients and Methods: We performed a genome-wide association study (GWAS) involving 1063 clinical outpatients at a tertiary hospital in Taiwan. Migraineurs with and without insomnia were genotyped using the Affymetrix Axiom Genome-Wide TWB 2.0. We performed association analyses for the entire cohort and stratified patients into the following subgroups: episodic migraine (EM), chronic migraine (CM), migraine with aura (MA), and migraine without aura (MoA). Potential correlations between SNPs and clinical indices in migraine patients with insomnia were examined using multivariate regression analysis.Results: The SNP rs1178326 in the gene HDAC9 was significantly associated with insomnia. In the EM, CM, MA, and MoA subgroups, we identified 30 additional susceptibility loci. Multivariate regression analysis showed that SNP rs1178326 also correlated with higher migraine frequency and the Migraine Disability Assessment (MIDAS) questionnaire score. Finally, two SNPs that had been previously reported in a major insomnia GWAS were also significant in our migraineurs, showing a concordant effect.Conclusion: In this GWAS, we identified several novel loci associated with insomnia in migraineurs in a Han Chinese population in Taiwan. These results provide insights into the possible genetic basis of insomnia and migraine comorbidity.Keywords: insomnia, migraine, GWAS, SNP, gene, comorbidity

Chia-Liang Tsai,1 Ching-Yun Huang,2 Yi-Ching Lu,1 Li-Mei Pai,3,4 Daniel Horák,5 Yunn-Hwa Ma1,6 1Department of Physiology and Pharmacology, Chang Gung University, Taoyuan, 33302, Taiwan, Republic of China; 2Institute of Biomedical Sciences, Chang Gung University, Taoyuan, 33302, Taiwan, Republic of China; 3Department of Biochemistry & Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan, Republic of China; 4Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, 33305, Taiwan, Republic of China; 5Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague 6, 162 06, Czech Republic; 6Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Taoyuan, 33305, Taiwan, Republic of ChinaCorrespondence: Yunn-Hwa Ma, Department of Physiology and Pharmacology, Chang Gung University, Guishan, Taoyuan, 33302, Taiwan, Republic of China, Email yhma@mail.cgu.edu.twBackground: Intravascular delivery of nanoparticles for theranostic application permits direct interaction of nanoparticles and vascular cells. Since vascular smooth muscle cells (VSMCs), the major components of the vascular wall, are constantly subjected to mechanical stimulation from hemodynamic influence, we asked whether cyclic strain may modulate internalization of magnetic nanoparticles (MNPs) by cultured VSMCs.Methods: Cyclic strain (1 Hz and 10%) was applied with Flexcell system in cultured VSMCs from rats, with cell-associated MNPs (MNPcell) determined by a colorimetric iron assay. Transmission and scanning electron microscopy were used for morphology studies. Confocal microscopy was used to demonstrate distribution of actin assembly in VSMCs.Results: Incubation of poly(acrylic acid) (PAA)-coated MNPs with VSMCs for 4 h induced microvilli formation and MNP internalization. Application of cyclic strain for 4– 12 h significantly reduced MNPcell by up to 65% (p < 0.05), which was associated with blunted microvilli and reduced vesicle size/cell, but not vesicle numbers/cell. Confocal microscopy demonstrated that both cyclic strain and fibronectin coating of the culture plate reduced internalized MNPs, which were co-localized with vinculin. Furthermore, cytochalasin D reduced MNPcell, suggesting a role of actin polymerization in MNP uptake by VSMCs; however, a myosin II ATPase inhibitor, blebbistatin, exhibited no effect. Cyclic strain also attenuated uptake of PAA-MNPs by LN-229 cells and uptake of poly-L-lysine-coated MNPs by VSMCs.Conclusion: In such a dynamic milieu, cyclic strain may impede cellular internalization of nanocarriers, which spares the nanocarriers and augments their delivery to the target site in the lumen of vessels or outside of the circulatory system.Graphical Abstract: Keywords: cyclic strain, magnetic nanoparticles, endocytosis, actin

Silicone (polydimethylsiloxane) injections are used for cosmetic augmentation. Their use is associated with life-threatening complications such as acute pneumonitis, alveolar hemorrhage, and acute respiratory distress among others [1,2]. We report a case of a Hispanic woman who developed severe respiratory distress syndrome after gluteal silicone injections.

Background: The aim of this study was to validate and compare the performance of statistical (Utstein-Based Return of Spontaneous Circulation and Shockable Rhythm-Witness-Age-pH) and machine learning-based (Prehospital Return of Spontaneous Circulation and Swedish Cardiac Arrest Risk Score) models in predicting the outcomes following out-of-hospital cardiac arrest and to assess the impact of the COVID-19 pandemic on the models' performance., Methods and Results: This retrospective analysis included adult patients with out-of-hospital cardiac arrest treated at 3 academic hospitals between 2015 and 2023. The primary outcome was neurological outcomes at hospital discharge. Patients were divided into pre- (2015-2019) and post-2020 (2020-2023) subgroups to examine the effect of the COVID-19 pandemic on out-of-hospital cardiac arrest outcome prediction. The models' performance was evaluated using the area under the receiver operating characteristic curve and compared by the DeLong test. The analysis included 2161 patients, 1241 (57.4%) of whom were resuscitated after 2020. The cohort had a median age of 69.2 years, and 1399 patients (64.7%) were men. Overall, 69 patients (3.2%) had neurologically intact survival. The area under the receiver operating characteristic curves for predicting neurological outcomes were 0.85 (95% CI, 0.83-0.87) for the Utstein-Based Return of Spontaneous Circulation score, 0.82 (95% CI, 0.81-0.84) for the Shockable Rhythm-Witness-Age-pH score, 0.79 (95% CI, 0.78-0.81) for the Prehospital Return of Spontaneous Circulation score, and 0.79 (95% CI, 0.77-0.81) for the Swedish Cardiac Arrest Risk Score model. The Utstein-Based Return of Spontaneous Circulation score significantly outperformed both the Prehospital Return of Spontaneous Circulation score ( P <0.001) and the Swedish Cardiac Arrest Risk Score model ( P =0.007). Subgroup analysis indicated no significant difference in predictive performance for patients resuscitated before versus after 2020., Conclusions: In this external validation, both statistical and machine learning-based models demonstrated excellent and fair performance, respectively, in predicting neurological outcomes despite different model architectures. The predictive performance of all evaluated clinical scoring systems was not significantly influenced by the COVID-19 pandemic.

Cave automatic virtual environment (CAVE), as a novel approach to promoting physical activity, shows great potential for improving the mental health and healthy lifestyle of older adults. Based on stress reduction theory, tree density is regarded as a main characteristic of a virtual sportscape that will affect the experience and benefits of exercising. However, the effect of tree density on the experience of exercising remains unclear. The current study was undertaken to investigate the effects of tree cover density on the alpha waves induced and the enjoyment and satisfaction derived by engaging in physical activity in a virtual environment. Eighty-seven late middle-aged and older adults were randomly assigned to one of the following conditions: a high tree density sportscape (HTDS = 36-60 %), a medium tree density sportscape, (MTDS = 20-35 %), and a control condition. Questionnaires and electroencephalogram read-outs of alpha waves were used to evaluate the changes in stress levels experienced by the participants before, during, and after 20 min of cycling. The results showed that participants exposed to an HTDS exhibited to physical activity with significantly more enjoyment and satisfaction than those in the MTDS and control groups. In contrast, the highest degree of relaxation was exhibited in the MTDS condition, suggesting that an MTDS is more effective at reducing perceived stress among late middle-aged and older adults engaging in virtual cycling. These findings demonstrate that exercising in a virtual reality setting with different densities of tree cover comes with physiological and psychological wellbeing for late middle-aged and older adults., (Copyright © 2024. Published by Elsevier Inc.)

Background: Collaborative learning is an essential pedagogy in medical education, within which small group learning constitutes an integral component. Online small group teaching has been widely applied and blended with in-person sessions in the aftermath of the Covid-19 pandemic. This study examined whether group metacognition was associated with teamwork satisfaction in an online small group teaching curriculum for medical students., Methods: We enrolled medical students of the 2nd and 4th years during the 2021 fall semester after they participated in 3 consecutive sessions of online small group tutorials (SGTs), which have been implemented in our medical school for more than 20 years. The students completed a group metacognitive scale (GMS) and a teamwork satisfaction scale (TSS) after the sessions. We analyzed whether group metacognition in 4 dimensions (knowledge of cognition, planning, evaluating, and monitoring) could be connected with medical students' teamwork satisfaction using partial least squares-structural equation modeling (PLS-SEM)., Results: A total of 263 medical students participated in this study. Both GMS and TSS exhibited good reliability and validity. Three of the 4 dimensions of group metacognition (cognition, planning, and evaluating) positively correlated with teamwork satisfaction (path coefficients 0.311, 0.279, and 0.21; p = 0.002, 0.002, and 0.043, respectively) following the online SGT curriculum, whereas the monitoring dimension did not (path coefficient 0.087; p = 0.357). The model achieved an adjusted R square of 0.683., Conclusion: We discovered that group metacognition correlated positively with better teamwork satisfaction, supporting the importance of group metacognitive competency for online collaborative learning., (© 2024. The Author(s).)

Nucleotide excision repair (NER) is vital for genome integrity. Yet, our understanding of the complex NER protein machinery remains incomplete. Combining cryo-EM and XL-MS data with AlphaFold2 predictions, we build an integrative model of the NER pre-incision complex(PInC). Here TFIIH serves as a molecular ruler, defining the DNA bubble size and precisely positioning the XPG and XPF nucleases for incision. Using simulations and graph theoretical analyses, we unveil PInC's assembly, global motions, and partitioning into dynamic communities. Remarkably, XPG caps XPD's DNA-binding groove and bridges both junctions of the DNA bubble, suggesting a novel coordination mechanism of PInC's dual incision. XPA rigging interlaces XPF/ERCC1 with RPA, XPD, XPB, and 5' ssDNA, exposing XPA's crucial role in licensing the XPF/ERCC1 incision. Mapping disease mutations onto our models reveals clustering into distinct mechanistic classes, elucidating xeroderma pigmentosum and Cockayne syndrome disease etiology., (© 2024. The Author(s).)

Background: Immune checkpoint inhibitors (ICIs) that against programmed cell death protein-1 (PD-1) and its ligand PD-L1 have been approved as a promising treatment of many human cancers. However, the responses to these ICIs were limited in patients with ovarian cancer. Studies have indicated that the response to PD-1/PD-L1 blockade might be correlated with the PD-L1 expression level in cancer cells. Nucleophosmin (NPM/B23) was found to be a potential target for immunotherapy. Whether NPM/B23 plays a role in cancer-associated immunity, such as PD-1/PD-L1 axis, and its underlying mechanisms remain largely unknown in ovarian cancer., Methods: We applied ovarian cancer cell lines as research models. The effect of modulating PD-L1 by NPM/B23 was subsequently confirmed via Western blot, flow cytometry, qRT-PCR, luciferase reporter assays, and immunoprecipitation. Protein stability and ubiquitin assay assays were used to analyze the interplay between NPM/B23 and NF-ĸB/p65 in PD-L1 regulation. The MOSEC/Luc xenograft mouse model was used to validate the role of NPM/B23-PD-L1 through tumor growth in vivo., Results: Our results revealed that NPM/B23 negatively regulates PD-L1 expression via a protein complex with NF-κB/p65 and through an IFN-γ pathway. Moreover, NPM/B23 inhibitor/modulator sensitized ovarian cancer cells to the anti-PD-1 antibody by regulating PD-L1 expression in the immunocompetent mouse model. Compared to anti-PD-1 antibody alone, a combination of anti-PD-1 antibody and NPM/B23 inhibitor/modulator showed reduced tumorigenesis and increased CD8 + T-cell expansion, thus contributing to prolonged survival on MOSEC/Luc-bearing mouse model., Conclusion: Targeting NPM/B23 is a novel and potential therapeutic approach to sensitize ovarian cancer cells to immunotherapy., 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 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

An imbalance between the generation of reactive oxygen species and the body's antioxidant defense mechanisms is closely related to the development and progression of Parkinson's disease (PD). Considering that physical exercise is a potential therapeutic intervention for modulating oxidative stress markers and cognitive function in PD, the primary purpose of this study was to compare the effects of different long-term exercise modalities on antioxidants and cognitive performance in patients with PD. In addition, the secondary purpose was to explore whether changes in the levels of these biochemical markers are associated with alterations in cognitive performance pre- and post-intervention. In all, 61 participants were randomly divided into the aerobic exercise (AE, n=20), Tai Chi exercise (TCE, n=21), or control (n=20) group. Blood samples were collected before and after a 12-week intervention period for the analysis of antioxidant markers [leukocyte 8-hydroxydeoxyguanosine (8-OHdG), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-Px), oxidized glutathione (GSSG), superoxide dismutase (SOD), and uric acid (UA)]. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE). Although no significant changes were observed in the activity of 8-OhdG, GSH-Px, GSSG, GSH:GSSG ratio, SOD, and cognitive performance in the AE and TCE groups, the 12-week AE intervention led to a significant increase in CAT and GSH levels, along with a significantly decrease in UA levels among individuals with PD. Conversely, the TCE intervention resulted in a significant increase in GSH levels. However, SOD activity and MMSE scores were significantly decreased after 12 weeks in the control group. The correlations between changes in MMSE scores and changes in the levels of GSH and UA prior to and after the intervention reached significance in the AE group. Thus, long-term AE and TCE might serve as effective strategies for reducing oxidative damage and preserving cognitive function in PD, with AE exhibiting greater benefits compared with TCE. These findings hold potential clinical relevance as complementary measures to standard medical treatments and alternative therapies, such as antioxidant supplements and dietary adjustments, particularly for individuals in the early stages of PD., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare. Conflict of Interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tumor suppressor protein BRCA2 acts with RAD51 in replication-fork protection (FP) and homology-directed DNA break repair (HDR). Critical for cancer etiology and therapy resistance, BRCA2 C-terminus was thought to stabilize RAD51-filaments after they assemble on single-stranded (ss)DNA. Here we determined the detailed crystal structure for BRCA2 C-terminal interaction-domain (TR2i) with ATP-bound RAD51 prior to DNA binding. In contrast to recombinogenic RAD51-filaments comprising extended ATP-bound RAD51 dimers, TR2i unexpectedly reshapes ATP-RAD51 into a unique dimer conformation accommodating double-stranded B-DNA binding unsuited for HDR initiation. Structural, biochemical, and molecular results with interface-guided mutations uncover TR2i's FP mechanism. Proline-driven secondary-structure stabilizes residue triads and spans the RAD51 dimer engaging pivotal interactions of RAD51 M210 and BRCA2 S3291/P3292, the cyclin-dependent kinase (CDK) phosphorylation site that toggles between FP during S-phase and HDR in G2. TR2i evidently acts as an allosteric clamp switching RAD51 from ssDNA to double-stranded and B-DNA binding enforcing FP over HDR.

Anemia of inflammation (AI) is a common comorbidity associated with obesity, diabetes, cardiac disease, aging, and during anti-cancer therapies. Mounting evidence illustrates that males are disproportionally affected by AI, but not why. Here we demonstrate a molecular cause for a sex-bias in inflammation. The data shows that mitochondrial DNA (mtDNA) instability induced by dietary stress causes anemia associated with inflamed macrophages and improper iron recycling in mice. These phenotypes are enhanced in mice with mutations in Fanco/Rad51c , which predisposes to the progeroid disease Fanconi Anemia. The data reveals a striking sex-bias whereby females are protected. We find that estrogen acts as a mitochondrial antioxidant that reduces diet-induced oxidative stress, mtDNA replication instability and the distinctively mtDNA-dependent unphosphorylated STAT1 response. Consequently, treatment of male Rad51c mutant mice with estrogen or mitochondrial antioxidants suppresses the inflammation-induced anemia. Collectively, this study uncovers estrogen-responsive mtDNA replication instability as a cause for sex-specific inflammatory responses and molecular driver for AI.

Persistent DNA double-strand breaks (DSBs) are enigmatically implicated in neurodegenerative diseases including Huntington's disease (HD), the inherited late-onset disorder caused by CAG repeat elongations in Huntingtin (HTT). Here we combine biochemistry, computation and molecular cell biology to unveil a mechanism whereby HTT coordinates a Transcription-Coupled Non-Homologous End-Joining (TC-NHEJ) complex. HTT joins TC-NHEJ proteins PNKP, Ku70/80, and XRCC4 with chromatin remodeler Brahma-related Gene 1 (BRG1) to resolve transcription-associated DSBs in brain. HTT recruitment to DSBs in transcriptionally active gene- rich regions is BRG1-dependent while efficient TC-NHEJ protein recruitment is HTT-dependent. Notably, mHTT compromises TC-NHEJ interactions and repair activity, promoting DSB accumulation in HD tissues. Importantly, HTT or PNKP overexpression restores TC-NHEJ in a Drosophila HD model dramatically improving genome integrity, motor defects, and lifespan. Collective results uncover HTT stimulation of DSB repair by organizing a TC-NHEJ complex that is impaired by mHTT thereby implicating dysregulation of transcription-coupled DSB repair in mHTT pathophysiology., Highlights: BRG1 recruits HTT and NHEJ components to transcriptionally active DSBs.HTT joins BRG1 and PNKP to efficiently repair transcription related DSBs in brain.Mutant HTT impairs the functional integrity of TC-NHEJ complex for DSB repair.HTT expression improves DSB repair, genome integrity and phenotypes in HD flies.

Background: Anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies have emerged as promising therapeutic options for the treatment of chronic migraine. However, treatment response varies considerably among individuals, suggesting a potential role for genetic factors. This study aimed to identify genetic variants affecting the efficacy of anti-CGRP monoclonal antibody therapy in chronic migraine among the Han Chinese population in Taiwan to enhance treatment precision and to understand the genetic architecture of migraine., Methods: We conducted a quantitative trait locus (QTL) association study in patients with chronic migraines from a tertiary medical center in Taiwan using the Taiwan Precision Medicine Array Chip. The patients received fremanezumab or galcanezumab for at least 12 weeks. Treatment efficacy was assessed based on the improvement rate in monthly migraine days. Genetic variants were identified, and their associations with treatment efficacy were examined through quantitative trait loci analysis, linkage disequilibrium studies, and functional annotations using the Gene Ontology database., Results: Six single nucleotide polymorphisms (SNPs) relative variants were significantly associated with anti-CGRP therapy response (p < 1 × 10 - 7 ): rs116870564, rs75244870, rs56216870, rs12938101, rs74655790, and rs149540851. These variants are located in or near genes, including LRRC4C, ATAD2B, and OXR1, which are involved in neuronal development, DNA-dependent ATPase activity, and oxidation-reduction processes, respectively. The rs116870564 variant in LRRC4C showed the strongest association (β = -0.551, p = 6.65 × 10 - 9 ). The functional impact of these variants is attributed to their regulatory effects on gene expression, which are influenced by intron splicing regulation, transcription factors, and changes in chromatin structure., Conclusion: The identification of key genetic markers associated with response to anti-CGRP therapy emphasizes the importance of genetic variability in treatment efficacy. This could lead to more personalized chronic migraine management strategies and tailored therapeutic approaches based on individual genetic profiles. Further research in larger, diverse populations is warranted to validate these findings and refine our understanding of the role of CGRP in chronic migraine pathophysiology., Trial Registration: Not applicable., (© 2024. The Author(s).)

Background and Objectives: Stereotactic radiosurgery (SRS) has been widely adopted as an important adjunctive treatment modality for managing nonfunctioning pituitary adenomas (NFPAs). However, current studies on the long-term effects of SRS on pituitary adenomas have been largely limited by small sample sizes and short follow-up periods. The aim of this study was to evaluate the long-term outcomes of SRS for NFPAs., Methods: We conducted a retrospective review of 178 patients with NFPAs who received Cyberknife radiosurgery at a single institution between February 2008 and July 2021. Long-term outcomes of tumor control, new-onset hypopituitarism, and new visual disorders were assessed., Results: During a median radiological follow-up of 49.7 months (range, 2.5-158.1 months), only 11 (7.0%) patients experienced tumor progression. The progression-free survival at 3, 5, and 10 years was 97.47%, 95.57%, and 93.04%, respectively. New-onset hypopituitarism was diagnosed in 27 (16.9%) patients with a median clinical follow-up duration of 71.2 months (range, 11.5-175.4 months). The median time from SRS to new-onset hypopituitarism was 28.3 months (range, 2.8-101.7 months). The cumulative incidence of new-onset hypopituitarism at 3, 5, and 10 years was 8.47%, 12.43%, and 15.25%, respectively. Biological effective dose >140 Gy and single fraction equivalent dose >16.0 Gy were significant risk factors for new-onset hypopituitarism (P = .046). Other adverse events were experienced by 15 (8.4%) patients, 9 (5.1%) of whom presented with new visual disorders. Development of new visual disorders was associated with a pretreatment tumor volume of >2.5 mL (P = .044)., Conclusion: SRS is an effective and relatively safe means of managing both primary and residual/recurrent NFPAs., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Background/aim: Matrix metalloproteinase-2 (MMP-2) has been implicated in the pathogenesis of breast cancer (BC). However, there is limited research on the role of MMP-2 genotypes in BC risk. This study aimed to investigate the associations between two MMP-2 promoter polymorphisms, rs243865 and rs2285053, and BC risk., Materials and Methods: MMP-2 genotypes were analyzed using PCR-based RFLP methodology in a cohort comprising 1,232 BC cases and 1,232 controls., Results: Genotypic frequencies of MMP-2 rs243865 and rs2285053 in controls were consistent with Hardy-Weinberg equilibrium (p=0.3702 and 0.2036, respectively). There were no significant differences in the distribution of rs243865 and rs2285053 genotypes between BC cases and controls (p for trend=0.1602 and 0.2170, respectively). Variant genotypes at rs243865 and rs2285053 appeared to confer a protective effect, although not statistically significant (all p>0.05). Similarly, the variant T allele at rs243865 and rs2285053 showed a non-significant trend towards decreased BC risk (OR=0.84 and 0.89, 95%CI=0.69-1.02 and 0.78-1.02, p=0.0811 and 0.1043, respectively). There was no interaction observed between MMP-2 rs243865 or rs2285053 genotypes and age. Stratified analysis did not reveal significant associations between MMP-2 rs243865 or rs2285053 genotypes and triple-negative breast cancer (TNBC) (p=0.6458 and 0.8745, respectively). Among both TNBC and non-TNBC cases, none of the variant genotypes at rs243865 or rs2285053 showed significant associations with TNBC (all p>0.05)., Conclusion: MMP-2 rs243865 and rs2285053 genotypes appear to have a minimal impact on individual susceptibility to BC or TNBC., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The primary function of the skin is to form a mechanical, permeability, antimicrobial, and ultraviolet radiation barrier, which is essential for maintaining physiological homeostasis. Our previous studies demonstrated that cutaneous pigmentation could promote skin barrier function in addition to providing anti-ultraviolet irradiation defense. The present study aimed to develop a new regimen that enhances skin barrier function by regulating skin pigmentation using low-concentration imiquimod. Results showed that topical application of low-concentration imiquimod effectively induced skin hyperpigmentation in the dorsal skin and external ear of mice without inducing inflammatory cell infiltration. An in vitro study also revealed that low-concentration imiquimod did not induce any cytotoxic effects on melanoma cells but triggered excessive melanin synthesis. In coculture systems, low-concentration imiquimod was noted to increase tyrosinase activity in a broader cellular context, revealing the potential role of neighboring cells in melanin production. The next-generation sequencing result indicated that PKCη and Dnm3 might regulate melanin synthesis and release during imiquimod treatment. Overall, our study presents new insights into the regulation of melanin production by low-concentration imiquimod, both in a mice model and cultured cells. Furthermore, our study highlights the potential benefits of imiquimod in promoting melanin synthesis without causing skin disruptions or inducing inflammation, validating its potential to serve as a method for enhancing skin barrier functions by regulating the epidermal melanization reaction., (© 2024 Wiley Periodicals LLC.)

The 5-year survival is poor for stage IV non-small cell lung cancer (NSCLC). Recently, cell immunotherapy has emerged as a new treatment strategy. This study aimed to evaluate the efficacy and safety of Immune killer cells (IKC) in patients with stage IV NSCLC after the failure of prior chemotherapy. This study enrolled 26 patients with stage IV NSCLC who failed at least two lines of chemotherapy with or without targeted therapy. The IKC was given alone weekly for 24 weeks. The primary endpoint was progression-free survival (PFS). Secondary outcomes included overall survival (OS), pain intensity, quality of life (QOL), and safety. The median PFS for the intent-to-treat (ITT) population (i.e., all enrolled patients) was 3.8 month. In the per-protocol (PP) population (i.e., patients receiving > 12 IKC infusions), the median PFS was 5.6 months. Moreover, the ITT population showed a 1-year survival rate of 60.0%, while that for the PP population was 85.7%. Only 7 out of 200 AEs (3.5%) were related to the IKC infusion, and they were all rated as grade 1 in severity. The IKC infusion was well tolerated. This novel immunotherapy prolonged the PFS and improved the survival compared with historical data. It might be a potential treatment strategy for stage IV NSCLC patient who failed prior chemotherapy.ClinicalTrials.gov identifier: NCT03499834., (© 2024. The Author(s).)

Prostate cancer (PCa) is a multifactorial disease influenced by genetic, environmental, and immunological factors. Genetic polymorphisms in the interleukin-10 ( IL-10 ) gene have been implicated in PCa susceptibility, development, and progression. This study aims to assess the contributions of three IL-10 promoter single nucleotide polymorphisms (SNPs), A-1082G (rs1800896), T-819C (rs3021097), and A-592C (rs1800872), to the risk of PCa in Taiwan. The three IL-10 genotypes were determined using PCR-RFLP methodology and were evaluated for their contributions to PCa risk among 218 PCa patients and 436 non-PCa controls. None of the three IL-10 SNPs were significantly associated with the risks of PCa ( p all > 0.05) in the overall analyses. However, the GG at rs1800896 combined with smoking behavior was found to significantly increase the risk of PCa by 3.90-fold (95% confidence interval [95% CI] = 1.28-11.89, p = 0.0231). In addition, the rs1800896 AG and GGs were found to be correlated with the late stages of PCa (odds ratio [OR] = 1.90 and 6.42, 95% CI = 1.05-3.45 and 2.30-17.89, p = 0.0452 and 0.0003, respectively). The IL-10 promoter SNP, A-1082G (rs1800896), might be a risk factor for PCa development among smokers and those at late stages of the disease. These findings should be validated in larger and more diverse populations.

Anemia is a significant global health issue, affecting over a billion people worldwide, according to the World Health Organization. Generally, the gold standard for diagnosing anemia relies on laboratory measurements of hemoglobin. To meet the need in clinical practice, physicians often rely on visual examination of specific areas, such as conjunctiva, to assess pallor. However, this method is subjective and relies on the physician's experience. Therefore, we proposed a deep learning prediction model based on three input images from different body parts, namely, conjunctiva, palm, and fingernail. By incorporating additional body part labels and employing a fusion attention mechanism, the model learns and enhances the salient features of each body part during training, enabling it to produce reliable results. Additionally, we employ a dual loss function that allows the regression model to benefit from well-established classification methods, thereby achieving stable handling of minority samples. We used a retrospective data set (EYES-DEFY-ANEMIA) to develop this model called Body-Part-Anemia Network (BPANet). The BPANet showed excellent performance in detecting anemia, with accuracy of 0.849 and an F1-score of 0.828. Our multi-body-part model has been validated on a prospectively collected data set of 101 patients in National Taiwan University Hospital. The prediction accuracy as well as F1-score can achieve as high as 0.716 and 0.788, respectively. To sum up, we have developed and validated a novel non-invasive hemoglobin prediction model based on image input from multiple body parts, with the potential of real-time use at home and in clinical settings., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Cluster headache (CH) is a debilitating neurological disorder characterized by severe, unilateral pain and ipsilateral autonomic symptoms. Chronic CH is exceedingly rare in Taiwan, constituting approximately 1% of all CH cases. This narrative review provides an up-to-date overview of the acute and preventive treatment strategies for CH in Taiwan, focusing on currently available pharmacological options in the country. The treatment approach for CH in Taiwan involves a stepwise strategy. High-flow oxygen and triptan nasal sprays are the mainstays of acute treatment, providing rapid relief and good tolerability. Transitional treatments, such as oral steroids and suboccipital steroid injections, serve as a crucial bridge between acute and long-term preventive therapies, offering temporary relief while minimizing side effects through a carefully limited duration. For preventive treatment, verapamil is the first-line option, with lithium and topiramate being the second-line alternatives. Among the CGRP monoclonal antibodies, galcanezumab has demonstrated efficacy in the prevention of episodic CH. Preventive treatments are personalized to individual patients, starting with low doses and close monitoring for adverse effects. Neuromodulatory therapies, such as non-invasive vagus nerve stimulation, show promise for chronic and refractory CH but have limited availability in Taiwan. In conclusion, despite the availability of various acute and preventive treatment options, unmet needs in the management of CH in Taiwan remain. In particular, increased awareness and education among healthcare professionals to improve the diagnosis and management of CH in Taiwan should be implemented., 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.)

Background: Several risk factors for peptic ulcer disease (PUD) have been identified; however, the recurrence rates of PUD are still high even with standard ulcer treatments. A high cholesterol level has been proposed as a risk factor for PUD, but clinical evidence remains limited. Therefore, this database study investigated whether hyperlipidemia increases PUD risk and whether antihyperlipidemic drugs reduce this risk., Methods: A long-term cohort design was adopted, and Taiwan's National Health Insurance Research Database was used to enroll patients diagnosed as having hyperlipidemia between 2000 and 2016. Patients without hyperlipidemia were randomly matched based on variables such as age and gender to establish a comparison cohort at a 1:1 ratio. Another cohort study was conducted to determine whether antihyperlipidemic drugs or red yeast rice prescriptions (LipoCol Forte®) can reduce the incidence of PUD in patients with hyperlipidemia., Results: The overall incidence of PUD was 1.48 times higher in the hyperlipidemia cohort (203,235 patients) than in the nonhyperlipidemia cohort (adjusted hazard ratio, 1.48; 95% CI, 1.46-1.50; p < 0.001). Among the patients with hyperlipidemia, those who used antihyperlipidemic drugs with or without red yeast rice prescriptions exhibited a lower risk of developing PUD relative to those who did not use them; the adjusted hazard ratios were 0.33 (95% CI, 0.21-0.52) and 0.81 (95% CI, 0.78-0.84), respectively. When the cumulative exposure to antihyperlipidemic drugs and red yeast rice prescriptions increased, the risk of developing PUD showed a decreasing trend, which was statistically significant for antihyperlipidemic drugs but not for red yeast rice., Conclusion: Hyperlipidemia is associated with a higher risk of PUD, which can be reduced through antihyperlipidemic drugs with or without red yeast rice prescriptions administration., 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.)

Background: Parkinson's disease (PD) is a neurodegenerative condition characterized by movement disorders and probable cognitive impairment. Exercise plays an important role in PD management, and recent studies have reported improvement in motor symptoms and cognitive function following aerobic and Tai Chi Chuan exercise., Aim: To explore the different effects of Tai Chi Chuan and aerobic exercise on the clinical motor status and neurocognitive performance of patients with early-stage PD., Design: A randomized controlled trial., Setting: Parkinson's Disease Center at Kaohsiung Chang Gung Memorial Hospital and National Cheng Kung University Hospital., Population: Patients with idiopathic PD., Methods: Fifty-six patients with PD were recruited and divided into three groups: aerobic exercise (AE, N.=14), Tai Chi Chuan exercise (TE, N.=16), and control (CG, N.=13). Before and after a 12-week intervention period, we used unified Parkinson's disease rating scale Part III (UPDRS-III) scores and neuropsychological (e.g., accuracy rates [ARs] and reaction times [RTs]) and neurophysiological (e.g., event-related potential [ERP] N2 and P3 latencies and amplitudes) parameters to respectively assess the patients' clinical motor symptoms and neurocognitive performance when performing a working memory (WM) task., Results: Compared to baseline, UPDRS-III scores were significantly lower in the AE and TE groups after the intervention period, whereas those for the CG group were higher. In terms of the neurocognitive parameters, when performing the WM task after the intervention period, the AE group exhibited significantly faster RTs and larger ERP P3 amplitudes, the TE group exhibited an improvement only in ERP P3 amplitude, and the CG group exhibited a significantly reduced ERP P3 amplitude. However, neither the TE nor the AE group exhibited improved ARs and ERP N2 performance., Conclusions: The present study supported the distinct effectiveness of Tai Chi Chuan and aerobic exercise for improving motor symptoms and providing neurocognitive benefits in PD patients., Clinical Rehabilitation Impact: These results have important implications regarding the use of these exercise interventions for managing PD, particularly in the early stages.

Visuospatial attention (VSA) is a cognitive function that enables athletes, particularly those engaged in open-skill sports, to allocate attentional resources efficiently to the appropriate target and in the appropriate direction. Studies have indicated that expert players exhibit superior cognitive performance to that of novices. However, no study has investigated differences in VSA performance among elite, expert, and intermediate badminton players or the potential neurophysiological mechanisms underlying such differences. Accordingly, the present study explored neuropsychological and neurophysiological parameters during VSA tasks among badminton players of varying competitive levels. The study included 54 participants and divided them into three groups according to their competition records: elite (n = 18), expert (n = 18), and intermediate (n = 18). Their neuropsychological performance and brain event-related potentials (ERPs) during the Posner cueing paradigm were collected. Although the three groups did not differ in their accuracy rates, ERP N2 amplitudes, or N2 or P3 latencies, the elite and expert groups exhibited notably faster reaction times and more pronounced P3 amplitudes than did the intermediate group during the cognitive task. However, we did not observe these between-group differences when we controlled for the covariate training years. Additionally, the elite and expert groups exhibited comparable neurocognitive performance. These findings indicate that badminton players' competitive levels influence their VSA. However, the beneficial effects on neuropsychological and neurophysiological performance could stabilize after a certain level of badminton competence is reached. Year of training could also be a major factor influencing badminton players' neurocognitive performance in VSA tasks., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ga-doped Li 7 La 3 Zr 2 O 12 garnet solid electrolytes exhibit the highest Li-ion conductivities among the oxide-type garnet-structured solid electrolytes, but instabilities toward Li metal hamper their practical application. The instabilities have been assigned to direct chemical reactions between LiGaO 2 coexisting phases and Li metal by several groups previously. Yet, the understanding of the role of LiGaO 2 in the electrochemical cell and its electrochemical properties is still lacking. Here, we are investigating the electrochemical properties of LiGaO 2 through electrochemical tests in galvanostatic cells versus Li metal and complementary ex situ studies via confocal Raman microscopy, quantitative phase analysis based on powder X-ray diffraction, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and electron energy loss spectroscopy. The results demonstrate considerable and surprising electrochemical activity, with high reversibility. A three-stage reaction mechanism is derived, including reversible electrochemical reactions that lead to the formation of highly electronically conducting products. The results have considerable implications for the use of Ga-doped Li 7 La 3 Zr 2 O 12 electrolytes in all-solid-state Li-metal battery applications and raise the need for advanced materials engineering to realize Ga-doped Li 7 La 3 Zr 2 O 12 for practical use.

Electroencephalographic Neurofeedback Training (EEG NFT) aims to improve sport performance by teaching athletes to control their mental states, leading to better cognitive, emotional, and physical outcomes. The psychomotor efficiency hypothesis suggests that optimizing brain function could enhance athletic ability, indicating the potential of EEG NFT. However, evidence for EEG-NFT's ability to alter critical brain activity patterns, such as sensorimotor rhythm and frontal midline theta-key for concentration and relaxation-is not fully established. Current research lacks standardized methods and comprehensive studies. This shortfall is due to inconsistent EEG target selection and insufficient focus on coherence in training. This review aims to provide empirical support for EEG target selection, conduct detailed control analyses, and examine the specificity of electrodes and frequencies to relation to the psychomotor efficiency hypothesis. Following the PRISMA method, 2,869 empirical studies were identified from PubMed, Science Direct, Web of Science, Embase, CNKI, and PsycINFO. Thirteen studies met the inclusion criteria: (i) proficient skill levels; (ii) use of EEG; (iii) neurofeedback training (NFT); (iv) motor performance metrics (reaction time, precision, dexterity, balance); (v) control group for NFT comparison; (vi) peer-reviewed English-language publication; and (vii) randomized controlled trial (RCT) design. Studies indicate that NFT can enhance sports performance, including improvements in shooting accuracy, golf putting, and overall motor skills, as supported by the psychomotor efficiency hypothesis. EEG NFT demonstrates potential in enhancing sports performance by optimizing performers' mental states and psychomotor efficiency. However, the current body of research is hampered by inconsistent methodologies and a lack of standardized EEG target selection. To strengthen the empirical evidence supporting EEG NFT, future studies need to focus on standardizing target selection, employing rigorous control analyses, and investigating underexplored EEG markers. These steps are vital to bolster the evidence for EEG NFT and enhance its effectiveness in boosting sport performance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer ES declared a past co-authorship with the authors M-YC to the handling editor., (Copyright © 2024 Cheng, Yu, An, Wang, Tsai, Qi and Wang.)

The up-to-date lifespan of zero-excess lithium (Li) metal batteries is limited to a few dozen cycles due to irreversible Li-ion loss caused by interfacial reactions during cycling. Herein, a chemical prelithiated composite interlayer, made of lithiophilic silver (Ag) and lithiophobic copper (Cu) in a 3D porous carbon fiber matrix, is applied on a planar Cu current collector to regulate Li plating and stripping and prevent undesired reactions. The Li-rich surface coating of lithium oxide (Li 2 O), lithium carboxylate (RCO 2 Li), lithium carbonates (ROCO 2 Li), and lithium hydride (LiH) is formed by soaking and directly heating the interlayer in n -butyllithium hexane solution. Although only a thin coating of ∼10 nm is created, it effectively regulates the ionic and electronic conductivity of the interlayer via these surface compounds and reduces defect sites by reactions of n -butyllithium with heteroatoms in the carbon fibers during formation. The spontaneously formed lithiophilic-lithiophobic gradient across individual carbon fiber provides homogeneous Li-ion deposition, preventing concentrated Li deposition. The porous structure of the composite interlayer eliminates the built-in stress upon Li deposition, and the anisotropically distributed carbon fibers enable uniform charge compensation. These features synergistically minimize the side reactions and compensate for Li-ion loss while cycling. The prepared zero-excess Li metal batteries could be cycled 300 times at 1.17 C with negligible capacity fading.

Background and Purpose: Migraine is a condition that is often observed to run in families, but its complex genetic background remains unclear. This study aimed to identify the genetic factors influencing migraines and their potential association with the family medical history., Methods: We performed a comprehensive genome-wide association study of a cohort of 1,561 outpatients with migraine and 473 individuals without migraine in Taiwan, including Han Chinese individuals with or without a family history of migraine. By analyzing the detailed headache history of the patients and their relatives we aimed to isolate potential genetic markers associated with migraine while considering factors such as sex, episodic vs. chronic migraine, and the presence of aura., Results: We revealed novel genetic risk loci, including rs2287637 in DEAD-Box helicase 1 and long intergenic non-protein coding RNA 1804 and rs12055943 in engulfment and cell motility 1, that were correlated with the family history of migraine. We also found a genetic location downstream of mesoderm posterior BHLH transcription factor 2 associated with episodic migraine, whereas loci within the ubiquitin-specific peptidase 26 exonic region, dual specificity phosphatase 9 and pregnancy-upregulated non-ubiquitous CaM kinase intergenic regions, and poly (ADP-ribose) polymerase 1 and STUM were linked to chronic migraine. We additionally identified genetic regionsassociated with the presence or absence of aura. A locus between LINC02561 and urocortin 3 was predominantly observed in female patients. Moreover, three different single-nucleotide polymorphisms were associated with the family history of migraine in the control group., Conclusions: This study has identified new genetic locations associated with migraine and its family history in a Han Chinese population, reinforcing the genetic background of migraine. The findings point to potential candidate genes that should be investigated further., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 Korean Neurological Association.)

The claim between hypertension and dementia needs more evidence due to limited data. We aim to examine the risk of dementia in patients with hypertension, and determine whether the use of antihypertensive medications (AHMs) could decrease the incidence of dementia diagnosed following the onset of hypertension. We employed the Taiwan National Health Insurance Research Database from 2000 to 2016 and performed a retrospective cohort study. We also carried out a case-control study to see if AHMs could reduce the incidence of newly diagnosed dementia in hypertensive patients. In the retrospective cohort study, we selected 587,762 participants with age and gender matched in experimental and control groups. The hypertension group had significantly higher adjusted hazard ratios (aHRs) of getting newly diagnosed dementia, including all-cause dementia, Alzheimer's disease, and vascular dementia (aHR, 2.86; 95 % confidence interval (CI), 2.74-2.99) than the control group. Three kinds of specific AHMs, namely, angiotensin II receptor blockers (aHR, 0.55; 95 % CI, 0.53-0.57), calcium channel blockers (aHR, 0.76; 95 % CI, 0.73-0.80), and diuretics (aHR,0.93; 95 % CI, 0.89-0.97) could significantly decrease the incidence of getting newly diagnosed dementia. Also, the application of traditional Chinese medicine (TCM) significantly associates with the lower aHRs of newly diagnosed dementia in hypertensive patients compared to patients without TCM (aHR, 0.90; 95 % CI, 0.81-1.00). Hypertension may be a significant risk factor for dementia. Both AHMs and TCM significantly associate with the lower incidence of newly diagnosed dementia in hypertensive patients., 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: This study aimed to investigate the association between the temporal transitions in heart rhythms during cardiopulmonary resuscitation (CPR) and outcomes after out-of-hospital cardiac arrest., Methods: This was an analysis of the prospectively collected databases in 3 academic hospitals in northern and central Taiwan. Adult patients with out-of-hospital cardiac arrest transported by emergency medical service between 2015 and 2022 were included. Favorable neurological recovery and survival to hospital discharge were the primary and secondary outcomes, respectively. Time-specific heart rhythm shockability was defined as the probability of shockable rhythms at a particular time point during CPR. The temporal changes in the time-specific heart rhythm shockability were calculated by group-based trajectory modeling. Multivariable logistic regression analyses were performed to examine the association between the trajectory group and outcomes. Subgroup analyses examined the effects of extracorporeal CPR in different trajectories., Results: The study comprised 2118 patients. The median patient age was 69.1 years, and 1376 (65.0%) patients were male. Three distinct trajectories were identified: high-shockability (52 patients; 2.5%), intermediate-shockability (262 patients; 12.4%), and low-shockability (1804 patients; 85.2%) trajectories. The median proportion of shockable rhythms over the course of CPR for the 3 trajectories was 81.7% (interquartile range, 73.2%-100.0%), 26.7% (interquartile range, 16.7%-37.5%), and 0% (interquartile range, 0%-0%), respectively. The multivariable analysis indicated both intermediate- and high-shockability trajectories were associated with favorable neurological recovery (intermediate-shockability: adjusted odds ratio [aOR], 4.98 [95% CI, 2.34-10.59]; high-shockability: aOR, 5.40 [95% CI, 2.03-14.32]) and survival (intermediate-shockability: aOR, 2.46 [95% CI, 1.44-4.18]; high-shockability: aOR, 2.76 [95% CI, 1.20-6.38]). The subgroup analysis further indicated extracorporeal CPR was significantly associated with favorable neurological outcomes (aOR, 4.06 [95% CI, 1.11-14.81]) only in the intermediate-shockability trajectory., Conclusions: Heart rhythm shockability trajectories were associated with out-of-hospital cardiac arrest outcomes, which may be a supplementary factor in guiding the allocation of medical resources, such as extracorporeal CPR., Competing Interests: None.

Limited research exists regarding the effects of resistance exercise (RE) combined with whole body vibration (WBV), blood flow restriction (BFR), or both on the neuropsychological performance of working memory (WM) in late-middle-aged and older adults and regarding the physiological mechanisms underlying this effect. This study thus explored the acute molecular and neurophysiological mechanisms underlying WM performance following RE combined with WBV, BFR, or both. Sixty-six participants were randomly assigned into a WBV, BFR, or WBV + BFR group. Before and after the participants engaged in a single bout of isometric RE combined with WBV, BFR, or both, this study gathered data on several neurocognitive measures of WM performance, namely, accuracy rate (AR), reaction time (RT), and brain event-related potential (specifically P3 latency and amplitude), and data on biochemical indices, such as the levels of insulin-like growth factor-1 (IGF-1), norepinephrine (NE), and brain-derived neurotrophic factor (BDNF). Although none of the RE modalities significantly affected RTs and P3 latencies, ARs and P3 amplitudes significantly improved in the WBV and WBV + BFR groups. The WBV + BFR group exhibited greater improvements than the WBV group did. Following acute RE combined with WBV, BFR, or both, IGF-1 and NE levels significantly increased in all groups, whereas BDNF levels did not change. Crucially, only the changes in NE levels were significantly correlated with improvements in ARs in the WBV + BFR and WBV groups. The findings suggest that combining acute RE with WBV, BFR, or both could distinctively mitigate neurocognitive decline in late-middle-aged and older adults., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: During cardiopulmonary resuscitation (CPR), end-tidal carbon dioxide (EtCO 2 ) is primarily determined by pulmonary blood flow, thereby reflecting the blood flow generated by CPR. We aimed to develop an EtCO 2 trajectory-based prediction model for prognostication at specific time points during CPR in patients with out-of-hospital cardiac arrest (OHCA)., Methods: We screened patients receiving CPR between 2015-2021 from a prospectively collected database of a tertiary-care medical center. The primary outcome was survival to hospital discharge. We used group-based trajectory modeling to identify the EtCO 2 trajectories. Multivariable logistic regression analysis was used for model development and internally validated using bootstrapping. We assessed performance of the model using the area under the receiver operating characteristic curve (AUC)., Results: The primary analysis included 542 patients with a median age of 68.0 years. Three distinct EtCO 2 trajectories were identified in patients resuscitated for 20 minutes (min): low (average EtCO 2 10.0 millimeters of mercury [mm Hg]; intermediate (average EtCO 2 26.5 mm Hg); and high (average EtCO 2 : 51.5 mm Hg). Twenty-min EtCO 2 trajectory was fitted as an ordinal variable (low, intermediate, and high) and positively associated with survival (odds ratio 2.25, 95% confidence interval [CI] 1.07-4.74). When the 20-min EtCO 2 trajectory was combined with other variables, including arrest location and arrest rhythms, the AUC of the 20-min prediction model for survival was 0.89 (95% CI 0.86-0.92). All predictors in the 20-min model remained statistically significant after bootstrapping., Conclusion: Time-specific EtCO 2 trajectory was a significant predictor of OHCA outcomes, which could be combined with other baseline variables for intra-arrest prognostication. For this purpose, the 20-min survival model achieved excellent discriminative performance in predicting survival to hospital discharge., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. Chih-Hung Wang received a grant (111-FTN0003) from the Far Eastern Memorial Hospital and National Taiwan University Hospital Joint Research Program. Chun-Yen Huang received a grant (111-FTN0003) from the Far Eastern Memorial Hospital and National Taiwan University Hospital Joint Research Program. Both Far Eastern Memorial Hospital and National Taiwan University Hospital had no involvement in designing the study, collecting, analysing or interpreting the data, writing the manuscript, or deciding whether to submit the manuscript for publication. There are no other conflicts of interest or sources of funding to declare.

Solid-state polymer electrolytes (SPEs), such as poly(ethylene oxide) (PEO), have good flexibility when compared to ceramic-type solid electrolytes. Therefore, it could be an ideal solid electrolyte for zero-excess all-solid-state Li metal battery (ZESSLB), also known as anode-free all-solid-state Li battery, development by offering better contact to the Cu current collector. However, the low Coulombic efficiencies observed from polymer type solid-state Li batteries (SSLBs) raise the concern that PEO may consume the limited amount of Li in ZESSLB to fail the system. Here, we designed ZESSLBs by using all-ceramic half-cells and an extra PEO electrolyte interlayer to study the reactivity between PEO and freshly deposited Li under a real battery operating conduction. By shuttling active Li back from the anode to the cathode, the PEO SPEs can be separated from the ZESSLBs for experimental studies without the influence from cathode materials or possible contamination from the usage of Li foil as the anode. Electrochemical cycling of ZESSLBs shows that the capacities of ZESSLBs with solvent-free and solvent-casted PEO SPEs significantly degraded compared to the ones with Li metal as the anode for the all-solid-state Li batteries. The fast capacity degradation of ZESSLBs using different types of PEO SPEs is evidenced to be associated with Li reacting with PEO, residual solvent, and water in PEO and dead Li formation upon the presence or absence of residual solvent. The results suggest that avoiding direct contact between the PEO electrolyte and deposited lithium is necessary when there is only a limited amount of Li available in ZESSLBs.

CRISPR prime editing ( PE ) requires a Cas9 nickase-reverse transcriptase fusion protein (known as PE2) and a prime editing guide RNA ( pegRNA ), an extended version of a standard guide RNA ( gRNA ) that both specifies the intended target genomic sequence and encodes the desired genetic edit. Here, we show that sequence complementarity between the 5' and the 3' regions of a pegRNA can negatively impact its ability to complex with Cas9, thereby potentially reducing PE efficiency. We demonstrate this limitation can be overcome by a simple pegRNA refolding procedure, which improved ribonucleoprotein-mediated PE efficiencies in zebrafish embryos by up to nearly 25-fold. Further gains in PE efficiencies of as much as sixfold could also be achieved by introducing point mutations designed to disrupt internal interactions within the pegRNA. Our work defines simple strategies that can be implemented to improve the efficiency of PE., Competing Interests: WZ, JM, HL, CT, JY No competing interests declared, KP has a financial interest in SeQure Dx, Inc. KP's interests and relationships have been disclosed to Massachusetts General Hospital and Mass General Brigham in accordance with their conflict of interest policies, JJ has, or had during the course of this research, financial interests in several companies developing gene editing technology: Beam Therapeutics, Blink Therapeutics, Chroma Medicine, Editas Medicine, EpiLogic Therapeutics, Excelsior Genomics, Hera Biolabs, Monitor Biotechnologies, Nvelop Therapeutics (f/k/a ETx, Inc), Pairwise Plants, Poseida Therapeutics, SeQure Dx, Inc, and Verve Therapeutics. JKJ's interests were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict of interest policies. JKJ is a co-inventor on various patents and patent applications that describe gene editing and epigenetic editing technologies, (© 2023, Zhang et al.)

To date, information on associations between motor skills and executive functions (EF) in autistic children is limited. The purpose of this study was to compare motor skills and EF performance between autistic children and typically developing (TD) children and to examine the relationships between motor skills and EF in these two groups. Forty-eight autistic children and 48 TD children aged 6 to 12 years were recruited for this study. Motor skills were measured with the Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2). EF was assessed with the Stroop Color and Word Test, the Wisconsin Card Sorting Task (WCST), and the Test of Attentional Performance: Go/No-go test. Independent sample t-tests were used to compare the BOT-2 scores and EF measures between autistic children and TD children. Pearson product-moment correlation and regressions were conducted to assess the relationships between the BOT-2 scores and the EF measures for each group. Results showed that autistic children scored significantly lower than TD children on all four BOT-2 composite scores and a total motor composite. Autistic children also demonstrated significantly lower levels of performance on all EF measures than TD children. Further, autistic children showed more significant associations between motor skills and EF than TD children, particularly pronounced in the domains of fine manual control and manual coordination to cognitive flexibility, as well as manual coordination and inhibitory control. Continued development of motor skills and EF in autistic children is important. The relationships between motor skills and EF were significant among autistic children, suggesting future research on promoting EF through motor skill interventions in autistic children is required., (© 2024 International Society for Autism Research and Wiley Periodicals LLC.)

In this study, we investigate the effects of miRNA-138-5p and probable G-protein coupled receptor 124 (GPR124)-regulated inflammasome and downstream leukemia inhibitory factor (LIF)-STAT and adhesion molecule signaling in human decidual stromal cells. After informed consent was obtained from women aged 25-38 years undergoing surgical termination of the normal pregnancy and spontaneous miscarriage after 6-9 weeks of gestation, human decidual stromal cells were extracted from the decidual tissue. Extracellular vesicles (EVs) with microRNA (miRNA) between cells have been regarded as critical factors for embryo-maternal interactions on embryo implantation and programming of human pregnancy. MicroRNA-138-5p acts as the transcriptional regulator of GPR124 and the mediator of downstream inflammasome. LIF-regulated STAT activation and expression of integrins might influence embryo implantation. Hence, a better understanding of LIF-STAT and adhesion molecule signaling would elucidate the mechanism of microRNA-138-5p- and GPR124-regulated inflammasome activation on embryo implantation and pregnancy. Our results show that microRNA-138-5p, purified from the EVs of decidual stromal cells, inhibits the expression of GPR124 and the inflammasome, and activates the expression of LIF-STAT and adhesion molecules in human decidual stromal cells. Additionally, the knockdown of GPR124 and NLRP3 through siRNA increases the expression of LIF-STAT and adhesion molecules. The findings of this study help us gain a better understanding the role of EVs, microRNA-138-5p, GPR124, inflammasomes, LIF-STAT, and adhesion molecules in embryo implantation and programming of human pregnancy.

Background: Individuals experiencing subjective cognitive decline (SCD) are at an increased risk of developing mild cognitive impairment and dementia. Early identification of SCD and neurodegenerative diseases using biomarkers may help clinical decision-making and improve prognosis. However, few cross-sectional and longitudinal studies have explored plasma biomarkers in individuals with SCD using immunomagnetic reduction., Objective: To identify plasma biomarkers for SCD., Methods: Fifty-two participants [38 with SCD, 14 healthy controls (HCs)] underwent baseline assessments, including measurements of plasma Aβ 42 , Aβ 40 , t-tau, p-tau, and α-synuclein using immunomagnetic reduction (IMR) assays, cognitive tests and the Mini-Mental State Examination (MMSE). Following initial cross-sectional analysis, 39 individuals (29 with SCD, 10 HCs) entered a longitudinal phase for reassessment of these biomarkers and the MMSE. Biomarker outcomes across different individual categories were primarily assessed using the area under the receiver operating characteristic (ROC) curve. The SCD subgroup with an MMSE decline over one point was compared to those without such a decline., Results: Higher baseline plasma Aβ 1-42 levels significantly discriminated participants with SCD from HCs, with an acceptable area under the ROC curve (AUC) of 67.5% [95% confidence interval (CI), 52.7-80.0%]. However, follow-up and changes in MMSE and IMR data did not significantly differ between the SCD and HC groups ( p > 0.05). Furthermore, lower baseline plasma Aβ 1-42 levels were able to discriminate SCD subgroups with and without cognitive decline with a satisfied performance (AUC, 75.0%; 95% CI, 55.6-89.1%). At last, the changes in t-tau and Aβ 42 × t-tau could differentiate between the two SCD subgroups ( p < 0.05)., Conclusion: Baseline plasma Aβ 42 may help identify people with SCD and predict SCD progression. The role of plasma Aβ 42 levels as well as their upward trends from baseline in cases of SCD that progress to mild cognitive impairment and Alzheimer's disease require further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hsieh, Ko, Liang, Yeh, Tsai, Tsai, Lin, Lin, Tsai and Yang.)

In this paper, we have developed a 2D optical scanning module comprising cascaded 3D-printed one-axis rotating mirrors with large areas (30×30 m m 2 for the X-direction scan and 60×25 m m 2 for the Y-direction scan). Each mirror device contains a square or rectangular silicon substrate coated with aluminum, serving as the mirror. A 3D-printed structure, including the mirror frame (with four embedded mini permanent magnets on the backside), torsion springs, and base, is combined with the mirror; two electromagnets are situated under the mirror as the actuation mechanism. We apply DC voltage to the electromagnets to create magnetic force. The electromagnets can interact with the permanent magnets to make the mirror rotate. The X scan of the 2D scanning module can achieve a static optical scan angle of ∼11.8 deg at the -X corners, and the corresponding Y-scan angle is ∼4.5 deg , both with 12 VDC. Moreover, we have observed a fan-shaped distortion, a phenomenon not thoroughly studied previously for combining two single-axis scan mirrors. Therefore, we also perform a simulation to establish and demonstrate a correlation between the simulation prediction and experimental results. The 2D scanning module can be a low-cost alternative to the expensive conventional galvanometer scanners, and it can be used to upgrade a rangefinder to a simplified LiDAR.

(1) Background: Early interventions may effectively reduce the risk of mental disorders in individuals with ultra-high risk. Specifying the health needs of individuals with ultra-high risk is crucial before the implementation of successful early intervention. This study aimed to explore the differences in lifestyles, mental risks, and physical indices among individuals with ultra-high risk, patients with schizophrenia, and healthy subjects. (2) Methods: A cross-section design applying seven questionnaires with physical examinations for 144 participants aged 13-45 years old was conducted in this study. The questionnaires included one about personal data, four on mental risks, and two for lifestyles. (3) Results: The individuals with ultra-high risk scored similarly in many dimensions as the patients with schizophrenia, but they displayed lower positive symptoms, lower negative symptoms, lower prodromal symptoms, higher interpersonal deficits, lower nutrition intake, and higher levels of exercise than the patients with schizophrenia. Female individuals with ultra-high risk had lower self-esteem, higher positive symptoms, lower nutrition intake, and higher exercise levels than male ones. (4) Conclusions: The study pinpointed specific health needs with interpersonal deficits, nutrition intake, and physical activity for the individuals with ultra-high risk. Future interventions targeted on improving social function, dietary pattern, and exercise will be beneficial.

Numerous previous studies have shown the effectiveness of music therapy in enhancing cognitive functions in patients with dementia. Despite this, robust evidence in this field, especially concerning the comparison of different music therapy types, is lacking. Therefore, randomized controlled trials (RCTs) focusing on music therapy and cognitive functions in dementia patients, termed by "music" AND "dementia" OR "Alzheimer's disease" AND "cognitive", were identified from primary electronic databases to conduct this network meta-analysis (NMA). The primary outcome focused on the impact on cognitive functions, and the secondary outcome was the comparison of dropout rates between the intervention groups and the usual care control groups. Standardized mean difference (SMD) values and the corresponding 95% confidence intervals (CIs) were computed for effect evaluation. This study protocol has been registered in IPLASY (INPLASY202430082). A total of 14 RCTs with 1056 participants were enrolled, examining interventions including Active Music Therapy (AMT), Active Music Therapy with Singing (AMT + Sing), Rhythmic Music Therapy (RMT), Listening to Music (LtM), and Singing (Sing). The results indicated that RMT, AMT + Sing, and AMT all significantly improve cognitive functions in dementia patients, of which the SMD were 0.76 (95% CI = 0.32-1.21), 0.79 (95% CI = 0.03-1.49), and 0.57 (0.18-0.96), respectively. Compared with the control group (usual care), no music therapy type was associated with an increased dropout risk. In conclusion, music therapy can improve cognitive functions in patients with dementia without increasing the risk of dropout, particularly RMT, AMT + Sing, and AMT.

Purpose: Clinical risk scores are essential for predicting outcomes in stroke patients. The advancements in deep learning (DL) techniques provide opportunities to develop prediction applications using magnetic resonance (MR) images. We aimed to develop an MR-based DL imaging biomarker for predicting outcomes in acute ischemic stroke (AIS) and evaluate its additional benefit to current risk scores., Method: This study included 3338 AIS patients. We trained a DL model using deep neural network architectures on MR images and radiomics to predict poor functional outcomes at three months post-stroke. The DL model generated a DL score, which served as the DL imaging biomarker. We compared the predictive performance of this biomarker to five risk scores on a holdout test set. Additionally, we assessed whether incorporating the imaging biomarker into the risk scores improved the predictive performance., Results: The DL imaging biomarker achieved an area under the receiver operating characteristic curve (AUC) of 0.788. The AUCs of the five studied risk scores were 0.789, 0.793, 0.804, 0.810, and 0.826, respectively. The imaging biomarker's predictive performance was comparable to four of the risk scores but inferior to one (p = 0.038). Adding the imaging biomarker to the risk scores improved the AUCs (p-values) to 0.831 (0.003), 0.825 (0.001), 0.834 (0.003), 0.836 (0.003), and 0.839 (0.177), respectively. The net reclassification improvement and integrated discrimination improvement indices also showed significant improvements (all p < 0.001)., Conclusions: Using DL techniques to create an MR-based imaging biomarker is feasible and enhances the predictive ability of current risk scores., 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.)

The availability of big data can transform the studies in biomedical research to generate greater scientific insights if expert labeling is available to facilitate supervised learning. However, data annotation can be labor-intensive and cost-prohibitive if pixel-level precision is required. Weakly supervised semantic segmentation (WSSS) with image-level labeling has emerged as a promising solution in medical imaging. However, most existing WSSS methods in the medical domain are designed for single-class segmentation per image, overlooking the complexities arising from the co-existence of multiple classes in a single image. Additionally, the multi-class WSSS methods from the natural image domain cannot produce comparable accuracy for medical images, given the challenge of substantial variation in lesion scales and occurrences. To address this issue, we propose a novel anomaly-guided mechanism (AGM) for multi-class segmentation in a single image on retinal optical coherence tomography (OCT) using only image-level labels. AGM leverages the anomaly detection and self-attention approach to integrate weak abnormal signals with global contextual information into the training process. Furthermore, we include an iterative refinement stage to guide the model to focus more on the potential lesions while suppressing less relevant regions. We validate the performance of our model with two public datasets and one challenging private dataset. Experimental results show that our approach achieves a new state-of-the-art performance in WSSS for lesion segmentation on OCT images., 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/aim: Cancer cachexia is a wasting syndrome that has a devastating impact on the prognosis of patients with cancer. It is well-documented that pro-inflammatory cytokines are involved in the progression of this disorder. Therefore, this study was conducted to investigate the protective effect of taurine, an essential nonprotein amino acid with great anti-inflammatory properties, in attenuating muscle atrophy induced by cancer., Materials and Methods: Conditioned media (CM) derived from T24 human bladder carcinoma cells with or without 5 mM taurine were incubated with human skeletal muscle cells (HSkMCs) and their differentiation was examined. The intracellular reactive oxygen species (ROS), morphology, and the catabolic pathway were monitored., Results: T24-derived CM with high levels of TNF-α and IL-6 caused aberrant ROS accumulation and formation of atrophic myotubes by HSkMCs. In T24 cancer cells, taurine significantly inhibited the production of TNF-α and IL-6. In HSkMCs, taurine increased ROS clearance during differentiation and preserved the myotube differentiation ability impaired by the inflammatory tumor microenvironment. In addition, taurine ameliorated myotube atrophy by regulating the Akt/FoxO1/MuRF1 and MAFbx signaling pathways., Conclusion: Taurine rescues cancer-induced atrophy in human skeletal muscle cells by ameliorating the inflammatory tumor microenvironment. Taurine supplementation may be a promising approach for intervening with the progression of cancer cachexia., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Badminton is a sport demanding both high aerobic and anaerobic fitness levels, and fatigue can significantly impact game performance. However, relevant studies are limited, and none have employed a wearable inertial measurement unit (IMU) to investigate the effects of fatigue on athletic performance in the field., Hypothesis: Overall performance and body acceleration in both time and frequency domains during the fundamental badminton skills of vertical jumping and changes of direction will be affected by fatigue., Study Design: Cross-sectional study., Level of Evidence: Level 3., Methods: A total of 38 young badminton players competing at the Division I level participated. Body accelerations while performing vertical jump and agility-T tests before and immediately after undergoing a fatigue protocol were measured by an IMU, positioned at the L4 to L5 level., Results: Jumping height decreased significantly by 4 cm ( P < 0.01) after fatigue with greater downward acceleration (1.03 m/s 2 , P < 0.05) during the squatting subphase. Finishing time increased significantly by 50 ms only during the 10-m side-shuffling of the agility-T test ( P = 0.02) after fatigue with greater peak and mean accelerations (3.83 m/s 2 , P = 0.04; 0.43 m/s 2 , P < 0.01), and higher median and mean frequency (0.38 Hz, P = 0.04, 0.11 Hz, P = 0.01)., Conclusion: This study using a wearable IMU demonstrates the effects of fatigue on body acceleration in badminton players. The frequency-domain analysis further indicated that fatigue might lead to loss of voluntary control of active muscles and increased impacts on the passive elastic elements., Clinical Relevance: The findings imply that fatigue can lead to diminished athletic performance and highlight the potential for an increased risk of sports injuries. Consequently, maintaining precision in monitoring fatigue is crucial for elite young badminton players., Competing Interests: The authors report no potential conflicts of interest in the development and publication of this article.

Pancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of various apoptotic pathways. Here, we find that development of apoptotic resistance and metastasis of Kras G12D -driven PDAC in mice is accelerated by deleting Plk3, explaining the often-reduced Plk3 expression in human PDAC. Importantly, a 41-kDa Plk3 (p41Plk3) that contains the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) is removed by proteasome degradation, preventing the inhibition of p41Plk3 by PBD. We find that p41Plk3 is the activated form of Plk3 that regulates a feed-forward mechanism to promote apoptosis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn induces expression of Plk3 and pro-apoptotic genes. These findings uncover an NRDC-regulated post-translational mechanism that activates Plk3, establishing a prototypic regulation by scission mechanism., (© 2024. The Author(s).)

Background: Triage is the process of accurately assessing patients' symptoms and providing them with proper clinical treatment in the emergency department (ED). While many countries have developed their triage process to stratify patients' clinical severity and thus distribute medical resources, there are still some limitations of the current triage process. Since the triage level is mainly identified by experienced nurses based on a mix of subjective and objective criteria, mis-triage often occurs in the ED. It can not only cause adverse effects on patients, but also impose an undue burden on the health care delivery system., Objective: Our study aimed to design a prediction system based on triage information, including demographics, vital signs, and chief complaints. The proposed system can not only handle heterogeneous data, including tabular data and free-text data, but also provide interpretability for better acceptance by the ED staff in the hospital., Methods: In this study, we proposed a system comprising 3 subsystems, with each of them handling a single task, including triage level prediction, hospitalization prediction, and length of stay prediction. We used a large amount of retrospective data to pretrain the model, and then, we fine-tuned the model on a prospective data set with a golden label. The proposed deep learning framework was built with TabNet and MacBERT (Chinese version of bidirectional encoder representations from transformers [BERT])., Results: The performance of our proposed model was evaluated on data collected from the National Taiwan University Hospital (901 patients were included). The model achieved promising results on the collected data set, with accuracy values of 63%, 82%, and 71% for triage level prediction, hospitalization prediction, and length of stay prediction, respectively., Conclusions: Our system improved the prediction of 3 different medical outcomes when compared with other machine learning methods. With the pretrained vital sign encoder and repretrained mask language modeling MacBERT encoder, our multimodality model can provide a deeper insight into the characteristics of electronic health records. Additionally, by providing interpretability, we believe that the proposed system can assist nursing staff and physicians in taking appropriate medical decisions., (©Yu-Ting Lin, Yuan-Xiang Deng, Chu-Lin Tsai, Chien-Hua Huang, Li-Chen Fu. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 01.04.2024.)

Hypertension is a global health problem and leads to cardiovascular disease and renal injury. Solanum muricatum Aiton leaf extract, rich in flavonoids, is known for its antioxidant capacity. However, the effects of Solanum muricatum Aiton leaf extract on hypertension combined with inflammatory complications were unknown. This study aimed to investigate the impact of Solanum muricatum Aiton leaf extract on hypertension in vivo and in vitro. In vivo, Solanum muricatum Aiton leaf extract led to decrease high blood pressure, improve heart, aorta, and kidney pathology, and enhance the antioxidative activity in spontaneously hypertensive rats (SHR). Our study demonstrated Solanum muricatum Aiton leaf extract inhibited angiotensin-converting enzyme (ACE), epithelial sodium channel (ENaC), sodium glucose co-transporters-1 (SGLT-1), nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). In vitro, Solanum muricatum Aiton leaf extract improved the angiotensin II-induced reactive oxygen species (ROS) and mitochondrial membrane depolarization in NRK-52E cells. Besides, Solanum muricatum Aiton leaf extract could also decrease the expressions of ENaC, SGLT-1, and NF-κB in angiotensin II-treated NRK-52E cells. Solanum muricatum Aiton leaf can be suggested as a novel antihypertensive agent ameliorating hypertension via ACE inhibition, inflammation reduction, and ROS. PLE is a novel anti-hypertensive agent to ameliorate hypertension and its complications, including inflammation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to assess the efficacy of various music therapy interventions in ameliorating depressive symptoms in dementia patients, utilizing a network meta-analysis approach. We rigorously selected randomized controlled trials focused on music therapy for dementia with depressive symptoms from major electronic databases. The primary outcome measured was the impact on depressive symptoms, with the secondary outcome evaluating dropout rates across different intervention groups and standard care control groups. The research protocol has been duly registered with PROSPERO (Registration ID: CRD42023393059). Our network meta-analysis incorporated 14 randomized controlled trials involving a total of 1080 participants and examined a range of interventions, including active music therapy, listening to music, rhythmic music therapy, singing, and tailored music interventions. The analysis revealed that active music therapy combined with singing emerged as the most effective intervention, demonstrating a significant improvement in depressive symptoms in dementia patients (Standardized Mean Difference [SMD] = -0.89, 95% Confidence Interval [CI]: -1.48 to -0.30). In contrast, listening to music alone showed a smaller effect (SMD = -0.26, 95% CI: -0.71 to 0.20). This study was particularly noteworthy for not showing higher dropout rates compared to standard care, indicating its feasibility and acceptability in clinical settings. The findings of our study indicate that active music therapy combined with singing is an effective approach to reducing depressive symptoms in dementia patients, potentially due to enhanced social interaction. These results offer new perspectives for dementia care, suggesting a promising direction for further research and clinical application.