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Algal biomass is important for aquaculture in terms of eutrophication, as a secondary metabolite threat, and as a food source for suspension feeders and benthos. In order to evaluate the applicability of an in situ FluoroProbe instrument, chlorophyll a (chl a) measured with this device was compared to chl a measured by a fluorometer and to algal densities and biovolumes determined by direct counts. Monthly surveys were conducted in 3 types of aquaculture ponds (tilapia, milk fish, and common orient clam) from October 2011 through April 2012 in the Cigu region of Tainan City, Taiwan. Results showed that green algae were the predominant phytoplankton group, followed by cyanobacteria, euglenoids, and diatoms. The 3 types of aquaculture ponds had wide ranges of chl a, pH, salinity, turbidity, PO4-3-P, and suspended solids. Chl a measured by the FluoroProbe had significant regressions with chl a values measured by a fluorometer, and with algal densities and biovolumes determined by counting; however, when chl a was >250 µg l-1, the correlation between the FluoroProbe and the fluorometer diminished. The difference in chl a reads between these 2 methods increased when chl a concentration exceeded 200 µg l-1. Of the 4 differently colored algal groups measured by the FluoroProbe, only the green and blue groups had significant regressions with their respective biovolumes, whereas the red and brown groups had no significant regression with their respective biovolumes. Our results show the applicability of the FluoroProbe in algal monitoring of aquaculture ponds, although caution is needed at higher chl a levels.

Purpose: We aimed to evaluate the effects of folate and vitamin B12 on psychopathology in patients with schizophrenia and low serum folate levels., Methods: Fifty-five schizophrenia patients with serum folate levels lower than 6 mg/L were randomized in a 2:1 ratio to supplementation with 5 mg of folate and 500 μg of vitamin B12 per day (the folate group, n = 36) or placebo (the placebo group, n = 19) for 24 weeks. We evaluated patients' symptomatology with the Positive and Negative Symptom Scale (PANSS) and cognitive functions with Cogstate., Results: During the 24-week intervention, serum folate and vitamin B12 levels significantly increased, and homocysteine level significantly decreased in the folate group, but these markers did not significantly change in the placebo group. There were no significant changes in scores of total and each subscale of PANSS, and Cogstate between the folate and placebo groups. A subgroup analysis within the folate groups revealed no significant differences in the changes of psychotic symptoms severity or cognitive functions among patients with different degrees of folate level increments., Conclusion: Our finding suggested that the extent of increased folate levels did not exert a notable impact on the changes of psychotic symptoms severity or cognitive function in our patients. It may also due to the relatively stable condition in our recruited patients, so supplementation of folate cannot show its effectiveness. Whether folate can improve psychopathology in moderate to severe patients with schizophrenia should be evaluated with a larger sample size in the future., Competing Interests: Declaration of any potential financial and nonfinancial conflicts of interest none., (Copyright © 2024 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Attempts to furnish antitumor structural templates that can prevent the occurrence of drug-induced hyperuricemia spurred us to generate xanthine oxidase inhibitor-based hydroxamic acids and anilides. Specifically, the design strategy involved the insertion of febuxostat (xanthine oxidase inhibitor) as a surface recognition part of the HDAC inhibitor pharmacophore model. Investigation outcomes revealed that hydroxamic acid 4 elicited remarkable antileukemic effects mediated via HDAC isoform inhibition. Delightfully, the adduct retained xanthine oxidase inhibitory activity, though xanthine oxidase inhibition was not the underlying mechanism of its cell growth inhibitory effects. Also, compound 4 demonstrated significant in-vivo anti-hyperuricemic (PO-induced hyperuricemia model) and antitumor activity in an HL-60 xenograft mice model. Compound 4 was conjugated with poly (ethylene glycol) poly(aspartic acid) block copolymer to furnish pH-responsive nanoparticles (NPs) in pursuit of circumventing its cytotoxicity towards the normal cell lines. SEM analysis revealed that NPs had uniform size distributions, while TEM analysis ascertained the spherical shape of NPs, indicating their ability to undergo self-assembly. HDAC inhibitor 4 was liberated from the matrix due to the polymeric nanoformulation's pH-responsiveness, and the NPs demonstrated selective cancer cell targeting ability., 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 Masson SAS. All rights reserved.)

Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis and high recurrence rates. The complex immune microenvironment of GBM is highly infiltrated by tumor-associated microglia and macrophages (TAM). TAMs are known to be heterogeneous in their functional and metabolic states and can transmit either protumoral or antitumoral signals to glioma cells. Here, we performed bulk RNA sequencing and single-cell RNA sequencing on samples from patients with GBM, which revealed increased ATP synthase expression and oxidative phosphorylation activity in TAMs located in the tumor core relative to the tumor periphery. Both in vitro and in vivo models displayed similar trends of augmented TAM mitochondrial activity, along with elevated mitochondrial fission, glucose uptake, mitochondrial membrane potential, and extracellular ATP (eATP) production by TAMs in the presence of GBM cells. Tumor-secreted factors, including GM-CSF, induced the increase in TAM eATP production. Elevated eATP in the GBM microenvironment promoted glioma growth and invasion by activating the P2X purinoceptor 7 (P2X7R) on glioma cells. Inhibition of the eATP-P2X7R axis attenuated tumor cell viability in vitro and reduced tumor size and prolonged survival in glioma-bearing mouse models. Overall, this study revealed elevated TAM-derived eATP in GBM and provided the basis for targeting the eATP-P2X7R signaling axis as a therapeutic strategy in GBM. Significance: Glioblastoma-mediated metabolic reprogramming in tumor-associated microglia increases ATP secretion that supports cancer cell proliferation and invasion by activating P2X7R, which can be inhibited to attenuate tumor growth., (©2024 American Association for Cancer Research.)

Triple negative breast cancer (TNBC) is characterized by high heterogenicity and aggressiveness and autophagy plays a complicated role in cancer development. Zingerone is reported to possess multiple pharmacological activities, including antitumors. This study explored the biological role and the relevant mechanisms of zingerone in TNBC. Following zingerone treatment, the viability of normal breast cancer cells MCF-10A and TNBC cells (MDA-MB-231 and MDA-MB-468) was detected with CCK-8 assay. The proliferation, migration and invasion of TNBC cells were detected with colony formation, wound healing, and transwell assays. Western blot was used to detect the expressions of migration-, apoptosis- and autophagy-related proteins. Flow cytometry was used to detect the cell apoptotic level and immunofluorescence assay measured the autophagy. The experimental data revealed that zingerone with varying concentrations suppressed cell viability, proliferation, migration and invasion while promoting the apoptosis in TNBC, which might be mediated by autophagy activation. Besides, zingerone decreased HDAC1 expression in TNBC cells and regulated autophagy via HDAC1. Collectively, zingerone impeded the malignant progression of TNBC via inducing HDAC1-mediated autophagy., (© 2024 Wiley Periodicals LLC.)

Background: E. coli ST8346 is a unique strain associated with the potential carriage of multiple carbapenemases. Three unique E. coli ST8346 isolates were identified, each concurrently harboring multiple carbapenemases, including bla NDM-5 , bla KPC-2 , and/or bla OXA-181 . This study aimed to characterize the genetic and plasmid structures of these isolates to understand their transmission and resistance mechanisms., Methods: Antibiotic resistance profiles, genetic relatedness, and plasmid structures were determined using antibiotic susceptibility testing, multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), S1 nuclease PFGE, and long-read sequencing., Results: All the strains were carbapenem resistant. PFGE revealed close genetic relationships among the isolates, despite the lack of geographical or epidemiological connections. bla NDM-5 , bla KPC-2 , and bla OXA-181 were located on separate plasmids. Plasmids harboring bla NDM-5 showed genetic similarities to bla NDM-5 -bearing IncF plasmids in the United Kingdom. The IncA/C plasmids harboring bla KPC-2 had identical sequences resembling a plasmid from a K. pneumoniae strain in Taiwan, except for the bla KPC-2 region, which matched a strain from China, indicating a hybrid plasmid., Conclusion: This study is the first to identify and characterize the coexistence of bla NDM-5 , bla KPC-2 , and bla OXA-181 in E. coli ST8346 isolates. The spread appears to be due to independent acquisition events. We identified the putative origins of these plasmids and detected a possible recombination event in a novel IncA/C plasmid. These findings emphasize the importance of ongoing surveillance and further investigations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Endometrial cancer is the most common malignant tumor of the uterus, but the underlying genetic mechanisms of EC remain unclear. To identify candidate genes and investigate genetic mechanisms for endometrial cancer, we utilized the summary-data-based Mendelian randomization (SMR) method to investigate causal associations between genetic variants, gene expression, DNA methylation, and endometrial cancer. Three main analyses were conducted utilizing cis-expression and methylation quantitative trait loci (eQTLs and mQTLs) as instrumental variables to examine causal relationships with endometrial cancer, and assessing the causal relationship between DNA methylation and gene expression. Data sources included genetic association data from O'Mara et al. eQTL data from the GTEx database, and mQTL data from McRae et al. Analysis involved the HEIDI test to distinguish pleiotropy, SMR analysis with multiple testing correction, and colocalization analysis to assess associations driven by linkage disequilibrium. Functional enrichment analysis was performed by the Metascape tool. Our study showed that three genes, SNX11, LINC00243, and EVI2A, were identified as causally related to endometrial cancer. SNX11 exhibited a positive causal relationship, while LINC00243 and EVI2A showed negative ones. Furthermore, 24 CpG sites were identified as causally related to endometrial cancer, with cg14424631 (CYP19A1) being the most significant. The study revealed common genes implicated in endometrial cancer, gene expression, and methylation sites, with LINC00243 playing a key role. Colocalization analysis confirmed significant causal relationships between LINC00243, SNX11, and endometrial cancer. Enrichment analysis uncovered pathways like interferon gamma signaling enriched in both endometrial cancer GWAS and e/mQTL. These findings shed light on the molecular mechanisms underlying endometrial cancer development. The study identified candidate genes and DNA methylation loci causally associated with endometrial cancer, which are expected to serve as potential targets for treatment.

ELNES/XANES spectra can be observed using TEM or synchrotron radiation and can elucidate the unoccupied state electronic structures of an excited states. The computation of their features is usually demanding substantial computational resources due to the requisite structure optimization and electronic structure calculations. Herein, we leverage a machine learning technique alongside an atomic-coordinate-independent descriptor, SMILES, to yield the ELNES/XANES spectra, directly, with heightened precision. Moreover, our approach extends to obtain ground state electronic structure, namely PDOS at both occupied and unoccupied ground states, underscoring its viability for a ground-state spectroscopy. Our study revealed that incorporation of long-SMILES molecules into the training dataset enhances prediction accuracy for such molecular structures. This study's direct derivation of spectroscopy from SMILES strings holds promise for expediting spectroscopic inquiries., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Periodic leg movements during sleep (PLMS) may have crucial consequences in adults. This study aimed to identify baseline characteristics, symptoms, or questionnaires that could help to identify sleep-disordered breathing patients with significant PLMS. Patients aged 20-80 years who underwent polysomnography for assessing sleep disturbance were included. Various factors such as sex, age, body measurements, symptoms, apnea-hypopnea index (AHI), and sleep quality scales were analysed to determine the presence of PLMS. The study included 1480 patients with a mean age of 46.4 ± 13.4 years, among whom 110 (7.4%) had significant PLMS with a PLM index of 15 or higher. There were no significant differences observed in terms of sex or BMI between patients with and without significant PLMS. However, the odds ratios (OR) for PLMS were 4.33, 4.41, and 4.23 in patients who were aged over 50 years, had insomnia, or had an ESS score of less than 10, respectively. Notably, the OR increased up to 67.89 times in patients who presented with all three risk factors. Our analysis identified significant risk factors for PLMS: age over 50, self-reported insomnia, and lower daytime sleepiness levels. These findings aid in identifying potential PLMS patients, facilitating confirmatory examinations and managing associated comorbidities., (© 2024 European Sleep Research Society.)

The basal endosperm transfer layer (BETL) of the maize (Zea mays L.) kernel is composed of transfer cells for nutrient transport to nourish the developing kernel. To understand the spatiotemporal processes required for BETL development, we characterized 2 unstable factor for orange1 (Zmufo1) mutant alleles. The BETL defects in these mutants were associated with high levels of reactive oxygen species, oxidative DNA damage, and cell death. Interestingly, antioxidant supplementation in in vitro cultured kernels alleviated the cellular defects in mutants. Transcriptome analysis of the loss-of-function Zmufo1 allele showed differential expression of tricarboxylic acid cycle, redox homeostasis, and BETL-related genes. The basal endosperms of the mutant alleles had high levels of acetyl-CoA and elevated histone acetyltransferase activity. The BETL cell nuclei showed reduced electron-dense regions, indicating sparse heterochromatin distribution in the mutants compared with wild-type. Zmufo1 overexpression further reduced histone methylation marks in the enhancer and gene body regions of the pericarp color1 (Zmp1) reporter gene. Zmufo1 encodes an intrinsically disordered nuclear protein with very low sequence similarity to known proteins. Yeast two-hybrid and luciferase complementation assays established that ZmUFO1 interacts with proteins that play a role in chromatin remodeling, nuclear transport, and transcriptional regulation. This study establishes the critical function of Zmufo1 during basal endosperm development in maize kernels., Competing Interests: Conflict of interest statement: The authors declare no competing financial interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. 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.)

Giant thrombotic aneurysms of the anterior cerebral artery (ACA) are rare and pose significant challenges due to their variable clinical presentations. While complications following surgical interventions for these aneurysms are known, they have not been fully characterized. We present a novel case of postoperative infarction in the recurrent artery of Heubner (RAH) following resection of a thrombotic giant aneurysm in the ACA. A 53-year-old man with no prior systemic illnesses presented with progressive weakness in his left hand and foot, along with slurred speech. Imaging studies revealed a giant thrombotic aneurysm in the proximal A2 segment of the right ACA, which was completely occluded. Additionally, a chronic infarction was identified in the territory of the right ACA. The patient underwent successful surgical resection of the aneurysm. However, he subsequently developed an infarction in the RAH territory, a complication rarely reported in the literature. This case highlights the importance of comprehensive preoperative evaluation and underscores the need to anticipate and manage potential complications following surgery., Competing Interests: The authors declare that they have no competing interests., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Morphinan antagonists, which block opioid effects at mu-opioid receptors, have been studied for their analgesic potential. Previous studies have suggested that these antagonists elicit analgesia with fewer adverse effects in the presence of the mutant mu-opioid receptor (MOR; S196A). However, introducing a mutant receptor for medical applications represents significant challenges. We hypothesize that binding a chemical compound to the MOR may elicit a comparable effect to the S196A mutation. Through high-throughput screening and structure-activity relationship studies, we identified a modulator, 4-(2-(4-fluorophenyl)-4-oxothiazolidin-3-yl)-3-methylbenzoic acid (BPRMU191), which confers agonistic properties to small-molecule morphinan antagonists, which induce G protein-dependent MOR activation. Co-application of BPRMU191 and morphinan antagonists resulted in MOR-dependent analgesia with diminished side effects, including gastrointestinal dysfunction, antinociceptive tolerance, and physical and psychological dependence. Combining BPRMU191 and morphinan antagonists could serve as a potential therapeutic strategy for severe pain with reduced adverse effects and provide an avenue for studying G protein-coupled receptor modulation., Competing Interests: Declaration of interests S.-H.U., S.-H.Y., S.-Y.L., H.H.L., and C.S. have a granted patent (no. US10544113 B2) covering BPRMU191., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Trastuzumab-targeted therapy is currently the standard of care for advanced human epidermal growth factor receptor 2 (HER2)-positive gastric cancer. However, the emergence of resistance to trastuzumab poses significant challenges., Aim: To identify the key genes associated with trastuzumab resistance. These results provide a basis for the development of interventions to address drug resistance and improve patient outcomes., Methods: High-throughput sequencing and bioinformatics were used to identify the differentially expressed pivotal gene BIRC3 and delineate its potential function and pathway regulation. Tumor samples were collected from patients with HER2-positive gastric cancer to evaluate the correlation between BIRC3 expression and trastuzumab resistance. We established gastric cancer cell lines with both highly expressed and suppressed levels of BIRC3 , followed by comprehensive in vitro and in vivo experiments to confirm the involvement of BIRC3 in trastuzumab resistance and to elucidate its underlying mechanisms., Results: In patients with HER2-positive gastric cancer, there is a significant correlation between elevated BIRC3 expression in tumor tissues and higher T stage, tumor node metastasis stage, as well as poor overall survival and progression-free survival. BIRC3 is highly expressed in trastuzumab-resistant gastric cancer cell lines, where it inhibits tumor cell apoptosis and enhances trastuzumab resistance by promoting the phosphorylation and activation of the phosphoinositide 3-kinase-Akt (PI3K-AKT) pathway in HER2-positive gastric cancer cells, both in vivo and in vitro ., Conclusion: This study revealed a robust association between high BIRC3 expression and an unfavorable prognosis in patients with HER2-positive gastric cancer. Thus, the high expression of BIRC3 stimulated PI3K-AKT phosphorylation and activation, stimulating the proliferation of HER2-positive tumor cells and suppressing apoptosis, ultimately leading to trastuzumab resistance., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Neuropathic pain (NP) affects countless people worldwide; however, few effective treatments are currently available. Histone deacetylases (HDACs) participate in epigenetic modifications in neuropathy-induced nociceptive sensitization. Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that can inhibit NP. The present study aimed to examine the role of spinal HDAC and its isoforms in neuropathy., Methods: Male Wistar Rat with chronic constriction injury (CCI)-induced peripheral neuropathy and HDAC inhibitor, panobinostat, was administrated intrathecally. We performed quantitative real-time polymerase chain reaction (RT-qPCR), western blot, and immunohistochemical analysis of lumbar spinal cord dorsal horn and nociceptive behaviors (thermal hyperalgesia and mechanical allodynia) measurements., Results: Herein, RT-qPCR analysis revealed that spinal hdac3 , hdac4 , and hdac6 were upregulated in CCI rats. Western blotting and immunofluorescence staining further confirmed that HDAC3, HDAC4, and HDAC6 were significantly upregulated, whereas GABA and its synthesis key enzyme glutamic acid decarboxylase (GAD) 65 were dramatically downregulated. Intrathecal panobinostat attenuated nociceptive behavior and restored the downregulated spinal GAD65 and GABA expression in CCI rats., Conclusions: HDAC upregulation might induce nociception through GAD65 and GABA inhibition in CCI-induced neuropathy. These findings strongly suggest that HDACs negatively regulate inhibitory neurotransmitters, constituting a potential therapeutic strategy for an epigenetic approach to manage NP., Competing Interests: The authors have no conflict of interest to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

The accurate monitoring of vital physiological parameters, exemplified by heart rate, respiratory rate, and intracranial pressure (ICP), is of paramount importance, particularly for managing severe cranial injuries. Despite the rapid development of implantable ICP sensing systems over the past decades, they still suffer from, for example, wire connection, low sensitivity, poor resolution, and the inability to monitor multiple variables simultaneously. Here, we propose an ultrasensitive multimodal biotelemetric system that amalgamates an iontronic pressure transducer with exceptional point (EP) operation for the monitoring of ICP signals. The proposed system can exhibit extraordinary performance regarding the detection of minuscule ICP fluctuation, demonstrated by the sensitivity of 115.95 kHz/mmHg and the sensing resolution down to 0.003 mmHg. Our system excels not only in the accurate quantification of ICP levels but also in distinguishing respiration and cardiac activities from ICP signals, thereby achieving the multimodal monitoring of ICP, respiratory, and heart rates within a single system. Our work may provide a pragmatic avenue for the real-time wireless monitoring of ICP and thus hold great potential to be extended to the monitoring of other vital physiological indicators., (© 2024. The Author(s).)

Arabidopsis (Arabidopsis thaliana) HISTONE DEACETYLASE 6 (HDA6) and HISTONE DEMETHYLASES LSD-LIKE 1 (LDL1) and LDL2 synergistically regulate the expression of long non-coding RNAs associated with H3Ac and H3K4me2. The underlying mechanisms of such highly coordinated interactions among genetic and epigenetic factors contributing to this collaborative regulation remain largely unclear. We analyzed all transposable elements (TEs) across the Arabidopsis genome and the individual and combined roles of HDA6 and LDL1/LDL2 by dissecting multilayered epigenomes and their association with transcription. Instead of an individual synergistic effect, we observed dual synergistic and antagonistic effects, which are positively associated with H3Ac and H3K4me2 while maintaining a negative but moderate association with DNA methylation. Specifically, 2 modes of synergistic regulation were discovered in TEs: 74% are primarily regulated by HDA6, with less dependence on LDL1/LDL2, and the remaining 26% are co-regulated by both. Between the 2 modes, we showed that HDA6 has a strong effect on TE silencing, whereas LDL1/LDL2 plays a weaker yet crucial role in co-regulation with HDA6. Our results led to a model of epigenomic regulation-the differential de-repression between the 2 modes of synergistic regulation of TEs was determined by H3Ac and H3K4me2 levels, where TEs are in accessible chromatins free of DNA methylation, and this open chromatin environment precedes transcriptional changes and epigenome patterning. Our results discovered unbalanced effects of genetic factors in synergistic regulation through delicately coordinated multilayered epigenomes and chromatin accessibility., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Nanoparticles of zeolitic imidazole framework-8 (ZIF-8 NPs), which are the subclass of metal-organic frameworks consisting of Zn ion and 2-methylimidazole, have been identified as promising drug carriers since their large microporous structure is suited for encapsulating hydrophobic drug molecules. However, one of the limitations of ZIF-8 NPs is their low stability in physiological solutions, especially in the presence of water and phosphate anions. These molecules can interact with the coordinatively unsaturated Zn sites at the external surface to induce the degradation of ZIF-8 NPs. In this study, herein a facile approach is reported to enhance the chemical stability of ZIF-8 NPs by surface coating with polyacrylic acid (PAA). The PAA-coated ZIF-8 (PAA-ZIF-8) NPs are prepared by mixing ZIF-8 NPs and PAA in water. PAA coating inhibits the degradation of ZIF-8 NPs in water as well as phosphate-buffered saline over 6 days, which seems to be due to the coordination of carboxyl groups of PAA to the reactive Zn sites. Furthermore, the PAA-ZIF-8 NPs loaded with the anticancer drug doxorubicin (Dox) show cytotoxicity in human colon cancer cells. These results clearly show the feasibility of the PAA coating approach to improve the chemical stability of ZIF-8 NPs without impairing their drug delivery capability., (© 2024 The Author(s). Macromolecular Bioscience published by Wiley‐VCH GmbH.)

Purpose: The role of tumor resection remains undetermined in treating primary central nervous system lymphomas (PCNSLs). This study aimed to clarify the impact of tumor resection on survival and functional outcomes, and to identify subgroups benefiting from resection., Methods: We retrospectively reviewed records from 2010 to 2021 for PCNSL diagnosed at Chang Gung Memorial Hospital, Linkou. Patients were categorized by extent of resection: gross total resection (GTR), partial resection (PR), and biopsy. Univariate and multivariate analyses were performed to identify prognostic factors for survival and functional outcomes. Subgroup analysis was conducted to characterize patients who benefit from tumor resection., Results: Of 88 patients, 12 had GTR, 25 had PR, and 51 received biopsy. GTR correlated with longer progression free survival (PFS) (HR 0.25, p=0.039), remaining significant in multivariate analysis (adjusted HR 0.09, p=0.004). In solitary PCNSLs, GTR also independently predicted longer PFS (adjusted HR 0.13, p= 0.023). Patients with dominant tumors measuring ≥ 3 cm trended towards improved overall survival (OS) with cytoreductive surgery versus biopsy (median survival 38.6 months vs 22.3 months, p=0.083). Age ≥ 60 years (adjusted OR 16.9, p = 0.008) and preoperative Karnofsky Performance Scale ≤ 70 (adjusted OR 4.97, p = 0.049) predicted poorer functional outcomes, while radiation therapy (adjusted OR 0.10, p = 0.033) was protective., Conclusions: GTR significantly improved PFS in treating PCNSLs, particularly in solitary cases. For patients with dominant tumors measuring ≥ 3 cm, cytoreductive surgery may improve OS. Neither cytoreductive surgery nor GTR correlated with poor functional outcomes., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Concerns regarding bleeding remain in cold snare polypectomy (CSP) for small pedunculated (0-Ip) polyps. The aim of this study was to compare the risk of CSP and hot snare polypectomy (HSP) for such lesions., Methods: Data on 0-Ip colorectal polyps ≤10 mm were extracted from a large, pragmatic, randomized trial. Immediate postpolypectomy bleeding (IPPB), defined as the perioperative use of a clip for bleeding, was evaluated through polyp-level analysis. Delayed postpolypectomy bleeding (DPPB), defined as bleeding occurring within 2 weeks postoperatively, was assessed at the patient-level among patients whose polyps were all ≤10 mm, including at least one 0-Ip polyp., Results: A total of 647 0-Ip polyps (CSP: 306; HSP: 341) were included for IPPB analysis and 386 patients (CSP: 192; HSP: 194) for DPPB analysis. CSP was associated with a higher incidence of IPPB (10.8% vs 3.2%, P < 0.001) but no adverse clinical events. The procedure time of all polypectomies was shorter for CSP than for HSP (123.0 ± 117.8 vs 166.0 ± 237.7 seconds, P = 0.003), while the procedure time of polypectomies with IPPB were similar (249.8 ± 140.2 vs 227.4 ± 125.9 seconds, P = 0.64). DPPB was observed in 3 patients (1.5%) in the HSP group, including one patient (0.5%) with severe bleeding, but not in the CSP group., Discussion: Despite CSP being associated with more IPPB events, it could be timely treated without adverse outcomes. Notably, no delayed bleeding occurred in the CSP group. Our findings support the use of CSP for 0-Ip polyps ≤ 10 mm., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Purpose: This multicenter study investigates the efficacy of 18F-FDG PET/CT in postradiotherapy (post-RT) response evaluation in salivary gland carcinoma (SGC)., Methods: We retrospectively reviewed 115 SGC patients who underwent definitive or adjuvant RT followed by 18F-FDG PET/CT between 2004 and 2021. Most tumors were parotid gland malignancies (50%). The most common histological subtypes were adenoid cystic (29%) and mucoepidermoid carcinomas (18%)., Results: The median follow-up was 65 months. Post-RT anatomic images (CT/MRI) revealed complete response (CR) in 51 patients (44%). Among 53 patients with partial response or stable disease, only 17 (32%) patients experienced locoregional recurrence, with a 5-year locoregional control rate of 69%. Post-RT 18F-FDG PET/CT documented metabolic CR in 81 patients (70%). Metabolic complete responders had significantly higher 5-year locoregional control (90% vs 43%), distant metastasis-free survival (80% vs 48%), progression-free survival (76% vs 24%), and overall survival rates (89% vs 42%) compared with non-complete responders (all P < 0.001), as confirmed in both univariate and multivariate analyses. It identified additional viable tumors in 18 cases (16%) and facilitated salvage local therapies in 7 patients (6%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of post-RT 18F-FDG PET/CT were 63%, 91%, 70%, 88%, and 84%, respectively, in predicting locoregional recurrence. 18F-FDG PET/CT showed significantly higher sensitivity (88% vs 36%, P = 0.011) in tumors with pre-RT SUVmax ≥7.39 compared with those with SUVmax <7.39., Conclusions: Post-RT 18F-FDG PET/CT demonstrates high negative predictive value and specificity, with metabolic CR predicting excellent outcomes. Additionally, it exhibits higher sensitivity for high-SUVmax SGC, facilitating early detection of viable tumors., Competing Interests: Conflicts of interest and sources of funding: none declared. This study was made possible through the financial support of grants NMRPG3M6301 (NSTC111-2314-B-182A-160-MY2) and NMRPG3N6111 (NSTC112-2628-B-182A-007-MY3) from the National Science and Technology Council, the Yushan Fellow Program (MOE-113-YSFMN-1009-001-P1) from the Ministry of Education, as well as grants CMRPG3N0522 and CPRPG3P0031 from the Chang Gung Medical Foundation in Taiwan., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate monosyllable word recognition in noise under different conditions in bilateral sequential cochlear implants (CIs). Second, to assess subjective hearing benefits among bilateral sequential CIs, bimodal hearing, and CI-only groups. Lastly, to analyze the prognostic factors affecting CI outcomes in children with bilateral sequential CIs., Methods: Sixty-five children with CI were enrolled. Mandarin monosyllable recognition tests in noise and the Speech, Spatial, and Qualities of Hearing Scale (SSQ) were used to assess post-CI outcomes. The SSQ benefits were compared among children with bilateral CIs, bimodal hearing, and CI-only., Results: Bilateral CIs significantly outperformed the first or second CI alone using in noise. The bilateral CI group had significantly better SSQ scores for speech, qualities, and total scores compared to the CI-only group. Additionally, 41% of the variance in speech perception of the second CI can be attributed to the inter-implantation interval between bilateral CIs., Conclusion: Bilateral sequential CIs can enhance speech perception in noise and daily life-functioning for children. Earlier implantation of bilateral sequential CIs results in better outcomes, while inter-implantation interval exceeding 9.6 years between bilateral CIs may lead to poor second CI performance in noise. Therefore, early bilateral sequential CIs should be encouraged., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Histone modifications can regulate transcription epigenetically by marking specific genomic loci, which can be mapped using chromatin immunoprecipitation sequencing (ChIP-seq). Here we present QHistone, a predictive database of 1534 ChIP-seqs from 27 histone modifications in Arabidopsis, offering three key functionalities. Firstly, QHistone employs machine learning to predict the epigenomic profile of a query protein, characterized by its most associated histone modifications, and uses these modifications to infer the protein's role in transcriptional regulation. Secondly, it predicts synergistic regulatory activities between two proteins by comparing their profiles. Lastly, it detects previously unexplored co-regulating protein pairs by screening all known proteins. QHistone accurately identifies histone modifications associated with specific known proteins, and allows users to computationally validate their results using gene expression data from various plant tissues. These functions demonstrate an useful approach to utilizing epigenome data for gene regulation analysis, making QHistone a valuable resource for the scientific community ( https://qhistone.paoyang.ipmb.sinica.edu.tw )., (© 2024. The Author(s).)

Autoimmune inner ear disease (AIED) is an uncommon cause of fluctuating sensorineural hearing loss (SNHL), which is diagnosed by exclusion and required a high index of suspicion. Secondary AIED, which accompanies other autoimmune diseases, occurs in up to 30% of AIED cases. Secondary AIED is a rare manifestation of paraneoplastic syndrome, and the causal malignancy may be occult initially. Detecting and treating associated diseases, along with the use of immunosuppressants, are the mainstay for the management of AIED. Herein, we presented a woman with bilateral fluctuating and progressive SNHL, partially responding to steroid or immunosuppressant treatment. Her hearing eventually stabilized after completing the treatment for diffuse large B cell lymphoma, which was diagnosed 6 months after the onset of hearing loss. This case serves as a reminder to physicians to be aware of AIED in cases of fluctuating SNHL and the possibility of associated malignancy alongside autoimmune disturbance. Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Workplace violence is a serious safety hazard in the healthcare sector and has attracted much attention worldwide, especially for nursing staff. Equipping nursing personnel with protective capabilities for workplace violence can reduce the risk they face in work settings. This study explored scenarios of common violent patient-nurse conflicts in the workplace of hospital nursing staff and their capabilities for de-escalating such conflicts., Methods: We used a qualitative content analysis for this study. Qualitative interviews were conducted with 21 nurses in two teaching hospitals in New Taipei City, Taiwan, until data saturation was reached. The data were transcribed, encoded, and analyzed and similar concepts were grouped under the same category., Results: Four categories of workplace violence scenarios common to hospital nursing staff were identified: unreasonable requests, caring for high-risk patients, long waiting times for medical consultation, and close contact when caring for patients. Two protective capabilities were recognized: communication and interpersonal capabilities and problem-solving skills. Each scenario may require a different combination of abilities., Conclusion: Our findings suggest that a violence-prevention training program could be designed for various workplace violence scenarios to enhance nurses' abilities to de-escalate workplace violence in hospitals., (© 2024. The Author(s).)

While luminescent stimuli-responsive materials (LSRMs) have become one of the most sought-after materials owing to their potential in optoelectronic applications, the use of earth-scarce lanthanides remains a crucial problem to be solved for further development. In this work, two manganese-based LSRMs, ( R )-(+)-1-phenylethylammonium manganese bromide, (R-PEA) 2 MnBr 4 , and ( S )-(-)-1-phenylethylammonium manganese bromide, (S-PEA) 2 MnBr 4 , are successfully demonstrated. Both (R-PEA) 2 MnBr 4 and (S-PEA) 2 MnBr 4 show a kinetically stable red-emissive amorphous state and a thermodynamically stable green-emissive crystalline state at room temperature, where the fully reversible transition can be done through melt-quenching and annealing processes. Based on this property, a reusable manganese-halide-based time-temperature indicator is demonstrated for the first time. Furthermore, an X-ray scintillator with a low limit of detection (18.1 nGy/s) and a high spatial resolution limit (30.0 lp/mm) are achieved by exploiting the high transparency of amorphous states. These results uncover the multifunctionality of manganese halides and pave the way for upcoming research.

Background: The challenge of preventing in-patient falls remains one of the most critical concerns in health care., Objective: This study aims to investigate the effect of an integrated Internet of Things (IoT) smart patient care system on fall prevention., Methods: A quasi-experimental study design is used. The smart patient care system is an integrated IoT system combining a motion-sensing mattress for bed-exit detection, specifying different types of patient calls, integrating a health care staff scheduling system, and allowing health care staff to receive and respond to alarms via mobile devices. Unadjusted and adjusted logistic regression models were used to investigate the relationship between the use of the IoT system and bedside falls compared with a traditional patient care system., Results: In total, 1300 patients were recruited from a medical center in Taiwan. The IoT patient care system detected an average of 13.5 potential falls per day without any false alarms, whereas the traditional system issued about 11 bed-exit alarms daily, with approximately 4 being false, effectively identifying 7 potential falls. The bedside fall incidence during hospitalization was 1.2% (n=8) in the traditional patient care system ward and 0.1% (n=1) in the smart ward. We found that the likelihood of bedside falls in wards with the IoT system was reduced by 88% (odds ratio 0.12, 95% CI 0.01-0.97; P=.047)., Conclusions: The integrated IoT smart patient care system might prevent falls by assisting health care staff with efficient and resilient responses to bed-exit detection. Future product development and research are recommended to introduce IoT into patient care systems combining bed-exit alerts to prevent inpatient falls and address challenges in patient safety., (©Ming-Huan Wen, Po-Yin Chen, Shirling Lin, Ching-Wen Lien, Sheng-Hsiang Tu, Ching-Yi Chueh, Ying-Fang Wu, Kelvin Tan Cheng Kian, Yeh-Liang Hsu, Dorothy Bai. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 03.10.2024.)

Background/purpose: Clear aligners are popular orthodontic tools because of their relatively aesthetic appearance and convenience of use. Nevertheless, bodily tooth movements still present challenges. This study evaluated various configurations of attachments placed on the mandibular canine in terms of the efficiency of canine bodily movement and correction of tipping., Materials and Methods: A finite element model of the mandible was constructed to investigate the effects of various attachment configurations on the overall bodily movement and undesirable tipping of a mandibular canine. Canine movements were categorized into four types, namely tipping and bodily movements in the mesial and distal directions. The size and shape of the attachments were fixed, but their placement and orientation were varied. Five and seven attachment configurations were evaluated for their influence on tipping and bodily movements, respectively., Results: Attachment configuration significantly influenced mandibular canine tipping. The mesial occlusal-distal cervical and mesial occlusal-mesial cervical configurations had notable effects on mesial tipping, and the mesial occlusal-mesial cervical configuration excelled in distal tipping by increasing strain by 33.1%. The mesial occlusal-mesial cervical attachment configuration consistently had superior efficiency in facilitating both mesial and distal bodily movements of the canine., Conclusion: The mesial occlusal-mesial cervical attachment configuration excelled in all four types of canine movement. Irrespective of the attachment configuration, canines tend to move overall with slight tipping due to skeletal resistance and their center of rotation. The attachment configuration is crucial to the success of clear aligner treatment and must be carefully considered in clinical practice., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2024 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Core binding factor acute myeloid leukemia (CBF-AML) stands out as the most common type of adult AML, characterized by specific chromosomal rearrangements involving CBF genes, particularly t(8;21). Shikonin (SHK), a naphthoquinone phytochemical widely employed as a food colorant and traditional Chinese herbal medicine, exhibits antioxidant, anti-inflammatory, and anti-cancer activities. In this study, we aim to investigate the antileukemic effects of SHK and its underlying mechanisms in human CBF-AML cells and zebrafish xenograft models. Our study revealed that SHK reduced the viability of CBF-AML cells. SHK induced cell cycle arrest, promoted cell apoptosis, and induced differentiation in Kasumi-1 cells. Additionally, SHK downregulated the gene expression of AML1-ETO and c-KIT in Kasumi-1 cells. In animal studies, SHK showed no toxic effects in zebrafish and markedly inhibited the growth of leukemia cells in zebrafish xenografts. Transcriptomic analysis showed that differentially expressed genes (DEGs) altered by SHK are linked to key biological processes like DNA repair, replication, cell cycle regulation, apoptosis, and division. Furthermore, KEGG pathways associated with cell growth, such as the cell cycle and p53 signaling pathway, were significantly enriched by DEGs. Analysis of AML-associated genes in response to SHK treatment using DisGeNET and the STRING database indicated that SHK downregulates the expression of cell division regulators regarding AML progression. Finally, we found that SHK combined with cytarabine synergistically reduced the viability of Kasumi-1 cells. In conclusion, our findings provide novel insights into the mechanisms of SHK in suppressing leukemia cell growth, suggesting its potential as a chemotherapeutic agent for human CBF-AML., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Multi-informant studies are popular in social and behavioral science. However, their data analyses are challenging because data from different informants carry both shared and unique information and are often incomplete. Using Monte Carlo Simulation, the current study compares three approaches that can be used to analyze incomplete multi-informant data when there is a distinction between reference and nonreference informants. These approaches include a two-method measurement model for planned missing data (2MM-PMD), treating nonreference informants' reports as auxiliary variables with the full-information maximum likelihood method or multiple imputation, and listwise deletion. The result suggests that 2MM-PMD, when correctly specified and data are missing at random, has the best overall performance among the examined approaches regarding point estimates, type I error rates, and statistical power. In addition, it is also more robust to data that are not missing at random., (© 2024. The Psychonomic Society, Inc.)

Purpose: Although the validity of the Epworth Sleepiness Scale (ESS) as an effectiveness measure for sleep apnea treatments such as continuous positive airway pressure (CPAP) has been supported by multiple studies, some researchers continue to challenge it. They suggest that in addition to its impact on relieving patients' daytime sleepiness, CPAP also alters the internal standards patients use to evaluate their sleepiness (i.e., response shift; RS), confounding the meaning of the difference in the ESS scores. We believe an issue yet to be addressed in this debate is that all existing evidence of RS has been obtained through the then-test approach, a retrospective method sensitive to various cognitive mechanisms. Thus, in the current study, we re-examined this issue using the structural equation modeling (SEM) approach, a method that can be directly applied to randomized clinical trial (RCT) data without retrospective measures., Methods: With the ESS data from two independent RCTs, we conducted cross-sectional and longitudinal measure invariance tests in SEM to examine whether CPAP would lead to RS., Results: The ESS demonstrated cross-sectional and longitudinal scalar invariance against CPAP treatments. Its factorial pattern, loadings, and thresholds were invariant between the treatment and control groups and pre- and post-treatment, supporting the comparability of the observed mean ESS scores across time and groups., Conclusion: Our results support the validity of the average difference scores of the ESS for quantifying the effectiveness of CPAP on group-level daytime sleepiness in RCTs with relatively large sample sizes., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Prediction of the risk of developing surgical site infection (SSI) in patients following total knee arthroplasty (TKA) is of clinical importance. Genetic susceptibility is involved in developing TKA-related SSI. Previously reported models for predicting SSI were constructed using nongenetic risk factors without incorporating genetic risk factors. To address this issue, we performed a genome-wide association study (GWAS) using the UK Biobank database., Methods: Adult patients who underwent primary TKA (n = 19,767) were analyzed and divided into SSI (n = 269) and non-SSI (n = 19,498) cohorts. Nongenetic covariates, including demographic data and preoperative comorbidities, were recorded. Genetic variants associated with SSI were identified by GWAS and included to obtain standardized polygenic risk scores (zPRS, an estimate of genetic risk). Prediction models were established through analyses of multivariable logistic regression and the receiver operating characteristic curve., Results: There were 4 variants (rs117896641, rs111686424, rs8101598, and rs74648298) achieving genome-wide significance that were identified. The logistic regression analysis revealed 7 significant risk factors: increasing zPRS, decreasing age, men, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid arthritis, and peripheral vascular disease. The areas under the receiver operating characteristic curve were 0.628 and 0.708 when zPRS (model 1) and nongenetic covariates (model 2) were used as predictors, respectively. The areas under the receiver operating characteristic curve increased to 0.76 when both zPRS and nongenetic covariates (model 3) were used as predictors. A risk-prediction nomogram was constructed based on model 3 to visualize the relative effect of statistically significant covariates on the risk of SSI and predict the probability of developing SSI. Age and zPRS were the top 2 covariates that contributed to the risk, with younger age and higher zPRS associated with higher risks., Conclusions: Our GWAS identified 4 novel variants that were significantly associated with susceptibility to SSI following TKA. Integrating genome-wide zPRS with nongenetic risk factors improved the performance of the model in predicting SSI., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sepsis constitutes a condition that involves life-threatening organ dysfunction induced by severe infection. This nested case-control study investigated risk factors for severe sepsis and whether antipsychotic use is associated with severe sepsis risk in patients with schizophrenia, a topic that has not been comprehensively explored in previous studies., Methods: We selected 39,432 patients with schizophrenia aged between 15 and 65 years from Taiwan's Psychiatric Inpatient Medical Claims database for the period 2000-2012. The case group comprised patients with severe sepsis after their first psychiatric admission ( n  = 1382). The case and control groups were randomly matched (1:4) by age, sex and first psychiatric admission (year) and finally comprised 1382 and 5528 individuals, respectively. We employed multivariable conditional logistic regression to identify (1) risk factors (physical illnesses and nonpsychiatric medications) and (2) antipsychotic-severe sepsis associations., Results: Higher numbers of psychiatric admissions and physical illnesses such as delirium, cerebrovascular disease and cancer were significantly associated with a higher risk of severe sepsis. Furthermore, severe sepsis was associated with the use of antithrombotic agents, systemic corticosteroids and agents targeting the renin-angiotensin system. Clozapine (adjusted risk ratio = 1.65) and quetiapine (adjusted risk ratio = 1.59) use were associated with an increased risk of severe sepsis. The use of more than one antipsychotic drug could further increase this risk., Conclusion: Several physical illnesses and nonpsychiatric medications increase the risk of severe sepsis in patients with schizophrenia. Specifically, clozapine or quetiapine use significantly increased the risk of severe sepsis in these patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Objectives: Ketamine can induce persisting psychosis in a subset of individuals who use it chronically and heavily. Previously, we found that the psychopathology and cognitive impairments in patients with ketamine dependence (KD) exhibiting persistent psychosis (KPP) bear resemblances with schizophrenia, albeit with less severity in those with no persistent psychosis (KNP). Furthermore, we also showed that patients with KD had higher blood levels of neurofilament light chain (NFL), a biomarker for neuroaxonal injury, compared to healthy controls. In this study, we aimed to investigate the differences in NFL levels between patients with KPP and KNP while comparing the levels of individuals with schizophrenia and healthy controls., Methods: We enrolled 64 treatment-seeking ketamine-dependent patients (53 with KNP and 11 with KPP), 37 medication-free patients with schizophrenia, and 80 healthy controls. Blood NFL levels were measured by single molecule array immunoassay., Results: NFL levels were highest in the KPP subgroup, followed by the KNP subgroup, and then the schizophrenia and control groups (mean ± SD: 24.5 ± 24.7, 12.9 ± 10.9, 9.2 ± 12.2, and 6.2 ± 2.2 pg/mL, respectively), with no significant difference observed between the schizophrenia and control groups., Conclusions: We found that KD is associated with higher NFL levels compared to schizophrenia, with the KPP subgroup showing the most consistent alterations. The observation of accentuated neuroaxonal pathology in individuals with KPP implies that this clinical manifestation is associated with a specific neurobiological phenotype, despite prior evidence suggesting syndromal similarity between schizophrenia and KPP., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abnormal vascular smooth muscle cell (VSMC) proliferation and migration play crucial roles in neointimal hyperplasia and restenosis progression in response to stimulation with various inflammatory cytokines, such as platelet-derived growth factor-BB (PDGF-BB) and tumour necrosis factor-α (TNF-α). Hydroxygenkwanin (HGK) exerts remarkable anti-inflammatory, antitumour, antiproliferative and antimigratory effects. The aim of the study was to elucidate the therapeutic effect and regulatory mechanism of HGK on neointimal hyperplasia. The results showed that HGK inhibited the abnormal proliferation, migration, and inflammation of PDGF-BB- or TNF-α-treated VSMCs through regulation of the PDK1/AKT/mTOR pathway. In addition, HGK promoted circulating endothelial progenitor cell (EPC) chemotaxis. In an in vivo assay, HGK dramatically enhanced re-endothelization and reduced neointimal hyperplasia after femoral artery denudation with a guide wire in mice. These results suggest that HGK can serve as a therapeutic target drug or a functional food supplement for the treatment of restenosis., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Genetic causes are often overlooked in patients with epilepsy of unknown etiology, particularly in adults. We aimed to evaluate clinical features of genetic epilepsy and the utility of genetic testing., Methods: We retrospectively screened consecutive unrelated adult epilepsy patients at an epilepsy clinic from April 2022 to May 2023. Patients with unknown etiology or special brain lesions were classified as unexplained epilepsy. In them, patients with young-onset seizures or family history of seizures who were recommended for and ultimately underwent genetic testing using either panel next-generation sequencing (NGS) or whole-exome sequencing (WES) were enrolled. A definite or probable genetic diagnosis was established through genotype-phenotype correlation. We compared the demographic characteristics between genetic epilepsy and other etiologies., Results: Of the 374 adult epilepsy patients, 258 were classified as unexplained epilepsy, 129 were suspected of having genetic epilepsy due to young-onset seizures or a positive family history, 33 underwent genetic testing; 13 harbored variants classified as pathogenic, and 6 reached a definite genetic diagnosis, resulting in a yield of 18%. Among the 27 patients without a definite genetic diagnosis, 7 had a nongenetic structural etiology. Patients with genetic etiology exhibited greater multisystem involvement particularly multiple structural anomalies and early childhood-onset seizures, but wasn't directly correlated with young-onset seizures or a positive family history. The diagnostic yield was comparable between panel NGS and WES., Significance: In adult patients with unexplained epilepsy, genetic epilepsy is more associated with multisystem involvement and multiple structural anomalies but not family history of seizures or young-onset seizures., (© 2024 International League Against Epilepsy.)

Fine-grain copper (Cu) films (grain size: 100.36 nm) with a near-atomic-scale surface (0.39 nm) were electroplated. Without advanced post-surface treatment, Cu-Cu direct bonding can be achieved with present-day fine-grain Cu films at 130℃ in air ambient with a minimum pressure of 1 MPa. The instantaneous growth rate on the first day is 164.29 nm d -1 . Also, the average growth rate (∆ R /∆ t ) is evaluated by the present experimental results: (i) 218.185 nm d -1 for the first-day period and (ii) 105.58 nm d -1 during the first 14-day period. Ultrafast grain growth and near-atomic-scale surface facilitate grain boundary motion across the bonding interface, which is the key to achieve Cu-Cu direct bonding at 130℃ in air ambient., Competing Interests: We declare we have no competing interests., (© 2024 The Author(s).)

Internal photoemission or hot-electron injection (HEJ) occurring at the metal-semiconductor (MS) Schottky interface has shown great promise in sub-bandgap photodetection and photovoltaics. In this paper, we put forward a plasmonic metagrating-interlayer-semiconductor (PMIS) structure that can significantly enhance the photon-to-electron conversion efficiency of HEJ-based optoelectronic devices. Thanks to the effect of image force-induced barrier lowering, a metal-interlayer-semiconductor (MIS) heterojunction with an ultrathin 2D material interlayer can considerably facilitate the hot electron transport across the Schottky barrier, resulting in a high internal quantum efficiency (IQE). Meanwhile, nanopatterning the MIS heterojunction into the plasmonic metagrating enables high optical absorption such that the device's external quantum efficiency (EQE) can be nearly equal to its IQE. In addition, this device can be wavelength- and polarization-selective by tailoring the geometry and dimensions of plasmonic metagrating, thereby paving a promising path toward bandgap-independent photodetection, energy harvesting, and photocatalysis.

This study aims to discuss the identification of the C1 nerve root as an effective surgical approach to successfully locate the shunting point of craniocervical junction spinal dural arteriovenous fistula (CCJ-SDAVF) intraoperatively. This study included all patients with CCJ-SDAVF who underwent surgical treatment using the far-lateral transcondylar approach at a single institution from January 2017 to June 2023. Data on patient demographics, clinical and angiographic characteristics of CCJ-SDAVF, surgical details, and treatment outcomes were collected. Follow-up assessments were conducted for all patients until December 31, 2023. The study included a total of 7 patients, comprising 5 men(71.4%) and 2 women (28.6%), with an average age of 57.6 years. Among them, 4 patients (57.1%) developed diffuse subarachnoid hemorrhage(SAH), while 2 patients (28.6%) experienced progressive cervical myelopathy. The shunting points of all CCJ-SDAVFs, which exhibited engorged veins, were identified next to the C1 root. Complete obliteration of CCJ-SDAVFs was successfully achieved in all patients, as confirmed by postoperative angiography one month later. No recurrent CCJ-SDAVFs were observed two years after the operation. Among the patients, 5 (71.4%) experienced good functional recovery, as indicated by an mRS score ranging from 0 to 1, while the remaining 2 patients (28.6%) showed incomplete functional recovery. The surgical interruption of CCJ-SDAVFs is the preferred treatment option, given its high obliteration rate and favorable functional recovery outcomes. We advocate the identification of C1 spinal nerve root as a crucial surgical step to identify the shunting points of CCJ- SDAVFs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A decrease in the levels of low-density lipoprotein receptors (LDLRs) leads to the accumulation of LDL cholesterol (LDL-C) in the bloodstream, resulting in hypercholesterolemia and atherosclerotic cardiovascular diseases. Increasing the expression level or inducing the activity of LDLR in hepatocytes can effectively control hypercholesterolemia. Proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, primarily produced in the liver, promotes the degradation of LDLR. Inhibiting the expression and/or function of PCSK9 can increase the levels of LDLR on the surface of hepatocytes and promote LDL-C clearance from the plasma. Thus, targeting PCSK9 represents a new strategy for developing preventive and therapeutic interventions for hypercholesterolemia. Currently, monoclonal antibodies are used as PCSK9 inhibitors in clinical practice. However, the need for oral and affordable anti-PCSK9 medications limits the perspective of choosing PCSK9 inhibitors for clinical usage. Emerging research reports have demonstrated that natural phytochemicals have efficacy in maintaining cholesterol stability and regulating lipid metabolism. Developing novel natural phytochemical PCSK9 inhibitors can serve as a starting point for developing small-molecule drugs to reduce plasma LDL-C levels in patients. In this review, we summarize the current literature on the critical role of PCSK9 in controlling LDLR degradation and hypercholesterolemia, and we discuss the results of studies attempting to develop PCSK9 inhibitors, with an emphasis on the inhibitory effects of natural phytochemicals on PCSK9. Furthermore, we provide insight into the mechanisms of action by which the reported phytochemicals exert their potential PCSK9 inhibitory effects against hypercholesterolemia., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Tzu Chi Medical Journal.)