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Mi Ha Ju,1 Eun Jeong Jang,2 Sung Hwa Kang,2 Young Hoon Roh,2 Jin Sook Jeong,1,* Song-Hee Han1,* 1Department of Pathology, Dong-A University College of Medicine, Busan, Republic of Korea; 2Department of Surgery, Dong-A University College of Medicine, Busan, Republic of Korea*These authors contributed equally to this workCorrespondence: Song-Hee Han, Department of Pathology, Dong-A University College of Medicine, 26, Daesingongwon-ro, Seo-gu, Busan, 49201, Republic of Korea, Tel +82-51-240-2863, Fax +82-51-240-7396, Email pshsh625@gmail.comPurpose: The six-transmembrane epithelial antigen of prostate 4 (STEAP4) has been linked to tumor progression via its involvement in inflammatory responses, oxidative stress, and metabolism. However, STEAP4 has rarely been studied in hepatocellular carcinoma (HCC). We explored STEAP4 expression associated with tumor prognosis to understand its role in tumor biology in HCC.Patients and Methods: STEAP4 mRNA and protein expressions were primarily analyzed using bioinformatics tools based on The Cancer Genome Atlas database to understand the expression pattern, molecular mechanism, prognostic impact, and association with immune cell infiltration. We further investigated the association between STEAP4 protein expression and clinicopathological parameters and their predictive value in HCC patients using immunohistochemical staining of tissue microarrays.Results: The expression of STEAP4 mRNA and protein in HCC tissues was significantly lower than in normal liver tissues. Reduced expression of STEAP4 was linked to advanced HCC stages, poor recurrence-free survival (RFS), and overall survival. Furthermore, reduced STEAP4 expression was a significant predictor of worse RFS in univariate and multivariate analyses in the immunohistochemical cohort. GO, KEGG, and GSEA analyses revealed that STEAP4 is related to numerous biological processes and pathways, including drug metabolism, DNA replication, RNA metabolism, and immune response. In terms of the immune system, the decreased level of STEAP4 was correlated with the immunosuppressive microenvironment.Conclusion: Our data indicated that reduced STEAP4 expression was significantly associated with tumor aggressiveness and poor prognosis, possibly because of its link to various biological processes and induction of HCC immune evasion. Therefore, STEAP4 expression may serve as a potential prognostic biomarker for cancer progression and immunity, as well as a therapeutic target in HCC.Keywords: immunohistochemistry, bioinformatics, Hepatocellular carcinoma, prognostic factor

RyungA Kang,1,* Seungwon Lee,1,* Gaab Soo Kim,1 Ji Seon Jeong,1 Mi Sook Gwak,1 Jong Man Kim,2 Gyu-Seong Choi,2 Yoon Jee Cho,1 Justin Sangwook Ko1 1Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 2Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea*These authors contributed equally to this workCorrespondence: Justin Sangwook KoDepartment of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon ro, Gangnam gu, Seoul, 06351, KoreaTel +82-2-3410-2454Fax +82-2-3410-0361Email jsko@skku.eduPurpose: Ultrasound-guided fascial plane blocks, including the erector spinae plane (ESP) and quadratus lumborum (QL) blocks, provide effective postoperative abdominal analgesia. However, there is limited evidence on the analgesic efficacy of ESP and QL blocks after liver surgery. Therefore, we aimed to compare the cumulative opioid consumption between the ESP and QL blocks in patients with hepatocellular carcinoma undergoing laparoscopic liver resection.Patients and Methods: Eighty-eight patients scheduled to undergo laparoscopic liver resection were randomized to receive bilateral single injection of ESP block at T8 (ESP group) or bilateral single injection of posterior QL block (QL group; 20 mL of 0.375% ropivacaine for each side, ie, total 150 mg of ropivacaine), in addition to intravenous (IV) fentanyl patient-controlled analgesia and multimodal analgesia. The primary outcome was cumulative opioid consumption over the first 24 h, expressed as IV morphine equivalents. Secondary outcomes included serial plasma ropivacaine concentrations, pain scores, time to first flatus, and Quality of Recovery-15 scores.Results: Eighty-five patients were analyzed (ESP group, n = 42; QL group, n = 43). Cumulative 24-h opioid consumption was similar between the ESP and QL groups (41.4 ± 22.6 mg vs 44.2 ± 20.0 mg, mean difference (QL-ESP), 2.8 mg, 95% confidence interval, − 6.4 to 12 mg, p > 0.99). There were no significant differences in resting pain scores at 24, 48 and 72 h postoperatively or recovery outcomes. The peak plasma ropivacaine concentration 30 min after injection was significantly higher in the ESP group (1.5 ± 0.3 μg/mL) than in the QL group (1.3 ± 0.5 μg/mL, p = 0.035); however, both were lower than the arterial threshold value of systemic toxicity (4.3 μg/mL).Conclusion: ESP and QL blocks provided similar postoperative analgesia in patients undergoing laparoscopic liver resection.Keywords: regional anesthesia, erector spinae plane block, laparoscopic liver resection, quadratus lumborum block, ropivacaine

Doyeon Kim,1,* Ji Seon Jeong,1* Huigyeong Park,1 Ki-Sun Sung,2 Soo Joo Choi,1 Mi Sook Gwak,1 Gaab Soo Kim,1 Tae Soo Hahm,1 Justin Sangwook Ko11Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 2Department of Orthopedics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea*These authors contributed equally to this workBackground: Dexmedetomidine is widely used for conscious sedation in patients undergoing lower-extremity surgery under regional anesthesia. We evaluated the postoperative analgesic effects of intravenous dexmedetomidine given during ankle surgery under spinal anesthesia.Methods: Forty-three participants underwent repair of lateral angle ligaments under spinal anesthesia. For sedation during surgery, participants were allocated to a dexmedetomidine group (n=22) that received a loading dose of 1 mcg.kg−1, over 10 min, followed by a maintenance dose of 0.2–0.7 μg.kg−1,.h−1,; and a propofol group (n=21) that received an effective site concentration of 0.5–2.0 μg.mL−1, via target-controlled infusion. The primary outcome was the postoperative, cumulative, intravenous (IV) morphine equivalent dose delivered via IV patient-controlled anesthesia (PCA) and rescue analgesic consumption in the first 24 h after surgery. We recorded sensory and motor block durations.Results: The postoperative IV morphine equivalent dose was 14.5 mg (0.75–31.75 mg) in the dexmedetomidine group compared to 48.0 mg (31.5–92.5 mg) in the propofol group (median difference, 33.2 mg; 95% confidence interval, 21.0–54.8 mg; P

Hae Hyuk Jung, Ji In Park, Jin Seon Jeong Department of Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Gangwon-do, South Korea Purpose: The purpose of this study was to assess diabetes incidence and all-cause mortality according to baseline body mass index (BMI) and to compare relative risks of mortality associated with incident diabetes across various BMI classes in a cohort of South Korean adults.Patients and methods: Based on data from the National Health Insurance database of Korean individuals aged 40–79 years without preexisting diabetes, we calculated BMI at the baseline health examination. We estimated the relative risk of mortality associated with incident diabetes using time-dependent Cox models and considering the time of diabetes diagnosis.Results: We noted 29,307 incident diabetes cases and 22,940 deaths during an 8-year follow-up of the initial cohort (n=436,692) and 73,756 incident diabetes cases and 57,556 deaths during a 10-year follow-up of the replication cohort (n=850,282). Regarding all-cause mortality, time-dependent Cox models revealed statistically significant interactions between diabetes status and baseline BMI class (P=0.018 and P

Background: Hypoxia influences tumor growth by inducing angiogenesis and genetic alterations. Hypoxia-inducible factor 1alpha (HIF-1alpha), p53, and vascular endothelial growth factor (VEGF) are all important factors in the mechanisms inherent to tumor progression. In this work, we have investigated the clinicopathologic significance of HIF-1alpha, p53, and VEGF expression and preoperative serum VEGF (sVEGF) level in gastric cancer.We immunohistochemically assessed the HIF-1alpha, p53, and VEGF expression patterns in 114 specimens of gastric cancer. Additionally, we determined the levels of preoperative serum VEGF (sVEGF).Results: The positive rates of p53 and HIF-1alpha (diffuse, deep, intravascular pattern) were 38.6% and 15.8%, respectively. The VEGF overexpression rate was 57.9%. p53 and HIF-1alpha were correlated positively with the depth of invasion (P = 0.015, P = 0.001, respectively). Preoperative sVEGF and p53 levels were correlated significantly with lymph node involvement (P = 0.010, P = 0.040, respectively). VEGF overexpression was more frequently observed in the old age group (> or = 60 years old) and the intestinal type (P = 0.013, P = 0.014, respectively). However, correlations between preoperative sVEGF level and tissue HIF-1alpha, VEGF, and p53 were not observed. The median follow-up duration after operation was 24.5 months. HIF-1alpha was observed to be a poor prognostic factor of disease recurrence or progression (P = 0.002).Conclusion: p53, HIF-1alpha and preoperative sVEGF might be markers of depth of invasion or lymph node involvement. HIF-1alpha expression was a poor prognostic factor of disease recurrence or progression in patients with gastric cancers. [ABSTRACT FROM AUTHOR]

Multicollinearity, characterized by significant co-expression patterns among genes, often occurs in high-throughput expression data, potentially impacting the predictive model's reliability. This study examined multicollinearity among closely related genes, particularly in RNA-Seq data obtained from embryoid bodies (EB) exposed to 5-fluorouracil perturbation to identify genes associated with embryotoxicity. Six genes-Dppa5a, Gdf3, Zfp42, Meis1, Hoxa2, and Hoxb1-emerged as candidates based on domain knowledge and were validated using qPCR in EBs perturbed by 39 test substances. We conducted correlation studies and utilized the variance inflation factor (VIF) to examine the existence of multicollinearity among the genes. Recursive feature elimination with cross-validation (RFECV) ranked Zfp42 and Hoxb1 as the top two among the seven features considered, identifying them as potential early embryotoxicity assessment biomarkers. As a result, a t test assessing the statistical significance of this two-feature prediction model yielded a p value of 0.0044, confirming the successful reduction of redundancies and multicollinearity through RFECV. Our study presents a systematic methodology for using machine learning techniques in transcriptomics data analysis, enhancing the discovery of potential reporter gene candidates for embryotoxicity screening research, and improving the predictive model's predictive accuracy and feasibility while reducing financial and time constraints., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Individuals are exposed to a wide arrays of hazardous chemicals on a daily basis through various routes, many of which have not undergone comprehensive toxicity assessments. While traditional developmental toxicity tests involving pregnant animals are known for their reliability, they are also associated with high costs and time requirements. Consequently, there is an urgent demand for alternative, cost-efficient, and rapid in vitro testing methods. This study aims to address the challenges related to automating and streamlining the screening of early developmental toxicity of chemicals by introducing a mouse embryoid body test (EBT) model in a 384-ultra low attachment well format. Embryoid bodies (EBs) generated in this format were characterized by a spontaneous differentiation trajectory into cardiac mesoderm by as analyzed by RNA-seq. Assessing prediction accuracy using reference compounds suggested in the ICH S5(R3) guideline and prior studies resulted in the establishment of the acceptance criteria and applicability domain of the EBT model. The results indicated an 84.38% accuracy in predicting the developmental toxicity of 23 positive and 9 negative reference compounds, with an optimized cutoff threshold of 750 µM. Overall, the developed EBT model presents a promising approach for more rapid, high-throughput chemical screening, thereby facilitating well-informed decision-making in environmental management and safety assessments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sageretia thea, a notable species within the mock buckthorn genus, is recognized for its intriguing biogeographical distribution and diverse medicinal properties. Despite this significance, genomic studies on S. thea are still in the nascent stages. We present the first chromosome-level genome assembly of S. thea that was generated using a combination of Oxford Nanopore long-read and Illumina short-read sequencing technologies complemented by Pore-C chromatin conformation capture. The genome assembly had a size of 197.8 Mb with 12 chromosomal scaffolds and a scaffold N50 length of 15.9 Mb. A total of 25,434 protein-coding genes were identified and functionally annotated, and the gene model indicated 96.5% complete eukaryotic BUSCOs. Additionally, orthologous gene profiling and synteny analysis were performed to elucidate the evolutionary relationships within the Rhamnaceae family and Rosales. This high-quality chromosomal genome is the first genomic view of S. thea, which will serve as the basis for future studies on its biological and medicinal properties, and evolutionary history., (© 2024. The Author(s).)

Bisphenol A (BPA), a widespread environmental contaminant, poses concerns due to its disruptive effects on physiological functions of the uterine endometrium. In contrast, melatonin (MT) and Resveratrol (RSV) are under scrutiny for their potential protective roles against BPA-induced damage. For the efficacy and ethical concerns in the animal test, endometrial organoids, three-dimensional models mimicking endometrium, serve as crucial tools for unraveling the impact of environmental factors on reproductive health. This study aimed to comprehensively characterize the morphological, molecular and metabolic responses of porcine endometrial organoids to BPA and assess the potential protective effects of MT and RSV. Porcine uteri were prepared, digested with collagenase, mixed with Matrigel, and incubated at 38°C with 5 % CO 2 . Passaging involved dissociation through trypsin-EDTA treatment and subculturing. The culture medium was refreshed every 2-3 days. To investigate the environmental impact on reproductive health, endometrial organoids were treated with BPA (0.5 µM), MT (with/without BPA at 0.1 µM), and/or RSV (10 µM). Various molecular screening using gene expression, western blotting, immunofluorescence staining, and metabolites profiling were assessed the effects of BPA, MT, and RSV in terms of cell viability, morphology, reproductivity, and metabolism alteration in the endometrial organoids. As expected, BPA induced structural and molecular disruptions in organoids, affecting cytoskeletal proteins, Wnt/β-catenin signaling, and epithelial/mesenchymal markers. It triggered oxidative stress and apoptotic pathways, altered miRNA expression, and disrupted the endocannabinoid system. The level of glucose, galactose, and essential amino acids were increased or decreased by approximately 1.5-3 times in BPA-treated groups compared to the control groups (p-value < 0.05), indicating metabolic changes. Moreover, MT and RSV treated groups exhibited protective effects, mitigating BPA-induced disruptions across multiple pathways. For the first time, our study models endometrial organoids, advancing understanding of environmental impacts on reproductive health., 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 Inc. All rights reserved.)

Turmeric (Curcuma longa L.) extract (CLE) has been shown to elicit several pharmacological properties and is widely used in Asian traditional medicine. Herein, we assessed the impact of CLE on airway inflammation in BALB/c mice and A549 cells to clarify the underlying mechanism. An asthmatic mouse model was established by administering ovalbumin (OVA). CLE (100 or 300 mg/kg/day) was orally administered daily from days 18 to 23, with dexamethasone (3 mg/kg/day) used as the positive control. Human airway epithelial cells, A549, were stimulated using recombinant tumor necrosis factor-α. The CLE100 and CLE400 groups exhibited a significant downregulation in eosinophil counts, cytokine levels, and immunoglobulin-E levels. Moreover, CLE administration dose-dependently suppressed oxidative stress and airway inflammation in the lung tissue. CLE administration inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and the expression and activity of matrix metalloproteinase (MMP)-9. In vitro, CLE treatment reduced mRNA levels of proinflammatory cytokines, MAPK phosphorylation, and the expression and activity of MMP-2 and MMP-9. Additionally, 50 µg/mL CLE and 2.5 µg/mL curcumin showed similar anti-inflammatory effects. Collectively, our findings revealed that CLE could suppress airway inflammation in asthmatic mice and A549 cells via oxidative stress-driven MAPK/MMPs signaling, suggesting that CLE could be developed as a potential treatment option for patients with asthma., 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.)

Our case highlights the importance of follow-up. Previous meta-analysis has shown that patients with sub-centimetre nodules may have extended follow-up intervals before requiring intervention, unlike those with larger nodules exceeding 1 cm. However, referring to our case, we can see the importance of regular and dense follow-up., Competing Interests: None declared., (© 2024 The Author(s). Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

Programmed cell death-ligand 1 (PD-L1) expression is a predictive biomarker for response to immune checkpoint inhibitor in head and neck squamous cell carcinoma. Given the range of antibodies and platforms for PD-L1 testing, it is essential to understand the performance of different staining and scoring methods. PD-L1 expression in 156 head and neck mucosal squamous cell carcinoma (HNmSCC) cases at Asan Medical Center was assessed using 106 tissue microarray (TMA) cores and 50 whole slides. Three standardised PD-L1 assays (22C3 pharmDx, SP263, and 28-8 pharmDx) and one laboratory-developed test (22C3 LDT) were evaluated: the combined positive score (CPS) with ≥1, ≥20, and ≥50 cut-offs, and the tumour positive score (TPS) with ≥1%, ≥20%, ≥50% cut-offs. Concordance on a continuous scale among the assays was good to excellent for CPS [intraclass correlation coefficient (ICC) range 0.73-0.94] and TPS (ICC range 0.70-0.94) and in both TMA and whole slides cohorts. Stratification by variable cut-offs demonstrated moderate to good agreement among most assays, as analysed by Gwet's AC1. PD-L1 expression was significantly correlated with tumour location using the 22C3 pharmDx assay (CPS, p=0.014; TPS, p=0.033). Notable concordance was found among PD-L1 assays, suggesting their potential interchangeability in HNmSCC., (Copyright © 2024 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

The recent emergence of innovative learning spaces, Future Classroom Lab (FCL), provides educators the use of physical learning spaces (to research, interact, exchange, develop, create, and present) and diverse technological tools to work according to active methodologies. Learners become more active in the learning process with the introduction of innovative learning environments that enable the application of interdisciplinary STEAM methodology and foster the development of 21st century competences. This study aims to uncover the probable link between application active and gamified STEAM educational interventions in the FCL and Pre-Service Teachers' (PSTs) affective domain. The findings obtained showed statistically significant variations and, therefore, positive effects on the PSTs' affective domain (self-efficacy, attitude, and emotion) after performing the intervention. The sample consisted of a total of 54 PSTs enrolled in the second year of Primary Education. Limited studies regarding the affective domain in the FCL were found, which restricted the comparison with prior research. This study has several implications, such as the introduction of innovative educational proposals to PSTs at the university level and, consequently, the implementation of similar interventions in elementary schools. This research intended to reveal how the different variables work as a support system for students' learning process in mathematics and science disciplines., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Fritillariae thunbergii Bulbus (FTB), a member of the Liliaceae family, has a long history of use in many herbal formulations for traditional and modern clinical applications to treat various infections and inflammation. To understand FTB's diverse physiochemical properties, it is important to determine the pharmacokinetic properties of its active constituents, the steroidal alkaloids. The aim of the present study was to investigate the pharmacokinetic alterations of the alkaloids, the active components of FTB, in the presence of colitis. A single oral dose of FTB (1 g/kg) was treated to a 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis rat model to assess whether the colitis condition could influence the pharmacokinetics of the major alkaloids present in FTB. Among the four major alkaloids, peimisine exhibited a significantly increased systemic exposure, approximately five times higher, under the colitis condition compared with the normal state. Meanwhile, peimine, peiminine, and sipeimine exhibited shorter half-lives in the DNBS group without significant changes in systemic absorption. As herbal medicine may contain active substances with different or opposing efficacies, careful consideration of pharmacokinetic changes in individual components due to diseases is necessary. Further experiments on peimisine are required to ensure the effectiveness and safety of FTB's clinical application in the presence of colitis.

Pulmonary paragonimiasis may be accompanied by a rare infectious disease, such as cryptococcal pneumonia. To our knowledge, this is the first case ever reported in the English literature., Competing Interests: None declared., (© 2024 The Author(s). Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

We report the synthesis and characterization of novel antimony(III) complexes: Sb(mpa) 3 ( 1 ), Sb(mmpa) 3 ( 2 ), Sb(mdpa) 3 ( 3 ), Sb(epa) 3 ( 4 ), Sb(empa) 3 ( 5 ), and Sb(edpa) 3 ( 6 ) (mpa = N -methoxypropanamide, mmpa = N -methoxy-2-methyl-propanamide, mdpa = N -methoxy-2,2-dimethylpropanamide, epa = N -ethoxypropanamide, empa = N -ethoxy-2-methylpropanamide, and edpa = N -ethoxy-2,2-dimethylpropanamide, via a salt-elimination reaction with SbCl 3 and sodium-substituted carboxamide. The molecular structure of 6 revealed the formation of a homoleptic conformer with a highly distorted pentagonal bipyramidal geometry, as determined by X-ray crystallography. Thermogravimetric analysis showed excellent volatility at elevated temperatures, with complex 4 displaying the lowest residual mass of 0.16% at 500 °C. For complexes 4 , 5 , and 6 , the temperature at a vapor pressure of 1 Torr and the enthalpy of vaporization were estimated to be 58, 64, and 45 °C and 83.31, 103.58, and 99.93 kJ/mol, respectively., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Dried Blood Spots (DBS) revolutionize therapeutic drug monitoring using LC-MS for the precise quantification of cardiovascular drugs (CDs), enabling personalized treatment adapted to patient-specific pharmacokinetics with minimal invasiveness. This study aims to achieve simultaneous quantification of eight CDs in DBS, overcoming physicochemical challenges. A two-step protein precipitation method was used for simple and precise sample preparation. The drugs were analyzed using LC-MS/MS in ESI positive-ion mode, showing high sensitivity and linearity, with a correlation coefficient (r 2 ) exceeding 0.999, after being separated on a reversed-phase chromatography by gradient elution of DW-acetonitrile containing 0.1 % formic acid + 2 mM ammonium formate. The validation results indicate good selectivity, with no observed matrix effect and carry-over. The intra- and inter-day accuracy and precision were within 6 % for most drugs, except for digoxin and deslanoside at low therapeutic levels where the variation was within 20 %. Stability tests confirmed suitable DBS handling and storage conditions, indicating drug stability for at least 30 days at room temperature. The analysis of whole spot has demonstrated remarkable precision and reliability in all target drugs. The analysis of 3 mm internal diameter discs, punched in and out of DBS, presumed to contain 3 µL of blood, showed acceptable accuracy for most drugs, with less polar drugs like digoxin and deslanoside showing lower accuracy, indicating a need for further correction due to non-uniform drug distribution. Consequently, the developed LC-MS/MS method enables the quantification of multiple CDs in a single DBS analysis, while suggesting the potential for accuracy-based analysis., 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 B.V. All rights reserved.)

Ageratum conyzoides , an annual herbaceous plant that inhabits tropical and subtropical regions, has been traditionally used in Asia, Africa, and South America for phytotherapy to treat infectious and inflammatory conditions. However, the pharmacological effects of standardized ethanolic extract of Ageratum conyzoides (ACE) on benign prostatic hyperplasia (BPH) remain unexplored. The objective of this research is to examine the potential physiological impacts of ACE, a traditionally utilized remedy for inflammatory ailments, in a rat model with BPH induced by testosterone propionate (TP). Rats were subcutaneously administered TP (3 mg/kg) to induce BPH and concurrently orally administered ACE (20, 50, and 100 mg/kg) daily for 42 days. ACE markedly improved BPH characteristics, including prostate weight, prostate index, and epithelial thickness, while also suppressing androgens and related hormones. The findings were supported by a decrease in androgen receptor and downstream signals associated with BPH in the prostate tissues of the ACE groups. Furthermore, increased apoptotic signals were observed in the prostate tissue of the ACE groups, along with heightened detection of the apoptotic nucleus compared to the BPH alone group. These changes seen in the group that received finasteride were similar to those observed in this group. These findings suggest that ACE shows promise as an alternative phytotherapeutic agent for treating BPH.

Introduction: Cissus quadrangularis is a vining plant widely used as a traditional herbal remedy for various ailments. In this study, the therapeutic effects of C. quadrangularis extract (CQR-300) on type 2 diabetes mellitus (T2DM) were investigated in a leptin receptor-mutated db/db mouse model. Methods: CQR-300 was orally administered to db/db mice (n = 6/group) at different doses (50, 100, and 200 mg/kg) for 8 weeks. Blood glucose levels and oral glucose tolerance were assessed using the AccuCheck glucometer. Enzyme-linked immunosorbent assay was performed to evaluate insulin and hemoglobin A1c (HbA1c) levels in the blood of db/db mice. Liver and pancreatic tissues from db/db mice were examined by hematoxylin and eosin (H&E) and immunohistochemical staining. The protein levels of gluconeogenesis-, lipogenesis-, and oxidative stress-related factors were evaluated using western blotting. Results and discussion: CQR-300 treatment effectively reduced body weight, blood glucose, and insulin levels. HbA1c levels were increased by leptin receptor mutation. Additionally, in the oral glucose tolerance tests, the CQR-300 treated group had a faster blood glucose recovery rate than the db/db group. H&E and Oil red-O staining of the liver showed decreased lipid accumulation in the CQR-300 treated group than the db/db group. Western blot analysis confirmed that CQR-300 effectively inhibited gluconeogenesis, lipogenesis, and oxidative stress-related factors. Our findings suggest that CQR-300 has the potential to be used as a T2DM supplement., Competing Interests: Authors D-RL, B-KC were employed by NUON Co., Ltd. Authors J-HL were employed by EveryH Co., Ltd. The remaining 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 Kim, Jeong, Kim, Chung, Kim, Lee, Choi, Lim, Ko and Kim.)

Peritoneal dialysis is a common treatment for end-stage renal disease, but complications often force its discontinuation. Preventive treatments for peritoneal inflammation and fibrosis are currently lacking. Cyclo(His-Pro) (CHP), a naturally occurring cyclic dipeptide, has demonstrated protective effects in various fibrotic diseases, yet its potential role in peritoneal fibrosis (PF) remains uncertain. In a mouse model of induced PF, CHP was administered, and quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry was employed to identify PF-related protein signaling pathways. The results were further validated using human primary cultured mesothelial cells. This analysis revealed the involvement of histone deacetylase 3 (HDAC3) in the PF signaling pathway. CHP administration effectively mitigated PF in both peritoneal tissue and human primary cultured mesothelial cells, concurrently regulating fibrosis-related markers and HDAC3 expression. Moreover, CHP enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while suppressing forkhead box protein M1 (FOXM1), known to inhibit Nrf2 transcription through its interaction with HDAC3. CHP also displayed an impact on spleen myeloid-derived suppressor cells, suggesting an immunomodulatory effect. Notably, CHP improved mitochondrial function in peritoneal tissue, resulting in increased mitochondrial membrane potential and adenosine triphosphate production. This study suggests that CHP can significantly prevent PF in peritoneal dialysis patients by modulating HDAC3 expression and associated signaling pathways, reducing fibrosis and inflammation markers, and improving mitochondrial function., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Although presepsin, a crucial biomarker for the diagnosis and management of sepsis, has gained prominence in contemporary medical research, its relationship with routine laboratory parameters, including demographic data and hospital blood test data, remains underexplored. This study integrates machine learning with explainable artificial intelligence (XAI) to provide insights into the relationship between presepsin and these parameters. Advanced machine learning classifiers provide a multilateral view of data and play an important role in highlighting the interrelationships between presepsin and other parameters. XAI enhances analysis by ensuring transparency in the model's decisions, especially in selecting key parameters that significantly enhance classification accuracy. Utilizing XAI, this study successfully identified critical parameters that increased the predictive accuracy for sepsis patients, achieving a remarkable ROC AUC of 0.97 and an accuracy of 0.94. This breakthrough is possibly attributed to the comprehensive utilization of XAI in refining parameter selection, thus leading to these significant predictive metrics. The presence of missing data in datasets is another concern; this study addresses it by employing Extreme Gradient Boosting (XGBoost) to manage missing data, effectively mitigating potential biases while preserving both the accuracy and relevance of the results. The perspective of examining data from higher dimensions using machine learning transcends traditional observation and analysis. The findings of this study hold the potential to enhance patient diagnoses and treatment, underscoring the value of merging traditional research methods with advanced analytical tools., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Obesity is associated with an increased incidence of asthma. However, the mechanisms underlying this association are not fully understood. In this study, we investigated the role of thioredoxin-interacting protein (TXNIP) in obesity-induced asthma. Asthma was induced by intranasal injection of a protease from Aspergillus oryzae in normal diet (ND)- or high fat diet (HFD)-fed mice to investigate the symptoms. We measured TXNIP expression in the lungs of patients with asthma and in ND or HFD asthmatic mice. To explore the role of TXNIP in asthma pathogenesis, we induced asthma in the same manner in alveolar type 2 cell-specific TXNIP deficient (TXNIP Cre ) mice. In addition, the expression levels of pro-inflammatory cytokines were compared based on TXNIP gene expression in A549 cells stimulated with recombinant human tumor necrosis factor alpha. Compared to ND-fed mice, HFD-fed mice had elevated levels of free fatty acids and adipokines, resulting in high reactive oxygen species levels and more severe asthma symptoms. TXNIP expression was increased in both, asthmatic patients and HFD asthmatic mice. However, in experiments using TXNIP Cre mice, despite being TXNIP deficient, TXNIP Cre mice exhibited exacerbated asthma symptoms. Consistent with this, in vitro studies showed highest expression levels of pro-inflammatory cytokines in TXNIP-silenced cells. Overall, our findings suggest that increased TXNIP levels in obesity-induced asthma is compensatory to protect against inflammatory responses., 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 B.V. All rights reserved.)

This study is the first to sequence the complete mitochondrial genome (mitogenome) of Perforatus perforatus Bruguière, 1789 (Balanomorpha: Balanidae). The 15,536-bp long P. perforatus mitogenome contained a typical set of animal mitochondrial genes, along with one control region. The P. perforatus mitogenome had an inverted gene block ( trnP - ND4L - ND4 - trnH - ND5 - trnF ) between trnS (gct) and trnT . This inverted gene block had been detected six species in three subfamilies of the Balanidae family (Balaninae, Acastinae and Megabalaninae), but our results show that it is also present in Concavinae, in which P. perforatus is included. The phylogenetic tree based on the concatenated sequences of the 13 protein-coding genes and two rRNA genes showed that P. perforatus is closely associated with Acasta sulcate and Balanus trigonus within Balanidae., Competing Interests: The authors report there are no competing interests to declare., (© 2024 Honam National Institute of Biological Resources. Published by Informa UK Limited, trading as Taylor & Francis Group.)

The management of neurological disorders heavily relies on neurotherapeutic drugs, but notable concerns exist regarding their possible negative effects on reproductive health. Traditional preclinical models often fail to accurately predict reprotoxicity, highlighting the need for more physiologically relevant systems. Organoid models represent a promising approach for concurrently studying neurotoxicity and reprotoxicity, providing insights into the complex interplay between neurotherapeutic drugs and reproductive systems. Herein, we have examined the molecular mechanisms underlying neurotherapeutic drug-induced reprotoxicity and discussed experimental findings from case studies. Additionally, we explore the utility of organoid models in elucidating the reproductive complications of neurodrug exposure. Have discussed the principles of organoid models, highlighting their ability to recapitulate neurodevelopmental processes and simulate drug-induced toxicity in a controlled environment. Challenges and future perspectives in the field have been addressed with a focus on advancing organoid technologies to improve reprotoxicity assessment and enhance drug safety screening. This review underscores the importance of organoid models in unraveling the complex relationship between neurotherapeutic drugs and reproductive health., 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 author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Abady, Jeong, Kwon, Assiri, Cho and Saadeldin.)

Background: Remimazolam is a short-acting benzodiazepine newly approved for the induction and maintenance of general anesthesia. Remimazolam emerges as an ideal drug for the neurosurgical population due to its rapid emergence, enabling early neurological assessment, and its ability to maintain perfusion pressure, which is crucial for preventing cerebral ischemia. However, the use of benzodiazepine has been associated with an increased risk of postoperative delirium (POD). There is currently limited evidence about the relationship between remimazolam-based total intravenous anesthesia (TIVA) and POD., Methods: In this double-blind, randomized, non-inferiority trial, we plan to include 696 adult patients with American Society of Anesthesiologists physical status class I to III, undergoing elective neurovascular surgery under general anesthesia. After informed consent, the patients will be randomized to receive either remimazolam or propofol-based TIVA with a 1:1 ratio. The primary outcome is the incidence of POD within 5 days after surgery. Secondary outcomes include subtypes, number of positive assessments and severity of POD, emergence agitation, intraoperative awareness and undesirable patient movement, intraoperative hypotension, and postoperative cognitive function. The data will be analyzed in modified intention to treat., Discussion: This trial will evaluate the effect of remimazolam on the development of POD compared to propofol anesthesia. The results of this trial will provide evidence regarding the choice of optimal anesthetics to minimize the risk of POD in neurosurgical patients., Trial Registration: The study protocol was prospectively registered at the Clinical trials ( https://clinicaltrials.gov , NCT06115031, principal investigator: Jiseon Jeong; date of first registration: November 2, 2023, before the recruitment of the first participant., (© 2024. The Author(s).)

This study aims to establish an LC-MS/MS method to simultaneously analyze 11 antiepileptic drugs with a particular focus on maintaining accuracy while reducing the number of isotope-labeled internal standards employed for cost-effectiveness. By applying a water/acetonitrile gradient elution containing 0.1 % formic acid and 2 mM ammonium formate as the mobile phase, optimal sensitivity for the target drugs could be obtained in positive ESI mode in LC-MS/MS. After optimizing various extraction techniques, extraction with 70 % acetonitrile was selected as it provided good recoveries (>93 %) for all targets without matrix effects. Accuracies within 3 % were achieved from the combination of six internal standards, while accuracies of 5 % and 10 % were obtained by reducing the number of internal standards to four and two, respectively, for more economical analysis. The accuracy of the established method was maintained in hyperglycemia, hyperlipidemia, and hyperalbuminemia sera, suggesting that it can be successfully applied to individual serum samples with various properties., 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 B.V. All rights reserved.)

Bisphosphonates are commonly used to treat osteoporosis. While renal toxicity is common with pamidronate and zoledronate, few ibandronate-related cases are reported. We describe a rare case of ibandronate-associated nephrotoxicity. An 88-year-old woman was admitted for edema. She had been receiving intravenous ibandronate treatment for postmenopausal osteoporosis and had no other diagnosed diseases. She was presented with proteinuria, hypoalbuminemia (1.9 g/dL), and an elevated serum creatinine level (1.8 mg/dL). Renal biopsy revealed podocyte disease, favoring a diagnosis of focal segmental glomerulosclerosis. She was treated with diuretics, tacrolimus, and fimasartan. Steroids were avoided due to severe osteoporosis. Three months later, the edema had subsided and the laboratory findings had improved (serum albumin 3.5 g/dL, serum creatinine 0.97 mg/dL). This case emphasizes the importance of careful monitoring of proteinuria and renal function during ibandronate treatment. In older adult patients, kidney biopsy and immunosuppressive treatment may be considered based on physical activity and underlying diseases.

Background: Non-alcoholic fatty liver disease (NAFLD) encompasses a heterogeneous spectrum ranging from simple steatosis to fibrosis and cirrhosis. Fibrosis, associated with long-term overall mortality and liver-related events, requires evaluation. Traditionally, liver biopsy has been the gold standard for diagnosing fibrosis. However, its invasive nature, potential complications, and sampling variability limit widespread use. Consequently, various non-invasive tests have been developed as alternatives for diagnosing fibrosis in NAFLD patients., Aim: This study aimed to compare the accuracy of non-invasive tests (NITs) and evaluate the diagnostic accuracy of acoustic radiation force impulse (ARFI), one of the point shear wave techniques, compared to conventional methods, assessing its effective role in diagnosis., Methods: This is a retrospective study; a total of 136 patients diagnosed with fatty liver disease through ultrasonography were enrolled. The anthropometric data of the patients were collected on the day of admission and blood tests, measurements of ARFI, and a point shear test were conducted using abdominal ultrasound; a biopsy was performed the following day. In addition, we calculated the aspartate aminotransferase-to-platelet ratio index (APRI) index based on four factors (FIB-4) and the NAFLD fibrosis score (NFS). Subsequently, we assessed the diagnostic accuracy of NITs within various subgroups based on the extent of obesity, steatosis, or NAFLD activity score., Results: ARFI has been shown to have the highest diagnostic value among various NITs, with AUROC values of 0.832, 0.794, 0.767, and 0.696 for ARFI, APRI, FIB-4, and NFS, respectively. In the morbidly obese subgroup, the AUROC values of ARFI, APRI, FIB-4, and NFS were 0.805, 0.769, 0.736, and 0.674. In the group with severe steatosis or non-alcoholic steatohepatitis (NASH), the AUROC values were 0.679, 0.596, 0.661, and 0.612, respectively, for severe steatosis and 0.789, 0.696, 0.751, and 0.691, respectively, for NASH., Conclusions: In conclusion, ARFI is not affected by various factors and maintains diagnostic accuracy compared to serum NITs. Therefore, we can recommend ARFI as a valuable diagnostic test to screen for advanced fibrosis in patients with NAFLD.

Practical application of lithium- and manganese-rich layered oxide cathodes has been hindered despite their high performance and low cost owing to high gas evolution accompanying capacity loss even in a conservative voltage window. Here, we control the surface structure and primary particle size of lithium- and manganese-rich layered oxide cathodes not only to enhance the electrochemical performance but also to reduce gas evolution. Sulfur-coated Fm3̅m/R3̅m double reduced surface layers and Mo doping dramatically reduce gas evolution, which entails the improvement of electrochemical performance. With the optimization, we prove that it is competitive enough to conventional high-nickel cathodes in the aspects of gas evolution as well as electrochemical performance in the conservative voltage window of 2.5-4.4 V. Our findings provide invaluable insights on the improvement of electrochemical performance and gas evolution properties in lithium- and manganese-rich layered oxide cathodes.

Study Objective: To investigate the analgesic efficacy of erector spinae plane block (ESPB) in major gynecologic surgery, expressed as cumulative opioid consumption 24 h after surgery., Design: A single-center, patient-assessor blinded, randomized controlled study., Setting: Samsung medical center (tertiary university hospital), between February 2022 to January 2023., Patients: Eighty-eight females undergoing major surgery with long midline incision for gynecologic malignancy., Interventions: Patients were randomly assigned to receive standard systemic analgesia (Control group) or ESPB (ESPB group). ESPB was performed bilaterally at the level of the 9th thoracic vertebra with a mixture of 20 mL of 0.5% ropivacaine and 100 μg of epinephrine., Measurements: The primary outcome was cumulative opioid consumption at 24 h postoperatively. Secondary outcomes included opioid consumption and pain severity during the 72 h after surgery. The variables regarding postoperative recovery and patient-centered outcomes were compared., Main Results: The mean cumulative opioid consumption 24 h after surgery was 35.8 mg in the ESPB group, which was not significantly different from 41.4 mg in the control group (mean difference, 5.5 mg; 95% CI -1.7 to 12.8 mg; P = 0.128). However, patient satisfaction regarding analgesia was significantly higher in the ESPB group compared with the control group at 24 h postoperative (median difference, -1; 95% CI -3 to 0; P = 0.038). There were no significant differences in the variables associated with postoperative recovery., Conclusion: ESPB did not reduce opioid consumption during the 24 h postoperative but attenuated pain intensity during the early period after surgery., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Korean red ginseng (KRG) is a product from ginseng roots, which is enriched with ginsenosides and has been utilized for a long time as an adaptogen to alleviate various physiological or disease conditions. While KRG is generally considered safe, conducting a thorough toxicological assessment of the spray-dried powder G1899 during the juvenile period is essential to establish its safety profile. This study aimed to assess the safety of G1899 during the juvenile period using Sprague-Dawley rats., Methods: Two studies were conducted separately: a juvenile toxicity study and a uterotrophic bioassay. To assess the potential toxicity at systemic, postnatal developmental, and reproductive levels, G1899 was orally gavaged once a day in post-weaning juvenile Sprague-Dawley (SD) rats at 0, 1250, 2500, or 5000 mg/kg/day. Estrogenicity was assessed by orally gavaging G1899 in immature female SD rats at 0, 2500, or 5000 mg/kg/day on postnatal days (PND) 19-21, followed by a uterotrophic bioassay. These studies were conducted in accordance with the Good Laboratory Practice (GLP) regulations and regulatory test guidelines., Results: Regarding juvenile toxicity, no abnormalities related to the G1899 treatment were observed in any group during the experiment. Moreover, no uterotrophic responses were observed in the dosed female group. Based on these results, the no observed adverse effect level (NOAEL) of G1899 was determined to be at least 5000 mg/kg/day for general systemic function, developmental/reproductive function, and estrogenic activity., Conclusion: Our results suggest that G1899 is not toxic to juveniles at doses of up to 5000 mg/kg/day., Competing Interests: Byung-Cheol Han and Eunji Kim are current employees of the Korea Ginseng Corporation that are responsible for the research and development of G1899. The others declare that there are no conflicts of interest., (© 2024 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Introduction: The anti-inflammatory effect of green tea extract (GTE) has been confirmed in asthmatic mice, however, the pharmacological mechanism is not fully elucidated., Methods: To investigate the therapeutic efficacy of GTE in asthma and identify specific pathways, murine model of allergic asthma was established by ovalbumin (OVA) sensitization and the challenge for 4 weeks, with oral treatment using GTE and dexamethasone (DEX). Inflammatory cell counts, cytokines, OVA-specific IgE, airway hyperreactivity, and antioxidant markers in the lung were evaluated. Also, pulmonary histopathological analysis and western blotting were performed. In vitro , we established the model by stimulating the human airway epithelial cell line NCI-H292 using lipopolysaccharide, and treating with GTE and mitogen-activated protein kinases (MAPKs) inhibitors., Results: The GTE100 and GTE400 groups showed a decrease in airway hyperresponsiveness and the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) compared to the OVA group. GTE treatment also reduced interleukin (IL)-13, IL-5, and IL-4 levels in the BALF, and OVA-specific immunoglobulin E levels in the serum compared to those in the OVA group. GTE treatment decreased OVA-induced mucus secretion and airway inflammation. In addition, GTE suppressed the oxidative stress, and phosphorylation of MAPKs, which generally occurs after exposure to OVA. GTE administration also reduced matrix metalloproteinase-9 activity and protein levels., Conclusion: GTE effectively inhibited asthmatic respiratory inflammation and mucus hyperproduction induced by OVA inhalation. These results suggest that GTE has the potential to be used for the treatment of asthma., 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 Kim, Kim, Jeong, Kim, Chung, Kim, Hong, Kwon, Ko and Kim.)

In general, it is difficult to visualize internal ocular structure and detect a lesion such as a cataract or glaucoma using the current ultrasound brightness-mode (B-mode) imaging. This is because the internal structure of the eye is rich in moisture, resulting in a lack of contrast between tissues in the B-mode image, and the penetration depth is low due to the attenuation of the ultrasound wave. In this study, the entire internal ocular structure of a bovine eye was visualized in an ex vivo environment using the compound acoustic radiation force impulse (CARFI) imaging scheme based on the phase-inverted ultrasound transducer (PIUT). In the proposed method, the aperture of the PIUT is divided into four sections, and the PIUT is driven by the out-of-phase input signal capable of generating split-focusing at the same time. Subsequently, the compound imaging technique was employed to increase signal-to-noise ratio (SNR) and to reduce displacement error. The experimental results demonstrated that the proposed technique could provide an acoustic radiation force impulse (ARFI) image of the bovine eye with a broader depth-of-field (DOF) and about 80% increased SNR compared to the conventional ARFI image obtained using the in-phase input signal. Therefore, the proposed technique can be one of the useful techniques capable of providing the image of the entire ocular structure to diagnose various eye diseases.

Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc&#95;1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc&#95;1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc&#95;1409 promoted E-cadherin/β-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/β-catenin signaling. Our results demonstrate that Amuc&#95;1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health., (© 2024. The Author(s).)

Given the absence of COVID-19 treatments, the best way to control the spread of the virus is to break the chain of infection by increasing public participation in preventive behaviors recommended by health authorities. This study proposes a moderated mediation model of information behaviors (e.g. information seeking and information verification) and trust in government that explores the relationship between risk perception and preventive behaviors regarding COVID-19. Using a survey study in South Korea, we conducted the moderated mediation analysis with latent moderated structural equation modeling (LMS). We found serial mediation effects for risk perception, information behaviors, and preventive behaviors, as people both seek out information and verify that information before adopting preventive behaviors. Additionally, trust in government moderated information behaviors in the relationship between risk perception and preventive behaviors, suggesting that trust in government encourages people to adopt more preventive actions via information seeking and information verification. Further implications are discussed to promote public understanding of the health crisis and public participation in preventive measures.

Background/aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression., Methods: Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD., Results: After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort., Conclusion: We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

This study presents a methodology to prevent the overdesign of electric dispensers for dental impression materials by analyzing the necessary load and determining the appropriate pressurization speed and drive motor capacity. We derived an equation to calculate the required torque and rotational speed of the motor based on the extrusion load and the speed of the impression material. A specialized load measurement system was developed to measure the load necessary to extrude the impression material. Through experiments and image processing, we measured the radius of curvature of the trajectory of the impression material and correlated it with the pressurization speed. Techniques such as position coordinate plotting, curve fitting, and circle fitting were employed to determine the pressurization speed that aligns with the manufacturer's recommended curvature radius. These findings led to a substantial decrease in the necessary motor torque and rotational speed compared with the current standards. This research provides a systematic approach to sizing drive motors using extrusion load and pressurization speed, aiming to reduce overdesign, power consumption, and the weight and size of the motor and battery, thereby contributing to the development of more efficient and compact dental impression material dispensers., Competing Interests: The authors declare no conflicts of interest.

Recent advancements in deep learning have achieved significant progress by increasing the number of parameters in a given model. However, this comes at the cost of computing resources, prompting researchers to explore model compression techniques that reduce the number of parameters while maintaining or even improving performance. Convolutional neural networks (CNN) have been recognized as more efficient and effective than fully connected (FC) networks. We propose a column row convolutional neural network (CRCNN) in this letter that applies 1D convolution to image data, significantly reducing the number of learning parameters and operational steps. The CRCNN uses column and row local receptive fields to perform data abstraction, concatenating each direction's feature before connecting it to an FC layer. Experimental results demonstrate that the CRCNN maintains comparable accuracy while reducing the number of parameters and compared to prior work. Moreover, the CRCNN is employed for one-class anomaly detection, demonstrating its feasibility for various applications., (© 2024 Massachusetts Institute of Technology.)