Search

BACKGROUND AND PURPOSE Recently, the DNA damage response (DDR) has emerged as a promising target for anticancer drug development. In our previous study, we identified several DDR-inhibiting compounds via high-content screening of a small molecule library using γH2AX foci as a biomarker. Here, we studied the effects of the DNA damage response inhibitor DDRI-18 (3,3′-(1 H,3′ H-5,5′-bibenzo[ d]imidazole-2,2′-diyl)dianiline) on DDR. EXPERIMENTAL APPROACH Osteosarcoma U2OS cells were treated with etoposide to induce DDR. The nuclear foci of γH2AX and other signalling molecules in DDR were visualized by immunofluorescence and quantified using an IN Cell Analyzer. The DNA repair capacity of cells was analysed using the comet assay and in vivo DNA end-joining assay. Cell survival after drug treatment was quantified using the MTT assay, and apoptotic cell death was analysed by Annexin V staining and flow cytometry. KEY RESULTS DDRI-18 inhibited the non-homologous end-joining (NHEJ) DNA repair process and delayed the resolution of DNA damage-related proteins (γH2AX, ATM and BRCA1) from DNA lesions at a later phase of DDR. Furthermore, DDRI-18 enhanced the cytotoxic effects of anticancer DNA-damaging drugs, including etoposide, camptothecin, doxorubicin and bleomycin. This synergistic effect on cell death was shown to be due to caspase-dependent apoptosis. CONCLUSIONS AND IMPLICATIONS We identified a chemical compound, DDRI-18, that has chemosensitization activity. Although the target molecule and mechanism of action of DDRI-18 remain unknown, DDRI-18 is an effective chemosensitizing agent and may improve the therapy with classical anticancer drugs. [ABSTRACT FROM AUTHOR]

Background: Caregiver burden significantly affects both patients and caregivers but is often overlooked in clinical practice. Physical and emotional strain on caregivers can compromise the quality of care. Care robots are emerging as solutions to alleviate these burdens by assisting with routine tasks, thereby reducing caregivers' physical strain and stress. Therefore, a prospective, non-randomized, interventional clinical trial was designed to identify changes in caregivers' physical activities due to care robot use and explore the associated benefits., Methods: Twenty-two caregivers (1 male and 21 female; mean age, 62.05 years) were participated. We analyzed the impact of care robots on reducing physical burden and assessed caregivers' satisfaction with these robots by examining care activity history, pain levels, muscle activities, and data for each physical care activity (e.g., transfer, reposition, feeding, and toileting), categorizing them based on whether a care robot was used. Care robots that assist in transfer, repositioning, feeding, and toileting activities were used in a clinical trial. Muscle activity was measured during maximum voluntary isometric contraction using electromyography sensors placed on the upper trapezius, biceps brachii, and erector spinae muscles., Results: During care robot use, we observed a statistically significant decrease in the distance and number of steps required for assisting with repositioning. However, the caregiving activity time increased when the robots assisted with transfer, feeding, and toileting (P < .001). Pain was significantly reduced during transfer and toileting activities using the care robot (P < .001) as well as during feeding activity (P = .040). Maximum voluntary isometric contraction showed a significant reduction in the upper trapezius, biceps brachii, and erector spinae muscles during the 4 care activities when using the robot, and these findings were consistent across the 3 sessions (P < .001). In the survey, caregivers indicated that "transfer-assisting" care robots were the most needed (15 respondents, 68.2%)., Conclusion: In this study, we demonstrated that employing care robots can aid in mitigating muscle overuse among caregivers, potentially alleviating pain due to musculoskeletal conditions., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Subarachnoid hemorrhage (SAH) is a devastating type of stroke, leading to high mortality and morbidity rates. Cerebral vasospasm and delayed cerebral ischemia (DCI) are common complications following SAH that contribute significantly to the poor outcomes observed in these patients. Intrathecal (IT) nicardipine delivered via an existing external ventricular drain is an off-label intervention that has been shown to be correlated with reduced DCI and improved patient outcomes. The current study aims to characterize the population pharmacokinetic (popPK) properties of intermittent IT nicardipine. Following informed consent, serial cerebrospinal fluid (CSF) samples were obtained from 16 SAH patients (50.4 ± 9.3 years old; 13 females) treated with IT nicardipine every 6 h (q6h, n = 8) or every 8 h (q8h, n = 8) for an average of 72 ± 21 doses. High-performance liquid chromatography was used to quantify CSF concentration from each sample. Our popPK analysis showed that the CSF pharmacokinetics of IT nicardipine in the cohort was adequately described by a two-compartment model with a lag time. Model parameter estimates were reliable (relative standard error <50%). Intracranial pressure influenced both the total clearance and the central volume of nicardipine (i.e., negative correlation, P <-.001). Calculated PK parameters were similar between q6h and q8h dosing regimens. Despite a small cohort of SAH patients, we successfully developed a popPK model to describe the nicardipine disposition kinetics in the CSF following IT administration. These findings may help inform future clinical trials designed to examine the optimal dosing of IT nicardipine., (© 2024 The Author(s). The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

This 20-year study (2001-2020) conducted in Jangmok Bay, Korea, assessed the intricate relationships between environmental factors and Noctiluca scintillans blooms. Granger causality tests and PCA analysis were used to assess the impact of sea surface temperature (SST), salinity, dissolved oxygen (DO) concentration, wind patterns, rainfall, and chlorophyll-a (Chl-a) concentration on bloom dynamics. The results revealed significant, albeit delayed, influences of these variables on bloom occurrence, with SST exhibiting a notable 2-month lag and salinity a 1-month lag in their impact. Additionally, the analysis highlighted the significant roles of phosphate, ammonium, and silicate, which influenced N. scintillans blooms with lags of 1 to 3 months. The PCA demonstrates how SST and wind speed during spring and summer, along with wind direction and salinity in winter, significantly impact N. scintillans blooms. We noted not only an increase in large-scale N. scintillans blooms but also a cyclical pattern of occurrence every 3 years. These findings underscore the synergistic effects of environmental factors, highlighting the complex interplay between SST, salinity, DO concentration, and weather conditions to influence bloom patterns. This research enhances our understanding of harmful algal blooms (HABs), emphasizing the importance of a comprehensive approach that considers multiple interconnected environmental variables for predicting and managing N. scintillans blooms., 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.)

Pre-trained chemical language models (CLMs) have attracted increasing attention within the domains of cheminformatics and bioinformatics, inspired by their remarkable success in the natural language processing (NLP) domain such as speech recognition, text analysis, translation, and other objectives associated with language. Furthermore, the vast amount of unlabeled data associated with chemical compounds or molecules has emerged as a crucial research focus, prompting the need for CLMs with reasoning capabilities over such data. Molecular graphs and molecular descriptors are the predominant approaches to representing molecules for property prediction in machine learning (ML). However, Transformer-based LMs have recently emerged as de-facto powerful tools in deep learning (DL), showcasing outstanding performance across various NLP downstream tasks, particularly in text analysis. Within the realm of pre-trained transformer-based LMs such as, BERT (and its variants) and GPT (and its variants) have been extensively explored in the chemical informatics domain. Various learning tasks in cheminformatics such as the text analysis that necessitate handling of chemical SMILES data which contains intricate relations among elements or atoms, have become increasingly prevalent. Whether the objective is predicting molecular reactions or molecular property prediction, there is a growing demand for LMs capable of learning molecular contextual information within SMILES sequences or strings from text inputs (i.e., SMILES). This review provides an overview of the current state-of-the-art of chemical language Transformer-based LMs in chemical informatics for de novo design, and analyses current limitations, challenges, and advantages. Finally, a perspective on future opportunities is provided in this evolving field., 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.)

Providing food with nutrition and functionality is crucial for sustaining human life. Rice (Oryza sativa L.) is a representative staple crop with high carbohydrate content but low amounts of essential amino acids, micronutrients, and carotenoids such as provitamin A. To improve the nutritional quality, rice endosperm was biofortified to accumulate carotenoids such as β-carotene through genetic engineering (i.e., using synthetic carotenoid biosynthetic genes, a nonmammalian viral polycistronic sequence, and an optimized promoter and transit peptide) and high-throughput rice transformation (approximately 300 transgenic plants per construct). To facilitate the safety assessment of genetically modified food, molecular characterization was performed to select elite lines equipped with a single intergenic insertion of T-DNA, high transgene expression, in this case leading to high carotenoid content, and with phenotypic and compositional substantial equivalence. In this study, we present β-carotene-biofortified rice event candidate lines eligible for commercial use and a disclosed molecular protocol for the development of biotech rice crops., 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.)

Background/aims: Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge., Methods: Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full model. We further validated ISS10 in an independent HCC cohort treated with nivolumab plus ipilimumab., Results: The study identified a significant association between the ISS and treatment response. Among patients classified as high responders, those treated with the atezolizumab plus bevacizumab combination exhibited improved overall and progression-free survival as well as better objective response rate compared to those treated with sorafenib. We also observed a significant correlation between ISS10 and response to nivolumab plus ipilimumab treatment. Analysis of immune cell subpopulations revealed distinct characteristics associated with ISS subtypes. In particular, the ISS10 high subtype displayed a more favorable immune environment with higher proportions of antitumor macrophages and activated T-cells, potentially explaining its better response., Conclusion: Our study suggests that ISS and ISS10 are promising predictive biomarkers for enhanced therapeutic outcomes in HCC patients undergoing combination immunotherapy. These markers are crucial for refining patient stratification and personalized treatment approaches to advance the effectiveness of standard-of-care regimens.

In this study, we aimed to evaluate the health effects of heavy metals and volatile organic compounds (VOCs) in fine particulate matter (PM 2.5 ) in the air around the Sinpyeong-Jangrim Industrial Complex, Busan, and the necessity of reduction measures. We measured the concentrations of heavy metals and VOCs in PM 2.5 in five areas with dense population around the Sinpyeong-Jangrim Industrial Complex. A health risk assessment was conducted, and the spatial risk distribution for the entire Saha-gu area was predicted using inverse distance weighting (IDW). Our results indicated that the carcinogens benzene, As, and Cr 6+ , and the non-carcinogen m,p-xylene, have the potential to adversely affect health. In particular, As was found to have the potential to express health effects at all measurement points. Additionally, based on the IDW results, the minimum values of benzene, arsenic, and m,p-xylene exceeded the threshold level, potentially affecting the health of residents across the entire Saha-gu area. In contrast, Cr 6+ could potentially impact health only in some parts of Saha-gu as only its maximum value exceeded the threshold level. We demonstrated the importance of reducing air pollutant emissions from general industrial complexes. Our results will be useful in establishing more systematic mitigation measures to protect the health of residents near the Sinpyeong-Jangrim Industrial Complex and developing air pollutant management systems.

Background: Surgical site infection (SSI) is not rare after loop ileostomy reversal. This study assessed the effects of a subcutaneous closed suction drain on reducing SSIs after loop ileostomy reversal with purse-string skin closure., Methods: This retrospective study included 229 patients who underwent loop ileostomy reversal with purse-string closure at the Pusan National University Yangsan Hospital between January 2017 and December 2021. We divided the patients into those with a subcutaneous drain (SD group) and those without it (ND group). We analyzed variables that affected SSI occurrence in both groups., Results: The SD and ND groups included 109 and 120 patients, respectively. The number of incisional SSIs was significantly lower in the SD than in the ND group (0 vs. 7 events). An average of 35.7 mL of fluid was collected in the drainage bulb during hospitalization. The C-reactive protein level on postoperative day 4 was significantly lower in the SD group than in the ND group. The insertion of a subcutaneous drain was the only factor associated with a reduced incidence of SSIs (p = 0.015)., Conclusions: Subcutaneous closed suction drain with purse-string skin closure in loop ileostomy reversal can reduce incisional SSI occurrence., (© 2024. The Author(s).)

Introduction: Tularemia, caused by the bacterium Francisella tularensis , poses health risks to humans and can spread through a variety of routes. It has also been classified as a Tier 1 Select agent by the CDC, highlighting its potential as a bioterrorism agent. Moreover, it is difficult to diagnose in a timely fashion, owing to the non-specific nature of tularemia infections. Rapid, sensitive, and accurate detection methods are required to reduce mortality rates. We aimed to develop antibodies directed against the outer membrane protein A of F. tularensis (FopA) for rapid and accurate diagnosis of tularemia., Methods: We used a baculovirus insect cell expression vector system to produce the FopA antigen and generate anti-FopA antibodies through immunization of BALB/c mice. We then employed hybridoma and phage display technologies to screen for antibodies that could recognize unique epitopes on FopA., Result: Two monoclonal antibodies, 6B12 and 3C1, identified through phage display screening specifically bound to recombinant FopA in a dose-dependent manner. The binding affinity of the anti-FopA 6B12 and 3C1 antibodies was observed to have an equilibrium dissociation constant of 1.76 × 10-10 M and 1.32 × 10-9 M, respectively. These antibodies were used to develop a sandwich ELISA system for the diagnosis of tularemia. This assay was found to be highly specific and sensitive, with detection limits ranging from 0.062 ng/mL in PBS to 0.064 ng/mL in skim milk matrices., Discussion: Our findings demonstrate the feasibility of a novel diagnostic approach for detecting F. tularensis based on targeting FopA, as opposed to existing tests that target the bacterial lipopolysaccharide., 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 Jang, Kwon, Jang, Lee, Chang, Jeon, Jeong, Song, Min, Park, Lee, Han, Yang, Lee and Lee.)

A 30-year-old Korean man with myelodysplastic syndrome admitted hospital due to undifferentiated fever and recurrent skin lesions. He received combination therapy with high doses of meropenem, tigecycline and amikacin, yielding carbapenem resistant Klebsiella pneumoniae (CRKP) harboring K. pneumoniae carbapenemase (KPC)-2 from blood cultures on hospital day (HD) 23. Ceftazidime/avibactam was started at HD 37 and CRKP was eradicated from blood cultures after 5 days. However, ceftazidime/avibactam-resistant CRKP carrying KPC-44 emerged after 26 days of ceftazidime/avibactam treatment and then ceftazidime/avibactam-resistant, carbapenem-susceptible K. pneumoniae carrying KPC-135 was isolated on HD 65. The 3-D homology of KPC protein showed that hot spot changes in the omega loop could be attributed to ceftazidime/avibactam resistance and loss of carbapenem resistance. Whole genome sequencing of serial isolates supported that phenotypic variation was due to clonal evolution than clonal replacement. The treatment regimen was changed from CAZ/AVI to meropenem-based therapy (meropenem 1 g iv q 8 hours and amikacin 600 mg iv per day) starting with HD 72. CAZ/AVI-susceptible CRKP was presented again from blood cultures on HD 84, and the patient expired on HD 85. This is the first Korean report on the acquisition of ceftazidime/avibactam resistance through the emergence of bla KPC variants., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Indoor fires may cause casualties and property damage, so it is important to develop a system that predicts fires in advance. There have been studies to predict potential fires using sensor values, and they mostly exploited machine learning models or recurrent neural networks. In this paper, we propose a stack of Transformer encoders for fire prediction using multiple sensors. Our model takes the time-series values collected from the sensors as input, and predicts the potential fire based on the sequential patterns underlying the time-series data. We compared our model with traditional machine learning models and recurrent neural networks on two datasets. For a simple dataset, we found that the machine learning models are better than ours, whereas our model gave better performance for a complex dataset. This implies that our model has a greater potential for real-world applications that probably have complex patterns and scenarios.

Distinct neutrophil populations arise during certain pathological conditions. The generation of dysfunctional neutrophils during sepsis and their contribution to septicemia-related systemic immune suppression remain unclear. In this study, using an experimental sepsis model that features immunosuppression, we identified a novel population of pathogenic CD200R high neutrophils that are generated during the initial stages of sepsis and contribute to systemic immune suppression by enhancing regulatory T (T reg ) cells. Compared to their CD200R low counterparts, sepsis-generated CD200R high neutrophils exhibit impaired autophagy and dysfunction, with reduced chemotactic migration, superoxide anion production, and TNF-α production. Increased soluble CD200 blocks autophagy and neutrophil maturation in the bone marrow during experimental sepsis, and recombinant CD200 treatment in vitro can induce neutrophil dysfunction similar to that observed in CD200R high neutrophils. The administration of an α-CD200R antibody effectively reversed neutrophil dysfunction by enhancing autophagy and protecting against a secondary infection challenge, leading to increased survival. Transcriptome analysis revealed that CD200R high neutrophils expressed high levels of Igf1, which elicits the generation of T reg cells, while the administration of an α-CD200R antibody inhibited T reg cell generation in a secondary infection model. Taken together, our findings revealed a novel CD200R high neutrophil population that mediates the pathogenesis of sepsis-induced systemic immunosuppression by generating T reg cells., (© 2024. The Author(s), under exclusive licence to CSI and USTC.)

This study investigates a real-time handheld bioaerosol monitoring system for the detection of biological particles using UV-LED and light-induced fluorescence technology. Biological particles produce both scattering and fluorescence signals simultaneously, which can help distinguish them from general particles. The detected scattering, fluorescence, and simultaneous signals are then converted into photon signals and categorized based on predetermined criteria. A reliable biological particle generator was required to validate the performance of the system. This study explores the use of an M13 bacteriophage as a virus simulant of biological agents and employs a customized inkjet aerosol generator to produce M13 bacteriophage aerosols of a specific size by controlling the concentration of M13. We confirmed that micro-sized, narrowly dispersed M13 aerosols were efficiently generated. Additionally, we confirmed the performance of this real-time handheld bioaerosol monitoring system by detecting viruses.

The classical organ clearance models have been proposed to relate the plasma clearance CL p to probable mechanism(s) of hepatic clearance. However, the classical models assume the intrinsic capability of drug elimination (CL u,int ) that is physically segregated from the vascular blood but directly acts upon the unbound drug concentration in the blood (f ub C avg ), and do not handle the transit-time delay between the inlet/outlet concentrations in their closed-form clearance equations. Therefore, we propose unified model structures that can address the internal blood concentration patterns of clearance organs in a more mechanistic/physiological manner, based on the fractional distribution parameter f d operative in PBPK. The basic partial/ordinary differential equations for four classical models are revisited/modified to yield a more complete set of extended clearance models, i.e., the Rattle, Sieve, Tube, and Jar models, which are the counterparts of the dispersion, series-compartment, parallel-tube, and well-stirred models. We demonstrate the feasibility of applying the resulting extended models to isolated perfused rat liver data for 11 compounds and an example dataset for in vitro-in vivo extrapolation of the intrinsic to the systemic clearances. Based on their feasibilities to handle such real data, these models may serve as an improved basis for applying clearance models in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Active pharmaceutical ingredients (APIs) have gained direct pharmaceutical interest, along with their in vitro properties, and thus utilized as auxiliary solid dosage forms upon FDA guidance and approval on pharmaceutical cocrystals when reacting with coformers, as a potential and attractive route for drug substance development., Methods: However, screening and selecting suitable and appropriate coformers that may potentially react with APIs to successfully form cocrystals is a time-consuming, inefficient, economically expensive, and labour-intensive task. In this study, we implemented GNNs to predict the formation of cocrystals using our introduced API-coformers relational graph data. We further compared our work with previous studies that implemented descriptor-based models (e.g., random forest, support vector machine, extreme gradient boosting, and artificial neural networks)., Results: All built graph-based models show compelling performance accuracies (i.e., 91.36, 94.60 and 95. 95% for GCN, GraphSAGE, and RGCN respectively). RGCN demonstrated effectiveness and prevailed among the built graph-based models due to its capability to capture intricate and learn nuanced relationships between entities such as non-ionic and non-covalent interactions or link information between APIs and coformers which are crucial for accurate predictions and representations., Conclusion: These capabilities allows the model to adeptly learn the topological structure inherent in the graph data., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Oxide semiconductor thin-film transistors (TFTs) are used in the pixel array and gate driver circuits of organic light emitting diode (OLED) display panels. Long-term reliability characteristics of the TFTs are a barometer of the lifetime of OLED display panels. The long-term reliability of the driver TFTs is evaluated in a short time under high voltages and high temperature for an accelerated degradation test. If reliability parameters from the power law or stretched-exponential functions are the same for individual devices and devices in an operating panel, the lifetime of the panel can be accurately estimated. However, since compensation circuits are designed into operating panels, an environmental discrepancy exists between the accelerated test of single devices and the operation of devices in the panel. Herein, we propose a novel compensation stretched-exponential function (CSEF) model which captures the effect of the threshold voltage compensation circuit in the panel. The CSEF model not only bridges the discrepancy between individual devices and panel devices, but also provides a method to accurately and efficiently estimate the long-term lifetime of all display panels that utilize compensation circuits., (© 2023. Springer Nature Limited.)

Background: Hand hygiene (HH) is a fundamental component of infection prevention and control in healthcare settings. This study aimed to identify knowledge, attitude, and barriers to HH according to occupational groups and strategies to increase the rate of HH compliance among healthcare workers (HCWs)., Methods: This cross-sectional survey was conducted in July 2018 at four university-affiliated hospitals. The survey comprised seven parts with 49 items, including self-reported HH compliance, knowledge, attitudes, behaviours, barriers to HH, and improvement strategies., Results: A total of 1046 HCWs participated in the survey. The nursing group's self-reported HH compliance rate was the highest, followed by other HCWs and physicians. The scores regarding knowledge, attitudes, and behaviours regarding HH were the highest in the nursing group. The nursing group also had higher internal and emotional motivation scores. Physicians and nurses found HH the most challenging in emergencies, while other HCWs considered skin problems caused by HH products the most significant barrier. Among 12 improvement measures, approximately 20% of the respondents ranked "diversify types of hand sanitisers," "install soap and paper towels in each hospital room," and "change perception through various HH campaigns" as the top three priorities. The physician group deemed the timely reminder of HH compliance as the second most critical improvement measure., Conclusion: Differences in knowledge, attitude and barriers hindering HH compliance and improvement plans were identified for each group. The findings suggest that targeted interventions tailored to the specific needs of different occupational groups may effectively improve HH compliance in healthcare settings., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately high immune reactivity that are characteristic of microsatellite instable tumors. Most CGS6 tumors are positive for Epstein Barr virus and show extremely high levels of methylation and high immune reactivity. In a systematic analysis of genomic and proteomic data, we estimated the potential response rate of each consensus subtype to standard and experimental treatments such as radiation therapy, targeted therapy, and immunotherapy. Interestingly, CGS3 was significantly associated with a benefit from chemoradiation therapy owing to its high basal level of ferroptosis. In addition, we also identified potential therapeutic targets for each consensus subtype. Thus, the consensus subtypes produced a robust classification and provide for additional characterizations for subtype-based customized interventions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: The aim of this study was to evaluate the potential implications of fusion imaging with C-arm computed tomography (CACT) scans for repetitive conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma., Materials and Methods: Fifty-six cTACE sessions were performed using fusion CACT images from September 2020 to June 2021 in a tertiary referral center, and the data were retrospectively analyzed. Fusion of unenhanced and enhanced CACT images was considered when previously accumulated iodized oil hampered the identification of local tumor progression or intrahepatic distant metastasis (indication A), when a tumor was supplied by multiple arteries with different origins from the aorta and missing tumor enhancement was suspected (indication B), or when iodized oil distribution on immediate post-cTACE CACT images needed to be precisely compared with the pre-cTACE images (indication C). Fusion image quality, initial tumor response, time to local progression (TTLP) of index tumors, and time to progression (TTP) were evaluated., Results: The fusion quality was satisfactory with a mean misregistration distance of 1.4 mm. For the 40 patients with indication A, the initial tumor responses at 3 months were nonviable, equivocal, and viable in 27 (67.5%), 4 (10.0%), and 9 (22.5%) index tumors, respectively. The median TTLP and TTP were 14.8 months and 4.5 months, respectively. For 10 patients with indication B, the median TTLP and TTP were 8.3 months and 2.6 months, respectively. Among the 6 patients with indication C, 2 patients were additionally treated at the same cTACE session after confirming incomplete iodized oil uptake on fusion imaging., Conclusions: Fusion CACT images are useful in patients with hepatocellular carcinoma undergoing repetitive cTACE., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Institutional hand hygiene (HH) behavior is difficult to monitor and improve consistently, especially over long periods. This study aimed to investigate the long-term effects of HH promotion activities., Method: We launched the HH promotion team in 2010 and conducted interventions including goal setting, observation and feedback, education, reward incentives, and accountability. Optimal HH compliance rates were calculated based on adherence to all 6-step HH technique and appropriate time recommended by the World Health Organization. HH and optimal HH compliance were calculated over 12 years. Poisson regression analysis was used to determine the trend in HH compliance according to year., Results: In 2010, HH and optimal HH compliance were 59.7% and 15.6%, respectively. HH compliance increased by 83.9% in 2013 and remained over 75%. HH compliance increased significantly, with a relative risk (RR) of 1.014 (95% CI 1.002-1.025, P = .018). Optimal HH compliance increased by 67.8% in 2013 and remained over 60%, except in 2016 (58.8%) and 2019 (59.8%). Optimal HH compliance increased with RR 1.033 (95% CI 0.991-1.076, P = .123)., Discussion: HH and optimal HH compliance increased significantly over the 12 years when subgroup analysis was performed by job category., Conclusions: HH promotion team activities improved and maintained optimal HH compliance among HCWs., (Copyright © 2023. Published by Elsevier Inc.)

Background: This study aimed to investigate ventilation strategies to prevent nosocomial transmission of coronavirus disease 2019 (COVID-19)., Methods: We conducted a retrospective epidemiological investigation of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a teaching hospital (February-March 2021). The largest outbreak ward was studied, and measurements were taken to determine the pressure difference and air change per hour (ACH) of the rooms. Airflow dynamics were assessed using an oil droplet generator, indoor air quality sensor, and particle image velocimetry in the index patient's room, corridor, and opposite rooms, by varying the opening and closing of windows and doors., Results: During the outbreak, 283 COVID-19 cases were identified. The SARS-CoV-2 spread occurred sequentially from the index room to the nearest room, especially the opposite. The aerodynamic study demonstrated that droplet-like particles in the index room diffused through the corridor and the opposite room through the opening door. The mean ACH of the rooms was 1.44; the air supply volume was 15.9% larger than the exhaust volume, forming a positive pressure. Closing the door prevented diffusion between adjacent rooms facing each other, and natural ventilation reduced the concentration of particles within the ward and minimised their spread to adjacent rooms., Conclusions: Spread of droplet-like particles between rooms could be attributed to the pressure difference between the rooms and corridor. To prevent spread of SARS-CoV-2 between rooms, increasing the ACH in the room by maximising ventilation and minimising the positive pressure through supply/exhaust control and closing the room door are essential., Competing Interests: Declaration of Competing Interest All authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Despite the enormous interest in inorganic/polymer composite solid-state electrolytes (CSEs) for solid-state batteries (SSBs), the underlying ion transport phenomena in CSEs have not yet been elucidated. Here, we address this issue by formulating a mechanistic understanding of bi-percolating ion channels formation and ion conduction across inorganic-polymer electrolyte interfaces in CSEs. A model CSE is composed of argyrodite-type Li 6 PS 5 Cl (LPSCl) and gel polymer electrolyte (GPE, including Li + -glyme complex as an ion-conducting medium). The percolation threshold of the LPSCl phase in the CSE strongly depends on the elasticity of the GPE phase. Additionally, manipulating the solvation/desolvation behavior of the Li + -glyme complex in the GPE facilitates ion conduction across the LPSCl-GPE interface. The resulting scalable CSE (area = 8 × 6 (cm × cm), thickness ~ 40 μm) can be assembled with a high-mass-loading LiNi 0.7 Co 0.15 Mn 0.15 O 2 cathode (areal-mass-loading = 39 mg cm -2 ) and a graphite anode (negative (N)/positive (P) capacity ratio = 1.1) in order to fabricate an SSB full cell with bi-cell configuration. Under this constrained cell condition, the SSB full cell exhibits high volumetric energy density (480 Wh L cell -1 ) and stable cyclability at 25 °C, far exceeding the values reported by previous CSE-based SSBs., (© 2023. The Author(s).)

Introduction: Multiple sclerosis (MS) is a potentially disabling disease that damages the brain and spinal cord, inducing paralysis of the body. While MS has been known as a T-cell mediated disease, recent attention has been drawn to the involvement of B cells in its pathogenesis. Autoantibodies from B cells are closely related with the damage lesion of central nervous system and worse prognosis. Therefore, regulating the activity of antibody secreting cell could be related with the severity of the MS symptoms., Methods: Total mouse B cells were stimulated with LPS to induce their differentiation into plasma cells. The differentiation of plasma cells was subsequently analyzed using flow cytometry and quantitative PCR analysis. To establish an experimental autoimmune encephalomyelitis (EAE) mouse model, mice were immunized with MOG 35-55 /CFA emulsion., Results: In this study, we found that plasma cell differentiation was accompanied by upregulation of autotaxin, which converts sphingosylphosphorylcholine (SPC) to sphingosine 1-phosphate in response to LPS. We observed that SPC strongly blocked plasma cell differentiation from B cells and antibody production in vitro . SPC downregulated LPS-stimulated IRF4 and Blimp 1, which are required for the generation of plasma cells. SPC-induced inhibitory effects on plasma cell differentiation were specifically blocked by VPC23019 (S1PR1/3 antagonist) or TY52159 (S1PR3 antagonist), but not by W146 (S1PR1 antagonist) and JTE013 (S1PR2 antagonist), suggesting a crucial role of S1PR3 but not S1PR1/2 in the process. Administration of SPC against an EAE mouse model significantly attenuated the symptoms of disease, showing decreased demyelinated areas of the spinal cord and decreased numbers of cells infiltrated into the spinal cord. SPC markedly decreased plasma cell generation in the EAE model, and SPC-induced therapeutic effects against EAE were not observed in μMT mice., Conclusion: Collectively, we demonstrate that SPC strongly inhibits plasma cell differentiation, which is mediated by S1PR3. SPC also elicits therapeutic outcomes against EAE, an experimental model of MS, suggesting SPC as a new material to control MS., Competing Interests: Authors BP and Yoe-SB are preparing patent applications. 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 © 2023 Park, Jeong, Hu, Lee, Kim, Bae, Bae and Bae.)

As more documents appear on the Internet, it becomes important to detect malware within the documents. Malware of non-executables might be more dangerous because people usually open them without worrying about inherent danger. Recently, deep learning models are used to analyze byte streams of the non-executables for malware detection. Although they have shown successful results, they are commonly designed for stream-level detection, but not for file-level detection. In this paper, we propose a new method that aggregates the stream-level results to get file-level results for malware detection. We demonstrate its effectiveness by experimental results with our annotated dataset, and show that it gives performance gain of 3.37-5.89% of F1 scores., (© 2023. The Author(s).)

Three novel bacterial strains, 321 T , 335 T , and 353 T , were isolated from the intestines of Aegosoma sinicum larvae collected from Paju-Si, South Korea. The strains were Gram-negative, obligate aerobe and had rod-shaped cells with a single flagellum. The three strains belonged to the genus Luteibacter in the family Rhodanobacteraceae and shared < 99.2% similarity in their 16S rRNA gene sequence and < 83.56% similarity in thier whole genome sequence. Strains 321 T , 335 T , and 353 T formed a monophyletic clade with Luteibacter yeojuensis KACC 11405 T , L. anthropi KACC 17855 T , and L. rhizovicinus KACC 12830 T , with sequence similarities of 98.77-98.91%, 98.44-98.58%, and 97.88-98.02%, respectively. Further genomic analyses, including the construction of the Up-to-date Bacterial Core Gene (UBCG) tree and assessment of other genome-related indices, indicated that these strains were novel species belonging to the genus Luteibacter. All three strains contained ubiquinone Q8 as their major isoprenoid quinone and iso-C 15:0 and summed feature 9 (C 16:0 10-methyl and/or iso-C 17:1 ω9c) as their major cellular fatty acids. Phosphatidylethanolamine and diphosphatidylglycerol were the major polar lipids in all the strains. The genomic DNA G + C contents of strains 321 T , 335 T , and 353 T were 66.0, 64.5, and 64.5 mol%, respectively. Based on multiphasic classification, strains 321 T , 335 T , and 353 T were classified into the genus Luteibacter as the type strains of novel species, for which the names Luteibacter aegosomatis sp. nov., Luteibacter aegosomaticola sp. nov., and Luteibacter aegosomatissinici sp. nov. are proposed, respectively., (© 2023. The Author(s), under exclusive licence to Microbiological Society of Korea.)

Various studies have been conducted on multi-task learning techniques in natural language understanding (NLU), which build a model capable of processing multiple tasks and providing generalized performance. Most documents written in natural languages contain time-related information. It is essential to recognize such information accurately and utilize it to understand the context and overall content of a document while performing NLU tasks. In this study, we propose a multi-task learning technique that includes a temporal relation extraction task in the training process of NLU tasks such that the trained model can utilize temporal context information from the input sentences. To utilize the characteristics of multi-task learning, an additional task that extracts temporal relations from given sentences was designed, and the multi-task model was configured to learn in combination with the existing NLU tasks on Korean and English datasets. Performance differences were analyzed by combining NLU tasks to extract temporal relations. The accuracy of the single task for temporal relation extraction is 57.8 and 45.1 for Korean and English, respectively, and improves up to 64.2 and 48.7 when combined with other NLU tasks. The experimental results confirm that extracting temporal relations can improve its performance when combined with other NLU tasks in multi-task learning, compared to dealing with it individually. Also, because of the differences in linguistic characteristics between Korean and English, there are different task combinations that positively affect extracting the temporal relations., (© 2023. The Author(s).)

Background: Different scoring tools aid prediction of pediatric trauma patients' prognosis but there's no consensus on when to apply each. Pediatric Trauma Score (PTS) was one of the first tools developed. Shock Index Pediatric Adjusted (SIPA) adapts Shock Index (SI) in predicting outcomes adjusted for age. It is unclear if either scoring tool is better at predicting outcomes., Objective: To compare SIPA and PTS for level I and II pediatric traumas to determine if both are equally effective in predicting outcomes for pediatric trauma patients., Design/methods: This is a retrospective review of patients 1-17 years with level 1 and 2 activated trauma (1/2013 - 11/2019)., Outcomes of Interest: disposition, length of stay, ventilator use, moderate/major spleen/liver lacerations, and Index Severity Score (ISS). Patient visits were scored using both scores and placed into high/low risk category as predefined by the individual scoring tools: High risk SIPA, low risk SIPA, high risk PTS, low risk PTS., Results: There were 750 patients who met inclusion criteria, 35 visits scored high with both tools and 543 visits scored low. The odds ratio (OR) for each tool showed high risk scores were more likely to be associated with increased likelihood of outcomes. When both high-risk groups were compared, PTS had an increased OR for most outcomes. SIPA had an increased OR for receiving fluid bolus., Conclusion: This study externally validates both scoring tools for the same cohort. Both tools were reliable predictors, but PTS identifies more "high risk" visits. PTS requires more variables to calculate than SIPA. SIPA may be an effective way to triage when resources are scarce. However, there's still a need for a pediatric trauma triage score that can encompass the accuracy of PTS and the convenience of SIPA., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Background: To describe the radiological features of Gorham-Stout disease (GSD) as evaluated using plain radiography and dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) imaging techniques., Methods: Clinical and conventional imaging data were retrospectively reviewed for 15 patients with GSD between January 2001 and December 2020. After December 2018, DCMRL examinations were performed for lymphatic vessel evaluation in patients with GSD and reviewed in four patients., Results: The median age at diagnosis was 9 years (range: 2 months-53 years). The clinical manifestations were dyspnea in seven patients (46.7%), sepsis in 12 (80.0%), orthopedic problems in seven (46.7%), and bloody chylothorax in seven (46.7%). The common sites of osseous involvement were the spine (73.3%) and pelvic bone (60.0%). Among the non-osseous involvements, peri-osseous infiltrative soft-tissue abnormalities adjacent to the area of bone involvement were the most common (86.7%), followed by splenic cysts (26.7%) and interstitial thickening (26.7%). DCMRL demonstrated weak central conducting lymphatic flow in two patients with abnormal giant tortuous thoracic ducts and no flow in one patient. All patients who underwent DCMRL in this study presented with altered anatomical lymphatics and functional flow with collateralization., Conclusion: DCMRL imaging and plain radiography are very useful for determining the extent of GSD. DCMRL is a novel imaging tool for the visualization of abnormal lymphatics in patients with GSD, which helps in further treatment. Therefore, in patients with GSD, it might be necessary to obtain not only plain radiographs but also MR and DCMRL images., (© 2023. The Author(s).)

Purpose: The purpose of this study is to assess the safety and clinical outcomes of transcatheter arterial embolization (TAE) via the cystic artery for treating patients with bleeding from the cystic artery., Materials and Methods: This retrospective study included 20 patients who underwent TAE via the cystic artery between January 2010 and May 2022. Radiological images and clinical data were reviewed to evaluate causes of bleeding, procedure-related complications, and clinical outcomes. Technical success was defined as the disappearance of contrast media extravasation or pseudoaneurysm, as demonstrated on completion angiography. Clinical success was defined as discharge from the hospital without any bleeding-related issues., Results: Hemorrhagic cholecystitis ( n  = 10) was the most common cause of bleeding, followed by iatrogenic ( n  = 4), duodenal ulcer ( n  = 3), tumor ( n  = 2), and trauma ( n  = 1). Technical success was achieved in all cases, and clinical success was achieved in 70% ( n  = 14) of patients. Three patients developed ischemic cholecystitis as a complication. Six patients with clinical failure died within 45 days after embolization., Conclusion: TAE through the cystic artery has a high technical success rate in treating cystic artery bleeding, but clinical failure remains a common occurrence due to concurrent medical conditions and the development of ischemic cholecystitis., 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., (© 2023 Kim, Jeong, Han and Kim.)

Cluster validity indices (CVIs) for evaluating the result of the optimal number of clusters are critical measures in clustering problems. Most CVIs are designed for typical data-type objects called certain data objects. Certain data objects only have a singular value and include no uncertainty, so they are assumed to be information-abundant in the real world. In this study, new CVIs for uncertain data, based on kernel probabilistic distance measures to calculate the distance between two distributions in feature space, are proposed for uncertain clusters with arbitrary shapes, sub-clusters, and noise in objects. By transforming original uncertain data into kernel spaces, the proposed CVI accurately measures the compactness and separability of a cluster for arbitrary cluster shapes and is robust to noise and outliers in a cluster. The proposed CVI was evaluated for diverse types of simulated and real-life uncertain objects, confirming that the proposed validity indexes in feature space outperform the pre-existing ones in the original space.

This study sought to determine the feasibility and clinical value of using a novel mobile application (app) to record the muscle/physical activity (PA) of caregivers. In all, 23 caregivers were enrolled and they were trained to use the app and a wearable device that automatically recorded their care activities and PA/burden. Data were collected for 42 days. Muscle activity was measured for 3 weeks during maximum voluntary isometric contraction (MVIC) and PA. Approximately 80% of the caregivers agreed that they conveniently used the wearable device through the mobile app. The most active %MVIC was noted for the back muscles during feeding assistance. As regard subjective pain evaluation, back pain was the most prevalent and pain level in the left knee was the highest. Incorporating mobile apps with wearable devices to record every activity of the caregivers may be feasible and can provide valuable clinical data for optimizing their pain management.

This study proposes a stand-off Raman spectroscopy system using dual-wavelength in the ultraviolet (UV) region to detect hazardous chemicals. The Raman spectrum generated by the UV excitation source avoids solar background noise during daytime for chemical detection as the spectrum is in the solar blind range. Wavelengths of 213 and 266 nm by 5th and 4th harmonics are generated from Nd:YAG laser. However, Raman spectra of chemicals exhibit different signal-to-noise ratios for both the excitation wavelengths; therefore, to detect such chemicals, Raman spectra by two sources are required. Raman spectra were acquired using a dual-wavelength laser and spectrometer with a single grating and detector at the wavelengths of 213 and 266 nm simultaneously. The Raman spectra of sulfuric acid, 2-chloroethyl ethyl sulfide, and dimethyl methylphosphonate were acquired and analyzed, thus highlighting the application of dual-wavelength Raman spectroscopy. For efficient chemical detection in the field, we have ensured that the system developed in this study is robust., 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 © 2022 Elsevier B.V. All rights reserved.)

Objectives: Atrial fibrillation (AF), a significant cause of ischemic stroke, often goes undetected because of its asymptomatic nature. This study investigated whether the total bolus-tracking time (TTT) and average slope (AS) of a bolus-tracking graph could be used to predict AF., Methods: This single-center, retrospective study included patients who underwent carotid CTA and a 24-h Holter test. TTT and the average degree of enhancement during bolus-tracking, derived from carotid CTA, were defined as variables of interest. All patients underwent transthoracic echocardiography. Left ventricular diastolic dysfunction and elevated left atrial pressure (LAP) were identified according to the guidelines of the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging., Results: The final cohort comprised 716 patients, 80 of whom presented with AF. The TTT of the AF group was significantly longer (23.8 ± 5.2 s) than that of the non-AF group (18.7 ± 2.8 s); p < 0.001. The AS of the bolus-tracking graph of the AF group was 0.80 ± 0.24, which was significantly lower than that of the non-AF group 1.38 ± 0.21 (p < 0.001). TTT was associated with a significantly higher risk of AF (odds ratio [OR]: 1.36; p < 0.001) and elevated LAP (OR: 1.46; p < 0.001). In contrast, the AS of the bolus-tracking graph was not significantly associated with either AF or an elevated LAP., Conclusion: TTT derived from bolus-tracking carotid CTA is an effective adjuvant tool for detecting AF related to left ventricular diastolic dysfunction and elevated LAP, confirmed using echocardiography., Key Points: • Atrial fibrillation is not only a significant cause of ischemic stroke but is also often masked because of its atypical and asymptomatic features. • The total tracking time, derived from bolus tracking of carotid computed tomography angiography, may be an effective adjuvant tool for detecting undiagnosed atrial fibrillation and elevated left atrial pressure in patients., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

In minimal physiologically based pharmacokinetic (mPBPK) models, physiological (e.g., cardiac output) and anatomical (e.g., blood/tissue volumes) variables are utilized in the domain of differential equations (DEs) for mechanistic understanding of the plasma concentration-time relationships [Formula: see text]. Although fundamental biopharmaceutical variables in terms of distribution (e.g., [Formula: see text] and [Formula: see text]) and elimination kinetics (e.g., [Formula: see text]) in mPBPK provide greater insights in comparison to classical compartment models, an absence of kinetic elucidation of slopes and intercepts in light of such DE model parameters hinders more intuitive appreciation of [Formula: see text]. Therefore, this study seeks the tangible physical meanings of slopes and intercepts of the plasma concentration-time relationships in one- and two-tissue mPBPK models (i.e., m2CM and m3CM), with respect to time parameters that are readily understandable in PK analyses, i.e., the mean residence ([Formula: see text]) and transit ([Formula: see text]) times. Utilizing the explicit equations (EEs) for the slopes, intercepts, and areas of each exponential phase in the m2CM and m3CM, we theoretically and numerically examined the limiting/boundary conditions of such kinetic properties, based on the ratio of the longest tissue [Formula: see text] to the [Formula: see text] in the body (i.e., [Formula: see text]) that is useful for dissecting complex PBPK systems. The kinetic contribution of the area of each exponential phase to the total drug exposure was assessed to identify the elimination phase between the terminal and non-terminal phases of the [Formula: see text] in the m2CM and m3CM. This assessment provides improved understanding of the complexities inherent in all PBPK profiles and models., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

The diversity of A mating type in wild strains of Lentinula edodes was extensively analyzed to characterize and utilize them for developing new cultivars. One hundred twenty-three A mating type alleles, including 67 newly discovered alleles, were identified from 106 wild strains collected for the past four decades in Korea. Based on previous studies and current findings, a total of 130  A mating type alleles have been found, 124 of which were discovered from wild strains, indicating the hyper-variability of A mating type alleles of L. edodes . About half of the A mating type alleles in wild strains were found in more than two strains, whereas the other half of the alleles were found in only one strain. About 90% of A mating type combinations in dikaryotic wild strains showed a single occurrence. Geographically, diverse A mating type alleles were intensively located in the central region of the Korean peninsula, whereas only allele A17 was observed throughout Korea. We also found the conservation of the TCCCAC motif in addition to the previously reported motifs, including ATTGT, ACAAT, and GCGGAG, in the intergenic regions of A mating loci. Sequence comparison among some alleles indicated that accumulated mutation and recombination would contribute to the diversification of A mating type alleles in L. edodes . Our data support the rapid evolution of A mating locus in L. edodes , and would help to understand the characteristics of A mating loci of wild strains in Korea and help to utilize them for developing new cultivars., Competing Interests: No potential conflict of interest was reported by the authors., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the Korean Society of Mycology.)

Background: We aimed to identify the long-term risk of recurrence and mortality in patients who experienced acute ischemic stroke (AIS), acute myocardial infarction (AMI), or acute hemorrhagic stroke (AHS) using a population-level database. Methods: This retrospective cohort study included adults aged ≥55 years diagnosed with AIS, AMI, and AHS in the National Health Insurance Service Database between 2004 and 2007. The target outcomes were secondary AIS, AMI, AHS, and all-cause mortality. Predetermined covariates, such as age, sex, socioeconomic status, hypertension, diabetes, and dyslipidemia, were adjusted. Results: We included 151,181, 49,077, and 41,636 patients in the AIS, AHS, and AMI groups, respectively. The AMI (adjusted hazard ratio [aHR], 0.318; 95% confidence interval [CI], 0.306−0.330; p < 0.001) and AHS (aHR, 0.489; 95% CI, 0.472−0.506; p < 0.001) groups had a significantly lower risk of developing secondary AIS than the AIS group. The risk of developing secondary AMI was significantly lower in the AMI (aHR, 0.388; 95% CI, 0.348−0.433; p < 0.001) and AHS (aHR, 0.711; 95% CI, 0.640−0.790; p < 0.001) groups than in the AIS group. Initial AHS was a decisive risk factor for secondary AHS (aHR, 8.546; 95% CI, 8.218−8.887; p < 0.001). The AMI (aHR, 1.436; 95% CI, 1.412−1.461; p < 0.001) and AHS (aHR, 1.328; 95% CI, 1.309−1.348; p < 0.001) groups were associated with a significantly higher risk of long-term mortality than the AIS group. Conclusion: Our results elucidated that initial AIS was a significant risk factor for recurrent AIS and AMI; initial AHS was a decisive risk factor for developing secondary AHS. Further, AMI and AHS were more closely related to long-term mortality than AIS.

Recently, interest in e-learning has increased rapidly owing to the lockdowns imposed by COVID-19. A major disadvantage of e-learning is the difficulty in maintaining concentration because of the limited interaction between teachers and students. The objective of this paper is to develop a methodology to predict e-learners' concentration by applying recurrent neural network models to eye gaze and facial landmark data extracted from e-learners' video data. One hundred eighty-four video data of ninety-two e-learners were obtained, and their frame data were extracted using the OpenFace 2.0 toolkit. Recurrent neural networks, long short-term memory, and gated recurrent units were utilized to predict the concentration of e-learners. A set of comparative experiments was conducted. As a result, gated recurrent units exhibited the best performance. The main contribution of this paper is to present a methodology to predict e-learners' concentration in a natural e-learning environment., Competing Interests: Conflict of interestAll authors declare that they have no conflicts of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: The authors' facility established a novel integrated wound care team (IWCT), which included the implementation of a strict treatment algorithm by the patients' attending providers and a specialized wound care team led by a plastic surgeon. Investigators then retrospectively analyzed clinical outcomes of pressure injury (PI) management by the IWCT over 5 years., Methods: The authors performed a retrospective chart review and periodic statistical analysis of the data for all patients with PI referred to the IWCT in the authors' center from May 2015 to April 2019. Data including patients' demographic information, first and last consultation dates, referring department, PI stage, site of PI, and Braden Scale scores were collected and analyzed., Results: Patients (N = 15,556) did not differ significantly in age, sex, or Braden Scale score. A preimplementation/postimplementation analysis of PI data before and after establishing the IWCT showed that the incidence of stage 3 or 4 PIs had significantly decreased during the study period (19.1% vs 15.2%, P < .05). Conversely, the incidence of stage 1 PIs significantly increased in the same period (38.0% vs 57.4%, P < .05). The proportion of completely healed PIs also increased, and the median treatment period was significantly shortened (P < .05)., Conclusions: Implementation of the IWCT in a tertiary hospital setting led to a significant increase in early-stage PI detection and a decrease in severe PIs., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

High metabolic activity is a hallmark of cancers, including hepatocellular carcinoma (HCC). However, the molecular features of HCC with high metabolic activity contributing to clinical outcomes and the therapeutic implications of these characteristics are poorly understood. We aimed to define the features of HCC with high metabolic activity and uncover its association with response to current therapies. By integrating gene expression data from mouse liver tissues and tumor tissues from HCC patients ( n = 1038), we uncovered three metabolically distinct HCC subtypes that differ in clinical outcomes and underlying molecular biology. The high metabolic subtype is characterized by poor survival, the strongest stem cell signature, high genomic instability, activation of EPCAM and SALL4, and low potential for benefitting from immunotherapy. Interestingly, immune cell analysis showed that regulatory T cells (Tregs) are highly enriched in high metabolic HCC tumors, suggesting that high metabolic activity of cancer cells may trigger activation or infiltration of Tregs, leading to cancer cells' evasion of anti-cancer immune cells. In summary, we identified clinically and metabolically distinct subtypes of HCC, potential biomarkers associated with these subtypes, and a potential mechanism of metabolism-mediated immune evasion by HCC cells.