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Separatatusmegagnathus sp. nov. is recorded as new to science from South Korea. Due to this record, the genus Separatatus Chen & Wu, 1994 (Braconidae: Alysiinae) is recognized for the first time from South Korea. The genus and species are described and illustrated herein plus an identification key including the Korean new species is provided. In addition, the DNA barcode region of the mitochondrial cytochrome c oxidase subunit I ( COI ) has been analyzed for the new species., (Ju-Hyoeng Sohn, Cornelis van Achterberg, Sangjin Kim, Jongok Lim, Hyojoong Kim.)

Background: The platelet-to-white blood cell ratio (PWR) is a hematologic marker of the systemic inflammatory response. Recently, the PWR was revealed to have a role as an independent prognostic factor for mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic failure (ACLF) and HBV-related liver cirrhosis (LC) with acute decompensation (AD). However, the prognostic role of the PWR still needs to be investigated in LC patients with AD. In this study, we analyzed whether the PWR could stratify the risk of adverse outcomes (death or liver transplantation (LT)) in these patients. Methods: A prospective cohort of 1670 patients with AD of liver cirrhosis ((age: 55.2 ± 7.8, male = 1226 (73.4%)) was enrolled and evaluated for 28-day and overall adverse outcomes. Results: During a median follow-up of 8.0 months (range, 1.9−15.5 months), 424 (25.4%) patients had adverse outcomes (death = 377, LT = 47). The most common etiology of LC was alcohol use (69.7%). The adverse outcome rate was higher for patients with a PWR ≤ 12.1 than for those with a PWR > 12.1. A lower PWR level was a prognostic factor for 28-day adverse outcomes (PWR: hazard ratio 1.707, p = 0.034) when adjusted for the etiology of cirrhosis, infection, ACLF, and the MELD score. In the subgroup analysis, the PWR level stratified the risk of 28-day adverse outcomes regardless of the presence of ACLF or the main form of AD but not for those with bacterial infection. Conclusions: A lower PWR level was associated with 28-day adverse outcomes, indicating that the PWR level can be a useful and simple tool for stratifying the risk of 28-day adverse outcomes in LC patients with AD.

Background: Primary analyses of the phase III BrighTNess trial showed addition of carboplatin with/without veliparib to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) rates with manageable acute toxicity in patients with triple-negative breast cancer (TNBC). Here, we report 4.5-year follow-up data from the trial., Patients and Methods: Women with untreated stage II-III TNBC were randomized (2 : 1 : 1) to paclitaxel (weekly for 12 doses) plus: (i) carboplatin (every 3 weeks for four cycles) plus veliparib (twice daily); (ii) carboplatin plus veliparib placebo; or (iii) carboplatin placebo plus veliparib placebo. All patients then received doxorubicin and cyclophosphamide every 2-3 weeks for four cycles. The primary endpoint was pCR. Secondary endpoints included event-free survival (EFS), overall survival (OS), and safety. Since the co-primary endpoint of increased pCR with carboplatin plus veliparib with paclitaxel versus carboplatin with paclitaxel was not met, secondary analyses are descriptive., Results: Of 634 patients, 316 were randomized to carboplatin plus veliparib with paclitaxel, 160 to carboplatin with paclitaxel, and 158 to paclitaxel. With median follow-up of 4.5 years, the hazard ratio for EFS for carboplatin plus veliparib with paclitaxel versus paclitaxel was 0.63 [95% confidence interval (CI) 0.43-0.92, P = 0.02], but 1.12 (95% CI 0.72-1.72, P = 0.62) for carboplatin plus veliparib with paclitaxel versus carboplatin with paclitaxel. In post hoc analysis, the hazard ratio for EFS was 0.57 (95% CI 0.36-0.91, P = 0.02) for carboplatin with paclitaxel versus paclitaxel. OS did not differ significantly between treatment arms, nor did rates of myelodysplastic syndromes, acute myeloid leukemia, or other secondary malignancies., Conclusions: Improvement in pCR with the addition of carboplatin was associated with long-term EFS benefit with a manageable safety profile, and without increasing the risk of second malignancies, whereas adding veliparib did not impact EFS. These findings support the addition of carboplatin to weekly paclitaxel followed by doxorubicin and cyclophosphamide neoadjuvant chemotherapy for early-stage TNBC., Competing Interests: Role of the funder AbbVie sponsored the study, contributed to its design, and participated in the collection, analysis, and interpretation of the data and in the writing, reviewing, and approval of the manuscript. All authors had access to all relevant data and participated in writing, review, and approval of this manuscript, with editorial assistance funded by the study funder. No honoraria or payments were made for authorship. Disclosure CEG received travel funding from Genentech, Roche, Daiichi Sankyo, and AstraZeneca; has received writing support from Roche and AbbVie; has been on uncompensated advisory boards for Genentech, Roche, Daiichi Sankyo, and Seattle Genetics; has been on compensated advisory boards for Exact Sciences; has an uncompensated consulting role for Daiichi Sankyo; and has a compensated consulting role for Athenex. WMS is an unpaid member of the Steering Committee for AbbVie. JH received research funding from Celgene, Hexal, and Novartis; received honoraria from AbbVie, AstraZeneca, Celgene, Eisai, Gilead, Lilly, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Roche, and Seagen; has a consulting and advisory role for AbbVie, AstraZeneca, Celgene, Lilly, Hexal, MSD, Novartis, and Roche; reports travel expenses from Celgene, Daiichi, Novartis, Pfizer, and Roche. HSR received research support for clinical trials through the University of California from AstraZeneca, Boehringer Ingelheim, Daiichi, Genentech, Immunomedics, Lilly, Macrogenics, Merck, Novartis, Odonate, Pfizer, Polyphor, Seattle Genetics, and Sermonix; received honoraria from Mylan, Puma, and Samsung. JO received honoraria for consulting and/or advisory boards from AbbVie, Agendia, and Amgen Biotechnology, Aptitude Health, AstraZeneca, Bayer, Bristol Myers Squibb (BMS), Celgene Corporation, Clovis Oncology, Daiichi Sankyo, Eisai, G1 Therapeutics, Genentech, Gilead Sciences, GRAIL, Halozyme Therapeutics, Heron Therapeutics, Immunomedics, Ipsen Biopharmaceuticals, Lilly, Merck, Myriad, Nektar Therapeutics, Novartis, Pfizer, Pharmacyclics, Pierre Fabre Pharmaceuticals, Prime Oncology, Puma Biotechnology, Roche, Samsung Bioepis, Sanofi, Seagen, Syndax Pharmaceuticals, Taiho Oncology, Takeda, and Synthon. DM and MD are AbbVie employees and may hold stock or options. MU is on lectures and advisory boards for AbbVie, Agendia, Amgen, AstraZeneca, BioNTech, BMS, Celgene, Daiichi Sankyo, Eisai, GlaxoSmithKline (GSK), Jansen Cilag, Johnson & Johnson, Lilly, Molecular Health, MSD, Mundipharma, Myriad, Novartis, Pfizer, Pierre Fabre, Roche, and Seagen; has a consulting role for AbbVie. MG is an unpaid member of the Steering Committee for AbbVie. JPL received honoraria for consulting and/or advisory boards from Novartis, Pfizer, AstraZeneca, Lilly, and Roche. OM received consulting fee from AbbVie and G1 Therapeutics; received research funding from AbbVie, Genentech, Pfizer, and Roche; reports travel expenses from AbbVie and Grupo Oncoclinicas; is uncompensated co-chair of advisory board for Pfizer. WFS holds founder shares from Delphi Diagnostics; has intellectual property from Delphi Diagnostics; holds public company shares from Eiger Biopharmaceuticals and IONIS Pharmaceuticals; is on compensated advisory board for Merck; is on uncompensated advisory boards for Delphi Diagnostics and Roche. PR reports unpaid advisory boards, travel, and accommodations from Genentech/Roche; reports travel and accommodations from Lilly and AstraZeneca. JHS received research funding from MSD, Roche, Novartis, AstraZeneca, Lilly, Pfizer, GSK, Daiichi Sankyo, Sanofi, and Boehringer Ingelheim. RY is on Speakers bureau for Genentech. GSW received grants or contracts from AbbVie, Astellas, AstraZeneca, Roche, Innocrine Pharm, H3BioMedicine Inc., G1 Therapeutics, Daiichi Sankyo, Sermonix Pharm, Taiho Oncology, Seattle Genetics, Inc., Immunogen, Incyte, Genentech, Novartis, Lilly, Janssen, Celgene, Bristol Myers Squibb, Boehringer Ingelheim, Medivation, Macrogenics, Merrimack, Tesaro, and Pfizer. DY has a consulting or advisory role for Novartis, Biotheranostics, Bristol Myers Squibb, G1 Therapeutics, Athenex, Immunomedics, Sanofi/Aventis, R-Pharm, Lilly; is on speakers bureau for Novartis and Genentech/Roche; received research funding from Genentech/Roche, Novartis, MedImmune, Lilly, Medivation, Pfizer, Tesaro, Macrogenics, AbbVie, Merck, Clovis Oncology, Amgen, Biomarin, Biothera, Dana Farber Cancer Hospital, Incyte, Innocrin Pharma, Nektar, NSABP Foundation, Odonate Therapeutics, Polyphor; reports travel expenses from Novartis and Genentech/Roche. SL reports grant paid to from AbbVie, Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Immunomedics/Gilead, Novartis, Pfizer, Roche, and Vifor; received honorarium for advisory boards paid to institute: AbbVie, Amgen, AstraZeneca, Bayer, BMS, Celgene, Daiichi Sankyo, Eirgenix, GSK, Lilly, Merck KG, Novartis, Pfizer, Pierre Fabre, Prime/Medscape, Puma, Roche, and Seagen; is on lectures paid to institute for Chugai (personal), Daiichi Sankyo, Novartis, Pfizer, Pierre Fabre, PriME/Medscape, Roche, and Samsung; has a medical writing role for AbbVie, Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Novartis, Pfizer, and Roche. All other authors have declared no conflicts of interest. Data sharing AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual, and trial-level data (analysis datasets), as well as other information (e.g. protocols and Clinical Study Reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan and execution of a Data Sharing Agreement. Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered. For more information on the process, or to submit a request, visit the following link: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: This study evaluated the prevalence and characteristics of tonsillar human papillomavirus (HPV) infection in tumor-free patients undergoing tonsillectomy., Methods: We prospectively enrolled healthy patients who underwent tonsillectomy for tumor-free tonsillar disease. Their tonsillar HPV infections were evaluated using CLART HPV2, and subsequent p16 immunohistochemistry was performed in patients with positive HPV infection. Moreover, the results of tonsillar HPV infection were analyzed according to sex, age, and indication of tonsillectomy., Results: A total of 362 patients were included. HPV test was positive in 8 patients, with an overall prevalence of 2.2%. All detected HPV types were high-risk, including HPV 16 in six patients, HPV 52 in one patient, and HPV 58 in one patient. P16 was negative in all 8 patients with HPV infection. The prevalence of tonsillar HPV infection in males and females was 2.4% (6/246) and 1.7% (2/116), respectively (P > 0.999), and in pediatric and adult patients, 2.2% (5/228) and 2.2% (3/134), respectively (P > 0.999). The prevalence showed a bimodal peak at 1st and 6th decades, with the prevalence of 2.6% (5/194) and 7.9% (3/38), respectively. The prevalence of tonsillar HPV infection in tonsillitis and non-tonsillitis groups were 0.0% (0/104) and 3.1% (8/258), respectively (P = 0.111)., Conclusion: The prevalence of tonsillar HPV infection in tumor-free patients was low, but all detected HPV infections were high-risk types. Our results support using a 9-valent vaccine which covers all high-risk HPV types found in this study., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier B.V.)

Purpose: Central retinal artery occlusion (CRAO) is a vision-threatening condition with a potentially poor visual prognosis. Many different treatment modalities are suggested but controversy remains regarding effectiveness of these treatments. The purpose of this study is to perform a systematic review and meta-analysis in addition to analyzing retrospective data at our own tertiary care center regarding effectiveness of hyperbaric oxygen therapy (HBOT) in treatment of CRAO., Methods: The PubMed, Scopus, and the Cochrane Library are searched from the date of database inception to September 2021 to conduct a review based on the PRISMA (preferred reporting items for systematic review and meta-analysis), evaluating the role of HBOT in visual recovery of CRAO patients. In addition, a retrospective chart review of patients clinically diagnosed with CRAO at our university-based hospital (University of Texas Health, San Antonio, TX, USA) from year 2011 to 2021 was conducted., Results: After a review of 376 articles, three articles met the inclusion criteria for meta-analysis, where a total of 207 patients received HBOT versus 89 patients that did not receive any form of oxygen therapy. Analysis of these results demonstrate that HBOT in CRAO patients does not enhance the final visual outcome (p = 0.83). Similar conclusion was also drawn from retrospective analysis of 48 patients (15 HBOT versus 33 controls) at our tertiary care center, where no visual benefit was observed in the HBOT group., Conclusions: HBOT does not appear to improve final visual outcome and concerns remain regarding adverse reactions such as barotrauma and generalized seizures. Large, randomized studies are required for further understanding of the role of HBOT in treatment of CRAO.

Multifocal intraocular lenses (MF-IOLs) are increasingly implanted as the need for good near- and intermediate-distance vision increases. Although retinal disease is known to be a relative contraindication for MF-IOL implantation, there are no detailed guidelines for MF-IOL implantation with respect to the type and severity of retinal diseases/statuses. In this study, because retinal diseases can affect the performance of MF-IOLs, we analyzed the opinions of 111 retinal specialists, who were members of the Korean Retina Society, on the implantation of diffractive MF-IOLs in eyes with 15 retinal diseases/statuses using a web-based survey. For each underlying condition, retinal specialists were asked to rate their approval regarding implantation of MF-IOLs on a scale from 1 (completely disapprove) to 7 (completely approve), under the assumption that there were no known contraindications except for a given retinal disease/status. As a result, retinal specialists disapproved MF-IOL implantation (median value of Likert score < 4) in the eyes with wet age-related macular degeneration, dry age-related macular degeneration with geographic atrophy, proliferative diabetic retinopathy, nonproliferative diabetic retinopathy with macular edema, previous macula-off retinal detachment, previous retinal vein occlusion, and epiretinal membrane, but the scores varied by disease/status. The factors that affected the specialists’ opinions were the type of practice and the frequency of MF-IOL implantation (p = 0.013 and p = 0.021, respectively; one-way ANOVA).

The relationship between dementia and surgery remains unclear. Research to elucidate the relationship between them is scarce, and conducting epidemiological research is complicated. This study aimed to investigate the incidence and risk of dementia according to the surgery type. We performed a retrospective propensity score-matched cohort study using nationwide representative cohort sample data from the Korean National Health Insurance Service in South Korea between 2003 and 2004. Incidence rates for dementia were obtained by dividing the number of patients with dementia by person-years at risk. To identify the risk of dementia according to the type of surgery, we investigated the hazard ratio by each surgery type. The incidence rates of dementia in control, musculoskeletal, and two or more surgeries groups were 9.66, 13.47, and 13.36 cases per 1000 person-years, respectively. The risk of dementia in the musculoskeletal and two or more surgeries groups was 1.44-fold higher (95% confidence interval (95% CI), 1.22-1.70) and 1.42-fold higher (95% CI, 1.17-1.72) than that in the control group, respectively. Patients who underwent musculoskeletal surgery and two or more surgeries had a higher risk of dementia; however, there was no association with the type of anesthesia administered.

In mammals, white adipose tissues are largely divided into visceral epididymal adipose tissue (EAT) and subcutaneous inguinal adipose tissue (IAT) with distinct metabolic properties. Although emerging evidence suggests that subpopulations of adipose stem cells (ASCs) would be important to explain fat depot differences, ASCs of two fat depots have not been comparatively investigated. Here, we characterized heterogeneous ASCs and examined the effects of intrinsic and tissue micro-environmental factors on distinct ASC features. We demonstrated that ASC subpopulations in EAT and IAT exhibited different molecular features with three adipogenic stages. ASC transplantation experiments revealed that intrinsic ASC features primarily determined their adipogenic potential. Upon obesogenic stimuli, EAT-specific SDC1 + ASCs promoted fibrotic remodeling, whereas IAT-specific CXCL14 + ASCs suppressed macrophage infiltration. Moreover, IAT-specific BST2 high ASCs exhibited a high potential to become beige adipocytes. Collectively, our data broaden the understanding of ASCs with new insights into the origin of white fat depot differences., Competing Interests: Declaration of interests The authors declare no competing financial interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background & Aims: The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction., Methods: PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included., Results: Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses., Conclusions: Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis., Lay Summary: The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized., Competing Interests: Conflict of interest MP is funded by BONFOR-Forschungskommission der Medizinischen Fakultät Bonn and by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy–EXC2151–390873048 and Ernst-und-Berta Grimmke Foundation. TB: Grants: Abbvie, BMS, Gilead, Humedics, Intercept, Janssen, MSD/Merck, Merz, Novartis, and Sequana Medical; Consulting or advisory board: Abbvie, Alexion, Bayer, BMS, Gilead, Intercept, Janssen, MSD/Merck, Merz, Novartis, Sequana Medical, and Spring Bank; Speaker: Abbvie, Alexion, Bayer, BMS, Eisai, Gilead, Intercept, Ipsen, Janssen, MSD/Merck, Merz, Novartis, Sirtex and Sequana Medical in the past 2 years. JT was supported by grants of Deutsche Forschungsgemeinschaft (SFB TRR57 P18, CRC 1382 A09), the European Union’s Horizon 2020 research and innovation program’s GALAXY study (No. 668031), LIVERHOPE (No. 731875), MICROB-PREDICT (No. 825694), DECISION (No. 84794) and the Cellex Foundation (PREDICT). JT: Grants: Gore; Consultant: Martins Pharma, Ironwood, Gore, Alexion, BMS, Grifols, Sequana Medicals, Versantis; Sponsored lectures (National or International): Gilead Sciences, Gore, Alexion, BMS, Grifols, Sequana Medicals, Norgine, Intercept. FJ: Speaker: Gilead Sciences, MSD and Ascletis. Consulting or advisory board: Gilead Sciences and MSD. MHN: Grants: Gilead, Pfizer, Enanta, Vir, Glycotest, National Cancer Institute, B. K. Kee Foundation, Exact Sciences; Helio Health; Consulting or advisory board: Intercept, Gilead, Exact Sciences, Laboratory of Advanced Medicine, Bayer, Eisai, GSK, Novartis. All other authors report no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Cluster headache (CH) is a rare, primary headache disorder, characterized of excruciating, strictly one-sided pain attacks and ipsilateral cranial autonomic symptoms. Given the debilitating nature of CH, delayed diagnosis can increase the disease burden. Thus, we aimed to investigate the diagnostic delay, its predictors, and clinical influence among patients with CH., Methods: Data from a prospective multicenter CH registry over a 4-year period were analyzed. CH was diagnosed according to the International Classification of Headache Disorders (ICHD)-3 criteria, and diagnostic delay of CH was assessed as the time interval between the year of the first onset and the year of CH diagnosis. Patients were classified into three groups according to the tertiles of diagnostic delay (1st tertile, <1 year; 2nd tertile, 1-6 years; and 3rd tertile, ≥7 years)., Results: Overall, 445 patients were evaluated. The mean duration of diagnosis delay was 5.7 ± 6.7 years, (range, 0-36 years). Regarding the age of onset, majority of young patients (age <20 years) belonged to the third tertile (60%), whereas minority of old patients (>40 years) belonged to the third tertile (9.0%). For year of onset, the proportion of patients in the 3rd tertile was the highest for the groups before the publication year of the ICHD-2 (74.7%) and the lowest for the groups after the publication year of the ICHD-3 beta version (0.5%). Compared with the first CH, episodic CH [multivariable-adjusted odds ratio (aOR) = 5.91, 95% CI = 2.42-14.48], chronic CH (aOR = 8.87, 95% CI = 2.66-29.51), and probable CH (aOR = 4.12, 95% CI = 1.48-11.43) were associated with the tertiles of diagnostic delay. Age of onset (aOR = 0.97, 95% CI = 0.95-0.99) and PHQ-9 score (aOR = 0.96, 95% CI = 0.93-0.99) were inversely associated with the tertile of diagnostic delay. The prevalence of suicidal ideation was highest in the patients of the third tertile. The mean HIT-6 score increased significantly with the diagnostic delay ( p = 0.041)., Conclusions: Patients with a younger onset of CH have a higher risk of diagnostic delay. Nevertheless, the rate of delayed diagnosis gradually improved over time and with the publication of the ICHD criteria, supporting the clinical significance of diagnostic clinical criteria and headache education to reduce the disease burden of CH., Competing Interests: SJC was involved as a site investigator of multicenter trial sponsored Otsuka Korea, Allergan, Ildong Pharmaceutical Co., Ltd., Novartis International AG, Eli Lilly and Company, Hyundaipharm. Co. Ltd., Biohaven Asia Pacific Ltd., H. Lundbeck A/S (Lundbeck), and Parexel Korea Co., Ltd., and received lecture honoraria from Allergan Korea, WhanIn Pharm Co., Ltd., Shinpoong Pharma. Co., Ltd., and SK chemicals in the past 24 months. MC was a site investigator for a multicenter trial sponsored by Otsuka Korea, Novartis International AG, and Eli Lilly and Company. He worked as an advisory member for Teva and has received lecture honoraria from Allergan Korea, Handok-Teva, and Yuyu Pharmaceutical Company in the past 24 months. He received grants from the Yonsei University College of Medicine and the National Research Foundation of Korea (2019R1F1A1053841). 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 © 2022 Kim, Chung, Kim, Lee, Chu, Ahn, Bae, Song, Sohn, Oh, Kim, Kim, Park, Chung, Moon, Cho, Seo, Kim, Choi, Park, Chung and Cho.)

Background: The comprehensiveness and maintenance of the American College of Radiology (ACR) Appropriateness Criteria (AC) makes it a unique resource for evidence-based clinical imaging decision support, but it is underutilized by clinicians. To facilitate the use of imaging recommendations, we develop a natural language processing (NLP) search algorithm that automatically matches clinical indications that physicians write into imaging orders to appropriate AC imaging recommendations., Methods: We apply a hybrid model of semantic similarity from a sent2vec model trained on 223 million scientific sentences, combined with term frequency inverse document frequency features. AC documents are ranked based on their embeddings' cosine distance to query. For model testing, we compiled a dataset of simulated simple and complex indications for each AC document (n = 410) and another with clinical indications from randomly sampled radiology reports (n = 100). We compare our algorithm to a custom google search engine., Results: On the simulated indications, our algorithm ranked ground truth documents as top 3 for 98% of simple queries and 85% of complex queries. Similarly, on the randomly sampled radiology report dataset, the algorithm ranked 86% of indications with a single match as top 3. Vague and distracting phrases present in the free-text indications were main sources of errors. Our algorithm provides more relevant results than a custom Google search engine, especially for complex queries., Conclusions: We have developed and evaluated an NLP algorithm that matches clinical indications to appropriate AC guidelines. This approach can be integrated into imaging ordering systems for automated access to guidelines., (© 2022. The Author(s).)

Background and Aim: Besifovir dipivoxil maleate (BSV) was reported to have comparable antiviral efficacy and superior renal and bone safety to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. The present study aims to evaluate changes of liver histology and intrahepatic covalently closed circular DNA (cccDNA) levels by BSV treatment in comparison with TDF therapy., Methods: This is a subset study of the phase 3 trial comparing BSV with TDF. Among them, only CHB patients willing to participate in a histologic evaluation study were enrolled. Liver histologic examination and intrahepatic cccDNA quantification were performed., Results: A total of 46 CHB patients received liver biopsies (BSV, n = 29; TDF, n = 17). After 48 weeks of treatment, virological response rate was comparable between the groups (P = 0.707). Follow-up liver biopsies showed that necroinflammation was significantly improved in the both groups. However, the histological response rate defined as the proportion of subjects whose modified histologic activity index score decreased by ≥ 2 without deterioration in fibrosis was higher in the BSV group than in the TDF group (77.8% vs 36.4%, P = 0.048). The proportion of subjects with Ishak fibrosis score 3 or more decreased from 77.7% to 55.5% in the BSV and that decreased from 72.7% to 45.4% in the TDF group. The intrahepatic cccDNA significantly decreased from baseline after 48 weeks of BSV or TDF treatment (P < 0.001) without intergroup differences (P = 0.349)., Conclusions: The BSV therapy improves hepatic histology and decreases intrahepatic cccDNA in CHB patients., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

The advancements of artificial intelligence (AI) for osteoarthritis (OA) applications have been rapid in recent years, particularly innovations of deep learning for image classification, lesion detection, cartilage segmentation, and prediction modeling of future knee OA development. This review article focuses on AI applications in OA research, first describing machine learning (ML) techniques and workflow, followed by how these algorithms are used for OA classification tasks through imaging and non-imaging-based ML models. Deep learning applications for OA research, including analysis of both radiographs for automatic detection of OA severity, and MR images for detection of cartilage/meniscus lesions and cartilage segmentation for automatic T 2 quantification will be described. In addition, information on ML models that identify individuals at high risk of OA development will be provided. The future vision of machine learning applications in imaging of OA and cartilage hinges on implementation of AI for optimizing imaging protocols, quantitative assessment of cartilage, and automated analysis of disease burden yielding a faster and more efficient workflow for a radiologist with a higher level of reproducibility and precision. It may also provide risk assessment tools for individual patients, which is an integral part of precision medicine., (© 2021. ISS.)

Background & Aims: Several models have recently been developed to predict risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Our aims were to develop and validate an artificial intelligence-assisted prediction model of HCC risk., Methods: Using a gradient-boosting machine (GBM) algorithm, a model was developed using 6,051 patients with CHB who received entecavir or tenofovir therapy from 4 hospitals in Korea. Two external validation cohorts were independently established: Korean (5,817 patients from 14 Korean centers) and Caucasian (1,640 from 11 Western centers) PAGE-B cohorts. The primary outcome was HCC development., Results: In the derivation cohort and the 2 validation cohorts, cirrhosis was present in 26.9%-50.2% of patients at baseline. A model using 10 parameters at baseline was derived and showed good predictive performance (c-index 0.79). This model showed significantly better discrimination than previous models (PAGE-B, modified PAGE-B, REACH-B, and CU-HCC) in both the Korean (c-index 0.79 vs. 0.64-0.74; all p <0.001) and Caucasian validation cohorts (c-index 0.81 vs. 0.57-0.79; all p <0.05 except modified PAGE-B, p = 0.42). A calibration plot showed a satisfactory calibration function. When the patients were grouped into 4 risk groups, the minimal-risk group (11.2% of the Korean cohort and 8.8% of the Caucasian cohort) had a less than 0.5% risk of HCC during 8 years of follow-up., Conclusions: This GBM-based model provides the best predictive power for HCC risk in Korean and Caucasian patients with CHB treated with entecavir or tenofovir., Lay Summary: Risk scores have been developed to predict the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. We developed and validated a new risk prediction model using machine learning algorithms in 13,508 antiviral-treated patients with chronic hepatitis B. Our new model, based on 10 common baseline characteristics, demonstrated superior performance in risk stratification compared with previous risk scores. This model also identified a group of patients at minimal risk of developing HCC, who could be indicated for less intensive HCC surveillance., Competing Interests: Conflict of interest Hwi Young Kim: Nothing to declare; Pietro Lampertico: Speaking bureau/advisor for AbbVie, Eiger, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck/Merck Sharp & Dohme, MYR Pharma, Roche; Joon Yeul Nam: Nothing to declare; Hyung-Chul Lee: Nothing to declare; Seung Up Kim: Receiving grants from Yuhan Pharmaceuticals, and lecture fees from Bristol-Myers Squibb, Gilead Science and Yuhan Pharmaceuticals; Dong Hyun Sinn: Nothing to declare; Yeon Seok Seo: Nothing to declare; Han Ah Lee: Nothing to declare; Soo Young Park: Nothing to declare; Young-Suk Lim: Advisory board member of and receives research funding from Gilead Sciences; Eun Sun Jang: Nothing to declare; Eileen L. Yoon: Nothing to declare; Hyoung Su Kim: Nothing to declare; Sung Eun Kim: Nothing to declare; Sang Bong Ahn: Nothing to declare; Jae-Jun Shim: Nothing to declare; Soung Won Jeong: Nothing to declare; Yong Jin Jung: Nothing to declare; Joo Hyun Sohn: Nothing to declare; Yong Kyun Cho: Nothing to declare; Dae Won Jun: Nothing to declare; George N. Dalekos: Advisor/lecturer for AbbVie, Bayer, Bristol-Myers Squibb, Gilead, Janssen, Novartis, Roche; grant support from Bristol-Myers Squibb, Gilead, Roche; Ramazan Idilman: Nothing to declare; Vana Sypsa: Advisor/lecturer for AbbVie, Gilead, Janssen; research grants from AbbVie, Gilead; Thomas Berg: Advisor/consultant/lecturer for AbbVie, Alexion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck Sharp & Dohme/Merck, Novartis, Roche, and Vertex; Research support from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp & Dohme/Merck, Novartis and Roche; Maria Buti: Advisor/lecturer for AbbVie, Arbutus, Bristol-Myers Squibb, Gilead, Glaxo Smith-Kleine, Merck, Roche, Spring Bank; Jose Luis Calleja: Advisor/lecturer for AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck; John Goulis: advisor/lecturer for Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck Sharp & Dohme, Roche; research grant from Bristol-Myers Squibb; Spilios Manolakopoulos: Advisor/lecturer for AbbVie, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Roche; grants from Bristol-Myers Squibb, Gilead; Harry LA Janssen: Consultant for and grants from AbbVie, Arbutus, Bristol Myers Squibb, Enyo, Gilead Sciences, Janssen, Medimmune, Merck, Roche, Vir Biotechnology Inc., Viroclinics; Myoung-jin Jang: Nothing to declare; Yun Bin Lee: Research grant from Samjin Pharmaceuticals and Yuhan Pharmaceuticals; Yoon Jun Kim: Research grants from Bristol-Myers Squibb, Roche, JW Creagene, Bukwang Pharmaceuticals, Handok Pharmaceuticals, Hanmi Pharmaceuticals, Yuhan Pharmaceuticals and Pharmaking, and lecture fees from Bayer HealthCare Pharmaceuticals, Gilead Science, MSD Korea, Yuhan Pharmaceuticals, Samil Pharmaceuticals, CJ Pharmaceuticals, Bukwang Pharmaceuticals and Handok Pharmaceuticals; Jung-eHwan Yoon: Research grant from Bayer HealthCare Pharmaceuticals, Bukwang Pharmaceuticals and Daewoong Pharmaceuticals; Jeong-Hoon Lee: Lecture fees from GreenCross Cell, Daewoong Pharmaceuticals and Gilead Korea; George V. Papatheodoridis: Advisor/lecturer for AbbVie, Dicerna, Gilead, GlaxoSmithKline, Ipsen, Janssen, Merck Sharp & Dohme, Roche, Spring Bank; research grants AbbVie, Gilead. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

We evaluated the impact of prestroke glycemic variability estimated by glycated albumin (GA) on symptomatic hemorrhagic transformation (SHT) in patients with intravenous thrombolysis (IVT). Using a multicenter database, we consecutively enrolled acute ischemic stroke patients receiving IVT. A total of 378 patients were included in this study. Higher GA was defined as GA ≥ 16.0%. The primary outcome measure was SHT. Multivariate regression analysis and a receiver operating characteristic curve were used to assess risks and predictive ability for SHT. Among the 378 patients who were enrolled in this study, 27 patients (7.1%) had SHT as defined by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SHT SITS ). The rate of SHT SITS was higher in the higher GA group than in the lower GA group (18.0% vs. 1.6%, p < 0.001). A higher GA level (GA ≥ 16.0%) significantly increased the risk of SHT SITS (adjusted odds ratio [OR], [95% confidence interval, CI], 12.57 [3.08-41.54]) in the logistic regression analysis. The predictive ability of the GA level for SHT SITS was good (AUC [95% CI]: 0.83 [0.77-0.90], p < 0.001), and the cutoff value of GA in SHT was 16.3%. GA was a reliable predictor of SHT after IVT in acute ischemic stroke in this study., (© 2022. The Author(s).)

Purpose: We aimed to evaluate the true prevalence and characteristics of vagus nerve (VN) variations using the carotid artery (CA) and the internal jugular vein (C-I axis)., Methods: We examined patients who underwent neck ultrasonography (US) conducted by a single operator. A VN variation was defined as a VN located anterior or medial to the C-I axis. The subtypes of VN variation were classified as anterolateral, anteromiddle, anteromedial, and medial based on the relative location of the VN to the CA. The primary outcome parameters were the prevalence of VN variations and differences according to side, age, and sex., Results: Out of 536 patients, right and left VN variations were identified in 20 (3.7%) and 186 (34.7%), respectively (P<0.001). The anteromiddle type was the commonest type observed on both sides. Eight right (1.5%) and 50 left VNs (9.3%) were located <2 mm from the lateral border of the ipsilateral thyroid gland (P<0.001). The prevalence of VN variations in male and female patients was 42.1% and 32.7%, respectively (P=0.029), and that in patients aged <20, 20-39, 40-59, and ≥60 years was 23.8%, 22.5%, 34.4%, and 47.4%, respectively (P<0.001)., Conclusion: Variations in the VN position were relatively common on US. The variations primarily involved the left VN in the lower cervical region, and an increasing prevalence with age was observed.

For the efficient production of heterologous proteins in the yeast Saccharomyces cerevisiae, we screened for a novel fusion partner from the yeast secretome. From twenty major proteins identified from the yeast secretome, we selected Scw4p, a cell wall protein with similarity to glucanase, and modified to develop a general fusion partner for the secretory expression of heterologous proteins in yeast. The optimal size of the SCW4 gene to act as an efficient fusion partner was determined by C-terminal truncation analysis; two of the variants, S1 (truncated at codon 115Q) and S2 (truncated at codon 142E), were further used for the secretion of heterologous proteins. When fused with S2, the secretion of three target proteins (hGH, exendin-4, and hPTH) significantly increased. Conserved O-glycosylation sites (Ser/Thr-rich domain) and hydrophilic sequences of S2 were deemed important for the function of S2 as a secretion fusion partner. Approximately 5 g/L of the S2-exendin-4 fusion protein was obtained from fed-batch fermentation. Intact target proteins were easily purified by affinity chromatography after in vitro processing of the fusion partner. This system may be of general application for the secretory production of heterologous proteins in S. cerevisiae. KEY POINTS : • Target proteins were efficiently secreted with their N-terminus fused to Scw4p. • O-glycosylation and hydrophilic stretches in Scw4p were important for protein secretion. • A variant of Scw4p (S2) was successfully applied for the secretory expression of heterologous proteins., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Haeckel's recapitulation theory has been a controversial topic in evolutionary biology. However, we have seen some recent cases applying Haeckel's view to interpret the interspecific variation of prenatal ontogeny. To revisit the validity of Haeckel's recapitulation theory, we take bats that have undergone drastic morphological changes and possess a characteristic ecology as a case study. All members of Rhinolophoidea and Yangochiroptera can generate an ultrasonic pulse from the larynx to interpret surrounding objects (laryngeal echolocation) whereas Pteropodidae lacks such ability. It is known that the petrosal bone is particularly derived in shape and expanded in laryngeal echolocators. If Haeckel's recapitulation theory holds, the formation of this derived trait should occur later than those of other bones. Therefore, we compared the prenatal ossification timing of the petrosal in 15 bat species and five outgroup species. We found that the ossification of the petrosal is accelerated in laryngeal echolocators while it is the last bone to ossify in non-laryngeal echolocating bats and non-volant mammals, which runs counter to the prediction generated by Haeckel's recapitulation theory. We point out the evolutionarily labile nature of trait developmental timing and emphasize that Haeckel's recapitulation theory does not hold in many cases. We caution that generating predictions on ancestral conditions and evolutionary history leading from Haeckel's recapitulation theory is not well supported., (© 2021 Wiley Periodicals LLC.)

Background: Proteins with novel functions or advanced activities developed by various protein engineering techniques must have sufficient solubility to retain their bioactivity. However, inactive protein aggregates are frequently produced during heterologous protein expression in Escherichia coli. To prevent the formation of inclusion bodies, fusion tag technology has been commonly employed, owing to its good performance in soluble expression of target proteins, ease of application, and purification feasibility. Thus, researchers have continuously developed novel fusion tags to expand the expression capacity of high-value proteins in E. coli., Results: A novel fusion tag comprising carbohydrate-binding module 66 (CBM66) was developed for the soluble expression of heterologous proteins in E. coli. The target protein solubilization capacity of the CBM66 tag was verified using seven proteins that are poorly expressed or form inclusion bodies in E. coli: four human-derived signaling polypeptides and three microbial enzymes. Compared to native proteins, CBM66-fused proteins exhibited improved solubility and high production titer. The protein-solubilizing effect of the CBM66 tag was compared with that of two commercial tags, maltose-binding protein and glutathione-S-transferase, using poly(ethylene terephthalate) hydrolase (PETase) as a model protein; CBM66 fusion resulted in a 3.7-fold higher expression amount of soluble PETase (approximately 370 mg/L) compared to fusion with the other commercial tags. The intact PETase was purified from the fusion protein upon serial treatment with enterokinase and affinity chromatography using levan-agarose resin. The bioactivity of the three proteins assessed was maintained even when the CBM66 tag was fused., Conclusions: The use of the CBM66 tag to improve soluble protein expression facilitates the easy and economic production of high-value proteins in E. coli., (© 2021. The Author(s).)

The incidence of dementia in patients with surgery under neuraxial anesthesia and the possibility of surgery under neuraxial anesthesia as a risk factor for dementia were investigated. We performed a retrospective matched cohort study with nationwide, representative cohort sample data of the Korean National Health Insurance Service in South Korea between 1 January 2003, and 31 December 2004. The participants were divided into control ( n = 4488) and neuraxial groups ( n = 1122) using propensity score matching. After 9 years of follow-up, the corresponding incidences of dementia were 11.5 and 14.8 cases per 1000 person-years. The risk of dementia in the surgery under neuraxial group was 1.44-fold higher (95% confidence interval [95%CI], 1.17-1.76) than that in the control group. In the subgroup analysis of dementia, the risk of Alzheimer's disease in those who underwent surgery under neuraxial anesthesia was 1.48-fold higher (95%CI, 1.17-1.87) than that in those who did not undergo surgery under anesthesia. Our findings suggest that patients who underwent surgery under neuraxial anesthesia had a higher risk of dementia and Alzheimer's disease than those who did not undergo surgery under neuraxial anesthesia.

Purpose: The purpose of this study was to investigate neuronal and vascular functional deficits in the retina and their association in a diabetic mouse model. We measured electroretinography (ERG) responses and choroidal and retinal blood flow (ChBF, RBF) with magnetic resonance imaging (MRI) in healthy and diabetic mice under basal conditions and under hypercapnic challenge., Methods: Ins2Akita diabetic (Diab, n = 8) and age-matched, wild-type C57BL/6J mice (Ctrl, n = 8) were studied under room air and moderate hypercapnia (5% CO2). Dark-adapted ERG a-wave, b-wave, and oscillatory potentials (OPs) were measured for a series of flashes. Regional ChBF and RBF under air and hypercapnia were measured using MRI in the same mice., Results: Under room air, Diab mice had compromised ERG b-wave and OPs (e.g., b-wave amplitude was 422.2±10.7 μV in Diab vs. 600.1±13.9 μV in Ctrl, p < 0.001). Under hypercapnia, OPs and b-wave amplitudes were significantly reduced in Diab (OPs by 30.3±3.0% in Diab vs. -3.0±3.6% in Ctrl, b-wave by 17.9±1.4% in Diab vs. 1.3±0.5% in Ctrl). Both ChBF and RBF had significant differences in regional blood flow, with Diab mice having substantially lower blood flow in the nasal region (ChBF was 5.4±1.0 ml/g/min in Diab vs. 8.6±1.0 ml/g/min in Ctrl, RBF was 0.91±0.10 ml/g/min in Diab vs. 1.52±0.24 ml/g/min in Ctrl). Under hypercapnia, ChBF increased in both Ctrl and Diab without significant group difference (31±7% in Diab vs. 17±7% in Ctrl, p > 0.05), but an increase in RBF was not detected for either group., Conclusions: Inner retinal neuronal function and both retinal and choroidal blood flow were impaired in Diab mice. Hypercapnia further compromised inner retinal neuronal function in diabetes, while the blood flow response was not affected, suggesting that the diabetic retina has difficulty adapting to metabolic challenges due to factors other than impaired blood flow regulation., Competing Interests: DN is a salaried employee of the commercial company Biogen. SC is a salaried employee of the commercial company Calyx. There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Headaches, especially migraines, have been associated with various vestibular symptoms and syndromes. Tinnitus and hearing loss have also been reported to be more prevalent among migraineurs. However, whether headaches, including migraine or non-migraine headaches (nMH), are associated with vestibular and cochlear disorders remains unclear. Thus, we sought to investigate possible associations between headache and vestibulocochlear disorders. We analyzed 10 years of data from the Smart Clinical Data Warehouse. In patients with migraines and nMH, meniere's disease (MD), BPPV, vestibular neuronitis (VN) and cochlear disorders, such as sensorineural hearing loss (SNHL) and tinnitus, were collected and compared to clinical data from controls who had health check-ups without headache. Participants included 15,128 with migraines, 76,773 patients with nMH and controls were identified based on propensity score matching (PSM). After PSM, the odds ratios (OR) in subjects with migraine versus controls were 2.59 for MD, 2.05 for BPPV, 2.98 for VN, 1.74 for SNHL, and 1.97 for tinnitus, respectively ( p < 0.001). The OR for MD (1.77), BPPV (1.73), VN (2.05), SNHL (1.40), and tinnitus (1.70) in patients with nMH was also high after matching ( p < 0.001). Our findings suggest that migraines and nMH are associated with an increased risk of cochlear disorders in addition to vestibular disorders.

Alaska pollack roe (APR) is a protein source that is usually salted and fermented, containing a high salt content. Using a combination of superheated steam roasting and smoking, we developed a new low-salt ready-to-eat APR variant, whose quality characteristics we analyzed. The optimal conditions for roasting (216 °C for 4 min) and smoking (64 °C for 14 min) were obtained from sensorial attributes using response surface methodology. Under the optimal conditions, smoke-roasted APR had an overall acceptance (OA) score of 8.89. The combination of roasting and smoking significantly increased volatile basic nitrogen (VBN, 18.6%) and decreased the total bacterial count (TBC, 38.6%), while thiobarbituric acid reactive substances (TBARS) were not affected. Smoke-roasting APR also increased its nutritional content to 30% protein with 44% essential amino acids, and more than 40% DHA and EPA in 4.3% fat. During 30 days of storage, the OA, VBN, TBARS, and TBC values significantly changed with time and storage temperature ( p < 0.05). The shelf life of the product was estimated to be 24 d. In conclusion, the combination of roasting and smoking APR could improve product quality and may be an alternative to diversify processed APR.

Background: Inflammation is emerging as a potential mechanism of cervical carcinogenesis. However, few studies have investigated the association between host inflammatory status and the natural course of cervical precursor lesion. The aim of this study was to assess the probability of LSIL regression, associated with an inflammatory biomarker, high-sensitivity C-reactive protein (hs-CRP)., Methods: In a longitudinal cohort study, female participants were examined annually or biannually using cervical cytology between 2006 and 2015. Incident LSIL cases were included in the analysis, with regression defined as at least one consecutive normal cytologic result. A total of 520 women aged 22-64 years were followed up for LSIL regression. The multivariable-adjusted hazard ratios (HRs) for LSIL regression were estimated using a parametric proportional hazards model., Results: During 827.5 person-years of follow-up, 486 out of 520 subjects (93.5%) showed LSIL regression. After adjusting several important potential confounders, a higher quartile of hs-CRP levels was significantly associated with a lower rate of regression (for quartile 4 vs quartile 1, inverse HR 1.33; 95% CI, 1.04-1.69; P for trend = 0.028)., Conclusions: The low rate of spontaneous regression recorded in women with higher hs-CRP lends support to the role of the perturbated host inflammatory status in cervical carcinogenesis, and suggests that hs-CRP level could help monitor LSIL.

Skeletal muscle satellite cells (SkMSCs) play crucial roles in muscle fiber maintenance, repair, and remodeling; however, it remains unknown if these properties are preserved in cultured SkMSCs. In this study, we investigated the characteristics of cultured SkMSCs and their ability to regulate the activity of M1 macrophages. SkMSCs grew well with an average population doubling time of 26.26 ± 6.85 h during 10 passages (P). At P5, Pax7, MyoD, cluster of differentiation (CD)34, and CD56 were not expressed in SkMSCs, but the MSC markers CD73, CD105, and CD90 were expressed and the cells were differentiated into adipocytes and osteoblasts. When SkMSCs were cocultured with macrophages, interleukin (IL)-1β secretion was decreased, prostaglandin (PG)E2 was produced in coculture, and cyclooxygenase-2 protein was induced in an SkMSC-dependent manner. Hepatocyte growth factor (HGF) was highly secreted by monocultured SkMSCs; interferon-γ and lipopolysaccharide reduced its expression level. However, HGF expression recovered when SkMSCs and macrophages were cocultured. Although exogenous PGE2 upregulated macrophage pro-IL-1β expression, it suppressed the secretion of cleaved IL-1β. In contrast, HGF decreased active IL-1β secretion without affecting pro-IL-1β expression. Co-treatment of macrophages with HGF and PGE2 reduced pro-IL-1β expression level and active IL-1β secretion. Our results suggest that SkMSCs lose their satellite cell properties during serial passaging but acquire mesenchymal stem cell properties including the ability to exert an anti-inflammatory response for macrophages through PGE2 and HGF., (© 2021 International Federation for Cell Biology.)

Reactive oxygen species (ROS) are associated with various roles of brown adipocytes. Glucose-6-phosphate dehydrogenase (G6PD) controls cellular redox potentials by producing NADPH. Although G6PD upregulates cellular ROS levels in white adipocytes, the roles of G6PD in brown adipocytes remain elusive. Here, we found that G6PD defect in brown adipocytes impaired thermogenic function through excessive cytosolic ROS accumulation. Upon cold exposure, G6PD-deficient mutant (G6PD mut ) mice exhibited cold intolerance and downregulated thermogenic gene expression in brown adipose tissue (BAT). In addition, G6PD-deficient brown adipocytes had increased cytosolic ROS levels, leading to extracellular signal-regulated kinase (ERK) activation. In BAT of G6PD mut mice, administration of antioxidant restored the thermogenic activity by potentiating thermogenic gene expression and relieving ERK activation. Consistently, body temperature and thermogenic execution were rescued by ERK inhibition in cold-exposed G6PD mut mice. Taken together, these data suggest that G6PD in brown adipocytes would protect against cytosolic oxidative stress, leading to cold-induced thermogenesis., (© 2021 by the American Diabetes Association.)

Background: The COVID-19 pandemic has radically shifted living practices, thereby influencing changes in the health status and behaviors of every person., Objective: The aim of this study was to investigate the impact of COVID-19 on the self-reported health status and health behaviors along with any associated factors in adults in the Republic of Korea wherein no stringent lockdown measures were implemented during the pandemic., Methods: We conducted a web-based self-reported survey from November 2020 to December 2020. The study participants (N=2097) were identified through quota sampling by age, sex, and geographical regions among residents aged 19 years or older in Korea. The survey collected information on basic demographics, changes in self-reported health status, and health behaviors during the COVID-19 pandemic. Self-reported health status and health behaviors were categorized into 3 groups: unchanged, improved, or worsened. A chi-square test and logistic regression analyses were conducted., Results: With regard to changes in the self-reported health status, the majority (1478/2097, 70.5%) of the participants reported that their health was unchanged, while 20% (420/2097) of the participants reported having worser health after the COVID-19 outbreak. With regard to changes in health behaviors, the proportion of participants who increased tobacco consumption was similar to that of those who decreased tobacco consumption (110/545, 20.2% vs 106/545, 19.5%, respectively), while the proportion of those who decreased their drinking frequency was more than twice as many as those who increased their drinking frequency (578/1603, 36.1% vs 270/1603, 16.8%, respectively). Further, those who decreased their exercising frequency were more than those who increased their exercising frequency (333/823, 15.9% vs 211/823, 10%, respectively). The factor that had the greatest influence on lifestyle was age. In the subgroup analysis, the group aged 20-29 years had the highest number of individuals with both a worsened (100/377, 26.5%) and an improved (218/377, 15.7%) health status. Further, individuals aged 20-29 years had greater odds of increased smoking (6.44, 95% CI 2.15-19.32), increased alcohol use (4.64, 95% CI 2.60-8.28), and decreased moderate or higher intensity aerobic exercise (3.39, 95% CI 1.82-6.33) compared to individuals aged 60 years and older. Younger adults showed deteriorated health behaviors, while older adults showed improved health behaviors., Conclusions: The health status and the behavior of the majority of the Koreans were not found to be heavily affected by the COVID-19 outbreak. However, in some cases, changes in health status or health behavior were identified. This study highlighted that some groups were overwhelmingly affected by COVID-19 compared to others. Certain groups reported experiencing both worsening and improving health, while other groups reported unchanged health status. Age was the most influential factor for behavior change; in particular, the younger generation's negative health behaviors need more attention in terms of public health. As COVID-19 prolongs, public health interventions for vulnerable groups may be needed., (©EunKyo Kang, Hyejin Lee, Jee Hoon Sohn, Jieun Yun, Jin Yong Lee, Yun-Chul Hong. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 26.11.2021.)

Background: Xylose contained in lignocellulosic biomass is an attractive carbon substrate for economically viable conversion to bioethanol. Extensive research has been conducted on xylose fermentation using recombinant Saccharomyces cerevisiae expressing xylose isomerase (XI) and xylose reductase/xylitol dehydrogenase (XR/XDH) pathways along with the introduction of a xylose transporter and amplification of the downstream pathway. However, the low utilization of xylose in the presence of glucose, due to the varying preference for cellular uptake, is a lingering challenge. Studies so far have mainly focused on xylose utilization inside the cells, but there have been little trials on the conversion of xylose to xylulose by cell before uptake. We hypothesized that the extracellular conversion of xylose to xylulose before uptake would facilitate better utilization of xylose even in the presence of glucose. To verify this, XI from Piromyces sp. was engineered and hyper-secreted in S. cerevisiae for the extracellular conversion of xylose to xylulose., Results: The optimal pH of XI was lowered from 7.0 to 5.0 by directed evolution to ensure its high activity under the acidic conditions used for yeast fermentation, and hyper-secretion of an engineered XI-76 mutant (E56A and I252M) was accomplished by employing target protein-specific translational fusion partners. The purified XI-76 showed twofold higher activity than that of the wild type at pH 5. The secretory expression of XI-76 in the previously developed xylose utilizing yeast strain, SR8 increased xylose consumption and ethanol production by approximately 7-20% and 15-20% in xylose fermentation and glucose and xylose co-fermentation, respectively., Conclusions: Isomerisation of xylose to xylulose before uptake using extracellular XI was found to be effective in xylose fermentation or glucose/xylose co-fermentation. This suggested that glucose competed less with xylulose than with xylose for uptake by the cell. Consequently, the engineered XI secretion system constructed in this study can pave the way for simultaneous utilization of C5/C6 sugars from the sustainable lignocellulosic biomass., (© 2021. The Author(s).)

An aerobic Cu-promoted oxidative dehydrosulfurative carbon-oxygen cross-coupling of 3,4-dihydropyrimidin-1 H -2-thiones (DHPMs) with both aliphatic and aromatic alcohols is described. Together with the ready availability of DHPMs and both alcohols, the method furnishes facile access to biologically valuable 2-alkoxypyrimidines with rapid diversification., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The association between exposure to general anesthesia (GA) and the risk of dementia is still undetermined. To investigate a possible link to the development of dementia in older people who have undergone GA, we analyzed nationwide representative cohort sample data from the Korean National Health Insurance Service. The study cohort comprised patients over 55 years of age who had undergone GA between January 2003 and December 2004 and consisted of 3100 patients who had undergone GA and 12,400 comparison subjects who had not received anesthesia. After the nine-year follow-up period, we found the overall incidence of dementia was higher in the patients who had undergone GA than in the comparison group (10.5 vs. 8.8 per 1000 person-years), with the risk being greater for women (adjusted HR of 1.44; 95% CI, 1.19-1.75) and those with comorbidities (adjusted HR of 1.39; 95% CI, 1.18-1.64). Patients who underwent GA showed higher risks for Alzheimer's disease and vascular dementia (adjusted HR of 1.52; 95% CI, 1.27-1.82 and 1.64; 95% CI, 1.15-2.33, respectively). This longitudinal study using a sample cohort based on a nationwide population sample demonstrated a significant positive association between GA and dementia, including Alzheimer's disease and vascular dementia.

The species of the genus Hylcalosia Fischer, 1967 (Braconidae: Alysiinae) from South Korea are revised. One species, Hylcalosiabicolor sp. nov. , is new to science. They are described and illustrated herein and an identification key to the Korean species is added. In addition, the DNA barcode region of the mitochondrial cytochrome c oxidase subunit I (COI) has been analysed for the new species and H.sutchanica is used for genetic comparison., (Ju-Hyeong Sohn, Cornelis van Achterberg, Yunjong Han, Hyojoong Kim.)

Objectives: Investigate long-term effects of repeated transarterial chemoembolization (TACE) on portal venous pressure (PVP) using non-invasive surrogate markers of portal hypertension., Methods: Retrospective, Institutional Review Board-approved study. 99 patients [hepatocellular carcinoma (HCC) group (n=57); liver metastasis group (n=42)] who underwent 279TACEs and had longitudinal pre-/post-therapy contrast-enhanced-MRI (n=388) and complete blood work were included. Outcomes of interest were platelet count (PC), spleen volume, ascites and portosystemic collaterals. Variables included TACE type/number, tumor type, microcatheter location, Child-Pugh, baseline tumor burden (tumor number/total/largest size), vessel invasion, alpha-fetoprotein, Eastern Cooperative Oncology Group (ECOG) performance status, and Model for End-Stage Liver Disease (MELD) score. Generalized Estimating Equations assessed the associations between TACE and outcomes. Power analysis determined the sample size was sufficient., Results: No significant change in PC over time was observed in either groups, regardless of liver function ( P >0.05). Baseline spleen volume was 226 cm 3 for metastatic group, and was larger by 204 cm 3 for HCC group ( P <0.001). Spleen volume increased by 20 cm 3 (95%CI: 8-32; P =0.001) for both groups after 1 st TACE and by 16cm 3 /TACE ( P =0.099) over the full follow-up (up to 9TACEs). Spleen volume also tended to increase by 23cm 3 (95%CI: -1-48; P =0.064) with higher tumor burden. Odds of developing moderate/severe ascites for metastatic patients was decreased by 0.5 (95%CI: 0.3-0.9; P =0.014), regardless of the Child-Pugh, and increased by 1.5 (95%CI: 1.2-1.9; P <0.001) among HCC patients with unstable Child-Pugh, whereas no change was noted with stable Child-Pugh. HCC patients with unstable Child-Pugh demonstrated a significant increase in portosystemic collaterals number over time ( P =0.008). PVP-related complications such as variceal bleeding post-TACE were low (0.4%)., Conclusion: Repeated TACEs did seem to have an impact on PVP. However, the increase in PVP had marginal effects with low portal hypertension-related complications., Competing Interests: RD: Consultant: Boston Scientific/BTG, Guerbet. Grant Support: Boston Scientific/BTG, Guerbet, Society of Interventional Oncology. JC: Grant Support: Boston Scientific/BTG, Guerbet, Society of Interventional Oncology, Philips, Rolf W Guenther Foundation for Radiological Research. RS: grant support from the Max Kade Foundation and Siemens Healthineers. ML: former employee of Philips Research North America and is now an employee and stockholder of Visage Imaging, Inc. KKH: Advisory board for Boston Scientific, AStraZaeneca; Reasearch Support: Boston Scientific/BTG. 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 © 2021 Frangakis, Sohn, Bas, Chapiro, Schernthaner, Lin, Hamilton, Pawlik, Hong and Duran.)

Bacterial colonization and transmission via surfaces increase the risk of infection. In this study, we design and employ novel adhesive antimicrobial peptides to prevent bacterial contamination of surfaces. Repeats of 3,4-dihydroxy-L-phenylalanine (DOPA) were added to the C-terminus of NKC, a potent synthetic antimicrobial peptide, and the adhesiveness and antibacterial properties of the resulting peptides are evaluated. The peptide is successfully immobilized on polystyrene, titanium, and polydimethylsiloxane surfaces within 10 min in a one-step coating process with no prior surface functionalization. The antibacterial effectiveness of the NKC-DOPA 5 -coated polystyrene, titanium, and polydimethylsiloxane surfaces is confirmed by complete inhibition of the growth of Escherichia coli , Pseudomonas aeruginosa , and Staphylococcus aureus within 2 h. The stability of the peptide coated on the substrate surface is maintained for 84 days, as confirmed by its bactericidal activity. Additionally, the NKC-DOPA 5 -coated polystyrene, titanium, and polydimethylsiloxane surfaces show no cytotoxicity toward the human keratinocyte cell line HaCaT. The antimicrobial properties of the peptide-coated surfaces are confirmed in a subcutaneous implantation animal model. The adhesive antimicrobial peptide developed in this study exhibits potential as an antimicrobial surface-coating agent for efficiently killing a broad spectrum of bacteria on contact.

Background: We evaluated the impact of prior statin use on successful reperfusion and stroke outcomes after endovascular treatment (EVT)., Method: Using consecutive multicenter databases, we enrolled acute ischemic stroke patients receiving EVT between 2015 and 2021. Patients were classified into prior statin users and no prior statin users after a review of premorbid medications. The primary outcome measure was successful reperfusion defined as modified TICI grade 2b or 3 after EVT. Secondary outcome measures were early neurologic deterioration (END) and a 3-month modified Rankin Scale (mRS) score of 0 to 2., Results: Among 385 patients receiving EVT, 74 (19.2%) were prior statin users, who had a significantly higher successful reperfusion rate compared with no prior statin users (94.6% versus 78.8%, p = 0.002). Successful reperfusion and END occurrence were improved according to statin intensity with a dose-response relationship. In multivariate analysis, prior statin was associated with successful reperfusion after EVT (adjusted odds ratio (95% confidence interval) 5.31 (1.67-16.86)). In addition, prior statin was associated with a lower occurrence of END and good functional status., Conclusion: Our study showed that prior statin use before ischemic stroke might improve successful reperfusion and stroke outcomes after EVT.

Ultrafast optical excitation of matter leads to highly excited states that are far from equilibrium. In this study, femtosecond x-ray absorption spectroscopy was used to visualize the ultrafast dynamics in photoexcited warm dense Cu. The rich dynamical features related to d vacancies are observed on femtosecond timescales. Despite the success in explaining x-ray absorption data in the picosecond regime, the new femtosecond data are poorly understood through the traditional two-temperature model based on the fast thermalization concept and the static electronic structure for high-temperature metals. An improved understanding can be achieved by including the recombination dynamics of nonthermal electrons and changes in the screening of the excited d block. The population balance between the 4sp and 3d bands is mainly determined by the recombination rate of nonthermal electrons, and the underpopulated 3d block is initially strongly downshifted and recovered in several hundreds of femtoseconds.

TAS-117 is a potent and selective allosteric pan-v-akt murine thymoma viral oncogene homolog (Akt) inhibitor. We conducted a single-arm single-center phase 2 study of TAS-117 in heavily treated patients with tumors refractory to systemic chemotherapy and harboring phosphatidylinositol 3-kinase (PI3K)/Akt mutations. Patients with gastrointestinal (GI) cancers were orally administered 16 mg TAS-117 daily, and those with non-GI tumors were administered 24 mg on a 4 days on/3 days off schedule. The primary endpoint was overall response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), PFS ratio, safety, and tolerability. Thirteen patients were enrolled: eight with non-GI (breast, ovarian, endometrial, and non-small cell lung) and five with GI (colon, rectal, gastric, and gallbladder) cancers. Ten patients were treated with TAS-117 after ≥ 4 lines of therapy. Twelve patients showed PIK3 catalytic subunit alpha (PIK3CA) mutations; one harbored an Akt1 E17K mutation. The median treatment duration was 1.4 months; the median number of treatment cycles was 2. The ORR was 8 %, and DCR was 23 %. The median PFS and OS were 1.4 and 4.8 months, respectively. Grade 3-4 treatment-related adverse events were anorexia (grade 3, 8 %) and hyperglycemia (grade 3, 8 %; grade 4, 8 %).Grade 3-4 treatment-related adverse events occurred in 27 % of grade 3 anorexia (9 %) and hyperglycemia (grade 3, 8 %; grade 4, 9\%). TAS-117 showed limited antitumor activity and manageable toxicity. Clinical efficacy was observed in patients with ovarian cancer harboring PIK3CA E545K mutations and in patients with breast cancer harboring PIK3CA H1047R and Akt1 E17K mutations.Trial registration: This study was retrospectively registered with ClinicalTrial.gov (NCT03017521 on January 11, 2017)., (© 2021. The Author(s).)

Federated learning (FL) is a method used for training artificial intelligence models with data from multiple sources while maintaining data anonymity, thus removing many barriers to data sharing. Here we used data from 20 institutes across the globe to train a FL model, called EXAM (electronic medical record (EMR) chest X-ray AI model), that predicts the future oxygen requirements of symptomatic patients with COVID-19 using inputs of vital signs, laboratory data and chest X-rays. EXAM achieved an average area under the curve (AUC) >0.92 for predicting outcomes at 24 and 72 h from the time of initial presentation to the emergency room, and it provided 16% improvement in average AUC measured across all participating sites and an average increase in generalizability of 38% when compared with models trained at a single site using that site's data. For prediction of mechanical ventilation treatment or death at 24 h at the largest independent test site, EXAM achieved a sensitivity of 0.950 and specificity of 0.882. In this study, FL facilitated rapid data science collaboration without data exchange and generated a model that generalized across heterogeneous, unharmonized datasets for prediction of clinical outcomes in patients with COVID-19, setting the stage for the broader use of FL in healthcare., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Triple-negative breast cancer (TNBC) is one of the most heterogeneous diseases in solid tumors and has limited therapeutic options. Due to the lack of appropriate targetable markers, the mainstay therapeutic strategy for patients with TNBC has been chemotherapy for the last several decades. Indeed, TNBC tumors have no expression of estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2 (HER2); therefore, they do not respond to hormone therapy and HER2-targeted therapy. In this review paper, the molecular heterogeneities, possible therapeutic targets, and recently approved and upcoming drugs for TNBC will be summarized.

Fucosterol (24-ethylidene cholesterol) is a bioactive compound belonging to the sterol group that can be isolated from marine algae. Fucosterol of marine algae exhibits various biological activities including anti-osteoarthritic, anticancer, anti-inflammatory, anti-photoaging, immunomodulatory, hepatoprotective, anti-neurological, antioxidant, algicidal, anti-obesity, and antimicrobial. Numerous studies on fucosterol, mainly focusing on the quantification and characterization of the chemical structure, bioactivities, and health benefits of fucosterol, have been published. However, there is no comprehensive review on safety and toxicity levels of fucosterol of marine algae. This review aims to discuss the bioactivities, safety, and toxicity of fucosterol comprehensively, which is important for the application and development of fucosterol as a bioactive compound in nutraceutical and pharmaceutical industries. We used four online databases to search for literature on fucosterol published between 2002 and 2020. We identified, screened, selected, and analyzed the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method and identified 43 studies for review. Despite the potential applications of fucosterol, we identified the need to fill certain related research gaps. Fucosterol exhibited low toxicity in animal cell lines, human cell lines, and animals. However, studies on the safety and toxicity of fucosterol at the clinical stage, which are required before fucosterol is developed for the industry, are lacking.

Chemical investigation of the Antarctic lichen-derived fungal strain Acremonium sp. SF-7394 yielded a new amphilectane-type diterpene, acrepseudoterin ( 1 ), and a new acorane-type sesquiterpene glycoside, isocordycepoloside A ( 2 ). In addition, three known fungal metabolites, (-)-ternatin ( 3 ), [D-Leu]-ternatin ( 4 ), and pseurotin A ( 5 ), were isolated from the EtOAc extract of the fungal strain. Their structures were mainly elucidated by analyzing their NMR and MS data. The absolute configuration of 1 was proposed by electronic circular dichroism calculations, and the absolute configuration of the sugar unit in 2 was determined by a chemical method. The inhibitory effects of the isolated compounds on protein tyrosine phosphatase 1B (PTP1B) were evaluated by enzymatic assays; results indicated that acrepseudoterin ( 1 ) and [D-Leu]-ternatin ( 4 ) dose-dependently inhibited the enzyme activity with IC 50 values of 22.8 ± 1.1 μM and 14.8 ± 0.3 μM, respectively. Moreover, compound 1 was identified as a competitive inhibitor of PTP1B.

Chemical investigation of the Antarctic fungi Pleosporales sp. SF-7343 revealed four known secondary fungal metabolites: alternate C ( 1 ), altenusin ( 2 ), alternariol ( 3 ), and altenuene ( 4 ). The compound structures were identified primarily by NMR and MS analyses. Atopic dermatitis, an inflammatory disease, is driven by the abnormal activation of T helper (Th) 2 cells and barrier dysfunction. We attempted to identify the anti-inflammatory components of SF-7343. Initial screening showed that compounds 1 and 3 inhibited the secretion of interleukin-8 and -6 in tumor necrosis factor-α/interferon-γ-treated HaCaT cells, and these compounds also showed inhibitory effects on CCL5 and CCL22. Compounds 1 and 3 also downregulated the protein expression levels of intercellular adhesion molecule-1 and upregulated the expression of filaggrin and involcurin. The mechanism study results showed that compounds 1 and 3 inhibited nuclear translocation of nuclear factor-kappa B p65 and the phosphorylation of STAT1 and STAT3. Compound 1 , but not compound 3 , significantly promoted the expression of heme oxygenase (HO)-1. The effects of compound 1 were partly reversed by co-treatment with a HO-1 inhibitor, tin protoporphyrin IX. Taken together, this study demonstrates the potential value of Antarctic fungal strain SF-7343 isolates as a bioresource for bioactive compounds to prevent skin inflammation.

Background: Pokemon is an oncogenic transcription regulator that plays a critical role in cellular differentiation. Although it has been found to be overexpressed in several types of cancer involving different organs, its role in thyroid gland has yet to be reported. The objective of this study was to evaluate the expression of Pokemon in papillary thyroid carcinoma (PTC) based on clinicopathological parameters., Methods: Tissue microarray samples derived from patients with PTC or benign thyroid disease were used to evaluate Pokemon expression based on immunohistochemical analysis. Correlations of its expression with various clinicopathological parameters were then analyzed., Results: Pokemon expression was observed in 22.0% of thyroid follicular cells from the normal group, 44.0% from the group with benign thyroid diseases, and 92.1% from the group with PTC (p < .001). The intensity of Pokemon expression was markedly higher in the PTC group. Pokemon expression level and PTC tumor size showed an inverse correlation. T1a tumors showed strong expression levels of Pokemon. However, larger tumors showed weak expression (p = .006)., Conclusions: Pokemon expression is associated with tumorigenesis of PTC, with expression showing an inverse correlation with PTC tumor size. This might be related to the negative regulation of aerobic glycolysis by Pokemon.

Objective: We evaluated the prognostic impacts of body composition components measured by computed tomography (CT) in patients with liver cirrhosis., Methods: A total of 160 cirrhotic patients who underwent CT and hepatic venous pressure gradient measurements were retrospectively enrolled. Cross-sectional areas of skeletal muscle, visceral and subcutaneous fat, and mean CT attenuation of trabecular bone of the fourth lumbar vertebral level (L4HU) were measured., Results: Multivariate analysis showed model for end-stage liver disease score [hazard ratio (HR), 1.086; 95% confidence interval (CI), 1.020-1.156; P = 0.010], hepatic venous pressure gradient (HR, 1.076; 95% CI, 1.021-1.135; P = 0.006), sarcopenia (HR, 1.890; 95% CI, 1.032-3.462; P = 0.039), and L4HU (HR, 1.960 for L4HU <145 Hounsfield units; 95% CI, 1.094-3.512; P = 0.024) were independently associated with long-term mortality. In patients with decompensated cirrhosis, subcutaneous adipose tissue index was the only independent predictor (HR, 0.984; 95% CI, 0.969-0.999; P = 0.039)., Conclusion: Body composition abnormalities determined by CT are associated with long-term prognosis in cirrhotic patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Hemorrhagic transformation (HT) is one of the leading causes of a poor prognostic marker after acute ischemic stroke (AIS). We compared the performances of the several machine learning (ML) algorithms to predict HT after AIS using only structured data. A total of 2028 patients with AIS, who were admitted within seven days of symptoms onset, were included in this analysis. HT was defined based on the criteria of the European Co-operative Acute Stroke Study-II trial. The whole dataset was randomly divided into a training and a test dataset with a 7:3 ratio. Binary logistic regression, support vector machine, extreme gradient boosting, and artificial neural network (ANN) algorithms were used to assess the performance of predicting the HT occurrence after AIS. Five-fold cross validation and a grid search technique were used to optimize the hyperparameters of each ML model, which had its performance measured by the area under the receiver operating characteristic (AUROC) curve. Among the included AIS patients, the mean age and number of male subjects were 69.6 years and 1183 (58.3%), respectively. HT was observed in 318 subjects (15.7%). There were no significant differences in corresponding variables between the training and test dataset. Among all the ML algorithms, the ANN algorithm showed the best performance in terms of predicting the occurrence of HT in our dataset (0.844). Feature scaling including standardization and normalization, and the resampling strategy showed no additional improvement of the ANN's performance. The ANN-based prediction of HT after AIS showed better performance than the conventional ML algorithms. Deep learning may be used to predict important outcomes for structured data-based prediction.

Chub mackerel (CM) is a commercial fish in Korea, owing to its availability and nutritional values. This study aimed to develop a ready-to-heat (RTH) Korean preparation of CM, known as Godeungo gangjeong. We utilized vacuum frying technology to fry the CM and evaluated its quality. Conventional frying with a deep fryer was performed in parallel to assess the superiority of the vacuum fryer. We optimized the frying conditions of vacuum frying (VBF) and deep frying (DBF) using response surface methodology. At optimum conditions of 95 °C for 7 min 42 s, VBF produced better sensory, chemical, and microbial properties than DBF at 190 °C for 5 min 30 s. The nutritional values, including amino acid and fatty acid contents, were investigated and found to be higher in VBF than in DBF. Sensory properties also showed better scores on VBF than DBF, especially in appearance, aroma, taste, and overall acceptability. The VBF produced lower volatile basic nitrogen (VBN), thiobarbituric acid reactive substances (TBARS), and total bacterial count (TBC) than DBF. The findings confirmed that vacuum frying is a better option to produce RTH Godeungo gangjeong , since it provides less oxidation and maintains the product quality. Using the Arrhenius approach, the product was concluded to preserve both quality and safety for 9 months of storage at -18 °C.

Background: Studies assessing the prognostic effect of inflammatory markers of blood cells on the outcomes of patients with acute ischemic stroke treated with endovascular treatment (EVT) are sparse. We evaluated whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) affect reperfusion status in patients receiving EVT., Methods: Using a multicenter registry database, 282 patients treated with EVT were enrolled in this study. The primary outcome measure was unsuccessful reperfusion rate after EVT defined by thrombolysis in cerebral infarction grades 0-2a. Logistic regression analysis was performed to analyze the association between NLR/PLR and unsuccessful reperfusion rate after EVT., Results: Both NLR and PLR were higher in the unsuccessful reperfusion group than in the successful reperfusion group ( p < 0.001). Multivariate analysis showed that both NLR and PLR were significantly associated with unsuccessful reperfusion (adjusted odds ratio (95% confidence interval): 1.11 (1.04-1.19), PLR: 1.004 (1.001-1.01)). The receiver operating characteristic curve showed that the predictive ability of both NLR and PLR was close to good (area under the curve (AUC) of NLR: 0.63, 95% CI (0.54-0.72), p < 0.001; AUC of PLR: 0.65, 95% CI (0.57-0.73), p < 0.001). The cutoff values of NLR and PLR were 6.2 and 103.6 for unsuccessful reperfusion, respectively., Conclusion: Higher NLR and PLR were associated with unsuccessful reperfusion after EVT. The combined application of both biomarkers could be useful for predicting outcomes after EVT.

The brown seaweed Hizikia fusiformis (syn. Sargassum fusiforme ), commonly known as "Hijiki", has been utilized in traditional cuisine and medicine in East Asian countries for several centuries. H. fusiformis has attracted much attention owing to its rich nutritional and pharmacological properties. However, there has been no comprehensive review of the nutritional and pharmacological properties of H. fusiformis . The aim of this systematic review was to provide detailed information from the published literature on the nutritional and pharmacological properties of H. fusiformis . A comprehensive online search of the literature was conducted by accessing databases, such as PubMed, SpringerLink, ScienceDirect, and Google Scholar, for published studies on the nutritional and pharmacological properties of H. fusiformis between 2010 and 2021. A total of 916 articles were screened from all the databases using the preferred reporting items for systematic reviews and meta-analyses method. Screening based on the setdown criteria resulted in 59 articles, which were used for this review. In this review, we found that there has been an increase in the number of publications on the pharmacological and nutritional properties of H. fusiformis over the last 10 years. In the last 10 years, studies have focused on the proximate, mineral, polysaccharide, and bioactive compound composition, and pharmacological properties, such as antioxidant, anticancer, antitumor, anti-inflammatory, photoprotective, neuroprotective, antidiabetic, immunomodulatory, osteoprotective, and gastroprotective properties of H. fusiformis extracts. Overall, further studies and strategies are required to develop H. fusiformis as a promising resource for the nutrition and pharmacological industries.