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Jing-Hui Hu,1,2,* Hai-Jing Shi,1,2,* Zhen-Yu Han,3,* Hong Liu,4 Fu-Hai Ji,1,2 Ke Peng1,2 1Departments of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 4Department of Anesthesiology and Pain Medicine, University of California Davis Health, Sacramento, CA, USA*These authors contributed equally to this workCorrespondence: Ke Peng, Department of Anesthesiology, First Affiliated Hospital of Soochow University, 188 Shizi St, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-159-6215-5989, Email pengke0422@163.comPurpose: Chronic postsurgical pain (CPSP) is a common complication after thoracic surgery and associated with long-term adverse outcomes. This study aims to develop two prediction models for CPSP after video-assisted thoracic surgery (VATS).Methods and Analysis: This single-center prospective cohort study will include a total of 500 adult patients undergoing VATS lung resection (n = 350 for development and n = 150 for external validation). Patients will be enrolled continuously at The First Affiliated Hospital of Soochow University in Suzhou, China. The cohort for external validation will be recruited in another time period. The outcome is CPSP, which is defined as pain with the numerical rating scale score of 1 or higher 3 months after VATS. Univariate and multivariable logistic regression analyses will be performed to develop two CPSP prediction models based on patients’ data of postoperative day 1 and day 14, respectively. For internal validation, we will use the bootstrapping validation technique. For external validation, the discrimination capability of the models will be assessed using the area under the receiver operating characteristic curve, and the calibration will be evaluated using the calibration curve and Hosmer–Lemeshow goodness-of-fit statistic. The results will be presented in model formulas and nomograms.Conclusion: Based on the development and validation of the prediction models, our results contribute to early prediction and treatment of CPSP after VATS.Trial Registration: Chinese Clinical Trial Register (ChiCTR2200066122).Keywords: chronic postsurgical pain, prediction, video-assisted thoracoscopic surgery

Hye Jin Shi, Jae Hee Wee, Joong Sik Eom Division of Infectious Diseases, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, KoreaCorrespondence: Joong Sik EomDivision of Infectious Diseases, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, (21565) 774 Beon-gil 21, Namdongdae-ro, Namdong-gu, Incheon, KoreaTel +82-32-460-2630Fax +82-32-460-2631Email helppl@gachon.ac.krBackground: Urinary tract infections (UTIs) caused by extended spectrum beta-lactamase (ESBL) producing pathogens have increased and are treated with carbapenem in general. Carbapenem use is associated with prolonged hospitalization or daily outpatient visit. The aim of this study was to investigate patients with UTIs by ESBL-producing pathogens for early discharge using an old oral antibiotic, trimethoprim-sulfamethoxazole (TMP-SMX), which is susceptible to ESBL-producing pathogens.Methods: Data on UTIs caused by ESBL-producing pathogens from a single tertiary hospital were collected retrospectively. Patients who had been treated with intravenous carbapenems or oral TMP/SMX were included. Patients’ clinical and microbiological outcomes were compared between oral TMP/SMX and ertapenem treatment groups.Results: A total of 103 patients were included, 21 of whom had been treated with TMP/SMX, whereas 82 with ertapenem. Clinical outcomes between the two groups were not significantly different (TMP/SMX: 90.5%; ertapenem: 84.1%, p = 0.73). The microbiological cure rate was higher in the TMP/SMX group than in the ertapenem group (90.5% vs 58.5%, respectively, p = 0.01). The mean duration of hospitalization was significantly shorter in the TMP/SMX group than in the ertapenem group (8.00 ± 10.50 days vs 14.00 ± 37.00 days, p = 0.07). The mean duration of antibiotic treatment was longer in the ertapenem group than in the TMP/SMX group (16.45 ± 4.77 vs 12.76 ± 5.37 days, p = 0.006).Conclusion: For susceptible pathogens, TMP/SMX may enable early discharge as an effective oral antibiotic treatment option for UTIs caused by ESBL-positive pathogens. Additionally, use of oral antibiotics can shorten hospital stays and reduce medical costs.Keywords: oral antibiotics, ESBL, UTI, TMP/SMX, outpatient treatment

Hye Jin Shi,1 Jin Seo Lee,2 Yong Kyun Cho,1 Joong Sik Eom1 1Division of Infectious Diseases, Department of Internal Medicine, Gil Medical Center, Gachon University School of Medicine, Incheon, Republic of Korea; 2Division of Infectious Diseases, Department of Internal Medicine, Kangdong Sacred Hospital, Hallym University School of Medicine, Seoul, Republic of KoreaCorrespondence: Joong Sik EomDivision of Infectious Diseases, Department of Internal Medicine, Gil Medical Center, Gachon University School of Medicine, 774 Namdongdaero, Namdong-Gu, Incheon 21565, South KoreaTel +82-32-460-2630Fax +82-32-460-4884Email helppl@gachon.ac.krPurpose: The incidences of carbapenem-resistant gram-negative bacilli (CRGNB) and vancomycin-resistant Enterococci (VRE) have increased rapidly in South Korea since 2000. The mortality rate for CRGNB or VRE bacteremia cases is higher than that for non-resistant bacteremia cases. The factors associated with higher mortality are unclear. We investigated the factors associated with mortality from CRGNB or VRE bacteremia and compared the relative risk of these factors.Patients and Methods: We retrospectively collected data from adult patients with CRGNB or VRE bacteremia. Patients were grouped according to whether they survived or died. The data from both groups were compared.Results: During the study period, 171 cases of CRGNB or VRE bacteremia were identified, of which 100 were CRGNB bacteremia cases and 71 were VRE bacteremia cases. Multivariate analysis revealed significant associations with Pitt bacteremia score (PBS) (odds ratio [OR] 1.329, 95% confidence interval [CI] 1.049– 1.684). In the multivariate analysis, negative conversion of follow-up blood culture (FUBC) was related with one-week mortality from CRGNB or VRE bacteremia (OR 17.623, 95% CI 5.726– 54.244). In the multivariate analysis of risk factors for 28-day mortality for CRGNB or VRE bacteremia, the significant risk factors were bacteremia of respiratory origin (OR 4.491, 95% CI 1.622– 12.435) and positive FUBC (OR 4.082, 95% CI 1.626– 10.204).Conclusion: Despite the high mortality rate in patients with CRGNB or VRE bacteremia, the related mortality could be predicted by independent risk factors of PBS, positive FUBC, and bacteremia of respiratory origin.Keywords: prognostic factor, carbapenem-resistant, vancomycin-resistant, bacteremia, mortality

Objective: Green tea has been widely acknowledged in Japan to induce a pleasurable mental feeling. Recent laboratory studies have suggested positive psychological effects as a result of consuming green tea. The present study examined whether green tea consumption in everyday life in Japan is associated with positive mental health.Design: A cross-sectional study was performed in February-March 2002.Setting and Subjects: The subjects of the study consisted of a general population of 600 Japanese aged 20-69 years. Responses of 380 subjects, obtained by home-visit interview, were analysed. The questionnaire inquired about consumption of brewed green tea and other beverages, perceived mental health status, lifestyle and others. The 12-item General Health Questionnaire (GHQ 12) was used for the assessment of mental ill-health (GHQ score >or=4).Results: After adjustments for age, area, perceived mental stress, lifestyle and daily caffeine intake, the consumption of brewed green tea was not statistically associated with any decrease in risk of mental ill-health among either males or females (odds ratio (OR)=0.78, 95% confidence interval (CI)=0.47-1.29 for males; OR=0.77, 95% CI=0.51-1.14 for females). Daily caffeine intake (100 mg) inclusive of green tea, black tea, coffee and other caffeine-containing beverages was associated with a higher risk of mental ill-health among females (OR=1.26, 95% CI=1.01-1.56).Conclusions: The results provide population-based evidence on the consumption of brewed green tea in everyday life and mental health, together with information on consumption patterns of various beverages and lifestyles. [ABSTRACT FROM AUTHOR]

Background: Mortality from colorectal cancer is mainly due to metastatic liver disease. Improved understanding of the molecular events underlying metastasis is crucial for the development of new methods for early detection and treatment of colorectal cancer. Loss of chromosome 8p is frequently seen in colorectal cancer and implicated in later stage disease and metastasis, although a single metastasis suppressor gene has yet to be identified. We therefore examined 8p for genes involved in colorectal cancer progression.Methods: Loss of heterozygosity analyses were used to map genetic loss in colorectal liver metastases. Candidate genes in the region of loss were investigated in clinical samples from 44 patients, including 6 with matched colon normal, colon tumour and liver metastasis. We investigated gene disruption at the level of DNA, mRNA and protein using a combination of mutation, semi-quantitative real-time PCR, western blotting and immunohistochemical analyses.Results: We mapped a 2 Mb region of 8p21-22 with loss of heterozygosity in 73% of samples; 8/11 liver metastasis samples had loss which was not present in the corresponding matched primary colon tumour. 13 candidate genes were identified for further analysis. Both up and down-regulation of 8p21-22 gene expression was associated with metastasis. ADAMDEC1 mRNA and protein expression decreased during both tumourigenesis and tumour progression. Increased STC1 and LOXL2 mRNA expression occurred during tumourigenesis. Liver metastases with low DcR1/TNFRSF10C mRNA expression were more likely to present with extrahepatic metastases (p = 0.005). A novel germline truncating mutation of DR5/TNFRSF10B was identified, and DR4/TNFRSF10A SNP rs4872077 was associated with the development of liver metastases (p = 0.02).Conclusion: Our data confirm that genes on 8p21-22 are dysregulated during colorectal cancer progression. Interestingly, however, instead of harbouring a single candidate colorectal metastasis suppressor 8p21-22 appears to be a hot-spot for tumour progression, encoding at least 13 genes with a putative role in carcinoma development. Thus, we propose that this region of 8p comprises a metastatic susceptibility locus involved in tumour progression whose disruption increases metastatic potential. [ABSTRACT FROM AUTHOR]

Background: Multimodal analgesic strategy is pivotal for enhanced recovery after surgery. The objective of this trial was to assess the effect of subanesthetic esketamine vs. placebo combined with erector spinae plane block (ESPB) vs. intercostal nerve block (ICNB) on postoperative recovery following thoracoscopic lung resection., Materials and Methods: This randomized, controlled, 2×2 factorial trial was conducted at a university hospital in Suzhou, China. One hundred adult patients undergoing thoracoscopic lung surgery were randomized to one of four groups (esketamine-ESPB, esketamine-ICNB, placebo-ESPB, and placebo-ICNB) to receive i.v. esketamine 0.3 mg/kg or normal saline placebo combined with ESPB or ICNB using 0.375% ropivacaine 20 mL. All patients received flurbiprofen axetil and patient-controlled fentanyl. The primary outcome was quality of recovery (QoR) at 24 h postoperatively, assessed using the QoR-15 scale, with a minimal clinically important difference of 6.0., Results: The median age was 57 years and 52% were female. No significant interaction effect was found between esketamine and regional blocks on QoR (P=0.215). The QoR-15 score at 24 h was 111.5±5.8 in the esketamine group vs. 105.4±4.5 in the placebo group (difference=6.1, 95% CI, 4.0-8.1; P<0.001); 109.7±6.2 in the ESPB group vs. 107.2±5.6 in the ICNB group (difference=2.5, 95% CI, 0.2-4.9; P=0.033; not statistically significant after Bonferroni correction). Additionally, esketamine resulted in higher QoR-15 scores at 48 h (difference=4.6) and hospital discharge (difference=1.6), while ESPB led to a higher QoR-15 score at 48 h (difference=3.0)., Conclusions: For patients undergoing thoracoscopic lung resection, subanesthetic esketamine improved QoR after surgery, while ICNB can be used interchangeably with ESPB as a component of multimodal analgesia., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Multimodal analgesia plays a key role in enhanced recovery after surgery. Herein, we describe a trial protocol investigating the effects of oxycodone-vs. sufentanil-based patient-controlled analgesia in combination with quadratus lumborum block (QLB) vs. transverse abdominis plane block (TAPB) on quality of recovery following major laparoscopic gastrointestinal surgery., Methods: and analysis: This is a prospective, randomized, controlled clinical trial with a 2 × 2 factorial design. A total of 120 adult patients undergoing laparoscopic major gastrointestinal surgery will be randomized, in a 1:1:1:1 ratio, to receive one of two patient-controlled analgesia regimens (based on oxycodone or sufentanil) and one of two regional blocks (QLB or TAPB). The primary outcome measure of this trial is the quality of recovery at 24 h after surgery, assessed using the 15-item quality of recovery (QoR-15) scale. The secondary outcomes include QoR-15 scores at 48 and 72 h after surgery; visceral and incisional pain at rest and while coughing at 1, 6, 24 and 48 h postoperatively; analgesic consumption within 0-24 h and 24-48 h postoperatively; need for rescue analgesia; postoperative flatus time; postoperative adverse events (sedation, nausea and vomiting, use of antiemetics, respiratory depression, and dizziness); and length of postoperative hospital stay., Discussion: The results of this trial will provide evidence for the optimal multimodal analgesic strategy to improve the quality of recovery for patients undergoing laparoscopic major gastrointestinal surgery., Trial Registration: This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, identifier: ChiCTR2400080766)., 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.)

Objective: Urinary tract infection is one of the most prevalent bacterial infectious diseases in outpatient treatment, and 50-80% of women experience it more than once, with a recurrence rate of 40-50% within a year; consequently, preventing re-hospitalization of patients is critical. However, in the field of urology, no research on the analysis of the re-hospitalization status for urinary tract infections using machine learning algorithms has been reported to date. Therefore, this study uses various machine learning algorithms to analyze the clinical and nonclinical factors related to patients who were re-hospitalized within 30 days of urinary tract infection., Methods: Data were collected from 497 patients re-hospitalized for urinary tract infections within 30 days and 496 patients who did not require re-hospitalization. The re-hospitalization factors were analyzed using four machine learning algorithms: gradient boosting classifier, random forest, naive Bayes, and logistic regression., Results: The best-performing gradient boosting classifier identified respiratory rate, days of hospitalization, albumin, diastolic blood pressure, blood urea nitrogen, body mass index, systolic blood pressure, body temperature, total bilirubin, and pulse as the top-10 factors that affect re-hospitalization because of urinary tract infections. The 993 patients whose data were collected were divided into risk groups based on these factors, and the re-hospitalization rate, days of hospitalization, and medical expenses were observed to decrease from the high- to low-risk group., Conclusions: This study showed new possibilities in analyzing the status of urinary tract infection-related re-hospitalization using machine learning. Identifying factors affecting re-hospitalization and incorporating preventable and reinforcement-based treatment programs can aid in reducing the re-hospitalization rate and average number of days of hospitalization, thereby reducing medical expenses., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

To study a new method for establishing animal models of prenatal bronchopulmonary dysplasia (BPD), we used lung ultrasound score (LUS) to semi-quantitatively assess the severity of lung lesions in model rats. Lipopolysaccharide (LPS) was injected into the right lung of the fetus of the rat under ultrasound-guided, and the right lung of the neonates were scanning for LUS. Specimens were collected for pathological scoring and detection of pulmonary surfactant-associated glycoprotein (SP)-C and vascular endothelial growth factor (VEGF) expression quantity. The correlation between LUS and pathological scores was analyzed. (1) The animal models were consistent with the pathological manifestations of BPD. (2) It showed a strong positive correlation between LUS and pathological scores in animal models (r = 0.84, P < 0.005), and the expression quantity of SP-C and VEGF in lung tissue were decreased (both P < 0.05). Animal models established by ultrasound-guided puncture of the lung of rats and injection of LPS were consistent with the manifestation of BPD. This method could be used to establish animal models of BPD before birth, and the severity of BPD could be assessed by using LUS., (© 2024. The Author(s).)

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Background: Postoperative sleep disturbance (PSD) occurs frequently in patients who undergo major abdominal surgical procedures. Dexmedetomidine is a promising agent to improve the quality of sleep for surgical patients. We designed this trial to investigate the effects of two different doses of intraoperative dexmedetomidine on the occurrence of PSD in elderly patients who have major abdominal surgery., Methods: In this randomized, double-blind, controlled trial, 210 elderly patients aged ≥65 years will be randomized, with an allocation ratio of 1:1:1, to two dexmedetomidine groups (intraoperative infusion of 0.3 or 0.6 μg/kg/h) and a normal saline placebo group. The primary endpoint is the occurrence of PSD on the first night after surgery, assessed using the Athens Insomnia Scale. The secondary endpoints are (1) the incidence of PSD during the 2nd, 3rd, 5th, 7th, and 30th nights postoperatively; (2) pain at rest and on movement at 24 and 48 h postoperatively, assessed using the Numerical Rating Scale; (3) the incidence of postoperative delirium during 0-7 days postoperatively or until hospital discharge, assessed using the 3-min Confusion Assessment Method; (4) depressive symptoms during 0-7 days postoperatively or until hospital discharge, assessed using the 15-items Geriatric Depression Scale; and (5) quality of recovery on postoperative days 1, 2, and 3, assessed using the 15-items Quality of Recovery Scale. Patients' sleep data will also be collected by Xiaomi Mi Band 7 for further analysis., Discussion: The findings of this trial will provide clinical evidence for improving the quality of sleep among elderly patients undergoing major abdominal surgery., Ethics and Dissemination: This trial was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University (No. 2023-160). The results will be published in a peer-reviewed journal., Trial Registration: Chinese Clinical Trial Registry (ChiCTR2300073163)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Cytomegalovirus (CMV) is the most important opportunistic viral pathogen in solid organ transplant (SOT) recipients. The Korean guideline for the prevention of CMV infection in SOT recipients was developed jointly by the Korean Society for Infectious Diseases and the Korean Society of Transplantation. CMV serostatus of both donors and recipients should be screened before transplantation to best assess the risk of CMV infection after SOT. Seronegative recipients receiving organs from seropositive donors face the highest risk, followed by seropositive recipients. Either antiviral prophylaxis or preemptive therapy can be used to prevent CMV infection. While both strategies have been demonstrated to prevent CMV infection post-transplant, each has its own advantages and disadvantages. CMV serostatus, transplant organ, other risk factors, and practical issues should be considered for the selection of preventive measures. There is no universal viral load threshold to guide treatment in preemptive therapy. Each institution should define and validate its own threshold. Valganciclovir is the favored agent for both prophylaxis and preemptive therapy. The evaluation of CMV-specific cell-mediated immunity and the monitoring of viral load kinetics are gaining interest, but there was insufficient evidence to issue recommendations. Specific considerations on pediatric transplant recipients are included., Competing Interests: WBP is associate editor and NJK, LS-O, KRP are editorial board of Infect Chemother; however, they did not involve in the peer reviewer selection, evaluation, and decision process of this article., (Copyright © 2024 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Background: Previous studies demonstrated a controversial relationship between sarcopenia (SP) and osteoarthritis (OA) and their genetic causality is unclear. Thus, we conducted a Mendelian randomization (MR) analysis to evaluate the possible causal association between sarcopenia-related traits (appendicular lean mass (ALM), grip strength, usual walking pace) and OA. Method: We used pooled genetic data from the UK Biobank for ALM(n = 450,243), left-hand grip strength (n = 461,026), right-hand grip strength (n = 461,089) and usual walking pace (n = 459,915). Moreover, summary statistics for OA were obtained from the latest study conducted by the Genetics of Osteoarthritis Consortium, including all OA (n = 826,690), hand OA (n = 303,7782), hip OA (n = 353,388) and knee OA (n = 396,054). The primary method for estimating causal effects was the inverse-variance weighted (IVW) method, with the utilizing of false discovery rate adjusted p values ( P FDR ). Additional MR methods such as MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), weighted median were employed as supplementary analyses. Results: We discovered ALM (odds ratio (OR) = 1.103, 95% confidence interval (CI) = 1.052-1.156, P FDR = 2.87E-04), hand grip strength (left, IVW OR = 0.823, 95% CI = 0.712 to 0.952, P FDR = 0.020; right, OR = 0.826, 95% CI = 0.718 to 0.950, P FDR = 0.020), and usual walking pace (OR = 0.339, 95% CI = 0.204 to 0.564, P FDR = 2.38E-04) were causally associated with OA risk. In the reverse MR analysis, we identified a causal effect of OA on ALM (β = -0.258, 95% CI = -0.369 to 0.146, P FDR = 0.6.07E-06), grip strength (left, β = -0.064, 95% CI = -0.104 to 0.024, P FDR = 0.002; right, β = -0.055, 95% CI = -0.095 to 0.014, P FDR = 0.008), and usual walking pace (β = -0.104, 95% CI = -0.147 to 0.061, P FDR = 1.61E-05). Conclusion: This present study suggests an obvious causality of SP on OA, with condition exhibiting site-specific effects, while evidence was also provided for the causal effect of OA on SP., 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 Jia, Deng, Su, Shi, Qin, Yu, Yin, Liu and Shi.)

Background: Nocardiosis is a rare, but potentially life-threatening condition. It is difficult to diagnose, and bacterial culture identification can be time consuming. We investigated the characteristics of nocardiosis and the suitability of the treatment approach in Korea., Materials and Methods: This retrospective study was conducted at 5 medical institutions between 2011 and 2021. We reviewed the medical records of patients with microbiologically confirmed nocardiosis. Appropriate antibiotic selection was defined as follows: (1) selecting antibiotics according to the species, (2) if the species of Nocardia was unknown, trimethoprim-sulfamethoxazole-based therapy or linezolid-based therapy was administered, and (3) selection of antibiotics using the antibiotic susceptibility test. The appropriate treatment periods for antibiotics were defined as treatment maintained from 3 to 12 months, depending on involvement of the organs. Descriptive analysis and Fisher exact test were used. Statistical significance was set at P -values of <0.05., Results: Thirty patients were enrolled. Of these patients, 18 (60.0%) were male. The median age was 70.5 years. Among the diagnosed patients, 12 (40.0%) had an immunocompromised status. Eight (30.0%) patients received optimal treatment for the appropriate treatment period. Appropriate dosing duration was observed in 3 of the 12 (25.0%) immunocompromised patients. There was no significant difference between the presence or absence of immunosuppression and the adequacy of treatment for nocardiosis ( P = 1.000). Skin and soft tissue (14 patients) were most frequently involved in this study. Nocardia species (spp.) were isolated from culture at a median of 6.0 days. There were 7 cases with N. farcinica (23.3%)., Conclusion: We found that 60.0% of the patients with nocardiosis did not have an immunocompromised status. Further, 26.7% of the total patients received adequate treatment for nocardiosis. The reasons for suboptimal management of nocardiosis in Korea are presumed to be diagnostic difficulties, lack of awareness about nocardiosis, and difficulties in selecting antibiotics for Nocardia spp. among clinicians. The lack of antibiotic susceptibility tests for Nocardia spp. could be the source of these problems. Nocardiosis should be suspected in cases of recurrent infections with skin and soft tissue, musculoskeletal, or respiratory system involvement with or without an immunocompromised status. Clinical microbiological support is required for the diagnosis and selection of antibiotics in Korea. High clinical index of suspicion and clinical microbiological support are required for the accurate diagnosis of nocardiosis in Korea., Competing Interests: No conflict of interest., (Copyright © 2023 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Background: The purpose of this study was to investigate the mechanism of sanguinarine (SAN) against nasopharyngeal carcinoma (NPC) by means of network pharmacology, molecular docking technique, and experimental verification., Methods: The SAN action targets were predicted using the Swiss Target Prediction database, the related NPC targets were determined using the GEO database, and the intersection of drug and disease pathway targets were considered to be the potential targets of SAN against NPC. The target-protein interaction network map was constructed using the STRING database, and the core target genes of SAN against NPC were obtained via topological network analysis. "R" language gene ontology (GO) function and Kyoto encyclopedia of genes and genome (KEGG) pathway enrichment analyses were used to dock the core target genes with SAN with the help of AutodockVina. Cell proliferation was detected using MTT and xCELLigence real-time cell analysis. Apoptosis was identified via Hoechst 33342 staining, JC-1 mitochondrial membrane staining, and annexin V-FITC/PI double fluorescence staining, while protein expression was quantified using western blotting., Results: A total of 95 SAN against NPC targets were obtained using target intersection, and 8 core targets were obtained by topological analysis and included EGFR, TP53, F2, FN1, PLAU, MMP9, SERPINE1, and CDK1. Gene ontology enrichment analysis identified 530 items, and 42 items were obtained by Kyoto encyclopedia of genes and genome pathway enrichment analysis and were mainly related to the PI3K/AKT, MAPK, and p53 signaling pathways. Molecular docking results showed that SAN had good binding activity to the core target. SAN inhibited the proliferation of NPC cells, induced apoptosis, reduced the expression levels of survivin and Bcl2, and increased the expression levels of Bax and cleaved caspase-8. It also decreased the expression levels of the key proteins p-c-Raf, p-MEK, and p-ERK1/2 in the MAPK/ERK signaling pathway in NPC cells., Conclusion: SAN inhibits the proliferation and induces the apoptosis of NPC cells through the MAPK/ERK signaling pathway., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

We present a summary of the evidence on testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and organ procurement from deceased donors and provide recommendations based on current clinical data and the guidelines from major transplant organizations. Because of the limited historical experience with coronavirus disease 2019 (COVID-19), certain recommendations in this document are based on theoretical rationales rather than clinical data. The recommendations in this manuscript may be subject to revision as subsequent clinical studies provide definitive evidence regarding COVID-19 in organ procurement.

Background: To explore the independent association between lumbar endplate damage and bone mineral density (BMD) in patients with degenerative disc disease (DDD)., Methods: This retrospective investigation was based out of a prospectively collected database from the Affiliated Kunshan Hospital of Jiangsu University. Data from 192 DDD patients, collected between December 2018 and January 2022, were chosen for the final analysis. The average total endplate score (TEPS) of lumbar(L) 1-L4 was assessed by magnetic resonance imaging (MRI), and represents the extent of endplate damage. Osteoporosis severity was assessed via the L1-L4 BMD evidenced by dual-energy x-ray absorptiometry (DXA). Other analyzed information included gender, age, body mass index (BMI), and osteophyte score (OSTS). Uni- and multivariate linear regression analyses were employed to evaluate the association between average TEPS and BMD of L1-L4. Moreover, the generalized additive model (GAM) was employed for non-linear association analysis., Results: Upon gender, age, BMI, and OSTS adjustments, a strong independent inverse relationship was observed between average TEPS and BMD (β, -0.021; 95% CI, -0.035 to -0.007, P-value = 0.00449). In addition, the gender stratification analysis revealed a linear relationship in males, and a non-linear relationship in females. Specifically, there was a significantly stronger negative relationship between average TEPS and BMD in females, when the average TEPS was < 3.75 (β, -0.063; 95% CI, -0.114 to -0.013; P-value = 0.0157). However, at an average TEPS > 3.75, the relationship did not reach significance (β, 0.007; 95% CI, -0.012 to 0.027; P-value = 0.4592)., Conclusions: This study demonstrated the independent negative association between average TEPS and BMD values of L1-L4. Upon gender stratification, a linear relationship was observed in males, and a non-linear association in females. The findings reveal that patients with osteoporosis or endplate damage require more detailed examinations and treatment regimen., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Post-induction hypotension (PIH) is a common event in elderly surgical patients and is associated with increased postoperative morbidity and mortality. This study aims to develop and validate a PIH prediction model for elderly patients undergoing elective non-cardiac surgery to identify potential PIH in advance and help to take preventive measures., Methods and Analysis: A total of 938 elderly surgical patients (n=657 for development and internal validation, n=281 for temporal validation) will be continuously recruited at The First Affiliated Hospital of Soochow University in Suzhou, China. The main outcome is PIH during the first 15 min after anaesthesia induction or before skin incision (whichever occurs first). We select candidate predictors based on published literature, professional knowledge and clinical expertise. For model development, we will use the least absolute shrinkage and selection operator regression analysis and multivariable logistic regression. For internal validation, we will apply the bootstrapping technique. After model development and internal validation, temporal validation will be conducted in patients recruited in another time period. We will use the discrimination, calibration and max-rescaled Brier score in the temporal validation cohort. Furthermore, the clinical utility of the prediction model will be assessed using the decision curve analysis, and the results will be presented in a nomogram and a web-based risk calculator., Ethics and Dissemination: Ethical approval was obtained from the Ethics Committee of the First Affiliated Hospital of Soochow University (Approval No. 2023-012). This PIH risk prediction model will be published in a peer-reviewed journal., Trial Registration Number: ChiCTR2200066201., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Schools play an organizational role in managing myopia-related behavioral habits among students. We evaluated the effects of school myopia management measures on myopia onset and progression in a school-based prospective 1-year observational study., Methods: In total, 8319 children from 26 elementary schools were included. Online questionnaire completed by a parent, in which school myopia management experience including outdoor activities in recess or physical education class, teachers' supervision, and teaching facilities. Variables were defined as implemented well or poorly, according to the Comprehensive Plan to Prevent Myopia among Children and Teenagers. Children underwent ophthalmic examinations, and the incidence and progression of myopia from 2019 to 2020 were estimated. Multilevel logistic regression models were constructed to analyze the association between school management measures and myopia development in 8,9 years and 10,11 years students., Results: From 2019 to 2020, the incidence of myopia among primary school students was 36.49%; the mean difference of spherical equivalent in myopic children was - 0.29 ± 1.22 diopters. The risk of incident myopia was reduced by 20% in 8,9 years participants with well-implemented class recess compared with those with poorly implemented class recess (adjusted odds ratio [aOR]: 0.80, p = 0.032). PE outdoor time was significantly associated with myopia incidence in 10,11 years students (aOR: 0.76, p = 0.043). Compared with poorly implemented reading and writing posture, desk and chair height, 10,11 participants with well-implemented desk and chair height were less likely to have rapid myopic progression (p = 0.029, p = 0.022)., Conclusion: In Shanghai, children's myopia is associated with better implementation of school myopia management measures. The present findings suggest that outdoor activities during class recess or PE class, providing suitable desks and chairs, and adequate instruction in reading and writing postures might protect against pathological eye growth. An age-specific myopia prevention and control programs in school is of primary importance., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused the death of thousands of patients worldwide. Although age is known to be a risk factor for morbidity and mortality in COVID-19 patients, critical illness or death is occurring even in the younger age group as the epidemic spreads. In early 2022, omicron became the dominant variant of the COVID-19 virus in South Korea, and the epidemic proceeded on a large scale. Accordingly, this study aimed to determine whether young adults (aged ≤ 50 years) with critical COVID-19 infection during the omicron period had different characteristics from older patients and to determine the risk factors for mortality in this specific age group., Methods: We evaluated 213 critical adult patients (high flow nasal cannula or higher respiratory support) hospitalized for polymerase chain reaction-confirmed COVID-19 in nine hospitals in South Korea between February 1, 2022 and April 30, 2022. Demographic characteristics, including body mass index (BMI) and vaccination status; underlying diseases; clinical features and laboratory findings; clinical course; treatment received; and outcomes were collected from electronic medical records (EMRs) and analyzed according to age and mortality., Results: Overall, 71 critically ill patients aged ≤ 50 years were enrolled, and 142 critically ill patients aged over 50 years were selected through 1:2 matching based on the date of diagnosis. The most frequent underlying diseases among those aged ≤ 50 years were diabetes and hypertension, and all 14 patients who died had either a BMI ≥ 25 kg/m² or an underlying disease. The total case fatality rate among severe patients (S-CFR) was 31.0%, and the S-CFR differed according to age and was higher than that during the delta period. The S-CFR was 19.7% for those aged ≤ 50 years, 36.6% for those aged > 50 years, and 38.1% for those aged ≥ 65 years. In multivariate analysis, age (odds ratio [OR], 1.084; 95% confidence interval [CI], 1.043-1.127), initial low-density lipoprotein > 600 IU/L (OR, 4.782; 95% CI, 1.584-14.434), initial C-reactive protein > 8 mg/dL (OR, 2.940; 95% CI, 1.042-8.293), highest aspartate aminotransferase > 200 IU/L (OR, 12.931; 95% CI, 1.691-98.908), and mechanical ventilation implementation (OR, 3.671; 95% CI, 1.294-10.420) were significant independent predictors of mortality in critical COVID-19 patients during the omicron wave. A similar pattern was shown when analyzing the data by age group, but most had no statistical significance owing to the small number of deaths in the young critical group. Although the vaccination completion rate of all the patients (31.0%) was higher than that in the delta wave period (13.6%), it was still lower than that of the general population. Further, only 15 (21.1%) critically ill patients aged ≤ 50 years were fully vaccinated. Overall, the severity of hospitalized critical patients was significantly higher than that in the delta period, indicating that it was difficult to find common risk factors in the two periods only with a simple comparison., Conclusion: Overall, the S-CFR of critically ill COVID-19 patients in the omicron period was higher than that in the delta period, especially in those aged ≤ 50 years. All of the patients who died had an underlying disease or obesity. In the same population, the vaccination rate was very low compared to that in the delta wave, indicating that non-vaccination significantly affected the progression to critical illness. Notably, there was a lack of prescription for Paxlovid for these patients although they satisfied the prescription criteria. Early diagnosis and active initial treatment was necessary, along with the proven methods of vaccination and personal hygiene. Further studies are needed to determine how each variant affects critically ill patients., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

PIWI-clade proteins harness piRNAs of 24-33 nt in length. Of great puzzles are how PIWI-clade proteins incorporate piRNAs of different sizes and whether the size matters to PIWI/piRNA function. Here we report that a PIWI-Ins module unique in PIWI-clade proteins helps define the length of piRNAs. Deletion of PIWI-Ins in Miwi shifts MIWI to load with shorter piRNAs and causes spermiogenic failure in mice, demonstrating the functional importance of this regulatory module. Mechanistically, we show that longer piRNAs provide additional complementarity to target mRNAs, thereby enhancing the assembly of the MIWI/eIF3f/HuR super-complex for translational activation. Importantly, we identify a c.1108C>T (p.R370W) mutation of HIWI (human PIWIL1) in infertile men and demonstrate in Miwi knock-in mice that this genetic mutation impairs male fertility by altering the property of PIWI-Ins in selecting longer piRNAs. These findings reveal a critical role of PIWI-Ins-ensured longer piRNAs in fine-tuning MIWI/piRNA targeting capacity, proven essential for spermatid development and male fertility., (© 2023. Science China Press.)

Background: We aimed to identify the genes of 35 pathogens, including viruses, bacteria, and protozoa that cause waterborne infectious diseases, and to assess the feasibility of a wastewater-based surveillance system., Materials and Methods: Wastewater was aseptically sampled once a month from 2 sites. A total of 1 L of wastewater from each site underwent 0.2 µm filtration to generate the sample A. Subsequently, 200 ul of the filtered water was ultra-filtered and concentrated to generate the sample B, which was mixed with sample A in a 1:1 ratio. We performed a Filmarray ® Gastrointestinal (GI) panel (BioFire Diagnnostics', Salt Lake City, UT, USA) test to simultaneously detect 13 enterobacteria, 5 enterovirus, and 4 protozoa. RNA was extracted to assess 18 types of viruses., Results: Severe acute respiratory syndrome coronavirus 2 adenovirus, bocavirus, and rhinovirus was detected at both site. Norovirus GI/GII was continuously detected at both sites. Moreover, adenovirus, group A rotaviruses, and hepatitis A virus were frequently detected; however, hepatitis E virus was absent at either site. Campylobacter, enteroaggregative Escherichia coli , enterotoxigenic E. coli , Shiga toxin-producing E. coli , and Clostridioides difficile toxin A/B were detected at both sites. Giardia lamblia was also detected in both sites., Conclusion: We analyze multiple infectious disease pathogens under sample surveillance with incidence. Further in-depth studies on wastewater-based surveillance will be feasible and important., Competing Interests: No conflict of interest., (Copyright © 2023 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

Anxiety disorders are currently a major psychiatric and social problem, the mechanisms of which have been only partially elucidated. The hippocampus serves as a major target of stress mediators and is closely related to anxiety modulation. Yet so far, its complex anatomy has been a challenge for research on the mechanisms of anxiety regulation. Recent advances in imaging, virus tracking, and optogenetics/chemogenetics have permitted elucidation of the activity, connectivity, and function of specific cell types within the hippocampus and its connected brain regions, providing mechanistic insights into the elaborate organization of the hippocampal circuitry underlying anxiety. Studies of hippocampal neurotransmitter systems, including glutamatergic, GABAergic, cholinergic, dopaminergic, and serotonergic systems, have contributed to the interpretation of the underlying neural mechanisms of anxiety. Neuropeptides and neuroinflammatory factors are also involved in anxiety modulation. This review comprehensively summarizes the hippocampal mechanisms associated with anxiety modulation, based on molecular, cellular, and circuit properties, to provide tailored targets for future anxiety treatment., (© 2023. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Advanced paternal age has been overlooked, and its effect on fertility remains controversial. Previous studies have focused mainly on intracytoplasmic sperm injection (ICSI) cycles in men with oligozoospermia. However, few studies have reported on men with semen parameters within reference ranges. Therefore, we conducted a retrospective cohort study analyzing the reproductive outcomes of couples with non-male-factor infertility undergoing in vitro fertilization (IVF) cycles. In total, 381 cycles included were subgrouped according to paternal age (<35-year-old, 35-39-year-old, or ≥40-year-old), and maternal age was limited to under 35 years. Data on embryo quality and clinical outcomes were analyzed. The results showed that fertilization and high-quality embryo rates were not significantly different (all P > 0.05). The pregnancy rate was not significantly different in the 35-39-year-old group (42.0%; P > 0.05), but was significantly lower in the ≥40-year-old group (26.1%; P < 0.05) than that in the <35-year-old group (40.3%). Similarly, the implantation rate significantly decreased in the ≥40-year-old group (18.8%) compared with that in the <35-year-old group (31.1%) and 35-39-year-old group (30.0%) (both P < 0.05). The live birth rate (30.6%, 21.7%, and 19.6%) was not significantly different across the paternal age subgroups (<35-year-old, 35-39-year-old, and ≥40-year-old, respectively; all P > 0.05), but showed a declining trend. The miscarriage rate significantly increased in the 35-39-year-old group (44.8%) compared with that in the <35-year-old group (21.0%; P < 0.05). No abnormality in newborn birth weight was found. The results indicated that paternal age over 40 years is a key risk factor that influences the assisted reproductive technology success rate even with good semen parameters, although it has no impact on embryo development., Competing Interests: None

Background: This study aimed to describe the maternal, obstetrical, and neonatal outcomes in pregnant women with coronavirus disease 2019 (COVID-19) and identify the predictors associated with the severity of COVID-19., Methods: This multicenter observational study included consecutive pregnant women admitted because of COVID-19 confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR) test at 15 hospitals in the Republic of Korea between January 2020 and December 2021., Results: A total of 257 women with COVID-19 and 62 newborns were included in this study. Most of the patients developed this disease during the third trimester. Nine patients (7.4%) developed pregnancy-related complications. All pregnant women received inpatient treatment, of whom 9 (3.5%) required intensive care, but none of them died. The gestational age at COVID-19 diagnosis (odds ratio [OR], 1.096, 95% confidence interval [CI], 1.04-1.15) and parity (OR, 1.703, 95% CI, 1.13-2.57) were identified as significant risk factors of severe diseases. Among women who delivered, 78.5% underwent cesarean section. Preterm birth (38.5%), premature rupture of membranes (7.7%), and miscarriage (4.6%) occurred, but there was no stillbirth or neonatal death. The RT-PCR test of newborns' amniotic fluid and umbilical cord blood samples was negative for severe acute respiratory syndrome coronavirus 2., Conclusion: At the time of COVID-19 diagnosis, gestational age and parity of pregnant women were the risk factors of disease severity. Vertical transmission of COVID-19 was not observed, and maternal severity did not significantly affect the neonatal prognosis., Competing Interests: The authors have no potential conflicts of interest to disclosure., (© 2022 The Korean Academy of Medical Sciences.)

Background: Coronavirus disease 2019 (COVID-19) during pregnancy is associated with increased disease severity and an increased risk of perinatal complications. However, few studies of pregnant women with COVID-19 have been conducted in Korea. The purpose of this study was to describe the clinical course and pregnancy outcomes of pregnant women admitted to our hospital with COVID-19 according to the severity., Materials and Methods: This retrospective cohort study included women aged 18 years of age or older who were hospitalized in the Gachon University Gil Medical Center with COVID-19 during pregnancy between July 1, 2021 and January 31, 2022. COVID-19 severity was classified according to the "Criteria for severity classification by symptoms of COVID-19" presented by the Korea Disease Control and Prevention Agency. Severe cases were defined as those who required oxygen treatment administered via a high-flow nasal cannula or invasive mechanical ventilation or should be applied extracorporeal membrane oxygenation (ECMO) or continuous renal replacement therapy., Results: A total of 103 pregnant women were hospitalized with COVID-19 during the study period. Their mean age was 33 (± 4.14) years, and 4 (3.9%) had been vaccinated against COVID-19. At the time of diagnosis of COVID-19, 3 (2.9%), 33 (32.0%), and 67 (65.1%) patients were in the first, second, and third trimester, respectively. The most common symptoms were cough (99 patients, 96.1%) and fever (85 patients, 82.5%). There was 1 (1.0%) asymptomatic patient. Forty patients (38.8%) required supplemental oxygen and 19 patients (18.4%) had severe disease. Of the 19 severe cases, 7 were in the 2nd trimester and 12 were in the 3rd trimester. Forty-one (39.8%) patients delivered, including two twin deliveries. Of the 41 cases of delivery, 14 were premature, 4 out of 21 (19.0%) in mild, 4 out of 12 (25.0%) in moderate, and 6 out of 8 (75.0%) in severe. Severe disease was associated with an increased rate of preterm birth ( P = 0.012). Four of the 43 neonates (9.1%) received oxygen treatment., Conclusion: Pregnant women with COVID-19 had a high rate of severe disease and a high preterm delivery rate, especially among those with severe disease., Competing Interests: No conflict of interest., (Copyright © 2022 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)

42Sp50 is an isoform of the eukaryotic translation elongation factor 1 A (eEF1A) and is vital for fish ovarian development. Spotted scat ( Scatophagus argus ) is a popular marine cultured fish species in Southern Asia and China, and its artificial reproduction is complicated, with a relatively low success ratio in practice. In this study, the 42Sp50 gene was cloned from spotted scat. Tissue distribution analysis showed that 42Sp50 was mainly expressed in the ovary. qRT-PCR showed that 42Sp50 expression levels gradually decreased insignificantly in the ovaries from phase II to IV. Western blot analysis showed that 42Sp50 was highly expressed in the ovary, while it was almost undetectable in the testis. Immunohistochemistry analysis stained 42Sp50 mainly in the cytoplasm of the previtellogenic oocytes in ovaries of normal XX-female and sex-reversed XY-female. Aside from fish and amphibians, 42Sp50 was also identified in some reptile species using genomic database searching. Analyses of the transcriptome data from four different fish species (Hainan medaka ( Oryzias curvinotus ), silver sillago ( Sillago sihama ), Nile tilapia ( Oreochromis niloticus ), and Hong Kong catfish ( Clarias fuscus )) revealed ovaries biased expression of 42Sp50 in all, similar to spotted scat. While the neighbor genes of 42Sp50 did not show ovary biased expression in the fish species analyzed. Bisulfite Sequencing PCR (BSP) results showed that the DNA methylation level of 42Sp50 promoter was low in ovaries, testes, and muscles. The luciferase reporter assay demonstrated that Dmrt4 activated 42Sp50 expression in the presence of Sf1 or Foxh1 . These results suggest that 42Sp50 may be involved in regulating the early phase oocytes development of spotted scat., 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 © 2022 Zhi, Jiang, Mustapha, Li, Shi, Li and Zhu.)

Background: We evaluated clinical effectiveness of regdanvimab (CT-P59), a severe acute respiratory syndrome coronavirus 2 neutralizing monoclonal antibody, in reducing disease progression and clinical recovery time in patients with mild-to-moderate coronavirus disease 2019 (COVID-19), primarily Alpha variant., Methods: This was phase 3 of a phase 2/3 parallel-group, double-blind, randomized clinical trial. Outpatients with mild-to-moderate COVID-19 were randomized to single-dose regdanvimab 40 mg/kg (n = 656) or placebo (n = 659), alongside standard of care. The primary endpoint was COVID-19 disease progression up to day 28 among "high-risk" patients. Key secondary endpoints were disease progression (all randomized patients) and time to recovery (high-risk and all randomized patients)., Results: Of 1315 randomized patients, 880 were high risk; the majority were infected with Alpha variant. The proportion with disease progression was lower (14/446, 3.1% [95% confidence interval {CI}, 1.9%-5.2%] vs 48/434, 11.1% [95% CI, 8.4%-14.4%]; P  < .001) and time to recovery was shorter (median, 9.27 days [95% CI, 8.27-11.05 days] vs not reached [95% CI, 12.35-not calculable]; P  < .001) with regdanvimab than placebo. Consistent improvements were seen in all randomized and non-high-risk patients who received regdanvimab. Viral load reductions were more rapid with regdanvimab. Infusion-related reactions occurred in 11 patients (4/652 [0.6%] regdanvimab, 7/650 [1.1%] placebo). Treatment-emergent serious adverse events were reported in 5 of (4/652 [0.6%] regdanvimab and 1/650 [0.2%] placebo)., Conclusions: Regdanvimab was an effective treatment for patients with mild-to-moderate COVID-19, significantly reducing disease progression and clinical recovery time without notable safety concerns prior to the emergence of the Omicron variant., Clinical Trials Registration: NCT04602000; 2020-003369-20 (EudraCT)., Competing Interests: Potential conflicts of interest. J. Y. K. has been an investigator in COVID-19 clinical trials by Daewoong Pharmaceuticals, Enzychem Lifesciences, and GC Pharma, outside the scope of the submitted work, and by Celltrion, Inc, within the scope of the submitted work. O. S., An. S.-C., and Ad. S.-C. have been investigators in COVID-19 clinical trials by Algernon Pharmaceuticals, Atea Pharmaceuticals, Diffusion Pharmaceuticals, and Regeneron Pharmaceuticals, outside the scope of the submitted work, and by Celltrion, Inc, within the scope of the submitted work. L.-L. P., N. E. R.-M., M. D., V. B., E. G. M., N. G., O. C.-S., S.-A. F., and H. J. S. have been investigators in COVID-19 clinical trials by Celltrion, Inc, within the scope of the submitted work. S. J. L. and S. H. K. are employees of, and hold shares in, Celltrion, Inc. I. C., Y. J. B., J. H. S., D. R. C., S. J. K., M. R. K., S. G. L., and G. P. are employees of Celltrion, Inc. J. S. E. has been an investigator in COVID-19 clinical trials by Enzychem Lifesciences, Bukwang Pharm. Co., Ltd, and SK Chemicals outside the scope of the submitted work, and by Celltrion, Inc, within the scope of the submitted work., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Numerous patients around the globe are dying from coronavirus disease 2019 (COVID-19). While age is a known risk factor, risk analysis in the young generation is lacking. The present study aimed to evaluate the clinical features and mortality risk factors in younger patients (≤ 50 years) with a critical case of COVID-19 in comparison with those among older patients (> 50 years) in Korea., Methods: We analyzed the data of adult patients only in critical condition (requiring high flow nasal cannula oxygen therapy or higher respiratory support) hospitalized with PCR-confirmed COVID-19 at 11 hospitals in Korea from July 1, 2021 to November 30, 2021 when the delta variant was a dominant strain. Patients' electronic medical records were reviewed to identify clinical characteristics., Results: During the study period, 448 patients were enrolled. One hundred and forty-two were aged 50 years or younger (the younger group), while 306 were above 50 years of age (the older group). The most common pre-existing conditions in the younger group were diabetes mellitus and hypertension, and 69.7% of the patients had a body mass index (BMI) > 25 kg/m². Of 142 younger patients, 31 of 142 patients (21.8%, 19 women) did not have these pre-existing conditions. The overall case fatality rate among severity cases was 21.0%, and it differed according to age: 5.6% (n = 8/142) in the younger group, 28.1% in the older group, and 38% in the ≥ 65 years group. Age (odds ratio [OR], 7.902; 95% confidence interval [CI], 2.754-18.181), mechanical ventilation therapy (OR, 17.233; 95% CI, 8.439-35.192), highest creatinine > 1.5 mg/dL (OR, 17.631; 95% CI, 8.321-37.357), and combined blood stream infection (OR, 7.092; 95% CI, 1.061-18.181) were identified as independent predictors of mortality in total patients. Similar patterns were observed in age-specific analyses, but most results were statistically insignificant in multivariate analysis due to the low number of deaths in the younger group. The full vaccination rate was very low among study population (13.6%), and only three patients were fully vaccinated, with none of the patients who died having been fully vaccinated in the younger group. Seven of eight patients who died had a pre-existing condition or were obese (BMI > 25 kg/m²), and the one remaining patient died from a secondary infection., Conclusion: About 22% of the patients in the young critical group did not have an underlying disease or obesity, but the rate of obesity (BMI > 25 kg/m²) was high, with a fatality rate of 5.6%. The full vaccination rate was extremely low compared to the general population of the same age group, showing that non-vaccination has a grave impact on the progression of COVID-19 to a critical condition. The findings of this study highlight the need for measures to prevent critical progression of COVID-19, such as vaccinations and targeting young adults especially having risk factors., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Background: Since the global coronavirus disease 2019 (COVID-19) pandemic, non-pharmacological interventions (NPIs) such as extensive and comprehensive hand hygiene, mask-wearing, and social distancing have been implemented globally. This study aimed to investigate changes in respiratory viruses other than severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that occurred following the implementation of these NPIs., Methods: From January 2018 to December 2021, influenza-like illness patient specimens and specimens from the Korea Influenza and Respiratory Viruses Surveillance System were analyzed at the Incheon Metropolitan City Institute of Public Health and Environment. Oropharyngeal or nasopharyngeal swab samples from respiratory infection patients were transferred in a virus transport medium at 4°C. After RNA or DNA extraction, respiratory virus-specific genes for human influenza virus (IFV), adenovirus (ADV), parainfluenza virus (PIV), respiratory syncytial virus (RSV), human rhinovirus (hRV), human coronavirus, human bocavirus, and human metapneumovirus were detected by individual real-time reverse transcription polymerase chain reaction., Results: A total 3,334 samples were collected. After NPI was implemented, the detection of respiratory viruses other than SARS-CoV-2 decreased overall. The yearly detection rate of respiratory viruses was decreased from 69.5% (399/574) in 2018 and 73.3% (505/689) in 2019 to 19.8% (206/1,043) in 2020 and 34.9% (365/1,028) in 2021. The epidemic was more prominent in respiratory viruses such as IFV and RSV, which were considered dominant viruses, especially those with viral envelopes. Among viruses that were not considered dominant, hRV showed no clear change before and after NPI, while PIV showed a rapid increase compared to the existing dominant viruses between October-December 2021, after the increase in the number of gatherings started at the end of September and the "Relaxing COVID19 and mitigation policy," which was implemented on November 1., Conclusion: NPI seems to have influenced the isolation and transmission of respiratory viruses in South Korea. In the future, additional studies focusing on the isolation and transmission patterns of respiratory viruses following NPI are needed., Competing Interests: This study used laboratory surveillance data corresponding to the Incheon Metropolitan City among Korea Influenza and Respiratory Viruses Surveillance System (KINRESS). Other authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Background: Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated., Methods: This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model., Results: Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids ( P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03-13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26-14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P = 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089)., Conclusion: Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Obtaining high-quality embryos is one of the key factors to improve the clinical pregnancy rate of assisted reproductive technologies (ART). So far, the clinical evaluation of embryo quality depends on embryo morphology. However, the clinical pregnancy rate is still low. Therefore, new indicators are needed to further improve the evaluation of embryo quality. Several studies have shown that the decrease of sperm-specific protein actin-like 7A (ACTL7A) leaded to low fertilization rate, poor embryo development, and even infertility. The aim of this study was to study whether the different expression levels of ACTL7A on sperm can be used as a biomarker for predicting embryo quality. In this study, excluding the factors of severe female infertility, a total of 281 sperm samples were collected to compare the ACTL7A expression levels of sperms with high and low effective embryo rates and analyze the correlation between protein levels and in-vitro fertilization (IVF) laboratory outcomes. Our results indicated that the ACTL7A levels were significantly reduced in sperm samples presenting poor embryo quality. Furthermore, the protein levels showed a significant correlation with fertilization outcomes of ART. ACTL7A has the potential to be a biomarker for predicting success rate of fertilization and effective embryo and the possibility of embryo arrest. In conclusion, sperm-specific protein ACTL7A has a strong correlation with IVF laboratory outcomes and plays important roles in fertilization and embryo development., Competing Interests: None

Background: Adult hippocampal neurogenesis and synaptic plasticity are necessary for the behavioral response to the selective serotonin reuptake inhibitor (SSRI) fluoxetine, but the molecular mechanisms underlying these effects are only partially understood. Methods: Anxiety and depressive-like behaviors in mice were developed by chronic mild stress (CMS) or chronic corticosterone (CORT) treatment. Pharmacological and genetic approaches were used to investigate the role of the neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS (CAPON) interaction in behavioral and neuroplasticity effects of serotoninergic system. Molecular biological and morphological studies were performed to examine the mechanisms underlying the behavioral effects of nNOS-CAPON interaction that modulated by 5-HT1A receptor (5-HT1AR). Results: Fluoxetine prevented chronic stress-induced nNOS-CAPON upregulation and coupling in the dentate gyrus (DG), and promoting nNOS-CAPON association weakened the anxiolytic and antidepressant effects of fluoxetine in stressed mice. The chronic fluoxetine elevated 5-HT and 5HT1AR agonist 8-OH-DPAT decreased the expression and binding of nNOS with CAPON, whereas 5-HT1AR antagonist NAN-190 had the opposite effects. Importantly, augmenting nNOS-CAPON binding neutralized 8-OH-DPAT-upregulated spine density of DG granule cells and well-characterized synaptic-related proteins, including brain-derived neurotrophic factor (BDNF) and phosphorylation of extracellular signal regulated kinase (ERK), cAMP-response element binding protein (CREB), and synapsin in the DG and abolished the anxiolytic and antidepressant-like effects of 8-OH-DPAT. In contrast, dissociation of nNOS from CAPON rescued the effects of NAN-190 on behavior and neuroplasticity. Conclusion: Taken together, our results indicated that fluoxetine modifies mood behaviors and hippocampal neuroplasticity by disrupting the nNOS-CAPON interaction that links postsynaptic 5-HT1AR activation., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: The timing of adiposity peak (AP) or adiposity rebound (AR) is a determinant of overweight or obesity in adolescence and adulthood. However, limited studies have reported the association in young school-age children. We aimed to evaluate this association and explore the role of health behaviours in it., Methods: Routinely collected, sequential, anthropometric data from the 1st to 80th months of age were used to estimate AP and AR timings in 2330 children born in Shanghai between 2010 and 2013. Multivariate regression analyses were applied to identify the associations between the AP or AR timings and the risk of developing overweight or obesity in first-grade school children. The roles of health behaviours, including dietary patterns, physical activity level, sleep and snacking habits, and screen time, were also evaluated., Results: Children with a late AP or an early AR were at higher risk of overweight but not obesity or central obesity in their first grade. A high physical activity level was associated with a lower risk of having overweight in children with a late AP, and limited screen time was associated with a decreased risk of having overweight or obesity in children with an early AR. The absence of a late-night snacking habit in children with a non-early AR indicated a decreased risk of having overweight. However, this association was not observed among children with an early AR., Conclusion: The timings of AP and AR are tied to overweight in middle childhood. Prevention strategies are suggested to move forward to control late AP and early AR., (© 2022. The Author(s).)

Importance: Evidence on the timing of fetal growth alterations associated with gestational diabetes or on the association of the maternal glycemic trajectory with fetal growth during pregnancy remains lacking., Objective: To examine the associations between maternal glucose levels and offspring intrauterine growth., Design, Setting, and Participants: This cohort study used data from 4574 eligible pregnant women and their offspring in the Shanghai Maternal-Child Pairs Cohort collected from April 10, 2016, to April 30, 2018. Group-based trajectory modeling was used to classify fasting plasma glucose levels during pregnancy into 3 glycemic trajectories (trajectory 1, consistently normal glucose levels in all 3 trimesters; trajectory 2, hyperglycemia only in late pregnancy; and trajectory 3, hyperglycemia in all 3 trimesters [ie, consistently high glucose levels]). Statistical analysis was performed from April 25, 2020, to October 1, 2021., Exposures: Gestational diabetes, which was defined using the results of an oral glucose tolerance test., Main Outcomes and Measures: Longitudinal fetal biometrics during gestational weeks 11 to 40 and birth outcomes were obtained from medical records. Pregnancy was partitioned into 3 periods (<24, 24-34, and >34 weeks' gestational age). The differences in offspring growth (log-transformed) and maternal glucose levels were compared using generalized linear mixed models., Results: A total of 4121 pregnant women had oral glucose tolerance test results (mean [SD] age, 28.8 [4.1] years), 3746 of whom had glycemic trajectory data (mean [SD] age, 28.6 [4.1] years); 983 women (23.8%) had gestational diabetes. Throughout the pregnancy period and compared with the women without gestational diabetes or with women in the trajectory 1 group, the fetal biometrics for the women with gestational diabetes or for those in the trajectory 3 group were significantly higher (except for biparietal diameter), with an estimated increase in fetal weight in the group with gestational diabetes (β = 1.82; 95% CI, 1.03-2.61) and in the trajectory 3 group (β = 1.50; 95% CI, 0.54-2.47; P = .002). Fetal biometric alterations among women with gestational diabetes appeared before 24 weeks' gestational age, with neonatal birth weight significantly higher than in the group without gestational diabetes at 40.4 g (95% CI, 9.8-71.1 g) along with an increased risk of large size for gestational age (odds ratio, 1.36; 95% CI, 1.05-1.75) and macrosomia (odds ratio, 1.47; 95% CI, 1.12-1.94). However, pregnant women in the trajectory 2 group manifested significantly reduced fetal biometrics, and abdominal circumference was significantly augmented after 34 weeks' gestational age (increase, β = 1.92; 95% CI, 0.87-2.99)., Conclusions and Relevance: In this cohort study, pregnant women who received a diagnosis of gestational diabetes in midpregnancy or had hyperglycemia during all 3 trimesters showed an association with altered fetal growth patterns, including increased estimated fetal weight that appeared before 24 weeks' gestational age, increased birth weight, and the risk for large size for gestational age and macrosomia.

Objective: To observe the association between exposure to midazolam within 24 hours prior to delirium assessment and the risk of delirium., Methods: We performed a systematic cohort study with two sets of cohorts to estimate the relative risks of outcomes among patients administered midazolam within 24 hours prior to delirium assessment. Propensity score matching was performed to generate a balanced 1:1 matched cohort and identify potential prognostic factors. The outcomes included the odds of delirium, mortality, length of intensive care unit stay, length of hospitalization, and odds of being discharged home., Results: A total of 78,364 patients were included in this study, of whom 22,159 (28.28%) had positive records. Propensity matching successfully balanced covariates for 9348 patients (4674 per group). Compared with no administration of midazolam, midazolam administration was associated with a significantly higher risk of delirium, higher mortality, and a longer intensive care unit stay. Patients treated with midazolam were relatively less likely to be discharged home. There was no significant difference in hospitalization duration., Conclusions: Midazolam may be an independent risk factor for delirium in critically ill patients.

Siwu-Yin (SWY), a traditional Chinese medicinal formula, can replenish blood and nourish Yin. It was recorded in ancient Chinese medicine books in treating esophageal dysphagia, which has similar symptoms and prognosis with esophageal precancerous lesions and esophageal cancer. However, its effect has not been established in vivo . This study explores the antiesophageal cancer effect of SWY on rats with esophageal precancerous lesions. By performing 16S rRNA gene sequencing and metabolomics, it was suggested that SWY may improve the composition of intestinal flora of rats by regulating the synthesis and secretion of bile acids. In addition, flow cytometry results showed that SWY treatment modified tumor microenvironment by improving macrophage polarization and therefore inhibiting the occurrence of esophageal precancerous lesions., Competing Interests: Y-QS was employed by the Company Shijiazhuang Yiling Pharmaceutical Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shi, Chen, Chen, Wu, Li, Sun, Shi and Li.)

Gonadal somatic cell-derived factor (Gsdf) is a member of the TGF-β superfamily, which exists mainly in fishes. Homozygous gsdf mutations in Japanese medaka and zebrafish resulted in infertile females, and the reasons for their infertility remain unknown. This study presents functional studies of Gsdf in ovary development using CRISPR/Cas9 in Nile tilapia ( Oreochromis niloticus ). The XX wild type (WT) female fish regularly reproduced from 12 months after hatching (mah), while the XX gsdf -/- female fish never reproduced and were infertile. Histological observation showed that at 24 mah, number of phase IV oocyte in the XX gsdf -/- female fish was significantly lower than that of the WT fish, although their gonadosomatic index (GSI) was similar. However, the GSI of the XX gsdf -/- female at 6 mah was higher than that of the WT. The mutated ovaries were hyperplastic with more phase I oocytes. Transcriptome analysis identified 344 and 51 up- and down-regulated genes in mutants compared with the WT ovaries at 6 mah. Some TGF-β signaling genes that are critical for ovary development in fish were differentially expressed. Genes such as amh and amhr2 were up-regulated, while inhbb and acvr2a were down-regulated in mutant ovaries. The cyp19a1a , the key gene for estrogen synthesis, was not differentially expressed. Moreover, the serum 17β-estradiol (E 2 ) concentrations between XX gsdf -/- and WT were similar at 6 and 24 mah. Results from real-time PCR and immunofluorescence experiments were similar and validated the transcriptome data. Furthermore, Yeast-two-hybrid assays showed that Gsdf interacts with TGF-β type II receptors (Amhr2 and Bmpr2a). Altogether, these results suggest that Gsdf functions together with TGF-β signaling pathway to control ovary development and fertility. This study contributes to knowledge on the function of Gsdf in fish oogenesis., 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 © 2022 Jiang, Peng, Liu, Mustapha, Huang, Shi, Li, Li and Wang.)

Tissue engineering is a promising strategy to repair spinal cord injury (SCI). However, a bioscaffold with mechanical properties that match those of the pathological spinal cord tissue and a pro-regenerative matrix that allows robust neurogenesis for overcoming post-SCI scar formation has yet to be developed. Here, we report that a mechanically enhanced decellularized spinal cord (DSC) scaffold with a thin poly (lactic-co-glycolic acid) (PLGA) outer shell may fulfill the requirements for effective in situ neuroengineering after SCI. Using chemical extraction and electrospinning methods, we successfully constructed PLGA thin shell-ensheathed DSC scaffolds (PLGA-DSC scaffolds) in a way that removed major inhibitory components while preserving the permissive matrix. The DSCs exhibited good cytocompatibility with neural stem cells (NSCs) and significantly enhanced their differentiation toward neurons in vitro. Due to the mechanical reinforcement, the implanted PLGA-DSC scaffolds showed markedly increased resilience to infiltration by myofibroblasts and the deposition of dense collagen matrix, thereby creating a neurogenic niche favorable for the targeted migration, residence and neuronal differentiation of endogenous NSCs after SCI. Furthermore, PLGA-DSC presented a mild immunogenic property but prominent ability to polarize macrophages from the M1 phenotype to the M2 phenotype, leading to significant tissue regeneration and functional restoration after SCI. Taken together, the results demonstrate that the mechanically matched PLGA-DSC scaffolds show promise for effective tissue repair after SCI., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Identifying practical and distinguished indicators and influencing factors of male aging may be useful in predicting subsequent aging trends, designing personalized prevention, and improving lifestyle and health., Methods: A cross-sectional, population-based study was performed in Jiashan County, China in 2016. A total of 690 local male residents, aged 40 to 80 years, were eligible for recruitment. Demographic and lifestyle information was collected through structured interviews. A self-designed head scale, the Medical Outcomes Study 36-item Short Form (SF-36), International Index of Erectile Function (IIEF5), Aging Males' Symptoms (AMS), and International Prostate Symptom Score (IPSS) were used. Analysis of variance, local polynomial regression smoothing curves, multiple linear regression, and partial correlation analyses were performed., Results: All the scales deteriorated with increasing age (P < 0.01), especially from the age of 60. The most significant changes between adjacent age groups were found in IIEF5 scores (16.7, 43.5 and 39.4%). Income, nutrition, personality and neighborhood relationship had an effect on SF-36 and AMS after adjusting for age (P < 0.01). Furthermore, neighborhood relationship modified the age effect on the head scale score and IIEF5 (P = 0.03); nutrition modified the relationship between age and SF-36 (P < 0.01)., Conclusions: Recession of reproductive health may be a distinct predictor of male aging. The associations of social inequalities or personality and health offer potential interventions for men's health in aging. Self-reported scales may limit the precision and more physical fitness tests could be combined for a more precise assessment., (© 2021. The Author(s).)

The objective of the current study was to explore the relationship between longitudinal change in body mass index (BMI) and reproductive hormones in middle-aged and elderly Chinese men. A cohort study was conducted in a rural area of China. Local male residents aged 40-80 years were recruited at baseline in 2012 and were followed up in 2016. Information about weight, height, waist circumference, sex hormones, smoking status, and medical history were obtained. The change in BMI reported no significant relationship with the change in total testosterone (TT), calculated free testosterone (cFT), and bioavailable testosterone (BioT) in Pearson correlation analyses. When the change in BMI was divided into three groups-"great loss," "normal fluctuation," and "great gain"-TT, cFT and BioT had the highest increase (or the lowest decrease) in men with "normal fluctuation" in BMI compared with the other two groups. The advantage of maintaining a stable BMI was more evident for those who were overweight, non-smoking, and disease-free. There was a tendency of a continuous increase in cFT and BioT with BMI increase in smoking and diseased populations. Maintaining a stable BMI is associated with maintaining normal levels of reproductive hormones, especially in overweight, non-smoking, and healthy men aged over 40 years.

Eukaryotic translation initiation factor 4E (eIF4E) mediates cap-dependent translation. Genetic and inhibitor studies show that eIF4E expression is required for the successful transition from maternal to embryonic control of mouse embryo development. eIF4E was present in the oocyte and in the cytoplasm soon after fertilization and during each stage of early development. Functional knockout (Eif4e-/-) by PiggyBac [Act-RFP] transposition resulted in peri-implantation embryonic lethality because of the failure of normal epiblast formation. Maternal stores of eIF4E supported development up to the two- to four-cell stage, after which new expression occurred from both maternal and paternal inherited alleles. Inhibition of the maternally acquired stores of eIF4E (using the inhibitor 4EGI-1) resulted in a block at the two-cell stage. eIF4E activity was required for new protein synthesis in the two-cell embryo and Eif4e-/- embryos had lower translational activity compared with wild-type embryos. eIF4E-binding protein 1 (4E-BP1) is a hypophosphorylation-dependent negative regulator of eIF4E. mTOR activity was required for 4E-BP1 phosphorylation and inhibiting mTOR retarded embryo development. Thus, this study shows that eIF4E activity is regulated at key embryonic transitions in the mammalian embryo and is essential for the successful transition from maternal to embryonic control of development., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)