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Wei-Yao Wang,1,2 Yi-Hsin Chen,3– 5 Yu-Lin Lee,1,2 Chen-Feng Chiu,6 Shih-Ming Tsao1,2 1School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 2Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan; 3Department of Nephrology, Taichung Tzu Chi Hospital, Taichung, Taiwan; 4School of Medicine, Tzu Chi University, Hualien, Taiwan; 5Department of Artificial Intelligence and Data Science, National Chung Hsing University, Taichung, Taiwan; 6Department of Internal Medicine, Feng Yuan Hospital, Ministry of Health and Welfare, Taichung, TaiwanCorrespondence: Shih-Ming Tsao, Department of Internal Medicine, Chung Shan Medical University Hospital, &num; 110, Section 1, Jianguo North Road, Taichung City, 40201, Taiwan, Tel +886 4 24739595 ext.34718, Fax +886-4-23248172, Email tsmhwy@ms24.hinet.netBackground: Determining oxacillin susceptibility using reference methods and automated systems is crucial for treating invasive infections caused by Staphylococcus aureus. This study compares the oxacillin susceptibility results from the two automated systems with agar dilution and correlates them with genotypes of invasive S. aureus.Methods: Non-duplicate S. aureus invasive isolates were collected over an 11-year period. The oxacillin susceptibility was determined with Phoenix 100 (Jan 2011 to Aug 2018) or Vitek 2 (Sep 2018 to Dec 2021), and susceptibility for oxacillin and cefoxitin was determined with agar dilution. Methicillin-resistant S. aureus (MRSA) was confirmed with mecA existence, and the genotype was determined using SCCmec. The association between genotype and antibiotic susceptibility using two automated systems and agar dilution was evaluated.Results: A total of 842 invasive S. aureus, including 443 mecA+ MRSA and 399 mecA- MSSA, were collected. The susceptibility rates of oxacillin determined by two automated systems and agar dilution were 68.8% (76.8% for Phoenix 100 and 57.6% for Vitek 2) and 54.0%, respectively. When compared with the oxacillin susceptibility using agar dilution, the categorical agreement for Phoenix 100 and Vitek 2 were 0.46% and 0.88%, respectively (p < 0.001). One hundred and forty-three isolates were misinterpreted as oxacillin-susceptible S. aureus (OSSA) using automated systems while comparing with agar dilution, among which molecularly community-associated MRSA (CA-MRSA) outnumbered healthcare-associated MRSA (HA-MRSA) (99 vs 34, p < 0.001). There were 70 mecA+ OSSA (OS-MRSA) using agar dilution, among which 42 harbored SCCmec types were predominantly categorized as CA-MRSA (38, p < 0.001).Conclusion: The categorical agreement of Vitek 2 in determining oxacillin susceptibility and predicting mecA existence is comparable with agar dilution, whereas Phoenix 100 is not. Most of those ORSA determined by agar dilution but misinterpreted as OSSA by automated systems and OS-MRSA are categorized as CA-MRSA.Keywords: oxacillin susceptibility, automated systems, agar dilution, SCCmec, CA-MRSA

Tsan-Min Wang,1 Yi-Liang Lee,2,3 Chi-Hsiang Chung,1,4,5 Chien-An Sun,6,7 Chieh-Yi Kang,8 Gwo-Jang Wu,1,2,9 Wu-Chien Chien1,4,5,10 1Department of Medical Research, Tri-Service General Hospital, Taipei, 11490, Taiwan; 2Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 3Department of Obstetrics and Gynecology, Kang Ning Hospital, Taipei, Taiwan, Republic of China; 4School of Public Health, National Defense Medical Center, Taipei, 11490, Taiwan; 5Taiwanese Injury Prevention and Safety Promotion Association (TIPSPA), Taipei, 11490, Taiwan; 6Department of Public Health, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, Republic of China; 7Big Data Research Center, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, Republic of China; 8Department of Obstetrics & Gynecology, Chi Mei Medical Center Gynecologic Oncologist Division, Tainan City, Taiwan, Republic of China; 9Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, 11490, Taiwan; 10Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 11490,TaiwanCorrespondence: Wu-Chien Chien; Gwo-Jang Wu, Email chienwu@ndmctsgh.edu.tw; gwojang@yahoo.comObjective: A multitude of previous studies has substantiated that endometriosis correlated highly with psychiatric health. This study aims to investigate the association between endometriosis and psychiatric health.Methods: Utilizing the National Health Insurance Research Database of Taiwan, 100,770 enrolled participants, including 20,154 patients with endometriosis and 80,616 in the control group (1:4), matched for age, and index date from Taiwan’s Longitudinal Health Insurance Database between January 1, 2000, and December 31, 2015. The Cox proportional regression model was used to compare the risk of mental disorders during the 16 years of follow-up after adjusting for confounding factors.Results: Of the study patients, 4083 (20.26%) developed mental disorders; 9225 of the 80,616 controls (11.44%) developed mental disorders. The Cox regression demonstrated that, after adjusting for age, monthly income, urbanization level, etc., people with endometriosis are more likely to suffer from mental disorders compared to those without endometriosis (hazard ratio [HR]=2.131; 95% confidence interval [CI]= 1.531– 2.788; p< 0.001). The result illustrated that women over 40 years old had a more significant risk.Conclusion: Compared to people without endometriosis, this study provides evidence that patients with endometriosis are at a 2.131-fold higher risk of developing mental disorders, especially in elder women. Regular psychiatric follow-up might be needed for those patients.Keywords: endometriosis, mental disorders, national health insurance research database, cohort study, Taiwan, women

Tsan-Min Wang,1,2 Cheng-Hao Chou,1,2 Yi-Liang Lee,3,4 Chi-Hsiang Chung,1,5,6 Yao-Ching Huang,1,7 Xiao-Cheng Lai,8 Chien-An Sun,9,10 Chieh-Yi Kang,11 Gwo-Jang Wu,1,3,12 Wu-Chien Chien1,5,6,8 1Department of Medical Research, Tri-Service General Hospital, Taipei, Taiwan; 2Taipei Municipal Jianguo High School, Taipei, Taiwan; 3Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China; 4Department of Obstetrics and Gynecology, Kang Ning Hospital, Taipei, Taiwan, Republic of China; 5School of Public Health, National Defense Medical Center, Taipei, Taiwan; 6Taiwanese Injury Prevention and Safety Promotion Association (TIPSPA), Taipei, Taiwan; 7Department of Chemical Engineering and Biotechnology, National Taipei University of Technology (Taipei Tech), Taipei, Taiwan; 8Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; 9Department of Public Health, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, Republic of China; 10Big Data Research Center, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, Republic of China; 11Chi Mei Medical Center Gynecologic Oncologist Division, Department of Obstetrics & Gynecology, Tainan City, Taiwan, Republic of China; 12Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, TaiwanCorrespondence: Gwo-Jang Wu; Chieh-Yi Kang, Email gwojang@yahoo.com; albert0113@yahoo.com.twObjective: Previous studies have shown an increased in psychiatric disorders in women with disorders associated with hyperandrogenism, but few nationwide cohorts have studied this phenomenon. Therefore, this study is aimed to examine the association between the clinical manifestations of hyperandrogenism and subsequent psychiatric disorders.Methods: Based on the National Health Insurance Research Database, 49,770 enrolled participants were matched for age and index date between January 1, 2000, and December 31, 2015. Hirsutism, polycystic ovary syndrome, and acne are characterized by hyperandrogenism. After adjusting for confounding factors, we used Cox proportional analysis to compare the risk of psychiatric disorders during the 16 years of follow-up.Results: Of all the participants, 1319 (13.25%) had psychiatric disorders in the study group, whereas only 3900(9.80%) had psychiatric disorders in the control group. After adjusting for age, and monthly income, the Cox regression analysis showed that the study patients were more likely to develop psychiatric disorders (hazard ratio [HR]: 2.004, 95% confidence interval [CI] = 1.327– 2.724, P < 0.001). The results demonstrated that women aged 20– 29 years had a more significant risk.Conclusion: Women with clinical characteristics of hyperandrogenism have a higher risk of developing psychiatric disorders, especially those aged 20– 29 years.Keywords: hyperandrogenism, psychiatric disorders, national health insurance research database, cohort study, women, Taiwan

Ing-Moi Hii,1 Chun-Eng Liu,1 Yu-Lin Lee,1 Wei-Lun Liu,2,3 Ping-Feng Wu,4,5 Min-Han Hsieh,6 Mao-Wang Ho,7 Yen-Hsu Chen,8–10 Fu-Der Wang4,5 1Division of Infectious Disease, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 2Department of Emergency and Critical Care Medicine, Fu Jen Catholic University Hospital, New Taipei City, Taiwan; 3School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; 4Division of Infectious Disease, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 5School of Medicine, National Yang-Ming University, Taipei, Taiwan; 6Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Division of Infectious Diseases, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan; 8Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, HsinChu, Taiwan; 9Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; 10School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, Center of Dengue Fever Control and Research, Kaohsiung Medical University, Kaohsiung, Taiwan Purpose: In 2012, the Clinical and Laboratory Standards Institute (CLSI) revised its breakpoints for drugs and species because of the increase in non-albicans Candida infections and their drug resistance. Following global trends, the non-albicans candidemia resistance rate has increased in Taiwan as well. To update the antifungal susceptibility of non-albicans candidemia isolates, we conducted a multicenter study using the revised break points.Patients and methods: Patients with non-albicans candidemia infections were identified at five tertiary hospitals in Taiwan from July 1, 2011, to June 30, 2014. The broth microdilution method using a Sensititre YeastOne system was performed for the determination of minimum inhibitory concentration (MIC). The susceptibility was interpreted based on the guidelines of the CLSI (CLSI M27-S4 and M27-S3).Results: Candida tropicalis was the predominant non-albicans candidemia pathogen (42.4%), and it showed increased fluconazole non-susceptibility (36.3%) when compared to the results from previous studies. In particular, C. tropicalis showed high cross-resistance to azole agents. C. tropicalis isolates that were found to be resistant to fluconazole also showed increased resistance to voriconazole (82.2%) and posaconazole (100%). The increased non-susceptibility of Candida glabrata to multiple antifungal agents, based on the revised break points, resulted from an increase in dose-dependent susceptibility (94.4%) rather than from an increase in resistance (5.6%).Conclusion: The resistance rate of non-albicans candidemia isolates is increasing, particularly for C. tropicalis and C. glabrata. Keywords: non-albicans candidemia, resistance, susceptibility

Bor-Shiunn Lee,1,2 Hong-Ping Lin,3 Jerry Chun-Chung Chan,4 Wei-Chuan Wang,2 Ping-Hsuan Hung,2 Yu-Hsin Tsai,4 Yuan-Ling Lee1,2 1Graduate Institute of Oral Biology, 2Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University and Hospital, Taipei, 3Department of Chemistry, National Cheng Kung University, Tainan, 4Department of Chemistry, National Taiwan University, Taipei, Taiwan, Republic of China Abstract: Mineral trioxide aggregate (MTA) is the most frequently used repair material in endodontics, but the long setting time and reduced mechanical strength in acidic environments are major shortcomings. In this study, a novel sol-gel-derived calcium silicate cement (sCSC) was developed using an initial Ca/Si molar ratio of 3, with the most effective mixing orders of reactants and optimal HNO3 catalyst volumes. A Fourier transform infrared spectrometer, scanning electron microscope with energy-dispersive X-ray spectroscopy, and X-ray powder diffractometer were used for material characterization. The setting time, compressive strength, and microhardness of sCSC after hydration in neutral and pH 5 environments were compared with that of MTA. Results showed that sCSC demonstrated porous microstructures with a setting time of ~30 min, and the major components of sCSC were tricalcium silicate, dicalcium silicate, and calcium oxide. The optimal formula of sCSC was sn200, which exhibited significantly higher compressive strength and microhardness than MTA, irrespective of neutral or pH 5 environments. In addition, both sn200 and MTA demonstrated good biocompatibility because cell viability was similar to that of the control. These findings suggest that sn200 merits further clinical study for potential application in endodontic repair of perforations. Keywords: acidic environment, compressive strength, mesoporous, mineral trioxide aggregate, mixing order, sol-gel reaction

Sarcopenia is an age-related muscle atrophy syndrome characterized by the loss of muscle strength and mass. Although many agents have been used to treat sarcopenia, there are no successful treatments to date. In this study, we identified Danshensu sodium salt (DSS) as a substantial suppressive agent of muscle atrophy. We used a D-galactose (DG)-induced aging-acceleration model, both in vivo and in vitro, to confirm the effect of DSS on sarcopenia. DSS inhibits the expression of muscle atrophy-related factors (MuRF1, MAFbx, myostatin, and FoxO3a) in DG-induced mouse C2C12 and human skeletal muscle cells. Additionally, DSS restored the diameter of reduced C2C12 myotubes. Next, we demonstrated that DSS stimulates AMPK and PGC1α through CaMKII. DSS inhibits the translocation of FoxO3a into the nucleus, thus inhibiting muscle atrophy in a calcium-dependent manner. DSS initiated the protein-protein interaction between FoxO3a and PGC1α. The reduction of the PGC1α-FoxO3a interaction by DG was restored by DSS. Also, DSS suppressed increased intracellular reactive oxygen species (ROS) by DG. In animal models, DSS administration improved mouse muscle mass and physical performance (grip strength and hanging test) under DG-induced accelerated aging conditions. These findings demonstrated that DSS attenuates muscle atrophy by inhibiting the expression of muscle atrophy-related factors. Therefore, DSS may be a potential therapeutic agent for the treatment of sarcopenia., (© 2025 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Aim: To describe the long-term neurodevelopmental outcomes of asphyxiated neonates treated with hypothermia in association with neonatal magnetic resonance imaging (MRI) findings., Methods: We evaluated, retrospectively, clinical and radiological single-centre data at 0, 2, and 5 years of age of 53 asphyxiated neonates born between 2005 and 2015. Neonatal cranial MRI was re-evaluated using the Weeke score ranging from 0 (normal finding) to 55 (cerebral devastation) by a single neuroradiologist blinded to patient outcomes. Neurodevelopmental outcomes were evaluated using the Bayley Scales of Infant Development (BSID) at 2 years, and tests assessing intellectual performance at 5 years of age., Results: Of the 191 asphyxiated neonates treated with hypothermia, 53 returned for their 5-year follow-up. There were 10 children with MRI scores ≥ 10, all of whom had epilepsy, 9 had severe cognitive impairment, and 9 had cerebral palsy. In contrast, MRI scores < 10 were poorly predictive of later development. BSID at 2 years of age showed good correlation with IQ scores at 5 years of age (R s  = 0.58, p < 0.001)., Conclusion: The Weeke score can be used to identify severely impaired children in the neonatal period. In contrast, the neurocognitive test results at 2 years of age were indicative of mild or moderate impairment at 5 years of age., (© 2025 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Background: Hepatocellular carcinoma (HCC) has a rising incidence and mortality in North America. Liver transplantation (LT) with adjunctive therapies offers excellent outcomes. However, HCC recurrences are associated with high mortality. We investigate whether adjuvant systemic therapy can reduce recurrence, as shown with other malignancies., Methods: Medical records of patients undergoing LT for HCC at a single center between January 2016 and December 2022 were retrospectively reviewed. Patients were stratified into 3 groups: (1) recipients of adjuvant sorafenib, (2) nonrecipients at high recurrence risk, and (3) nonrecipients at low risk by explant pathology features. The outcomes were overall survival (OS) and recurrence-free survival (RFS). Adjuvant sorafenib recipients were also propensity score matched 1:2 to nonadjuvant recipients based on recurrence risk features., Results: During the study period, 273 patients with HCC underwent LT and 16 (5.9%) received adjuvant sorafenib therapy. Adjuvant sorafenib recipients were demographically similar to nonrecipients and, on explant pathology, had greater tumor burden, lymphovascular invasion, and poorer differentiation (all P  < 0.001). Adverse events were observed in 12 adjuvant sorafenib recipients (75%). OS was similar among the 3 groups ( P  = 0.2), and adjuvant sorafenib was not associated with OS in multivariable analysis (hazard ratio, 1.31; 95% confidence interval, 0.45-3.78; P  = 0.62). RFS was significantly lower in sorafenib patients (hazard ratio, 6.99; 95% confidence interval, 2.12-23.05; P  = 0.001). Following propensity matching, adjuvant sorafenib use was not associated with either OS ( P  = 0.24) or RFS rates ( P  = 0.65)., Conclusions: In this single-center analysis, adjuvant sorafenib was not associated with OS. Recipients were observed to have shorter RFS, likely due to the increased prevalence of high-risk features, and sorafenib use was associated with high frequencies of adverse events., (Copyright © 2025 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Purpose: To examine the feasibility of a social networking site-based self-management intervention involving pain neuroscience education (PNE) for temporomandibular joint disorders (TMD) among young adults and its initial efficacy in exploratory outcomes, including pain and somatization., Design: Pilot randomized controlled trial., Methods: Korean-speaking adults aged 20-29 with temporomandibular joint pain having smartphone Internet access. The one-week intervention included two animated videos on pain neuroscience and self-management instructions addressing poor habits limiting jaw movement and exercises to alleviate TMD symptoms. The control group received self-management guidance only. Besides pain, the Research Diagnostic Criteria for Temporomandibular Disorders Axis II assessed oral health and psychological aspects. The Generalized Anxiety Disorder 7 Scale and Central Sensitization Inventory (CSI) Part A measured anxiety and central sensitization, respectively. Besides feasibility benchmarks, a t-test and Mann-Whitney U test were used to examine the initial efficacy of PNE plus self-management on self-management alone., Results: Sixty-six participants were included in the study, with 33 participants in each group. Most participants expressed satisfaction with both interventions, with retention rates exceeding 87%. Differences in pain somatization were reported (t = 2.03, p = .046) in the intervention group compared to the control group. Differences in pain (t = 1.80, p = .077) and depression (t = 1.88, p = .061) did not reach statistical significance., Conclusions: The feasibility of the PNE and self-management education was favorable. PNE, when combined with self-management, significantly reduced pain somatization compared with self-management alone., Clinical Implications: A social networking site-assisted self-management intervention for TMD can help nurses provide education in primary care settings and communities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Variant calling using long-read RNA sequencing (lrRNA-seq) can be applied to diverse tasks, such as capturing full-length isoforms and gene expression profiling. It poses challenges, however, due to higher error rates than DNA data, the complexities of transcript diversity, RNA editing events, etc. In this paper, we propose Clair3-RNA, the first deep learning-based variant caller tailored for lrRNA-seq data. Clair3-RNA leverages the strengths of the Clair series' pipelines and incorporates several techniques optimized for lrRNA-seq data, such as uneven coverage normalization, refinement of training materials, editing site discovery, and the incorporation of phasing haplotype to enhance variant-calling performance. Clair3-RNA is available for various platforms, including PacBio and ONT complementary DNA sequencing (cDNA), and ONT direct RNA sequencing (dRNA). Our results demonstrated that Clair3-RNA achieved a ~91% SNP F1-score on the ONT platform using the latest ONT SQK-RNA004 kit (dRNA004) and a ~92% SNP F1-score in PacBio Iso-Seq and MAS-Seq for variants supported by at least four reads. The performance reached a ~95% and ~96% F1-score for ONT and PacBio, respectively, with at least ten supporting reads and disregarding the zygosity. With read phased, the performance reached ~97% for ONT and ~98% for PacBio. Extensive evaluation of various GIAB samples demonstrated that Clair3-RNA consistently outperformed existing callers and is capable of distinguishing RNA high-quality editing sites from variants accurately. Clair3-RNA is open-source and available at (https://github.com/HKU-BAL/Clair3-RNA)., Competing Interests: R.L. receives research funding from ONT. F.S. receives research support from Illumina, PacBio and ONT. J.M. has received reimbursement for travel, accommodation, and conference fees to speak at events organized by ONT. The remaining authors declare no competing interests.

Understanding human endometrial dynamics in the establishment of endometrial receptivity remains a challenge, which limits early diagnosis and treatment of endometrial-factor infertility. Here, we decode the endometrial dynamics of fertile women across the window of implantation and characterize the endometrial deficiency in women with recurrent implantation failure. A computational model capable of both temporal prediction and pattern discovery is used to analyze single-cell transcriptomic data from over 220,000 endometrial cells. The time-series atlas highlights a two-stage stromal decidualization process and a gradual transitional process of the luminal epithelial cells across the window of implantation. In addition, a time-varying gene set regulating epithelium receptivity is identified, based on which the recurrent implantation failure endometria are stratified into two classes of deficiencies. Further investigation uncovers a hyper-inflammatory microenvironment for the dysfunctional endometrial epithelial cells of recurrent implantation failure. The holistic characterization of the physiological and pathophysiological window of implantation and a computational tool trained on this temporal atlas provide a platform for future therapeutic developments., Competing Interests: Competing interests: X.X. was an employee of Geneplus-Shenzhen. All the other authors declare no competing interests., (© 2024. The Author(s).)

Background/aims: Elevated troponin levels predict in-hospital mortality and influence decisions regarding thrombolytic therapy in patients with acute pulmonary embolism (PE). However, the usefulness of high-sensitivity troponin T (hsTnT) regarding PE remains uncertain. We aimed to establish the optimal cut-off level and compare its performance for precise risk stratification., Methods: 374 patients diagnosed with acute PE were reviewed. PE-related adverse outcomes, a composite of PE-related deaths, cardiopulmonary resuscitation incidents, systolic blood pressure < 90 mmHg, and all-cause mortality within 30 days were evaluated. The optimal hsTnT cut-off for all-cause mortality, and the net reclassification index (NRI) was used to assess the incremental value in risk stratification., Results: Among 343 normotensive patients, 17 (5.0%) experienced all-cause mortality, while 40 (10.7%) had PE-related adverse outcomes. An optimal hsTnT cut-off value of 60 ng/L for all-cause mortality (AUC 0.74, 95% CI 0.61-0.85, p < 0.001) was identified, which was significantly associated with PE-related adverse outcomes (OR 4.07, 95% CI 2.06-8.06, p < 0.001). Patients with hsTnT ≥ 60 ng/L were older, hypotensive, had higher creatinine levels, and right ventricular dysfunction signs. Combining hsTnT ≥ 60 ng/L with simplified pulmonary embolism severity index ≥1 provided additional prognostic information. Reclassification analysis showed a significant shift in risk categories, with an NRI of 1.016 ± 0.201 (p < 0.001)., Conclusion: We refined troponin's predictive value in patients with acute PE, proposing a new cut-off value of hsTnT ≥ 60 ng/L. Validation through large-scale studies is essential to offer clinically useful guidance for managing patient population.

According to the predictive processing framework, our brain constantly generates predictions based on past experiences and compares these predictions with incoming sensory information. When an event contradicts these predictions, it results in a prediction error (PE), which has been shown to enhance subsequent memory. However, the neural mechanisms underlying the influence of PEs on subsequent memory remain unclear. This study investigated the electrophysiological correlates during encoding and retrieval of events eliciting PEs. We employed a statistical learning task in which participants were presented with pairs of objects in sequence. Subsequently, while recording electroencephalography (EEG), we introduced PEs by replacing the second object of each pair with new objects and we then tested the participants' memory. Behaviorally, PEs did not enhance memory. During retrieval, we observed higher amplitudes in the recollection-related late positive component for violation items that were remembered compared to those that were forgotten. In contrast, no evidence for the presence of the FN400 component associated with familiarity was found. These results suggest that recollection, but not familiarity, plays a crucial role in the interplay between PE and memory. Contrary to our hypothesis, we did not observe a relationship between PEs and the P3 component during encoding. In conclusion, our study contributes to the growing body of knowledge concerning the intricate relationship between PEs and episodic memory. It sheds light on the underlying neural mechanisms involved and emphasizes the importance of recollection in this context., (© 2024 The Author(s). Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Fungal and bacterial culture is currently the primary method for pathogen detection and identification. Next-generation sequencing is a powerful method for detecting and identifying the presence of microbial DNA in samples. We evaluated the correlation between fungal and bacterial culture with next-generation sequencing in equine uterine samples. Fungal cultures (n=63) were evaluated based on their culture results. In culture positive (n=16) samples, next-generation sequencing identified the same organism in 10 samples (62.5%), 5 samples did not identify fungal agents, and 1 sample identified other species of fungal agents. In no growth samples (n=42), next-generation sequencing did not identify fungal agents in 37 samples (88.1%), 4 samples had a potential fungal pathogen identified, and one sample identified only non-pathogenic fungal organisms. Fungal culture and next-generation sequencing had an 80% agreement and moderate correlation by Kappa coefficient (0.508). Bacterial culture (n=57) was also evaluated based on bacterial culture results. In bacterial culture Positive samples (n=32), next-generation sequencing identified the same organism in 25 (78.1%) samples, and identified different organisms from the remaining 7 samples. In bacterial no growth samples (n=14), next-generation sequencing detected bacterial presence in 5 samples, and 9 samples had no bacterial DNA identified. The agreement between bacterial culture and next-generation sequencing was 74% with a moderate correlation by Kappa coefficient (0.46). In conclusion, culture and next-generation sequencing have moderate correlation, and next-generation sequencing has the potential as a diagnostic option for enhancing pathogen detection for equine endometritis., Competing Interests: Declaration of competing interest SHC received honoraria as a speaker at a veterinary conference from MicrogenVet., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Regardless of approach, safe and effective parenchymal transection is critical for hepatectomies. 1 In robotic surgery, this can be accomplished via several methods. The authors highlight some of the more common tools and techniques used to transect the liver. The Vessel Sealer Extend is a console-controlled device with bipolar energy, mechanical cutting, full-wristed articulation, and grasping abilities that allow it to replicate the clamp-crush technique while sealing small vessels. However, the jaw is bulky and suboptimal for firm/fibrotic livers. 2,3 The Synchroseal shares many features of the Vessel Sealer Extend but has thinner jaws, making it easier to advance in firm livers, and lacks a cutting blade, relying instead on a cut electrode to divide tissue. Proteinaceous char can accumulate on the jaws, impairing its effectiveness, but intermittent irrigation can mitigate this. The robotic Harmonic Scalpel coagulates, transects, and precisely dissects parenchyma. However, it is limited in length and lacks wristed articulation. 4,5 Ultrasonic surgical aspiratory devices allow for precise, atraumatic dissection around vasculobiliary structures, but no robotic-integrated versions currently exist. Therefore, application of this technology in robotic surgery requires an experienced bedside assistant operating the laparoscopic version while the console surgeon uses robotic instruments to coagulate, clip, and divide larger structures. 6-9 The dual bipolar technique is useful for spot coagulation and dissection but has limited transection ability. 10 It often is an adjunct to other transection techniques. 11-13 Several methods exist for robotic parenchymal transection, and although none are perfect, they can be combined for safe and effective transection., Competing Interests: Disclosure: Dr. Tran Cao is the recipient of a research grant from Intuitive Foundation. Dr. Hawksworth is a proctor for Intuitive. The remaining authors have no conflicts of interest., (© 2024. Society of Surgical Oncology.)

Acetaminophen (APAP) is a well-known analgesic used globally. Generally, APAP has been proven to be safe and effective at therapeutic doses; however, it can cause serious liver damage when administered at high levels. We prepared Codium fragile extract (CFE) using the seaweed C. fragile and confirmed that the CFE contains a substance called Loliolide with antioxidant activity. We performed the present study to determine whether CFE protects HEPG2 cells and BALB/c mice from oxidative stress-induced liver damage. We confirmed that CFE and Loliolide were non-cytotoxic and protected against liver damage by reducing the activities of ALT and AST, which were increased by APAP treatment, and that CFE reduced the mRNA expression of inflammatory cytokines TNF-α and IL-6 and inhibited the phosphorylation of ERK and p38 in HEPG2 cells as determined by RT-PCR and Western blot analyses. Furthermore, the TNF-α and IL-6 levels, which were increased after APAP treatment in BALB/c mice, decreased after CFE treatment. Therefore, we demonstrated that CFE exerts a protective effect against APAP-induced liver injury by suppressing the inflammatory response through anti-inflammatory activity. Our findings provide new perspectives for developing functional foods that utilize seaweeds to improve liver function.

Background: Suicide attempts are a major concern in major depressive disorder (MDD), especially for those with multiple prior unsuccessful treatment trials. This report compares baseline demographic, clinical features, and treatment history of participants with marked treatment-resistant, nonpsychotic MDD based on lifetime history of suicide attempt (SA vs NSA)., Methods: RECOVER is a randomized, sham-controlled trial of vagus nerve stimulation and the largest such trial of a psychiatric neuromodulation intervention. Baseline data were analyzed. Univariate analyses (SA vs NSA) and logistic regression with backward selection (variables with univariate p < 0.1) were performed., Results: SA group (N = 196) was more likely than NSA group (N = 297) to be female (72.4 % vs 61.6 %), <65 years of age (73.5 % vs 61.6 %), have earlier onset of depressive symptoms (mean, 19.1 vs 22.5 years), earlier diagnosis of MDD (mean, 25.0 vs 29.2 years), higher percentage of lifetime in depressive episodes (mean, 56.0 % vs 51.0 %), more failed antidepressants (mean, 15.0 vs 12.1), and greater lifetime use of electroconvulsive therapy (ECT; 55.1 % vs 40.1 %). Female sex, age at MDD diagnosis, number of failed antidepressants, number of psychiatric hospitalizations, and baseline suicide score retained association with logistic regression analysis., Limitations: Information on medical morbidity of suicide attempts was not collected and timing of suicide attempts relative to treatment exposures was unknown., Conclusions: For marked treatment-resistant MDD, those with prior suicide attempts have more complex course of illness with earlier onset of depressive symptoms, earlier diagnosis of MDD, more lifetime spent in depressive illness, more failed antidepressant medication trials, and greater use of ECT., Trial Registration: ClinicalTrials.gov Identifier NCT03887715., Competing Interests: Declaration of competing interest MAB, YIS, JCE, CLK, BMG, and HB have no conflicts of interest to declare. VDL receives funding from the Washington University Institute of Clinical and Translational Sciences, UL1 TR002345, and sub-award TL1 TR002344. RMA is one of the owners of a multi-site interventional psychiatry and clinical trials company, Seattle Neuropsychiatric Treatment Center; receives research funding from LivaNova and Compass Pathways; and previously received research funding from Alto Neuroscience. JQ has received clinical research support from LivaNova; has speaker bureau membership with Myriad Neuroscience and AbbVie; consultant for Eurofarma; stockholder at Instituto de Neurociencias; and receives copyrights from Artmed Editora, Artmed Panamericana, and Elsevier/Academic Press. PRP is a consultant for LivaNova, Janssen Pharmaceuticals, MotifNeuro, and Abbott Neuromodulation. STA is a consultant to Genomind, LivaNova, Janssen, Neuronetics, and Sage Therapeutics; and has received research support from Compass Pathways and Neuronetics. JZ has received research support from Boehringer-Ingelheim, Compass Pathways, Hoffman-LaRoche, Johnson and Johnson (Janssen), LivaNova, Otsuka, Neurocrine Bioscience, and Sage Therapeutics; and received consulting fees from Alphasigma USA, Johnson and Johnson (Janssen), and Novartis Pharmaceuticals. MDB is a consultant for LivaNova and received speaker's honoraria from Intracellular, Janssen, Teva, Axsome, Abbvie, and Supernus. LMM is a consultant to and speaker for Janssen Pharmaceuticals; and has received research support from Janssen Pharmaceuticals and LivaNova. JF has conducted clinical studies sponsored by Navidea Biopharmaceuticals, Compass Pathways, Jazz Pharmaceuticals, LivaNova PLC, Boehringer Ingelheim, Sage Therapeutics, Relmada Therapeutics, and Reunion Neuroscience; provided expert testimony for Thornton, Biechlin, Reynolds and Guerra Law Firm; and received grants from CPRIT, NIH, and NIMH. JB and Y-CL are employees of LivaNova. MTB is a former employee and a current consultant of LivaNova. AJR has received consulting fees from Compass, Curbstone Consultant, Emmes, Evecxia Therapeutics, Holmusk Technologies, ICON, Johnson and Johnson (Janssen), LivaNova, MindStreet, Neurocrine Biosciences, Otsuka-US; speaking fees from LivaNova, Johnson and Johnson (Janssen), and Wolters Kluwer Health; royalties from Guilford Press and UT Southwestern Medical Center (for the Inventory of Depressive Symptoms and its derivatives); named co-inventor on US Patent 7,795,033 (Methods to Predict the Outcome of Treatment with Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S, Wilson AS) and US Patent 7,906,283 (Methods to Identify Patients at Risk of Developing Adverse Events During Treatment with Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S). HAS serves as a scientific adviser and receives consulting fees from Cerebral Insights, Cerebral Therapeutics, Holmusk Technologies, LivaNova, MECTA Corporation, Neurolief, Neuronetics, Parow Entheobiosciences, and SigmaStim; receives honoraria and royalties from Elsevier and Oxford University Press; is the inventor of non-remunerative US patents for Focal Electrically Administered Seizure Therapy (FEAST), titration in the current domain in ECT, and the adjustment of current in ECT devices, each held by the SigmaStim Corporation; and is also the originator of magnetic seizure therapy (MST). CRC has received research support from the American Foundation for Suicide Prevention, Assurex Health, August Busch IV Foundation, Barnes-Jewish Hospital Foundation, LivaNova, National Institute of Mental Health, and the Taylor Family Institute for Innovative Psychiatric Research; consulted for LivaNova and Sage Therapeutics; and was a part-time employee at the John Cochran VA Medical Center in St. Louis., (Copyright © 2024. Published by Elsevier B.V.)

Background: Few treatments are available for individuals with marked treatment-resistant depression (TRD)., Objective: Evaluate the safety and effectiveness of FDA-approved adjunctive vagus nerve stimulation (VNS) in patients with marked TRD., Methods: This 12-month, multicenter, double-blind, sham-controlled trial included 493 adults with marked treatment-resistant major depression who were randomized to active or no-stimulation sham VNS for 12 months. The primary outcome was percent time in response across months 3-12, with response defined as a ≥50 % change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS). Several secondary endpoints were evaluated., Results: Overall, 88.4 % of participants completed the trial. Percent time in MADRS response did not distinguish active from sham VNS. However, ratings from on-site clinicians (Clinical Global Inventory-Impression [CGI-I]), patients (Quick Inventory of Depressive Symptomology-Self Report [QIDS-SR]), and offsite masked raters (Quick Inventory of Depressive Symptomology-Clinician [QIDS-C]) revealed antidepressant benefits significantly favoring active VNS. Active VNS demonstrated significantly more percent time in response on the CGI-I (P = 0.004) and QIDS-SR (P = 0.049), and significantly more percent time in partial response (PR; symptom improvement ≥30 %) on the CGI-I (P < 0.001) and QIDS-C (P = 0.006) versus sham VNS. Active VNS exceeded sham VNS in rate of dyspnea (P = 0.035), a known side effect of VNS. No new adverse events were identified., Conclusions: Percent time in MADRS response did not distinguish the treatment groups, but on multiple instruments time in response and PR showed a positive treatment effect. VNS was found safe and effective in participants with marked TRD., Competing Interests: Declaration of competing interest CRC has received research support from the American Foundation for Suicide Prevention, Assurex Health, August Busch IV Foundation, Barnes-Jewish Hospital Foundation, LivaNova, National Institute of Mental Health, and the Taylor Family Institute for Innovative Psychiatric Research; consulted for LivaNova and Sage Therapeutics; and was a part-time employee at the John Cochran VA Medical Center in St Louis. STA is a consultant to Genomind, LivaNova, Janssen, Neuronetics, and Sage Therapeutics and has received research support from Compass Pathways and Neuronetics. HAS serves as a scientific advisor and receives consulting fees from Cerebral Therapeutics, Holmusk Technologies, LivaNova, MECTA Corporation, Neurolief, Neuronetics, Parow Entheobiosciences, and SigmaStim; receives honoraria and royalties from Elsevier and Oxford University Press; is the inventor of nonremunerative US patents for Focal Electrically Administered Seizure Therapy (FEAST), titration in the current domain in ECT, and the adjustment of current in ECT devices, each held by the SigmaStim Corporation; and is also the originator of magnetic seizure therapy (MST). MSG has received research support from Abbott, LivaNova, Neurolief, and Magnus Medical and consults for Abbott, Hospital Corp of America, Jacob Zabara Family Foundation, Neurolief, and Sooma. JZ receives research support from Boehringer-Ingelheim, Compass Pathways, Hoffman-LaRoche, Johnson and Johnson (Janssen), LivaNova, Otsuka, Neurocrine Bioscience, and Sage Therapeutics and has received consulting fees from Alfasigma USA and Johnson and Johnson (Janssen). MTB is a former employee and a current consultant of LivaNova. WJD has received research support from Abbott Nutrition, AbbVie, Acadia, Akili, Alkermes, Allergan, Alto Neuroscience, AriBio, Axsome, Biohaven, Bionomics, Clexio, Compass Pathways, Corcept, Corium, Denovo BioPharma, Emalex, GlaxoSmithKline Biologicals, Hoffmann-LaRoche, Intra-Cellular, Ironshore, Janssen, Jazz, LivaNova, Lumos, Merck Sharp & Dohme, MindMed, Neurocrine Bioscience, NRx, Otsuka, Sage Therapeutics, Sanofi Pasteur, Shire, Sirtsei, Spark Neuro, Sumitomo, Sunovion, and Supernus and is a speakers bureau, advisory board, or consultant for Abbott Neuromodulation, Corium, and LivaNova. MS is a Principal Investigator for Cassava Sciences, Eisai, Lilly, and LivaNova. JQ received clinical research support from LivaNova; has speaker bureau membership with Myriad Neuroscience and AbbVie; is a consultant for Eurofarma; is a stockholder at Instituto de Neurociencias; and receives copyrights from Artmed Editora, Artmed Panamericana, and Elsevier/Academic Press. RMA is one of the owners of a multisite interventional psychiatry and clinical trials company, Seattle Neuropsychiatric Treatment Center; receives research funding from LivaNova and Compass Pathways; and previously received research funding from Alto Neuroscience. PRP is a consultant for LivaNova, Janssen Pharmaceuticals, Motif Neurotech, and Abbott Neuromodulation. MB has no conflicts to disclose. GA receives research support from AbbVie, Accera, Axsome, Axovant, Biogen, Eisai, Eli-Lily, Neurotrope, Genentech, Intra-Cellular, Janssen, Lundbeck, Neurim, Novartis, Otsuka, Roche, Sage, Suven, and TransTech and is on the speakers bureau of and is a consultant for AbbVie, Acadia, Alkermes, Axsome, Biogen, Janssen, Idorsia, Lundbeck, Myriad, Neurocrine, Nestle, Otsuka, Sage, Sunovion, Teva, and Takeda. MAM has received research support and/or speaker honoraria from Axsome, AbbVie, Alkermes, Intracellular, Janssen, Otsuka, and Teva. DLD receives payment for clinical services for a former research patient from LivaNova. He is a speaker for Janssen (esketamine nasal spray) and conducts forensic consultations, independent medical evaluations, and legal testimony for various firms. IC is co-owner of Mindful Behavioral Health, PLLC and receives speaker fees from Janssen (Johnson and Johnson). MB has the following disclosures to declare: AbbVie, Intra-Cellular, Axsome, Janssen, and Teva. He is also a consultant for LivaNova. LM has received research funding administered through Stony Brook University from Janssen Pharmaceuticals (developer of esketamine) to conduct clinical trials with esketamine, received research funding administered through Stony Brook University from LivaNova (developer of VNS technology) to conduct clinical trials with VNS, and served as a consultant and member of the Spravato Speaker Bureau for Janssen Pharmaceuticals. ZN is a consultant to LivaNova, Magnus Medical, and Motif and has also received research support from LivaNova. MM discloses the following over the last 24 months: 1) Received research support from Alto, Boehringer-Ingeleheim, LivaNova, Janssen, Merck, Neurocrine, Otsuka, SAGE, PCORI, and NIH/NIMH. All clinical trial payments were made to the University of Alabama at Birmingham. 2) Served as a paid consultant for CME Institute, NuSachi Labs, PharmaTher, Residents Medical, Tactical Mind Solutions, and the University of Missouri. 3) Received royalties from Springer Nature for textbooks published. BJM received research support from NIH, NSF, Wellcome Leap, PCORI, Health Rhythms, LivaNova, Compass, and Abbott. YS has no conflict of interest to declare. CLK has no conflicts to disclosure. Y-CL, CG, OS, QT, and LY are employees of LivaNova, and CG holds LivaNova stock. AJR has received consulting fees from Compass Inc, Curbstone Consultant LLC, Emmes Corp, Evecxia Therapeutics, Inc, Holmusk Technologies, Inc, ICON, PLC, Johnson and Johnson (Janssen), LivaNova, MindStreet, Inc, Neurocrine Biosciences Inc, and Otsuka-US; speaking fees from LivaNova and Johnson and Johnson (Janssen); and royalties from Wolters Kluwer Health, Guilford Press, and the University of Texas Southwestern Medical Center, Dallas, TX (for the Inventory of Depressive Symptoms and its derivatives). He is also named co-inventor on 2 patents: US Patent No. 7,795,033: Methods to Predict the Outcome of Treatment With Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S, Wilson AS; and US Patent No. 7,906,283: Methods to Identify Patients at Risk of Developing Adverse Events During Treatment With Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S., (Copyright © 2024. Published by Elsevier Inc.)

Background & Aims: Burnout is a global concern, and critical healthcare professionals have been identified as a high-risk population of burnout. Early identification is crucial, but the prevalence of burnout and its risk factors demonstrate significant geographical variations. This study aims to investigate the prevalence of burnout among critical healthcare professionals and explore potential risk factors during the post-pandemic era in Taiwan., Methods: A web-based questionnaire survey was conducted from December 1, 2023, to January 31, 2024, targeting critical healthcare professionals employed in selected medical institutions affiliated with the Chang Gung Memorial Hospital Foundation, one of Taiwan's largest healthcare organizations. Demographic information, the Subjective Happiness Scale (SHS), current work stressors and self-reported general health data were collected. The study utilized the Maslach Burnout Inventory Human Services Survey for Medical Personnel (MBI-MP). Univariate and multivariate logistic regression were employed to investigate the association between risk factors and each burnout subscales. A systematic review of Asian literature concerning burnout among critical care practitioners was also conducted., Results: In our study, 254 participants were enrolled, with an overall burnout rate of 35.4%. The prevalence of high emotional exhaustion (EE) was 70.9%, high depersonalization (DP) was 56.3%, and low personal accomplishment (PA) was 60.6%. Young, unmarried populations, individuals with limited work experience, longer working hours, and night shifts are potential vulnerable groups susceptible to burnout. The top three stressors identified were excessive workload, the burden of administrative tasks, and a shortage of vacation time. Our systematic review included 20 Asian studies on the same issue, with variable burnout prevalence ranging from 16.3 to 82.1%., Conclusion: The prevalence of burnout was high among critical healthcare professionals in post-pandemic Taiwan, particularly affecting younger, unmarried populations and individuals with limited work experience, longer hours, and more night shifts. The influence of pandemic-related factors has decreased. Regional variations in burnout have been observed across Asia, highlighting the need for further research to identify local risk factors and protect the well-being of professionals and healthcare quality., Competing Interests: Declarations. Ethics approval and consent to participate: This research received approval from the Jen-Ai Hospital Institutional Review Board (IRB Number: 202300085B0). All participants fully understood the study’s goal and reviewed the informed consent form before proceeding. Consent for publication: not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Depression treatments aim to minimize symptom burden and optimize quality of life (QoL) and psychosocial function., Objective: Compare the effects of adjunctive versus sham vagus nerve stimulation (VNS) on QoL and function in markedly treatment-resistant depression (TRD)., Methods: In this multicenter, double-blind, sham-controlled trial, 493 adults with TRD and ≥4 adequate but unsuccessful antidepressant treatment trials (current episode) were randomized to active (n = 249) or sham (n = 244) VNS (plus treatment as usual) over a 12-month observation period. Quarterly outcomes included QoL with the Q-LES-Q, Mini-Q-LES-Q, and EQ-5D-5L, and function with the WHODAS 2.0 and Work Productivity and Activity Impairment Questionnaire (WPAI) item 6. Differences between treatment groups in change in scores from baseline and percentage of time with a meaningful response in Q-LES-Q, Mini-Q-LES-Q, and WPAI item 6 scores were analyzed., Results: Active VNS was superior to sham in mean change in scores from baseline in the Mini-Q-LES-Q (P = 0.050) and WPAI item 6 (health condition's effect on regular activities [P = 0.050]) used as continuous variables, with a similar trend for Q-LES-Q (P = 0.061). Active VNS was superior to sham in time spent in clinically meaningful benefit (categorical analyses) using the Q-LES-Q (P = 0.029), Mini-Q-LES-Q (P = 0.011), and WPAI item 6 (P = 0.039). The WHODAS 2.0 (P = 0.304) and EQ-5D visual analog scale (P = 0.125) failed to reveal between-group differences., Conclusion: Active VNS was superior to sham VNS in improving QoL and psychosocial function in patients with TRD. VNS has a broader therapeutic impact than symptom improvement alone in patients with marked psychosocial impairment., Competing Interests: Declaration of competing interest AJR has received consulting fees from Compass Inc., Curbstone Consultant LLC, Emmes Corp., Evecxia Therapeutics, Inc., Holmusk Technologies, Inc., ICON, PLC, Johnson & Johnson (Janssen), LivaNova, MindStreet, Inc., Neurocrine Biosciences Inc., and Otsuka-US; speaking fees from LivaNova and Johnson & Johnson (Janssen); and royalties from Wolters Kluwer Health, Guilford Press, and the University of Texas Southwestern Medical Center, Dallas, TX (for the Inventory of Depressive Symptoms and its derivatives). He is also named coinventor on 2 patents: US Patent No. 7,795,033: Methods to Predict the Outcome of Treatment With Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S, Wilson AS; and US Patent No. 7,906,283: Methods to Identify Patients at Risk of Developing Adverse Events During Treatment With Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S. CRC has received research support from the American Foundation for Suicide Prevention, Assurex Health, August Busch IV Foundation, Barnes-Jewish Hospital Foundation, LivaNova, National Institute of Mental Health, and the Taylor Family Institute for Innovative Psychiatric Research; consulted for LivaNova and Sage Therapeutics; and was a part-time employee at the John Cochran VA Medical Center in St Louis. STA is a consultant to Genomind, LivaNova, Janssen, Neuronetics, and Sage Therapeutics and has received research support from Compass Pathways and Neuronetics. DLD receives payment for clinical services for a former research patient from LivaNova, is a speaker for Janssen (esketamine nasal spray), and conducts forensic consultations, independent medical evaluations, and legal testimony for various firms. MSG has received research support from Abbott, LivaNova, Neurolief, and Magnus Medical. He consults for Abbott, Hospital Corp of America, Jacob Zabara Family Foundation, Neurolief, and Sooma. JZ receives research support from Boehringer-Ingelheim, Compass Pathways, Hoffman-LaRoche, Johnson & Johnson (Janssen), LivaNova, Otsuka, Neurocrine Bioscience, and Sage Therapeutics and received consulting fees from Alfasigma USA and Johnson & Johnson (Janssen). MTB and BO are former employees of and current consultants for LivaNova. JQ received clinical research support from LivaNova; has speaker bureau membership with Myriad Neuroscience and AbbVie; is a consultant for Eurofarma; is a stockholder at Instituto de Neurociencias; and receives copyrights from Artmed Editora, Artmed Panamericana, and Elsevier/Academic Press. RMA is one of the owners of a multisite interventional psychiatry and clinical trials company, Seattle Neuropsychiatric Treatment Center; receives research funding from LivaNova and Compass Pathways; and previously received research funding from Alto Neuroscience. PRP is a consultant for LivaNova, Janssen Pharmaceuticals, Motif Neurotech, and Abbott Neuromodulation. GA receives research support from AbbVie, Accera, Axsome, Axovant, Biogen, Eisai, Eli Lilly, Neurotrope, Genentech, Intra-Cellular, Janssen, Lundbeck, Neurim, Novartis, Otsuka, Roche, Sage, Suven, and TransTech and is on the speakers bureau of and is a consultant for AbbVie, Acadia, Alkermes, Axsome, Biogen, Janssen, Idorsia, Lundbeck, Myriad, Neurocrine, Nestle, Otsuka, Sage, Sunovion, Teva, and Takeda. HL has received consulting and/or speaking fees from Alkermes, Axsome, Intra-Cellular, Janssen, Karuna, Sage, Teva, and Vanda Pharmaceuticals; conducts forensic consultations, independent medical evaluations, and legal testimony for various firms; and co-owns Florida Center for TMS. ZN is a consultant to LivaNova, Magnus Medical, and Motif and has also received research support from LivaNova. LM has received research funding administered through Stony Brook University from Janssen Pharmaceuticals (developer of esketamine) to conduct clinical trials with esketamine, received research funding administered through Stony Brook University from LivaNova (developer of VNS technology) to conduct clinical trials with VNS, and served as a consultant and member of the Spravato Speaker Bureau for Janssen Pharmaceuticals. JIB receives research support from Teva Pharmaceutical Industries Ltd and from Relmada Therapeutics for clinical trials both administered through Southern Illinois UniversitySchool of Medicine. He has received research support from Janssen Research and Development to conduct clinical trials with esketamine also administered through the Southern Illinois UniversitySchool of Medicine. BJM received research support from NIH, NSF, Wellcome Leap, PCORI, Health Rhythms, LivaNova, Compass, and Abbott. JB is a partner and shareholder for the Neuroscience and TMS Treatment Center, as well as a co-owner of Cromwell Medical, a management service organization. He receives speaking fees for the Clinical TMS Society and is a paid clinical content reviewer for the Neuroscience Education Institute. YS has no conflict of interest to declare. CC has received research support for conducting clinical trials from AFSP, Clexio, ATAI, and Janssen and consulting fees from Compass Therapeutics and Boehringer. JWM has received consulting fees from Biohaven Pharmaceuticals, Inc., Clinilabs, Inc., Clexio Biosciences, Ltd., Compass Pathfinder, Plc., Janssen Pharmaceuticals, KetaMed, Inc., LivaNova, Merck & Co., Inc., Otsuka Pharmaceutical, Ltd., and Xenon Pharmaceuticals, Inc. KR has no conflict of interest to declare. PBR receives research support for conducting clinical trials from LivaNova Corporation and The George Institute. He has also participated in an advisory board for LivaNova Corporate. Y-CL is an employee of LivaNova. SM and JW are employees of LivaNova and hold stock options. HAS serves as a scientific advisor and receives consulting fees from Cerebral Therapeutics, Holmusk Technologies, LivaNova, MECTA Corporation, Neurolief, Neuronetics, Parow Entheobiosciences, and SigmaStim; receives honoraria and royalties from Elsevier and Oxford University Press; is the inventor of nonremunerative US patents for Focal Electrically Administered Seizure Therapy (FEAST), titration in the current domain in ECT, and the adjustment of current in ECT devices, each held by the SigmaStim Corporation; and is also the originator of magnetic seizure therapy (MST)., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Recent studies investigating emergency department (ED) thoracotomies (EDTs) focus on patient outcomes to identify optimal candidates for this procedure. However, there is limited but concerning literature regarding healthcare workers occupational exposures resulting from EDT. In this study, we compare rates of blood-borne exposure to immediate procedural success (i.e., regaining pulses) as well as patient outcome., Methods: A retrospective chart review of the trauma registry was performed from January 2019 to January 2023. We included all trauma patients who underwent EDT during the study period. 58 patients met the inclusion criteria and were reviewed, and no patients were excluded. The primary endpoint was the rate of occupational exposure as defined by mucous membrane or percutaneous exposure to the patient's blood during the procedure. Additional endpoints include rate of survival to operating room, intensive care unit (ICU), and discharge, type of exposure, Glasgow Coma Score score, and blood products transfused., Results: Of the 58 patients, 10 EDTs (17%) had reported healthcare occupational exposure, 24 patients (41%) were resuscitated in the ED and moved to the OR or the ICU. 9 patients (16%) survived the OR, with 2 patients (3%) surviving to discharge from the hospital. Of the 10 patients with reported exposures, 4 (40%) regained spontaneous circulation in the ED, 2 patients (20%) survived the OR to the post anesthesia care unit and ICU, but neither survived to discharge (0%). Of the 48 patients without exposures reported, 20 (42%) regained spontaneous circulation in the ED, 7 (15%) survived to the ICU after the OR, and 2 (4%) survived to discharge. Of the 9 patients that survived the OR, 3 showed improvement in neurologic status shown by an improved Glasgow Coma Score., Conclusions: The noted rate of healthcare worker exposures during these procedures is higher than expected. The rate of survival to the operating room and subsequently to the ICU was higher than current reported rates. Further research needs to be done to investigate ways to improve training and protocols to make this procedure safer for the patient and the team of providers., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Gene editing using CRISPR/Cas9 is an innovative tool for developing new mushroom strains, offering a promising alternative to traditional breeding methods that are time-consuming and labor-intensive. However, plasmid-based gene editing presents several challenges, including the need for selecting appropriate promoters for Cas9 expression, optimizing codons for the Cas9 gene, the unintended insertion of fragmented plasmid DNA into genomic DNA (gDNA), and regulatory concerns related to genetically modified organisms (GMOs). To address these issues, we utilized a Ribonucleoprotein (RNP) complex consisting of Cas9 and gRNA for gene editing to modify the A mating-type gene of Lentinula edodes . To overcome the challenges posed by the large size of the Cas9 protein, which limits its penetration through the protoplast membrane, and the susceptibility of sgRNA to degradation, we developed a nanoparticle complex using calcium phosphate and polyacrylic acid. This approach significantly improved gene editing efficiency. Consequently, we successfully edited the mating-controlling genes hd1 and hd2 in L. edodes and examined the effects of their disruption on mating. Disruption of the hd1 gene, which is known to influence mycelial growth, did not significantly affect growth or mating. In contrast, editing the hd2 gene disrupted mating with compatible partners, highlighting its critical role in the mating process. The RNP-based transformation technology presented here offers significant advancement over traditional plasmid-based methods, enhancing the efficiency of targeted gene modification while avoiding the insertion of foreign genetic material, thereby mitigating GMO-related regulatory concerns.

Interdisciplinary learning is essential for equipping future health professionals to tackle the complexities of contemporary public health. This mixed-methods study investigates the experiences and perspectives of undergraduate public health students in Singapore on interdisciplinary learning in higher education and employed a convergent parallel design by combining a cross-sectional survey with in-depth interviews. Quantitative data were used to assess the relationship between students' exposure to interdisciplinary learning and its perceived value, while qualitative analysis explored key themes related to facilitators and barriers. Among 52 survey respondents and 11 interview participants, nearly half regularly engaged in interdisciplinary learning. Students with greater exposure to interdisciplinary experiences demonstrated more positive perceptions. Facilitators identified included career development opportunities, faculty engagement, and diverse learning experiences. Barriers such as disciplinary disconnects and the challenge of managing varied skill sets were also highlighted. This study provides valuable insights into interdisciplinary learning in higher education pertaining to public health, particularly within the context of health professions training. The findings suggest that enhancing curricular design, integrating interdisciplinary approaches more effectively, and increasing faculty support can address identified barriers and better prepare students for the demands of their future public health careers., 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 Lim, Tan, Voo, Lee and Teng.)

Background: Chronic Obstructive Pulmonary Disease (COPD) remains a significant public health challenge due to its high morbidity and mortality rates. Emerging research has identified eosinophilic inflammation as a crucial factor in the pathogenesis and exacerbation of COPD, warranting a detailed exploration of its underlying mechanisms and therapeutic implications., Objective: This review aims to elucidate the role of eosinophils in COPD, focusing on their contribution to airway remodeling, exacerbation frequency, and the inflammatory cascade., Methods: We conducted a comprehensive literature review of recent studies that discuss the pathophysiological role of eosinophils in COPD and the clinical outcomes associated with modulating eosinophilic activity., Results: Eosinophils contribute to COPD progression by releasing cytotoxic proteins and cytokines that intensify the inflammatory response and airway alterations. Targeting specific eosinophil-related cytokines with monoclonal antibodies or receptor antagonists may potentially reduce eosinophil counts, mitigate exacerbations, and improve patient outcomes., Conclusion: Understanding eosinophilic involvement in COPD can facilitate the development of precision medicine approaches, offering more tailored and effective treatment options. Future research should continue to focus on the integration of eosinophil biomarkers in clinical practice to enhance therapeutic decisions and management strategies for COPD patients.

Background: Hemorrhage, particularly from noncompressible torso hemorrhage (NCTH) in the abdominopelvic region, is a leading cause of preventable trauma deaths. Resuscitative endovascular balloon occlusion of the aorta (REBOA), designed for aortic occlusion, has emerged as a tool for temporary hemorrhage control in recent years. However, attaining optimal REBOA placement in diverse demographic groups, such as Asian populations, may pose challenges owing to unique anatomical and physiological differences., Materials and Methods: This retrospective study analyzed trauma patients who underwent torso computed tomography (CT) at tertiary hospitals in Taiwan from January 2014 to January 2017. The OsiriX software was used to measure the endovascular lengths in the CT images., Results: Among the 223 patients, the median vascular lengths and body measurements were higher in males. The optimal fixed insertion length was identified as 47.5 cm for zone 1 with 99.43% accuracy and 25.5 cm with 82.1% accuracy for zone 3. The landmark-guided method showed 100% accuracy for zone 1 when using the mid-sternum and 94.6% for zone 3 with the umbilicus as the guide with the distance between the umbilicus, xiphoid process, and pubic ramus. External validation confirmed the accuracy of the landmark-guided method., Conclusions: For zone 1 occlusions, a range of 44-48 cm insertion length cross-referenced with the mid-sternal landmark is recommended. For zone 3 occlusions, using the umbilicus as a guide with the distance between the umbilicus, xiphoid process, and pubic ramus provided the highest accuracy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Allergic asthma is a chronic bronchial inflammatory disease closely associated with abnormal immune responses of dendritic cells (DCs) and allergen-specific type 2 T helper (Th2) cells. Indirubin (IR), a natural aryl hydrocarbon receptor (AhR) ligand, exerts anti-inflammatory and immunomodulatory properties., Purpose: In this study, we aimed to clarify whether IR exhibits immunomodulatory action on DCs via AhR activation and investigated the antiallergic effects of IR in a mouse model of allergic asthma., Methods: Lipopolysaccharide (LPS)-activated bone marrow-derived DCs were treated with IR. Their mRNA expressions, cytokine production, and phenotype patterns were determined by a quantitative real-time PCR, ELISA, flow cytometry, and RNA sequencing. The mixed lymphocyte reaction was utilized to evaluate the regulatory function of IR-treated DCs on T-cell differentiation. Moreover, mice with ovalbumin (OVA)-induced allergic asthma were treated with IR. Thereafter, the airway hyperresponsiveness (AHR), allergen-specific IgE production, cytokine levels, airway inflammation, and T-cell responses were evaluated., Results: Treatment of LPS-stimulated DCs with 20 μM IR significantly reduced IL-12 and TNF-α production while increasing IL-10 secretion. Meanwhile, these DCs expressed decreased levels of CD80 but increased levels of Jagged 1 surface molecules. However, the effects of IR on DCs were reversed by pretreatment with the AhR antagonist, CH223191. Additionally, the coculture of these tolerogenic-like DCs with allogeneic CD4 + T cells promoted the generation of Foxp3 + regulatory T (Treg) cells. A transcriptomic analysis identified several downregulated genes that are involved in regulating cell migration, cytokine secretion, and inflammatory responses in DCs after IR treatment. In an asthmatic murine model, oral administration of 25 mg kg -1 body weight of IR efficiently alleviated the development of AHR, OVA-specific IgE production, and levels of Th2-type cytokines (IL-4, IL-5, and IL-13) and the CCL11 chemokine. IR treatment also attenuated inflammatory cell recruitment and mucus production in the lungs. Notably, an enhanced frequency of Foxp3 + Treg cells and reduced effector T-cell proliferation associated with increased levels of IL-10 and TGF-β were observed in IR-treated mice., Conclusion: IR can induce tolerogenic-like BMDCs which promote the differentiation of Treg cells. Importantly, the expansion of Foxp3 + Treg cells contributed to the therapeutic efficacy of IR against allergic asthma., Competing Interests: Declaration of competing interest The authors declare that they have no financial conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Visual observation surveys from ships are commonly used for monitoring floating marine debris, but their detection performance has not yet been fully verified. Here, simultaneous visual observation surveys and surface trawling were conducted in three coastal areas of South Korea, each with distinct characteristics. The extent of floating debris missed by visual observations was assessed, and the characteristics of overlooked debris were identified. The mean density of floating debris observed visually was five-fold lower than that obtained from surface trawling. Loss of buoyancy and transparent colour of debris were identified as major factors contributing to the significant difference in density between the two survey methods. Our findings suggest that visual observation can underestimate the density of floating debris, especially in areas with abundant plastic bags and sheets. Supplementary methods such as surface trawls with macro-sized mesh are recommended to accurately assess the level of contamination from floating debris., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The deceased donor shortage in the United States has led to increased utilization extended criteria donor (ECD) liver grafts. Centers often utilize ECD grafts in patients with low Model for End-Stage Liver Disease (MELD) scores, like patients with hepatocellular carcinoma (HCC). However, few studies have directly examined the outcomes of using ECD grafts in patients with HCC., Methods: Adults receiving liver transplantation (LT) for HCC between 2010 and 2020 were identified in the Organ Procurement and Transplantation Network database. Recipients were categorized according to donor type: standard criteria donor (SCD), extended criteria donor, donation after brain death (ECD-DBD), and donation after circulatory death (DCD). Multivariable Cox regression analysis identified variables associated with overall or graft survival at 3 years post-LT., Results: Most patients received ECD-DBD grafts (51.4%); only 8.3% received DCD grafts. The time on the waitlist was similar for ECD and SCD recipients (P = .79). SCD recipients had higher 5-year overall survival post-LT than ECD-DBD or DCD recipients (79.1%, 77.1%, and 76.8%, respectively, P < .001). Similarly, 5-year graft survival was also highest in SCD recipients (SCD = 77.8%, ECD-DBD = 75.7%, and DCD = 72.2%, P < .001). In multivariable analysis, DCD grafts increased mortality risk (hazard ratio [HR] = 1.33, 95% confidence interval [CI] = 1.12-1.57, P = .001), but ECD-DBD grafts did not (HR = 1.10, 95% CI = 1.00-1.22, P = .052)., Conclusions: DCD and ECD-DBD recipients had significantly lower overall and graft survival. However, the survival benefit of LT for patients with HCC greatly outweighs the small differences in patient and graft survival from using ECD grafts. Further research should investigate whether treatment of ECD grafts with machine perfusion may ameliorate this discrepancy., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare for this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Allergic asthma is a chronic disease tied to unusual immune reactions involving type 2 T helper (Th2) cells specific to allergens. Dendritic cells (DCs) play a crucial role in guiding T-cell responses. Regulatory T (Treg) cells have the ability to suppress effector T-cell responses, and interleukin (IL)-38 is involved in Treg cell differentiation. In this study, we explored impacts of IL-38 on the activation and function of DCs, and we then developed an IL-38-overexpressing adenovirus (Ad-IL38) to evaluate its effectiveness in treating allergic asthma in mice through the adaptive transfer of Ad-IL38-infected DCs (IL38-DCs). Treating lipopolysaccharide (LPS)-activated bone marrow-derived DCs with recombinant IL-38 reduced cluster of differentiation 80 (CD80), CD86, and major histocompatibility complex (MHC) II expressions and decreased IL-1β, IL-6, and tumor necrosis factor (TNF)-α while increasing IL-10 secretion. The simultaneous culture of these semi-mature DCs with allogeneic CD4 + T cells facilitated the production of Forkhead box protein P3-positive (Foxp3 + ) Treg cells. A transcriptomic analysis revealed downregulation of the Chil3, Inhba, and Ctgf genes that are crucial for regulating inflammatory responses and cytokine-mediated signaling pathways in IL-38-treated DCs. In an animal model of asthma, IL38-DC treatment effectively decreased levels of an ovalbumin (OVA)-specific immunoglobulin E (IgE) antibody in serum, attenuated the severity of airway hyperresponsiveness, reduced the production of Th2-type cytokines (IL-4, IL-5, and IL-13) and proinflammatory cytokines (IL-6 and TNF-α) in bronchoalveolar lavage fluid, lowered expressions of the Th2-related cytokines IL-25 and thymic stromal-derived lymphopoietin (TSLP) by lung epithelial cells, and mitigated airway inflammation. Notably, enhanced expression of Foxp3 + Treg cells was linked to increased mRNA levels of transforming growth factor (TGF)-β production in vivo. In conclusion, we comprehensively clarified the immunomodulatory effects of IL-38 on DCs and provide a new treatment with IL-38 genetically modified DCs for alleviating Th2-mediated allergic diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: Elizabethkingia spp. are resistant to multiple antibiotics. This study aimed to determine in vitro and in vivo activities of cefiderocol against Elizabethkingia spp. and to investigate resistance mechanisms., Methods: Bloodstream isolates were collected from four hospitals. In vitro and in vivo activities were determined using broth microdilution and the wax moth model, respectively. Genome comparison and gene editing were used to confirm the contribution of target genes. Conjugation experiments and serial passage were used to determine transferability and stability, respectively. A MIC of ≤4 mg/L was designated as the susceptibility breakpoint., Results: Among 228 non-duplicated isolates, 226 exhibited a MIC of ≤4 mg/L with MIC 50/90 of 1/2 mg/L. Two isolates had a MIC of 128 mg/L; both patients had multiple comorbidities, were ventilator-dependent and had not received cefiderocol previously. Resistance was attributable to acquisition of bla CfxA-3 , carried by a conjugative transposon from Prevotella jejuni, and duplication of intrinsic bla CME-3 , which led to its overexpression. tetQ coexisted with bla CfxA-3 in this conjugative transposon and minocycline facilitated its transfer among E. anophelis. Antibiotics prescribed for source patients did not induce bla CME-3 duplication. The stabilities of bla CfxA-3 and double bla CME-3 were 100% and > 90%, respectively, after 10-day serial passage. Cefiderocol failed to rescue moth larvae infected with resistant strains, but removal of resistance mechanisms restored in vivo efficacy., Conclusions: Cefiderocol was in vitro and in vivo active against Elizabethkingia spp. but resistance may emerge due to the availability, transferability, and/or stability of resistance mechanisms., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The roles of aryl hydrocarbon receptor (AhR), AhR -nuclear translocator (ARNT), and AhR repressor (AhRR) genes in the elevation of cord blood IgE (CbIgE) remained unclear. Our aims were to determine the polymorphisms of AhR, ARNT, and AhRR genes, cord blood AhR (CBAhR) level, and susceptibility to elevation of CbIgE. 206 infant-mother pairs with CbIgE>=0.35 IU/ml and 421 randomly selected controls recruited from our previous study. Genotyping was determined using TaqMan assays. Statistical analysis showed AhR rs2066853 (GG vs. AA+AG: adjusted OR (AOR)=1.5, 95%CI=1.10-2.31 and AOR=1.60, 95%CI=1.06-2.43, respectively) and the combination of AhR rs2066853 and maternal total IgE (mtIgE)>=100 IU/ml were significantly correlated with CbIgE>=0.35 IU/ml or CbIgE>=0.5 IU/ml. CBAhR in a random subsample and CbIgE levels were significantly higher in infants with rs2066853GG genotype. We suggest that infant AhR rs2066853 and their interactions with mtIgE>=100 IU/ml significantly correlate with elevated CbIgE, but AhRR and ARNT polymorphisms do not.

Aims: One effective clinical strategy to combat obesity is intragastric botulinum toxin (BTX) injection, which increases gastric emptying time and regulates appetite. However, it remains unknown if and how BTX affects ghrelin levels., Materials and Methods: An obese animal model was established by feeding male mice with high-fat diet (HFD). BTX was administered by subserosal injection in the antrum via an upper midline laparotomy. The mice were monitored in terms of body weight and blood biochemical parameters. Glucose utility and insulin sensitivity were measured by intraperitoneal glucose and insulin tolerance tests. Additionally, stomach and liver were histologically examined after BTX treatment. AGS gastric adenocarcinoma cells were used to investigate the molecular mechanism by which BTX affects ghrelin expression., Key Findings: In HFD-fed mice, BTX injection significantly decreased both food intake and body weight over a 3-week monitoring period. Moreover, HFD-induced hyperglycemia, hyperinsulinemia, dyslipidemia and obesity readouts were improved after BTX injection. Importantly, mice also exhibited decreased plasma and gastric ghrelin levels after BTX injection. In cultured AGS cells, BTX significantly increased reactive oxygen species (ROS) levels and activated nuclear factor-κB (NF-κB), which led to decreased ghrelin expression. Pre-treatment with inhibitors of either ROS or NF-κB reversed the effects of BTX on ghrelin expression in the cultured cells., Significance: BTX decreases ghrelin expression in HFD-fed animals and in AGS cells through an ROS/NF-κB-dependent pathway. This mechanism may contribute to decreased food intake in obese subjects receiving intragastric BTX injection for weight control., Competing Interests: Declaration of competing interest We confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Transition-metal sulfides are emerging as promising materials for chemiresistive gas sensors─a field still dominated by semiconducting metal oxides. Despite the availability of materials with tunable electronic, optical, physical, and chemical properties, few studies have moved beyond synthesis to provide strategies for enhancing gas sensing performance through material modification. Here, we present a simple, scalable synthetic strategy for developing an optically semitransparent, flexible NH 3 gas sensor with a highly uniform, ultrathin CuS (covellite) active sensing layer. The optical and chemical properties of the CuS were precisely controlled near the percolation threshold of thin-film formation by varying key experimental parameters such as the Cu film thickness (<10 nm) and the sulfurization time (∼90 s) under ambient conditions. Experimental and computational studies of CuS and its NH 3 sensing characteristics identify key physicochemical properties. The controlled surface chemistry and morphology of the ultrathin CuS layer demonstrate its effectiveness in functional NH 3 sensing devices, which achieve a calculated detection limit of 1.38 ppm for NH 3 gas at 150 °C, along with exceptional mechanical robustness and optical semitransparency in the visible-light spectrum.

Link prediction is a paradigmatic and challenging problem in network science, which aims to predict missing links, future links, and temporal links based on known topology. Along with the increasing number of link prediction algorithms, a critical yet previously ignored risk is that the evaluation metrics for algorithm performance are usually chosen at will. This paper implements extensive experiments on hundreds of real networks and 26 well-known algorithms, revealing significant inconsistency among evaluation metrics, namely different metrics probably produce remarkably different rankings of algorithms. Therefore, we conclude that any single metric cannot comprehensively or credibly evaluate algorithm performance. In terms of information content, we suggest the usage of at least two metrics: one is the area under the receiver operating characteristic curve, and the other is one of the following three candidates, say the area under the precision-recall curve, the area under the precision curve, and the normalized discounted cumulative gain. When the data are imbalanced, say the number of negative samples significantly outweighs the number of positive samples, the area under the generalized Receiver Operating Characteristic curve should also be used. In addition, as we have proved the essential equivalence of threshold-dependent metrics, if in a link prediction task, some specific thresholds are meaningful, we can consider any one threshold-dependent metric with those thresholds. This work completes a missing part in the landscape of link prediction, and provides a starting point toward a well-accepted criterion or standard to select proper evaluation metrics for link prediction., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

The predictive processing framework posits that one of the main functions of the brain is to anticipate the incoming information. Internal models facilitate interactions with the world by predicting future states against which actual evidence is compared. The difference between predicted and actual states, the prediction error (PE), signals novel information. However, how PE affects cognitive processing downstream is not fully understood: one such aspect pertains to how PE influences episodic memories, and whether those effect on memory differ across the lifespan. We examine the relationship between PE and episodic memory in children, young and older adults. We use a novel paradigm whereby rich visual narratives are used to build action schemas that enable probing different mnemonic aspects. To create different levels of PE, we manipulate the story endings to be either expected, neutral or unexpected with respect to the unfolded action. We show that (i) expected endings are better encoded than neutral endings and (ii) unexpected endings improve the encoding of mismatching events and other aspects of the narrative. These effects are differentially modulated across the lifespan with PE-driven encoding being more prominent in children and young adults and with schema integration playing a larger role on memory encoding in older adults. These results highlight the role of predictions by enriching past experiences and informing future anticipations.This article is part of the theme issue 'Elements of episodic memory: lessons from 40 years of research'.

Background: The use of matrix-assisted laser desorption/ionisation-time-of-flight mass spectra (MALDI-TOF MS) with machine learning (ML) has been explored for predicting antimicrobial resistance. This study evaluates the effectiveness of MALDI-TOF MS paired with various ML classifiers and establishes optimal models for predicting antimicrobial resistance and the presence of mecA gene among Staphylococcus aureus., Materials and Methods: Antimicrobial resistance against tier 1 antibiotics and MALDI-TOF MS of S. aureus were analysed using data from the Database of Resistance against Antimicrobials with MALDI-TOF Mass Spectrometry (DRIAMS) and one medical centre (CS database). Five ML classifiers were used to analyse performance metrics. The Shapley value quantified the predictive contribution of individual features., Results: The LightGBM demonstrated superior performance in predicting antimicrobial resistance for most tier 1 antibiotics among oxacillin-resistant S. aureus (ORSA) compared with all S. aureus and oxacillin-susceptible S. aureus (OSSA) in both databases. In DRIAMS, Multilayer Perceptron (MLP) was associated with excellent predictive performance, expressed as accuracy/AUROC/AUPR, for clindamycin (0.74/0.81/0.90), tetracycline (0.86/0.87/0.94), and trimethoprim-sulfamethoxazole (0.95/0.72/0.97). In the CS database, Ada and Light Gradient Boosting Machine (LightGBM) showed excellent performance for erythromycin (0.97/0.92/0.86) and tetracycline (0.68/0.79/0.86). Mass-to-charge ratio (m/z) features of 2411-2414 and 2429-2432 correlated with clindamycin resistance, whereas 5033-5036 was linked to erythromycin resistance in DRIAMS. In the CS database, overlapping features of 2423-2426, 4496-4499, and 3764-3767 simultaneously predicted the presence of mecA and oxacillin resistance., Conclusion: The predictive performance of antimicrobial resistance against S. aureus using MALDI-TOF MS depends on database characteristics and the ML algorithm selected. Specific and overlapping mass spectra features are excellent predictive markers for mecA and specific antimicrobial resistance., Competing Interests: Declarations Funding: This project was supported by Chung Shan Medical University (grant number: CSMUH No:CS1-23228). This funding source played no role in study design or conduct, data collection, analysis or interpretation, writing of the manuscript, or the decision to submit the manuscript for publication. Competing interests: The authors declare no conflicts of interest in relation to this study. Ethical approval: CSMUH No. CS1-23228 of Chung Shan Medical University and REC112-51 of Taichung Tzu Chi Hospital). Sequence information: Not applicable., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

The tendency of falsely remembering events that did not happen in the past increases with age. This is particularly evident in cases in which features presented at study are re-presented at test in a recombined constellation (termed rearranged pairs). Interestingly, older adults also express high confidence in such false memories, a tendency that may indicate reduced metacognitive efficiency. Within an existing cohort study, we aimed at investigating age-related differences in memory metacognitive efficiency (as measured by meta d ' ratio) in a sample of 1522 older adults and 397 young adults. The analysis showed an age-related deficit in metacognition which was more pronounced for rearranged pairs than for new pairs. We then explored associations between cortical thickness and memory metacognitive efficiency for rearranged pairs in a subsample of 231 older adults. By using partial least square analysis, we found that a multivariate profile composed by ventromedial prefrontal cortex, insula, and parahippocampal cortex was uniquely associated with between-person differences in memory metacognitive efficiency. These results suggest that the impairment in memory metacognitive efficiency for false alarms is a distinct age-related deficit, above and beyond a general age-related decline in memory discrimination, and that it is associated with brain regions involved in metacognitive processes.

Acute fish toxicity (AFT) tests are performed in aquatic risk assessments of chemical compounds globally. However, the specific endpoint of in vivo AFT is based on the lethal concentration 50 (LC 50 ), which is a serious challenge in terms of animal welfare. To support the 3Rs principle of replacing, reducing, and refining use of animals, integrated testing strategies (ITS) have recently been developed for environmental risk assessment. ITS efficiently integrates multiple types of information, especially new approach methodologies (NAMs), and further supports regulatory decision-making. Currently, an effective ITS framework for evaluating aquatic toxicity is lacking. Therefore, we aimed to develop a promising ITS for AFT using in silico, in vitro, and in vivo data. We established the ITS via in silico (OECD QSAR Toolbox 4.6), fish cell line acute toxicity (FCT), and fish embryo acute toxicity (FET) tests and then validated the NAMs with AFT testing. The NAM data were derived from the European Chemicals Agency (ECHA) dossier, toxicology databases, peer-reviewed research articles, and this study. For the first step in the ITS process, we aimed to design a high-throughput screening tool to identify non-toxic and toxic chemicals. We found that results of in silico, FCT, and FET tests alone were strongly correlated with AFT. Among the models, the in silico model was most suitable for identifying toxicants due to its high sensitivity and minimal animal use. Next, considering regulatory purposes and flexibility, we determined the predictive LC 50 of toxic chemicals by pursuing a preference-dependent strategy, sequential testing strategy, and sensitivity-dependent strategy. All the strategies demonstrated a predictive power equal to or greater than 73%. In addition, to meet user preferences, our ITS approach has high flexibility and supports animal welfare and environmental protection. We have therefore developed multiple powerful, flexible, and more humane ITS methods for acute fish toxicity assessment by integrating NAMs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

This phase 3, observer-blinded, non-inferiority randomized trial (ClinicalTrials.gov: NCT05517642), conducted from September 2022 to May 2023 at three Malaysian sites, involved 540 adults previously vaccinated with three COVID-19 doses. Participants were randomized 1:1 to receive either one dose of inhaled Recombinant COVID-19 Vaccine (Ad5-nCoV-IH) or intramuscular tozinameran (BNT-IM). The study assessed safety, vaccine efficacy (VE) and immunogenicity against SARS-CoV-2 variants. The primary outcome was the non-inferiority of anti-spike protein receptor-binding domain (S-RBD IgG) antibodies, with a 97.5% confidence interval lower limit for the geometric mean concentration (GMC) ratio >0.67. Ad5-nCoV-IH showed lower immunogenicity than BNT-IM, with a GMC ratio of 0.22 and a seroconversion rate difference of -71.91%. Adverse drug reactions (ADRs) were less frequent with Ad5-nCoV-IH (39.26%) compared to BNT-IM (64.68%). No serious vaccine-related adverse events were reported. Both vaccines had comparable efficacy against COVID-19 variants. This study was funded by Tianjin Biomedical Science and Technology Major Project., (© 2024. The Author(s).)