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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

Ya-Ling Lee,1,2 Hsiao-Yun Hu,2,3 Pesus Chou,2 Dachen Chu2,4,5 1Department of Dentistry, Taipei City Hospital, 2Institute of Public Health and Community Medicine Research Center, National Yang-Ming University, 3Department of Education and Research, Taipei City Hospital, 4Department of Health Care Management, National Taipei University of Nursing and Health Sciences, 5Department of Neurosurgery, Taipei City Hospital, Taipei, Taiwan Purpose: To investigate the association between periodontal disease (PD) and acute ­myocardial infarction (AMI), and evaluate the effect of dental prophylaxis on the incidence rate (IR) of AMI.Methods: The Longitudinal Health Insurance Database 2000 from the National Health Insurance program was used to identify 511,630 patients with PD and 208,713 without PD during 2000–2010. Subjects with PD were grouped according to treatment (dental prophylaxis, intensive treatment, and PD without treatment). The IRs of AMI during the 10-year follow-up period were compared among groups. Cox regression analysis adjusted for age, sex, socioeconomic status, residential urbanicity, and comorbidities was used to evaluate the effect of PD treatment on the incidence of AMI.Results: The IR of AMI among subjects without PD was 0.19%/year. Among those with PD, the IR of AMI was lowest in the dental prophylaxis group (0.11%/year), followed by the intensive treatment (0.28%/year) and PD without treatment (0.31%/year; P

Silicate glasses were synthesized with additional CdO and ZnSe of varying content. When CdO was added up to 3 mol% with the amount of ZnSe fixed at 1 mol%, absorption due to Se2− color centers significantly decreased and the color of glasses was bleached without any evidence of CdSe quantum dots ( QDs). However, characteristic absorption due to CdSe QDs appeared without additional heat treatment when the ZnSe content exceeded 1.5 mol%, whereas the CdO content was fixed at 1 mol%. Raman spectra and transmission electron microscopy verified the formation of CdSe QDs. The role of CdO and ZnSe in CdSe QD formation has been discussed in relation to their structural contribution within silicate glasses. [ABSTRACT FROM AUTHOR]

Hypoxia-inducible factor-1α (HIF-1α) is a key regulator of cellular response to hypoxia and has been suggested to play an important role in tumorigenesis and metastasis. The aim of this study was to investigate the role of HIF-1α-1772 C/T (P582S) and -1790 G/A (A588T) polymorphisms in the susceptibility to and severity of non-small-cell lung cancer (NSCLC). Using a case-control study design and polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis, the allele frequencies and genotype distributions of each single nucleotide polymorphism in 285 NSCLC cases and 300 gender-matched controls were compared. The distribution of the genotype frequencies of HIF-1α-1772 C/T and -1790 G/A were significantly different between the NSCLC and the controls. Logistic regression analysis revealed that higher odds ratios (ORs) for lung cancer were observed for individuals with HIF-1α-1772 T/T genotype against CC/CT genotypes (an OR of 4.04, 95% confidence interval [CI] = 2.02-8.08, P = 0.0001), and HIF-1α-1790 A/A genotype against GG/GA genotypes (an OR of 4.42, 95% CI 2.22-8.78, P < 0.0001). There were no relationship between HIF-1α-1772 C/T or -1790 G/A allele distribution and disease severity of NSCLC (P > 0.05). However, those patients carrying a HIF-1α-1772 T/T genotype or a HIF-1α-1790 A/A had a tendency toward inferior prognosis compared with other patients. [ABSTRACT FROM AUTHOR]

The sodium iodine symporter (NIS) or mutant Herpes-simplex virus type1 sr39 thymidine kinase (HSV1-sr39tk) gene is used for in vivo imaging and cancer therapy. Transfection of both NIS and HSV1-sr39tk genes to hepatocellular carcinoma cells (Huh-7/NTG) could enhance intracellular accumulation of therapeutic radionuclides and guanosine nucleoside analogue prodrugs to produce better outcomes than single gene therapy. Non-invasive imaging with I-124, F-18 FHBG and combination therapy with I-131 and GCV were performed in hepatocellular carcinoma cells transfected with NIS, HSV1-sr39tk and GFP. Our results show that: (1) all three genes are stably expressed in Huh-7/NTG cells, (2) I-125 and H3-PCV uptake were markedly increased in the Huh-7/NTG cells in vitro, (3) cellular survival and tumor growth of Huh-7/NTG was inhibited by I-131 or GCV both in vitro and in vivo, and was much prominent with combination therapy, (4) in vivo imaging with I-124 and F-18 FHBG revealed increased uptake in the Huh-7/NTG tumor. Our results demonstrated the potential of combination gene therapy using NIS and HSV1-sr39tk followed by radioiodine treatment and chemotherapy in human hepatocellular carcinoma cells. [ABSTRACT FROM AUTHOR]

Few studies have investigated the factors related to the disability and physical function in degenerative lumbar spondylolisthesis using axially loaded magnetic resonance imaging (MRI). Therefore, we aimed to investigate the effect of axial loading on the morphology of the spine and the spinal canal in patients with degenerative spondylolisthesis of L4-5 and to correlate morphologic changes to their disability and physical functions. From March 2003 to January 2004, 32 consecutive cases (26 females, 6 males) with degenerative L4-5 spondylolisthesis, grade 1-2, intermittent claudication, and low back pain without sciatica were included in this study. All patients underwent unloaded and axially loaded MRI of the lumbo-sacral spine in supine position to elucidate the morphological findings and to measure the parameters of MRI, including disc height (DH), sagittal translation (ST), segmental angulation (SA), dural sac cross-sectional area (DCSA) at L4-5, and lumbar lordotic angles (LLA) at L1-5 between the unloaded and axially loaded condition. Each patient's disability was evaluated by the Oswestry Disability Index (ODI) questionnaire, and physical functioning (PF) was evaluated by the Physical Function scale proposed by Stucki et al. (Spine 21:796-803, 1996). Three patients were excluded due to the presence of neurologic symptoms found with the axially loaded MRI. Finally, a total of 29 (5 males, 24 females) consecutive patients were included in this study. Comparisons and correlations were done to determine which parameters were critical to the patient's disability and PF. The morphologies of the lumbar spine changed after axially loaded MRI. In six of our patients, we observed adjacent segment degeneration (4 L3-L4 and 2 L5-S1) coexisting with degenerative spondylolisthesis of L4-L5 under axially loaded MRI. The mean values of the SA under pre-load and post-load were 7.14 degrees and 5.90 degrees at L4-L5 (listhetic level), respectively. The mean values of the LLA under pre-load and post-load were 37.03 degrees and 39.28 degrees , respectively. There were significant correlations only between the ODI, PF, and the difference of SA, and between PF and the post-loaded LLA. The changes in SA (L4-L5) during axial loading were well correlated to the ODI and PF scores. In addition, the LLA (L1-L5) under axial loading was well correlated to the PF of patients with degenerative L4-L5 spondylolisthesis. We suggest that the angular instability of the intervertebral disc may play a more important role than neurological compression in the pathogenesis of disability in degenerative lumbar spondylolisthesis. [ABSTRACT FROM AUTHOR]

Objective: Parental atopy and environmental exposures at home have been recognized risk factors for adulthood asthma. However, the relative contributions of specific risk factors and the overall contributions of heredity or home exposure remain unexplored. The purpose of this study was to identify predictors and estimate the population attributable risk (PAR) of each exposure for typical asthma symptoms among 26- to 50-year-old Taiwanese. We also investigated whether an interactive effect existed between parental atopy and home exposures on the occurrence of asthma symptoms in adulthood.Design: A cross-sectional study with retrospective components.Setting: Elementary and middle schools in Southern Taiwan.Subjects: Between March and October 2004, we conducted a cross-sectional survey among schoolchildren's parents from 94 elementary and middle schools in Southern Taiwan. The main outcome measure was typical asthma-like symptoms occurring within the preceding 5 years. Information on hereditary and home exposures was collected by using a self-administered questionnaire.Results: After excluding unqualified questionnaires, data from 24,784 subjects were left for analysis. New-onset asthma was reported for 0.83% of male (n = 80 of 9,662) and 1.36% of female subjects (n = 206 of 15,122). Besides parental atopic factors, environmental tobacco smoke or pet avoidance and visible mold on walls at home were independently associated with the occurrence of asthma symptoms. Mutually adjusted models produced statistically significant associations between any home exposure (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.08 to 3.23; PAR, 28.04%), parental atopy (OR, 4.47; 95% CI, 3.47 to 5.75; PAR, 31.38%), and new-onset asthma. However, there was no interaction between parental atopy and home exposures.Conclusions: Home exposures and parental atopy both increased the risks of new-onset asthma in adulthood but did not show an interactive effect. These two exposure categories approximately contributed equally to the adulthood asthma. [ABSTRACT FROM AUTHOR]

When we use radiation to treat cancer patients, the irradiated volume usually encloses the detectable tumor and any metastatic areas that are thought to be at risk. Usually, in three-dimensional (3D) radiation therapy, we need to define the clinical target volume (CTV), which identifies the areas suspected of containing microscopic metastasis. We can use a set of computed tomographic (CT) images to define these suspected areas, which we relate to nodal station distributions. The traditional method uses special anatomic landmarks for such definition. This lymph node image guidance method uses a set of CT images to show the relevant nodal stations and find the correlation between the suspected areas and the lymphatic pathways. First, we used CT images from head and neck cancer patients. Then, we designed a program to delineate the regional lymphatic areas in order to distinguish the position of all the major lymph nodes in the head and neck region. These lymph nodes were then used to assist the oncologist in developing treatment references. Finally, we established a database management system to determine the relationships between different lesions and lymph nodes, as well as correlations, with metastatic pathways. Defining these relationships on the CT images provided oncologists specific information that could be used to define the CTV more precisely for 3D radiation therapy. [ABSTRACT FROM AUTHOR]

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.)

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.)

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 in 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. Published by Elsevier Inc.)

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.)

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.

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 source 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., Competing Interests: Competing Interests All authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)

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).)

Background: The discovery of glioblastoma (GBM)-initiating cells (GICs) has impacted GBM research. These cells are not only tumorigenic, but also exhibit resistance to radiotherapy and chemotherapy. Therefore, it is crucial to characterize GICs thoroughly and identify new therapeutic targets. In a previous study, we successfully identified Epithelial V-like antigen 1 (EVA1) as a novel functional factor specific to GICs., Methods: Hybridoma cells were generated by immunizing BALB/c mice with EVA1-Fc fusion protein. The reactivity of the supernatant from these hybridoma cells was examined using EVA1-overexpressing cells and GICs. Candidate antibodies were further selected using Biacore surface plasmon resonance analysis and two cytotoxicity assays, antibody-dependent cell cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Among the antibodies, the cytotoxicity of the B2E5-antibody drug conjugate (B2E5-ADC) was evaluated by both adding it to cultured GICs and injecting it into GIC tumor-bearing brains., Results: B2E5 demonstrated a high affinity for human EVA1 and effectively killed both EVA1-expressing cell lines and GICs in culture through ADCC and CDC. B2E5-ADC also exhibited strong cytotoxicity to GICs in culture and prevented their tumorigenesis in the brain when administered intracranially to the tumor-bearing brain., Conclusion: Our data indicate that B2E5-ADC is a new and promising therapeutic strategy for GBM., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

In response to the growing demand for immune-related products, this study evaluated the safety and immune-modulating potential of three newly discovered Lactiplantibacillus plantarum strains (GKM3, GKK1, and GKD7) through toxicity tests and whole-genome sequencing. Safety evaluations, including the analysis of antimicrobial resistance genes, virulence factors, plasmids, and prophages, classified these strains as safe for human consumption. Acute oral toxicity tests further supported their safety. To evaluate their immune-modulating potential, dendritic cells were exposed to these strains, and the secretion of key cytokines (IFN-β and IL-12) was measured. Among the strains, GKK1 exhibited the highest enhancement of IFN-β and IL-12 production, suggesting its potential as an immune-stimulating probiotic. Bioinformatics analysis revealed potential metabolic pathways and secondary metabolites, including predicted bacteriocins, associated with immune modulation. The presence of a nitrate reductase region in the GKK1 strain indicated its ability to produce nitric oxide, a critical molecule involved in immune regulation and host defense. The presence of glucorhamnan-related gene clusters in GKK1 also suggested immune-enhancing effects. Nitrate reductase expression was confirmed using qPCR, with the highest levels detected in GKK1. Moreover, this study is the first to show an anti-inflammatory effect of plantaricin A, linked to its presence in strain GKM3 and its potential therapeutic applications due to sequence similarity to known anti-inflammatory peptides. Overall, these three L. plantarum strains demonstrated a safe profile and GKK1 showed potential as an immunity-enhancing probiotic. However, additional investigation is required to confirm the involvement of specific metabolic pathways, secondary metabolites, and bacteriocins in immune responses.

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: Ectopic pregnancy (EP) occurs when a fertilized ovum is implanted outside the uterine cavity. Its incidence is 2% of all pregnancies and is known to decrease fertility. This study aimed to measure pregnancy rates after EP, identify the various parameters influencing pregnancy, and compare these variables in women with and without a history of EP, as well as determine in which medical facilities women with EP seek medical help., Methods: The data was extracted from the National Health Insurance Research Database during 2000-2013. The study group included of women with a history of one EP (study group) and women without EP (control group). The chi-square/Fisher exact test was performed for categorical variables, and t-tests were used for continuous variables., Results: The EP group had a higher cumulative pregnancy rate (41.55%) than the control group (37.14 %), and a 1.16 times higher rate in developing pregnancy ( p < 0.001). While the pregnancy rate in the EP group was initially lower than in the control group during the first 5 years, it surpassed the control group's rate between the 10 th and 14 th years., Conclusions: Fecundability after EP was lower at the beginning but increased at long-term follow-up., 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 Yin, Lee, Chang, Chien and Wu.)

With the increasing prevalence of antimicrobial-resistant bacterial infections, there is interest in using bacteriophages (phages) to treat such infections. However, the factors that govern bacteriophage pharmacokinetics in vivo remain poorly understood. Here, we have examined the contribution of neutrophils, the most abundant phagocytes in the body, to the pharmacokinetics of i.v. administered bacteriophage in uninfected mice. A single dose of LPS-5, a bacteriophage recently used in human clinical trials to treat drug-resistant Pseudomonas aeruginosa, was administered i.v. to both immunocompetent BALB/c and neutropenic CD1 mice. Phage concentrations were assessed in peripheral blood and spleen at 0.25, 1, 2, 4, 8, 12, and 24 hours after administration by plaque assay and qPCR. We observed that the phage clearance was only minimally affected by neutropenia. Indeed, the half-lives of phages in blood in BALB/c and CD1 mice were 3.45 and 3.66 hours, respectively. These data suggest that neutrophil-mediated phagocytosis is not a major determinant of phage clearance. Conversely, we observed a substantial discrepancy in circulating phage levels over time when measured by qPCR versus plaque assay, suggesting that significant inactivation of circulating phages occurs over time. These data indicate that alternative factors, but not neutrophils, inactivate i.v. administered phages.

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., (© 2024. Society of Surgical Oncology.)

Arboviruses can intensify epidemics by acquiring single nucleotide variants, leading to clade replacement and severe outbreaks. We investigated dengue virus serotype 2 evolution in consecutive outbreaks from 2001 to 2003 in Taiwan, coinciding with overwintering and increased epidemic severity. The virus evolved from the early-epidemic strain (Ia) to the late-epidemic strains (Ib and II), featuring three amino acid differences. The later strains demonstrated increased replication at lower temperatures, and the NS5 V357E mutation significantly boosts virus replication and virulence, regardless of the other two mutations (E T46I and NS5 I271T ). Crucially, the late NS5 V357E signature swiftly emerged after infecting mosquitos with the early Ia strain, through thoracic injection or by feeding on Ia-infected mice. Thus, we discover the molecular events involved in overwintering and increased disease severity between consecutive dengue outbreaks. This study enhances our understanding of dengue epidemiology, aiding in predicting and monitoring the emergence of dengue strains with increased epidemic potential., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: The spread of emerging SARS-CoV-2 immune escape sublineages, especially JN.1 and KP.2, has resulted in new waves of COVID-19 globally. The evolving memory B cell responses elicited by the parental Omicron variants to subvariants with substantial antigenic drift remain incompletely investigated., Methods: Using the single B cell antibody cloning technology, we isolated single memory B cells, delineated the B cell receptor repertoire and conducted the pseudovirus-based assay for recovered neutralizing antibodies (NAb) screening. We analyzed the cryo-EM structures of top broadly NAbs (bnAbs) and evaluated their in vivo efficacy (golden Syrian hamster model)., Findings: By investigating the evolution of human B cell immunity, we discovered a new panel of bnAbs arising from vaccinees after Omicron BA.2/BA.5 breakthrough infections. Two lead bnAbs neutralized major Omicron subvariants including JN.1 and KP.2 with IC 50 values less than 10 ng/mL, representing ultrapotent receptor binding domain (RBD)-specific class I bnAbs. They belonged to the IGHV3-53/3-66 clonotypes instead of evolving from the pre-existing vaccine-induced IGHV1-58/IGKV3-20 bnAb ZCB11. Despite sequence diversity, they targeted previously unrecognized, highly conserved conformational epitopes in the receptor binding motif (RBM) for ultrapotent ACE2 blockade. The lead bnAb ZCP3B4 not only protected the lungs of hamsters intranasally challenged with BA.5.2, BQ.1.1 and XBB.1.5 but also prevented their contact transmission., Interpretation: Our findings demonstrated that class I bnAbs have evolved an ultrapotent mode of action protecting against highly transmissible and broad Omicron escape variants, and their epitopes are potential targets for novel bnAbs and vaccine development., Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section., Competing Interests: Declaration of interests The other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Traumatic duodenal injuries are complex in nature and pose major challenges to trauma surgeons. These injuries are associated with high mortality rates ranging from 18% to 30% and require prompt, comprehensive care. Traumatic injury induces a hypercatabolic state that mobilizes body energy stores, leading to muscle wasting, delayed healing, and potential multi-organ failure. Nutritional support is vital in keeping up with the metabolic demands of traumatically injured patients. However, exactly when and how nutrition should be provided for traumatic duodenal injuries is unclear. We hypothesize that patients who sustain high-grade duodenal injuries (grades III-V) will be unable to tolerate enteral nutrition (EN) and may benefit from early initiation of total parenteral nutrition (TPN)., Methods: In this retrospective chart review study, we queried the trauma registry for patients admitted between January 2018 and December 2022 with duodenal injury. Individuals under the age of 18 and individuals who were pregnant were excluded. Twenty-eight patients met the inclusion/exclusion criteria. The primary endpoint was median number of days from initial injury to supplemental nutrition. We also evaluated the route used to achieve adequate nutrition based on duodenal injury grade (I-V), mortality based on duodenal injury grade, morbidity based on route of nutrition supplementation (hospital length of stay [LOS], intensive care unit LOS, and ventilator days), and complications based on route of nutrition supplementation., Results: Of the 28 patients analyzed, 11 received EN, 10 received TPN (6 of which survived to transition to EN), and 7 died within 3 d of admission and did not receive any form of nutrition. The median number of days post-trauma to toleration of enteral feeding (defined as by mouth or tube feeding that meet total caloric needs based on nutritionist recommendations) was 4 d for those who did tolerate and maintained tolerance of enteral feeding, compared to 7.5 d post-trauma to initiate total parenteral feeding (P = 0.061). Injury grades I and II tolerated EN within a median of 6 d, whereas injury grades III and IV showed inability to tolerate EN until after a median of 22 d or longer (P = 0.02). Mortality increased as injury grade increased. Patients who received TPN were more likely to develop abscesses than those receiving EN (80% vs 27%, P = 0.03) but not more likely to develop a duodenal leak (P = 0.31). Patients who received TPN had longer hospital LOS (35.5 d vs 9 d, P = 0.008), longer intensive care unit LOS (17 d vs 4 d, P = 0.005), and increased ventilator days (9 d vs 1 d, P = 0.005) when compared to patients who received EN., Conclusions: Individuals with higher grade duodenal injuries showed inability to tolerate EN until after a median of 22 d, and therefore, consideration should be given to initiating TPN early to mitigate the catabolic effects of malnutrition. Further studies need to be done with a larger number of patients to evaluate the effects of malnutrition in these patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Sacha Inchi ( Plukenetia volubilis ) seeds and oil have been integrated into daily diets. However, scientific reports have raised concerns regarding potential health risks associated with saponins and alkaloids in this seeds. This study employed a combination analysis using proton-NMR, GC-MS, LC-QTOF, and GNPS molecular networking to evaluate the chemical composition of these seeds. In silico toxicology analysis and in vitro cytotoxicity assays were conducted to investigate the potential toxicity effects of Sacha Inchi seeds and their contained metabolites. The results revealed that major components of these seeds are oils (linoleic, linolenic, and oleic acids) and sugars, with minor amounts of phytosterols and trigonelline, a pyridine alkaloid. GNPS analysis suggested the absence of saponins, instead, it identified trigonelline and a few other nitrogen-containing metabolites (amino acids and oligopeptides). In silico toxicology analysis indicated that this sample did not exhibit toxicity. Furthermore, in vitro cytotoxicity screening demonstrated no cytotoxic effects against NIH-3T3 cells, even at 400 μg mL -1 . In general, these findings collectively indicated the absence of saponins, the presence of phytosterols and trigonellin (a pyridine alkaloid), and a low safety risk related to saponin and alkaloid content in the Sacha Inchi seeds., Competing Interests: The authors declare there is no any conflict of interest related to this study., (This journal is © The Royal Society of Chemistry.)

Schistosoma mansoni infection leads to chronic schistosomiasis and severe hepatic fibrosis. We designed a liver-targeted lipid nanoparticle (LNP) carrying siRNA against type I TGF-β receptor (TGFβRI) mRNA to treat schistosomiasis-induced liver fibrosis in BALB/c mice. Knockdown of TGFβRI by LNP-siTGFβRI reduced LX-2 cell activation in vitro and alleviated liver fibrosis in S. mansoni-infected mice. αSMA and Col1a1 fibrotic markers in the liver tissues of infected mice were significantly suppressed in the treatment groups. In the serum of the LNP-siTGFβRI-treated groups, cytokines IFNγ, IL-1α, IL-6, IL-12, RANTES (CCL5), and TNFα increased, while GM-CSF, IL-2, IL-4, IL-10, IL-13, and KC (CXCL1) decreased compared to the control. Cell proportions were significantly altered in S. mansoni-infected mice, with increased CD56d NK cells and decreased CD19+ B cells and CD4+ T cells compared to naïve mice. Following LNP-siTGFβRI treatment, CD56d NK cells were downregulated, while B and memory Th cell populations were upregulated. The density of fibrotic regions significantly decreased with LNP-siTGFβRI treatment in a dose-dependent manner, and no systemic toxicity was observed in the major organs. This targeted siRNA delivery strategy effectively reduced granulomatous lesions in schistosomiasis-induced liver fibrosis without detectable side effects., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Hemorrhage, particularly from non-compressible 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., Competing Interests: Conflicts of interest: none, (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Successful navigation to spatial locations relies on lasting memories from previous experiences. Spatial navigation undergoes profound maturational changes during childhood. It is unclear how well children can consolidate navigation-based spatial memories and if age-related variations in navigation during training predict spatial memory. The present study examined the immediate and long-delay (after a 2-week period) consolidation of navigation-based spatial memories in 6- to 8-year-old children (n = 33, 18 female/15 male, M age = 7.61, SD age = 0.71), 9- to 11-year-old children ( n = 32, 13 female/19 male, M age = 9.90, SD age = 0.59), and 20- to 30-year-old adults ( n = 31, 15 female/16 male, M age = 23.71, SD age = 2.87). Our results showed that, with age, participants navigated more efficiently during training and formed better immediate spatial memories. Long-delay spatial memory retention after 2 weeks was comparable between children and adults, indicating robust consolidation even in children. Interestingly, while children successfully distinguished between perceptually detailed landmarks after 2 weeks, their abstract knowledge of spatial boundaries and cognitive map of landmark relations was poor. Developmental trajectories were similar for egocentric and allocentric spatial memory. Age-related variations in initial navigation were predictive of spatial memory, that is, children with a more mature initial navigation were more likely to find and remember spatial locations immediately and after a 2-week delay. Taken together, our results show an overall robust spatial memory consolidation in mid and late childhood that can be predicted by initial navigation behavior, coupled with nuanced age differences in the recall of spatial boundaries and cognitive maps. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Age-related osteoporosis is a metabolic skeletal disorder caused by estrogen deficiency in postmenopausal women. Prolonged use of anti-osteoporotic drugs such as bisphosphonates and FDA-approved anti-resorptive selective estrogen receptor modulators (SERMs) has been associated with various clinical drawbacks. We recently discovered a low-molecular-weight biocompatible and osteoanabolic phytoprotein, called HKUOT-S2 protein (32 kDa), from Dioscorea opposita Thunb that can accelerate bone defect healing. Here, we demonstrated that the HKUOT-S2 protein treatment can enhance osteoblasts-induced ossification and suppress osteoporosis development by upregulating skeletal estrogen receptors (ERs) ERα, ERβ, and GPR30 expressions in vivo . Also, HKUOT-S2 protein estrogenic activities promoted hMSCs-osteoblasts differentiation and functions by increasing osteogenic markers, ALP, and RUNX2 expressions, ALP activity, and osteoblast biomineralization in vitro . Fulvestrant treatment impaired the HKUOT-S2 protein-induced ERs expressions, osteoblasts differentiation, and functions. Finally, we demonstrated that the HKUOT-S2 protein could bind to ERs to exert osteogenic and osteoanabolic properties. Our results showed that the biocompatible HKUOT-S2 protein can exert estrogenic and osteoanabolic properties by positively modulating skeletal estrogen receptor signaling to promote ossification and suppress osteoporosis. Currently, there is no or limited data if any, on osteoanabolic SERMs. The HKUOT-S2 protein can be applied as a new osteoanabolic SERM for osteoporosis treatment., Competing Interests: Kelvin Wai Kwok Yeung is an associate editor and Wei Qiao an editorial board member for Bioactive Materials and were not involved in the editorial review or the decision to publish this article. The authors declare that they have no conflict of interest., (© 2024 The Authors.)