Background: Healthcare-associated central line associated bloodstream infection (HA-CLABSI) surveillance is important for monitoring healthcare-associated infections (HAIs) and evaluating effectiveness of infection prevention (IP) measures. However, implementing it is a laborious and time-consuming approach. Exclusive focus on central lines neglects HAI risk due to peripheral vascular catheters. This study aimed to assess whether HA-CLABSI incidence could be inferred from HA-bloodstream infection (BSI) trends and explore shift to HA-BSI surveillance. Methods: The study was performed in a Singaporean tertiary care hospital. Electronic medical records review was performed to determine whether positive blood cultures met Centers for Disease Control/National Health Safety Network (CDC/NHSN) definitions for HA-CLABSI and HA-BSI. Incident episodes of HA-BSI were included (excluding positive cultures repeated within 14 days). Incident organisms were explored to identify common causative pathogens (excluding same organisms isolated from cultures repeated within 14 days). CLABSI and BSI occurring ≥72hrs after admission were considered healthcare-associated. Patients under oncology or hematology service were considered immunocompromised. Incidence rates (IR) per 10,000 patient-days, patient characteristics and causative pathogens were compared between both indicators. Results: From January 2022 to October 2023, mean IR for HA-CLABSI was 0.63 (n=68) and for HA-BSI was 10.06 (n=1094). Median age of patients with HA-CLABSI was 66 years and HA-BSI was 68 years. HA-CLABSI and HA-BSI were more common in males (60.86% & 58.68%). Median duration between admission to HA-CLABSI was 20 days and to HA-BSI was 12 days. Median duration between central line insertion to HA-CLABSI was 16 days. Of 1094, 631 (57.7%) patients had vascular catheter(s) (i.e., IV cannula, port-a-cath, peripherally-inserted central catheter or central line) inserted at time of HA-BSI diagnosis, of whom 46 (7.3%) patients had CLABSI ±2days from positive blood culture. There was no significant correlation between monthly aggregate data from these indicators (Spearman’s correlation coefficient= 0.36, p-value=0.1). Predominant organisms causing HA-CLABSI and HA-BSI were gram negative bacteria (GNB, 40% & 57.21%), gram positive bacteria (24.71% & 22.23%), and fungi. Common GNB in CLABSI patients were Pseudomonas spp. and Stenotrophomonas maltophilia (8.24%), followed by Serratia marcescens and Klebsiella pneumoniae (5.88%). The frequent GNB in HA-BSI patients were Escherichia coli (15.4%), Klebsiella pneumonia (12.68%), and Pseudomonas spp. (6.69%). Common multi-drug resistant organisms were vancomycin-resistant Enterococcus faecium (10.59% & 3.69%) and methicillin-resistant Staphylococcus aureus (10.59% & 3.07%). Conclusion: HA-BSI did not correlate with HA-CLABSI. HA-BSI reflects heterogenous population outcomes. For utilization as surveillance indicator, further assessment on exclusion criteria is required to improve specificity.

Infection mechanism plays a significant role in epidemic models. To investigate the influence of saturation effect, a nonlocal (convolution) dispersal susceptible-infected-susceptible epidemic model with saturated incidence is considered. We first study the impact of dispersal rates and total population size on the basic reproduction number. Yang, Li and Ruan (J. Differ. Equ. 267 (2019) 2011–2051) obtained the limit of basic reproduction number as the dispersal rate tends to zero or infinity under the condition that a corresponding weighted eigenvalue problem has a unique positive principal eigenvalue. We remove this additional condition by a different method, which enables us to reduce the problem on the limiting profile of the basic reproduction number into that of the spectral bound of the corresponding operator. Then we establish the existence and uniqueness of endemic steady states by a equivalent equation and finally investigate the asymptotic profiles of the endemic steady states for small and large diffusion rates to provide reference for disease prevention and control, in which the lack of regularity of the endemic steady state and Harnack inequality makes the limit function of the sequence of the endemic steady state hard to get. Finally, we find whether lowing the movements of susceptible individuals can eradicate the disease or not depends on not only the sign of the difference between the transmission rate and the recovery rate but also the total population size, which is different from that of the model with standard or bilinear incidence.

As an important component of prehistoric subsistence, an understanding of bone-working is essential for interpreting the evolution of early complex societies, yet worked bones are rarely systematically collected in China. Here, the authors apply multiple analytical methods to worked bones from the Longshan site of Pingliangtai, in central China, showing that Neolithic bone-working in this area, with cervid as the main raw material, was mature but localised, household-based and self-sufficient. The introduction of cattle in the Late Neolithic precipitated a shift in bone-working traditions but it was only later, in the Bronze Age, that cattle bones were utilised in a specialised fashion and dedicated bone-working industries emerged in urban centres.

Noncrystalline aluminosilicates termed allophane and imogolite are common constituents of spodosols, soils derived from volcanic ash, and many inceptisols. The surface charge characteristics of their synthetic analogues may be used to better understand their ion retention properties. In this study, we determined the point of zero salt effect (PZSE) by potentiometric titration of allophanes with Al/Si ratios of 1.12, 1.52, and 2.04 and of imogolite with an Al/Si ratio of 2.02. We also used microelectrophoresis to determine the point of zero charge (PZC) at the particle shear plane for the same materials in CI solutions of Li, Na, Cs, and tetramethyl ammonium. The PZSE decreased with decreasing Al/Si ratio for the allophanes, but the imogolite PZSE was much lower than that of the allophane with 2.04 Al/Si. The PZC was always higher than the PZSE of the same material, especially for imogolite. The results are best explained if cations reside within the hollow tubes of imogolite. This conclusion is supported by a fluorescence study that showed that only quenchers smaller than the inner diameter of the imogolite tube could fully quench Ce-imogolite.

Here, we report the generation of MeV alpha-particles from H-11B fusion initiated by laser-accelerated boron ions. Boron ions with maximum energy of 6 MeV and fluence of 109/MeV/sr@5 MeV were generated from 60 nm-thick self-supporting boron nanofoils irradiated by 1 J femtosecond pulses at an intensity of 1019 W/cm2. By bombarding secondary hydrogenous targets with the boron ions, 3 × 105/sr alpha-particles from H-11B fusion were registered, which is consistent with the theoretical yield calculated from the measured boron energy spectra. Our results demonstrated an alternative way toward ultrashort MeV alpha-particle sources employing compact femtosecond lasers. The ion acceleration and product measurement scheme are referential for the studies on the ion stopping power and cross section of the H-11B reaction in solid or plasma.

Objectives. Accumulating evidence indicates that the expression and/or variants of several genes play an essential role in the progress of colorectal cancer (CRC). The current study is a meta-analysis undertaken to estimate the prognosis and survival associated with CTNNB1/β-catenin, APC, Wnt, SMAD3/4, TP53, and Cyclin D1 genes among CRC patients. Methods. The authors searched PubMed, EMBASE, and Science Direct for relevant reports published between 2000 and 2020 and analyzed them to determine any relationship between the (immunohistochemically/sequencing-detected) gene expression and variants of the selected genes and the survival of CRC patients. Results. The analysis included 34,074 patients from 64 studies. To evaluate association, hazard ratios (HRs) were estimated for overall survival (OS) or disease-free survival (DFS), with a 95% confidence interval (CIs). Pooled results showed that β-catenin overexpression, APC mutation, SMAD-3 or 4 loss of expression, TP53 mutations, and Cyclin D1 expression were associated with shorter OS. β-Catenin overexpression (HR: 0.137 (95% CI: 0.131–0.406)), loss of expression of SMAD3 or 4 (HR: 0.449 (95% CI: 0.146–0.753)), the mutations of TP53 (HR: 0.179 (95% CI: 0.126–0.485)), and Cyclin D1 expression (HR: 0.485 (95% CI: 0.772–0.198)) also presented risk for shorter DFS. Conclusions. The present meta-analysis indicates that overexpression or underexpression and variants of CTNNB1/β-catenin, APC, SMAD3/4, TP53, and Cyclin D1 genes potentially acted as unfavorable biomarkers for the prognosis of CRC. The Wnt gene was not associated with prognosis.

Background. Fetal growth restriction (FGR) is the impairment of the biological growth potential of the fetus and often leads to adverse pregnancy outcomes. The molecular mechanisms for the development of FGR, however, are still unclear. The purpose of this study is to identify critical genes associated with FGR through an integrated bioinformatics approach and explore the potential pathogenesis of FGR. Methods. We downloaded FGR-related gene microarray data, used weighted gene co-expression network analysis (WGCNA), differentially expressed genes (DEGs), and protein-protein interaction (PPI) networks to screen hub genes. The GSE24129 gene set was used for validation of critical gene expression levels and diagnostic capabilities. Results. A weighted gene co-expression network was constructed, and 5000 genes were divided into 12 modules. Of these modules, the blue module showed the closest relationship with FGR. Taking the intersection of the DEGs and genes in the blue module as pivotal genes, 277 genes were identified, and 20 crucial genes were screened from the PPI network. The GSE24129 gene set verified the expression of 20 genes, and CXCL9, CXCR3, and ITGAX genes were identified as actual pivotal genes. The expression levels of CXCL9, CXCR3, and ITGAX were increased in both the training and validation sets, and ROC curve validation revealed that these three pivotal genes had a significant diagnostic ability for FGR. Single-gene GSEA results showed that all three core genes activated “hematopoietic cell lineage” and “cell adhesion molecules” and inhibited the “cGMP-PKG signaling pathway” in the development of FGR. CXCL9, CXCR3, and ITGAX may therefore be closely associated with the development of FGR and may serve as potential biomarkers for the diagnosis and treatment of FGR.

Background. Non-small cell lung cancer (NSCLC) is the most prevalent malignant tumor of the lung cancer, for which the molecular mechanisms remain unknown. In this study, we identified novel biomarkers associated with the pathogenesis of NSCLC aiming to provide new diagnostic and therapeutic approaches for NSCLC by bioinformatics analysis. Methods. From the Gene Expression Omnibus database, GSE118370 and GSE10072 microarray datasets were obtained. Identifying the differentially expressed genes (DEGs) between lung adenocarcinoma and normal samples was done. By using bioinformatics tools, a protein-protein interaction (PPI) network was constructed, modules were analyzed, and enrichment analyses were performed. The expression and prognostic values of 14 hub genes were validated by the GEPIA database, and the correlation between hub genes and survival in lung adenocarcinoma was assessed by UALCAN, cBioPortal, String and Cytoscape, and Timer tools. Results. We found three genes (PIK3R1, SPP1, and PECAM1) that have a clear correlation with OS in the lung adenocarcinoma patient. It has been found that lung adenocarcinoma exhibits high expression of SPP1 and that this has been associated with poor prognosis, while low expression of PECAM1 and PIK3R1 is associated with poor prognosis (P < 0.05). We also found that the expression of SPP1 was associated with miR-146a-5p, while the high expression of miR-146a-5p was related to good prognosis (P < 0.05). On the contrary, the lower miR-21-5p on upstream of PIK3R1 is associated with a higher surviving rate in cancer patients (P < 0.05). Finally, we found that the immune checkpoint genes CD274(PD-L1) and PDCD1LG2(PD-1) were also related to SPP1 in lung adenocarcinoma. Conclusions. The results indicated that SPP1 is a cancer promoter (oncogene), while PECAM1 and PIK3R1 are cancer suppressor genes. These genes take part in the regulation of biological activities in lung adenocarcinoma, which provides a basis for improving detection and immunotherapeutic targets for lung adenocarcinoma.

Schistosomiasis, a parasite infectious disease caused by Schistosoma japonicum, often leads to egg granuloma and fibrosis due to the inflammatory reaction triggered by egg antigens released in the host liver. This study focuses on the role of the egg antigens CP1412 protein of S. japonicum (SjCP1412) with RNase activity in promoting liver fibrosis. In this study, the recombinant egg ribonuclease SjCP1412, which had RNase activity, was successfully prepared. By analysing the serum of the population, it has been proven that the anti-SjCP1412 IgG in the serum of patients with advanced schistosomiasis was moderately correlated with liver fibrosis, and SjCP1412 may be an important antigen associated with liver fibrosis in schistosomiasis. In vitro, the rSjCP1412 protein induced the human liver cancer cell line Hep G2 and liver sinusoidal endothelial cells apoptosis and necrosis and the release of proinflammatory damage-associated molecular patterns (DAMPs). In mice infected with schistosomes, rSjCP1412 immunization or antibody neutralization of SjCP1412 activity significantly reduced cell apoptosis and necroptosis in liver tissue, thereby reducing inflammation and liver fibrosis. In summary, the SjCP1412 protein plays a crucial role in promoting liver fibrosis during schistosomiasis through mediating the liver cells apoptosis and necroptosis to release DAMPs inducing an inflammatory reaction. Blocking SjCP1412 activity could inhibit its proapoptotic and necrotic effects and alleviate hepatic fibrosis. These findings suggest that SjCP1412 may be served as a promising drug target for managing liver fibrosis in schistosomiasis japonica.

OBJECTIVES/GOALS: Current clinical practice recommends occlusive dressings (e.g., film and hydrocolloid) for wounds with variable regenerative capacities. However, clinical evidence suggests that occlusion may hinder regeneration. Our objective was to test the impact of occlusion on regeneration using animal models. METHODS/STUDY POPULATION: The murine wound-induced hair neogenesis (WIHN) is a well-established model of regeneration characterized by de novo hair follicle (HF) formation in the center of large full-thickness wounds. The quantity of neogenic HFs depends on the robustness of Wnt signaling. Optimal tissue mechanics is also required for WIHN. Utilizing the murine WIHN model, we tested the hypothesis that wound occlusion impedes regeneration. We determined how (i) the timing and duration of wound occlusion impacts WIHN, (ii) Wnt signaling influences the occlusion-induced effects on regeneration and (iii) occlusion alters the tissue mechanics of the wound, which establishes the morphogenetic field needed for WIHN. RESULTS/ANTICIPATED RESULTS: Occlusion completely eliminated WIHN. Only a brief period of occlusion between post-wound days 0-3 or 4-7 was sufficient to abrogate WIHN. Microarray and qPCR of open and occluded wounds demonstrated that occlusion promotes fibrosis by upregulating TGF-β2 and mechanotransduction, a mechanosensitive profibrotic pathway. Recruitment of these potent profibrotic pathways generated a symmetrically rigid wound incapable of de novo HF regeneration. Using transgenic animal models with enhanced Wnt signaling, we determined that the ligand-dependent Wnt signaling protected against the occlusion-induced inhibition of WIHN, as well as the occlusion-induced upregulation of both profibrotic pathways. DISCUSSION/SIGNIFICANCE: In animal models, occlusion promoted fibrosis at the expense of regeneration during acute wound healing. Augmented Wnt signaling protected against this effect. Occluding wounds may reduce regeneration. Further studies are warranted to validate these findings.

Objectives: Influenza vaccination is encouraged for all healthcare workers (HCWs) to reduce the risk of acquiring the infection and onward transmission to colleagues and patients during the influenza season. Thus, vaccination was introduced at Singapore General Hospital (SGH) in 2007 and has been offered to all HCWs at no cost. The HCW influenza vaccination program is conducted annually in October and biannually during years with vaccine mismatch. However, influenza vaccine uptake remained low among HCWs. We sought to determine the impact of the coronavirus disease 2019 (COVID-19) pandemic on influenza vaccine uptake among HCWs. Methods: At SGH, 2 methods of vaccine delivery are offered: centralized (1-month drop-in system during office hours) and decentralized (administered by vaccination teams in offices or ward staff in inpatient locations). In the 4-year study period between 2018 and 2021, 6 influenza vaccination exercise campaigns were conducted during 8 influenza seasons. During each exercise, ~9,000 HCWs were eligible for vaccination. Results: Prior to the COVID-19 pandemic, vaccine uptake in the Southern Hemisphere was 77.6% (6,964 of 8,977) in 2018 and 84.2% (7,296 of 8,670) in 2019. During the COVID-19 pandemic in 2020, vaccine uptake in the Southern Hemisphere increased by 10% to 94.1% (8,361 of 8,889). In the Northern Hemisphere, vaccine uptake was 79.2% (7,114 of 8,977) in 2018, and this increased by 17.9% to 97.1% (8,926 of 9,194) during the COVID-19 pandemic in 2020. During the 2021 Southern Hemisphere influenza season, no vaccination program was conducted because the risk of influenza was considered low due to the closure of international borders and the implementation of public health measures. In addition, priority was given to COVID-19 vaccination efforts. Conclusions: Increased uptake of the influenza vaccination was observed during the COVID-19 pandemic. Anxiety created by the respiratory disease pandemic and debate surrounding vaccines likely contributed to increased awareness and uptake in influenza vaccine among HCWs.

In recent years, the incidence of teratospermia has been increasing, and it has become a very important factor leading to male infertility. The research on the molecular mechanism of teratospermia is also progressing rapidly. This article briefly summarizes the clinical incidence of teratozoospermia, and makes a retrospective summary of related studies reported in recent years. Specifically discussing the relationship between gene status and spermatozoa, the review aims to provide the basis for the genetic diagnosis and gene therapy of teratozoospermia.

Studies of ‘food globalisation’ have traced the dispersal of cereals across prehistoric Eurasia. The degree to which these crops were accompanied by knowledge of soil and water preparation is less well known, however. The authors use stable isotope and archaeobotanical analyses to trace long-term trends in cultivation practices on the Loess Plateau (6000 BC–AD 1900). The results indicate that ancient farmers cultivated grains originating in South-west Asia and used distinct strategies for different species. Barley was integrated into pre-existing practices, while wheat was grown using novel soil and water management strategies. These distinct approaches suggest that the spread of prehistoric crops and knowledge about them varied by local context.