Local polynomial regression for pooled response data

We propose local polynomial estimators for the conditional mean of a continuous response when only pooled response data are collected under different pooling designs. Asymptotic properties of these estimators are investigated and compared. Extensive simulation studies are carried out to compare finite sample performance of the proposed estimators under various model settings and pooling strategies. We apply the proposed local polynomial regression methods to two real-life applications to illustrate practical implementation and performance of the estimators for the mean function

Augmented reality based real-time subcutaneous vein imaging system

A novel 3D reconstruction and fast imaging system for subcutaneous veins by augmented reality is presented. The study was performed to reduce the failure rate and time required in intravenous injection by providing augmented vein structures that back-project superimposed veins on the skin surface of the hand. Images of the subcutaneous vein are captured by two industrial cameras with extra reflective near-infrared lights. The veins are then segmented by a multiple-feature clustering method. Vein structures captured by the two cameras are matched and reconstructed based on the epipolar constraint and homographic property. The skin surface is reconstructed by active structured light with spatial encoding values and fusion displayed with the reconstructed vein. The vein and skin surface are both reconstructed in the 3D space. Results show that the structures can be precisely back-projected to the back of the hand for further augmented display and visualization. The overall system performance is evaluated in terms of vein segmentation, accuracy of vein matching, feature points distance error, duration times, accuracy of skin reconstruction, and augmented display. All experiments are validated with sets of real vein data. The imaging and augmented system produces good imaging and augmented reality results with high speed

Complete mitochondrial genome of Penicillidia jenynsii (Diptera: Hippoboscoidea: Nycteribiidae) and phylogenetic relationship

In recent years, bat-associated pathogens, such as 2019 novel coronavirus, have been ravaging the world, and ectoparasites of bats have received increasing attention. Penicillidia jenynsii is a member of the family Nycteribiidae which is a group of specialized ectoparasites of bats. In this study, the complete mitochondrial genome of P. jenynsii was sequenced for the first time and a comprehensive phylogenetic analysis of the superfamily Hippoboscoidea was conducted. The complete mitochondrial genome of P. jenynsii is 16 165 base pairs (bp) in size, including 13 protein-coding genes (PCGs), 22 transfer RNA genes, 2 ribosomal RNA genes and 1 control region. The phylogenetic analysis based on 13 PCGs of the superfamily Hippoboscoidea known from the NCBI supported the monophyly of the family Nycteribiidae, and the family Nycteribiidae was a sister group with the family Streblidae. This study not only provided molecular data for the identification of P. jenynsii, but also provided a reference for the phylogenetic analysis of the superfamily Hippoboscoidea

Metal-Organic-Framework-based nanofiltration membranes for selective multi-cationic recovery from seawater and brines

Nanofiltration (NF) is gaining a role of increasing importance in Zero Liquid Discharge (ZLD)/Minimal Liquid Discharge (MLD) systems, enhancing the efficiency of downstream technologies to recover valuable minerals from seawater and brines. However, often the purity of the recovered minerals does not meet market specifications, making ZLD/MLD currently economically unfeasible. To such end, in this study, a novel positively charged NF membrane was developed to enhance magnesium and calcium selectivity. The membrane comprised: (i) an ultrafiltration substrate and (ii) an active layer that incorporated NH2-MIL-101(Al) and ZnO nanoparticles in a chitosan matrix. The influence of different loadings of NH2-MIL-101(Al) and ZnO on membrane structure, selectivity and water permeability was investigated. Initial filtration tests with single-salt solutions at 1000 ppm (NaCl, Na2SO4, MgCl2, CaCl2) showed that the membrane with 35%wt of ZnO presented the highest rejections of MgCl2 (90.10%) and CaCl2 (86.49%). Selectivity towards MgCl2 and CaCl2 was higher than those of commercial membranes (NF90 and NF270) and the positively charged membranes introduced in recent literature. The novel synthesized membrane in this work was also tested with synthetic seawater and brine at a trans-membrane pressure of 30 bar. Results highlighted the intriguing competitiveness of the novel membrane in terms of magnesium and calcium selectivity with NF90 and NF270 within the field of both seawater and brine valorization.The authors would like to acknowledge that parts of the research activities were carried out within the framework of "Programma Operativo Nazionale Ricerca e Innovazione2014-2020 (CCI 2014IT16M2OP005), Fondo Sociale Europeo, Azione I.1 “Dottorati Innovativi con caratterizzazione Industriale”, Code: DOT204NJ79, CUP: B73D20005110001. J. López research was developed under the Margarita Salas postdoctoral fellowship from Ministerio de Universidades (MIU) and founded by the European Union-NextGenerationEU. Moreover, J.L. Cortina received support for the research through the “ICREA Academia” recognition for excellence in research funded by the Generalitat de Catalunya.Peer ReviewedPostprint (published version

MiR-543 Promotes Migration, Invasion and Epithelial-Mesenchymal Transition of Esophageal Cancer Cells by Targeting Phospholipase A2 Group IVA

Background/Aims: The aim of this study was to investigate the roles of miR-543 and phospholipase A2 group IVA (PLA2G4A) in cell mobility and the invasiveness cascade in esophageal squamous cell carcinoma (ESCC) and to validate the interactive relationship between miR-543 and PLA2G4A. Methods: Microarray analysis showed the different expression levels of PLA2G4A in two ESCC cell lines (KYSE30 and KYSE180). The expression levels of miR-543 and PLA2G4A in ESCC tissues were confirmed by qRT-PCR and Western blotting. The targeted relationship between miR-543 and PLA2G4A was studied and verified by a luciferase activity assay. Then, the invasion and metastasis ability of ESCC cell lines transfected with miR-543 mimics, miR-543 inhibitor, or PLA2G4A and miR-543 mimics were analyzed separately by Transwell migration and invasion assays. In addition, the roles of miR-543 and PLA2G4A in the expression of E-cadherin and vimentin were also investigated. Results: PLA2G4A up-regulated the level of E-cadherin and down-regulated the level of vimentin, which curbed ESCC cell mobility and invasion. In ESCC cells, the expression of miR-543 was significantly higher, whereas the expression of PLA2G4A was markedly lower. MiR-543 facilitated ESCC cell mobility and invasion by repressing PLA2G4A. Conclusions: MiR-543 enhanced the cell mobility and the invasiveness cascade in ESCC cells via the down-regulation of PLA2G4A expression

New fusion transcripts identified in normal karyotype acute myeloid leukemia

Genetic aberrations contribute to acute myeloid leukemia (AML). However, half of AML cases do not contain the well-known aberrations detectable mostly by cytogenetic analysis, and these cases are classified as normal karyotype AML. Different outcomes of normal karyotype AML suggest that this subgroup of AML could be genetically heterogeneous. But lack of genetic markers makes it difficult to further study this subgroup of AML. Using paired-end RNAseq method, we performed a transcriptome analysis in 45 AML cases including 29 normal karyotype AML, 8 abnormal karyotype AML and 8 AML without karyotype informaiton. Our study identified 134 fusion transcripts, all of which were formed between the partner genes adjacent in the same chromosome and distributed at different frequencies in the AML cases. Seven fusions are exclusively present in normal karyotype AML, and the rest fusions are shared between the normal karyotype AML and abnormal karyotype AML. CIITA, a master regulator of MHC class II gene expression and truncated in B-cell lymphoma and Hodgkin disease, is found to fuse with DEXI in 48% of normal karyotype AML cases. The fusion transcripts formed between adjacent genes highlight the possibility that certain such fusions could be involved in oncological process in AML, and provide a new source to identify genetic markers for normal karyotype AML

Causal link between gut microbiota and four types of pancreatitis: a genetic association and bidirectional Mendelian randomization study

BackgroundA number of recent observational studies have indicated a correlation between the constitution of gut microbiota and the incidence of pancreatitis. Notwithstanding, observational studies are unreliable for inferring causality because of their susceptibility to confounding, bias, and reverse causality, the causal relationship between specific gut microbiota and pancreatitis is still unclear. Therefore, our study aimed to investigate the causal relationship between gut microbiota and four types of pancreatitis.MethodsAn investigative undertaking encompassing a genome-wide association study (GWAS) comprising 18,340 participants was undertaken with the aim of discerning genetic instrumental variables that exhibit associations with gut microbiota, The aggregated statistical data pertaining to acute pancreatitis (AP), alcohol-induced AP (AAP), chronic pancreatitis (CP), and alcohol-induced CP (ACP) were acquired from the FinnGen Consortium. The two-sample bidirectional Mendelian randomization (MR) approach was utilized. Utilizing the Inverse-Variance Weighted (IVW) technique as the cornerstone of our primary analysis. The Bonferroni analysis was used to correct for multiple testing, In addition, a number of sensitivity analysis methodologies, comprising the MR-Egger intercept test, the Cochran’s Q test, MR polymorphism residual and outlier (MR-PRESSO) test, and the leave-one-out test, were performed to evaluate the robustness of our findings.ResultsA total of 28 intestinal microflora were ascertained to exhibit significant associations with diverse outcomes of pancreatitis. Among them, Class Melainabacteria (OR = 1.801, 95% CI: 1.288–2.519, p = 0.008) has a strong causality with ACP after the Bonferroni-corrected test, in order to assess potential reverse causation effects, we used four types of pancreatitis as the exposure variable and scrutinized its impact on gut microbiota as the outcome variable, this analysis revealed associations between pancreatitis and 30 distinct types of gut microflora. The implementation of Cochran’s Q test revealed a lack of substantial heterogeneity among the various single nucleotide polymorphisms (SNP).ConclusionOur first systematic Mendelian randomization analysis provides evidence that multiple gut microbiota taxa may be causally associated with four types of pancreatitis disease. This discovery may contribute significant biomarkers conducive to the preliminary, non-invasive identification of Pancreatitis. Additionally, it could present viable targets for potential therapeutic interventions in the disease’s treatment

Use of Praziquantel as an Adjuvant Enhances Protection and Tc-17 Responses to Killed H5N1 Virus Vaccine in Mice

BACKGROUND: H5N1 is a highly pathogenic influenza A virus, which can cause severe illness or even death in humans. Although the widely used killed vaccines are able to provide some protection against infection via neutralizing antibodies, cytotoxic T-lymphocyte responses that are thought to eradicate viral infections are lacking. METHODOLOGY/PRINCIPAL FINDINGS: Aiming to promote cytotoxic responses against H5N1 infection, we extended our previous finding that praziquantel (PZQ) can act as an adjuvant to induce IL-17-producing CD8(+) T cells (Tc17). We found that a single immunization of 57BL/6 mice with killed viral vaccine plus PZQ induced antigen-specific Tc17 cells, some of which also secreted IFN-γ. The induced Tc17 had cytolytic activities. Induction of these cells was impaired in CD8 knockout (KO) or IFN-γ KO mice, and was even lower in IL-17 KO mice. Importantly, the inoculation of killed vaccine with PZQ significantly reduced virus loads in the lung tissues and prolonged survival. Protection against H5N1 virus infection was obtained by adoptively transferring PZQ-primed wild type CD8(+) T cells and this was more effective than transfer of activated IFN-γ KO or IL-17 KO CD8(+) T cells. CONCLUSIONS/SIGNIFICANCE: Our results demonstrated that adding PZQ to killed H5N1 vaccine could promote broad Tc17-mediated cytotoxic T lymphocyte activity, resulting in improved control of highly pathogenic avian influenza virus infection

Praziquantel Facilitates IFN-γ-Producing CD8+ T Cells (Tc1) and IL-17-Producing CD8+ T Cells (Tc17) Responses to DNA Vaccination in Mice

BACKGROUND: CD8(+) cytotoxic T lymphocytes (CTLs) are crucial for eliminating hepatitis B virus (HBV) infected cells. DNA vaccination, a novel therapeutic strategy for chronic virus infection, has been shown to induce CTL responses. However, accumulated data have shown that CTLs could not be effectively induced by HBV DNA vaccination. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that praziquantel (PZQ), an anti-schistoma drug, could act as an adjuvant to overcome the lack of potent CTL responses by HBV DNA vaccination in mice. PZQ in combination with HBV DNA vaccination augmented the induction of CD8(+) T cell-dependent and HBV-specific delayed hypersensitivity responses (DTH) in C57BL/6 mice. Furthermore, the induced CD8(+) T cells consisted of both Tc1 and Tc17 subtypes. By using IFN-γ knockout (KO) mice and IL-17 KO mice, both cytokines were found to be involved in the DTH. The relevance of these findings to HBV immunization was established in HBsAg transgenic mice, in which PZQ also augmented the induction of HBV-specific Tc1 and Tc17 cells and resulted in reduction of HBsAg positive hepatocytes. Adoptive transfer experiments further showed that PZQ-primed CD8(+) T cells from wild type mice, but not the counterpart from IFN-γ KO or IL-17 KO mice, resulted in elimination of HBsAg positive hepatocytes. CONCLUSIONS/SIGNIFICANCE: Our results suggest that PZQ is an effective adjuvant to facilitate Tc1 and Tc17 responses to HBV DNA vaccination, inducing broad CD8(+) T cell-based immunotherapy that breaks tolerance to HBsAg