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关键词： Glycemic variability   Insulin therapy   Sympathovagal effects  

摘要： Aims/Introduction This study compares the effects of two different insulin regimens - basal versus bolus insulin - on metabolic and cardiovascular autonomic function in Japanese participants with type 2 diabetes. Materials and Methods Participants were randomly assigned to groups for therapy with insulin glulisine (IGlu) or insulin glargine (IGla). The primary efficacy end-point was glycemic variability, including M-values, mean of glucose levels, and a blood glucose profile of seven time points before and after the intervention. The secondary end-points included pleiotropic effects, including endothelial and cardiac autonomic nerve functions. Results Blood glucose levels at all time points significantly decreased in both groups. Post-lunch, post-dinner, and bedtime blood glucose levels were significantly lower in the IGlu group than in the IGla group. Nadir fasting blood glucose levels at the end-point were significantly lower in the IGla group than in the IGlu group. The M-value and mean blood glucose levels were significantly decreased from baseline in both groups, although the former was significantly lower in the IGlu group than in the IGla group. IGla, but not IGlu, was found to elevate 24-h parasympathetic tone, especially during night-time, and it decreased 24-h sympathetic nerve activity, especially at dawn. Conclusions Both IGlu and IGla regimens reduced glucose variability, with IGlu bringing a greater reduction in M-value. IGla, but not IGlu, increased parasympathetic tone during night-time and decreased sympathetic nerve activity at dawn. These findings shed light on the previously unrecognized role of night-time basal insulin supplementation on sympathovagal activity in type 2 diabetes patients.

关键词： Porous media   VARANS equations   Perforated caisson   Rubble-mound foundation  

摘要： Rubble-mound foundation can be regarded as a form of porous structure that is widely used in engineering practice. Porous medium flow must be considered when simulating wave interactions with perforated caisson sitting on a rubble-mound foundation. In this paper, volume-averaged/Reynolds averaged Navier-Stokes (VARANS) equations are adopted to describe the flow inside and outside the porous structure. Moreover, they are combined with the volume averaged k - epsilon model to simulate the turbulence effect. In addition, the three-step finite element method is applied to solve VARANS equations numerically, and the CLEAR-VOF method is applied to capture the free fluid surface. The resistance-type porosity numerical model is proposed and verified by several test cases and then used to simulate wave interactions with perforated caisson sitting on a rubble-mound foundation. The porosity model gives reliable results compared to the experiments with respect to the wave height, the pressure distribution, and the total vertical wave force. The model can be adopted to study the wave interaction with perforated caisson sitting on a rubble-mound foundation and used for the design of such caisson in engineering practice.

关键词： head and neck squamous cell carcinoma   T-cell inflammation   immunotherapy   CT   texture analysis  

摘要： Purpose Immunotherapy has emerged as a treatment option for head and neck squamous cell carcinoma (HNSCC), with tumor response being linked to the CD8+ T-cell inflammation. The purpose of this study is to assess whether computed tomography (CT) radiomic analysis can predict CD8+ T-cell enrichment in HNSCC primary tumors. Methods This retrospective study included 71 patients from a head and neck cancer genomics cohort with CD8+ T-cell enrichment status. Pretreatment contrast-enhanced neck CT scans were retrospectively reviewed using 3D Slicer for primary lesion segmentation. The SlicerRadiomics extension was used to extract 107 radiomic features. Ridge regression and lasso regression were applied for feature selection and model construction. Results Lasso regression defined Coarseness as the most important variable, followed by SmallDependenceEmphasis, SmallAreaLowGrayLevelEmphasis, Contrast.1, and Correlation. Ridge regression defined Coarseness as the most important variable, followed by SmallDependenceLowGrayLevelEmphasis, Contrast.1, DependenceNonUniformityNormalized, and Idmn. These variables identified by lasso and ridge regressions were used to create a combined logistic regression model. The area under the curve (AUC) for the lasso-generated model was 0.786 (95% confidence interval [CI], 0.532-1.000), and the AUC for the ridge-generated model was 0.786 (95% CI, 0.544-1.000). Combining the radiomic variables identified by lasso and ridge regressions with clinical characteristics including alcohol use, tobacco use, anatomic site, and initial T stage produced a model with an AUC of 0.898 (95% CI, 0.731-1.000). Conclusions T-cell inflammation status of HNSCC primary tumors can be predicted using radiomic analysis of CT imaging and thereby help identify patients who would respond well to immunotherapy.

关键词： amacrine cell   ARL13B   eye   Muller glia   Pax6   primary ciliary retina   VGLUT3  

摘要： PURPOSE. Primary cilia are conserved organelles found in polarized cells within the eye that regulate cell growth, migration, and differentiation. Although the role of cilia in photoreceptors is well-studied, the formation of cilia in other retinal cell types has received little attention. In this study, we examined the ciliary profile focused on the inner nuclear layer of retinas in mice and rhesus macaque primates. METHODS. Retinal sections or flatmounts from Arl13b-Cetn2 tg transgenic mice were immunostained for cell markers (Pax6, Sox9, Chx10, Calbindin, Calretinin, ChaT, GAD67, Prox1, TH, and vGluT3) and analyzed by confocal microscopy. Primate retinal sections were immunostained for ciliary and cell markers (Pax6 and Ar113b). Optical coherence tomography (OCT) and ERGs were used to assess visual function of Vift88 mice. RESULTS. During different stages of mouse postnatal eye development, we found that cilia are present in Pax6-positive amacrine cells, which were also observed in primate retinas. The cilia of subtypes of amacrine cells in mice were shown by immunostaining and electron microscopy. We also removed primary cilia from vGluT3 amacrine cells in mouse and found no significant vision defects. In addition, cilia were present in the outer limiting membrane, suggesting that a population of Muller glial cells forms cilia. CONCLUSIONS. We report that several subpopulations of amacrine cells in inner nuclear layers of the retina form cilia during early retinal development in mice and primates.

关键词： alloimmunization   female   hemolytic disease of the fetus and newborn   low titer group O whole blood   pregnancy   red blood cell   RhD   transfusion  

摘要： Introduction: Early transfusion reduces mortality in bleeding patients. In this setting, RhD-positive blood products might be transfused. This study determined the association between the RhD-alloimmunization rate and the number of RhD-positive products transfused. Methods: RhD-negative patients between 13 and 50 years who were transfused with >= 1 RhD-positive red blood cell (RBC) or whole blood units between January 1, 2000 and December 31, 2019 in a healthcare network were identified. Study patients had to have had at least one antibody detection test performed >= 14 days after the index RhD-positive transfusion and not receive RhIg. Patients were stratified into groups that received 1, 2, 3-5, 6-10, 11-20, and >20 RhD-positive transfusions and the RhD-alloimmunization rate was determined for each group. Results: There were 335 patients included;52/335 (15.5%) were females. Overall, there were 117/335 (34.9%, CI: 29.8%-40.3%) recipients who became RhD-alloimmunized. There was no significant dosage effect in the RhD-alloimmunization rates as the exposure to RhD-positive units increased from one RhD-positive unit to more than 20 RhD-positive units (p = .270 for nonparametric trend test). In an exploratory analysis, patients who received 100% of their RhD-positive transfusions within 72 h of the index transfusion had a significantly higher rate of RhD-alloimmunization compared to those who were transfused over a longer period of time (42.3% vs. 21.4%, respectively;p = .001). Conclusion: These results suggest that there may not be an increased RhD-alloimmunization risk with transfusing multiple RhD-positive units after one RhD-positive unit has been transfused. These findings need confirmation in larger studies.

关键词： B cell development   RAG1   Immunoglobulin   Microplastics   Rainbow trout   Phagocytosis  

摘要： Environmental microplastic pollution (including polystyrene, PS) may have detrimental effects on the health of aquatic organisms. Accumulation of PS microplastics has been reported to affect innate immune cells and inflammatory responses in fish. To date, knowledge on effects of microplastics on the antibody response is still very limited. Here, we investigated effects of small (0.8-20 mu m) PS microplastics on the abundance of B lineage cells in primary cultures of developing immune cells from the anterior kidney of rainbow trout. Both purchased PS microbeads and PS microparticles generated from consumer products were used as microplastic sources. We first show that rainbow trout phagocytic B cells efficiently took up small (0.83-3.1 mu m) PS microbeads within hours of exposure. In addition, our data revealed that PS microplastic exposure most significantly decreased the abundance of a population of non-phagocytic developing B cells, using both flow cytometry and RT-qPCR. PS microplastics-induced loss of developing B cells further correlated with reduced gene expression of RAG1 and the membrane form of immunoglobulin heavy chains mu and tau. Based on the induced loss of developing B cells observed in our in vitro studies, we speculate that in vivo, chronic PS microplastic-exposure may lead to suboptimal IgM/IgT levels in response to pathogens in teleost species. Considering the highly conserved nature of vertebrate B lymphopoiesis it is likely that PS microplastics will similarly reduce antibody responses in higher vertebrate species, including humans. Further, RAG1 provides an effective biomarker to determine effects of PS microplastics on B cell development in teleost species.

关键词： colorectal cancer   stage III   adjuvant chemotherapy   circulating tumor cells   microbial DNA   three vs   six months adjuvant treatment  

摘要： Simple Summary Duration of adjuvant therapy in stage III CRC is now under re-evaluation. The aim of the current study was the detection of microbial DNA that could be originated from the intestine (16S rRNA, E. coli, B. fragilis and C. albicans) and the detection of CTCs during treatment with FOLFOX or CAPOX, in stage III CRC patients. CTCs were significantly decreased after 3 months of treatment, whereas 6 months resulted to their increase again. A significant increase of CTCs was demonstrated in patients under FOLFOX for 6 months. A significant correlation was demonstrated following microbial DNAs and both CTCs detection at baseline and CTCs increase, between baseline and 3 months of treatment. The results provide additional evidence of non-inferiority of 3 over 6 months of treatment, mainly in patients under CAPOX. Oxaliplatin-fluoropyrimidine combination therapy is the gold standard treatment for patients with stage III colorectal cancer (CRC);however, treatment duration is now under re-evaluation. The aim of the study was the evaluation of the non-inferiority of three over six months treatment with FOLFOX or CAPOX, in stage III CRC patients. Peripheral blood samples from 121 patients were collected, at three time points during treatment and evaluated for circulating tumor cells (CTCs) and microbial DNA detection (16S rRNA, Escherichia coli, Bacteroides fragilis, Candida albicans). Of all patients, 41.3% and 58.7% were treated with FOLFOX and CAPOX, respectively. CTCs were significantly decreased and increased after three and six months of treatment, respectively. CAPOX tends to reduce the CTCs after 3 months, whereas there is a statistically significant increase of CTCs in patients under FOLFOX after 6 months. A significant correlation was demonstrated between microbial DNA detection and both CTCs detection at baseline and CTCs increase between baseline and three months of treatment. To conclude, the current study provides additional evidence of non-inferiority

关键词： Hepatocellular carcinoma (HCC)   Mesenchymal circulating tumor cell (mCTC)   Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE)   Recurrence-free survival (RFS)   Overall survival (OS)  

摘要： Background We demonstrated that postoperative mesenchymal circulating tumor cell (mCTC) in peripheral blood were independent risk factors for the recurrence of hepatocellular carcinoma (HCC) after radical resection. However, few studies have been conducted on the efficacy and survival benefit of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) for patients with mCTC-positive HCC. We evaluated the effect of PA-TACE on the prognosis of mCTC-positive/mCTC-negative HCC patients. Methods A total of 261 HCC patients from February 2014 to December 2017 undergoing curative hepatectomy were included in this study. Recurrence-free survival (RFS) rates, overall survival (OS) rates, and prognostic factors were analyzed using the Kaplan-Meier method, log-rank test, and Cox proportional hazard model. Results The results showed that 57.8% (59/102) mCTC-positive and 43.4% (69/159) mCTC-negative patients underwent PA-TACE. Multivariate analyses demonstrated that PVTT (HR 2.370;95% CI, 1.535-3.660;P < 0.001), BCLC stage (B+C) (HR 3.871;95% CI, 2.544-5.892;P < 0.001), mCTC (HR 1.414;95% CI, 1.276-1.622;P < 0.001), and without PA-TACE (HR 1.724;95% CI, 1.152-2.580;P = 0.008) were independent risk factors for poor RFS. Meanwhile, PVTT (HR 1.744;95% CI, 1.261-2.412;P = 0.001), multinodularity (HR 1.416;95% CI, 1.069-1.876;P = 0.015), mCTC (HR 1.612;95% CI, 1.471-1.796;P < 0.001), and without PA-TACE (HR 1.311;95% CI, 1.010-1.701;P = 0.042) were independent risk factors for poor OS. Both RFS (P = 0.004) and OS (P = 0.045) in mCTC-positive patients who received PA-TACE were significantly improved relative to those who underwent hepatic resection alone. Among 102 mCTC-positive patients, the mCTC-positive rate was significantly lower in patients treated with PA-TACE than in those treated with liver resection alone (46.4% vs. 88.4%,P = 0.031). No differences were observed in DFS and OS among the mCTC-negative patients with or without PA-TACE. Early recurrence was more

关键词： Nelarabine   T cell acute lymphoblastic leukemia   Refractory disease   Allogeneic stem cell transplantation  

摘要： A significant proportion of T cell acute lymphoblastic leukemia (T-ALL) patients do not achieve complete remission after 4 weeks of induction chemotherapy or relapse early. Salvage chemotherapy for such patients usually results in poor outcome which can be up to 20-30% survival with allogeneic BMT. Nelarabine combined with chemotherapy, in COG AALL0434 study, showed 4-year disease-free survival of 54.8% in patients with primary refractory T ALL. An allogeneic BMT in such patients may further improve outcome. In this report, three patients with primary refractory T cell ALL including a case of ETP-ALL and near ETP-ALL were treated with Nelarabine combined with COG based regime and thereafter an allogeneic stem cell transplantation. All three patients achieved a complete remission with negative minimal residual disease status with one course of therapy, received allo SCT (MSD = 2, Haplo = 1) and are surviving in complete remission at 12 months, 14 months and 25 months of follow up. This report highlights that primary refractory T ALL patient can be successfully treated with Nelarabine in combination with chemotherapy and consolidation with allogeneic SCT to provide maximum chances of long-term survival and cure.

关键词： Capripoxviruses   Cell culture   Cell sensitivity   ESH-L cells   Primary cells   Immunoenzymatic staining and   immunofluorescence  

摘要： Lumpy skin disease virus (LSDV), sheeppox virus (SPPV) and goatpox (GTPV) virus have been usually grown on primary cells for diagnosis, production and titration purposes. The use of primary cells present several inconvenient, heavy preparation, heterogeneous cell population, non-reproducible viral titration and presence of potential endogenous contaminants. Therefore investigating sensitivity of candidate continuous cell lines is needed. In this study, we compared the above Capripox viruses (CaPVs) sensitivity of primary cells of four origin (heart, skin, testis and kidney), with three cell lines (Vero, *** and ESH-L). We tested sensitivity for virus isolation, replication cycle and titration, revealed by cytopathic effect (CPE), immunoenzymatic staining and immunofluorescence. Our results show that ESH-L cells and primary fetal heart cells present the highest sensitivity for CaPVs growth and detection. Vero cells can replicate those viruses but without showing any CPE while the titer obtained on *** is lower than primary and ESH-L cells. ESH-L cells are an effective alternative to primary cells use for growing Capripoxviruses and their diagnosis.