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关键词： Persistence   GLP-1 Receptor Agonist   Basal Insulin   Type 2 Diabetes   Loose Combination  

摘要： Aims: The purpose of this study is to assess the persistence of Canadians with Type 2 diabetes mellitus (T2D) on loose-dose combination treatment (i.e., administered by separate devices) with a glucagon-like peptide 1 receptor agonist (GLP-1 RA) and basal insulin over 12 months. Methods: This study is a retrospective cohort study of T2D adults using a Canadian longitudinal prescription database over a 5-year period. Cohort 1 (n = 12,411) is a primary cohort including only individuals inexperienced with the combination therapy at index. Cohort 2 (n =13,498) is an exploratory cohort and includes everyone regardless of previous experience on the loose-dose combination therapy. The primary endpoint is the proportion of individuals persistent and average days persistent to the loose-dose combination therapy at 12 months in Canada. Results: In Cohort 1, overall persistence was 47% in the 12-month period post-index. Persistence is similar when including all inexperienced and subsequent loose-dose combination experiences in Cohort 2 (45%). Conclusions: Canadian T2D adults taking a loose-dose combination therapy of a GLP-1 RA and basal insulin had overall low persistence and lower than reports from previous studies of GLP-1 RA or basal insulin alone. Improving persistence to combination therapy with GLP-1 RA plus basal insulin is an important issue to explore in clinical practice. (c) 2021 Elsevier B.V. All rights reserved.

关键词： Alien invasive species   Cryptic invasion   Distribution   Eragrostis albensis var   scholziana   Integrative taxonomy   Lovegrasses  

摘要： The Eragrostis pilosa complex (Poaceae) comprises five widely distributed and regionally invasive species-E. albensis, E. amurensis, E. imberbis, E. multicaulis, and E. pilosa, distinguished by tiny and variable morphological characters and with so far unknown phylogenetic relationships. Recently, some doubts have been raised about the status of an invasive glandular morphotype occurring in Central Europe assigned either to E. amurensis or to E. albensis. Here, we addressed this issue by analysing morphology, internal transcribed spacers of nuclear ribosomal DNA, and five inter-simple sequence repeat markers. The genetic evidence supported closer relationship of this glandular morphotype to eglandular E. albensis, widely established in Central Europe, than to glandular E. amurensis described from Asia. We propose to adopt a new taxonomic treatment that E. albensis includes both eglandular and glandular individuals, and to classify the glandular ones as E. albensis var. scholziana M. Nobis & A. Wrobel var. nova. Currently this new taxon is known from a dozen of localities in Central Europe and is invasive in the lower section of the Oder River valley, whereas Eragrostis albensis var. albensis has already spread widely across Europe in riparian phytocenoses and anthropogenic habitats. Since probably the first registered records in 1940s, it has been observed in European part of Russia, Belarus, Ukraine, Poland, Slovakia, Czech Republic, Germany, Austria, the Netherlands, and its further invasion is likely to proceed. We provided distribution maps concerning spread dynamics of E. albensis in Europe from 1947 to 2020. In total, the species has been observed on over 1300 localities so far, most of which were found after 2000.

关键词： HBV   Primary human hepatocytes   HBV replication   Hepatic stellate cells  

摘要： Primary human hepatocytes (PHHs) are considered the gold standard for the in vitro study of HBV replication as they directly reflect the metabolism and functionality of the human liver. However, several limitations of this system include PHH donor-to-donor variability, limited life span and low permissiveness to HBV infection, which precludes long-term infection studies and viral passaging. Here, an easy-to-set-up co-culture platform that combines PHH with hepatic stellate cells (HSCs) was developed. This platform does not rely on chemical supplementation to sustain robust HBV replication and viral antigen secretion making it a more physiologically relevant system for in vitro HBV infection studies compared to the traditional short-lived PHH monocultures.

关键词： Primary cutaneous acral CD8(+) T-cell lymphoma   Gold sodium thiosulfate   Lymphomatoid contact allergic dermatitis  

摘要： Primary cutaneous CD8(+) T-cell lymphoma has been included as a provisional entity within the new revised classification of lymphoid neoplasms of the World Health Organization in 2016(1). It was initially described as indolent CD8(+). lymphoid proliferation of the ear(2) and a total of 29 cases of such neoplasm have been published in the literature so far. None of them have been linked to delayed contact hypersensitivity reactions. We present a case of acral type primary cutaneous lymphoma T CD8(+). involving both earlobes clearly related with the prolonged use of gold earrings, confirmed with epicutaneous tests, histopathology, immunohistochemical and molecular studies. Auricular skin lesions were induced again with a provocation test with identical histopathologycal and the same clonality, confirming both the diagnosis of lymphoma and its induction by the antigenic stimulus of gold. (C) 2021 AEDV. Published by Elsevier Espana, S.L.U.

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.

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.

摘要： Background Goblet cell carcinoids (GCC) are an aggressive, albeit rare, subtype of appendiceal tumors that exhibit distinct histologic features and lack clear treatment guidelines. We aimed to ascertain the impact of adjuvant chemotherapy (AC) for GCC in a national cohort of patients. Methods Patients who underwent a right hemicolectomy for stage I-III GCC of the appendix between 2006 and 2016 were selected from the National Cancer Database (NCDB). Stratification based on AC receipt was performed. Kaplan-Meier survival estimates and Cox proportional hazard regression were used to identify predictors of overall survival (OS). Results A total of 867 patients were identified, of whom 124 (14%) received AC. Patients in the AC group were significantly younger (54 vs. 57 years;p = 0.006) and were predominantly of male sex (60 vs. 48%;p = 0.012). On histopathology, patients in the AC group had a higher proportion of poorly/undifferentiated grade (27 vs. 5%;p < 0.001), T4 disease (35 vs. 11%;p < 0.001), and lymph node-positive disease (45 vs. 7%;p < 0.001) than patients who did not receive AC. After excluding patients diagnosed in 2016 due to a lack of follow-up data (n = 162), a survival advantage for the AC group was detected only after stratification for lymph node-positive disease (p = 0.007). On Cox proportional hazard regression, AC demonstrated an independent association with improved OS (hazard ratio 0.24, 95% confidence interval 0.084-0.683;p = 0.007). Conclusion The current analysis from the NCDB supports the role of AC for GCC of the appendix, chiefly for patients with lymph node metastatic disease.

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： miR-101   Cyclooxygenase-2 (COX-2)   Endoplasmic reticulum (ER) stress   Cardiovascular dysfunction   Human umbilical vein endothelial cells    (HUVECs)  

摘要： Exposure to toxic metal contaminants, such as cadmium compounds (Cd2+), has been shown to induce adverse effects on various organs and tissues. In particular, blood vessels are severely impacted by Cd2+ exposure, which may lead to cardiovascular diseases (CVDs). According to previous studies, CVDs are associated with increased cyclooxygenase 2 (COX-2) levels. However, the mechanisms by which CdCl2-induced COX-2 overexpression leads to cardiovascular dysfunction remain unclear. Herein, we show that the relative gene expressions of VEGF and PTGS2 (COX-2 encoding gene) are positively correlated in CVDs patients. Moreover, we demonstrate that the in vitro administration of CdCl2 induces cytotoxicity and endoplasmic reticulum (ER) stress in primary human umbilical vein endothelial cells (HUVECs). The induction of ER stress and the overexpression of COX-2 in CdCl2treated cells alters the protein level of vascular endothelial growth factor (VEGF), resulting in abnormal angiogenesis and increased cytotoxicity. At the pre-transcription level, the inhibition of ER stress by siGRP78 (a key mediator of ER stress) can restore normal angiogenesis in the CdCl2-exposed cells. Meanwhile, at the transcription level, the adverse effects of CdCl2 exposure may be reversed via genetic modification with siRNA (siPTGS2) or by using phytochemical inhibitors (parthenolide, PN) of COX-2. Finally, at the post-transcription level, COX-2 expression may be restricted by the binding of microRNA-101 (miR-101) to the 3 '-UTR of PTGS2 mRNA. The use of mimic miR-101 (mi101) to induce the expression of miR-101 eventually leads to reduced COX2 protein levels, relieved ER stress, and less abnormal angiogenesis and cytotoxicity of CdCl2-exposed primary HUVECs. Overall, our results suggest that CdCl2-induced abnormal angiogenesis is mediated by miR-101/COX-2/ VEGF-axis-dependent ER stress, and that cardiovascular dysfunction may be controlled by manipulating COX-2 at the pre-transcription, transcription, a

关键词： Mediastinal lymphoma   Chemo-immunotherapy   Mediastinal radiotherapy   Dose adjusted R-EPOCH   Survival outcomes  

摘要： Introduction Primary Mediastinal B cell lymphoma (PMBCL) is a biologically and clinically distinct subset of diffuse large B cell lymphoma. We analysed the outcomes of our cohort of PMBCL patients treated with Dose adjusted (DA)-R-EPOCH regimen. Patients and Methods This is a retrospective analysis of consecutive PMBCL patients who received chemotherapy consisting of DA-R-EPOCH with filgrastim support. Survival analysis was done using Kaplan-Meier method. All calculations were performed using SPSS version 20 for windows. Results A total of 43 consecutive suspected PMBCL patients were reviewed for this study, 6 patients were excluded as diagnosis of PMBCL could not be established. All patients except one (97.3%) received 6 cycles of R-DA-EPOCH regimen. Median age of the patients was 27 years (range 15-58). Bulky disease (> 7 cm) was present in 97% patients and 54% patients had extranodal disease. With a median follow up of 40 months, 3-year overall survival was 80.6% (95% CI: 74.0-87.2). The 3-year event free survival was 78.4% (95% CI: 71.6-85.2). There were 6 (16.2%) relapses, 1 (2.7%) primary progression and 7 (23%) deaths. Mediastinal radiotherapy was administered to 17 (45.9%) patients. All the deaths were due to disease progression. Grade III/IV toxicities were seen in 28 (75.7%) patients, febrile neutropenia being the most common one. Conclusions DA-R-EPOCH regimen is an effective and tolerable regimen in PMBCL patients even with adverse features.