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关键词： Species delimitation methods   Haploweb   Groundwaters   Caves   Bayesian biogeographic analysis   SPECIES DELIMITATION   CRUSTACEA   GENUS   WATER   PERSPECTIVE   DIVERSITY   SOFTWARE   RANGES   TREE  

摘要： TheNiphargus tatrensisspecies complex, entirely subterranean, has a wide distribution range extending from Southern Poland to Austria and Slovenia. Because of its large and confusing morphological variability, it was subdivided into several 'forms', four of which described from Austrian caves. To shed light on this chaotic situation, we sampled the type localities of all described species and forms in the complex, as well as additional sites in Austria, and used nuclear (28S, ITS) and mtDNA (COI) sequences to revise its taxonomy. Phylogenetic analysis confirmed that theNiphargus tatrensisspecies complex is monophyletic. Applying four species delimitation methods to the COI dataset converged on the presence of four species in Austria; by contrast, the same methods applied to ITS concurred with a haploweb analysis of this marker in distinguishing only three species in the country. Reconstruction of ancestral ranges suggested that the Austrian clade originated in Eastern Europe. Bayesian biogeographical analyses revealed a complex history of lineage divergence and secondary contact during the Pleistocene climatic fluctuations, possibly responsible for the higher variability of COI in comparison with ITS. Based on the above, we conclude that only three valid species are present in Austria: considering all described forms as subspecies, two of them are elevated to species rank whereas one new species is formally described and illustrated.

关键词： Anatomical site   Adjuvant therapy   Basaloid squamous cell carcinoma   NCDB   Survival   IMPACT   HPV  

摘要： Purpose Basaloid squamous cell carcinoma (BSCC) of the head and neck is an aggressive and highly malignant variant of squamous cell carcinoma that accounts for 2% of head and neck cancers. Previous studies have not analyzed the significance of adjuvant chemoradiation and anatomical site within BSCC subtype and its impact on survival. Methods A cohort of 1999 patients with BSCC of the head and neck was formed from the National Cancer Database and analyzed with descriptive studies, median survival and 5- and 10-year survival. A multivariable Cox hazard regression was performed to determine the prognostic significance of anatomical site and adjuvant therapy. Results The most common primary anatomical site was the oropharynx (71.9%) followed by oral cavity (11.5%), larynx (10.1%), hypopharynx (3.5%), esophagus (1.9%), and nasopharynx (1.1%). The presence of metastasis increased the risk of mortality (HR = 2.14; 95% CI 1.40-3.26). Tumors localized to the oropharynx demonstrated better survival compared to all sites except nasopharynx, including the oral cavity (HR = 2.45; 95% CI 1.83-3.29), hypopharynx (HR = 2.58; 95% CI:1.64-4.05), and larynx (HR = 2.89; 95% CI:2.25-3.73). Adjuvant chemoradiation (HR = 0.36; 95% CI 0.23-0.58) and adjuvant radiation (HR = 0.38; 95% CI 0.23-0.64) had better survival outcomes compared to adjuvant chemotherapy. Patients with microscopic margins had better survival outcomes when compared to no surgery (HR = 0.38, 98% Cl 0.23-0.64) while there were no better survival outcomes of patients with macroscopic margins compared to no surgery. Conclusion This study illustrated that tumors in the oropharynx, lower age, adjuvant chemoradiation and radiation, and microscopic margins were associated with greater survival.

关键词： Colorectal cancer   NK cells   NKT cells   NK cell receptors   NK cell receptor ligands  

摘要： Introduction: Natural killer (NK) cells and natural killer T (NKT) cells are implicated in the development and progression of colorectal cancer (CRC). Tumor cells express NK cell receptor ligands that modulate their function. This study aimed to investigate the expression of such ligands in CRC in relation to the phenotype of circulating NK- and NKT cells, and clinical outcome. Methods: Primary tumor tissues were analyzed for protein expression of NK cell ligands using immunohistochemistry with automated image analysis in a cohort of 78 CRC patients. For 24 of the 78 patients, RNA expression of NK cell ligands was analyzed in primary tumor tissue using RNA sequencing. Receptor expression on circulating NK- and NKT cells was previously measured by us in 71 of the 78 patients using flow cytometry. Results: High Proliferating Cell Nuclear Antigen (PCNA) protein expression in the primary tumor associated with shorter disease-free survival (DFS) of CRC patients (P = 0.026). A trend was observed towards shorter DFS in CRC patients with above-median galectin-3 protein expression in the primary tumor (P = 0.055). High protein expression of galectin-3, CD1d, and human leukocyte antigen (HLA) class I, and high RNA expression of UL16-binding protein (ULBP)-1, -2, and -5, and HLA-E in the tumor tissue correlated with low expression of the corresponding receptors on circulating NK- or NKT cells (P < 0.05). Conclusions: Galectin-3 and PCNA expression in the primary tumor may be prognostic biomarkers in CRC patients. Furthermore, our results suggest that NK cell receptor ligands expressed by tumor cells may modulate the phenotype of circulating NK- and NKT cells, and facilitate immune escape of metastasizing cells.

关键词： Hepcidin expression   β-Thalassemia major   qRT-PCR   Cardiac iron (T2*)   Iron overload   SERUM HEPCIDIN   FERROPORTIN   ANEMIA   LIVER   HEMOCHROMATOSIS   BINDING  

摘要： Iron overload is the main cause of morbidity and mortality in beta-thalassemia major patients, and cardiac iron overload is the most common reason for death in these transfusion-dependent patients. Hepcidin, a liver-derived peptide hormone, plays a key role in plasma iron levels regulation by controlling two main stages, digestive iron absorption in enterocytes, and iron recycling in macrophages. Although hepcidin is mainly secreted from hepatocytes in the liver, it is also synthesized from mononuclear cells consisting of monocytes and lymphocytes. Binding of this molecule to ferroportin, a specific cellular exporter of iron, leads to degradation of the ligand-receptor complex, which reduces the iron overload by lowering the amounts of iron released into the plasma. Likewise, the same mechanism has been proved to be true for lymphocyte-drived hepcidin. The expression levels of hepcidin mRNA were evaluated using quantitative real time PCR (qRT-PCR) in 50 beta-thalassemia major patients, as well as 25 healthy volunteers as the group of control. There was a significantly positive correlation between the cardiac iron concentration, showed by higher T2 values, and hepcidin levels in the patients (p = 0.028; r = 0.311). However, hepcidin expression levels did not significantly correlate with ferritin and liver iron concentrations. Hepcidin can act as a beneficial marker to determine iron overload degrees, particularly in the heart, in beta-thalassemia major patients and be used as a logical therapeutic agent for treatment of beta-thalassemia disorders.

关键词： Liver fibrosis   Stellate cells   Hepatocytes   Acetaminophen   Bioreactor   Liver spheroids   HYDROGELS   VITRO   DIFFERENTIATION   MACROPHAGES  

摘要： A major obstacle in the development of efficient therapies for progressive liver fibrosis is the lack of representative in vitro models of liver fibrosis to aid in understanding the mechanisms of the disease and to promote the development of pharmaceuticals. Our aim was to develop a relevant in vitro mouse liver fibrosis model, based on the central hypothesis that liver fibrosis in vitro cannot be studied using only hepatic stellate cells (HSCs)-the main producer of scar tissue during fibrosis-, but requires cultures in which at least hepatocytes are integrated. We established robust methods to generate co-culture spheroids from freshly isolated mouse hepatocytes and HSCs. Characteristics and functionality of these spheroids were analyzed by qPCR of cell-type specific markers, CYP induction and immunohistochemistry. Compound toxicity was determined by ATP-assays. Hepatocytes and HSCs maintained their cell-type specific marker expression over a 15-day culture period without major hepatocyte dedifferentiation or HSC activation. Exposure of spheroids to TGFp can directly activate HSCs, while acetaminophen exposure mounts a hepatocyte damage dependent activation of HSCs. Pharmaceuticals with known anti-fibrotic properties, such as Valproic acid and Verteporfin, reduce HSC activation in response to hepatocyte damage in these cultures. A comparison between the fibrotic response of the spheroid co-cultures and in vivo activated HSCs showed that these 3D co-cultures are more representative than the commonly used 2D HSC monocultures. Finally, we showed that the 3D cultures can be integrated in microfluidic chips. We conclude that our hepatocyte-stellate cell-spheroid cultures are a robust in vitro model of liver fibrosis. This model could be used to further unravel the mechanism of HSC activation and facilitate the discovery of, or testing for novel anti-fibrotic compounds, as these spheroids better reproduce HSC in vivo activation compared to the more traditional 2D mono-cu

关键词： Cisplatin   Dipeptidyl peptidase-4   Linagliptin   Stromal cell-derived factor-1 alpha   Testicular injury   SPERMATOGONIAL STEM-CELLS   MALE-MICE LACKING   FACTOR-I   DIPEPTIDYL PEPTIDASE-4   DEFECTIVE SPERMATOGENESIS   ANDROGEN RECEPTOR   DAMAGE   PROLIFERATION   INFERTILITY   ACTIVATION  

摘要： Stromal cell-derived factor-1 alpha (SDF-1 alpha) plays a key role in trafficking of stem cells and regeneration of injured tissue through interaction with its receptor, CXCR4. This study investigated the probable therapeutic effect of linagliptin (LG) against cisplatin (CP)-induced testicular injury and the underlying mechanisms. 12 week old male Sprague-Dawley rats were randomly assigned into 6 groups (n = 10 each) as follow: (i) Control, (ii) LGtreated control, (iii) CP-exposed rats, (iv) CP-exposed rats received LG, (v) CP-exposed rats received AMD3100, as CXCR4 antagonist, and (vi) CP-exposed rats received AMD3100 prior to LG. After 15 days, blood, testes and epididymides were collected for analyses. There were significant increases in both circulatory and testicular levels of SDF-1 alpha in LG-treated rats. Conversely, higher levels of incretin hormones were found in serum but not in testicular tissue of rats, following LG therapy. CP injection significantly reduced body, testicular and epididymal weights of rats, and were restored by LG therapy. Treatment of CP-exposed rats with LG improved the deteriorated testicular architecture, reconstructed spermatogenesis, increased sperm count and quality, and normalized testosterone levels. LG therapy increased gene expression of Lin28a and Mvh, but did not alter the expressions of somatic-related genes. Additionally, LG therapy promoted germ cells survival and proliferation likely via activation of extracellular signal-regulated kinase1/2 (ERK1/2) signaling. These positive effects of LG therapy were almost blunted by administration of AMD3100. These results provided mechanistic insights into the ameliorative effect of LG on CP-induced testicular injury, through activation of SDF-1 alpha/CXCR4 signaling pathway. Our findings suggest that LG can be a promising therapeutic candidate for CP-induced testicular injury.

关键词： Deep learning   High resolution remote sensing   Network architecture search (NAS)   Image classification  

摘要： Remote sensing image scene classification (RSISC) is one of the bases of visual question answering for remote sensing data (RSVQA). In the conventional deep learning based solutions of RSISC, domain experts have to manually design the neural architecture, which is costly in both time and manpower. In this paper, AutoRSISC, a high resolution remote sensing image scene classification method based on neural architecture search (NAS) is proposed. AutoRSISC algorithm samples the neural architecture in a certain proportion to reduce the redundancy in the search space which is based on the continuous relaxation of the neural architecture representation. Edge normalization is introduced to make architecture search more efficient. The conventional deep learning approaches take days or more just to manually design the appropriate neural architecture according to the current data set. The experimental results show that our method saves time and manpower compared with the existing manually designed RSISC methods. Our AutoRSISC algorithm took 7.6 h from the automatic design of the most appropriate neural architecture to the end of all experiments according to the UCM data set, and the classification accuracy rate of the final test set reached 97.85%. And our AutoRSISC algorithm took 101.7 h from the automatic design of the most appropriate neural architecture to the end of all experiments according to the NWPU45 data set, and the classification accuracy rate of the final test set reached 94.66%. (C) 2020 Elsevier B.V. All rights reserved.

关键词： transfusion   postoperative outcomes   distinct-effects generalized estimating equation model   CLINICAL-TRIALS   TRANSFUSION   OUTCOMES   AGE   COLLECTION   MORTALITY   EVOLUTION   SURVIVAL   LESION   UNITS  

摘要： Background: Although observational studies suggest an association between transfusion of older red blood cell (RBC) units and increased postoperative risk, randomized trials have not supported this. The objective of this randomized trial was to test the effect of RBC storage age on outcomes after cardiac surgery. Methods: From July 2007 to May 2016, 3835 adults undergoing coronary artery bypass grafting, cardiac valve procedures, or ascending aorta repair, either alone or in combination, were randomized to transfusion of RBCs stored for <= 14 days (younger units) or for >= 20 days (older units) intraoperatively and throughout the postoperative hospitalization. According to protocol, 2448 patients were excluded because they did not receive RBC transfusions. Among the remaining 1387 modified intent-to-treat patients, 701 were randomized to receive younger RBC units (median age, 11 days) and the remaining 686 to receive older units (median age, 25 days). The primary endpoint was composite morbidity and mortality, analyzed using a generalized estimating equation (GEE) model. The trial was discontinued midway owing to enrollment constraints. Results: A total of 5470 RBC units were transfused, including 2783 in the younger RBC storage group and 2687 in the older RBC storage group. The GEE average relative-effect odds ratio was 0.77 (95% confidence interval [CI], 0.50-1.19; P = .083) for the composite morbidity and mortality endpoint. Inhospital mortality was lower for the younger RBC storage group (2.1% [n = 15] vs 3.4% [n = 23]), as was occurrence of other adverse events except for atrial fibrillation, although all CIs crossed 1.0. Conclusions: This clinical trial, which was stopped at its midpoint owing to enrollment constraints, supports neither the efficacy nor the futility of transfusing either younger or older RBC units. The effects of transfusing RBCs after even more prolonged storage (35-42 days) remains untested.

关键词： Equine   Hypercalcemia   Hypocalcemia   Parathyroid hormone   Hypophosphatemia  

摘要： Primary hyperparathyroidism is rare in large animal species, and little is known regarding its pathophysiology, endocrine and electrolyte derangements, diagnosis, medical management, and prognosis. This report describes the clinicopathologic diagnosis of a parathyroid (PT) gland chief cell adenoma in a 12-year-old Quarter Horse mare, including PT hormone (PTH) and electrolyte disarrangements associated with the neoplasia, the surgical removal of the adenoma, and medical management of the case. This report also describes for the first time the use PTH immunohistochemistry to confirm the nature of this neoplasia in a horse. (C) 2020 Elsevier Inc. All rights reserved.