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Neutropenia is an adverse effect of vincristine when used in multidrug chemotherapy protocols.
To determine the incidence of neutropenia, identify potential risk factors for neutropenia, and determine the effect of neutropenia on outcome, in dogs receiving vincristine for treatment of immune-mediated thrombocytopenia (ITP).
One hundred twenty-seven client-owned dogs presumptively diagnosed with ITP.
In this retrospective cohort study, medical records were reviewed to identify dogs presumptively diagnosed with ITP, and treated with vincristine, over a 15-year period. Logistic regression was used to identify risk factors for the development of neutropenia in dogs receiving vincristine. Time to platelet count ≥40 000 platelets/μL, survival, and duration of hospitalization were compared between neutropenic and non-neutropenic dogs.
Vincristine was administered to 127 dogs with presumptive ITP; 19 became neutropenic. Administration of cyclosporine was significantly (P < .001) associated with the develceiving vincristine treatment for ITP, particularly if administered in conjunction with cyclosporine.Genes involved in the homologous recombination repair pathway-as exemplified by BRCA1, BRCA2, PALB2, ATM, and CHEK2-are frequently associated with hereditary breast and ovarian cancer syndrome. Germline mutations in the loci of these genes with loss of heterozygosity or additional somatic truncation at the WT allele lead to the development of breast cancers with characteristic clinicopathological features and prominent genomic features of homologous recombination deficiency, otherwise referred to as “BRCAness.” Although clinical genetic testing for these and other genes has increased the chances of identifying pathogenic variants, there has also been an increase in the prevalence of variants of uncertain significance, which poses a challenge to patient care because of the difficulties associated with making further clinical decisions. To overcome this challenge, we sought to develop a methodology to reclassify the pathogenicity of these unknown variants using statistical modeling of BRCAness. The model was developed with Lasso logistic regression by comparing 116 genomic attributes derived from 37 BRCA1/2 biallelic mutant and 32 homologous recombination-quiescent breast cancer exomes. The model showed 95.8% and 86.7% accuracies in the training cohort and The Cancer Genome Atlas validation cohort, respectively. Through application of the model for variant reclassification of homologous recombination-associated hereditary breast and ovarian cancer causal genes and further assessment with clinicopathological features, we finally identified one likely pathogenic and five likely benign variants. As such, the BRCAness model developed from the tumor exome was robust and provided a reasonable basis for variant reclassification.Endemics co-occur because they evolved in situ and persist regionally or because they evolved ex situ and later dispersed to shared habitats, generating evolutionary or ecological endemicity centres, respectively. We investigate whether different endemicity centres can intertwine in the region ranging from Alps to Sicily, by studying their butterfly fauna. We gathered an extensive occurrence data set for butterflies of the study area (27,123 records, 269 species, in cells of 0.5 × 0.5 degrees of latitude-longitude). We applied molecular-based delimitation methods (GMYC model) to 26,557 cytochrome c oxidase subunit 1 (COI) sequences of Western Palearctic butterflies. We identified entities based on molecular delimitations and/or the checklist of European butterflies and objectively attributed occurrences to their most probable entity. We obtained a zoogeographic regionalisation based on the 69 endemics of the area. Using phylogenetic ANOVA we tested if endemics from different centres differ from each other and from nonendemics for key ecological traits and divergence time. Endemicity showed high incidence in the Alps and Southern Italy. The regionalisation separated the Alps from the Italian Peninsula and Sicily. The endemics of different centres showed a high turnover and differed in phylogenetic distances, phenology and distribution traits. Endemics are on average younger than nonendemics and the Peninsula-Sicily endemics also have lower variance in divergence than those from the Alps. The observed variation identifies Alpine endemics as paleoendemics, now occupying an ecological centre, and the Peninsula-Sicily ones as neoendemics, that diverged in the region since the Pleistocene. The results challenge the common view of the Alpine-Apennine area as a single “Italian refugium”.Invasive species have the ability to colonize new habitats across distinct areas of the globe, rapidly adjusting to new biotic and abiotic conditions, and often experiencing little impact from the decrease in effective population size and genetic diversity. Still, as each invading population represents a subsample of the original native distribution, it is common to see variability in terms of the genetic makeup of invading populations and consequently differences in invasion success rates across their non-native range (Blackburn et al., 2017). In a From the Cover article in this issue of Molecular Ecology, Stuart et al. (2020) used genotyping-by-sequencing to explore how landscape and environmental heterogeneity shaped the genetic population structure and adaptation of multiple invasions of the common starling in Australia, and compared it to the patterns observed in North America, examined in Hofmeister et al. (2019). Their results suggest that the common starling worldwide invasion has been driven by a handful of genes that allowed adaptation to extreme environmental conditions and might be the key for differences in invasion success.The influence of patient characteristics and immunosuppression management on COVID-19 outcomes in kidney transplant recipients (KTRs) remains uncertain. We performed a single-center, retrospective review of all adult KTRs admitted to the hospital with confirmed COVID-19 between 03/15/2020 and 05/15/2020. Patients were followed from the date of admission up to 1 month following hospital discharge or study conclusion (06/15/2020). SRI-011381 research buy Baseline characteristics, laboratory parameters, and immunosuppression were compared between survivors and patients who died to identify predictors of mortality. 38 KTRs with a mean baseline eGFR of 52.5 ml/min/1.73 m2 were hospitalized during the review period. Maintenance immunosuppression included tacrolimus (84.2%), mycophenolate (89.5%), and corticosteroids (81.6%) in the majority of patients. Eleven patients (28.9%) died during the hospitalization. Older age (OR = 2.05; 1.04-4.04), peak D-dimer (OR = 1.20; 1.04-1.39), and peak white blood cell count (OR = 1.11; 1.02-1.21) were all associated with mortality among KTRs hospitalized for COVID-19.