Notes

Quantitative neuronal morphometry simply by monitored as well as without supervision learning.
Most relapses of acute lymphoblastic leukemia (ALL) occur in patients with a medium risk (MR) for relapse on the Associazione Italiana di Ematologia e Oncologia Pediatrica and Berlin-Frankfurt-Münster (AIEOP-BFM) ALL protocol, based on persistence of minimal residual disease (MRD). New insights into biological features that are associated with MRD are needed. Here, we identify the glycosylphosphatidylinositol-anchored cell surface protein vanin-2 (VNN2; GPI-80) by charting the cell surface proteome of MRD very high-risk (HR) B-cell precursor (BCP) ALL using a chemoproteomics strategy. Selleckchem VX-11e The correlation between VNN2 transcript and surface protein expression enabled a retrospective analysis (ALL-BFM 2000; N = 770 cases) using quantitative polymerase chain reaction to confirm the association of VNN2 with MRD and independent prediction of worse outcome. Using flow cytometry, we detected VNN2 expression in 2 waves, in human adult bone marrow stem and progenitor cells and in the mature myeloid compartment, in line with proposed roles for fetal hematopoietic stem cells and inflammation. Prospective validation by flow cytometry in the ongoing clinical trial (AIEOP-BFM 2009) identified 10% (103/1069) of VNN2+ BCP ALL patients at first diagnosis, primarily in the MRD MR (48/103, 47%) and HR (37/103, 36%) groups, across various cytogenetic subtypes. We also detected frequent mutations in epigenetic regulators in VNN2+ ALLs, including histone H3 methyltransferases MLL2, SETD2, and EZH2 and demethylase KDM6A. Inactivation of the VNN2 gene did not impair leukemia repopulation capacity in xenografts. Taken together, VNN2 marks a cellular state of increased resistance to chemotherapy that warrants further investigations. Therefore, this marker should be included in diagnostic flow cytometry panels.Guidelines provide differing recommendations regarding direct-acting oral anticoagulants vs low-molecular-weight heparin (LMWH) for treatment of cancer-associated thrombosis (CAT). This study was undertaken to evaluate the effectiveness and safety of rivaroxaban vs LMWH for treatment of CAT. Using US Surveillance, Epidemiology and End Results-Medicare-linked data from 2013 through 2016, we evaluated adults with active breast, lung, ovarian, or pancreatic cancer, who were admitted to the hospital or treated in the emergency department for CAT and were prescribed rivaroxaban or LMWH for outpatient anticoagulation. Patients with luminal gastrointestinal or genitourinary cancers were excluded. Rivaroxaban and LMWH users were 11 propensity score matched. Outcomes included the composite of recurrent thrombosis or major bleeding, each outcome separately, and mortality at 6 months, using an intent-to-treat approach. On-treatment analysis after 12 months was also performed. Proportional hazards models for the subdistribution of competing risk were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). We included 529 rivaroxaban- and 529 LMWH-treated patients with CAT. Rivaroxaban was not associated with differences in risk of the composite outcome (HR, 0.71; 95% CI, 0.41-1.22), major bleeding (HR, 1.01; 95% CI, 0.50-2.01), or mortality (HR, 0.87; 95% CI, 0.70-1.07) vs LMWH, but it reduced recurrent thrombosis (HR, 0.37; 95% CI, 0.15-0.95). On-treatment analysis at 12 months showed similar results. Rivaroxaban may be a reasonable alternative to LMWH for patients with CAT without gastrointestinal or genitourinary cancer.Kinetoplastid flagellates are known for several unusual features, one of which is their complex mitochondrial genome, known as kinetoplast (k) DNA, composed of mutually catenated maxi- and minicircles. Trypanosoma lewisi is a member of the Stercorarian group of trypanosomes which is, based on human infections and experimental data, now considered a zoonotic pathogen. By assembling a total of 58 minicircle classes, which fall into two distinct categories, we describe a novel type of kDNA organization in T. lewisi. RNA-seq approaches allowed us to map the details of uridine insertion and deletion editing events upon the kDNA transcriptome. Moreover, sequencing of small RNA molecules enabled the identification of 169 unique guide (g) RNA genes, with two differently organized minicircle categories both encoding essential gRNAs. The unprecedented organization of minicircles and gRNAs in T. lewisi broadens our knowledge of the structure and expression of the mitochondrial genomes of these human and animal pathogens. Finally, a scenario describing the evolution of minicircles is presented.
Managing the presence of Salmonella in ground beef has been an ongoing challenge for the beef industry. Salmonella prevalence can vary regionally, seasonally, and within the animal, making the development of interventions difficult. The objective of this study was to assess the efficacy of an autogenous Salmonella vaccine in mitigating Salmonella in lymph nodes (LNs) of feedlot cattle. An autogenous vaccine was developed using the most common Salmonella enterica serovars (Salmonella Kentucky, Salmonella Anatum, Salmonella Muenchen, Salmonella Montevideo, and Salmonella Mbandaka) identified from cattle managed at a South Texas feedlot with historically high Salmonella prevalence. Fifty-five heifers were selected for even distribution across five groups (i) BASE, which received no autogenous vaccinations and were harvested after the stocker stage, (ii) CNTRL, which received no autogenous vaccinations, (iii) FARM, which received autogenous vaccinations at the ranch only, (iv) SPLIT, which received autogenous vaccinations at both the ranch and feedlot, and (v) YARD, which received vaccinations at the feedlot only. One heifer each from the BASE and CNTRL groups did not complete the study. All treatment groups except BASE were harvested after reaching market weight. Left and right superficial cervical and subiliac LNs from each carcass were collected and analyzed for Salmonella presence, and positive samples were serotyped. No salmonellae were recovered from LNs derived from BASE, FARM, SPLIT, or YARD groups. Cattle in the BASE group were expected to have a low occurrence of Salmonella based on previous research. However, the percentage of Salmonella-positive animals in the CNTRL group was 20.0% (2 of 10), which is lower than expected based on historical data from the same feeding location. There could be several causes of decreased Salmonella presence in the LNs of control cattle, creating an opportunity for future investigation into the development of preharvest interventions to combat Salmonella in feedlots.
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