Abnormal CD13/HLA-DR Expression Pattern on Myeloblasts Predicts Development of Myeloid Neoplasia in Patients With Clonal Cytopenia of Undetermined Significance.

OBJECTIVES: Patients with clonal cytopenia of undetermined significance (CCUS) are at increased risk of developing myeloid neoplasia (MN). We evaluated whether a simple flow cytometry immunophenotyping (FCIP) assay could differentiate the risk of development of MN in patients with CCUS. METHODS: Bone marrow aspirates were assessed by FCIP panel in a cohort of 80 patients identified as having CCUS based on next-generation sequencing or cytogenetics from March 2015 to May 2020, with available samples. Flow cytometric assay included CD13/HLA-DR expression pattern on CD34-positive myeloblasts; CD13/CD16 pattern on maturing granulocytic precursors; and aberrant expression of CD2, CD7, or CD56 on CD34-positive myeloblasts. Relevant demographic, comorbidity, and clinical and laboratory data, including the type and extent of genetic abnormalities, were extracted from the electronic health record. RESULTS: In total, 17 (21%) patients with CCUS developed MN over the follow-up period (median survival follow-up, 28 months [95% confidence interval, 19-31]). Flow cytometry immunophenotyping abnormalities, including the aberrant pattern of CD13/HLA-DR expression, as detected at the time of the diagnosis of CCUS, were significantly associated with risk of developing MN (hazard ratio, 2.97; P = .006). Additional FCIP parameters associated with the development of MN included abnormal expression of CD7 on myeloblasts and the presence vs absence of any FCIP abnormality. CONCLUSIONS: A simple FCIP approach that includes assessment of CD13/HLA-DR pattern on CD34-positive myeloblasts can be useful in identifying patients with CCUS at higher risk of developing MN.

A randomized phase 3 trial of interferon-α vs hydroxyurea in polycythemia vera and essential thrombocythemia.

The goal of therapy for patients with essential thrombocythemia (ET) and polycythemia vera (PV) is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for patients with ET and PV at high risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment-naïve, high-risk patients with ET/PV. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (P = .80) at 12 months. At 24 to 36 months, CR was 20% to 17% for HU and 29% to 33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, whereas grade 3/4 adverse events were more frequent with PEG (46% vs 28%). At 12 months of treatment, there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment, PEG was more effective in normalizing blood counts and reducing driver mutation burden, whereas HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk patients with ET/PV. This trial was registered at www.clinicaltrials.gov as #NCT01259856.

Genetic features and clinical outcomes of patients with isolated and comutated DDX41-mutated myeloid neoplasms.

DDX41 mutations (germline and somatic) are associated with late onset myelodysplastic syndromes/acute myeloid leukemia (MDS/AML). Myeloid neoplasms (MN) with germline predisposition was identified as a distinct category in the 2016 WHO classification revision, including MN with germline DDX41 mutation. We retrospectively analyzed the molecular findings and clinical characteristics of thirty-three DDX41-mutated (mDDX41) patients at our institution. We identified 14 distinct pathogenic DDX41 variants in 32 patients and 8 DDX41 variants of unknown significance (VUS) in 9 patients. Five (16%) patients had a second DDX41 somatic mutation p.R525H and 13 (40%) had at least one additional oncogenic co-mutation in other genes. The median age at the time of diagnosis was 66 years, with male predominance (72%) and the majority of patients had normal cytogenetics (91%). Two-year overall survival (OS) was 86% and 6 (21%) MDS/AML patients with relatively preserved hematopoietic function were observed without further intervention. In comparison to AML patients with prognostically more favorable subtypes [t(8;21), n=27 and inv(16), n=40], mDDX41 patients in our cohort showed similarly favorable OS. Our study highlights that mDDX41-MN patients often have an indolent course and mDDX41-AML has comparable OS to favorable-risk AML.

Neuro-Swarm heuristic using interior-point algorithm to solve a third kind of multi-singular nonlinear system.

The purpose of the present work is to solve a third kind of multi-singular nonlinear system using the neuro-swarm computing solver based on the artificial neural networks (ANNs) optimized with the effectiveness of particle swarm optimization (PSO) maintained by a local search proficiency of interior-point algorithm (IPA), i.e., ANN-PSO-IPA. An objective function is designed using the continuous mapping of ANN for nonlinear multi-singular third order system of Emden-Fowler equations and optimization of fitness function carried out with the integrated strength of PSO-IPA. The motivation to design the ANN-PSO-IPA is to present a feasible, reliable and feasible framework to handle with such complicated nonlinear multi-singular third order system of Emden-Fowler model. The designed ANN-PSO-IPA is tested for three different nonlinear variants of the multi-singular third kind of Emden-Fowler system. The obtained numerical results on single/multiple executions of the designed ANN-PSO-IPA are used to endorse the precision, viability and reliability.

Research on online advertising attention evaluation decision based on the stability of delay differential equations and Hopf bifurcation analysis.

This paper uses the stability of the delay differential equation to study its impact on online advertising, helps analyze Hopf branch characteristics in a big data environment, helps companies make online advertising decisions, and maximizes the benefits of product sales. The thesis fully considers various factors such as advertising volume, advertising schedule, and advertising investment level, discusses the singularity types of the advertising delay differential equation, and gives the best decision for advertising investment.The stability of the time-lag differential equation studied in this paper is to study its impact on online advertising, to help analyze the Hopf branch characteristics in the big data environment, and to help companies make online advertising decisions. structure of this article is also from the amount of advertising, the time of advertising, Advertising investment level gradually expands with a certain degree of continuity.

Calorie restriction promotes remyelination in a Cuprizone-Induced demyelination mouse model of multiple sclerosis.

Over the past few decades several attempts have been made to introduce a potential and promising therapy for Multiple sclerosis (MS). Calorie restriction (CR) is a dietary manipulation to reduce calorie intake which has been shown to improve neuroprotection and attenuate neurodegenerative disorders. Here, we evaluated the effect of 33% CR regimen for 4 weeks on the remyelination capacity of Cuprizone (CPZ) induced demyelination in a mouse model of MS. Results showed that CR induced a significant increase in motor coordination and balance performance in CPZ mice. Also, luxol fast blue (LFB) staining showed that CR regimen significantly improved the remyelination in the corpus callosum of CPZ + CR mice compared to the CPZ group. In addition, CR regimen significantly increased the transcript expression levels of BDNF, Sox2, and Sirt1 in the corpus callosum of CPZ mice, while decreasing the p53 levels. Moreover, CR regimen significantly decreased the apoptosis rate. Furthermore, astrogliosis (GFAP + astrocytes) and microgliosis (Iba-1 + microglia) were significantly decreased by CR regimen while oligodendrogenesis (Olig2+) and Sirt1 + cell expression were significantly increased in the corpus callosum of CPZ + CR mice compared to the CPZ group. In conclusion, CR regimen can promote remyelination potential in a CPZ-demyelinating mouse model of MS by increasing oligodendrocyte generation while decreasing their apoptosis.

Pain and fertility outcomes of nerve-sparing, full-thickness disk or segmental bowel resection for deep infiltrating endometriosis-A prospective cohort study.

INTODUCTION: Choosing the optimal treatment for bowel endometriosis, ie, conservative vs radical surgery, is under debate. We aimed to evaluate the surgical outcomes of segmental resection and disk resection regarding fertility, pain symptoms, and quality of life score of women with colorectal deep infiltrating endometriosis. MATERIAL AND METHODS: From March 2011 to December 2016, 134 consecutive patients with symptomatic deep infiltrating endometriosis of the rectosigmoid up to 25 cm from the anal verge undergoing segmental resection or disk resection were prospectively evaluated regarding reduction in pain symptoms, fertility outcomes, and complication rates according to Clavien-Dindo classification. RESULTS: Of the 134 women included, segmental resection was performed in 102 (76.1%) women and disk resection was performed in 32 (23.9%) women. There was no difference in duration of surgery, complication rates, mean hospital stay, or discrepancy in hemoglobin level comparing the two groups. There was no significant difference regarding reduction of pain symptoms, fertility, and functional outcomes. One hundred and twelve (83.6%) women were followed up long-term. In both cohorts, there was a significant reported decrease in pain symptoms and increase in quality of life scores. Of all the 61 infertile women, 26 (42.6%) became pregnant spontaneously, and 13 (21.3%) by in vitro fertilization with an overall pregnancy rate of 63.4%. The overall complication rate (Clavien-Dindo III-IV) was 8 of 134 (5.9%) without statistically significant difference between the cohorts. CONCLUSIONS: Both conservative surgery with disk resection, and nerve- and vessel-sparing segmental resection reduce pain symptoms with equal morbidity. Fertility is improved with surgery with both techniques.