Precision Medicine in Systemic Mastocytosis

Mastocytosis is a rare hematological neoplasm characterized by the proliferation of abnormal clonal mast cells (MCs) in different cutaneous and extracutaneous organs. Its diagnosis is based on well-defined major and minor criteria, including the pathognomonic dense infiltrate of MCs detected in bone marrow (BM), elevated serum tryptase level, abnormal MCs CD25 expression, and the identification of KIT D816V mutation. The World Health Organization (WHO) classification subdivides mastocytosis into a cutaneous form (CM) and five systemic variants (SM), namely indolent/smoldering (ISM/SSM) and advanced SM (AdvSM) including aggressive SM (ASM), SM associated to hematological neoplasms (SM-AHN), and mast cell leukemia (MCL). More than 80% of patients with SM carry a somatic point mutation of KIT at codon 816, which may be targeted by kinase inhibitors. The presence of additional somatic mutations detected by next generation sequencing analysis may impact prognosis and drive treatment strategy, which ranges from symptomatic drugs in indolent forms to kinase-inhibitors active on KIT. Allogeneic stem cell transplant (SCT) may be considered in selected SM cases. Here, we review the clinical, diagnostic, and therapeutic issues of SM, with special emphasis on the translational implications of SM genetics for a precision medicine approach in clinical practice

Comparison of metabolic, oxidative and inflammatory status of Simmental × Holstein crossbred with parental breeds during the peripartal and early lactation periods.

AbstractThe aim of the research reported in this paper was to evaluate plasma concentrations of energy, oxidative and inflammatory biomarkers of Simmental (sire) × Holstein (dam) crossbred cows, in comparison with the two parental breeds during the peripartal and early lactation periods and to estimate the effects of heterosis for these traits. Thirty-three animals, managed under the same conditions, 8 Simmental (SI), 9 Holstein (HO) and 16 crossbred (CR) cows were enrolled in this study. Glucose, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatine kinase (CK), total protein, albumin, creatinine and urea were determined in blood sampled at six different time points (30 ± 3 and 15 ± 3 d before the expected calving date, at calving and 15, 30 and 60 d after calving). Furthermore, derived reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), interleukin-6 (IL-6), haptoglobin (Hp) and serum amyloid A protein (SAA) were determined to evaluate inflammatory and oxidative status. Results showed that the CR group had significantly lower average values of glucose and NEFA when compared to HO group; signifcantly lower values of urea than SI group and significantly higher values of creatinine than HO. Furthermore, CR cows showed the lowest average value of d-ROMs with respect to SI and HO parental breeds. Finally, the average value of haptoglobin was significantly lower in CR and HO groups, when compared to SI group. As for the heterosis we found the highest (positive) percentage for CK (98%) and BAP (47%) and the lowest (negative) percentage for OSi (−75%) and d-ROMs (−39%). A negative percentage was also found for the glucose (−11%) and NEFA (−20%) toward the Simmental parental breed. Our results suggest a different response among the three genetic groups during the peripartal and early lactation periods. In particular, CR and SI cows seem more adaptable regarding energy metabolism and oxidative status. Heterosis led to a positive effect on those parameters in Simmental (sire) × Holstein (dam) crossbred cows F1 population (50% Simmental and 50% Holstein)

Determinants of frontline tyrosine kinase inhibitor choice for patients with chronic-phase chronic myeloid leukemia: A study from the Registro Italiano LMC and Campus CML

Background: Imatinib, dasatinib, and nilotinib are tyrosine kinase inhibitors (TKIs) approved in Italy for frontline treatment of chronic-phase chronic myeloid leukemia (CP-CML). The choice of TKI is based on a combined evaluation of the patient's and the disease characteristics. The aim of this study was to analyze the use of frontline TKI therapy in an unselected cohort of Italian patients with CP-CML to correlate the choice with the patient's features. Methods: A total of 1967 patients with CP-CML diagnosed between 2012 and 2019 at 36 centers throughout Italy were retrospectively evaluated; 1089 patients (55.4%) received imatinib and 878 patients (44.6%) received a second-generation (2G) TKI. Results: Second-generation TKIs were chosen for most patients aged <45 years (69.2%), whereas imatinib was used in 76.7% of patients aged >65 years (p < .001). There was a predominant use of imatinib in intermediate/high European long-term survival risk patients (60.0%/66.0% vs. 49.7% in low-risk patients) and a limited use of 2G-TKIs in patients with comorbidities such as hypertension, diabetes, chronic obstructive pulmonary disease, previous neoplasms, ischemic heart disease, or stroke and in those with >3 concomitant drugs. We observed a greater use of imatinib (61.1%) in patients diagnosed in 2018-2019 compared to 2012-2017 (53.2%; p = .002). In multivariable analysis, factors correlated with imatinib use were age > 65 years, spleen size, the presence of comorbidities, and ≥3 concomitant medications. Conclusions: This observational study of almost 2000 cases of CML shows that imatinib is the frontline drug of choice in 55% of Italian patients with CP-CML, with 2G-TKIs prevalently used in younger patients and in those with no concomitant clinical conditions. Introduction of the generic formulation in 2018 seems to have fostered imatinib use

AdaptMap: exploring goat diversity and adaptation

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Table_3_Bio-Hydrogen Production From Buffalo Waste With Rumen Inoculum and Metagenomic Characterization of Bacterial and Archaeal Community.xlsx

<p>Biogas production from agricultural and industrial wastes delivers two benefits: on one side, the treatment of organic residues prevents the environmental and economic impact of their disposal; on the other side, methane and/or hydrogen are generated. The aims of this study were both to produce bio-hydrogen from buffalo wastes and to investigate the relationship between biogas production and bacterial and archaeal community composition. Anaerobic codigestion of livestock by-products (buffalo sludge and low protein cheese whey-scotta), with buffalo rumen and buffalo sludge as inoculum, was performed. The microbial community was analyzed using next-generation sequencing of 16S rRNA gene amplicons. Codigestion showed to be positive because of both sludge buffering capability and highly degradable carbohydrates content in scotta. Rumen inoculum proved more efficient compared to sludge during fermentation. In fact, cumulated production was higher (120.8 vs. 65.4 ml H₂ g VS⁻¹ respectively) and the average percentage of hydrogen in biogas was 48.1 (v/v) with maximum peak at 64.6. Moreover, rumen bacterial profile showed higher genera richness. Taxonomic classification showed that among the bacteria, Firmicutes, 23.3% of whom Clostridia; Bacteroidetes, and in particular Bacteroidia; Proteobacteria and Tenericutes, accounted for 88.2% of total sequences. Concerning the Clostridia Family XIII, the C. Incertae Sedis was the most represented (6.6%), and its quantity was twice as much in rumen inoculated hydrogen-producing samples than those non-producing. In the archaeal, community predominated the phylum Euryarcheota, with Methanobrevibacter the most represented, which was higher when hydrogen was produced with rumen inoculum. Studies on buffalo rumen as inoculum for hydrogen production are limited and this paper gives a first overview of microbial community composition by NGS in producing and non-producing samples.</p

Table_1_Bio-Hydrogen Production From Buffalo Waste With Rumen Inoculum and Metagenomic Characterization of Bacterial and Archaeal Community.DOCX

<p>Biogas production from agricultural and industrial wastes delivers two benefits: on one side, the treatment of organic residues prevents the environmental and economic impact of their disposal; on the other side, methane and/or hydrogen are generated. The aims of this study were both to produce bio-hydrogen from buffalo wastes and to investigate the relationship between biogas production and bacterial and archaeal community composition. Anaerobic codigestion of livestock by-products (buffalo sludge and low protein cheese whey-scotta), with buffalo rumen and buffalo sludge as inoculum, was performed. The microbial community was analyzed using next-generation sequencing of 16S rRNA gene amplicons. Codigestion showed to be positive because of both sludge buffering capability and highly degradable carbohydrates content in scotta. Rumen inoculum proved more efficient compared to sludge during fermentation. In fact, cumulated production was higher (120.8 vs. 65.4 ml H₂ g VS⁻¹ respectively) and the average percentage of hydrogen in biogas was 48.1 (v/v) with maximum peak at 64.6. Moreover, rumen bacterial profile showed higher genera richness. Taxonomic classification showed that among the bacteria, Firmicutes, 23.3% of whom Clostridia; Bacteroidetes, and in particular Bacteroidia; Proteobacteria and Tenericutes, accounted for 88.2% of total sequences. Concerning the Clostridia Family XIII, the C. Incertae Sedis was the most represented (6.6%), and its quantity was twice as much in rumen inoculated hydrogen-producing samples than those non-producing. In the archaeal, community predominated the phylum Euryarcheota, with Methanobrevibacter the most represented, which was higher when hydrogen was produced with rumen inoculum. Studies on buffalo rumen as inoculum for hydrogen production are limited and this paper gives a first overview of microbial community composition by NGS in producing and non-producing samples.</p