AVALON: The Italian cohort study on real-life efficacy of hypomethylating agents plus venetoclax in newly diagnosed or relapsed/refractory patients with acute myeloid leukemia.

Background: Venetoclax in combination with hypomethylating agents (HMA) is revolutionizing the therapy of acute myeloid leukemia (AML). However, evidence on large sets of patients is lacking, especially in relapsed or refractory leukemia.

Methods: AVALON is a multicentric cohort study that was conducted in Italy on patients with AML who received venetoclax-based therapies from 2015 to 2020.

[Treatment-resistant depression. From classification to new therapies.].

Aims: This paper aims to investigate the advances in recent years in the recognition and therapy of treatment-resistant depression starting from the concepts of: depressive disorder, resistance and pseudoresistance to drug treatment in depression, and appropriate treatments of treatment-resistant depression.

Methods: An extensive research was carried out on scientific databases such as: PubMed, PsychInfo and Cochrane Library, until May 2022, using the keywords "major depression", "treatment-resistant depression", "staging", "instrumental therapies for resistant depression", "esketamine" and "psilocybin".

Results: Subjects who do not respond to antidepressants show a form of treatment resistance that requires an approach with additional pharmacological and/or instrumental therapies.

Intra- and Intermolecular Cooperativity in the Catalytic Activity of Phosphodiester Cleavage by Self-Assembled Systems Based on Guanidinylated Calix[4]arenes.

The calix[4]arene scaffold, blocked in the cone conformation through alkylation with long alkyl chains, and decorated at the upper rim with four guanidine or arginine units, effectively catalyzes the cleavage of the phosphodiester bond of DNA and RNA model compounds in water. An exhaustive kinetic investigation unequivocally points to the existence of spontaneous aggregation phenomena, driven by hydrophobic effect, occurring at different critical concentrations that depend on the identity of the compound. A pronounced superiority of the assembled structures compared with the monomers in solution was observed.

Targeting SARS-CoV-2 nsp13 Helicase and Assessment of Druggability Pockets: Identification of Two Potent Inhibitors by a Multi-Site In Silico Drug Repurposing Approach.

The SARS-CoV-2 non-structural protein 13 (nsp13) helicase is an essential enzyme for viral replication and has been identified as an attractive target for the development of new antiviral drugs. In detail, the helicase catalyzes the unwinding of double-stranded DNA or RNA in a 5' to 3' direction and acts in concert with the replication-transcription complex (nsp7/nsp8/nsp12). In this work, bioinformatics and computational tools allowed us to perform a detailed conservation analysis of the SARS-CoV-2 helicase genome and to further predict the druggable enzyme's binding pockets.

Carboxylic Acid Directed γ-Lactonization of Unactivated Primary C-H Bonds Catalyzed by Mn Complexes: Application to Stereoselective Natural Product Diversification.

Reactions that enable selective functionalization of strong aliphatic C-H bonds open new synthetic paths to rapidly increase molecular complexity and expand chemical space. Particularly valuable are reactions where site-selectivity can be directed toward a specific C-H bond by catalyst control. Herein we describe the catalytic site- and stereoselective γ-lactonization of unactivated primary C-H bonds in carboxylic acid substrates.

Impact of SARS-CoV-2 infection on tuberculosis outcome and follow-up in Italy during the first COVID-19 pandemic wave: a nationwide online survey.

Background: SARS-CoV-2 pandemic affected tuberculosis (TB) management. This Italian nationwide survey assessed COVID-19 impact on TB care and outcomes.

Materials And Methods: Twenty-one hospitals or referral centres fulfilled an online survey.

Relationship between aerobic fitness and metabolic power metrics in elite male soccer players.

The aim was to assess the relationship between aerobic fitness and metabolic power metrics in elite male soccer players, and the possible differences that playing positions might impose during match play over new metabolic power metrics. Sixty-two elite professional male soccer players (13 central backs, 13 side backs, 22 midfielders, and 14 forwards) took part in the study. Players were monitored during eleven months of full training (including pre-season and in-season) and over all official matches (Serie A matches, Italy Cup matches).

Autologous stem cell transplantation (ASCT) for acute myeloid leukemia in patients in first complete remission after one versus two induction courses: A study from the ALWP of the EBMT.

Background: Achieving complete remission (CR) is the main goal in AML treatment and a prerequisite for successful autologous stem cell transplantation (ACT).

Methods: Comparing results of peripheral blood ACT in patients with AML in CR1 attained following 1 versus 2 chemotherapy courses transplanted in 2000-2019.

Results: Patients 1532 (84%) with one and 293 (16%) patients with two induction chemotherapies courses (a total of 1825 patients) were included in the study.

Daratumumab combined with dexamethasone and lenalidomide or bortezomib in relapsed/refractory multiple myeloma (RRMM) patients: Report from the multiple myeloma GIMEMA Lazio group.

The multiple myeloma (MM) treatment has changed over the last years due to the introduction of novel drugs. Despite improvements in the MM outcome, MM remains an incurable disease. Daratumumab is a human IgGK monoclonal antibody targeting CD38 with tumor activity associated with immunomodulatory mechanism.

Factors Governing Reactivity and Selectivity in Hydrogen Atom Transfer from C(sp)-H Bonds of Nitrogen-Containing Heterocycles to the Cumyloxyl Radical.

A kinetic study of the hydrogen atom transfer (HAT) reactions from nitrogen-containing heterocycles (secondary and tertiary lactams, 2-imidazolidinones, 2-oxazolidinones, and succinimides) to the cumyloxyl radical has been carried out employing laser flash photolysis with ns time resolution. HAT occurs from the C-H bonds that are α to nitrogen, activated by hyperconjugative overlap with the N-C═O π system. In the lactam series, the second-order HAT rate constant () was observed to decrease by a factor of ∼4 going from the five- and six-membered ring derivatives to the eight-membered ones, a behavior that was rationalized on the basis of a reduced extent of hyperconjugative activation associated to the greater flexibility of the larger rings compared to the smaller ones.

Parents' and caregivers' role toward childhood vaccination in Albania: assessment of predictors of vaccine hesitancy.

Background: Vaccination has saved millions of lives through the protection of individuals and populations from communicable diseases. Vaccine hesitancy, defined as the delay in acceptance or refusal of vaccines despite the availability of vaccination services, has become a growing global concern. The objective of this study was to investigate parents'/caregivers' hesitancy toward childhood vaccination and its predictors in Albania.

Resolving Oxygenation Pathways in Manganese-Catalyzed C(sp)-H Functionalization via Radical and Cationic Intermediates.

The C(sp)-H bond oxygenation of the cyclopropane-containing mechanistic probes 6--butylspiro[2.5]octane and spiro[2.5]octane with hydrogen peroxide catalyzed by manganese complexes bearing aminopyridine tetradentate ligands has been studied.

Hydrogen Abstraction by Alkoxyl Radicals: Computational Studies of Thermodynamic and Polarity Effects on Reactivities and Selectivities.

Density functional theory calculations (ωB97X-D) are reported for the reactions of methoxy, -butoxy, trichloroethoxy, and trifluoroethoxy radicals with a series of 26 C-H bonds in different environments characteristic of a variety of hydrocarbons and substituted derivatives. The variations in activation barriers are analyzed with modified Evans-Polanyi treatments to account for polarity and unsaturation effects. The treatments by Roberts and Steel and by Mayer have inspired the development of a simple treatment involving the thermodynamics of reactions, the difference between the reactant radical and product radical electronegativities, and the absence or presence of α-unsaturation.

Electronic control over site-selectivity in hydrogen atom transfer (HAT) based C(sp)-H functionalization promoted by electrophilic reagents.

The direct functionalization of C(sp)-H bonds represents one of the most investigated approaches to develop new synthetic methodology. Among the available strategies for intermolecular C-H bond functionalization, increasing attention has been devoted to hydrogen atom transfer (HAT) based procedures promoted by radical or radical-like reagents, that offer the opportunity to introduce a large variety of atoms and groups in place of hydrogen under mild conditions. Because of the large number of aliphatic C-H bonds displayed by organic molecules, in these processes control over site-selectivity represents a crucial issue, and the associated factors have been discussed.

Refractory primary immune thrombocytopenia (ITP): current clinical challenges and therapeutic perspectives.

Chronic primary immune thrombocytopenia (ITP) can today benefit from multiple therapeutic approaches with proven clinical efficacy, including rituximab, thrombopoietin receptor agonists (TPO-RA), and splenectomy. However, some ITP patients are unresponsive to multiple lines of therapy with prolonged and severe thrombocytopenia. The diagnosis of refractory ITP is mainly performed by exclusion of other disorders and is based on the clinician's expertise.

Non-T depleted haploidentical stem cell transplantation in AML patients achieving first complete remission after one versus two induction courses: a study from the ALWP/EBMT.

There are no data indicating whether the number of induction courses needed to achieve first complete remission (CR1) is of prognostic significance in Haploidentical transplantation (HaploSCT). We compared transplantation outcomes of adults with AML that underwent HaploSCT in CR1, achieved following one or two induction courses. A total of 635 patients were included: 469 (74%) with 1 and 166 (26%) with two induction chemotherapy courses.

Post-exercise Hypotension in Patients With Coronary Artery Disease.

Blood pressure (BP) and hemodynamic changes occurring in the recovery phase after a single bout of exercise have not been extensively studied in coronary artery patients, despite the potential clinical implications of reducing BP through exercise. This study aimed at investigating the hemodynamic and arterial baroreflex mechanisms possibly involved in post-exercise hypotension (PEH) in patients with coronary artery disease. : In 42 normotensive coronary artery patients undergone a Cardiac Rehabilitation Program, we evaluated before and after their daily exercise training session: blood pressure (BP) and heart rate (HR).

Genetic variation patterns of β-thalassemia in Western Andalusia (Spain) reveal a structure of specific mutations within the Iberian Peninsula.

Background: Analyses of the genomic variation in the western Mediterranean population are being used to reveal its evolutionary history and to understand the molecular basis of particular diseases.

Aim: To observe the β-thalassemia mutational spectrum in western Andalusia, Spain, in the context of the Mediterranean. In addition, associations between disease and neutral gene variants within the β-globin gene (HBB) were also evaluated.

Allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome using treosulfan based compared to other reduced-intensity or myeloablative conditioning regimens. A report of the chronic malignancies working party of the EBMT.

Allogeneic haematopoietic-cell transplantation (allo-HCT) is a potentially curative therapy for high-risk myelodysplastic syndrome (MDS). Reduced-intensity conditioning (RIC) is usually associated with lower non-relapse mortality (NRM), higher relapse rate and similar overall-survival (OS) as myeloablative-conditioning (MAC). Fludarabine/treosulfan (FT) is a reduced-toxicity regimen with intense anti-leukaemia activity and a favourable toxicity profile.