Molecular complexity of diffuse large B-cell lymphoma: Can it be a roadmap for precision medicine?

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma; it features extreme molecular heterogeneity regardless of the classical cell-of-origin (COO) classification. Despite this, the standard therapeutic approach is still immunochemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone—R-CHOP), which allows a 60% overall survival (OS) rate, but up to 40% of patients experience relapse or refractory (R/R) disease. With the purpose of searching for new clinical parameters and biomarkers helping to make a better DLBCL patient characterization and stratification, in the last years a series of large discovery genomic and transcriptomic studies has been conducted, generating a wealth of information that needs to be put in order. We reviewed these researches, trying ultimately to understand if there are bases offering a roadmap toward personalized and precision medicine also for DLBCL

Observing planetesimal formation under streaming instability in the rings of HD 163296

We introduce a new technique to determine the gas turbulence and surface density in bright disc rings, under the assumption that dust growth is limited by turbulent fragmentation at the ring centre. We benchmark this prescription in HD 163296, showing that our measurements are consistent with available turbulence upper limits and agree with independent estimates of the gas surface density within a factor of two. We combine our results with literature measurements of the dust surface density and grain size to determine the dust-to-gas ratio and Stokes number in the 67 au and 100 au rings. Our estimates suggest that particle clumping is taking place under the effect of streaming instability (SI) in the 100 au ring. Even though in the presence of external isotropic turbulence this process might be hindered, we provide evidence that turbulence is non-isotropic in both rings and likely originating from mechanisms (such as ambipolar diffusion) that could ease particle clumping under SI. Finally, we determine the mass accretion rate under the assumption that the disc is in steady state and turbulence regulates angular momentum transport. Our results are in tension with spectroscopic measurements and suggest that other mechanisms might be responsible for accretion, in qualitative agreement with the detection of a magneto-centrifugal wind in this system. Applying our method to larger samples can be used to statistically assess if SI is a viable mechanism to form planetesimals in bright rings.Comment: 13 pages, 4 figures; accepted for publication on ApJ

The Humble Charisma of a White-Dressed Man in a Desert Place: Pope Francis’ Communicative Style in the Covid-19 Pandemic

The context of deep uncertainty, fear, and “social distancing” characterizing the COVID-19 pandemic has led to a need for cultural anchorages and charismatic leaders who may conjointly and effectively support human beings, strengthen their identity, and empower social commitment. In this perspective, the charismatic leadership of Pope Francis, which is widely shared not only within the religious world, may play a crucial role in facing emergency with existential reasons and psychological resources. The general aim of this work is to shed light on the communicative features of the charismatic leadership of Pope Francis during the pandemic emergency; in order to better understand his effectiveness, we analyzed both the core issues and his multimodal body signals in the global TV event of the Universal Prayer with the Urbi et Orbi Blessing. The multimodal and discursive analyses of the homily enabled us to define the “humble” charisma of the Pope, which is based upon on authentic and informal presence, manifested emotional signals (and, in particular commotion) showing features of equity and familiarity. From a discursive point of view, the common and overarching affiliation is constructed through a multiple focus on the “we” pronoun, which is constructed through socio-epistemic rhetoric. The results show how this integrated methodological perspectives, which is multimodal and discursive, may offer meaningful pathways detection of effective and persuasive signals

FLT3 mutational analysis in acute myeloid leukemia: Advantages and pitfalls with different approaches

FMS-like tyrosine kinase 3 (FLT3) is one of the most closely studied genes in blood diseases. Numerous methods have been adopted for analyses, mainly in acute myeloid leukemia (AML) diagnostic work-up. According to international recommendations, the current gold standard approach allows FLT3 canonical mutations to be investigated, providing the main information for risk assessment and treatment choice. However, the technological improvements of the last decade have permitted “black side” gene exploration, revealing numerous hidden aspects of its role in leukemogenesis. The advent of the next-generation sequencing era emphasizes lights and shadows of FLT3 conventional mutational analysis, highlighting the need for a more comprehensive study of the gene. However, more extensive analysis is opening new, unexplored questions whose impact on clinical outcomes is still unknown. The present work is focused on the main topics regarding FLT3 mutational analysis in AML, debating the strengths and weaknesses of the current gold standard approach. The rights and wrongs of NGS introduction in clinical practice will be discussed, showing that a more extensive knowledge of FLT3 mutational status could lead to reconsidering its role in AML management

Can the new and old drugs exert an immunomodulatory effect in acute myeloid leukemia?

Acute myeloid leukemia (AML) is considered an immune-suppressive neoplasm capable of evading immune surveillance through cellular and environmental players. Increasing knowledge of the immune system (IS) status at diagnosis seems to suggest ever more attention of the crosstalk between the leukemic clone and its immunologic counterpart. During the last years, the advent of novel immunotherapeutic strategies has revealed the importance of immune dysregulation and suppression for leukemia fitness. Considering all these premises, we reviewed the “off-target” effects on the IS of different drugs used in the treatment of AML, focusing on the main advantages of this interaction. The data reported support the idea that a successful therapeutic strategy should consider tailored approaches for performing leukemia eradication by both direct blasts killing and the engagement of the IS

Nanopore Sequencing in Blood Diseases: A Wide Range of Opportunities

The molecular pathogenesis of hematological diseases is often driven by genetic and epigenetic alterations. Next-generation sequencing has considerably increased our genomic knowledge of these disorders becoming ever more widespread in clinical practice. In 2012 Oxford Nanopore Technologies (ONT) released the MinION, the first long-read nanopore-based sequencer, overcoming the main limits of short-reads sequences generation. In the last years, several nanopore sequencing approaches have been performed in various “-omic” sciences; this review focuses on the challenge to introduce ONT devices in the hematological field, showing advantages, disadvantages and future perspectives of this technology in the precision medicine era

Inside the biology of early T-cell precursor acute lymphoblastic leukemia: the perfect trick

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare, distinct subtype of T-ALL characterized by genomic instability, a dismal prognosis and refractoriness to standard chemotherapy. Since its first description in 2009, the expanding knowledge of its intricate biology has led to the definition of a stem cell leukemia with a combined lymphoid-myeloid potential: the perfect trick. Several studies in the last decade aimed to better characterize this new disease, but it was recognized as a distinct entity only in 2016. We review current insights into the biology of ETP-ALL and discuss the pathogenesis, genomic features and their impact on the clinical course in the precision medicine era today

Genomic segmental duplications on the basis of the t(9;22) rearrangement in chronic myeloid leukemia

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Insecure adult attachment and reflective functioning as mechanisms of the relationship between traumatic life events and suicidal ideation: A path analysis

The relationship between traumatic life events and increased suicide risk has been well reported in literature. However, the complex nature of suicidality phenomena still hinders our ability to comprehend the mediation mechanism underlying this association. In this study, we examined the mediating role of adult attachment and reflective functioning in the relationship between traumatic life events and suicidal ideation. Nine hundred and fifty Italian adults completed an online survey evaluating traumatic life events, adult attachment, reflective functioning and suicidal ideation. The path analysis showed that the positive relationship between traumatic life events and suicidal ideation was partially mediated by attachment anxiety and reflective functioning. From a clinical point of view, these results support the relevance of evaluating and improving patients’ ability to mentalize as a part of psychotherapeutic intervention aimed at reducing suicidality in people with a history of traumatic experiences and attachment anxiety

Epitranscriptomics in normal and malignant hematopoiesis

Epitranscriptomics analyze the biochemical modifications borne by RNA and their downstream influence. From this point of view, epitranscriptomics represent a new layer for the control of genetic information and can affect a variety of molecular processes including the cell cycle and the differentiation. In physiological conditions, hematopoiesis is a tightly regulated process that produces differentiated blood cells starting from hematopoietic stem cells. Alteration of this process can occur at different levels in the pathway that leads from the genetic information to the phenotypic manifestation producing malignant hematopoiesis. This review focuses on the role of epitranscriptomic events that are known to be implicated in normal and malignant hematopoiesis, opening a new pathophysiological and therapeutic scenario. Moreover, an evolutionary vision of this mechanism will be provided