T-cell acute lymphoblastic leukemia/lymphoma is an aggressive hematological neoplasm whose classification is still based on immunophenotypic findings. Frontline treatment encompass high intensity ...combination chemotherapy with good overall survival; however, relapsing/refractory patients have very limited options. In the last years, the understanding of molecular physiopathology of this disease, lead to the identification of a subset of patients with peculiar genetic profile, namely "early T-cell precursors" lymphoblastic leukemia, characterized by dismal outcome and indication to frontline allogeneic bone marrow transplant. In general, the most common mutations occur in the NOTCH1/FBXW7 pathway (60% of adult patients), with a positive prognostic impact. Other pathogenic steps encompass transcriptional deregulation of oncogenes/oncosuppressors, cell cycle deregulation, kinase signaling (including IL7R-JAK-STAT pathway, PI3K/AKT/mTOR pathway, RAS/MAPK signaling pathway, ABL1 signaling pathway), epigenetic deregulation, ribosomal dysfunction, and altered expression of oncogenic miRNAs or long non-coding RNA. The insight in the genomic landscape of the disease paves the way to the use of novel targeted drugs that might improve the outcome, particularly in relapse/refractory patients. In this review, we analyse available literature on T-ALL pathogenesis, focusing on molecular aspects of clinical, prognostic, and therapeutic significance.
Abstract
The Gas Pixel Detector (GPD) is an X-ray polarimeter to fly onboard IXPE and other missions. To correctly measure the source polarization, the response of IXPE’s GPDs to unpolarized ...radiation has to be calibrated and corrected. In this paper, we describe the way such response is measured with laboratory sources and the algorithm to apply such correction to the observations of celestial sources. The latter allows to correct the response to polarization of single photons, therefore allowing great flexibility in all the subsequent analysis. Our correction approach is tested against both monochromatic and nonmonochromatic laboratory sources and with simulations, finding that it correctly retrieves the polarization up to the statistical limits of the planned IXPE observations.
Epstein-Barr virus (EBV) infection is correlated with several lymphoproliferative disorders, including Hodgkin disease, Burkitt lymphoma, diffuse large B-cell lymphoma (DLBCL), and post-transplant ...lymphoproliferative disorder (PTLD). The oncogenic EBV is present in 80% of PTLD. EBV infection influences immune response and has a causative role in the oncogenic transformation of lymphocytes. The development of PTLD is the consequence of an imbalance between immunosurveillance and immunosuppression. Different approaches have been proposed to treat this disorder, including suppression of the EBV viral load, reduction of immune suppression, and malignant clone destruction. In some cases, upfront chemotherapy offers better and durable clinical responses. In this work, we elucidate the clinicopathological and molecular-genetic characteristics of PTLD to clarify the biological differences of EBV(+) and EBV(-) PTLD. Gene expression profiling, next-generation sequencing, and microRNA profiles have recently provided many data that explore PTLD pathogenic mechanisms and identify potential therapeutic targets. This article aims to explore new insights into clinical behavior and pathogenesis of EBV(-)/(+) PTLD with the hope to support future therapeutic studies.
Granular Computing is a powerful information processing paradigm, particularly useful for the synthesis of pattern recognition systems in structured domains (e.g., graphs or sequences). According to ...this paradigm, granules of information play the pivotal role of describing the underlying (possibly complex) process, starting from the available data. Under a pattern recognition viewpoint, granules of information can be exploited for the synthesis of semantically sound embedding spaces, where common supervised or unsupervised problems can be solved via standard machine learning algorithms. In this work, we show a comparison between different strategies for the automatic synthesis of information granules in the context of graph classification. These strategies mainly differ on the specific topology adopted for subgraphs considered as candidate information granules and the possibility of using or neglecting the ground-truth class labels in the granulation process. Computational results on 10 different open-access datasets show that by using a class-aware granulation, performances tend to improve (regardless of the information granules topology), counterbalanced by a possibly higher number of information granules.
The combination of bortezomib-melphalan-prednisone (VMP) is a new standard of care for newly diagnosed multiple myeloma. This phase III study examined the efficacy of the four-drug combination of ...bortezomib-melphalan-prednisone-thalidomide (VMPT) followed by maintenance with bortezomib-thalidomide (VMPT-VT) compared with VMP treatment alone in untreated multiple myeloma patients who are ineligible for autologous stem-cell transplantation.
A total of 511 patients were randomly assigned to receive nine cycles of VMPT followed by continuous VT as maintenance, or nine cycles of VMP at the same doses with no additional therapy. The primary end point was progression-free survival.
The 3-year estimates of progression-free survival were 56% in patients receiving VMPT-VT and 41% in those receiving VMP (hazard ratio HR, 0.67; 95% CI, 0.50 to 0.90; P = .008). At 3 years, the cumulative proportions of patients who did not go on to the next therapy were 72% with VMPT-VT and 60% with VMP (HR, 0.58; 95% CI, 0.50 to 0.90; P = .007). Complete response rates were 38% in the VMPT-VT group and 24% in the VMP group (P < .001). The 3-year overall survival was 89% with VMPT-VT and 87% with VMP (HR, 0.92; 95% CI, 0.53 to 1.60; P = .77). Grade 3 to 4 neutropenia (38% v 28%; P = .02), cardiologic events (10% v 5%; P = .04), and thromboembolic events (5% v 2%; P = .08) were more frequent among patients assigned to the VMPT-VT group than among those assigned to the VMP group; treatment-related deaths were 4% with VMPT-VT and 3% with VMP.
VMPT followed by VT as maintenance was superior to VMP alone in patients with multiple myeloma who are ineligible for autologous stem-cell transplantation.
In spite of an increasing array of investigations, the relationships between viral infections and allogeneic hematopoietic stem cell transplantation (HSCT) are still controversial, and almost ...exclusively regard DNA viruses. Viral infections
account for a considerable risk of morbidity and mortality among HSCT recipients, and available antiviral agents have proven to be of limited effectiveness. Therefore, an optimal management of viral infection represents a key point in HSCT strategies. On the other hand, viruses bear the potential of shaping immunologic recovery after HSCT, possibly interfering with control of the underlying disease and graft-
-host disease (GvHD), and eventually with HSCT outcome. Moreover, preliminary data are available about the possible role of some virome components as markers of immunologic recovery after HSCT. Lastly, HSCT may exert an immunotherapeutic effect against some viral infections, notably HIV and HTLV-1, and has been considered as an eradicating approach in these indications.
We present the NEFOCAST project (named by the contraction of "Nefele", which is the Italian spelling for the mythological cloud nymph Nephele, and "forecast"), funded by the Tuscany Region, about the ...feasibility of a system for the detection and monitoring of precipitation fields over the regional territory based on the use of a widespread network of new-generation Eutelsat "SmartLNB" (smart low-noise block converter) domestic terminals. Though primarily intended for interactive satellite services, these devices can also be used as weather sensors, as they have the capability of measuring the rain-induced attenuation incurred by the downlink signal and relaying it on an auxiliary return channel. We illustrate the NEFOCAST system architecture, consisting of the network of ground sensor terminals, the space segment, and the service center, which has the task of processing the information relayed by the terminals for generating rain field maps. We discuss a few methods that allow the conversion of a rain attenuation measurement into an instantaneous rainfall rate. Specifically, we discuss an exponential model relating the specific rain attenuation to the rainfall rate, whose coefficients were obtained from extensive experimental data. The above model permits the inferring of the rainfall rate from the total signal attenuation provided by the SmartLNB and from the link geometry knowledge. Some preliminary results obtained from a SmartLNB installed in Pisa are presented and compared with the output of a conventional tipping bucket rain gauge. It is shown that the NEFOCAST sensor is able to track the fast-varying rainfall rate accurately with no delay, as opposed to a conventional gauge.
Clouds cover substantial parts of the Earth's surface and they are one of the most essential components of the global climate system impacting the Earth's radiation balance as well as the water cycle ...redistributing water around the globe as precipitation. Therefore, continuous observation of clouds is of primary interest in climate and hydrological studies. This work documents the first efforts in Italy in remote sensing clouds and precipitation using a combination of K- and W-band (24 and 94 GHz, respectively) radar profilers. Such a dual-frequency radar configuration has not been widely used yet, but it could catch on in the near future given its lower initial cost and ease of deployment for commercially available systems at 24 GHz, with respect to more established configurations. A field campaign running at the Casale Calore observatory at the University of L'Aquila, Italy, nestled in the Apennine mountain range is described. The campaign features are preceded by a review of the literature and the underpinning theoretical background that might help newcomers, especially in the Italian community, to approach cloud and precipitation remote sensing. This activity takes place in interesting time for radar sensing clouds and precipitation, stimulated both by the launch of the ESA/JAXA EarthCARE satellite missions scheduled in 2024, which will have on-board, among other instruments, a W-band Doppler cloud radar and the proposal of new missions using cloud radars currently undergoing their feasibility studies (e.g., WIVERN and AOS in Europe and Canada, and U.S., respectively).
In-cloud motion vector retrieval is of great interest in several atmospheric science research fields. Short time extrapolation of radar data (precipitation nowcasting), assimilation into numerical ...weather prediction models, study of atmospheric circulation, as well as reference scenarios for future satellite missions, are glaring example where the knowledge of in-cloud motion vectors can play a relevant role. In this work, a dataset of nearly one-year and half of measurements collected by ground-based weather radars over the Italian peninsula, is used to perform the reconstruction of horizontal in-cloud rain motion vectors (RMVs) using both optical flow-based solutions from literature and an innovative extension of the multiple Doppler solution that make use of mosaicked Doppler radar data. The outcomes of the techniques imple-mented are analyzed in terms of reference Doppler measurements, reanalysis wind fields from ERA5 and evaluating the impact of the RMVs in a semilagrangian precipitation nowcasting framework. To the author knowledge, this is the first attempt in quantitatively evaluating RMVs. Results show that the use of Doppler information enhances the dynamic range of the retrieved RMV intensity with respect to optical flow-based solutions giving a better agreement with the ERA5 too. In terms of precipitation nowcasting, the use of Doppler-driven RMV does not give significant improvements due to gradients shown by RMV intensity when constrained with the measured Doppler.
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