Structure from motion systems for architectural heritage. A survey of the internal loggia courtyard of Palazzo dei Capitani, Ascoli Piceno, Italy

We present the results of a point-cloud-based survey deriving from the use of image-based techniques, in particular with multi-image monoscopic digital photogrammetry systems and software, the so-called “structure-from-motion” technique. The aim is to evaluate the advantages and limitations of such procedures in architectural surveying, particularly in conditions that are “at the limit”. A particular case study was chosen: the courtyard of Palazzo dei Capitani del Popolo in Ascoli Piceno, Italy, which can be considered the ideal example due to its notable vertical, rather than horizontal, layout. In this context, by comparing and evaluating the different results, we present experimentation regarding this single case study with the aim of identifying the best workflow to realise a complex, articulated set of representations—using 3D modelling and 2D processing—necessary to correctly document the particular characteristics of such an architectural object

POINT CLOUD-BASED SURVEY FOR CULTURAL HERITAGE. AN EXPERIENCE OF INTEGRATED USE OF RANGE-BASED AND IMAGE-BASED TECHNOLOGY FOR THE SAN FRANCESCO CONVENT IN MONTERUBBIANO

The paper aims at presenting some results of a point cloud-based survey carried out through integrated methodologies based on active and passive 3D acquisition techniques for processing 3D models. This experiment is part of a research project still in progress conducted by an interdisciplinary team from the School of Architecture and Design of Ascoli Piceno and funded by the University of Camerino. We describe an experimentation conducted on the convent of San Francesco located in Monterubbiano town center (Marche, Italy). The whole complex has undergone a number of substantial changes since the year of its foundation in 1247. The survey was based on an approach blending range-based 3D data acquired by a TOF laser scanner and image-based 3D acquired using an UAV equipped with digital camera in order to survey some external parts difficult to reach with TLS. The integration of two acquisition methods aimed to define a workflow suitable to process dense 3D models from which to generate high poly and low poly 3D models useful to describe complex architectures for different purposes such as photorealistic representations, historical documentation, risk assessment analyses based on Finite Element Methods (FEM)

Tumor-Associated Macrophages in Multiple Myeloma: Key Role in Disease Biology and Potential Therapeutic Implications

Multiple myeloma (MM) is characterized by multiple relapse and, despite the introduction of novel therapies, the disease becomes ultimately drug-resistant. The tumor microenvironment (TME) within the bone marrow niche includes dendritic cells, T-cytotoxic, T-helper, reactive B-lymphoid cells and macrophages, with a complex cross-talk between these cells and the MM tumor cells. Tumor-associated macrophages (TAM) have an important role in the MM pathogenesis, since they could promote plasma cells proliferation and angiogenesis, further supporting MM immune evasion and progression. TAM are polarized towards M1 (classically activated, antitumor activity) and M2 (alternatively activated, pro-tumor activity) subtypes. Many studies demonstrated a correlation between TAM, disease progression, drug-resistance and reduced survival in lymphoproliferative neoplasms, including MM. MM plasma cells in vitro could favor an M2 TAM polarization. Moreover, a possible correlation between the pro-tumor effect of M2 TAM and a reduced sensitivity to proteasome inhibitors and immunomodulatory drugs was hypothesized. Several clinical studies confirmed CD68/CD163 double-positive M2 TAM were associated with increased microvessel density, chemoresistance and reduced survival, independently of the MM stage. This review provided an overview of the biology and clinical relevance of TAM in MM, as well as a comprehensive evaluation of a potential TAM-targeted immunotherapy

Drug resistance and minimal residual disease in multiple myeloma

Great progress has been made in improving survival in multiple myeloma (MM) patients over the last 30 years. New drugs have been introduced and complete responses are frequently seen. However, the majority of MM patients do experience a relapse at a variable time after treatment, and ultimately the disease becomes drug-resistant following therapies. Recently, minimal residual disease (MRD) detection has been introduced in clinical trials utilizing novel therapeutic agents to measure the depth of response. MRD can be considered as a surrogate for both progression-free and overall survival. In this perspective, the persistence of a residual therapy-resistant myeloma plasma cell clone can be associated with inferior survivals. The present review gives an overview of drug resistance in MM, i.e., mutation of β5 subunit of the proteasome; upregulation of pumps of efflux; heat shock protein induction for proteasome inhibitors; downregulation of CRBN expression; deregulation of IRF4 expression; mutation of CRBN, IKZF1, and IKZF3 for immunomodulatory drugs and decreased target expression; complement protein increase; sBCMA increase; and BCMA down expression for monoclonal antibodies. Multicolor flow cytometry, or next-generation flow, and next-generation sequencing are currently the techniques available to measure MRD with sensitivity at 10-5. Sustained MRD negativity is related to prolonged survival, and it is evaluated in all recent clinical trials as a surrogate of drug efficacy

The star identification, pointing and tracking system of UVSTAR, an attached payload instrument system for the Shuttle Hitchhiker-M platform

We describe an algorithm for star identification and pointing/tracking of a spaceborne electro-optical system and simulation analyses to test the algorithm. The algorithm will be implemented in the guiding system of UVSTAR, a spectrographic telescope for observations of astronomical and planetary sources operating in the 500-1250 A waveband at approximately 1 A resolution. The experiment is an attached payload and will fly as a Hitchhiker-M payload on the Shuttle. UVSTAR includes capabilities for independent target acquisition and tracking. The spectrograph package has internal gimbals that allow angular movement of plus or minus 3 deg from the central position. Rotation about the azimuth axis (parallel to the Shuttle z axis) and elevation axis (parallel to the Shuttle x axis) will actively position the field of view to center the target of interest in the fields of the spectrographs. The algorithm is based on an on-board catalog of stars. To identify star fields, the algorithm compares the positions of stars recorded by the guiding imager to positions computed from the on-board catalog. When the field has been identified, its position within the guiding imager field of view can be used to compute the pointing corrections necessary to point to a target of interest. In tracking mode, the software uses the past history to predict the quasi-periodic attitude control motions of the shuttle and sends pointing commands to cancel the motion and stabilize UVSTAR on the target. The guiding imager (guider) will have an 80-mm focal length and f/1.4 optics giving a field of view of 6 deg x 4.5 deg using a 385 x 288 pixel intensified CCD. It will be capable of providing high accuracy (better than 2 arc-sec) attitude determination from coarse (6 deg x 4.5 deg) initial knowledge of the pointing direction; and of pointing toward the target. It will also be capable of tracking at the same high accuracy with a processing time of less than a few hundredths of a second

The third dose of mRNA SARS-CoV-2 vaccines enhances the spike-specific antibody and memory B cell response in myelofibrosis patients

Vaccination against SARS-CoV-2 using mRNA-based vaccines has been highly recommended for fragile subjects, including myelofibrosis patients (MF). Available data on the immune responsiveness of MF patients to mRNA SARS-CoV-2 vaccination, and the impact of the therapy with the JAK inhibitor ruxolitinib, are still fragmented. Here, we profile the spike-specific IgG and memory B-cell response in MF patients, treated or not with ruxolitinib, after the second and the third dose of SARS-CoV-2 BNT162b2 (BioNTech) and mRNA-1273 (Moderna) vaccines. Plasma and peripheral blood mononuclear cells samples were collected before vaccination, post the second and the third doses and tested for spike-specific antibodies, ACE2/RBD antibody inhibition binding activity and spike-specific B cells. The third vaccine dose significantly increased the spike-specific IgG titers in both ruxolitinib-treated and untreated patients, and strongly enhanced the percentage of subjects with antibodies capable of in vitro blocking ACE2/RBD interaction, from 50% up to 80%. While a very low frequency of spike-specific B cells was measured in blood 7 days after the second vaccination dose, a strong and significant increase was elicited by the third dose administration, generating a B cell response similar to the one detected in healthy controls. Despite the overall positive impact of the third dose in MF patients, two patients that were under active concomitant immunosuppressive treatment at the time of vaccination, and a patient that received lymphodepleting therapies in the past, remained low responders. The third mRNA vaccine dose strongly increases the SARS-CoV-2 specific humoral and B cell responses in MF patients, promoting a reactivation of the immune response similar to the one observed in healthy controls

Fludarabine, high-dose cytarabine and idarubicin-based induction may overcome the negative prognostic impact of flt3-itd in npm1 mutated aml, irrespectively of flt3-itd allelic Burden

The mutations of NPM1 and FLT3-ITD represent the most frequent genetic aberration in acute myeloid leukemia. Indeed, the presence of an NPM1 mutation reduces the negative prognostic impact of FLT3-ITD in patients treated with conventional \u201c3+7\u201d induction. However, little information is available on their prognostic role with intensified regimens. Here, we investigated the efficacy of a fludarabine, high-dose cytarabine and idarubicin induction (FLAI) in 149 consecutive fit AML patients (median age 52) carrying the NPM1 and/or FLT3-ITD mutation, treated from 2008 to 2018. One-hundred-and-twenty-nine patients achieved CR (86.6%). After a median follow up of 68 months, 3-year overall survival was 58.6%. Multivariate analysis disclosed that both NPM1mut (p < 0.05) and ELN 2017 risk score (p < 0.05) were significant predictors of survival. NPM1-mutated patients had a favorable outcome, with no significant differences between patients with or without concomitant FLT3-ITD (p = 0.372), irrespective of FLT3-ITD allelic burden. Moreover, in landmark analysis, performing allogeneic transplantation (HSCT) in first CR proved to be beneficial only in ELN 2017 high-risk patients. Our data indicate that FLAI exerts a strong anti-leukemic effect in younger AML patients with NPM1mut and question the role of HSCT in 1st CR in NPM1mut patients with concomitant FLT3-ITD

Fludarabine, high-dose cytarabine and idarubicin-based induction may overcome the negative prognostic impact of flt3-itd in npm1 mutated aml, irrespectively of flt3-itd allelic Burden

The mutations of NPM1 and FLT3-ITD represent the most frequent genetic aberration in acute myeloid leukemia. Indeed, the presence of an NPM1 mutation reduces the negative prognostic impact of FLT3-ITD in patients treated with conventional “3+7” induction. However, little information is available on their prognostic role with intensified regimens. Here, we investigated the efficacy of a fludarabine, high-dose cytarabine and idarubicin induction (FLAI) in 149 consecutive fit AML patients (median age 52) carrying the NPM1 and/or FLT3-ITD mutation, treated from 2008 to 2018. One-hundred-and-twenty-nine patients achieved CR (86.6%). After a median follow up of 68 months, 3-year overall survival was 58.6%. Multivariate analysis disclosed that both NPM1mut (p &lt; 0.05) and ELN 2017 risk score (p &lt; 0.05) were significant predictors of survival. NPM1-mutated patients had a favorable outcome, with no significant differences between patients with or without concomitant FLT3-ITD (p = 0.372), irrespective of FLT3-ITD allelic burden. Moreover, in landmark analysis, performing allogeneic transplantation (HSCT) in first CR proved to be beneficial only in ELN 2017 high-risk patients. Our data indicate that FLAI exerts a strong anti-leukemic effect in younger AML patients with NPM1mut and question the role of HSCT in 1st CR in NPM1mut patients with concomitant FLT3-ITD

Overview of the SMART-BEAR Technical Infrastructure

This paper describes a cloud-based platform that offers evidence-based, personalised interventions powered by Artificial Intelligence to help support efficient remote monitoring and clinician-driven guidance to people over 65 who suffer or are at risk of hearing loss, cardiovascular diseases, cognitive impairments, balance disorders, and mental health issues. This platform has been developed within the SMART-BEAR integrated project to power its large-scale clinical pilots and comprises a standards-based data harmonisation and management layer, a security component, a Big Data Analytics system, a Clinical Decision Support tool, and a dashboard component for efficient data collection across the pilot sites