Resilient Drone Mission Management and Route Optimization in Drone Delivery Context

The last two decades were characterized by a rapidly increasing of innovative solutions in the microelectronic field, having therefore a significant impact on a huge set of applicative scenarios. This aspect allows the development and improvement of new solutions, giving the possibility of growth and development of new markets, such as the drones ones. Actually, in the unmanned field we have seen an exponential growth of the market, given not only from the increased computing capabilities, but also by a more efficient developed hardware, thus leading to the definition of innovative uses, service paradigms and applications. The latter span in several different areas, from agriculture monitoring to society's services including the Package Delivery which immediately plays a strategic role in the modern society. These types of applications took place mainly in an urban environment, highlighting therefore new rules, needs and management system in order to accommodate the mission's achievement guaranteeing at the same time a high degree of resilience, citizen safety and risks minimization. Furthermore, to assist these types of operations, T-DROMES, a RPAS (Remotely Piloted Aerial Systems) fleet and mission management solution, was developed allowing to scale-up the use of drones in complex operations from a geographical and mission point of view, in different applicative scenarios. The paper aims therefore to presents the tools capabilities and how the developed architecture is able to manage the entire mission for any context scenario and how the developed platforms and tools can be a valid framework for developing new operative working models

Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication

The ability of PRC1 and PRC2 to promote proliferation is a main feature that links polycomb (PcG) activity to cancer. PcGs silence the expression of the tumour suppressor locus Ink4a/Arf, whose products positively regulate pRb and p53 functions. Enhanced PcG activity is a frequent feature of human tumours, and PcG inhibition has been proposed as a strategy for cancer treatment. However, the recurrent inactivation of pRb/p53 responses in human cancers raises a question regarding the ability of PcG proteins to affect cellular proliferation independently from this checkpoint. Here we demonstrate that PRCs regulate cellular proliferation and transformation independently of the Ink4a/Arf-pRb-p53 pathway. We provide evidence that PRCs localize at replication forks, and that loss of their function directly affects the progression and symmetry of DNA replication forks. Thus, we have identified a novel activity by which PcGs can regulate cell proliferation independently of major cell cycle restriction checkpoints. \ua92014 Macmillan Publishers Limited. All rights reserved

Attitudes and Beliefs towards Rotavirus Vaccination in a Sample of Italian Women: A Cross-Sectional Study

(1) Background: Rotavirus is the leading cause of severe diarrhea and dehydration in infants and young children worldwide. Despite the proven benefits of vaccination, vaccine hesitancy and refusal remains a significant barrier to achieving high vaccination coverage in many countries, such as Italy. (2) Methods: An online survey was conducted among women aged between 18 and 50 years from Abruzzo Region, Italy. The survey was composed of two main sections: demographic characteristics and attitudes and knowledge about rotavirus vaccination, based on a five-point Likert scale. Logistic regression analysis was performed to evaluate factors associated with willingness to get the rotavirus vaccination. (3) Results: A total of 414 women were enrolled in the study. Women who were unaware of rotavirus more frequently had a lower education level (university degree 62.5% vs. 78.7%, p = 0.004) and reported having no children (p p < 0.001). (4) Conclusions: The present study showed low levels of knowledge and attitudes towards rotavirus vaccination. These results highlight the need for developing and improving additional public education programs for parents

The Burden of Streptococcus pneumoniae-Related Admissions and In-Hospital Mortality: A Retrospective Observational Study between the Years 2015 and 2022 from a Southern Italian Province

Streptococcus pneumoniae (SP) has high worldwide incidence and related morbidity and mortality, particularly among children and geriatric patients. SP infection could manifest with pneumonia, bacteremia, sepsis, meningitis, and osteomyelitis. This was a retrospective study aimed at evaluating the incidence, comorbidities, and factors associated with in-hospital mortality of pneumococcal disease-related hospitalization in a province in southern Italy from the years 2015 to 2022. This study was performed in the Local Health Authority (LHA) of Pescara. Data were collected from hospital discharge records (HDRs): this database is composed of 288,110 discharge records from LHA Pescara’s hospitals from 2015 to 2022. Streptococcus Pneumoniae-related hospitalizations were about 5% of the hospitalizations; 67% of these were without comorbidities; 21% were with one comorbidity; and 13% were with two or more comorbidities. Regarding mortality of SP infection, the most affected age group was older people, with the percentage of cases among the over-65s being more than 50% compared to the other age groups. HDRs represent a valid and useful epidemiological tool for evaluating the direct impact of pneumococcal disease on the population and also indirectly for evaluating the effectiveness of vaccination strategies and directing them

Contrast-enhanced power doppler of the intestinal wall in the evaluation of patients with Crohn disease

Crohn disease (CD) manifests with highly variable signs and symptoms, and assessment of the status of the disease in the single patient can be difficult. This study was conducted to evaluate the efficacy of power colour Doppler ultrasonography, with and without echo-enhancement, in distinguishing active from quiescent CD

Immunostimulation of Fibrous Nucleic Acid Nanoparticles Can be Modulated through Aptamer-Based Functional Moieties: Unveiling the Structure–Activity Relationship and Mechanistic Insights

Fibrous nanomaterials containing silica, titanium oxide, and carbon nanotubes are notoriously known for their undesirable inflammatory responses and associated toxicities that have been extensively studied in the environmental and occupational toxicology fields. Biopersistance and inflammation of “hard” nanofibers prevent their broader biomedical applications. To utilize the structural benefits of fibrous nanomaterials for functionalization with moieties of therapeutic significance while preventing undesirable immune responses, researchers employ natural biopolymersRNA and DNAto design “soft” and biodegradable nanomaterials with controlled immunorecognition. Nucleic acid nanofibers have been shown to be safe and efficacious in applications that do not require their delivery into the cells such as the regulation of blood coagulation. Previous studies demonstrated that unlike traditional therapeutic nucleic acids (e.g., CpG DNA oligonucleotides) nucleic acid nanoparticles (NANPs), when used without a carrier, are not internalized by the immune cells and, as such, do not induce undesirable cytokine responses. In contrast, intracellular delivery of NANPs results in cytokine responses that are dependent on the physicochemical properties of these nanomaterials. However, the structure–activity relationship of innate immune responses to intracellularly delivered fibrous NANPs is poorly understood. Herein, we employ the intracellular delivery of model RNA/DNA nanofibers functionalized with G-quadruplex-based DNA aptamers to investigate how their structural properties influence cytokine responses. We demonstrate that nanofibers’ scaffolds delivered to the immune cells using lipofectamine induce interferon response via the cGAS-STING signaling pathway activation and that DNA aptamers incorporation shields the fibers from recognition by cGAS and results in a lower interferon response. This structure–activity relationship study expands the current knowledge base to inform future practical applications of intracellularly delivered NANPs as vaccine adjuvants and immunotherapies

Anagrelide in Essential Thrombocythemia (ET): Results from 150 patients over 25 years by the “Ph1‐negative Myeloproliferative Neoplasms Latium Group”

Background and aims: Anagrelide is a drug effective in reducing platelet counts in essential thrombocythemia (ET) and Ph1-negative myeloproliferative neoplasms. The aim of this study was to evaluate the real-life use of anagrelide in patients with ET followed over 25 years at the Haematological Institutes belonging to “Ph1-negative Myeloproliferative Neoplasms Latium Group.”. Patients and methods: Eligibility criteria were diagnosis of ET and treatment with anagrelide. Data were collected through an ad hoc case report form. Results: One hundred and fifty patients received anagrelide for a median time of 7.4 years (0.1-23.2). Anagrelide was administered as first-line therapy in 34.7% of patients, as second-line in 52% and as third-line in 13.3%: 85.4% responded to therapy. Sixty-eight/136 evaluable patients reported side effects: palpitations, peripheral vasodilation, anaemia, diarrhoea and gastric distress. Fourteen thrombotic (arterial 10, venous 4) and 51 bleeding events (minor 48, major 3) occurred. Sixteen/150 (10.6%) patients developed secondary myelofibrosis and 3/150 (2%) an acute myeloid leukaemia. Conclusions: In our experience, anagrelide is an effective drug in reducing platelet levels in a high percentage of patients with ET. It is especially addressed to younger people. A careful assessment of the thrombotic risk and monitoring of cardiac function, at diagnosis and during follow-up, is mandatory

Imatinib In Very Elderly CML Patients: What Can We Achieve?

In the “real world” of clinical practice, many very elderly CML patients have been treated with imatinib (IM), but there are few data on the results and the best initial dosage in such patients. To highlight peculiar aspects of toxicity and efficacy of IM in this subset which accounts for at least 10-15% of all CML cases, we retrospectively revised 156 CML patients in chronic phase treated with IM when aged > 75 years from 23 haematological Institutions in Italy; there were 85 males and 71 females, median age at IM start was 78.4 years (IR 76.1 – 81.4), Sokal Risk at diagnosis was low in 2 patients, intermediate in 90, high in 50 and not evaluable in 14. One or more concomitant diseases requiring specific treatments were present in 144/156 patients (92.3%), with 94 patients (60.2%) assuming 3 or more concomitant drugs. Thirty patients (19.2%) were in late chronic phase (≥ 12 months from diagnosis) and pretreated (25 with HU and 5 with IFN) before starting IM; on the whole, median time from diagnosis to IM was 1.2 months (IR 0.5 – 3.6). Starting dose of IM was 400 mg/day in 117 patients (75.0%) and 300 mg/day or less in 39 patients (25.0%); overall, 59 patients (37.8%) (52/117 at 400 mg starting dose and 7/39 at ³ 300 mg starting dose) needed a dose reduction and 18 (11.5%) discontinued IM for toxicity (early toxicity in 13 and late toxicity in 5). Excluding the 13 patients who discontinued IM due to early toxicity, maximum tolerated daily dose during treatment was 400 mg in 63 patients, 300 mg in 51 patients and < 300 mg in 29 patients. According to CTC-AE, grade 3 – 4 hematological and extra-hematological toxicities were observed in 34 (21.7%) and 34 (21.7%) patients, respectively; 5 patients (3.2%) presented a pleural effusion during IM treatment. After a median treatment period of 29.4 months (IR 7.9 – 54.4), 8 patients (5.1%) are still too early (< 6 months of treatment), 13 (8.3%) discontinued IM due to early toxicity, 3 (1.9%) were resistant and 1 (0.7%) died from unrelated cause early after IM initiation: the remaining 131 patients (84.6%) achieved a complete haematological response (CHR). Among these 131 patients in CHR, 11 refused any other karyotipic or molecular evaluation (1 lost CHR and shifted to hydroxyurea, 4 are still alive in CHR, 6 died in CHR from unrelated causes), 17 achieved CHR only and 103 (66.0% of all 156 patients) achieved a cytogenetic response (CyR), which was major in 11 patients and complete (CCyR) in 92 (58.9% of all 156 patients). In addition, among the 92 patients in CCyR, 62 (39.7% of all 156 patients) achieved a molecular response (major molecular response in 40 patients and complete molecular response with an undetectable BCR/ABL hybrid gene at qualitative nested PCR in 22 patients). After a median follow-up of 34.0 months (IR 12.9 – 60.0), 36 patients have died (5 from disease progression and 31 from unrelated causes), 4 patients were lost to follow-up and 116 are still alive: 2-year and 4-year overall survival were 90.2% (CI95% 84.8 - 95.6) and 76.8% (CI95% 68.6 - 85.0), respectively. In conclusion, results from this large unselected cohort of patients show that should be definitely considered unethical to avoid IM therapy to any elderly patient; no upper age limit should be given but also very elderly (and with concomitant severe diseases) patients should have this chance of cure. The role of a reduced starting dose of IM warrants further studies

Relevance of comorbidities on initial combination therapy in pulmonary arterial hypertension

Rationale Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting. Methods The study enrolled 181 treatment-naive PAH patients with a 6-month (IQR 144–363 days) right heart catheterisation and risk assessment after initial oral combination therapy. Results Group A included 96 (53.0%) patients without cardiac comorbidities; Group B included 54 (29.8%) patients with one cardiac comorbidity; Group C included 31 (17.1%) patients with two cardiac comorbidities or more. Group C patients were older with a balanced sex distribution. There was a significant difference in PVR reduction moving from the absence to one or at least two cardiac comorbidities, respectively: median −45.0%, −30.3%, −24.3%. A European Respiratory Society/European Society of Cardiology low-risk status was present at first follow-up in 50 (52.0%) patients in Group A, 19 (35.1%) in Group B and 9 (29.0%) in Group C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group A, 15 (27.7%) in Group B and 7 (22.6%) in Group C. Group A patients were 2.3 times more likely to achieve/maintain a low-risk status compared with Group B and C (OR 2.27, 95% CI 1.15–4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities. Conclusion Initial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment-induced decrease in PVR

The paradox of pulmonary arterial hypertension in Italy in the COVID-19 era: is risk of disease progression around the corner?

36noObjective The coronavirus disease-2019 (COVID-19) oubreak has led to significant restrictions on routine medical care. We conducted a multicenter nationwide survey of PAH patients aiming at determining the consequences of the Governance measures on PAH management and risk of poor outcome in patients with COVID-19. Meterials and Methods Demographic data, number of in-person visits, 6-min walk and echocardiographic tests, BNP/NT-proBNP tests, WHO functional class assessment, presence of elective and non-elective hospitalisation, need for treatment escalation/initiation, newly diagnosed PAH, incidence of COVID-19 and mortality rates were considered in the present study including 25 Italian centers. Data were collected, double checked and tracked by institutional records, between the 1st March and 1st May 2020 to coincide with the first peak of COVID-19 and compared with the same time-period in 2019. Results Among 1922 PAH patients the incidence of SARS- CoV-2 infection and COVID-19 was 1.0% and 0.46%, respectively, the latter comparable to the overall Italian population (0.34%), but associated with 100% mortality. Less systematic activities were converted into more effective remote interfacing between clinicians and PAH patients allowing lower rates of hospitalisation and related death compared with 2019 (1.2% and 0.3% versus 1.9% and 0.5%, respectively; p<0.001). High level of attention is needed to avoid the potential risk of disease progression related to less aggressive escalation of treatment and the reduction in new PAH diagnosis compared with 2019. Conclusion Cohesive partnership of health care providers with regional public health officials is needed to prioritise PAH patients for remote monitoring by dedicated tools.noneopenRoberto Badagliacca, Silvia Papa, Michele D'Alto, Stefano Ghio, Piergiuseppe Agostoni, Pietro Ameri, Paola Argiento, Natale Daniele Brunetti, Vito Casamassima, Gavino Casu, Nadia Cedrone, Marco Confalonieri, Marco Corda, Michele Correale, Carlo D'Agostino, Lucrezia De Michele, Giulia Famoso, Giuseppe Galgano, Alessandra Greco, Carlo Mario Lombardi, Giovanna Manzi, Rosalinda Madonna, Valentina Mercurio, Massimiliano Mulè, Giuseppe Paciocco, Antonella Romaniello, Emanuele Romeo, Laura Scelsi, Walter Serra, Davide Stolfo, Matteo Toma, Marco Vatrano, Patrizio Vitulo, Pietro Geri, Paola Confalonieri, Carmine Dario VizzaBadagliacca, Roberto; Papa, Silvia; D'Alto, Michele; Ghio, Stefano; Agostoni, Piergiuseppe; Ameri, Pietro; Argiento, Paola; Daniele Brunetti, Natale; Casamassima, Vito; Casu, Gavino; Cedrone, Nadia; Confalonieri, Marco; Corda, Marco; Correale, Michele; D'Agostino, Carlo; De Michele, Lucrezia; Famoso, Giulia; Galgano, Giuseppe; Greco, Alessandra; Mario Lombardi, Carlo; Manzi, Giovanna; Madonna, Rosalinda; Mercurio, Valentina; Mulè, Massimiliano; Paciocco, Giuseppe; Romaniello, Antonella; Romeo, Emanuele; Scelsi, Laura; Serra, Walter; Stolfo, Davide; Toma, Matteo; Vatrano, Marco; Vitulo, Patrizio; Geri, Pietro; Confalonieri, Paola; Dario Vizza, Carmin