Streamlining Temporal Formal Verification over Columnar Databases

Recent findings demonstrate how database technology enhances the computation of formal verification tasks expressible in linear time logic for finite traces (LTLf). Human-readable declarative languages also help the common practitioner to express temporal constraints in a straightforward and accessible language. Notwithstanding the former, this technology is in its infancy, and therefore, few optimization algorithms are known for dealing with massive amounts of information audited from real systems. We, therefore, present four novel algorithms subsuming entire LTLf expressions while outperforming previous state-of-the-art implementations on top of KnoBAB, thus postulating the need for the corresponding, leading to the formulation of novel xtLTLf-derived algebraic operators

Advancements and Challenges in IoT Simulators: A Comprehensive Review

The Internet of Things (IoT) has emerged as an important concept, bridging the physical and digital worlds through interconnected devices. Although the idea of interconnected devices predates the term “Internet of Things”, which was coined in 1999 by Kevin Ashton, the vision of a seamlessly integrated world of devices has been accelerated by advancements in wireless technologies, cost-effective computing, and the ubiquity of mobile devices. This study aims to provide an in-depth review of existing and emerging IoT simulators focusing on their capabilities and real-world applications, and discuss the current challenges and future trends in the IoT simulation area. Despite substantial research in the IoT simulation domain, many studies have a narrow focus, leaving a gap in comprehensive reviews that consider broader IoT development metrics, such as device mobility, energy models, Software-Defined Networking (SDN), and scalability. Notably, there is a lack of literature examining IoT simulators’ capabilities in supporting renewable energy sources and their integration with Vehicular Ad-hoc Network (VANET) simulations. Our review seeks to address this gap, evaluating the ability of IoT simulators to simulate complex, large-scale IoT scenarios and meet specific developmental requirements, as well as examining the current challenges and future trends in the field of IoT simulation. Our systematic analysis has identified several significant gaps in the current literature. A primary concern is the lack of a generic simulator capable of effectively simulating various scenarios across different domains within the IoT environment. As a result, a comprehensive and versatile simulator is required to simulate the diverse scenarios occurring in IoT applications. Additionally, there is a notable gap in simulators that address specific security concerns, particularly battery depletion attacks, which are increasingly relevant in IoT systems. Furthermore, there is a need for further investigation and study regarding the integration of IoT simulators with traffic simulation for VANET environments. In addition, it is noteworthy that renewable energy sources are underrepresented in IoT simulations, despite an increasing global emphasis on environmental sustainability. As a result of these identified gaps, it is imperative to develop more advanced and adaptable IoT simulation tools that are designed to meet the multifaceted challenges and opportunities of the IoT domain

IMPAβ: Incremental modal pushover analysis for bridges

In the present study, the incremental modal pushover analysis (IMPAβ), a pushover-based approach already proposed and applied to buildings by the same authors, was revised and proposed for bridges (IMPAβ). Pushover analysis considers the effects of higher modes on the structural response. Bridges are structurally very different from multi-story buildings, where multimodal pushover (MPA) has been developed and is currently used. In bridges, consideration for higher modes is often necessary: The responses of some structural elements of the bridge (e.g., piers) influence the overall bridge response. Therefore, the failure of these elements can determine the failure of the whole structure, even if they give a small contribution total base shear. Incremental dynamic analysis (IDA) requires input accelerograms for high intensities, which are rare in the databases, while scaling of generated accelerograms with a simple increment of the scaling acceleration is not appropriate. This fact renders IDA, which is by its nature time-consuming, not straightforward. On the contrary, the change of input spectrum required by IMPA is simple. IMPAβ also utilizes a simple complementary method coupled to MPA, to obtain bounds at very high seismic intensities. Finally, the two incremental methods based on static nonlinear and dynamic nonlinear analyses are compared

Time-dependent cyclic behavior of reinforced concrete bridge columns under chlorides-induced corrosion and rebars buckling

This study presents the results of a refined numerical investigation meant at understanding the time-dependent cyclic behavior of reinforced concrete (RC) bridge columns under chlorides-induced corrosion. The chloride ingress in the cross-section of the bridge column is simulated, taking into account the effects of temperature, humidity, aging, and corrosion-induced cover cracking. Once the partial differential equations governing such multiphysics problem are solved through the finite-element method, the loss of reinforcement steel bars cross-section is calculated based on the estimated corrosion current density. The nonlinear cyclic response of the RC bridge column under corrosion is, thus, determined by discretizing its cross-sections into several unidirectional fibers. In particular, the nonlinear modeling of the corroded longitudinal rebars exploits a novel proposal for the estimation of the ultimate strain in tension and also accounts for buckling under compression. A parametric numerical study is finally conducted for a real case study to unfold the role of corrosion pattern and buckling mode of the longitudinal rebars on the time variation of capacity and ductility of RC bridge columns

Case Report: Heterozygous Germline Variant in EIF6 Additional to Biallelic SBDS Pathogenic Variants in a Patient With Ribosomopathy Shwachman–Diamond Syndrome

Background: Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive ribosomopathy mainly characterized by exocrine pancreatic insufficiency, skeletal alterations, neutropenia, and a relevant risk of hematological transformation. At least 90% of SDS patients have pathogenic variants in SBDS, the first gene associated with the disease with very low allelic heterogeneity; three variants, derived from events of genetic conversion between SBDS and its pseudogene, SBDSP1, provided the alleles observed in about 62% of SDS patients.Methods: We performed a reanalysis of the available WES files of a group of SDS patients with biallelic SBDS pathogenic variants, studying the results by next bioinformatic and protein structural analysis. Parallelly, careful clinical attention was given to the patient focused in this study.Results: We found and confirmed in one SDS patient a germline heterozygous missense variant (c.100T>C; p.Phe34Leu) in the EIF6 gene. This variant, inherited from his mother, has a very low frequency, and it is predicted as pathogenic, according to several in silico prediction tools. The protein structural analysis also envisages the variant could reduce the binding to the nascent 60S ribosomal.Conclusion: This study focused on the hypothesis that the EIF6 germline variant mimics the effect of somatic deletions of chromosome 20, always including the locus of this gene, and similarly may rescue the ribosomal stress and ribosomal dysfunction due to SBDS mutations. It is likely that this rescue may contribute to the stable and not severe hematological status of the proband, but a definite answer on the role of this EIF6 variant can be obtained only by adding a functional layer of evidence. In the future, these results are likely to be useful for selected cases in personalized medicine and therapy

Suitability of nanoparticles to face benzo(A)pyrene-induced genetic and chromosomal damage in m. galloprovincialis. an in vitro approach

Benzo(a)pyrene (B(a)P) is a well-known genotoxic agent, the removal of which from environmental matrices is mandatory, necessitating the application of cleaning strategies that are harmless to human and environmental health. The potential application of nanoparticles (NPs) in the remediation of polluted environments is of increasing interest. Here, specifically designed NPs were selected as being non-genotoxic and able to interact with B(a)P, in order to address the genetic and chromosomal damage it produces. A newly formulated pure anatase nano-titanium (nano-TiO2), a commercial mixture of rutile and anatase, and carbon black-derived hydrophilic NPs (HNP) were applied. Once it had been ascertained that the NPs selected for the work did not induce genotoxicity, marine mussel gill biopsies were exposed in vitro to B(a)P (2 µg/mL), alone and in combination with the selected NPs (50 µg/mL nano-TiO2, 10 µg/mL HNP). DNA primary reversible damage was evaluated by means of the Comet assay. Chromosomal persistent damage was assessed on the basis of micronuclei frequency and nuclear abnormalities by means of the Micronucleus-Cytome assay. Transmission Electron Microscopy (TEM) was performed to investigate the mechanism of action exerted by NPs. Pure Anatase n-TiO2 was found to be the most suitable for our purpose, as it is cyto-and genotoxicity free and able to reduce the genetic and chromosomal damage associated with exposure to B(a)P

Immunogenicity and safety after the third dose of BNT162b2 anti-SARS-CoV-2 vaccine in patients with solid tumors on active treatment: a prospective cohort study

Background: Although a full course of coronavirus disease 2019 (COVID-19) vaccine is effective in cancer patients, the duration of the protection and the efficacy of a booster dose against the new variants remain unknown. We prospectively evaluated the immunogenicity of the third dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BNT162b2 messenger RNA vaccine in cancer patients undergoing active treatment. Patients and methods: Patients with solid cancer, vaccinated with a booster dose during active treatment, were enrolled in this study. Patients were classified into SARS-CoV-2 naïve (without previous COVID-19 infection) and SARS-CoV-2 experienced (with previous COVID-19 infection). Neutralizing antibody (NT Ab) titer and total anti-Spike immunoglobulin G (IgG) concentration were quantified in serum. Heparinized whole blood samples were used for SARS-CoV-2 Interferon Gamma Release Assay (IGRA). The primary endpoint was to assess the increase of IgG antibody level between baseline and 3 weeks after the booster. Results: One hundred and forty-two consecutive patients were recruited. In SARS-CoV-2-naïve subjects, the median level of IgG was 157 BAU/ml [interquartile range (IQR) 62-423 BAU/ml] at T0 and reached a median of 2080 BAU/ml (IQR 2080-2080 BAU/ml) at 3 weeks after booster administration (T1; P < 0.0001). A median 16-fold increase of SARS-CoV-2 NT Ab titer (IQR 4-32) was observed in naïve subjects (from median 20, IQR 10-40, to median 640, IQR 160-640; P < 0.0001). Median interferon-γ level at T1 was significantly higher than that measured at T0 in SARS-CoV-2-naïve subjects (P = 0.0049) but not in SARS-CoV-2-experienced patients. The median level of SARS-CoV-2 NT Abs was 32-fold lower against Omicron compared to the wild-type strain (P = 0.0004) and 12-fold lower compared to the Delta strain (P = 0.0110). Conclusions: The third dose is able to trigger both the humoral and the cell-mediated immune response in cancer patients on active treatment. Our preliminary data about the neutralization of the SARS-CoV-2 vaccine against variants of concern seem to confirm the lower vaccine activity

Analysis of the humoral and cellular immune response after a full course of BNT162b2 anti-SARS-CoV-2 vaccine in cancer patients treated with PD-1/PD-L1 inhibitors with or without chemotherapy: an update after 6 months of follow-up

Background: The durability of immunogenicity of SARS-CoV-2 vaccination in cancer patients remains to be elucidated. We prospectively evaluated the immunogenicity of the vaccine in triggering both the humoral and the cell-mediated immune response in cancer patients treated with anti-programmed cell death protein 1/programmed death-ligand 1 with or without chemotherapy 6 months after BNT162b2 vaccine. Patients and methods: In the previous study, 88 patients were enrolled, whereas the analyses below refer to the 60 patients still on immunotherapy at the time of the follow-up. According to previous SARS-CoV-2 exposure, patients were classified as SARS-CoV-2-naive (without previous SARS-CoV-2 exposure) and SARS-CoV-2-experienced (with previous SARS-CoV-2 infection). Neutralizing antibody (NT Ab) titer against the B.1.1 strain and total anti-spike immunoglobulin G concentration were quantified in serum samples. The enzyme-linked immunosorbent spot assay was used for quantification of anti-spike interferon-γ (IFN-γ)-producing cells/106 peripheral blood mononuclear cells. Fifty patients (83.0%) were on immunotherapy alone, whereas 10 patients (7%) were on chemo-immunotherapy. We analyzed separately patients on immunotherapy and patients on chemo-immunotherapy. Results: The median T-cell response at 6 months was significantly lower than that measured at 3 weeks after vaccination [50 interquartile range (IQR) 20-118.8 versus 175 IQR 67.5-371.3 IFN-γ-producing cells/106 peripheral blood mononuclear cells; P < 0.0001]. The median reduction of immunoglobulin G concentration was 88% in SARS-CoV-2-naive subjects and 2.1% in SARS-CoV-2-experienced subjects. SARS-CoV-2 NT Ab titer was maintained in SARS-CoV-2-experienced subjects, whereas a significant decrease was observed in SARS-CoV-2-naive subjects (from median 1 : 160, IQR 1 : 40-1 : 640 to median 1 : 20, IQR 1 : 10-1 : 40; P < 0.0001). A weak correlation was observed between SARS-CoV-2 NT Ab titer and spike-specific IFN-γ-producing cells at both 6 months and 3 weeks after vaccination (r = 0.467; P = 0.0002 and r = 0.428; P = 0.0006, respectively). Conclusions: Our work highlights a reduction in the immune response in cancer patients, particularly in SARS-CoV-2-naive subjects. Our data support administering a third dose of COVID-19 vaccine to cancer patients treated with programmed cell death protein 1/programmed death-ligand 1 inhibitors

Light chain deposition disease presenting as paroxysmal atrial fibrillation: a case report

<p>Abstract</p> <p>Introduction</p> <p>Light chain deposition disease (LCDD) can involve the heart and cause severe heart failure. Cardiac involvement is usually described in the advanced stages of the disease. We report the case of a woman in whom restrictive cardiomyopathy due to LCDD presented with paroxysmal atrial fibrillation.</p> <p>Case presentation</p> <p>A 55-year-old woman was admitted to our emergency department because of palpitations. In a recent blood test, serum creatinine was 1.4 mg/dl. She was found to have high blood pressure, left ventricular hypertrophy and paroxysmal atrial fibrillation. An ACE-inhibitor was prescribed but her renal function rapidly worsened and she was admitted to our nephrology unit. On admission serum creatinine was 9.4 mg/dl, potassium 6.8 mmol/l, haemoglobin 7.7 g/dl, N-terminal pro-brain natriuretic peptide 29894 pg/ml. A central venous catheter was inserted and haemodialysis was started. She underwent a renal biopsy which showed kappa LCDD. Bone marrow aspiration and bone biopsy demonstrated kappa light chain multiple myeloma. Echocardiographic findings were consistent with restrictive cardiomyopathy. Thalidomide and dexamethasone were prescribed, and a peritoneal catheter was inserted. Peritoneal dialysis has now been performed for 15 months without complications.</p> <p>Discussion</p> <p>Despite the predominant tubular deposition of kappa light chain, in our patient the first clinical manifestation of LCDD was cardiac disease manifesting as atrial fibrillation and the correct diagnosis was delayed. The clinical management initially addressed the cardiovascular symptoms without paying sufficient attention to the pre-existing slight increase in our patient's serum creatinine. However cardiac involvement is a quite uncommon presentation of LCDD, and this unusual case suggests that the onset of acute arrhythmias associated with restrictive cardiomyopathy and impaired renal function might be related to LCDD.</p