SARS-CoV-2 Evolution: Implications for Diagnosis, Treatment, Vaccine Effectiveness and Development

The COVID-19 pandemic, driven by the rapid evolution of the SARS-CoV-2 virus, presents ongoing challenges to global public health. SARS-CoV-2 is characterized by rapidly evolving mutations, especially in (but not limited to) the spike protein, complicating predictions about its evolutionary trajectory. These mutations have significantly affected transmissibility, immune evasion, and vaccine efficacy, leading to multiple pandemic waves with over half a billion cases and seven million deaths globally. Despite several strategies, from rapid vaccine development and administration to the design and availability of antivirals, including monoclonal antibodies, already having been employed, the persistent circulation of the virus and the emergence of new variants continue to result in high case numbers and fatalities. In the past four years, immense research efforts have contributed much to our understanding of the viral pathogenesis mechanism, the COVID-19 syndrome, and the host–microbe interactions, leading to the development of effective vaccines, diagnostic tools, and treatments. The focus of this review is to provide a comprehensive analysis of the functional impact of mutations on diagnosis, treatments, and vaccine effectiveness. We further discuss vaccine safety in pregnancy and the implications of hybrid immunity on long-term protection against infection, as well as the latest developments on a pan-coronavirus vaccine and nasal formulations, emphasizing the need for continued surveillance, research, and adaptive public health strategies in response to the ongoing SARS-CoV-2 evolution race

Neurophysiological Insights into the Pathophysiology of Stiff‐Person Spectrum Disorders

Background: Stiff Person Spectrum Disorders (SPSD) are classically defined by the presence of muscle stiffness, spasms and hyperactivity of the central nervous system. There is a notable correlation between neurophysiological features and the clinical hallmark of SPSD, which has greatly encouraged the use of these techniques for diagnostic purposes. Besides, electrophysiological techniques allow for a functional evaluation of the ‘hyperactivity of the CNS’, thus offering the opportunity to clarify the mechanisms underlying this disorder. This review delves into the current knowledge on the electrophysiological aspects of SPSD, highlighting the pivotal role of various studies in unravelling its pathophysiology. Methods: Literature review for studies on SPSD that included a neurophysiological evaluation. Results: We first examined the abnormal neurophysiological findings of SPSD across the central nervous system, from the spinal circuit to the motor cortex. Subsequently, we discussed their pathological implications and explored how these findings can be interpreted within the framework of an immune-mediated disorder. Conclusions: Two primary questions remain unanswered: the localization of the primary abnormality within the central nervous system and the connection between the autoimmune basis of SPSD and its neurophysiological aspects. Addressing these questions could provide invaluable insights into SPSD etiology and targeted therapeutic strategies

The UNICA sleep HRV analysis tool: an integrated open-source tool for heart rate variability analysis during sleep

Heart rate variability (HRV) analysis during sleep plays a key role for understanding autonomic nervous system function and assessing cardiovascular health. The UNICA Sleep HRV analysis (UNICA-HRV) tool is a novel, open-source MATLAB tool designed to fill the gap in current HRV analysis tools. In particular, the integration of ECG and HRV data with hypnogram information, which illustrates the progression through the different sleep stages, eases the computation of HRV metrics in polysomnographic recordings. This integration is crucial for accurate phase-specific analysis, as autonomic regulation changes markedly across different sleep stages. The tool supports single- and multiple-subject analyses and is tailored to enhance usability and accessibility for researchers and clinicians without requiring extensive technical expertise. It implements and supports a variety of data inputs and configurations, allowing for flexible, detailed HRV analyses across sleep stages, employing classical and advanced metrics, such as time-domain, frequency-domain, non-linear, complexity, and Poincaré plot indexes. Validation of the tool against established tools like Kubios and PhysioZoo indicates its robustness and precision in generating reliable HRV metrics, that are essential not only for sleep research, but also for clinical diagnostics. The introduction of UNICA-HRV represents a significant simplification for sleep studies, and its open-source nature (licensed under a Creative Commons Attribution 4.0 International License) allows to easily extend the functionality to other needs

Stato e rivoluzione. Problemi filosofico politici della trasformazione in un mondo al collasso

In a world dominated by warmongering imperialism in its phase of maximum expansion, when the nationalist convulsions of the Western powers had ended up overwhelming even the International, State and Revolution once again addresses the question of the Marxist theory of the State by reiterating the impossibility of a gradual and seamless transition from bourgeois democracy to socialism. If in general terms universal suffrage was not able to undermine the substance of the class contradictions inherent in capitalist society, in a historical phase such as that, according to Lenin, the way out of the barbarism responsible for having brought humanity to collapse had to be sought with even greater determination in new, more direct and less mediated forms of popular participation. In this work, considered Lenin's last theoretical work, the Russian revolutionary raises the problem of overcoming delegated representative forms of political functions, at the time organically co-opted in defense of the monopolistic interests of the respective national capitalisms

Oxidative Stress by H2O2 as a Potential Inductor in the Switch from Commensal to Pathogen in Oncogenic Bacterium Fusobacterium nucleatum

Background: Fusobacterium nucleatum is a pathobiont that plays a dual role as both a commensal and a pathogen. The oral cavity typically harbors this anaerobic, Gram-negative bacterium. At the same time, it is closely linked to colorectal cancer due to its potential involvement in tumor progression and resistance to chemotherapy. The mechanism by which it transforms from a commensal to a pathogen remains unknown. For this reason, we investigated the role of oxidative status as an initiatory factor in changing the bacterium’s pathogenicity profile. Methods: A clinical strain of F. nucleatum subsp. animalis biofilm was exposed to different oxidative stress levels through varying subinhibitory amounts of H2O2. Subsequently, we investigated the bacterium’s behavior in vitro by infecting the HT-29 cell line. We evaluated bacterial colonization, volatile sulfur compounds production, and the infected cell’s oxidative status by analyzing HMOX1, pri-miRNA 155, and 146a gene expression. Results: The bacterial colonization rate, dimethyl sulfide production, and pri-miRNA 155 levels all increased when stressed bacteria were used, suggesting a predominant pathogenic function of these strains. Conclusions: The response of F. nucleatum to different oxidative conditions could potentially explain the increase in its pathogenic traits and the existence of environmental factors that may trigger the bacterium’s pathogenicity and virulence

Corporate social responsibility disclosure: International evidence

This dissertation explores two different but linked settings: Corporate social responsibility (CSR) disclosure in executive compensation design among European countries and within European firms and the consequences of controversial industry-based CSR disclosure on Canadian cannabis firms. In Europe, the dissertation examines how firms disclose their executive compensation design when they adopt CSR criteria for the first time, studying the determinants of country-level characteristics and firm-specific factors. Meanwhile, in Canada, the dissertation explores how controversial industries, such as the cannabis sector, use CSR disclosure to gain legitimacy and societal acceptance. This study explores the effectiveness of these practices by studying the quality and consequences, whether such practices help firms improve their corporate responsibility or serve as mechanisms for corporate self-legitimation. This dissertation will provide helpful information to refine predictions on the extent of CSR criteria being disclosed in executive compensation design structures in Europe within European firms and controversial industries in Canadian cannabis firms

Riflessioni sull’estetica della tardività: lo Chevalier aux deux épées e il canone arturiano = Reflections on the aesthetics of tardiness: Le Chevalier aux deux épées and the Arthurian canon

A partire dal lavoro recente di Géraldine Toniutti (2021) sui romanzi arturiani in versi tardivi, il contributo indaga l’estetica della tardività attiva nello Chevalier aux deux épées. In questo romanzo arturiano in versi del XIII secolo, infatti, il riutilizzo della tradizione precedente non corrisponde sempre alla norma del genere, codificata dalle opere canoniche di Chrétien de Troyes, ma si attaglia, piuttosto, all’ambito dell’anomia tipica degli ultimi romanzi arturiani in versi.Building on Géraldine Toniutti’s research (2021) on late Arthurian verse romances, this paper explores the aesthetics of tardiness (tardivité) in Le Chevalier aux deux épées. In this 13th-century Arthurian verse romance, the reuse of earlier tradition does not always conform to the norm of the genre, as codified in the canonical works of Chrétien de Troyes, but rather aligns with the anomie characteristic of the last Arthurian verse romances

Literatur in der Sowjetukraine

Die Konsolidierung des Stalinismus zu Beginn der dreißiger Jahre beendete die sehr produktive Phase des ukrainischen Modernismus. Die Gängelung des literarischen Lebens und die Durchsetzung des „sozialistischen Realismus“ als einheitlicher ästhetischer Doktrin führten zu einer Verarmung der ukrainischen Literatur, die erst nach dem Tod Stalins wieder zu einer gewissen Pluralität und Kreativität zurückfand. Das Tauwetter, das bis Mitte der sechziger Jahre dauerte, stellt einen Schlüsselmoment in der Rekonstruktion der ukrainischen Kultur nach dem Stalinismus dar, sowohl ästhetisch als auch politisch. Der wichtigste Dichter der siebziger Jahre ist Vasyl’ Stus, der die modernistische Strömung der ukrainischen Lyrik wieder zum Leben erweckte und 1985 als Dissident in einem Lager umkam. Eine wichtige Rolle für die freie ukrainische Literatur spielte der Selbstverlag (samvydav). Erst gegen 1985 kam es erneut zu einer Liberalisierung des kulturellen Lebens, die mit dem Anfang der Postmoderne in der ukrainischen Literatur zusammenfiel

Study of Ds1(2460)+→Ds+π+π- in B→D ̅(*)Ds+π+π- decays

An amplitude analysis of the Ds1(2460)+→Ds+π+π- transition is performed simultaneously in B0→D-Ds+π+π-, B+→D ̅0Ds+π+π-, and B0→D*-Ds+π+π- decays. The study is based on a data sample of proton-proton collisions recorded with the LHCb detector at centre-of-mass energies of s=7,8, and 13 TeV, corresponding to a total integrated luminosity of 9fb-1. A clear double-peak structure is observed in the m(π+π-) spectrum of the Ds1(2460)+→Ds+π+π- decay. The data can be described either with a model including f0500,f0980, and f2(1270) resonances, in which the contributions of f0(980) and f2(1270) are unexpectedly large, or with a model including f0(500), a doubly charged open-charm tetraquark state Tcs ̄++ and its isospin partner Tcs ̄0. If the former is considered implausible, the Tcs ̄ states are observed with high significance, and the data are consistent with isospin symmetry. When imposing isospin constraints between the two Tcs ̄ states, their mass and width are determined to be (2327±13±13) MeV and (96±16-23+170) MeV, respectively, where the first uncertainty is statistical and the second is systematic. The mass is slightly below the DK threshold, and a spin-parity of 0+ is favoured with high significance

Multidisciplinary Optimization of Next-Generation Aero-Engine Fans

The last decade has seen rising concerns over the impact that the global civil aviation market has on climate. The role of sustainability in the modern aeronautics has gained a growing importance, and has been identified as a key challenge facing the aviation industry. Today, sustainability is one of the main agents pushing jet engine manufacturers towards the design of machines that consume less fuel and last longer. A key factor for achieving these targets is an increased adoption of high-fidelity numerical analyses and optimization methods, in order to effectively approach problems that can be efficiently, rapidily and affordably solved only through advanced mathematics. There is also the urge to deal with different engineering disciplines simultaneously, by formulating and solving multidisciplinary optimization problems, thereby saving time in the early design phases and delivering an improved, optimal product in the successive layout stages. An important aspect to be considered to improve aero-engine turbomachinery components’s life and performances is to control and reduce the secondary flows that develop in their blade passages. Secondary flows reduce the pressure ratio and efficiency of aero-engine compressors, alter their operations at off-design conditions and shorthen the life of downstream components. The work of this thesis makes use of multidisciplinary optimization and high-fidelity numerical CFD simulations, to control and reduce the secondary flows in aero-engine compressors, by using vortex generators. The capabilities of these devices are studied in an open testcase transonic compressor, the NASA Rotor 37, by carrying out an optimization and studying different metrics that measure the secondary flows intensity. Building on the gained knowledge, a single-objective constrained optimization of a vortex generator parameterized with 7 variables is performed on axial compressor representative of a real, modern high-bypass civil aero-engine fan. Different constraints are applied to ensure satisfactory performances. An additional weakly-coupled aero-structural analysis is also performed on the optimal vortex generator to assess its material integrity. A simplified vibrational analysis conducted on a representative downstream component demonstrates important reductions in the forced response, which is one of the primary responsible for the life of compressor blades