SARS-CoV-2 mRNA Vaccine Breakthrough Infections in Fully Vaccinated Healthcare Personnel: A Systematic Review

The number of people vaccinated against COVID-19 increases worldwide every day; however, it is important to study the risk of breakthrough infections in vaccinated individuals at high risk of exposure such as healthcare personnel (HCP). A systematic literature review (SLR) applying the PRISMA declaration and the PECOS format using the following entry terms was used: “Health Personnel OR Healthcare Worker OR Healthcare Provider OR Healthcare Personnel AND breakthrough OR infection after vaccine*”. The research was carried out utilizing the following databases: SCOPUS, PubMed, Embase, and Web of Sciences. An overall very low incidence of post-vaccination breakthrough infections was found, ranging from 0.011 to 0.001 (per 100 individuals at risk). Our findings further support the published high effectiveness rates of mRNA vaccines in preventing SARS-CoV-2 infections among fully vaccinated HCP. Additional studies are needed to define the duration of the vaccine-induced protection among HCP

Low escape-rate genome safeguards with minimal molecular perturbation of Saccharomyces cerevisiae

As the use of synthetic biology both in industry and in academia grows, there is an increasing need to ensure biocontainment. There is growing interest in engineering bacterial- and yeast-based safeguard (SG) strains. First-generation SGs were based on metabolic auxotrophy; however, the risk of cross-feeding and the cost of growth-controlling nutrients led researchers to look for other avenues. Recent strategies include bacteria engineered to be dependent on nonnatural amino acids and yeast SG strains that have both transcriptional- and recombinational-based biocontainment. We describe improving yeast Saccharomyces cerevisiae-based transcriptional SG strains, which have near-WT fitness, the lowest possible escape rate, and nanomolar ligands controlling growth. We screened a library of essential genes, as well as the best-performing promoter and terminators, yielding the best SG strains in yeast. The best constructs were fine-tuned, resulting in two tightly controlled inducible systems. In addition, for potential use in the prevention of industrial espionage, we screened an array of possible "decoy molecules" that can be used to mask any proprietary supplement to the SG strain, with minimal effect on strain fitness

Beyond the marrow:insights from comprehensive next-generation sequencing of extramedullary multiple myeloma tumors

Extramedullary multiple myeloma (EMM) is an aggressive form of multiple myeloma (MM). This study represents the most comprehensive next-generation sequencing analysis of EMM tumors (N = 14) to date, uncovering key molecular features and describing the tumor microenvironment. We observed the co-occurrence of 1q21 gain/amplification and MAPK pathway mutations in 79% of EMM samples, suggesting that these are crucial mutational events in EMM development. We also demonstrated that patients with mutated KRAS and 1q21 gain/amplification at the time of diagnosis have a significantly higher risk of EMM development (HR = 2.4, p = 0.011) using data from a large CoMMpass dataset. We identified downregulation of CXCR4 and enhanced cell proliferation, along with reduced expression of therapeutic targets (CD38, SLAMF7, GPRC5D, FCRH5), potentially explaining diminished efficacy of immunotherapy. Conversely, we identified significantly upregulated EZH2 and CD70 as potential future therapeutic options. For the first time, we report on the tumor microenvironment of EMM, revealing CD8+ T cells and NK cells as predominant immune effector cells using single-cell sequencing. Finally, this is the first longitudinal study in EMM revealing the molecular changes from the time of diagnosis to EMM relapse.</p

Nominal-Yield-Area Tradeoff in Automatic Synthesis of Analog Circuits: A Genetic Programming Approach Using Immune-Inspired Operators

The synthesis of analog circuits is a complex and expensive task; whilst there are various approaches for the synthesis of digital circuits, analog design is intrinsically more difficult since analog circuits process voltages in a continuous range. In the field of analog circuit design, the genetic programming approach has received great attention, affording the possibility to design and optimize a circuit at the same time. However, these algorithms have limited industrial relevance, since they work with ideal components. Starting from the well known results of Koza and co-authors, we introduce a new evolutionary algorithm, called elitist Immune Programming (EIP), that is able to synthesize an analog circuit using industrial components series in order to produce reliable and low cost circuits. The algorithm has been used for the synthesis of low-pass filters; the results were compared with the genetic programming, and the analysis shows that EIP is able to design better circuits in terms of frequency response and number of components. In addition we conduct a complete yield analysis of the discovered circuits, and discover that EIP circuits attain a higher yield than the circuits generated via a genetic programming approach, and, in particular, the algorithm discovers a Pareto Front which respects nominal performance (sizing), number of components (area) and yield (robustness)

Identification of Sensitive Enzymes in the Photosynthetic Carbon Metabolism

Understanding and optimizing the CO2 fixation process would allow human beings to address better current energy and biotechnology issues. We focused on modeling the C3 photosynthetic Carbon metabolism pathway with the aim of identifying the minimal set of enzymes whose biotechnological alteration could allow a functional re-engineering of the pathway. To achieve this result we merged in a single powerful pipe-line Sensitivity Analysis (SA), Single- (SO) and Multi-Objective Optimization (MO), and Robustness Analysis (RA). By using our recently developed multipurpose optimization algorithms (PAO and PMO2) here we extend our work exploring a large combinatorial solution space and most importantly, here we present an important reduction of the problem search space. From the initial number of 23 enzymes we have identified 11 enzymes whose targeting in the C3 photosynthetic Carbon metabolism would provide about 90% of the overall functional optimization. Both in terms of maximal CO2 Uptake and minimal Nitrogen consumption, these 11 sensitive enzymes are confirmed to play a key role. Finally we present a RA to confirm our findings. © 2012 Springer Science+Business Media, LLC

Large Scale Agent-Based Modeling of the Humoral and Cellular Immune Response

The Immune System is, together with Central Nervous System, one of the most important and complex unit of our organism. Despite great advances in recent years that shed light on its understanding and in the unraveling of key mechanisms behind its functions, there are still many areas of the Immune System that remain object of active research. The development of in-silico models, bridged with proper biological considerations, have recently improved the understanding of important complex systems [1,2]. In this paper, after introducing major role players and principal functions of the mammalian Immune System, we present two computational approaches to its modeling; i.e., two in-silico Immune Systems. (i) A large-scale model, with a complexity of representation of 106 - 108 cells (e.g., APC, T, B and Plasma cells) and molecules (e.g., immunocomplexes), is here presented, and its evolution in time is shown to be mimicking an important region of a real immune response. (ii) Additionally, a viral infection model, stochastic and light-weight, is here presented as well: its seamless design from biological considerations, its modularity and its fast simulation times are strength points when compared to (i). Finally we report, with the intent of moving towards the virtual lymph note, a cost-benefits comparison among Immune System models presented in this paper. © 2011 Springer-Verlag

Reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) as a user-friendly system to detect SARS-CoV-2 infection: A multicentric study

Although reverse transcriptase quantitative PCR remains the gold standard to perform viral detection, reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) is already used to perform diagnosis of various infections. This work reports the results of a multicentric study performed in Sicily to evaluate the diagnostic power of an RT-LAMP kit for the diagnosis of SARS-CoV-2 infection on a total of 551 samples collected in January and February 2021, revealing sensitivity, specificity, accuracy, positive and negative predictive values ≥95%. Our results suggest the potential employment of this kit as a screening test to be used where fast and reliable results are demanded without the need for expensive instruments and highly-skilled personnel

Testing surgical face masks in an emergency context: The experience of italian laboratories during the COVID-19 pandemic crisis

The first wave of the COVID-19 pandemic brought about a broader use of masks by both professionals and the general population. This resulted in a severe worldwide shortage of devices and the need to increase import and activate production of safe and effective surgical masks at the national level. In order to support the demand for testing surgical masks in the Italian context, Universities provided their contribution by setting up laboratories for testing mask performance before releasing products into the national market. This paper reports the effort of seven Italian university laboratories who set up facilities for testing face masks during the emergency period of the COVID-19 pandemic. Measurement set-ups were built, adapting the methods specified in the EN 14683:2019+AC. Data on differential pressure (DP) and bacterial filtration efficiency (BFE) of 120 masks, including different materials and designs, were collected over three months. More than 60% of the masks satisfied requirements for DP and BFE set by the standard. Masks made of nonwoven polypropylene with at least three layers (spunbonded–meltblown–spunbonded) showed the best results, ensuring both good breathability and high filtration efficiency. The majority of the masks created with alternative materials and designs did not comply with both standard requirements, resulting in suitability only as community masks. The effective partnering between universities and industries to meet a public need in an emergency context represented a fruitful example of the so-called university “third-mission”