Therapeutic Efficacy and Outcomes of Remdesivir versus Remdesivir with Tocilizumab in Severe SARS-CoV-2 Infection

The infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) generated many challenges to find an effective drug combination for hospitalized patients with severe forms of coronavirus disease 2019 (COVID-19) pneumonia. We conducted a retrospective cohort study, including 182 patients with severe COVID-19 pneumonia hospitalized between March and October 2021 in a Pneumology Hospital from Cluj-Napoca, Romania. Among patients treated with standard of care, 100 patients received remdesivir (R group) and 82 patients received the combination of remdesivir plus tocilizumab (RT group). We compared the clinical outcomes, the inflammatory markers, superinfections, oxygen requirement, intensive care unit (ICU) admission and mortality rate before drug administration and 7 days after in R group and RT group. Borg score and oxygen support showed an improvement in the R group (p < 0.005). Neutrophiles, C-reactive protein (CRP) and serum ferritin levels decreased significantly in RT group but with a higher rate of superinfection in this group. ICU admission and death did not differ significantly between groups. The combination of remdesivir plus tocilizumab led to a significantly improvement in the inflammatory markers and a decrease in the oxygen requirement. Although the superinfection rate was higher in RT group than in R group, no significant difference was found in the ICU admission and mortality rate between the groups.     

ONT-Based Alternative Assemblies Impact on the Annotations of Unique versus Repetitive Features in the Genome of a Romanian Strain of Drosophila melanogaster

To date, different strategies of whole-genome sequencing (WGS) have been developed in order to understand the genome structure and functions. However, the analysis of genomic sequences obtained from natural populations is challenging and the biological interpretation of sequencing data remains the main issue. The MinION device developed by Oxford Nanopore Technologies (ONT) is able to generate long reads with minimal costs and time requirements. These valuable assets qualify it as a suitable method for performing WGS, especially in small laboratories. The long reads resulted using this sequencing approach can cover large structural variants and repetitive sequences commonly present in the genomes of eukaryotes. Using MinION, we performed two WGS assessments of a Romanian local strain of Drosophila melanogaster, referred to as Horezu_LaPeri (Horezu). In total, 1,317,857 reads with a size of 8.9 gigabytes (Gb) were generated. Canu and Flye de novo assembly tools were employed to obtain four distinct assemblies with both unfiltered and filtered reads, achieving maximum reference genome coverages of 94.8% (Canu) and 91.4% (Flye). In order to test the quality of these assemblies, we performed a two-step evaluation. Firstly, we considered the BUSCO scores and inquired for a supplemental set of genes using BLAST. Subsequently, we appraised the total content of natural transposons (NTs) relative to the reference genome (ISO1 strain) and mapped the mdg1 retroelement as a resolution assayer. Our results reveal that filtered data provide only slightly enhanced results when considering genes identification, but the use of unfiltered data had a consistent positive impact on the global evaluation of the NTs content. Our comparative studies also revealed differences between Flye and Canu assemblies regarding the annotation of unique versus repetitive genomic features. In our hands, Flye proved to be moderately better for gene identification, while Canu clearly outperformed Flye for NTs analysis. Data concerning the NTs content were compared to those obtained with ONT for the D. melanogaster ISO1 strain, revealing that our strategy conducted to better results. Additionally, the parameters of our ONT reads and assemblies are similar to those reported for ONT experiments performed on various model organisms, revealing that our assembly data are appropriate for a proficient annotation of the Horezu genome.     

Whole Body Vibration Improves Brain and Musculoskeletal Health by Modulating the Expression of Tissue-Specific Markers: FNDC5 as a Key Regulator of Vibration Adaptations

Whole body vibration (WBV) is well known to exert beneficial effects on multiple tissues, improving synaptic transmission, muscle mass, bone quality, and reducing anxiety and depressive behavior. However, the underlying molecular mechanisms are not yet fully understood, and organs and tissues may respond differently to the vibratory stimulus depending on multiple factors. Therefore, we investigated the WBV effects on the brain and musculoskeletal tissue of 4-month-old young mice, evaluating synaptic plasticity by electrophysiological recordings and tissue organization by histology and histomorphometric analysis. Specifically, WBV protocols were characterized by the same vibration frequency (45 Hz), but different in vibration exposure time (five series of 3 min for the B protocol and three series of 2 min and 30 s for the C protocol) and recovery time between two vibration sessions (1 min for the B protocol and 2 min and 30 s for the C protocol). In addition, immunohistochemistry was conducted to evaluate the expression of fibronectin type III domain-containing protein 5 (FNDC5), as well as that of tissue-specific markers, such as brain-derived neurotrophic factor (BDNF) in brain, myostatin in muscle and collagen I (COL-1) in bone. Our results suggest that the WBV effects depend closely on the type of protocol used and support the hypothesis that different organs or tissues have different susceptibility to vibration. Further studies will be needed to deepen our knowledge of physiological adaptations to vibration and develop customized WBV protocols to improve and preserve cognitive and motor functions.     

Quantifying community resilience based on fluctuations in visits to points-of-interest derived from digital trace data

This research establishes a methodological framework for quantifying community resilience based on fluctuations in a population''s activity during a natural disaster. Visits to points-of-interests (POIs) over time serve as a proxy for activities to capture the combined effects of perturbations in lifestyles, the built environment and the status of business. This study used digital trace data related to unique visits to POIs in the Houston metropolitan area during Hurricane Harvey in 2017. Resilience metrics in the form of systemic impact, duration of impact, and general resilience (GR) values were examined for the region along with their spatial distributions. The results show that certain categories, such as religious organizations and building material and supplies dealers had better resilience metrics—low systemic impact, short duration of impact, and high GR. Other categories such as medical facilities and entertainment had worse resilience metrics—high systemic impact, long duration of impact and low GR. Spatial analyses revealed that areas in the community with lower levels of resilience metrics also experienced extensive flooding. This insight demonstrates the validity of the approach proposed in this study for quantifying and analysing data for community resilience patterns using digital trace/location-intelligence data related to population activities. While this study focused on the Houston metropolitan area and only analysed one natural hazard, the same approach could be applied to other communities and disaster contexts. Such resilience metrics bring valuable insight into prioritizing resource allocation in the recovery process.     

Electrochemical chlorination of azulene derivatives: Insight into the mechanism of anodic oxidative chlorination

The cyclic voltammetry behavior of a series of five 1-substituted azulenes has been investigated as well as the electrochemical chlorination of these compounds. In the case of azulene compounds containing electron withdrawing groups which have higher oxidation potentials than that of the chloride ion, the electrochemical chlorination led usually to 3-chloro derivatives. The electrochemical chlorination fails for azulenes with lower oxidation potentials. Additionally some polyhalogenated compounds were obtained by controlled potential electrolyses. The paper also discusses the reaction mechanism of the electrochemical halogenation of 1-substituted azulenes.     

Query language-based inverses of schema mappings: semantics, computation, and closure properties

The inversion of schema mappings has been identified as one of the fundamental operators for the development of a general framework for metadata management. During the last few years, three alternative notions of inversion for schema mappings have been proposed (Fagin-inverse (Fagin, TODS 32(4), 25:1–25:53, 2007), quasi-inverse (Fagin et?al., TODS 33(2), 11:1–11:52, 2008), and maximum recovery (Arenas et?al., TODS 34(4), 22:1–22:48, 2009)). However, these notions lack some fundamental properties that limit their practical applicability: most of them are expressed in languages including features that are difficult to use in practice, some of these inverses are not guaranteed to exist for mappings specified with source-to-target tuple-generating dependencies (st-tgds), and it has been futile to search for a meaningful mapping language that is closed under any of these notions of inverse. In this paper, we develop a framework for the inversion of schema mappings that fulfills all of the above requirements. It is based on the notion of ${\mathcal{C}}$ -maximum recovery, for a query language ${\mathcal{C}}$ , a notion designed to generate inverse mappings that recover back only the information that can be retrieved with queries in ${\mathcal{C}}$ . By focusing on the language of conjunctive queries (CQ), we are able to find a mapping language that contains the class of st-tgds, is closed under CQ-maximum recovery, and for which the chase procedure can be used to exchange data efficiently. Furthermore, we show that our choices of inverse notion and mapping language are optimal, in the sense that choosing a more expressive inverse operator or mapping language causes the loss of these properties.     

On fluidization of discrete event models: observation and control of continuous Petri nets

As a preliminary overview, this work provides first a broad tutorial on the fluidization of discrete event dynamic models, an efficient technique for dealing with the classical state explosion problem. Even if named as continuous or fluid, the relaxed models obtained are frequently hybrid in a technical sense. Thus, there is plenty of room for using discrete, hybrid and continuous model techniques for logical verification, performance evaluation and control studies. Moreover, the possibilities for transferring concepts and techniques from one modeling paradigm to others are very significant, so there is much space for synergy. As a central modeling paradigm for parallel and synchronized discrete event systems, Petri nets (PNs) are then considered in much more detail. In this sense, this paper is somewhat complementary to David and Alla (2010). Our presentation of fluid views or approximations of PNs has sometimes a flavor of a survey, but also introduces some new ideas or techniques. Among the aspects that distinguish the adopted approach are: the focus on the relationships between discrete and continuous PN models, both for untimed, i.e., fully non-deterministic abstractions, and timed versions; the use of structure theory of (discrete) PNs, algebraic and graph based concepts and results; and the bridge to Automatic Control Theory. After discussing observability and controllability issues, the most technical part in this work, the paper concludes with some remarks and possible directions for future research.     

Evaluation of registration methods on thoracic CT: the EMPIRE10 challenge

EMPIRE10 (Evaluation of Methods for Pulmonary Image REgistration 2010) is a public platform for fair and meaningful comparison of registration algorithms which are applied to a database of intrapatient thoracic CT image pairs. Evaluation of nonrigid registration techniques is a nontrivial task. This is compounded by the fact that researchers typically test only on their own data, which varies widely. For this reason, reliable assessment and comparison of different registration algorithms has been virtually impossible in the past. In this work we present the results of the launch phase of EMPIRE10, which comprised the comprehensive evaluation and comparison of 20 individual algorithms from leading academic and industrial research groups. All algorithms are applied to the same set of 30 thoracic CT pairs. Algorithm settings and parameters are chosen by researchers expert in the configuration of their own method and the evaluation is independent, using the same criteria for all participants. All results are published on the EMPIRE10 website (http://empire10.isi.uu.nl). The challenge remains ongoing and open to new participants. Full results from 24 algorithms have been published at the time of writing. This paper details the organization of the challenge, the data and evaluation methods and the outcome of the initial launch with 20 algorithms. The gain in knowledge and future work are discussed.     

Detection and identification of tyrDC + enterococcal strains from pasteurized commercial cheeses

The aim of this study was to isolate and identify strains of Enterococcus from commercial cheeses and then analyze their abilities to produce biogenic amines. The genotypic variability, studied by randomly amplified polymorphic DNA (RAPD)-PCR, showed a high degree of homogeneity among enterococcal strains. Afterward, genotypic analysis indicated that all strains contain genes encoding a tyrosine decarboxylase. Our results indicate that a potential health risk exists if the enterococcal strains are able to survive the pasteurization of milk or appear as post-pasteurization contaminants. These results highlight the importance of the hazard analysis and critical control point (HACCP) to minimize the risk of hazards associated with post-contamination during cheese elaboration