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Abstract We present a spatial testbed of simulated boundary data based on a set of very high-resolution census-based areal units surrounding Guadalajara, Mexico. From these input areal units, we simulated 10 levels of spatial resolutions, ranging from levels with 5,515–52,388 units and 100 simulated zonal configurations for each level – totalling 1,000 simulated sets of areal units. These data facilitate interrogating various realizations of the data and the effects of the spatial coarseness and zonal configurations, the Modifiable Areal Unit Problem (MAUP), on applications such as model training, model prediction, disaggregation, and aggregation processes. Further, these data can facilitate the production of spatially explicit, non-parametric estimates of confidence intervals via bootstrapping. We provide a pre-processed version of these 1,000 simulated sets of areal units, meta- and summary data to assist in their use, and a code notebook with the means to alter and/or reproduce these data.

Abstract Background and objective Olfactory disorders in COVID-19 impact quality of life and may lead to psychological impairments. Prevalence ranges from 8 to 85%, persisting in about 30% of cases. This study aimed to evaluate the 6-month post-COVID-19 impact on quality of life, hedonic experiences, anxiety and depression due to olfactory disorders. Additionally, it sought to compare psychophysical tests and self-perceived olfactory evaluations. Methods A prospective, longitudinal study was conducted over baseline (T0) and 6 months (T1) on individuals with persistent olfactory disorders post-COVID-19 for more than 6 weeks. Psychophysical tests employed the Sniffin’ Sticks Test® (TDI score), and self-perceived olfactory evaluation used a Visual Analogue Scale. Quality of life was assessed with an Olfactive Disorder Questionnaire and the French version of the Quality of Life and Diet Questionnaire. Hedonic experiences were gauged using the Snaith-Hamilton Pleasure Scale, while anxiety and depression dimensions were measured by The State-Trait Anxiety Inventory, The Post Traumatic Stress Checklist Scale, and Hamilton Rating Scale for Depression. Participants were classified into the “normosmic group” (NG) and the “olfactory disorders group” (ODG) at T0 and T1 based on the TDI score. Results Were included 56 participants (58.93% women, 41.07% men) with a mean age of 39.04 years and a mean duration of post-COVID-19 olfactory disorders of 5.32 months. At T1, ODG had a significantly lower quality of life and hedonic experiences than NG. No significant differences in anxiety and depression dimensions were observed between groups. At T0, psychophysical tests and self-perceived olfactory evaluations were significantly correlated with quality of life and hedonic experiences in both groups. At T1, self-perceived olfactory evaluation in NG correlated significantly with quality of life, hedonic experiences, anxiety and depression dimensions, whereas ODG only correlated with hedonic experiences. Conclusion Individuals with persistent post-COVID-19 olfactory disorders after six months demonstrated compromised quality of life and hedonic experiences. Self-perceived olfactory evaluation played a more significant role in influencing quality of life and the dimension of anxiety and depression than the psychophysical presence of olfactory disorders. These findings emphasize the importance of considering patients’ perceptions to comprehensively assess the impact of olfactory disorders on their well-being. Trial registration ClinicalTrials.gov number (ID: NCT04799977).

Abstract Background The benefit–risk balance and optimal timing of surgery for severe infective endocarditis (IE) with ischemic or hemorrhagic strokes is unknown. The study aim was to compare the neurological outcome between patients receiving surgery or not. Methods In a prospective register-based multicenter ICU study, patients were included if they met the following criteria: (i) left-sided IE with an indication for heart surgery; (ii) with cerebral complications documented by cerebral imaging before cardiac surgery; (iii) with Sequential Organ Failure Assessment score ≥ 3. Exclusion criteria were isolated right-sided IE, in-hospital acquired IE and patients with cerebral complications only after cardiac surgery. In the primary analysis, the prognostic value of surgery in term of disability at 6 month was assessed by using a propensity score-adjusted logistic regression. Results 192 patients were included including ischemic stroke (74.5%) and hemorrhagic lesion (15.6%): 67 (35%) had medical treatment and 125 (65%) cardiac surgery. In the propensity score-adjusted logistic regression, a favorable 6-month neurological outcome was associated with surgery (odds ratio 13.8 (95% CI 6.2–33.7). The 1-year mortality was strongly reduced with surgery in the fixed-effect propensity-adjusted Cox model (hazard ratio 0.18; 95% CI 0.11–0.27; p

Abstract Aims Outcomes reported for patients with hospitalization for acute heart failure (AHF) treatment vary worldwide. Ethnicity‐associated characteristics may explain this observation. This observational study compares characteristics and 1‐year outcomes of Kyrgyz and Swiss AHF patients against the background of European Society of Cardiology guidelines‐based cardiovascular care established in both countries. Methods and results The primary endpoint was 1 year all‐cause mortality (ACM); the secondary endpoint was 1 year ACM or HF‐related rehospitalization. A total of 538 Kyrgyz and 537 Swiss AHF patients were included. Kyrgyz patients were younger (64.0 vs. 83.0 years, P mild aortic stenosis was more prevalent (P

The use of unsupervised machine learning models for anomaly detection is a common thing nowadays. While many research papers focus on improving and testing these models, there is a lack of those that deal with threshold selection, which is an important step in implementing a good anomaly detection system. In this paper, we investigate different supervised and unsupervised threshold selection methods found in the network anomaly detection literature. A total of five supervised and twenty unsupervised methods were found, all of which are described, categorized, and implemented in this paper. The unsupervised methods were further categorized according to the input data they expect, the type of output data they produce, and whether they are parametric or not, and divided into six groups according to the idea behind these methods: Statistics-based, Distribution-based, Clustering-based, Density-based, Graphical-based methods and Other. To test all the methods found, two different testing scenarios are created. The first one focuses on using data with anomalies and the second one uses only the normal data. Based on these two scenarios, tests were performed with real firewall log data containing three types of injected anomalies. The results are presented in the form of boxplots of the Matthews correlation coefficient for nine datasets. To draw a conclusion, both the method groups and the individual methods were compared in terms of evaluation metrics and execution times as well as in comparison to the methods already implemented in the PyThresh toolkit.

Abstract The immune responses to Novavax’s licensed NVX-CoV2373 nanoparticle Spike protein vaccine against SARS-CoV-2 remain incompletely understood. Here, we show in rhesus macaques that immunization with Matrix-MTM adjuvanted vaccines predominantly elicits immune events in local tissues with little spillover to the periphery. A third dose of an updated vaccine based on the Gamma (P.1) variant 7 months after two immunizations with licensed NVX-CoV2373 resulted in significant enhancement of anti-spike antibody titers and antibody breadth including neutralization of forward drift Omicron variants. The third immunization expanded the Spike-specific memory B cell pool, induced significant somatic hypermutation, and increased serum antibody avidity, indicating considerable affinity maturation. Seven months after immunization, vaccinated animals controlled infection by either WA-1 or P.1 strain, mediated by rapid anamnestic antibody and T cell responses in the lungs. In conclusion, a third immunization with an adjuvanted, low-dose recombinant protein vaccine significantly improved the quality of B cell responses, enhanced antibody breadth, and provided durable protection against SARS-CoV-2 challenge.

Abstract CCDC88B is a risk factor for several chronic inflammatory diseases in humans and its inactivation causes a migratory defect in DCs in mice. CCDC88B belongs to a family of cytoskeleton-associated scaffold proteins that feature protein:protein interaction domains. Here, we identified the Rho/Rac Guanine Nucleotide Exchange Factor 2 (ARHGEF2) and the RAS Protein Activator Like 3 (RASAL3) as CCDC88B physical and functional interactors. Mice defective in Arhgef2 or Rasal3 show dampened neuroinflammation, and display altered cellular response and susceptibility to colitis; ARHGEF2 maps to a human Chromosome 1 locus associated with susceptibility to IBD. Arhgef2 and Rasal3 mutant DCs show altered migration and motility in vitro, causing either reduced (Arhgef2) or enhanced (Rasal3) migratory properties. The CCDC88B/RASAL3/ARHGEF2 complex appears to regulate DCs migration by modulating activation of RHOA, with ARHGEF2 and RASAL3 acting in opposite regulatory fashions, providing a molecular mechanism for the involvement of these proteins in DCs immune functions.

Objectives: To identify possible predictors of seizure cluster or status epilepticus (SE) and to evaluate whether these patients receive greater interventions in emergency departments. Methodology: We conducted a secondary analysis of the ACESUR Registry, a multipurpose, observational, prospective, multicentre registry of adult patients with seizures from 18 emergency departments. Clinical and care-related variables were collected. We identified risk factors and risk models for seizure cluster or SE and assessed the effect of interventions by prehospital emergency services and the hospital emergency department. Results: We identified a total of 186 (28%) patients from the ACESUR registry with seizure cluster (126 [19%]) or SE (60 [9%]); the remaining 478 patients (72%) had isolated seizures. The risk model for seizure cluster or SE in the emergency department included Charlson Comorbidity Index scores ≥ 3 (OR: 1.60; 95% CI, 1.05–2.46; P = .030), ≥ 2 habitual antiepileptic drugs (OR: 2.29; 95% CI, 1.49–3.51; P

RNA interference (RNAi) offers an efficient way to repress genes of interest, and it is widely used in research settings. Clinical applications emerged more recently, with 5 approved siRNAs (the RNA guides of the RNAi effector complex) against human diseases. The development of siRNAs against the SARS-CoV-2 virus could therefore provide the basis of novel COVID-19 treatments, while being easily adaptable to future variants or to other, unrelated viruses. Because the biochemistry of RNAi is very precisely described, it is now possible to design siRNAs with high predicted activity and specificity using only computational tools. While previous siRNA design algorithms tended to rely on simplistic strategies (raising fully complementary siRNAs against targets of interest), our approach uses the most up-to-date mechanistic description of RNAi to allow mismatches at tolerable positions and to force them at beneficial positions, while optimizing siRNA duplex asymmetry. Our pipeline proposes 8 siRNAs against SARS-CoV-2, and ex vivo assessment confirms the high antiviral activity of 6 out of 8 siRNAs, also achieving excellent variant coverage (with several 3-siRNA combinations recognizing each correctly-sequenced variant as of September 2022). Our approach is easily generalizable to other viruses as long as a variant genome database is available. With siRNA delivery procedures being currently improved, RNAi could therefore become an efficient and versatile antiviral therapeutic strategy.

We developed the LabVIEW-based virtual instruments (VIs) to bridge a gap in commercial software and to enable systematic peak-overlapping studies to recognise the concentration levels enabling reliable simultaneous determination of major and minor constituents in samples with wide concentration proportions. The VIs were applied to a case study of the ion chromatographic determination of potassium as minor and sodium as a major ion with an IonPac CS12A column and 50 μL injection loop. Two successive studies based on multilevel two-factorial response surface experimental designs, (1) a model peak-overlapping study based on single-ion injections, and (2) an accuracy and precision study, provided guidelines for real sample analyses. By adjusting sample dilutions so that the sodium mass concentration was set to 340 mg/L, the simultaneous determination of potassium in the presence of sodium was possible in samples with sodium over potassium concentration ratios between 14 and 341. The relative expanded uncertainty associated with potassium ion determination was between 0.52 and 4.4%, and the relative bias was between −3.8 and 1.9%. We analysed Ringer’s physiologic solutions, standard sea, trisodium citrate anticoagulant, and buffered citrate anticoagulant solutions. We confirmed that the VI-supported peak-overlapping studies contributed to the quality of results by enabling the evidence-based choices of concentration levels adjusted by a dilution.

Microalgae, stemming from a complex evolutionary lineage, possess a metabolic composition influenced by their evolutionary journey. They have the capacity to generate diverse polyunsaturated fatty acids (PUFAs), akin to those found in terrestrial plants and oily fish. Also, because of their numerous double bonds, these metabolic compounds are prone to oxidation processes, leading to the creation of valuable bioactive molecules called oxylipins. Moreover, owing to their adaptability across various environments, microalgae offer an intriguing avenue for biosynthesizing these compounds. Thus, modifying the culture conditions could potentially impact the profiles of oxylipins. Indeed, the accumulation of oxylipins in microalgae is subject to the influence of growth conditions, nutrient availability, and stressors, and adjusting these factors can enhance their production in microalgae culture. Consequently, the present study scrutinized the LC-MS/MS profiles of oxylipins from three marine microalgae species (two Haptagophytes and one Chlorophyte) cultivated in 1 L of photobioreactors under varying stress-inducing conditions, such as the introduction of H2O2, EtOAc, and NaCl, during their exponential growth phase. Approximately 50 oxylipins were identified, exhibiting different concentrations depending on the species and growth circumstances. This research suggests that microalgae metabolisms can be steered toward the production of bioactive oxylipins through modifications in the culture conditions. In this instance, the application of a low dose of hydrogen peroxide to Mi 124 appears to stimulate the production of nonenzymatic oxylipins. For Mi136, it is the application of salt stress that seems to increase the overall production of oxylipins. In the case of Mi 168, either a low concentration of H2O2 or a high concentration of AcOEt appears to have this effect.

Pathogenic Leptospira spp. causes leptospirosis in animals and humans globally, leading to systemic infections that can impact vital organs in affected animals. The purpose of this study was to evaluate kidney injury and to perform a retrospective analysis of leptospirosis infection in follow-up dog samples. The retrospective study collected epidemiological information obtained through paraclinical exams, immunohistochemistry (IHC), and molecular biology (qPCR) of cases from the Faculty of Veterinary Medicine from Timisoara between September 2016 and May 2023. No correlations were found between Leptospira infection and breed (p = 0.714), gender or castration status (p = 0.890), and anatomic pathology exam results (p = 0.608). Significant associations were found in cases with high levels of azotemia (p = 0.000) and immunological status (vaccinated vs. unvaccinated, p = 0.000), with the leptospirosis risk in unvaccinated animals calculated at OR = 85.500 (95%CI, 6.82–1071.26, p = 0.000). Retrospectively, leptospirosis was diagnosed in 27/65 cases (42%) using the IHC method, while the qPCR assay detected 29/65 cases (45%). This study demonstrates that qPCR is a robust and specific method for postmortem diagnosis of Leptospira spp. infection in dogs, offering higher specificity and reliability compared to traditional IHC methods, which showed 94.74% specificity in our study.

Cells of most bacterial species are around 2 micrometers in length, with some of the largest specimens reaching 750 micrometers. Using fluorescence, x-ray, and electron microscopy in conjunction with genome sequencing, we characterized Candidatus (Ca.) Thiomargarita magnifica, a bacterium that has an average cell length greater than 9000 micrometers and is visible to the naked eye. These cells grow orders of magnitude over theoretical limits for bacterial cell size, display unprecedented polyploidy of more than half a million copies of a very large genome, and undergo a dimorphic life cycle with asymmetric segregation of chromosomes into daughter cells. These features, along with compartmentalization of genomic material and ribosomes in translationally active organelles bound by bioenergetic membranes, indicate gain of complexity in the Thiomargarita lineage and challenge traditional concepts of bacterial cells.

The relationship between teaching and research in universities has been widely studied in the higher education literature, but no clear relationship between the two has been identified. Nevertheless, in recent years, research has been linked to a form of teaching that is more focused on the development of competences and learning capacity through enquiry and the generation of new knowledge. In this context, it is important for teachers and students to work together on the design of shared spaces for research and learning. This work examines the case of the University of Barcelona to analyse whether there is enough connection between research and teaching to allow students to experience this link and to successfully develop research competences. Teaching plans of the academic year 2018-19 were screened to identify research-related competences, the modules they appear in, and the descriptions of the evaluation systems. This information was compared to the students' perceptions of the actual training they had received on these research competences. Results showed that teaching plans establish numerous competences related to research and generating new knowledge. However, students consider that this knowledge is not developed until the final year project.