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Software developers encounter recurring problems during software development, which can be solved using proven solutions known as design patterns. Microservices architecture, a Service-Oriented Architecture (SOA) variant, presents common communication, deployment, and service definition challenges. However, selecting the appropriate design pattern from a vast pool of patterns to solve a problem is difficult for novice and experienced developers. This paper proposes a recommendation tool based on Information Retrieval (IR) to assist developers in choosing the suitable microservices pattern to solve a given problem. The tool leverages textual descriptions given by developers to provide relevant indications of microservices patterns. It has been evaluated using both toy and industrial problems, demonstrating promising results. The results showed that the tool was able to solve 60% of toy design problems, indicating that it can provide valuable and accurate recommendations. Furthermore, tests with industrial problems revealed that over 70% of the recommended patterns helped to address the problems at hand. Interviews with developers who work in the software industry corroborated the recommendation tool’s effectiveness and practicality.

In software engineering, there must be clarity in communication among interested parties to elicit the requirements aimed at software development through frameworks to achieve the behaviors expected by the software. Problem: A lack of clarity in the requirement-elicitation stage can impact subsequent stages of software development. Solution: We proposed a case study focusing on the performance efficiency characteristic expressed in the ISO/IEC/IEEE 25010 standard using Behavior-Driven Development (BDD). Method: The case study was performed with professionals who use BDD to elicit the non-functional requirements of a company that develops software. Summary of Results: The result obtained was the validation related to the elicitation of non-functional requirements aimed at the performance efficiency characteristic of the ISO/IEC/IEEE 25010 Standard using the BDD framework through a real case study in a software development company. Contributions and impact: The article’s main contribution is to demonstrate the effectiveness of using BDD to elicit non-functional requirements about the performance efficiency characteristic of the ISO/IEC/IEEE 25010 standard.

The COVID-19 pandemic has prompted a quest to understand why certain individuals remain uninfected or asymptomatic despite repetitive exposure to SARS-CoV-2. Here, we focused on six exposed females residing with their symptomatic and reinfected SARS-CoV-2 PCR-positive COVID-19 partners. Peripheral blood mononuclear cell samples from couples were analysed for poly (I:C)-induced mRNA expression of type I/III interferons and interferon-stimulated genes (ISGs). Remarkably, we found a significant upregulation of the ISG interferon-inducible protein with tetrapeptide repeats 3 (IFIT3) gene exclusively in exposed uninfected or asymptomatic females, suggesting a potential role in protective immunity against symptomatic COVID-19.

After reports in 2017 of Brucella neotomae infections among humans in Costa Rica, we sequenced 12 strains isolated from rodents during 1955–1964 from Utah, USA. We observed an exact strain match between the human isolates and 1 Utah isolate. Independent confirmation is required to clarify B. neotomae zoonotic potential.

Among the difficulties in developing software-intensive systems are the necessity of managing and controlling data that must be held for decades, as well as describing the needs and concerns of a variety of stakeholders. Therefore, one cannot neglect a good Software Engineering practice which is to develop software-intensive systems based on solid software architecture. However, the processes related to the software architecture of software-intensive systems are often considered only from a low level of abstraction. A recent architectural Standard, the ISO/IEC/IEEE 42020, defines 6 clauses for the architecture process, among them the Architecture Conceptual-ization process is the subject of this study. Considering that the ISO/IEC/IEEE 42020 has only recently been published, given the importance of establishing a well-defined software architecture, and considering the difficulties of understanding an architectural Standard, this work proposes a framework, and then the design and further evaluation of a web-based application to support soft-ware architects in using the activities and tasks of the Architecture Conceptualization clause based on the framework described. The ArchConcept was designed to address the high-level abstraction of the Standard ISO/IEC/IEEE 42020 and can be useful for software architects who want to follow ISO/IEC/IEEE 42020’s recommendation and achieve high-quality results in their work of software architecture conceptualization. A qualitative evaluation employing a questionnaire was carried out to obtain information about the perceptions of professionals regarding the ArchConcept, according to the Technology Acceptance Model (TAM). As ArchConcept is focused on activities of Archi-tecture Conceptualization, which is one of the early stages of a software project, the results found could be evidence of the short time dedicated to the initial phases of projects and their consequences.regarding the ArchConcept, according to the Technology Acceptance Model (TAM). As ArchConcept is focused on the early stages of the project (Architecture Conceptualization), the results found in this work could be evidence of the short time dedicated to the initial phase of projects and their consequences.

A smart city is an urban centre that integrates a variety of solutions to improve infrastructure performance and achieve sustainable urban development. Urban roads are a crucial infrastructure highly demanded by citizens and organisations interested in their deployment, performance, and safety. Urban traffic signal control is an important and challenging real-world problem that aims to monitor and improve traffic congestion. The deployment of traffic signals for vehicles or pedestrians at an intersection is a complex activity that changes constantly, so it is necessary to establish rules to control the flow of vehicles and pedestrians. Thus, this article describes the joint use of the SmartCitySysML, a profile proposed by the authors, with TCPN (Timed Coloured Petri Nets) to refine and formally model SysML diagrams specifying the internal behaviour, and then verify the developed model to prove behavioural properties of an urban traffic signal control system.

Objectives: The X-chromosome contains the largest number of immune-related genes, which play a major role in COVID-19 symptomatology and susceptibility. Here, we had a unique opportunity to investigate, for the first time, COVID-19 outcomes in six unvaccinated young Brazilian patients with Turner syndrome (TS; 45, X0), including one case of critical illness in a child aged 10 years, to evaluate their immune response according to their genetic profile. Methods: A serological analysis of humoral immune response against SARS-CoV-2, phenotypic characterization of antiviral responses in peripheral blood mononuclear cells after stimuli, and the production of cytotoxic cytokines of T lymphocytes and natural killer cells were performed in blood samples collected from the patients with TS during the convalescence period. Whole exome sequencing was also performed. Results: Our volunteers with TS showed a delayed or insufficient humoral immune response to SARS-CoV-2 (particularly immunoglobulin G) and a decrease in interferon-γ production by cluster of differentiation (CD)4+ and CD8+ T lymphocytes after stimulation with toll-like receptors 7/8 agonists. In contrast, we observed a higher cytotoxic activity in the volunteers with TS than the volunteers without TS after phorbol myristate acetate/ionomycin stimulation, particularly granzyme B and perforin by CD8+ and natural killer cells. Interestingly, two volunteers with TS carry rare genetic variants in genes that regulate type I and III interferon immunity. Conclusion: Following previous reports in the literature for other conditions, our data showed that patients with TS may have an impaired immune response against SARS-CoV-2. Furthermore, other medical conditions associated with TS could make them more vulnerable to COVID-19.

Abstract The inference of genetic ancestry plays an increasingly prominent role in clinical, population, and forensic genetics studies. Several genotyping strategies and analytical methodologies have been developed over the last few decades to assign individuals to specific biogeographic regions. However, despite these efforts, ancestry inference in populations with a recent history of admixture, such as those in Brazil, remains a challenge. In admixed populations, proportion and components of genetic ancestry vary on different levels: (i) between populations; (ii) between individuals of the same population, and (iii) throughout the individual's genome. The present study evaluated 1171 admixed Brazilian samples to compare the genetic ancestry inferred by tri-/tetra-hybrid admixture models and evaluated different marker sets from those with small numbers of ancestry informative markers panels (AIMs), to high-density SNPs (HDSNP) and whole-genome-sequence (WGS) data. Analyses revealed greater variation in the correlation coefficient of ancestry components within and between admixed populations, especially for minority ancestral components. We also observed positive correlation between the number of markers in the AIMs panel and HDSNP/WGS. Furthermore, the greater the number of markers, the more accurate the tri-/tetra-hybrid admixture models.

Abstract Background Although older adults are at a high risk of severe or critical Covid-19, there are many cases of unvaccinated centenarians who had a silent infection or recovered from mild or moderate Covid-19. We studied three Brazilian supercentenarians, older than 110 years, who survived Covid-19 in 2020 before being vaccinated. Results Despite their advanced age, humoral immune response analysis showed that these individuals displayed robust levels of IgG and neutralizing antibodies (NAbs) against SARS-CoV-2. Enrichment of plasma proteins and metabolites related to innate immune response and host defense was also observed. None presented autoantibodies (auto-Abs) to type I interferon (IFN). Furthermore, these supercentenarians do not carry rare variants in genes underlying the known inborn errors of immunity, including particular inborn errors of type I IFN. Conclusion These observations suggest that their Covid-19 resilience might be a combination of their genetic background and their innate and adaptive immunity.

Summary: MYC proto-oncogene dysregulation alters metabolism, translation, and other functions in ways that support tumor induction and maintenance. Although Myc+/− mice are healthier and longer-lived than control mice, the long-term ramifications of more complete Myc loss remain unknown. We now describe the chronic consequences of body-wide Myc inactivation initiated postnatally. “MycKO” mice acquire numerous features of premature aging, including altered body composition and habitus, metabolic dysfunction, hepatic steatosis, and dysregulation of gene sets involved in functions that normally deteriorate with aging. Yet, MycKO mice have extended lifespans that correlate with a 3- to 4-fold lower lifetime cancer incidence. Aging tissues from normal mice and humans also downregulate Myc and gradually alter many of the same Myc target gene sets seen in MycKO mice. Normal aging and its associated cancer predisposition are thus highly linked via Myc.

Summary: Background: Patients with haematological malignancies have impaired antibody responses to SARS-CoV-2 vaccination. We aimed to investigate whether a fourth mRNA COVID-19 vaccination improved antibody quantity and quality. Methods: In this cohort study, conducted at 5 sites in the Netherlands, we compared antibody concentrations 28 days after 4 mRNA vaccinations (3-dose primary series plus 1 booster vaccination) in SARS-CoV-2 naive, immunocompromised patients with haematological malignancies to those obtained by age-matched, healthy individuals who had received the standard primary 2-dose mRNA vaccination schedule followed by a first booster mRNA vaccination. Prior to and 4 weeks after each vaccination, peripheral blood samples and data on demographic parameters and medical history were collected. Concentrations of antibodies that bind spike 1 (S1) and nucleocapsid (N) protein of SARS-CoV-2 were quantified in binding antibody units (BAU) per mL according to the WHO International Standard for COVID-19 serological tests. Seroconversion was defined as an S1 IgG concentration >10 BAU/mL and a previous SARS-CoV-2 infection as N IgG >14.3 BAU/mL. Antibody neutralising activity was tested using lentiviral-based pseudoviruses expressing spike protein of SARS-CoV-2 wild-type (D614G), Omicron BA.1, and Omicron BA.4/5 variants. This study is registered with EudraCT, number 2021-001072-41. Findings: Between March 24, 2021 and May 4, 2021, 723 patients with haematological diseases were enrolled, of which 414 fulfilled the inclusion criteria for the current analysis. Although S1 IgG concentrations in patients significantly improved after the fourth dose, they remained significantly lower compared to those obtained by 58 age-matched healthy individuals after their first booster (third) vaccination. The rise in neutralising antibody concentration was most prominent in patients with a recovering B cell compartment, although potent responses were also observed in patients with persistent immunodeficiencies. 19% of patients never seroconverted, despite 4 vaccinations. Patients who received their first 2 vaccinations when they were B cell depleted and the third and fourth vaccination during B cell recovery demonstrated similar antibody induction dynamics as patients with normal B cell numbers during the first 2 vaccinations. However, the neutralising capacity of these antibodies was significantly better than that of patients with normal B cell numbers after two vaccinations. Interpretation: A fourth mRNA COVID-19 vaccination improved S1 IgG concentrations in the majority of patients with a haematological malignancy. Vaccination during B cell depletion may pave the way for better quality of antibody responses after B cell reconstitution. Funding: The Netherlands Organisation for Health Research and Development and Amsterdam UMC.

Introduction: Research in the field of pharmacogenomics (PGx) aims to identify genetic variants that modulate response to drugs, through alterations in their pharmacokinetics (PK) or pharmacodynamics (PD). The distribution of PGx variants differs considerably among populations, and whole-genome sequencing (WGS) plays a major role as a comprehensive approach to detect both common and rare variants. This study evaluated the frequency of PGx markers in the context of the Brazilian population, using data from a population-based admixed cohort from Sao Paulo, Brazil, which includes variants from WGS of 1,171 unrelated, elderly individuals.Methods: The Stargazer tool was used to call star alleles and structural variants (SVs) from 38 pharmacogenes. Clinically relevant variants were investigated, and the predicted drug response phenotype was analyzed in combination with the medication record to assess individuals potentially at high-risk of gene-drug interaction.Results: In total, 352 unique star alleles or haplotypes were observed, of which 255 and 199 had a frequency < 0.05 and < 0.01, respectively. For star alleles with frequency > 5% (n = 97), decreased, loss-of-function and unknown function accounted for 13.4%, 8.2% and 27.8% of alleles or haplotypes, respectively. Structural variants (SVs) were identified in 35 genes for at least one individual, and occurred with frequencies >5% for CYP2D6, CYP2A6, GSTM1, and UGT2B17. Overall 98.0% of the individuals carried at least one high risk genotype-predicted phenotype in pharmacogenes with PharmGKB level of evidence 1A for drug interaction. The Electronic Health Record (EHR) Priority Result Notation and the cohort medication registry were combined to assess high-risk gene-drug interactions. In general, 42.0% of the cohort used at least one PharmGKB evidence level 1A drug, and 18.9% of individuals who used PharmGKB evidence level 1A drugs had a genotype-predicted phenotype of high-risk gene-drug interaction.Conclusion: This study described the applicability of next-generation sequencing (NGS) techniques for translating PGx variants into clinically relevant phenotypes on a large scale in the Brazilian population and explores the feasibility of systematic adoption of PGx testing in Brazil.

Whole genome sequencing (WGS) data on non-European and admixed individuals remains scarce. Here, the authors analyse WGS data from 1,171 admixed elderly Brazilians from a census cohort, characterising population-specific genetic variation and exploring the clinical utility of this expanded dataset.

Brucella abortus is the main causative agent of brucellosis in cattle, leading to severe economic consequences in agriculture and affecting public health. The zoonotic nature of the infection increases the need to control the spread and dynamics of outbreaks in animals with the incorporation of high resolution genotyping techniques. Based on such methods, B. abortus is currently divided into three clades, A, B, and C. The latter includes subclades C1 and C2. This study presents the results of whole-genome sequencing of 49 B. abortus strains isolated in Kazakhstan between 1947 and 2015 and of 36 B. abortus strains of various geographic origins isolated from 1940 to 2004. In silico Multiple Locus Sequence Typing (MLST) allowed to assign strains from Kazakhstan to subclades C1 and to a much lower extend C2. Whole-genome Single-Nucleotide Polymorphism (wgSNP) analysis of the 46 strains of subclade C1 with strains of worldwide origins showed clustering with strains from neighboring countries, mostly North Caucasia, Western Russia, but also Siberia, China, and Mongolia. One of the three Kazakhstan strains assigned to subclade C2 matched the B. abortus S19 vaccine strain used in cattle, the other two were genetically close to the 104 M vaccine strain. Bayesian phylodynamic analysis dated the introduction of B. abortus subclade C1 into Kazakhstan to the 19th and early 20th centuries. We discuss this observation in view of the history of population migrations from Russia to the Kazakhstan steppes.

BackgroundChagas disease (CD) is a neglected endemic disease with worldwide impact due to migration. Approximately 50–70% of individuals in the chronic phase of CD present the indeterminate form, characterized by parasitological and/or serological evidence of Trypanosoma cruzi infection, but without clinical signs and symptoms. Subclinical abnormalities have been reported in indeterminate form of CD, including pro-inflammatory states and alterations in cardiac function, biomarkers and autonomic modulation. Moreover, individuals with CD are usually impacted on their personal and professional life, making social insertion difficult and impacting their mental health and quality of life (QoL). Physical exercise has been acknowledged as an important strategy to prevent and control numerous chronic-degenerative diseases, but unexplored in individuals with the indeterminate form of CD. The PEDI-CHAGAS study (which stands for “Home-Based Exercise Program in the Indeterminate Form of Chagas Disease” in Portuguese) aims to evaluate the effects of a home-based exercise program on physical and mental health outcomes in individuals with indeterminate form of CD.Methods and designThe PEDI-CHAGAS is a two-arm (exercise and control) phase 3 superiority randomized clinical trial including patients with indeterminate form of CD. The exclusion criteria are

Abstract HLA-G is a promiscuous immune checkpoint molecule. The HLA-G gene presents substantial nucleotide variability in its regulatory regions. However, it encodes a limited number of proteins compared to classical HLA class I genes. We characterized the HLA-G genetic variability in 4640 individuals from 88 different population samples across the globe by using a state-of-the-art method to characterize polymorphisms and haplotypes from high-coverage next-generation sequencing data. We also provide insights regarding the HLA-G genetic diversity and a resource for future studies evaluating HLA-G polymorphisms in different populations and association studies. Despite the great haplotype variability, we demonstrated that: (1) most of the HLA-G polymorphisms are in introns and regulatory sequences, and these are the sites with evidence of balancing selection, (2) linkage disequilibrium is high throughout the gene, extending up to HLA-A, (3) there are few proteins frequently observed in worldwide populations, with lack of variation in residues associated with major HLA-G biological properties (dimer formation, interaction with leukocyte receptors). These observations corroborate the role of HLA-G as an immune checkpoint molecule rather than as an antigen-presenting molecule. Understanding HLA-G variability across populations is relevant for disease association and functional studies.

Abstract Background Hereditary transthyretin-mediated amyloidosis, also known as ATTRv amyloidosis (v for variant), is a rare, autosomal dominant, fatal disease, in which systemic amyloid progressively impairs multiple organs, leading to disability and death. The recent approval of disease-modifying therapies offers the hope of stabilization or eventual reversal of disease progression, and yet highlights a lack of disease-management guidance. A multidisciplinary panel of expert clinicians from France and the US came to consensus on monitoring the disease and identifying progression through a clinical opinion questionnaire, a roundtable meeting, and multiple rounds of feedback. Monitoring disease and progression A multidisciplinary team should monitor ATTRv amyloidosis disease course by assessing potential target organs at baseline and during follow-up for signs and symptoms of somatic and autonomic neuropathy, cardiac dysfunction and restrictive cardiomyopathy, and other manifestations. Variability in penetrance, symptoms, and course of ATTRv amyloidosis requires that all patients, regardless of variant status, undergo regular and standardized assessment in all these categories. Progression in ATTRv amyloidosis may be indicated by: worsening of several existing quantifiable symptoms or signs; the appearance of a new symptom; or the worsening of a single symptom that results in a meaningful functional impairment. Conclusions We suggest that a multisystem approach to monitoring the signs and symptoms of ATTRv amyloidosis best captures the course of the disease. We hope this work will help form the basis of further, consensus-based guidance for the treatment of ATTRv amyloidosis.

ABSTRACT Enterovirus A71 (EV-A71) is a causative agent of life-threatening neurological diseases in young children. EV-A71 is highly infectious but it remains unclear how the virus disseminates from primary entry sites—the mucosa of the respiratory tract or the intestine—to secondary replication sites—skin or brain. Here, we investigated the role of dendritic cells (DCs) in EV-A71 dissemination. DCs reside in the mucosa of the airway and gut, and migrate to lymphoid tissues upon activation and, therefore, could facilitate EV-A71 dissemination to secondary replication sites. Monocyte-derived DCs were not permissive to different genotypes of EV-A71 but, notably, coculture with EV-A71-susceptiblle RD99 cells led to very efficient infection of RD99 cells. Notably, EV-A71 transmission of DCs to RD99 was independent of viral replication as a replication inhibitor did not affect transmission. Soluble heparin blocked EV-A71 transmission by DCs to RD99 cells, in contrast to antibodies against known attachment receptor DC-SIGN. These results strongly suggest that DCs might be a first target for EV-A71 and involved in viral dissemination via heparan sulfates and heparin derivatives might be an effective treatment to attenuate dissemination. IMPORTANCE EV-A71 is an emerging neurotropic virus that is of emerging concern and can result in polio-like illness. The exact mechanism of how EV-A71 results in neurological symptoms are unknown. In particular, the early dissemination of the virus from primary replication sites (airway and intestine) to secondary sites (central nervous system and skin) needs to be elucidated. There is evidence pointing toward a role for dendritic cells (DC) in EV-A71 transmission. Moreover, heparan sulfate (HS) binding mutations are observed in patients with severe diseases. Therefore, we evaluated the potential role of HS on DC in transmission. We find that HS are critical for transmitting EV-A71 by DC to target cells. Our data are consistent with other clinical and in vitro observations highlighting the importance of HS in EV-A71-induced disease.

BackgroundAlthough aging correlates with a worse prognosis for Covid-19, super elderly still unvaccinated individuals presenting mild or no symptoms have been reported worldwide. Most of the reported genetic variants responsible for increased disease susceptibility are associated with immune response, involving type I IFN immunity and modulation; HLA cluster genes; inflammasome activation; genes of interleukins; and chemokines receptors. On the other hand, little is known about the resistance mechanisms against SARS-CoV-2 infection. Here, we addressed polymorphisms in the MHC region associated with Covid-19 outcome in super elderly resilient patients as compared to younger patients with a severe outcome.MethodsSARS-CoV-2 infection was confirmed by RT-PCR test. Aiming to identify candidate genes associated with host resistance, we investigated 87 individuals older than 90 years who recovered from Covid-19 with mild symptoms or who remained asymptomatic following positive test for SARS-CoV-2 as compared to 55 individuals younger than 60 years who had a severe disease or died due to Covid-19, as well as to the general elderly population from the same city. Whole-exome sequencing and an in-depth analysis of the MHC region was performed. All samples were collected in early 2020 and before the local vaccination programs started.ResultsWe found that the resilient super elderly group displayed a higher frequency of some missense variants in the MUC22 gene (a member of the mucins’ family) as one of the strongest signals in the MHC region as compared to the severe Covid-19 group and the general elderly control population. For example, the missense variant rs62399430 at MUC22 is two times more frequent among the resilient super elderly (p = 0.00002, OR = 2.24).ConclusionSince the pro-inflammatory basal state in the elderly may enhance the susceptibility to severe Covid-19, we hypothesized that MUC22 might play an important protective role against severe Covid-19, by reducing overactive immune responses in the senior population.

BackgroundThe identification of variables obtained in the exercise test (ET) associated with increased risk of death is clinically relevant and would provide additional information for the management of Chagas disease (CD). The objective of the present study was to evaluate the association of ET variables with mortality in patients with chronic CD.MethodsThis retrospective longitudinal observational study included 232 patients (median age 46.0 years; 50% women) with CD that were followed at the Evandro Chagas National Institute of Infectious Diseases (Rio de Janeiro, Brazil) and performed an ET between 1989 and 2000. The outcome of interest was all-cause mortality.ResultsThere were 103 deaths (44.4%) during a median follow-up of 21.5 years (IQR 25–75% 8.0–27.8), resulting in 24.5 per 1,000 patients/year incidence rate. The ET variables associated with mortality after adjustments for potential confounders were increased maximal (HR 1.02; 95% CI 1.00–1.03 per mmHg) and change (HR 1.03; 95% CI 1.01–1.06 per mmHg) of diastolic blood pressure (DBP) during ET, ventricular tachycardia at rest (HR 3.95; 95% CI 1.14–13.74), during exercise (HR 2.73; 95% CI 1.44–5.20), and recovery (HR 2.60; 95% CI 1.14–5.91), and premature ventricular complexes during recovery (HR 2.06; 1.33–3.21).ConclusionOur findings suggest that ET provides important prognostic value for mortality risk assessment in patients with CD, with hemodynamic (increased DBP during exercise) and electrocardiographic (presence of ventricular arrhythmias) variables independently associated with an increased mortality risk in patients with CD. The identification of individuals at higher mortality risk can facilitate the development of intervention strategies (e.g., close follow-up) that may potentially have an impact on the longevity of patients with CD.

BackgroundThe influence of the host genome on coronavirus disease 2019 (COVID-19) susceptibility and severity is supported by reports on monozygotic (MZ) twins where both were infected simultaneously with similar disease outcomes, including several who died due to the SARS-CoV-2 infection within days apart. However, successive exposures to pathogens throughout life along with other environmental factors make the immune response unique for each individual, even among MZ twins.Case presentation and methodsHere we report a case of a young adult monozygotic twin pair, who caught attention since both presented simultaneously severe COVID-19 with the need for oxygen support despite age and good health conditions. One of the twins, who spent more time hospitalized, reported symptoms of long-COVID even 7 months after infection. Immune cell profile and specific responses to SARS-CoV-2 were evaluated as well as whole exome sequencing.ConclusionAlthough the MZ twin brothers shared the same genetic mutations which may be associated with their increased risk of developing severe COVID-19, their clinical progression was different, reinforcing the role of both immune response and genetics in the COVID-19 presentation and course. Besides, post-COVID syndrome was observed in one of them, corroborating an association between the duration of hospitalization and the occurrence of long-COVID symptoms.

Objectives Adherence to injury prevention programmes in football remains low, which is thought to drastically reduce the effects of injury prevention programmes. Reasons why (medical) staff and players implement injury prevention programmes, have been investigated, but player’s characteristics and perceptions about these programmes might influence their adherence. Therefore, this study investigated the relationships between player’s characteristics and adherence and between player’s perceptions and adherence following an implemented injury prevention programme.Methods Data from 98 of 221 football players from the intervention group of a cluster randomised controlled trial concerning hamstring injury prevention were analysed.Results Adherence was better among older and more experienced football players, and players considered the programme more useful, less intense, more functional and less time-consuming. Previous hamstring injuries, educational level, the programme’s difficulty and intention to continue the exercises were not significantly associated with adherence.Conclusion These player’s characteristics and perceptions should be considered when implementing injury prevention programmes.

ABSTRACT The quality of the basal cut of sugarcane during harvest can affect the longevity of the crop, and the cutting tool is one of the main causes of damage during harvesting. The aim of this study was to evaluate the performance of two cutting tools: an impact cutting system (ICS) using knives and a continuous cutting system (CCS) using saws. Laboratory tests were carried out to obtain the stalk damage index at different device travel speeds and to determine the invisible losses caused by each cutting system. The results showed that both cutting systems presented acceptable levels for the stalk damage index; however, the CCS obtained better cut quality, corresponding with decreased general damage. The invisible losses caused by the cutting tools in relation to the total harvested mass were 0.52% and 0.54% for the CCS and ICS, respectively. The highest invisible losses were obtained at speeds of 2, 3, and 4 km h-1 for the ICS, showing a statistical difference in relation to the CCS. No statistical difference was noted for both the systems at 5 and 6 km h-1.

Abstract Background Approximately 5% of the human genome shows common structural variation, which is enriched for genes involved in the immune response and cell-cell interactions. A well-established region of extensive structural variation is the glycophorin gene cluster, comprising three tandemly-repeated regions about 120 kb in length and carrying the highly homologous genes GYPA, GYPB and GYPE. Glycophorin A (encoded by GYPA) and glycophorin B (encoded by GYPB) are glycoproteins present at high levels on the surface of erythrocytes, and they have been suggested to act as decoy receptors for viral pathogens. They are receptors for the invasion of the protist parasite Plasmodium falciparum, a causative agent of malaria. A particular complex structural variant, called DUP4, creates a GYPB-GYPA fusion gene known to confer resistance to malaria. Many other structural variants exist across the glycophorin gene cluster, and they remain poorly characterised. Results Here, we analyse sequences from 3234 diploid genomes from across the world for structural variation at the glycophorin locus, confirming 15 variants in the 1000 Genomes project cohort, discovering 9 new variants, and characterising a selection of these variants using fibre-FISH and breakpoint mapping at the sequence level. We identify variants predicted to create novel fusion genes and a common inversion duplication variant at appreciable frequencies in West Africans. We show that almost all variants can be explained by non-allelic homologous recombination and by comparing the structural variant breakpoints with recombination hotspot maps, confirm the importance of a particular meiotic recombination hotspot on structural variant formation in this region. Conclusions We identify and validate large structural variants in the human glycophorin A-B-E gene cluster which may be associated with different clinical aspects of malaria.

Purpose - The purpose of this paper is to retrace past developments that occurred in the Alaskan and Canadian North as of result of the Second World War and illustrate the ramifications of these events in the Canadian and American political landscapes as it pertains to warfare tourism. The paper also intends to initiate a discussion on how certain narratives pertaining to warfare tourism are promoted, while others are overlooked. Design/methodology/approach - This paper analyses the political, economic, socio-cultural and technological factors that resulted in tourism growth or the lack thereof in the Canadian and American Norths. Findings - Warfare tourism, like most types of tourism, is expected to grow. Through this growth comes opportunities to expand and integrate the discussion pertaining to warfare tourism in the Canadian and American Norths while also providing a starting point for discussion about potential solutions to address warfare tourism and cultural dissonance. Research limitations/implications - This viewpoint is dependent on literature reviews. Practical implications - The relationship between Indigenous peoples and other marginalized populations in the Second World War and warfare tourism is a relatively new research area. For warfare tourism to become integrated into tourism policies and developments, a willingness to address cultural dissonance and integrate populations formerly marginalized in the Second World War will be required. This paper examines how northern and other marginalized voices can be integrated in future commemoration and interpretation strategies. Social implications - The paper provides an opportunity to examine the growth and healing that can result from warfare tourism. Originality/value - This interdisciplinary collaboration conducted by a military historian, a northern historian and a tourism research researcher provides one of the first examinations of the impacts of the Second World War in North America, and the relevance of these impacts to the interpretation of warfare tourism in Canada.

Introduction: Although parallel graft endovascular aortic repair (pg-EVAR) was initially described as a rescue technique for endovascular aneurysm repairs that unintentionally excluded visceral branches, its use has expanded to include endovascular repairs of paravisceral and thoracoabdominal aneurysms. However, there is limited literature on utilization in emergency repair of ruptured aortic aneurysms which previously underwent elective open repair. Case 1: A 73-year-old man with a remote history of an open AAA repair with a tube graft presented as a transfer with two weeks of worsening left chest pain and was found to have a 6–7 cm contained rupture of a type III thoracoabdominal aortic aneurysm on computed tomography (CT). Due to his anatomy, previous repair, and comorbidities, endovascular repair was preferred over a redo open approach. He was taken for an emergent endovascular repair – a planned sandwich graft with the proximal seal in the mid thoracic aorta and the distal seal in the infrarenal aortic graft. The stenotic celiac artery was nearly occluded, so visceral stents were placed into the superior mesenteric and bilateral renal arteries. His hospital course was complicated by acute kidney injury, deconditioning, and failure to thrive. CT on postoperative day 44 showed a technically successful pg-EVAR with no evidence of endoleak. Case 2: A 69-year-old woman who recently underwent an open AAA repair at an outside facility developed nausea, vomiting, abdominal pain and down-trending hemoglobin while hospitalized for workup of a new coagulopathy. She was found to have a contained rupture of a proximal anastomotic pseudoaneurysm. Due to her recent repair and current medical state, she was brought to the hybrid suite for emergent endovascular repair. The location of the rupture required entire visceral segment coverage, so a pg-EVAR with spinal drainage was planned. Her celiac, superior mesenteric, and left renal arteries were preserved with stents. Her postoperative course was complicated by a hematoma with persistent rebleeding at her brachial access site which resolved following the placement of a covered stent. CT on postoperative day 16 showed a technically successful pg-EVAR with no evidence of endoleak. Discussion: Many patients remain ineligible for conventional EVAR due to anatomic variations and supra-renal aneurysmal disease. Customized branched or fenestrated endografts have been developed to overcome these limitations. However, production time requires weeks, and grafts with greater than two fenestrations are not commercially available in the United States. Because they use readily available devices, parallel graft repairs may be beneficial when urgent repair is needed. There remains a paucity of data on their usage in emergency repairs of aortic aneurysms, particularly in aneurysms that had been previously repaired surgically. The technical success in the two cases detailed here suggest that parallel graft techniques can be used to expeditiously salvage complex emergency aneurysms with successful sealing of parallel grafts into a previous infrarenal aortic graft.

Summary: The question of whether host genetics plays a role in the development of the infant gut microbiota does not, as yet, have a clear answer. In order to throw additional light on this question, we have analyzed 16S rRNA amplicon sequences from 99 valid fecal samples of five sets of dichorionic triplet babies born by C-section from 1 to 36 months of age. Beta diversity analysis showed that monozygotic twins were more similar to each other than their dizygotic siblings. Monozygotic twins also tended to share more amplicon sequence variants between them. Heritability analysis showed that the genera Bacteroides and Veillonella are particularly susceptible to host genetics. We conclude that infant gut microbiota development is influenced by host genetics, but this effect is subtle and may affect only certain bacterial taxa during a limited time period early in life.

Mental health problems are a leading cause of health-related disability among children and adolescents. Organized activities are a possible preventive factor for mental health problems. An aggregated overview of evidence is relevant for youth policymakers and is lacking so far.Thus we aim to provide an overview of published systematic reviews and meta-analyses on the impact of participation in organized sport and non-sport activities (e.g. arts, music) on childhood and adolescent mental health. Systematic reviews were identified through a search in five databases (Embase, MEDLINE, Web of Science core collection, CINAHL and PsycINFO) on 25-March-2021. Systematic reviews about organized activities and mental health outcomes in 0–21-year-olds published in English were included. Two independent reviewers assessed titles, abstracts and full texts, performed data-extraction and quality assessment using the AMSTAR-2 and assessed the quality of evidence. Out of 833 studies, six were considered eligible. Quality of the reviews ranged from critically low to moderate. Most reviews focused on organized sport activities, focusing on: team sport, level of sport involvement, extracurricular and community sport activities. Indications of a positive impact on mental health outcomes were found for participation in team sport, in (school) clubs, and in extracurricular and community sport and non-sport activities. We found a small positive impact of organized sport activities on mental health outcomes among children and adolescents. This seems not to depend on any specific type of organized sport activity. Limited evidence was found for organized non-sport activities.

Recurrence of COVID-19 in recovered patients has been increasingly reported. However, the immune mechanisms behind the recurrence have not been thoroughly investigated. The presence of neutralizing antibodies (nAbs) in recurrence/reinfection cases suggests that other types of immune response are involved in protection against recurrence. Here, we investigated the innate type I/III interferon (IFN) response, binding and nAb assays and T-cell responses to severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) with IFN gamma (IFNγ) enzyme-linked spot assay (ELISPOT) in three pairs of young adult monozygotic (MZ) twins with previous confirmed COVID-19, one of them presenting a severe recurrence four months after the initial infection. Twin studies have been of paramount importance to comprehend the immunogenetics of infectious diseases. Each MZ twin pair was previously exposed to SARS-CoV-2, as seen by clinical reports. The six individuals presented similar overall recovered immune responses except for the recurrence case, who presented a drastically reduced number of recognized SARS-CoV-2 T-cell epitopes on ELISPOT as compared to her twin sister and the other twin pairs. Our results suggest that the lack of a broad T-cell response to initial infection may have led to recurrence, emphasizing that an effective SARS-CoV-2-specific T-cell immune response is key for complete viral control and avoidance of clinical recurrence of COVID-19.

Despite the high number of individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who develop coronavirus disease 2019 (COVID-19) symptoms worldwide, many exposed individuals remain asymptomatic and/or uninfected and seronegative. This could be explained by a combination of environmental (exposure), immunological (previous infection), epigenetic, and genetic factors. Aiming to identify genetic factors involved in immune response in symptomatic COVID-19 as compared to asymptomatic exposed individuals, we analyzed 83 Brazilian couples where one individual was infected and symptomatic while the partner remained asymptomatic and serum-negative for at least 6 months despite sharing the same bedroom during the infection. We refer to these as “discordant couples”. We performed whole-exome sequencing followed by a state-of-the-art method to call genotypes and haplotypes across the highly polymorphic major histocompatibility complex (MHC) region. The discordant partners had comparable ages and genetic ancestry, but women were overrepresented (65%) in the asymptomatic group. In the antigen-presentation pathway, we observed an association between HLA-DRB1 alleles encoding Lys at residue 71 (mostly DRB1*03:01 and DRB1*04:01) and DOB*01:02 with symptomatic infections and HLA-A alleles encoding 144Q/151R with asymptomatic seronegative women. Among the genes related to immune modulation, we detected variants in MICA and MICB associated with symptomatic infections. These variants are related to higher expression of soluble MICA and low expression of MICB. Thus, quantitative differences in these molecules that modulate natural killer (NK) activity could contribute to susceptibility to COVID-19 by downregulating NK cell cytotoxic activity in infected individuals but not in the asymptomatic partners.

The description of current load monitoring practices may serve to highlight developmental needs for both the training ground, academia and related industries. While previous studies described these practices in elite men's football, no study has provided an overview of load monitoring practices in elite women's football. Given the clear organizational differences (i.e., professionalization and infrastructure) between men's and women's clubs, making inferences based on men's data is not appropriate. Therefore, this study aims to provide a first overview of the current load monitoring practices in elite women's football. Twenty-two elite European women's football clubs participated in a closed online survey (40% response rate). The survey consisted of 33 questions using multiple choice or Likert scales. The questions covered three topics; type of data collected and collection purpose, analysis methods, and staff member involvement. All 22 clubs collected data related to different load monitoring purposes, with 18 (82%), 21 (95%), and 22 (100%) clubs collecting external load, internal load, and training outcome data, respectively. Most respondents indicated that their club use training models and take into account multiple indicators to analyse and interpret the data. While sports-science staff members were most involved in the monitoring process, coaching, and sports-medicine staff members also contributed to the discussion of the data. Overall, the results of this study show that most elite women's clubs apply load monitoring practices extensively. Despite the organizational challenges compared to men's football, these observations indicate that women's clubs have a vested interest in load monitoring. We hope these findings encourage future developments within women's football.

Load monitoring is considered important to manage the physical training process in team sports such as Association Football. Previous studies have described the load monitoring practices of elite English football clubs and clubs with an established sports-science department. An examination of a broader international sample is currently not available. In addition, previous research has suggested factors that may improve the implementation of load monitoring practices, such as a strong club belief on the benefit of evidence-based practice (EBP) and high club financial resources. However, no study has examined yet the actual impact of these factors on the monitoring practices. Therefore, this study aims (1) to provide an overview of load monitoring practices in European elite football and (2) to provide insight into the differences in implementation between clubs by examining the impact of the club beliefs on the benefit of EBP and the club financial resources. An online survey, consisting of multiple choice and Likert scale questions, was distributed among sports-science and sports-medicine staff (n = 99, 50% response rate). Information was asked about the types of data collected, collection purposes, analysis methods, and staff involvement. The results indicated that external load data (e.g., global navigation satellite system, accelerometer…) was collected the most whilst respondents also indicated to collect internal load (e.g., heart rate, rating of perceived exertion…) and training outcome data (e.g., aerobic fitness, neuromuscular fatigue…) for multiple purposes. Considerable diversity in data analysis was observed suggesting that analysis is often limited to reporting the gathered data. Sports-science staff were responsible for data collection and analysis. Other staff were involved in data discussion to share decision-making. These practices were positively impacted by a stronger club belief on the benefit of EBP and greater financial resources. Creating an organizational culture, characterized by a strong belief on the benefit of EBP, is important to increase the impact of load monitoring. However, the actual potential may still be largely determined by financial resources. High-level clubs could therefore play a leading role in generating and sharing knowledge to improve training practices and player health.

The genus Brucella comprises major pathogenic species causing disease in livestock and humans, e.g. B. melitensis. In the past few years, the genus has been significantly expanded by the discovery of phylogenetically more distant lineages comprising strains from diverse wildlife animal species, including amphibians and fish. The strains represent several potential new species, with B. inopinata as solely named representative. Being genetically more distant between each other, relative to the “classical” Brucella species, they present distinct atypical phenotypes and surface antigens. Among surface protein antigens, the Omp2a and Omp2b porins display the highest diversity in the classical Brucella species. The genes coding for these proteins are closely linked in the Brucella genome and oriented in opposite directions. They share between 85 and 100% sequence identity depending on the Brucella species, biovar, or genotype. Only the omp2b gene copy has been shown to be expressed and genetic variation is extensively generated by gene conversion between the two copies. In this study, we analyzed the omp2 loci of the non-classical Brucella spp. Starting from two distinct ancestral genes, represented by Australian rodent strains and B. inopinata, a stepwise nucleotide reduction was observed in the omp2b gene copy. It consisted of a first reduction affecting the region encoding the surface L5 loop of the porin, previously shown to be critical in sugar permeability, followed by a nucleotide reduction in the surface L8 loop-encoding region. It resulted in a final omp2b gene size shared between two distinct clades of non-classical Brucella spp. (African bullfrog isolates) and the group of classical Brucella species. Further evolution led to complete homogenization of both omp2 gene copies in some Brucella species such as B. vulpis or B. papionis. The stepwise omp2b deletions seemed to be generated through recombination with the respective omp2a gene copy, presenting a conserved size among Brucella spp., and may involve short direct DNA repeats. Successive Omp2b porin alteration correlated with increasing porin permeability in the course of evolution of Brucella spp. They possibly have adapted their porin to survive environmental conditions encountered and to reach their final status as intracellular pathogen.

Deciphering the evolutionary history of pathogenic bacteria and their near neighbors may help to understand the genetic or ecological bases which led to their pathogenic behavior. The Brucellaceae family comprises zoonotic pathogenic species belonging to the genus Brucella as well as the environmental genus Ochrobactrum for which some species are considered as opportunistic pathogens. Here, we used a phylogenomic approach including a set of 145 Brucellaceae genomes representative of the family diversity and more than 40 genomes of the order Rhizobiales to infer the taxonomic relationships between the family’s species. Our results clarified some unresolved phylogenetic ambiguities, conducting to the exclusion of Mycoplana spp. out of the family Brucellaceae and the positioning of all Brucella spp. as a single genomic species within the current Ochrobactrum species diversity. Additional analyses also revealed that Ochrobactrum spp. separate into two clades, one comprising mostly environmental species while the other one includes the species considered as pathogens (Brucella spp.) or opportunistic pathogens (mainly O. anthropi, O. intermedium, and O. pseudintermedium). Finally, we show that O. intermedium is undergoing a beginning of genome reduction suggestive of an ongoing ecological niche specialization, and that some lineages of O. intermedium and O. anthropi may shift toward an adaption to the human host.

Members of the genus Brucella cluster in two phylogenetic groups: classical and non-classical species. The former group is composed of Brucella species that cause disease in mammals, including humans. A Brucella species, labeled as Brucella sp. BCCN84.3, was isolated from the testes of a Saint Bernard dog suffering orchiepididymitis, in Costa Rica. Following standard microbiological methods, the bacterium was first defined as “Brucella melitensis biovar 2.” Further molecular typing, identified the strain as an atypical “Brucella suis.” Distinctive Brucella sp. BCCN84.3 markers, absent in other Brucella species and strains, were revealed by fatty acid methyl ester analysis, high resolution melting PCR and omp25 and omp2a/omp2b gene diversity. Analysis of multiple loci variable number of tandem repeats and whole genome sequencing demonstrated that this isolate was different from the currently described Brucella species. The smooth Brucella sp. BCCN84.3 clusters together with the classical Brucella clade and displays all the genes required for virulence. Brucella sp. BCCN84.3 is a species nova taxonomical entity displaying pathogenicity; therefore, relevant for differential diagnoses in the context of brucellosis. Considering the debate on the Brucella species concept, there is a need to describe the extant taxonomical entities of these pathogens in order to understand the dispersion and evolution.

La historia de un concepto a veces descubre representaciones mentales y expresiones particulares que revelan desarrollos teóricos distintos. Aunque el análisis económico de los derechos de propiedad fue iniciado a comienzos de los años sesenta por Alchian, Coase y Demsetz, el concepto era conocido para los economistas clásicos. En su sentido amplio, la definición de derechos de propiedad estaba presente en las Lecturas sobre jurisprudencia de Adam Smith. Evolucionó notablemente con Ricardo, Senior y J. S. Mill. Recordar las ideas de los clásicos acerca de los derechos de propiedad y del uso de los factores de producción –trabajo, tierra y capital– y su producto mejorará en forma visible el debate actual.

Inertial sensor-based measurements of lower body kinematics in football players may improve physical load estimates during training sessions and matches. However, the validity of inertial-based motion analysis systems is specific to both the type of movement and the intensity at which movements are executed. Importantly, such a system should be relatively simple, so it can easily be used in daily practice. This paper introduces an easy-to-use inertial-based motion analysis system and evaluates its validity using an optoelectronic motion analysis system as a gold standard. The system was validated in 11 football players for six different football specific movements that were executed at low, medium, and maximal intensity. Across all movements and intensities, the root mean square differences (means ± SD) for knee and hip flexion/extension angles were 5.3° ± 3.4° and 8.0° ± 3.5°, respectively, illustrating good validity with the gold standard. In addition, mean absolute flexion/extension angular velocities significantly differed between the three movement intensities. These results show the potential to use the inertial based motion analysis system in football practice to obtain lower body kinematics and to quantify movement intensity, which both may improve currently used physical load estimates of the players.

Background Insufficient postmatch recovery in elite players may cause an increased risk of injuries, illnesses and non-functional over-reaching.Objective To evaluate postmatch recovery time courses of physical performance and biochemical markers in team ball sport players.Study design Systematic review.Data sources PubMed and Web of Science.Eligibility criteria for selecting studies This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Critical Review Form for Quantitative Studies was used to evaluate quality. Studies were included if they met the following criteria: (1) original research evaluated players’ physical recovery postmatch; (2) team/intermittent sports; and (3) at least two postmeasurements were compared with baseline values.Results Twenty-eight studies were eligible. Mean methodological quality was 11.2±1.11. Most used performance tests and biochemical markers were the countermovement jump test, sprint tests and creatine kinase (CK), cortisol (C) and testosterone (T), respectively.Summary/conclusions The current evidence demonstrates that underlying mechanisms of muscle recovery are still in progress while performance recovery is already reached. CK recovery time courses are up to ≥72 hours. Soccer and rugby players need more time to recover for sprint performance, CK and C in comparison to other team ball sports. There are more high-quality studies needed regarding recovery in various team sports and recovery strategies on an individual level should be evaluated.Clinical relevance Ongoing insufficient recovery can be prevented by the use of the presented recovery time courses as specific practical recovery guidelines.

Brucellosis, an infectious disease caused by Brucella, is one of the most extended bacterial zoonosis in the world and an important cause of economic losses and human suffering. The lipopolysaccharide (LPS) of Brucella plays a major role in virulence as it impairs normal recognition by the innate immune system and delays the immune response. The LPS core is a branched structure involved in resistance to complement and polycationic peptides, and mutants in glycosyltransferases required for the synthesis of the lateral branch not linked to the O-polysaccharide (O-PS) are attenuated and have been proposed as vaccine candidates. For this reason, the complete understanding of the genes involved in the synthesis of this LPS section is of particular interest. The chemical structure of the Brucella LPS core suggests that, in addition to the already identified WadB and WadC glycosyltransferases, others could be implicated in the synthesis of this lateral branch. To clarify this point, we identified and constructed mutants in 11 ORFs encoding putative glycosyltransferases in B. abortus. Four of these ORFs, regulated by the virulence regulator MucR (involved in LPS synthesis) or the BvrR/BvrS system (implicated in the synthesis of surface components), were not required for the synthesis of a complete LPS neither for virulence or interaction with polycationic peptides and/or complement. Among the other seven ORFs, six seemed not to be required for the synthesis of the core LPS since the corresponding mutants kept the O-PS and reacted as the wild type with polyclonal sera. Interestingly, mutant in ORF BAB1_0953 (renamed wadD) lost reactivity against antibodies that recognize the core section while kept the O-PS. This suggests that WadD is a new glycosyltransferase adding one or more sugars to the core lateral branch. WadD mutants were more sensitive than the parental strain to components of the innate immune system and played a role in chronic stages of infection. These results corroborate and extend previous work indicating that the Brucella LPS core is a branched structure that constitutes a steric impairment preventing the elements of the innate immune system to fight against Brucella.

Previous studies have shown the usefulness of MLVA16 as a rapid molecular identification and classification method for Brucella species and biovars including recently described novel Brucella species from wildlife. Most studies were conducted on a limited number of strains from limited geographic/host origins. The objective of this study was to assess genetic diversity of Brucella spp. by MLVA16 on a larger scale. Thus, 1404 animal or human isolates collected from all parts of the world over a period of 32 years (1974-2006) were investigated. Selection of the 1404 strains was done among the approximately 4000 strains collection of the BCCN (Brucella Culture Collection Nouzilly), based on classical biotyping and on the animal/human/geographic origin over the time period considered. MLVA16 was performed on extracted DNAs using high throughput capillary electrophoresis. The 16 loci were amplified in four multiplex PCR reactions. This large scale study firstly confirmed the accuracy of MLVA16 typing for Brucella species and biovar identification and its congruence with the recently described Extended Multilocus Sequence Analysis. In addition, it allowed identifying novel MLVA11 (based upon 11 slowly evolving VNTRs) genotypes representing an increase of 15% relative to the previously known Brucella MLVA11 genotypes. Cluster analysis showed that among the MLVA16 genotypes some were genetically more distant from the major classical clades. For example new major clusters of B. abortus biovar 3 isolated from cattle in Sub-Saharan Africa were identified. For other classical species and biovars this study indicated also genotypic expansion within the population structure of classical Brucella species. MLVA proves to be a powerful tool to rapidly assess genetic diversity of bacterial populations on a large scale, as here on a large collection of strains of the genomically homogeneous genus Brucella. The highly discriminatory power of MLVA appears of particular interest as a first step for selection of Brucella strains for whole-genome sequencing. The MLVA data of this study were added to the public Brucella MLVA database at http://microbesgenotyping.i2bc.paris-saclay.fr. Current version Brucella_4_3 comprises typing data from more than 5000 strains including in silico data analysis of public whole genome sequence datasets.