CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma.

Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients. Methods: 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients. Results: Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients. Conclusion: CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.

Defining the Emergence of New Immunotherapy Approaches in Breast Cancer: Role of Myeloid-Derived Suppressor Cells.

Breast cancer (BC) continues to be the most diagnosed tumor in women and a very heterogeneous disease both inter- and intratumoral, mainly given by the variety of molecular profiles with different biological and clinical characteristics. Despite the advancements in early detection and therapeutic strategies, the survival rate is low in patients who develop metastatic disease. Therefore, it is mandatory to explore new approaches to achieve better responses. In this regard, immunotherapy arose as a promising alternative to conventional treatments due to its ability to modulate the immune system, which may play a dual role in this disease since the relationship between the immune system and BC cells depends on several factors: the tumor histology and size, as well as the involvement of lymph nodes, immune cells, and molecules that are part of the tumor microenvironment. Particularly, myeloid-derived suppressor cell (MDSC) expansion is one of the major immunosuppressive mechanisms used by breast tumors since it has been associated with worse clinical stage, metastatic burden, and poor efficacy of immunotherapies. This review focuses on the new immunotherapies in BC in the last five years. Additionally, the role of MDSC as a therapeutic target in breast cancer will be described.

Obesity and Risk for Lymphoma: Possible Role of Leptin.

Obesity, which is considered a pandemic due to its high prevalence, is a risk factor for many types of cancers, including lymphoma, through a variety of mechanisms by promoting an inflammatory state. Specifically, over the last few decades, obesity has been suggested not only to increase the risk of lymphoma but also to be associated with poor clinical outcomes and worse responses to different treatments for those diseases. Within the extensive range of proinflammatory mediators that adipose tissue releases, leptin has been demonstrated to be a key adipokine due to its pleotropic effects in many physiological systems and diseases. In this sense, different studies have analyzed leptin levels and leptin/leptin receptor expressions as a probable bridge between obesity and lymphomas. Since both obesity and lymphomas are prevalent pathophysiological conditions worldwide and their incidences have increased over the last few years, here we review the possible role of leptin as a promising proinflammatory mediator promoting lymphomas.

The effects of dendritic cell-based vaccines in the tumor microenvironment: Impact on myeloid-derived suppressor cells.

Dendritic cells (DCs) are a heterogenous population of professional antigen presenting cells whose main role is diminished in a variety of malignancies, including cancer, leading to ineffective immune responses. Those mechanisms are inhibited due to the immunosuppressive conditions found in the tumor microenvironment (TME), where myeloid-derived suppressor cells (MDSCs), a heterogeneous population of immature myeloid cells known to play a key role in tumor immunoevasion by inhibiting T-cell responses, are extremely accumulated. In addition, it has been demonstrated that MDSCs not only suppress DC functions, but also their maturation and development within the myeloid linage. Considering that an increased number of DCs as well as the improvement in their functions boost antitumor immunity, DC-based vaccines were developed two decades ago, and promising results have been obtained throughout these years. Therefore, the remodeling of the TME promoted by DC vaccination has also been explored. Here, we aim to review the effectiveness of different DCs-based vaccines in murine models and cancer patients, either alone or synergistically combined with other treatments, being especially focused on their effect on the MDSC population.

Complete Genome Sequences of Two Salmonella enterica subsp. enterica Serovar Anatum Strains Isolated from Papaya.

Salmonella enterica is a major global foodborne pathogen that causes gastroenteritis and, in some cases, death. Salmonella serovar Anatum has been increasingly associated with foodborne salmonellosis outbreaks. In this report, we announce two complete genome sequences of Salmonella Anatum isolated from papaya fruit.

Phylogenomic Pipeline Validation for Foodborne Pathogen Disease Surveillance.

Foodborne pathogen surveillance in the United States is transitioning from strain identification using restriction digest technology (pulsed-field gel electrophoresis [PFGE]) to shotgun sequencing of the entire genome (whole-genome sequencing [WGS]). WGS requires a new suite of analysis tools, some of which have long histories in academia but are new to the field of public health and regulatory decision making. Although the general workflow is fairly standard for collecting and analyzing WGS data for disease surveillance, there are a number of differences in how the data are collected and analyzed across public health agencies, both nationally and internationally. This impedes collaborative public health efforts, so national and international efforts are underway to enable direct comparison of these different analysis methods. Ultimately, the harmonization efforts will allow the (mutually trusted and understood) production and analysis of WGS data by labs and agencies worldwide, thus improving outbreak response capabilities globally. This review provides a historical perspective on the use of WGS for pathogen tracking and summarizes the efforts underway to ensure the major steps in phylogenomic pipelines used for pathogen disease surveillance can be readily validated. The tools for doing this will ensure that the results produced are sound, reproducible, and comparable across different analytic approaches.

In-depth comparative analysis of Illumina® MiSeq run metrics: Development of a wet-lab quality assessment tool.

Whole genome sequencing of bacterial isolates has become a daily task in many laboratories, generating incredible amounts of data. However, data acquisition is not an end in itself; the goal is to acquire high-quality data useful for understanding genetic relationships. Having a method that could rapidly determine which of the many available run metrics are the most important indicators of overall run quality and having a way to monitor these during a given sequencing run would be extremely helpful to this effect. Therefore, we compared various run metrics across 486 MiSeq runs, from five different machines. By performing a statistical analysis using principal components analysis and a K-means clustering algorithm of the metrics, we were able to validate metric comparisons among instruments, allowing for the development of a predictive algorithm, which permits one to observe whether a given MiSeq run has performed adequately. This algorithm is available in an Excel spreadsheet: that is, MiSeq Instrument & Run (In-Run) Forecast. Our tool can help verify that the quantity/quality of the generated sequencing data consistently meets or exceeds recommended manufacturer expectations. Patterns of deviation from those expectations can be used to assess potential run problems and plan preventative maintenance, which can save valuable time and funding resources.

Utilizing the Public GenomeTrakr Database for Foodborne Pathogen Traceback.

This protocol outlines the all the steps necessary to become a GenomeTrakr data contributor. GenomeTrakr is an international genomic reference database of mostly food and environmental isolates from foodborne pathogens. The data and analyses are housed at the National Center for Biotechnology Information (NCBI), which is a database freely available to anyone in the world. The Pathogen Detection browser at NCBI computes daily cluster results adding the newly submitted data to the existing phylogenetic clusters of closely related genomes. Contributors to this database can see how their new isolates are related to the real-time foodborne pathogen surveillance program established in the USA and a few other countries, and at the same time adding valuable new data to the reference database.

Correction to: Utilizing the Public GenomeTrakr Database for Foodborne Pathogen Traceback.

The chapter "Utilizing the Public GenomeTrakr Database for Foodborne Pathogen Traceback" is changed to open access, per the author's request in this revised version of the book.

Draft Genome Sequences of 57 Salmonella enterica Strains from Selected U.S. Swine Feed Mills.

The number of Salmonella infection cases linked to pork products has increased. Pathogen presence in the feed mill environment is one of the many potential transmission routes into the food production chain. Here, we describe the draft genome sequences of 57 Salmonella enterica isolates from selected U.S. swine feed mills.

Complete Genome Sequence of Listeria monocytogenes DFPST0073, Isolated from Imported Mexican Soft Cheese.

The genome of Listeria monocytogenes strain DFPST0073, isolated from imported fresh Mexican soft cheese in 2003, was sequenced using the Illumina MiSeq platform. Reads were assembled using SPAdes, and genome annotation was performed using the NCBI Prokaryotic Genome Annotation Pipeline.

Draft Genome Sequences of 112 Salmonella enterica Serovar Dublin Strains Isolated from Humans and Animals in Brazil.

Salmonella enterica serovar Dublin is a strongly adapted serovar that causes enteritis and/or systemic disease in cattle and results in high rates of mortality. Here, we report the draft genome sequences of 112 S. Dublin strains isolated from humans and animals in Brazil. These draft genome sequences will help enhance our understanding of this serovar in Brazil.

GenomeTrakr proficiency testing for foodborne pathogen surveillance: an exercise from 2015.

Pathogen monitoring is becoming more precise as sequencing technologies become more affordable and accessible worldwide. This transition is especially apparent in the field of food safety, which has demonstrated how whole-genome sequencing (WGS) can be used on a global scale to protect public health. GenomeTrakr coordinates the WGS performed by public-health agencies and other partners by providing a public database with real-time cluster analysis for foodborne pathogen surveillance. Because WGS is being used to support enforcement decisions, it is essential to have confidence in the quality of the data being used and the downstream data analyses that guide these decisions. Routine proficiency tests, such as the one described here, have an important role in ensuring the validity of both data and procedures. In 2015, the GenomeTrakr proficiency test distributed eight isolates of common foodborne pathogens to participating laboratories, who were required to follow a specific protocol for performing WGS. Resulting sequence data were evaluated for several metrics, including proper labelling, sequence quality and new single nucleotide polymorphisms (SNPs). Illumina MiSeq sequence data collected for the same set of strains across 21 different laboratories exhibited high reproducibility, while revealing a narrow range of technical and biological variance. The numbers of SNPs reported for sequencing runs of the same isolates across multiple laboratories support the robustness of our cluster analysis pipeline in that each individual isolate cultured and resequenced multiple times in multiple places are all easily identifiable as originating from the same source.

Draft Genome Sequences of 510 Listeria monocytogenes Strains from Food Isolates and Human Listeriosis Cases from Northern Italy.

Listeriosis outbreaks are frequently multistate/multicountry outbreaks, underlining the importance of molecular typing data for several diverse and well-characterized isolates. Large-scale whole-genome sequencing studies on Listeria monocytogenes isolates from non-U.S. locations have been limited. Herein, we describe the draft genome sequences of 510 L. monocytogenes isolates from northern Italy from different sources.

Draft Genome Sequences of 23 Salmonella enterica Strains Isolated from Cattle in Ibadan, Nigeria, Representing 21 Salmonella Serovars.

To provide a better understanding of the diversity of Salmonella enterica, we report the assembled genome sequences of 23 Salmonella enterica strains isolated from fecal samples of cattle in Nigeria comprising 21 different Salmonella serovars.

Draft Genome Sequences of 64 Salmonella enterica Serotype Enteritidis Isolates Obtained from Wild Mice.

Salmonella enterica serotype Enteritidis is a foodborne pathogen of global concern, because it is frequently isolated from foods and patients. Draft genome sequences are reported here for 64 S Enteritidis strains isolated from the intestines and spleens of mice caught live on chicken farms in the U.S. Northeast. The availability of these genomes provides baseline information on the genomic diversity of S Enteritidis during the 1990s, when foodborne outbreaks traced to internal contamination of eggs were prevalent.

Draft Genome Sequences of 256 Salmonella enterica subsp. enterica Serovar Enteritidis Strains Isolated from Humans, Food, Chickens, and Farm Environments in Brazil.

Salmonella enterica subsp. enterica serovar Enteritidis emerged in the late 1980s as the most isolated Salmonella serovar worldwide. Here, we report the draft genomes of 256 S Enteritidis strains isolated from humans, food, chickens, and farm environments in Brazil. These draft genomes will help enhance our understanding of this serovar in Brazil.

Hermenéutica e investigación social: narrativas generativas de paz, democracia y reconciliación / Hermeneutics and social research: narratives that generate peace, democracy and reconciliation / Hermenêutica e investigação social: narrativas generativas de paz, democracia e reconciliação

La pertinencia de los métodos de investigación implica la indagación por sus límites y posibilidades para comprender y transformar los fenómenos sociales. La hermenéutica ontológica política implica comprender sentidos y significados en su devenir, transformando a su vez las realidades sociales con otros según vivencias subjetivas e identitarias. Aquí presentamos el vínculo entre hermenéutica ontológica política y construccionismo social: primero, explicitando cómo la hermenéutica ontológica política, además de ser un modelo epistemológico para acceder a fenómenos sociales, es un aporte político a la comprensión y transformación de lo social; segundo, estableciendo un vínculo entre el socioconstruccionismo y la actitud hermenéutica que se instala en este modelo de comprensión; y finalmente, abordando la aplicación del vínculo metodológico entre hermenéutica ontológica política y socioconstruccionismo en la investigación con niños y niñas en contextos de conflicto armado.

The relevance of research methods implies the inquiry about their limits and possibilities for understanding and transforming social phenomena. Ontological political hermeneutics aims to comprehend meanings that are subject to continuous change, and at the same time transform social realities with others based on subjective and identity-based experiences. This article focuses on the link between ontological political hermeneutics and social constructionism: in the first instance, the authors detail how ontological political hermeneutics, in addition to providing an epistemological model for social research, acts as a political contribution to the comprehension and transformation of social processes; secondly, this article will show a link between social constructionism and the hermeneutical attitude that is located within this model of understanding. Finally, the authors apply the methodological link between ontological political hermeneutics and social constructionism in the field of social research with children living in armed conflict contexts. Key words: Methodology, social research, childhood (Unesco Social Sciences Thesaurus). Authors’ key words: Ontological political hermeneutics, social constructionism, narratives.

A pertinência dos métodos de investigação induz à indagação por seus limites e possibilidades para compreender e transformá-los em fenômenos sociais. A hermenêutica ontológica política implica compreender sentidos e significados em seu desenvolvimento, transformando, por sua vez, as realidades sociais com outros indivíduos por meio de vivências subjetivas e indenitárias. É apresentado o vínculo entre hermenêutica ontológica política e construcionismo social da seguinte maneira: primeiro, explicitando como a hermenêutica ontológica política, além de ser um modelo epistemológico para acessar fenômenos, é uma contribuição política para a compreensão e transformação do social; segundo, estabelecendo um vínculo entre o socioconstrutivismo e a atitude hermenêutica que se instala nesse modelo de compreensão; e, finalmente, abordando a aplicação do vínculo metodológico entre hermenêutica ontológica política e socioconstrutivismo na pesquisa com crianças em contextos de conflito armado.

Draft Genome Sequences of Histamine- and Non-Histamine-Producing Photobacterium Strains.

Histamine-producing bacteria (HPBs) have recently been identified from the marine environment. The identification and characterization of HPBs is important to developing effective mitigation strategies for scombrotoxin fish poisoning. We report here the draft genomes of seven histamine-producing and two non-histamine-producing marine Photobacterium strains.

Identification and Characterization of Imipenem-Resistant Klebsiella pneumoniae and Susceptible Klebsiella variicola Isolates Obtained from the Same Patient.

Klebsiella variicola, a bacterium closely genetically related to Klebsiella pneumoniae, is commonly misidentified as K. pneumoniae by biochemical tests. To distinguish between the two bacteria, phylogenetic analysis of the rpoB gene and the identification of unique genes in both bacterial species by multiplex-polymerase chain reaction (PCR) provide the means to reliably identify and genotype K. variicola. In recent years, K. variicola has been described both as the cause of an intrahospital outbreak in a pediatric hospital, which resulted in sepsis in inpatients, and as a frequent cause of bloodstream infections. In the present study, K. pneumoniae and K. variicola were isolated from a unique patient displaying different antimicrobial susceptibility phenotypes and different genotypes of virulence determinants. Eight clinical isolates were obtained at different time intervals; all during a 5-month period. The isolates were identified as K. pneumoniae by an automated identification system. The clinical (biochemical test) and molecular (multiplex-PCR and rpoB gene) characterization identified imipenem resistance in the first six K. pneumoniae ST258 isolates, which encode the SHV-12 cephalosporinase and KPC-3 carbapenemase genes. The two last remaining isolates corresponded to susceptible K. variicola. The bacterial species showed a specific profile of virulence-associated determinants, specifically the fimA, fimH, and ecpRAB fimbrial-encoding genes identified only in K. pneumoniae isolates. However, the entb (enterobactin), mrkD (fimbrial adhesin), uge (epimerase), ureA (urease), and wabG (transferase) genes were shared between both bacterial species. Recent studies attribute a higher mortality rate to K. variicola than to K. pneumonia. This work highlights the identification of K. pneumoniae and the closely related K. variicola isolated from the same patient. The value of distinguishing between these two bacterial species is in their clinical significance, their different phenotypes and genotypes, and the fact that they can be isolated from the same patient.