Host genetics and gut microbiome: Perspectives for multiple sclerosis

As a complex disease, Multiple Sclerosis (MS)’s etiology is determined by both genetic and environmental factors. In the last decade, the gut microbiome has emerged as an important environmental factor, but its interaction with host genetics is still unknown. In this review, we focus on these dual aspects of MS pathogenesis: we describe the current knowledge on genetic factors related to MS, based on genome-wide association studies, and then illustrate the interactions between the immune system, gut microbiome and central nervous system in MS, summarizing the evidence available from Experimental Autoimmune Encephalomyelitis mouse models and studies in patients. Finally, as the understanding of influence of host genetics on the gut microbiome composition in MS is in its infancy, we explore this issue based on the evidence currently available from other autoimmune diseases that share with MS the interplay of genetic with environmental factors (Inflammatory Bowel Disease, Rheumatoid Arthritis and Systemic Lupus Erythematosus), and discuss avenues for future research

Reviewing, indicating, and counting books for modern research evaluation systems

In this chapter, we focus on the specialists who have helped to improve the conditions for book assessments in research evaluation exercises, with empirically based data and insights supporting their greater integration. Our review highlights the research carried out by four types of expert communities, referred to as the monitors, the subject classifiers, the indexers and the indicator constructionists. Many challenges lie ahead for scholars affiliated with these communities, particularly the latter three. By acknowledging their unique, yet interrelated roles, we show where the greatest potential is for both quantitative and qualitative indicator advancements in book-inclusive evaluation systems.Comment: Forthcoming in Glanzel, W., Moed, H.F., Schmoch U., Thelwall, M. (2018). Springer Handbook of Science and Technology Indicators. Springer Some corrections made in subsection 'Publisher prestige or quality

Primera Etapa del Proyecto de manejo de colecciones osteológicas en el área de antropología biológica, Museo Etnográfico J. B. Ambrosetti

The paper presents the conservation, documentation and management of the collection of human remains at the Biological Anthropology Area of the Ethnographic Museums - University of Buenos Aires, Argentina. This pdf is a screen-print of the website (retrieved in 29th Aug, 2010) which is no longer available. However, the presentation can be cited as follows: _ Cite in English: Aranda, C., M.F. Robledo, D. Alunni, D. Avido, A. Salvarredy, P. Urtizberea, K. Zuccala & N. Villanucci. 2009. Primera etapa del Proyecto de manejo de colecciones osteológicas en el área de antropología biológica, Museo Etnográfico 'J. B. Ambrosetti'. Book of Abstracts of the IV Foro de Conservación del Patrimonio Cultural, pp: 28-29. Fundación Conservación del Patrimonio Cultural, Caracas. _ Cita en Castellano: Aranda, C., M.F. Robledo, D. Alunni, D. Avido, A. Salvarredy, P. Urtizberea, K. Zuccala y N. Villanucci. 2009. Primera etapa del Proyecto de manejo de colecciones osteológicas en el área de antropología biológica, Museo Etnográfico 'J. B. Ambrosetti'. Libro de resúmenes del IV Foro de Conservación del Patrimonio Cultural, pp: 28-29. Fundación Conservación del Patrimonio Cultural, Caracas

Towards automated analysis of research methods in library and information science

Previous studies of research methods in Library and Information Science (LIS) lack consensus in how to define or classify research methods, and there have been no studies on automated recognition of research methods in the scientific literature of this field. This work begins to fill these gaps by studying how the scope of “research methods” in LIS has evolved, and the challenges in automatically identifying the usage of research methods in LIS literature. A total of 2,599 research articles are collected from three LIS journals. Using a combination of content analysis and text mining methods, a sample of this collection is coded into 29 different concepts of research methods and is then used to test a rule-based automated method for identifying research methods reported in the scientific literature. We show that the LIS field is characterized by the use of an increasingly diverse range of methods, many of which originate outside the conventional boundaries of LIS. This implies increasing complexity in research methodology and suggests the need for a new approach towards classifying LIS research methods to capture the complex structure and relationships between different aspects of methods. Our automated method is the first of its kind in LIS, and sets an important reference for future research

A New Approach to Analyzing Patterns of Collaboration in Co-authorship Networks - Mesoscopic Analysis and Interpretation

This paper focuses on methods to study patterns of collaboration in co-authorship networks at the mesoscopic level. We combine qualitative methods (participant interviews) with quantitative methods (network analysis) and demonstrate the application and value of our approach in a case study comparing three research fields in chemistry. A mesoscopic level of analysis means that in addition to the basic analytic unit of the individual researcher as node in a co-author network, we base our analysis on the observed modular structure of co-author networks. We interpret the clustering of authors into groups as bibliometric footprints of the basic collective units of knowledge production in a research specialty. We find two types of coauthor-linking patterns between author clusters that we interpret as representing two different forms of cooperative behavior, transfer-type connections due to career migrations or one-off services rendered, and stronger, dedicated inter-group collaboration. Hence the generic coauthor network of a research specialty can be understood as the overlay of two distinct types of cooperative networks between groups of authors publishing in a research specialty. We show how our analytic approach exposes field specific differences in the social organization of research.Comment: An earlier version of the paper was presented at ISSI 2009, 14-17 July, Rio de Janeiro, Brazil. Revised version accepted on 2 April 2010 for publication in Scientometrics. Removed part on node-role connectivity profile analysis after finding error in calculation and deciding to postpone analysis

Increased sCD163 and sCD14 plasmatic levels and depletion of peripheral blood pro-inflammatory monocytes, myeloid and plasmacytoid dendritic cells in patients with severe COVID-19 pneumonia

Background: Emerging evidence argues that monocytes, circulating innate immune cells, are principal players in COVID-19 pneumonia. The study aimed to investigate the role of soluble (s)CD163 and sCD14 plasmatic levels in predicting disease severity and characterize peripheral blood monocytes and dendritic cells (DCs), in patients with COVID-19 pneumonia (COVID-19 subjects). Methods: On admission, in COVID-19 subjects sCD163 and sCD14 plasmatic levels, and peripheral blood monocyte and DC subsets were compared to healthy donors (HDs). According to clinical outcome, COVID-19 subjects were divided into ARDS and non-ARDS groups. Results: Compared to HDs, COVID-19 subjects showed higher sCD163 (p<0.0001) and sCD14 (p<0.0001) plasmatic levels. We observed higher sCD163 plasmatic levels in the ARDS group compared to the non-ARDS one (p=0.002). The cut-off for sCD163 plasmatic level greater than 2032 ng/ml was predictive of disease severity (AUC: 0.6786, p=0.0022; sensitivity 56.7% [CI: 44.1–68.4] specificity 73.8% [CI: 58.9–84.7]). Positive correlation between plasmatic levels of sCD163, LDH and IL-6 and between plasmatic levels of sCD14, D-dimer and ferritin were found. Compared to HDs, COVID-19 subjects showed lower percentages of non-classical (p=0.0012) and intermediate monocytes (p=0.0447), slanDCs (p<0.0001), myeloid DCs (mDCs, p<0.0001), and plasmacytoid DCs (pDCs, p=0.0014). Compared to the non-ARDS group, the ARDS group showed lower percentages of non-classical monocytes (p=0.0006), mDCs (p=0.0346), and pDCs (p=0.0492). Conclusions: The increase in sCD163 and sCD14 plasmatic levels, observed on hospital admission in COVID-19 subjects, especially in those who developed ARDS, and the correlations of these monocyte/macrophage activation markers with typical inflammatory markers of COVID-19 pneumonia, underline their potential use to assess the risk of progression of the disease. In an early stage of the disease, the assessment of sCD163 plasmatic levels could have clinical utility in predicting the severity of COVID-19 pneumonia

Manejo de colecciones osteológicas del Museo Etnográfico J. B. Ambrosetti (FFyL, UBA)

A finales de 2006 se dio inicio a un proyecto de conservación desarrollado en el Área de Antropología Biológica del Museo Etnográfico J. B. Ambrosetti, Facultad de Filosofía y Letras, Universidad de Buenos Aires, en el marco de un proceso de revalorización de los restos humanos que esta institución alberga. El proyecto general implementado tiene por objetivo desarrollar un protocolo que se base en el manejo ético de los restos, destacándose los conceptos de custodia, identidad y respeto, y que cubra en el largo plazo aspectos que se articulan en cuatro ejes principales: 1) ética, 2) educación, 3) conservación y 4) patrimonio. Esta forma de abordar las colecciones modifica sustancialmente las prácticas de manejo tal como se venían realizando con anterioridad, ya que establece estrategias novedosas que contemplan en un mismo plano de importancia la necesidad de desarrollar tareas de conservación y analizar su información científica para el desarrollo de actividades de investigación y docencia, todas las cuales deben ser necesariamente abordadas dentro de un marco que priorice los aspectos bioéticos de las políticas de manejo patrimonial. Se describen y discuten en este trabajo las diferentes líneas de trabajo implementadas desde hace cuatro años en el Área, y se detallan los logros alcanzados y las dificultades superadas, enfatizando tanto en aquellos aspectos del plan que están en proceso como en los que deberán ser desarrollados en el futuro. (Párrafo extraído del texto a modo de resumen)Eje 1: Manejo de Colecciones y GestiónRed de Museos de la Universidad Nacional de La Plat

Trabectedin triggers direct and NK-mediated cytotoxicity in multiple myeloma

Background: Genomic instability is a feature of multiple myeloma (MM), and impairment in DNA damaging response (DDR) has an established role in disease pathobiology. Indeed, a deregulation of DNA repair pathways may contribute to genomic instability, to the establishment of drug resistance to genotoxic agents, and to the escape from immune surveillance. On these bases, we evaluated the role of different DDR pathways in MM and investigated, for the first time, the direct and immune-mediated anti-MM activity of the nucleotide excision repair (NER)-dependent agent trabectedin. Methods: Gene-expression profiling (GEP) was carried out with HTA2.0 Affymetrix array. Evaluation of apoptosis, cell cycle, and changes in cytokine production and release have been performed in 2D and 3D Matrigel-spheroid models through flow cytometry on MM cell lines and patients-derived primary MM cells exposed to increasing nanomolar concentrations of trabectedin. DNA-damage response has been evaluated through Western blot, immunofluorescence, and DNA fragmentation assay. Trabectedin-induced activation of NK has been assessed by CD107a degranulation. miRNAs quantification has been done through RT-PCR. Results: By comparing GEP meta-analysis of normal and MM plasma cells (PCs), we observed an enrichment in DNA NER genes in poor prognosis MM. Trabectedin triggered apoptosis in primary MM cells and MM cell lines in both 2D and 3D in vitro assays. Moreover, trabectedin induced DDR activation, cellular stress with ROS production, and cell cycle arrest. Additionally, a significant reduction of MCP1 cytokine and VEGF-A in U266-monocytes co-cultures was observed, confirming the impairment of MM-promoting milieu. Drug-induced cell stress in MM cells led to upregulation of NK activating receptors ligands (i.e., NKG2D), which translated into increased NK activation and degranulation. Mechanistically, this effect was linked to trabectedin-induced inhibition of NKG2D-ligands negative regulators IRF4 and IKZF1, as well as to miR-17 family downregulation in MM cells. Conclusions: Taken together, our findings indicate a pleiotropic activity of NER-targeting agent trabectedin, which appears a promising candidate for novel anti-MM therapeutic strategies

Development and validation of a prediction model for tocilizumab failure in hospitalized patients with SARS-CoV-2 infection

Background The aim of this secondary analysis of the TESEO cohort is to identify, early in the course of treatment with tocilizumab, factors associated with the risk of progressing to mechanical ventilation and death and develop a risk score to estimate the risk of this outcome according to patients' profile. Methods Patients with COVID-19 severe pneumonia receiving standard of care + tocilizumab who were alive and free from mechanical ventilation at day 6 after treatment initiation were included in this retrospective, multicenter cohort study. Multivariable logistic regression models were built to identify predictors of mechanical ventilation or death by day-28 from treatment initiation and β-coefficients were used to develop a risk score. Secondary outcome was mortality. Patients with the same inclusion criteria as the derivation cohort from 3 independent hospitals were used as validation cohort. Results 266 patients treated with tocilizumab were included. By day 28 of hospital follow-up post treatment initiation, 40 (15%) underwent mechanical ventilation or died [26 (10%)]. At multivariable analysis, sex, day-4 PaO2/FiO2 ratio, platelets and CRP were independently associated with the risk of developing the study outcomes and were used to generate the proposed risk score. The accuracy of the score in AUC was 0.80 and 0.70 in internal validation and test for the composite endpoint and 0.92 and 0.69 for death, respectively. Conclusions Our score could assist clinicians in identifying, early after tocilizumab administration, patients who are likely to progress to mechanical ventilation or death, so that they could be selected for eventual rescue therapies