Diverse Epithelial Lymphocytes in Zebrafish Revealed Using a Novel Scale Biopsy Method.

Zebrafish (Danio rerio) are a compelling model for studying lymphocytes because zebrafish and humans have similar adaptive immune systems, including their lymphocytes. Antibodies that recognize zebrafish proteins are sparse, so many investigators use transgenic, lymphocyte-specific fluorophore-labeled lines. Human and zebrafish lymphocyte types are conserved, but many aspects of zebrafish lymphocyte biology remain uninvestigated, including lymphocytes in peripheral tissues, like epidermis.

Dynamic Changes in Lymphocyte Populations Establish Zebrafish as a Thymic Involution Model.

The thymus is the site of T lymphocyte development and T cell education to recognize foreign, but not self, Ags. B cells also reside and develop in the thymus, although their functions are less clear. During "thymic involution," a process of lymphoid atrophy and adipose replacement linked to sexual maturation, thymocytes decline.

Dynamic Changes in Lymphocyte Populations Establish Zebrafish as a Thymic Involution Model.

The thymus is the site of T lymphocyte development and T cell education to recognize foreign, but not self, antigens. B cells also reside and develop in the thymus, although their functions are less clear. During 'thymic involution,' a process of lymphoid atrophy and adipose replacement linked to sexual maturation, thymocytes decline.

Proprotein convertase subtilisin/kexin type 9 inhibitors treatment in dyslipidemic patients: a real world prescription.

Aim: Dyslipidemia is recognized as one of the major risk factors for cardiovascular diseases. This retrospective observational study was aimed to assess the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in dyslipidemic patients with a lipid profile not well controlled by maximally tolerated statin therapy or intolerant to these lipid-lowering drugs. We enrolled 151 patients, of whom, 119 were taking evolocumab and 32 alirocumab.

Predicting MHC I restricted T cell epitopes in mice with NAP-CNB, a novel online tool.

Lack of a dedicated integrated pipeline for neoantigen discovery in mice hinders cancer immunotherapy research. Novel sequential approaches through recurrent neural networks can improve the accuracy of T-cell epitope binding affinity predictions in mice, and a simplified variant selection process can reduce operational requirements. We have developed a web server tool (NAP-CNB) for a full and automatic pipeline based on recurrent neural networks, to predict putative neoantigens from tumoral RNA sequencing reads.

3DBionotes COVID-19 edition.

Summary: The web platform 3DBionotes-WS integrates multiple web services and an interactive web viewer to provide a unified environment in which biological annotations can be analyzed in their structural context. Since the COVID-19 outbreak, new structural data from many viral proteins have been provided at a very fast pace. This effort includes many cryogenic electron microscopy (cryo-EM) studies, together with more traditional ones (X-rays, NMR), using several modeling approaches and complemented with structural predictions.

Image Processing in Cryo-Electron Microscopy of Single Particles: The Power of Combining Methods.

Cryo-electron microscopy has established as a mature structural biology technique to elucidate the three-dimensional structure of biological macromolecules. The Coulomb potential of the sample is imaged by an electron beam, and fast semi-conductor detectors produce movies of the sample under study. These movies have to be further processed by a whole pipeline of image-processing algorithms that produce the final structure of the macromolecule.

A Randomized Open-Label Phase III Trial Evaluating the Addition of Denosumab to Standard First-Line Treatment in Advanced NSCLC: The European Thoracic Oncology Platform (ETOP) and European Organisation for Research and Treatment of Cancer (EORTC) SPLENDOUR Trial.

Introduction: Receptor activator of NF-kB ligand stimulates NF-kB-dependent cell signaling and acts as the primary signal for bone resorption. Retrospective analysis of a large trial comparing denosumab versus zoledronic acid in bone metastatic solid tumors suggested significant overall survival (OS) advantage for patients with lung cancer with denosumab (p = 0.01).

RECQL5: Another DNA helicase potentially involved in hereditary breast cancer susceptibility.

There is still around 50% of the familial breast cancer (BC) cases with an undefined genetic cause, here we have used next-generation sequencing (NGS) technology to identify new BC susceptibility genes. This approach has led to the identification of RECQL5, a member of RECQL-helicases family, as a new BC susceptibility candidate, which deserves further study. We have used a combination of whole exome sequencing in a family negative for mutations in BRCA1/2 throughout (BRCAX), in which we found a probably deleterious variant in RECQL5, and targeted NGS of the complete coding regions and exon-intron boundaries of the candidate gene in 699 BC Spanish BRCAX families and 665 controls.

Epidemiology of Strongyloides stercoralis infection in Bolivian patients at high risk of complications.

Background: Strongyloidiasis can be fatal in immunocompromised patients, but few epidemiological studies investigated the burden of this neglected tropical disease among these populations, particularly in low- and middle-income countries such as Bolivia. This study aimed to fill in this gap by estimating prevalence rate and risk factors associated with strongyloidiasis among patients at high risk of complications.

Methods: A cross-sectional study was carried out in Santa Cruz (elevation 400 meters, tropical climate) and Cochabamba (elevation 2,500 meters, temperate climate), among patients with cancer, HIV infection and rheumatic or hematologic disease, using four coproparasitological techniques and one serological (ELISA) test.

Analysis of Availability and Access of Anti-myeloma Drugs and Impact on the Management of Multiple Myeloma in Latin American Countries.

Introduction: Latin American countries (LATAMC) represent a large fraction of patients treated for multiple myeloma (MM) worldwide. In order to understand the difficulty of access to anti-myeloma therapy in LATAMC, we designed this study that explores areas involved in the availability of drugs, such as health care systems, approval times, coverage of new agents, old drugs, use of generics, and the first-line treatments.

Material And Methods: We collected data from 16 countries in 2015.

Monte Carlo verification of radiotherapy treatments with CloudMC.

Background: A new implementation has been made on CloudMC, a cloud-based platform presented in a previous work, in order to provide services for radiotherapy treatment verification by means of Monte Carlo in a fast, easy and economical way. A description of the architecture of the application and the new developments implemented is presented together with the results of the tests carried out to validate its performance.

Methods: CloudMC has been developed over Microsoft Azure cloud.

Automated assembly of species metabolomes through data submission into a public repository.

Following similar global efforts to exchange genomic and other biomedical data, global databases in metabolomics have now been established. MetaboLights, the first general purpose, publically available, cross-species, cross-application database in metabolomics, has become the fastest growing data repository at the European Bioinformatics Institute in terms of data volume. Here we present the automated assembly of species metabolomes in MetaboLights, a crucial reference for chemical biology, which is growing through user submissions.

Germline missense pathogenic variants in the BRCA1 BRCT domain, p.Gly1706Glu and p.Ala1708Glu, increase cellular sensitivity to PARP inhibitor olaparib by a dominant negative effect.

BRCA1-deficient cells show defects in DNA repair and rely on other members of the DNA repair machinery, which makes them sensitive to PARP inhibitors (PARPi). Although carrying a germline pathogenic variant in BRCA1/2 is the best determinant of response to PARPi, a significant percentage of the patients do not show sensitivity and/or display increased toxicity to the agent. Considering previously suggested mutation-specific BRCA1 haploinsufficiency, we aimed to investigate whether there are any differences in cellular response to PARPi olaparib depending on the BRCA1 mutation type.

Surgical Reconstruction of the Forefoot with Hallux Valgus Associated with Metatarsus Adductus.

Metatarsus adductus is a structural deformity that may be associated with hallux valgus and that may lead to metatarsal pain and functional abnormality of the foot. Correcting hallux valgus is complicated in these cases because of the deviation in adduction of the lesser metatarsals, especially the second metatarsal that occupies the first intermetatarsal space. We report the case of a 49-year-old man who underwent a scarf osteotomy in the first metatarsal, shortening and abductor oblique distal osteotomies of the lesser metatarsals, and arthrodesis of the central toes with Z-lengthening of the capsule and long extensor tendons of the toes.

DNA repair capacity is impaired in healthy BRCA1 heterozygous mutation carriers.

BRCA1 germline mutations increase the lifetime risk of developing breast and ovarian cancers. However, taking into account the differences in disease manifestation among mutation carriers, it is probable that different BRCA1 mutations have distinct haploinsufficiency effects and lead to the formation of different phenotypes. Using lymphoblastoid cell lines derived from heterozygous BRCA1 mutation carriers and non-carriers, we investigated the haploinsufficiency effects of various mutation types using qPCR, immunofluorescence, and microarray technology.

On the development of three new tools for organizing and sharing information in three-dimensional electron microscopy.

Electron microscopy is a valuable tool for elucidating the three-dimensional structures of macromolecular complexes. As the field matures and the number of solved structures increases, the existence of infrastructures that keep this information organized and accessible is crucial. At the same time, standards and clearly described conventions facilitate software maintenance, benefit interoperability with other packages and allow data interchange.

A meta-analysis approach to the effects of fish farming on soft bottom polychaeta assemblages in temperate regions.

Marine fish farms could cause environmental disturbances on the sediment due to uneaten food and fish faeces that impact the marine benthos. Polychaete assemblages are considered good indicators of environmental perturbations. The present study aimed to establish groups of polychaetes as potential indicators of fish farm pollution.

Policies to promote healthy eating in Europe: a structured review of policies and their effectiveness.

This review provides a classification of public policies to promote healthier eating as well as a structured mapping of existing measures in Europe. Complete coverage of alternative policy types was ensured by complementing the review with a selection of major interventions from outside Europe. Under the auspices of the Seventh Framework Programme's Eatwell Project, funded by the European Commission, researchers from five countries reviewed a representative selection of policy actions based on scientific papers, policy documents, grey literature, government websites, other policy reviews, and interviews with policy-makers.

Integrating human and murine anatomical gene expression data for improved comparisons.

Motivation: Information concerning the gene expression pattern in four dimensions (species, genes, anatomy and developmental stage) is crucial for unraveling the roles of genes through time. There are a variety of anatomical gene expression databases, but extracting information from them can be hampered by their diversity and heterogeneity.

Results: aGEM 3.

Palmar filiform parakeratotic hyperkeratosis: A report of 2 cases.

Palmar filiform parakeratotic hyperkeratosis (PFPH) is a rare dermatosis; hyperkeratotic lesions appear as small spines on the palms and/or soles. Palmar filiform parakeratotic hyperkeratosis has been associated with a variety of malignant tumors and endocrine disorders, although these associations have not been fully demonstrated. We report two new cases of this entity without systemic pathology associated.

aGEM: an integrative system for analyzing spatial-temporal gene-expression information.

Motivation: The work presented here describes the 'anatomical Gene-Expression Mapping (aGEM)' Platform, a development conceived to integrate phenotypic information with the spatial and temporal distributions of genes expressed in the mouse. The aGEM Platform has been built by extending the Distributed Annotation System (DAS) protocol, which was originally designed to share genome annotations over the WWW. DAS is a client-server system in which a single client integrates information from multiple distributed servers.

Customized treatment in non-small-cell lung cancer based on EGFR mutations and BRCA1 mRNA expression.

Background: Median survival is 10 months and 2-year survival is 20% in metastatic non-small-cell lung cancer (NSCLC) treated with platinum-based chemotherapy. A small fraction of non-squamous cell lung cancers harbor EGFR mutations, with improved outcome to gefitinib and erlotinib. Experimental evidence suggests that BRCA1 overexpression enhances sensitivity to docetaxel and resistance to cisplatin.

Integrating biological data--the Distributed Annotation System.

Background: The Distributed Annotation System (DAS) is a widely adopted protocol for dynamically integrating a wide range of biological data from geographically diverse sources. DAS continues to expand its applicability and evolve in response to new challenges facing integrative bioinformatics.

Results: Here we describe the various infrastructure components of DAS and present a new extended version of the DAS specification.