Mapping of electronic health records in Spanish to the unified medical language system metathesaurus

[EN] This work presents a preliminary approach to annotate Spanish electronic health records with concepts of the Unified Medical Language System Metathesaurus. The prototype uses Apache Lucene R to index the Metathesaurus and generate mapping candidates from input text. In addition, it relies on UKB to resolve ambiguities. The tool has been evaluated by measuring its agreement with MetaMap in two English-Spanish parallel corpora, one consisting of titles and abstracts of papers in the clinical domain, and the other of real electronic health record excerpts.[EU] Lan honetan, espainieraz idatzitako mediku-txosten elektronikoak Unified Medical Languge System Metathesaurus deituriko terminologia biomedikoarekin etiketatzeko lehen urratsak eman dira. Prototipoak Apache Lucene R erabiltzen du Metathesaurus-a indexatu eta mapatze hautagaiak sortzeko. Horrez gain, anbiguotasunak UKB bidez ebazten ditu. Ebaluazioari dagokionez, prototipoaren eta MetaMap-en arteko adostasuna neurtu da bi ingelera-gaztelania corpus paralelotan. Corpusetako bat artikulu zientifikoetako izenburu eta laburpenez osatutako dago. Beste corpusa mediku-txosten pasarte batzuez dago osatuta

Contributions to information extraction for spanish written biomedical text

285 p.Healthcare practice and clinical research produce vast amounts of digitised, unstructured data in multiple languages that are currently underexploited, despite their potential applications in improving healthcare experiences, supporting trainee education, or enabling biomedical research, for example. To automatically transform those contents into relevant, structured information, advanced Natural Language Processing (NLP) mechanisms are required. In NLP, this task is known as Information Extraction. Our work takes place within this growing field of clinical NLP for the Spanish language, as we tackle three distinct problems. First, we compare several supervised machine learning approaches to the problem of sensitive data detection and classification. Specifically, we study the different approaches and their transferability in two corpora, one synthetic and the other authentic. Second, we present and evaluate UMLSmapper, a knowledge-intensive system for biomedical term identification based on the UMLS Metathesaurus. This system recognises and codifies terms without relying on annotated data nor external Named Entity Recognition tools. Although technically naive, it performs on par with more evolved systems, and does not exhibit a considerable deviation from other approaches that rely on oracle terms. Finally, we present and exploit a new corpus of real health records manually annotated with negation and uncertainty information: NUBes. This corpus is the basis for two sets of experiments, one on cue andscope detection, and the other on assertion classification. Throughout the thesis, we apply and compare techniques of varying levels of sophistication and novelty, which reflects the rapid advancement of the field

Mapping of electronic health records in Spanish to the unified medical language system metathesaurus

[EN] This work presents a preliminary approach to annotate Spanish electronic health records with concepts of the Unified Medical Language System Metathesaurus. The prototype uses Apache Lucene R to index the Metathesaurus and generate mapping candidates from input text. In addition, it relies on UKB to resolve ambiguities. The tool has been evaluated by measuring its agreement with MetaMap in two English-Spanish parallel corpora, one consisting of titles and abstracts of papers in the clinical domain, and the other of real electronic health record excerpts.[EU] Lan honetan, espainieraz idatzitako mediku-txosten elektronikoak Unified Medical Languge System Metathesaurus deituriko terminologia biomedikoarekin etiketatzeko lehen urratsak eman dira. Prototipoak Apache Lucene R erabiltzen du Metathesaurus-a indexatu eta mapatze hautagaiak sortzeko. Horrez gain, anbiguotasunak UKB bidez ebazten ditu. Ebaluazioari dagokionez, prototipoaren eta MetaMap-en arteko adostasuna neurtu da bi ingelera-gaztelania corpus paralelotan. Corpusetako bat artikulu zientifikoetako izenburu eta laburpenez osatutako dago. Beste corpusa mediku-txosten pasarte batzuez dago osatuta

Dietary diversity and depression: cross-sectional and longitudinal analyses in Spanish adult population with metabolic syndrome. Findings from PREDIMED-Plus trial

Objective: To examine the cross-sectional and longitudinal (2-year follow-up) associations between dietary diversity (DD) and depressive symptoms. Design: An energy-adjusted dietary diversity score (DDS) was assessed using a validated FFQ and was categorised into quartiles (Q). The variety in each food group was classified into four categories of diversity (C). Depressive symptoms were assessed with Beck Depression Inventory-II (Beck II) questionnaire and depression cases defined as physician-diagnosed or Beck II >= 18. Linear and logistic regression models were used. Setting: Spanish older adults with metabolic syndrome (MetS). Participants: A total of 6625 adults aged 55–75 years from the PREDIMED-Plus study with overweight or obesity and MetS. Results: Total DDS was inversely and statistically significantly associated with depression in the cross-sectional analysis conducted; OR Q4 v. Q1 = 0·76 (95 % CI (0·64, 0·90)). This was driven by high diversity compared to low diversity (C3 v. C1) of vegetables (OR = 0·75, 95 % CI (0·57, 0·93)), cereals (OR = 0·72 (95 % CI (0·56, 0·94)) and proteins (OR = 0·27, 95 % CI (0·11, 0·62)). In the longitudinal analysis, there was no significant association between the baseline DDS and changes in depressive symptoms after 2 years of follow-up, except for DD in vegetables C4 v. C1 = (β = 0·70, 95 % CI (0·05, 1·35)). Conclusions: According to our results, DD is inversely associated with depressive symptoms, but eating more diverse does not seem to reduce the risk of future depression. Additional longitudinal studies (with longer follow-up) are needed to confirm these findings.T The PREDIMED-Plus trial was supported by the European Research Council (Advanced Research Grant 2013-2018; 340918) grant to Miguel Angel Martinez-Gonzalez, and by the official funding agency for biomedical research of the Spanish Government, ISCIII through the Fondo de Investigacion para la Salud (FIS), which is cofunded by the European Regional Development Fund (four coordinated FIS projects led by Jordi Salas-Salvado and Josep Vidal), including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, The Especial Action Project entitled: 'Implementacion y Evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus' grant to Jordi Salas-Salvado, the Recercaixa grant to Jordi Salas-Salvado (2013ACUP00194), grants from the Consejeria de Salud de la Junta de Andalucia (PI0458/2013; PS0358/2016; PI0137/2018), the PROMETEO/2017/017 grant from the Generalitat Valenciana, the SEMERGEN grant, and CIBEROBN and FEDER funds (CB06/03), ISCIII. International Nut&Dried Fruit Council-FESNAD N degrees 201302: Miguel Angel Martinez-Gonzalez (PI). None of the funding sources took part in the design, collection, analysis or interpretation of the data, or in the decision to submit the manuscript for publication. The corresponding author had full access to all the data in the study and had final responsibility to submit for publication

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems

Characterization of Monoclonal Antibodies to turbot (Scophthalmus maximus L.)

Monoclonal antibodies (mAbs) can be used in several applications, v.g in the aquaculture field. In attempt to study the immune system of the turbot fish, we wanted to develop mAbsdirected against turbot’s lymphocytes, mainly T cells. BALB/c mice were immunized with turbot thymic cells and mouse splenocytes were fused with mouse myeloma cells to genera-te hybridomas. The screening of secretory hybridomas was first performed by ELISA. Then, specificity of different monoclonal antibodies was determined by using immunohistoche-mical and immunofluorescence methods and, on the basis on their reactivity with cells from lymphoid tissues of turbot, three antibodies called RoA3, RoA4 and RoD4 were selected.RoA3 positively reacted with the membrane components of cells resembling to thymocytes, RoA4 stained cells with extended cytoplasmic processes, compatible with reticular cells.In the case of RoD4 mAb, it stains large cells mainly in the medullar zone of the thymus, compatible with macrophages and reticular cells. Flow cytometry studies showed its specifici-ty for thymic cells (no reaction with spleen or pronephros cells), further confirmed by western blot, indicating that RoD4 mAb recognizes a specific protein of 130-135 kD only onthymic tissue

Oncolytic DNX-2401 Virus for Pediatric Diffuse Intrinsic Pontine Glioma

BACKGROUND Pediatric patients with diffuse intrinsic pontine glioma (DIPG) have a poor prognosis, with a median survival of less than 1 year. Oncolytic viral therapy has been evaluated in patients with pediatric gliomas elsewhere in the brain, but data regarding oncolytic viral therapy in patients with DIPG are lacking. METHODS We conducted a single-center, dose-escalation study of DNX-2401, an oncolytic adenovirus that selectively replicates in tumor cells, in patients with newly diagnosed DIPG. The patients received a single virus infusion through a catheter placed in the cerebellar peduncle, followed by radiotherapy. The primary objective was to assess the safety and adverse-event profile of DNX-2401. The secondary objectives were to evaluate the effect of DNX-2401 on overall survival and quality of life, to determine the percentage of patients who have an objective response, and to collect tumor-biopsy and peripheral-blood samples for correlative studies of the molecular features of DIPG and antitumor immune responses. RESULTS A total of 12 patients, 3 to 18 years of age, with newly diagnosed DIPG received 1×10 10 (the first 4 patients) or 5×10 10 (the subsequent 8 patients) viral particles of DNX-2401, and 11 received subsequent radiotherapy. Adverse events among the patients included headache, nausea, vomiting, and fatigue. Hemiparesis and tetra-paresis developed in 1 patient each. Over a median follow-up of 17.8 months (range, 5.9 to 33.5), a reduction in tumor size, as assessed on magnetic resonance imaging, was reported in 9 patients, a partial response in 3 patients, and stable disease in 8 patients. The median survival was 17.8 months. Two patients were alive at the time of preparation of the current report, 1 of whom was free of tumor progression at 38 months. Examination of a tumor sample obtained during autopsy from 1 patient and peripheral-blood studies revealed alteration of the tumor microenvironment and T-cell repertoire. CONCLUSIONS Intratumoral infusion of oncolytic virus DNX-2401 followed by radiotherapy in pediatric patients with DIPG resulted in changes in T-cell activity and a reduction in or stabilization of tumor size in some patients but was associated with adverse events

Dietary diversity and depression: cross-sectional and longitudinal analyses in Spanish adult population with metabolic syndrome. Findings from PREDIMED-Plus trial.

To examine the cross-sectional and longitudinal (2-year follow-up) associations between dietary diversity (DD) and depressive symptoms. An energy-adjusted dietary diversity score (DDS) was assessed using a validated FFQ and was categorised into quartiles (Q). The variety in each food group was classified into four categories of diversity (C). Depressive symptoms were assessed with Beck Depression Inventory-II (Beck II) questionnaire and depression cases defined as physician-diagnosed or Beck II >= 18. Linear and logistic regression models were used. Spanish older adults with metabolic syndrome (MetS). A total of 6625 adults aged 55-75 years from the PREDIMED-Plus study with overweight or obesity and MetS. Total DDS was inversely and statistically significantly associated with depression in the cross-sectional analysis conducted; OR Q4 v. Q1 = 0·76 (95 % CI (0·64, 0·90)). This was driven by high diversity compared to low diversity (C3 v. C1) of vegetables (OR = 0·75, 95 % CI (0·57, 0·93)), cereals (OR = 0·72 (95 % CI (0·56, 0·94)) and proteins (OR = 0·27, 95 % CI (0·11, 0·62)). In the longitudinal analysis, there was no significant association between the baseline DDS and changes in depressive symptoms after 2 years of follow-up, except for DD in vegetables C4 v. C1 = (β = 0·70, 95 % CI (0·05, 1·35)). According to our results, DD is inversely associated with depressive symptoms, but eating more diverse does not seem to reduce the risk of future depression. Additional longitudinal studies (with longer follow-up) are needed to confirm these findings

mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer

Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#termsActivation of the PTEN-PI3K-mTORC1 pathway consolidates metabolic programs that sustain cancer cell growth and proliferation,. Here we show that mTORC1 regulates polyamine dynamics, a metabolic route that is essential for oncogenicity. Through the use of integrative metabolomics in a mouse model and human biopsies of prostate cancer, we identified alterations in tumours impacting on the production of decarboxylated S-adenosylmethionine (dcSAM) and polyamine synthesis. Mechanistically, this metabolic rewiring stems from mTORC1-dependent regulation of S-adenosylmethionine decarboxylase 1 (AMD1) stability. This novel molecular regulation was validated in murine and human cancer specimens. AMD1 was upregulated in prostate cancer specimens with activated mTORC1. Conversely, samples from a clinical trial with the mTORC1 inhibitor everolimus exhibited a predominant decrease in AMD1 immunoreactivity that was associated to a decrease in proliferation, in line with the requirement of dcSAM production for oncogenicity. These findings provide fundamental information about the complex regulatory landscape controlled by mTORC1 to integrate and translate growth signals into an oncogenic metabolic program

mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer

Activation of the PTEN-PI3K-mTORC1 pathway consolidates metabolic programs that sustain cancer cell growth and proliferation. Here we show that mechanistic target of rapamycin complex 1 (mTORC1) regulates polyamine dynamics, a metabolic route that is essential for oncogenicity. By using integrative metabolomics in a mouse model and human biopsies of prostate cancer, we identify alterations in tumours affecting the production of decarboxylated S-adenosylmethionine (dcSAM) and polyamine synthesis. Mechanistically, this metabolic rewiring stems from mTORC1-dependent regulation of S-adenosylmethionine decarboxylase 1 (AMD1) stability. This novel molecular regulation is validated in mouse and human cancer specimens. AMD1 is upregulated in human prostate cancer with activated mTORC1. Conversely, samples from a clinical trial with the mTORC1 inhibitor everolimus exhibit a predominant decrease in AMD1 immunoreactivity that is associated with a decrease in proliferation, in line with the requirement of dcSAM production for oncogenicity. These findings provide fundamental information about the complex regulatory landscape controlled by mTORC1 to integrate and translate growth signals into an oncogenic metabolic program