Machine Learning Based Microbiome Signature to Predict Inflammatory Bowel Disease Subtypes

Crohn's disease; Microbiome; Ulcerative colitisEnfermedad de Crohn; Microbioma; Colitis ulcerosaMalaltia de Crohn; Microbioma; Colitis ulcerosaInflammatory bowel disease (IBD) is a chronic disease with unknown pathophysiological mechanisms. There is evidence of the role of microorganims in this disease development. Thanks to the open access to multiple omics data, it is possible to develop predictive models that are able to prognosticate the course and development of the disease. The interpretability of these models, and the study of the variables used, allows the identification of biological aspects of great importance in the development of the disease. In this work we generated a metagenomic signature with predictive capacity to identify IBD from fecal samples. Different Machine Learning models were trained, obtaining high performance measures. The predictive capacity of the identified signature was validated in two external cohorts. More precisely a cohort containing samples from patients suffering Ulcerative Colitis and another from patients suffering Crohn's Disease, the two major subtypes of IBD. The results obtained in this validation (AUC 0.74 and AUC = 0.76, respectively) show that our signature presents a generalization capacity in both subtypes. The study of the variables within the model, and a correlation study based on text mining, identified different genera that play an important and common role in the development of these two subtypes.CF-L's work was supported by the Collaborative Project in Genomic Data Integration (CICLOGEN) PI17/01826 funded by the Carlos III Health Institute from the Spanish National plan for Scientific and Technical Research and Innovation 2013-2016 and the European Regional Development Funds (FEDER)–A way to build Europe. JS's work was funded by the Ramón y Cajal grant (RYC2019-026576-I) funded by Ministry of Science and Innovation of the Spanish government. GL-C's work was supported by a grant from the Biotechnology and Biological Sciences Research Council (BBSRC grant BB/S006281/1) and open access publication fees were supported by Queen's University of Belfast UKRI block grant

Expression of the alpha-thionin gene from barley in tobacco confers enhanced resistance to bacterial pathogens

Thionins are cysteine-rich, 5 kDa polypeptides which are toxic to plant pathogens in vitro. Expression of the gene encoding alpha-thionin from barley endosperm, under the 35S promoter from cauliflower mosaic virus, conferred to transgenic tobacco enhanced resistance to the bacterial plant pathogens Pseudomonas syringae pv. tabaci 153 and P. syringae pv. syringae. The barley alpha-thionin gene, which has two introns, was correctly spliced in tobacco. The alpha-thionin in transgenic plants had the expected mobility in the gradient, when separated by high- performance liquid chromatography, reacted with monospecific antibodies and showed the expected antibiotic properties in vitr

Domestic hot water production system in a hospital: Energy audit and evaluation of measures to boost the solar contribution

Hospitals consume large quantities of energy to produce hot water and offset the distribution and recirculation thermal losses. This paper analyses a solar thermal system combined with gas boilers for domestic hot water production in a medium-size hospital. The solar contribution to the total demand (27%) is below design expectations (75%), resulting in significant gas consumption. The energy audit conducted in the first part of the paper highlights the vast thermal loss through poorly insulated pipes as the primary cause of the poor solar fraction. This issue is endemic to hot water-intensive buildings. The second part of the paper addresses the techno-economic evaluation of energy retrofit measures to reach a solar fraction of 60%. The simulation results indicate that cost-optimised solutions generally expand the solar caption area by 43–57% and improve insulations to reduce thermal losses by 70%. Depending on carbon taxes, the cost of hot water production would be 31–41 cent-€/kWh, which represents a 15–45% reduction from the current costs. Under stringent climate policies, installing heat pumps may further enhance economic competitiveness. The indicators and charts developed in this work are helpful decision-making tools concerning the energy refurbishment of solar domestic hot water systems.The authors acknowledge the Universidad de Málaga and “Programa Operativo FEDER Andalucía 2014–2020″ the financial support of the contract UMA18-FEDERJA-247.Funding for open access charge: Universidad de Málaga / CBU

Subclinical Atherosclerosis Burden by 3D Ultrasound in Mid-Life: The PESA Study

BACKGROUND: Detection of subclinical atherosclerosis improves risk prediction beyond cardiovascular risk factors (CVRFs) and risk scores, but quantification of plaque burden may improve it further. Novel 3-dimensional vascular ultrasound (3DVUS) provides accurate volumetric quantification of plaque burden. OBJECTIVES: The authors evaluated associations between 3DVUS-based plaque burden and CVRFs and explored potential added value over simple plaque detection. METHODS: The authors included 3,860 (92.2%) PESA (Progression of Early Subclinical Atherosclerosis) study participants (age 45.8 ± 4.3 years; 63% men). Bilateral carotid and femoral territories were explored by 3DVUS to determine the number of plaques and territories affected, and to quantify global plaque burden defined as the sum of all plaque volumes. Linear regression and proportional odds models were used to evaluate associations of plaque burden with CVRFs and estimated 10-year cardiovascular risk. RESULTS: Plaque burden was higher in men (63.4 mm3 [interquartile range (IQR): 23.8 to 144.8 mm3] vs. 25.7 mm3 [IQR: 11.5 to 61.6 mm3] in women; p < 0.001), in the femoral territory (64 mm3 [IQR: 27.6 to 140.5 mm3] vs. 23.1 mm3 [IQR: 9.9 to 48.7 mm3] in the carotid territory; p < 0.001), and with increasing age (p < 0.001). Age, sex, smoking, and dyslipidemia were more strongly associated with femoral than with carotid disease burden, whereas hypertension and diabetes showed no territorial differences. Plaque burden was directly associated with estimated cardiovascular risk independently of the number of plaques or territories affected (p < 0.01). CONCLUSIONS: 3DVUS quantifies higher plaque burden in men, in the femoral territory, and with increasing age during midlife. Plaque burden correlates strongly with CVRFs, especially at the femoral level, and reflects estimated cardiovascular risk more closely than plaque detection alone. (Progression of Early Subclinical Atherosclerosis [PESA] Study; NCT01410318).The PESA study is cofunded equally by the Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain, and Banco Santander, Madrid, Spain. The study also receives funding from the Institute of Health Carlos III (PI15/02019) and the European Regional Development Fund (ERDF). The CNIC is supported by the Ministry of Economy, Industry and Competitiveness (MINECO) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). Dr. Sanchez-Gonzalez is an employee of Philips Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Stephen J. Nicholls, MD, served as Guest Editor for this paperS

Characterization and analysis of thionin genes

The general designation of thionins has been proposed for a family of homologous proteins that have been isolated from different tissues in a wide range of plant taxa and have been variously named purothionins, viscotoxins, crambins, etc. (see Garcia-Olmedo et al., 1989). The possible involvement of thionins in plant defense was first suggested, on the basis of their in vitro toxicity to plant pathogens, by Fernandez de Caleya et al., (1972). Those observations had been prompted by earlier reports concerning the antimicrobial properties of these polypeptides (Stuart and Harris, 1942; Balls and Harris, 1944). Work on the thionins, which has been actively pursued over the past half-century, has been recently reviewed in detail (Garcia-Olmedo et al., 1989). For this reason, earlier work will only be partially summarized in the present chapter, which will focus on recent developments concerning thionin genes and their potential role in plant defense mechanisms

A de novo complete BRCA1 gene deletion identified in a Spanish woman with early bilateral breast cancer

<p>Abstract</p> <p>Background</p> <p>Germline mutations in either of the two tumor-suppressor genes, <it>BRCA1 </it>and <it>BRCA2</it>, account for a significant proportion of hereditary breast and ovarian cancer cases. Most of these mutations consist of deletions, insertions, nonsense mutations, and splice variants, however an increasing number of large genomic rearrangements have been identified in these genes.</p> <p>Methods</p> <p>We analysed <it>BRCA1 </it>and <it>BRCA2 </it>genes by direct sequencing and MLPA. We confirmed the results by an alternative MLPA kit and characterized the <it>BRCA1 </it>deletion by Array CGH.</p> <p>Results</p> <p>We describe the first case of a patient with no strong family history of the disease who developed early-onset bilateral breast cancer with a <it>de novo </it>complete <it>BRCA1 </it>gene deletion in the germinal line. The detected deletion started from the region surrounding the <it>VAT1 </it><it>locus </it>to the beginning of <it>NBR1 </it>gene, including the <it>RND2</it>, Ψ<it>BRCA1</it>, <it>BRCA1 </it>and <it>NBR2 </it>complete genes.</p> <p>Conclusion</p> <p>This finding supports the large genomic rearrangement screening of <it>BRCA </it>genes in young breast cancer patients without family history, as well as in hereditary breast and ovarian cancer families previously tested negative for other variations.</p

The Holocene Cedrus pollen record from Sierra Nevada (S Spain), a proxy for climate change in N Africa

Comprehending the effects of climate variability and disturbance on forested ecosystems is paramount to successfully managing forest environments under future climate scenarios (e.g., global warming, aridi-fication increase). Changes in fossil pollen abundance in sedimentary archives record past vegetation dynamics at regional scales, mainly related to climate changes and, in the last few millennia, to human impact. Pollen records can thus provide long databases with information on how the environment reacted to climate change before the historical record. In this study, we synthesized fossil pollen data from seven sites from the Sierra Nevada in southern Spain to investigate the response of forests in the western Mediterranean area to millennial-scale climate changes and to human impact during the Holocene. In particular, here we focused on Cedrus pollen abundances, which most-likely originated from Northern Africa and were carried to Sierra Nevada by wind. Cedrus pollen has received little attention in the Iberian Peninsula palynological records, for it occurs in low concentrations and has an African source, and thus this article explores the potential to reconstruct its past history and climate. Although Cedrus abundances are generally lower than 1% in the studied pollen samples, a comparison with North African (Moroccan) Cedrus pollen records shows similar trends at long- and short-term time-scales. Therefore, this record could be used as a proxy for changes in this forest species in North Africa. As observed in the Sierra Nevada synthetic record, the increasing trend of Cedrus pollen during the Middle and Late Holocene closely correlates with decreasing summer insolation. This would have produced overall cooler annual temperatures in Northern Africa (Middle Atlas and Rif Mountains) as well as lower summer evaporation, benefiting the growth of this cool-adapted montane tree species while increasing available moisture during the summer, which is critical for this water-demanding species. Millennial-scale variability also characterizes the Sierra Nevada Cedrus synthetic pollen record. Cedrus abundance oscillations co-vary with well-known millennial-scale climatic variability that controlled cedar abundance and altitudinal distribution in montane areas of N Africa. (C) 2020 Elsevier Ltd. All rights reserved.Peer reviewe

Association Between a Social-Business Eating Pattern and Early Asymptomatic Atherosclerosis

BACKGROUND The importance of a healthy diet in relation to cardiovascular health promotion is widely recognized. Identifying specific dietary patterns related to early atherosclerosis would contribute greatly to inform effective primary prevention strategies. OBJECTIVES This study sought to quantify the association between specific dietary patterns and presence and extent of subclinical atherosclerosis in a population of asymptomatic middle-aged adults. METHODS The PESA (Progression of Early Subclinical Atherosclerosis) study enrolled 4,082 asymptomatic participants 40 to 54 years of age (mean age 45.8 years; 63\% male) to evaluate the presence of subclinical atherosclerosis in multiple vascular territories. A fundamental objective of this cohort study was to evaluate the life-style-related determinants, including diet, on atherosclerosis onset and development. We conducted a cross-sectional analysis of baseline data, including detailed information on dietary habits obtained as part of the overall life-style and risk factor assessment, as well as a complete vascular imaging study that was performed blinded to the clinical information. RESULTS Most PESA participants follow a Mediterranean (40\% of participants) or a Western (41\%) dietary pattern. A new pattern, identified among 19\% of participants, was labeled as a social-business eating pattern, characterized by a high consumption of red meat, pre-made foods, snacks, alcohol, and sugar-sweetened beverages and frequent eating-out behavior. Participants following this pattern presented a significantly worse cardiovascular risk profile and, after adjustment for risk factors, increased odds of presenting subclinical atherosclerosis (odds ratio: 1.31; 95\% confidence interval: 1.06 to 1.63) compared with participants following a Mediterranean diet. CONCLUSIONS A new social-business eating pattern, characterized by high consumption of red and processed meat, alcohol, and sugar-sweetened beverages, and by frequent snacking and eating out as part of an overall unhealthy life-style, is associated with an increased prevalence, burden, and multisite presence of subclinical atherosclerosis. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318) (C) 2016 by the American College of Cardiology Foundation.This study was supported by a noncompetitive unrestricted grant shared between the National Center for Cardiovascular Research Carlos III (CNIC) and the Bank of Santander. The PESA study is a noncommercial study independent of the health care and pharmaceutical industry. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505). Dr. Vedanthan is supported by the Fogarty International Center of the National Institutes of Health under award K01 TW 009218-05. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Bueno has received advisory/speaking fees from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, Novartis, and Servier; has received a research grant from AstraZeneca; has received advisory fees from Abbott; and has received speaking fees from Ferrer. Frank B. Hu, MD, served as Guest Editor for this paper