Mortality in Greenlanders with chronic hepatitis B virus infection

In‐depth reviewing of all medical records and clinical databases concluded a 7‐year shorter lifespan among Greenlanders infected with hepatitis B virus (HBV) compared with non‐infected. Mortality did not associate with liver disease or any other specific disease entity. A possible mechanism for the reduced lifespan is subclinical inflammation that may be augmented by chronic viral infection. We hypothesized that chronic HBV infection contributes to this process causing a reduced life span. We added measurement of two markers of inflammation to the 10‐year follow‐up on our study of HBV among 50‐ through 69‐years‐old subjects in Greenland. The markers were YKL40 related to liver disease and hsCRP as a global marker of inflammation. Survival was evaluated using Cox regression with time until death entered as dependent variable and age, sex, smoking, alcohol intake, BMI, the presence of HBsAg and one marker of inflammation as explanatory variables. Forty‐eight percent of participants with chronic HBV infection were alive after 10 years compared with 65% of participants without infection (p = 0.003). Survival associated with age (p < 0.001), BMI (p = 0.003) and both YKL40 and hsCRP (both, p < 0.001). Harbouring HBV influenced 10‐year survival in the Cox regression after adjusting for age, sex, BMI, smoking, alcohol intake and inflammation. In conclusion, chronic low‐grade inflammation and being infected with HBV were independent markers of mortality in otherwise healthy subjects. Thus, the 7‐year shorter lifespan among Greenlanders with chronic HBV infection seems related to the long‐lasting infection. Our findings call for caution in perceiving a chronic infection as benign

Thyroid autoimmunity in Greenlandic Inuit

OBJECTIVE: This study aimed to provide the first data on the occurrence of thyroid autoimmunity among Inuit in Greenland, a distinct ethnic group who is not iodine deficient. DESIGN: This study is a population-based cross-sectional study. METHODS: Data were collected in Nuuk in West Greenland and in Ammassalik district in East Greenland. Information on lifestyle, diet and diseases was obtained using questionnaires. Thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) and thyroid-stimulating hormone (TSH) were measured in serum. Iodine and creatinine were measured in spot urine samples. RESULTS: The participation rate was 95% with 434 Inuit participants; 75% were smokers. Iodine excretion was 169 µg/24 h in urban West Greenland, 224 µg/24 h in the main town and 228 µg/24 h in settlements in rural East Greenland. TPOAb, TgAb or either of these was measured in the serum from 3.7, 5.9 and 8.3% of participants, respectively. TPOAb or TgAb was found in 9.3% of Inuit women and 7.5% of men and more frequently, in East Greenland Inuit with the higher iodine excretion (P  = 0.02). There was some evidence suggesting that thyroid autoimmunity was more frequent among non-smokers (12.5%) compared to smokers (7.0%). Harbouring a thyroid autoantibody was most frequent in participants with TSH above 3.6 mIU/L (P  < 0.001). CONCLUSION: Thyroid autoantibodies were rare among Greenland Inuit. While iodine nutrition was associated with autoimmunity similarly to other ethnic groups, the influence of sex and smoking was limited. This could suggest genetic component in Inuit, but the impact of cold, selenium and persistent organic pollutants needs to be elucidated

Serum 25-hydroxyvitamin D, calcium and parathyroid hormone levels in Native and European populations in Greenland

AbstractCa homoeostasis is important to human health and tightly controlled by powerful hormonal mechanisms that display ethnic variation. Ethnic variations could occur also in Arctic populations where the traditional Inuit diet is low in Ca and sun exposure is limited. We aimed to assess factors important to parathyroid hormone (PTH) and Ca in serum in Arctic populations. We included Inuit and Caucasians aged 50–69 years living in the capital city in West or in rural East Greenland. Lifestyle factors were assessed by questionnaires. The intake of Inuit diet was assessed from a FFQ. 25-Hydroxyvitamin D (25OHD2and 25OHD3) levels were measured in serum as was albumin, Ca and PTH. The participation rate was 95 %, with 101 Caucasians and 434 Inuit. Median serum 25OHD (99·7 % was 25OHD3) in Caucasians/Inuit was 42/64 nmol/l (25, 75 percentiles 25, 54/51, 81) (P&lt;0·001). Total Ca in serum was 2·33/2·29 mmol/l (25, 75 percentiles 2·26, 2·38/2·21, 2·36) (P=0·01) and PTH was 2·7/2·2 pmol/l (25, 75 percentiles 2·2, 4·1/1·7, 2·7) (P&lt;0·001). The 69/97 Caucasians/Inuit with serum 25OHD &lt;50 nmol/l differed in PTH (P=0·001) that rose with lower 25OHD levels in Caucasians, whereas this was not the case in Inuit. Ethnic origin influenced PTH (β=0·27,P&lt;0·001) and Ca (β=0·22,P&lt;0·001) in multivariate linear regression models after adjustment for age, sex, BMI, smoking, alcohol and diet. In conclusion, ethnic origin influenced PTH, PTH response to low vitamin D levels and Ca levels in populations in Greenland. Recommendations are to evaluate mechanisms underlying the ethnic influence on Ca homoeostasis and to assess the impact of transition in dietary habits on Ca homoeostasis and skeletal health in Arctic populations.</jats:p

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis

<p>Abstract</p> <p>Background</p> <p>Accurate staging of rectal tumors is essential for making the correct treatment choice. In a previous study, we found that loss of 17p, 18q and gain of 8q, 13q and 20q could distinguish adenoma from carcinoma tissue and that gain of 1q was related to lymph node metastasis. In order to find markers for tumor staging, we searched for candidate genes on these specific chromosomes.</p> <p>Methods</p> <p>We performed gene expression microarray analysis on 79 rectal tumors and integrated these data with genomic data from the same sample series. We performed supervised analysis to find candidate genes on affected chromosomes and validated the results with qRT-PCR and immunohistochemistry.</p> <p>Results</p> <p>Integration of gene expression and chromosomal instability data revealed similarity between these two data types. Supervised analysis identified up-regulation of <it>EFNA1 </it>in cases with 1q gain, and <it>EFNA1 </it>expression was correlated with the expression of a target gene (<it>VEGF</it>). The <it>BOP1 </it>gene, involved in ribosome biogenesis and related to chromosomal instability, was over-expressed in cases with 8q gain. <it>SMAD2 </it>was the most down-regulated gene on 18q, and on 20q, <it>STMN3 </it>and <it>TGIF2 </it>were highly up-regulated. Immunohistochemistry for SMAD4 correlated with <it>SMAD2 </it>gene expression and 18q loss.</p> <p>Conclusion</p> <p>On basis of integrative analysis this study identified one well known CRC gene (<it>SMAD2</it>) and several other genes (<it>EFNA1, BOP1, TGIF2 </it>and <it>STMN3</it>) that possibly could be used for rectal cancer characterization.</p

Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches

Introduction: The COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. Methods: Extensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework can link biomolecules from omics data analysis and computational modelling to dysregulated pathways in a cell-, tissue- or patient-specific manner. Drug repurposing using text mining and AI-assisted analysis identified potential drugs, chemicals and microRNAs that could target the identified key factors. Results: Results revealed drugs already tested for anti-COVID-19 efficacy, providing a mechanistic context for their mode of action, and drugs already in clinical trials for treating other diseases, never tested against COVID-19. Discussion: The key advance is that the proposed framework is versatile and expandable, offering a significant upgrade in the arsenal for virus-host interactions and other complex pathologies.Peer Reviewe

Developmental roadmap for antimicrobial susceptibility testing systems

Antimicrobial susceptibility testing (AST) technologies help to accelerate the initiation of targeted antimicrobial therapy for patients with infections and could potentially extend the lifespan of current narrow-spectrum antimicrobials. Although conceptually new and rapid AST technologies have been described, including new phenotyping methods, digital imaging and genomic approaches, there is no single major, or broadly accepted, technological breakthrough that leads the field of rapid AST platform development. This might be owing to several barriers that prevent the timely development and implementation of novel and rapid AST platforms in health-care settings. In this Consensus Statement, we explore such barriers, which include the utility of new methods, the complex process of validating new technology against reference methods beyond the proof-of-concept phase, the legal and regulatory landscapes, costs, the uptake of new tools, reagent stability, optimization of target product profiles, difficulties conducting clinical trials and issues relating to quality and quality control, and present possible solutions

Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches

IntroductionThe COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. MethodsExtensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework can link biomolecules from omics data analysis and computational modelling to dysregulated pathways in a cell-, tissue- or patient-specific manner. Drug repurposing using text mining and AI-assisted analysis identified potential drugs, chemicals and microRNAs that could target the identified key factors.ResultsResults revealed drugs already tested for anti-COVID-19 efficacy, providing a mechanistic context for their mode of action, and drugs already in clinical trials for treating other diseases, never tested against COVID-19. DiscussionThe key advance is that the proposed framework is versatile and expandable, offering a significant upgrade in the arsenal for virus-host interactions and other complex pathologies