The Polygenic and Monogenic Basis of Blood Traits and Diseases

Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation. Analysis of blood cell traits in the UK Biobank and other cohorts illuminates the full genetic architecture of hematopoietic phenotypes, with evidence supporting the omnigenic model for complex traits and linking polygenic burden with monogenic blood diseases

Photostability of low cost dye-sensitized solar cells based on natural and synthetic dyes

Anthocyanin dye showed the maximum current efficiency η=0.27% •Application of natural pigments and synthetic dye sensitizers in dye-sensitized solar cells (DSSCs).•Photostability of the dyes over the TiO2 film electrodes.•The stability results favor selecting anthocyanin as a promising sensitizer candidate for DSSCs applications. This paper deals with the use of some natural pigments as well as synthetic dyes to act as sensitizers in dye-sensitized solar cells (DSSCs). Anthocyanin dye extracted from rosella (Hibiscus sabdariffa L.) flowers, the commercially available textile dye Remazole Red RB-133 (RR) and merocyanin-like dye based on 7-methyl coumarin are tested. The photostability of the three dyes is investigated under UV–Vis light exposure. The results show a relatively high stability of the three dyes. Moreover, the photostability of the solid dyes is studied over the TiO2 film electrodes. A very low decolorization rates are recorded as; rate constants k=1.6, 2.1 and 1.9×10−3min−1 for anthocyanin, RR and coumarin dyes, respectively. The stability results favor selecting anthocyanin as a promising sensitizer candidate in DSSCs based on natural products. Dyes-sensitized solar cells are fabricated and their conversion efficiency (η) is 0.27%, 0.14% and 0.001% for the anthocyanin, RR and coumarin dyes, respectively. Moreover, stability tests of the sealed cells based on anthocyanin and RR dyes are done under continuous light exposure of 100mWcm−2, reveals highly stable DSSCs

Spectrophotometric determination of erbium using kojic acid dye in different rare earth concentrates

A sensitive and selective spectrophotometric method was studied for the determination of erbium (Er) with kojic acid dye (koj) and cetylpyridinium chloride (CPC) as a cationic surfactant from Egyptian monazite and xenotime concentrates using third derivative spectrophotometry. The calibration curve was linear from 1 to 150 µg/mL erbium. The influence of various parameters and reaction conditions for optimum complex formation were investigated. The relative standard deviation for determination of 1 µg/mL erbium was found to be 1.5 after 5 repeated determinations with percentage error for Er determination from monazite and xenotime concentrates 6.4% and 4.48% respectively. The molar absorptivity of conventional and third derivative spectrum were 0.14 × 103 M−1 cm−1 and 0.13 × 103 M−1 cm−1 respectively and the detection limit was 1 µg/mL. Keywords: Erbium, Kojic acid dye, Cetylpyridinium chloride, Egyptian monazite, Xenotim

Prognostic value of dobutamine-atropine stress technetium-99m sestamibi perfusion scintigraphy in patients with chest pain

Objectives.This study investigated the prognostic value of dobutamine-atropine technetium-99m (Tc-99m) sestamibi singlephoton emission computed tomographic (SPECT) myocardial perfusion imaging.Background.Dobutamine-atropine Tc-99m sestamibi SPECT imaging is an accurate method for the detection of coronary disease. However, the prognostic value of this stress modality has not been assessed.Methods.Three hundred ninety-two consecutive patients with chest pain (mean [±SD] age 60 ± 12 years; 220 men, 190 with a previous myocardial infarction) underwent a dobutamineatropine Tc-99m sestamibi SPECT scintigraphic study. Patients were followed up for 22 ± 13 months to determine the univariate and multivariate variables associated with hard cardiac events (cardiac death, nonfatal myocardial infarction), to define their event-free survival and to determine whether the extent and severity of reversible perfusion defects correlated with events.Results.Forty-four patients (11%) had hard cardiac events. Multivariate models demonstrated that older age (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.0 to 4.4), history of heart failure (OR 2.6, 95% CI 1.3 to 5.2), abnormal sestamibi scan results (OR 10.0, 95% CI 2.3 to 43.0) and reversible perfusion defects (OR 3.2, 95% CI 1.6 to 6.4) had independent predictive value. Patients without perfusion defects, with fixed defects alone, reversible defects alone and fixed plus reversible defects had annual hard cardiac event rates of 0.8%, 6.8%, 8.1% and 11.6%, respectively. Patients with increasing reversible defect scores had increasing annual event rates of 2.1%, 5.0%, 5.5%, 13.0% and 14.6%, respectively.Conclusions.Dobutamine-atropine stress Tc-99m sestamibi SPECT imaging provides excellent prognostic information. The single most important independent predictor for future hard cardiac events is an abnormal pattern, and a reversible defect provides additional, independent prognostic information. Moreover, the extent and severity of reversible defects are major determinants for prognosis

Keratinocyte differentiation antigen-specific T cells in immune checkpoint inhibitor-treated NSCLC patients are associated with improved survival.

Immune checkpoint inhibitors (ICIs) have improved the survival of patients with non-small cell lung cancer (NSCLC) by reinvigorating tumor-specific T cell responses. However, the specificity of such T cells and the human leukocyte antigen (HLA)-associated epitopes recognized, remain elusive. In this study, we identified NSCLC T cell epitopes of recently described NSCLC-associated antigens, termed keratinocyte differentiation antigens. Epitopes of these antigens were presented by HLA-A 03:01 and HLA-C 04:01 and were associated with responses to ICI therapy. Patients with CD8 <sup>+</sup> T cell responses to these epitopes had improved overall and progression-free survival. T cells specific for such epitopes could eliminate HLA class I-matched NSCLC cells ex vivo and were enriched in patient lung tumors. The identification of novel lung cancer HLA-associated epitopes that correlate with improved ICI-dependent treatment outcomes suggests that keratinocyte-specific proteins are important tumor-associated antigens in NSCLC. These findings improve our understanding of the mechanisms of ICI therapy and may help support the development of vaccination strategies to improve ICI-based treatment of these tumors