A combined biomarker and clinical panel for chronic graft versus host disease diagnosis.

Whilst many chronic graft versus host disease (cGVHD) biomarkers have been previously reported, few have been verified in an independent cGVHD cohort. We aimed to verify the diagnostic accuracy of previously reported markers of cGVHD in a multi-centre Chronic GVHD Consortium. A total of 42 RNA and 18 protein candidate biomarkers were assessed amongst 59 cGVHD cases and 33 matched non-GVHD controls. Total RNA was isolated from PBMC, and RNA markers were quantified using PCR. Serum protein markers were quantified using ELISA. A combined 3 RNA biomarker (IRS2, PLEKHF1 and IL1R2) and 2 clinical variables (recipient CMV serostatus and conditioning regimen intensity) panel accurately (AUC 0.81) segregated cGVHD cases from controls. Other studied RNA and protein markers were not confirmed as accurate cGVHD diagnostic biomarkers. The studied markers failed to segregate higher risk cGVHD (per overall NIH 0-3 score, and overlap versus classic cGVHD status). These data support the need for multiple independent verification studies for the ultimate clinical application of cGVHD diagnostic biomarkers

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A combined biomarker and clinical panel for chronic graft versus host disease diagnosis.

Whilst many chronic graft versus host disease (cGVHD) biomarkers have been previously reported, few have been verified in an independent cGVHD cohort. We aimed to verify the diagnostic accuracy of previously reported markers of cGVHD in a multi-centre Chronic GVHD Consortium. A total of 42 RNA and 18 protein candidate biomarkers were assessed amongst 59 cGVHD cases and 33 matched non-GVHD controls. Total RNA was isolated from PBMC, and RNA markers were quantified using PCR. Serum protein markers were quantified using ELISA. A combined 3 RNA biomarker (IRS2, PLEKHF1 and IL1R2) and 2 clinical variables (recipient CMV serostatus and conditioning regimen intensity) panel accurately (AUC 0.81) segregated cGVHD cases from controls. Other studied RNA and protein markers were not confirmed as accurate cGVHD diagnostic biomarkers. The studied markers failed to segregate higher risk cGVHD (per overall NIH 0-3 score, and overlap versus classic cGVHD status). These data support the need for multiple independent verification studies for the ultimate clinical application of cGVHD diagnostic biomarkers

Late cardiovascular morbidity and mortality following pediatric allogeneic hematopoietic cell transplantation.

We analyzed late cardiovascular outcomes of 661 patients who survived at least 2 years from hematopoietic cell transplantation for childhood hematologic malignancy between 1995 and 2008. Center for International Blood and Marrow Transplant Research data was supplemented with surveys focused on cardiotoxicity and potential risk factors. The median duration of follow-up was 97 months (range 24-230). 4.2% of survivors experienced at least one of the primary outcomes including coronary artery disease (0.2%), cerebrovascular accident (0.6%), cardiomyopathy (3%), and cardiac-related death (0.5%). Patients who received anthracycline chemotherapy (HR 4.67, p = 0.036) or cranial or chest radiation (HR 5.58, p < 0.0001; HR 2.18, p = 0.0087) were at increased risk for developing one of the primary outcomes. Dyslipidemia was diagnosed in 18% of survivors. Pre-transplant anthracycline (HR 1.74, p < 0.0001) and chest radiation (HR 1.34, p = 0.0371) were risk factors for dyslipidemia. Overweight/obese body mass status was present in 63% of patients at baseline, 65% at 2 years, and 52% at most recent evaluation. Diabetes was diagnosed in 7% of subjects. In conclusion, severe cardiovascular complications were infrequently reported. The incidence of risk factors including obesity and dyslipidemia were significant and will likely increase the risk of cardiovascular disease over time in transplant survivors

Ocular Graft-versus-Host Disease after Hematopoietic Cell Transplantation: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation.

Ocular graft-versus-host disease (GVHD) occurs in more than one-half of patients who develop chronic GVHD after allogeneic hematopoietic cell transplantation (HCT), causing prolonged morbidity that affects activities of daily living and quality of life. Here we provide an expert review of ocular GVHD in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Recent updates in ocular GVHD regarding pathophysiology, preclinical models, risk factors, prevention, screening, diagnosis, response criteria, evaluation measures, and treatment are discussed. Ocular GVHD involves at least 3 biological processes: lacrimal gland dysfunction, meibomian gland dysfunction, and corneoconjunctival inflammation. Preclinical models have identified several novel pathogenic mechanisms, including the renin angiotensin system and endoplasmic reticulum stress signaling, which can be targeted by therapeutic agents. Numerous studies have identified reliable tests for establishing diagnosis and response assessment of ocular GVHD. The efficacy of systemic and topical treatment for ocular GVHD is summarized. It is important that all health professionals caring for HCT recipients have adequate knowledge of ocular GVHD to provide optimal care.status: publishe

TRY plant trait database - enhanced coverage and open access

10.1111/gcb.14904GLOBAL CHANGE BIOLOGY261119-18

Precision measurement of the structure of the CMS inner tracking system using nuclear interactions

The structure of the CMS inner tracking system has been studied using nuclear interactions of hadrons striking its material. Data from proton-proton collisions at a center-of-mass energy of 13 TeV recorded in 2015 at the LHC are used to reconstruct millions of secondary vertices from these nuclear interactions. Precise positions of the beam pipe and the inner tracking system elements, such as the pixel detector support tube, and barrel pixel detector inner shield and support rails, are determined using these vertices. These measurements are important for detector simulations, detector upgrades, and to identify any changes in the positions of inactive elements