KIR2DS4 and Its Variant KIR1D in KIR-AA Genotype Donors Showed Differential Survival Impact in Patients with Lymphoid Disease after HLA-Matched Unrelated Hematopoietic Stem Cell Transplantation.

Previous studies have illustrated associations between the presence of activating killer cell immunoglobulin-like receptor (KIR) genes and lower susceptibility to hematologic malignancies in humans. In addition, favorable hematopoietic stem cell transplantation (HSCT) outcomes have been reported in patients who received transplants from donors with KIR genotypes dominant for activating KIR receptors. However, the association of activating KIR genes on an allelic level with disease and their impact on HSCT outcome has been little investigated to date.

Evolutionary Conservation and Transcriptome Analyses Attribute Perenniality and Flowering to Day-Length Responsive Genes in Bulbous Barley (Hordeum bulbosum).

Rapid population growth and dramatic climatic turnovers are challenging global crop production. These challenges are spurring plant breeders to enhance adaptation and sustainability of major crops. One intriguing approach is to turn annual systems into perennial ones, yet long-term classical breeding efforts to induce perenniality have achieved limited success.

A designed photoenzyme for enantioselective [2+2] cycloadditions.

The ability to program new modes of catalysis into proteins would allow the development of enzyme families with functions beyond those found in nature. To this end, genetic code expansion methodology holds particular promise, as it allows the site-selective introduction of new functional elements into proteins as noncanonical amino acid side chains. Here we exploit an expanded genetic code to develop a photoenzyme that operates by means of triplet energy transfer (EnT) catalysis, a versatile mode of reactivity in organic synthesis that is not accessible to biocatalysis at present.

Donor genetic determinant of thymopoiesis rs2204985 impacts clinical outcome after single HLA mismatched hematopoietic stem cell transplantation.

A common genetic variant within the T cell receptor alpha (TCRA)-T cell receptor delta (TCRD) locus (rs2204985) has been recently found to associate with thymic function. Aim of this study was to investigate the potential impact of donor rs2204985 genotype on patient's outcome after unrelated hematopoietic stem cell transplantation (uHSCT). 2016 adult patients were retrospectively analyzed.

Emmer Wheat Eco-Geographic and Genomic Congruence Shapes Phenotypic Performance under Mediterranean Climate.

Emmer wheat ( ssp. ) is one of the world's oldest domesticated crops, and it harbors a potentially rich reservoir of agronomic and nutritional quality trait variations. The growing global demand for plant-based health-food niche markets has promoted new commercial interest in ancient grains, including Emmer wheat.

Matching Improves Outcome of Unrelated Hematopoietic Stem Cell Transplantation.

The loci are closely linked to the gene. Mismatches in these loci occur with a frequency of about 8%-12% in otherwise 10/10 HLA-matched transplant pairs. There is preliminary evidence that these disparities may associate with increased acute graft-versus-host disease (GvHD) rates.

Local MRI-based measures of thigh adipose tissue derived from fully automated deep convolutional neural network-based segmentation show a comparable responsiveness to bidirectional change in body weight as from quality controlled manual segmentation.

Background: Thigh intermuscular (IMF) and subcutaneous (SCF) fat are associated with joint function, inflammation and knee osteoarthritis. Fully automated segmentation from MRI is important to study the above relationship in larger cohorts. However, such algorithms are not clinically evaluated for longitudinal studies.

Association of Superficial Cartilage Transverse Relaxation Time With Osteoarthritis Disease Progression: Data From the Foundation for the National Institutes of Health Biomarker Study of the Osteoarthritis Initiative.

Objective: To study whether layer-specific cartilage transverse relaxation time (T2) and/or longitudinal change is associated with clinically relevant knee osteoarthritis (OA) disease progression.

Methods: The Foundation for the National Institutes of Health Biomarker Consortium was a nested case-control study on 600 knees from 600 Osteoarthritis Initiative participants. Progressor knees had both medial tibiofemoral radiographic joint space width (JSW) loss (≥0.

The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Analysis.

T-cell epitope matching according to the TCE3 algorithm classifies HLA-DPB1 mismatches in permissive and non-permissive. This classification has been shown to be predictive for mortality and acute GvHD (aGvHD) events in large international cohorts. We retrospectively genotyped HLA-DPB1 in 3523 patients transplanted in Germany between 2000 and 2014 and in their unrelated donors using an Illumina amplicon-NGS based assay.

Longitudinal Change in Knee Cartilage Thickness and Function in Subjects with and without MRI-Diagnosed Cartilage Damage.

Objective: Cartilage damage diagnosed by magnetic resonance imaging (MRI) is highly prevalent in the population. In this article, we explore whether such cartilage damage is associated with greater longitudinal change in 3D cartilage thickness and knee function in subjects without (risk factors of) knee osteoarthritis.

Design: Eighty-two knees of Osteoarthritis Initiative healthy reference cohort participants had baseline and 4-year follow-up MRI and knee function data.

Detection of Differences in Longitudinal Cartilage Thickness Loss Using a Deep-Learning Automated Segmentation Algorithm: Data From the Foundation for the National Institutes of Health Biomarkers Study of the Osteoarthritis Initiative.

Objective: To study the longitudinal performance of fully automated cartilage segmentation in knees with radiographic osteoarthritis (OA), we evaluated the sensitivity to change in progressor knees from the Foundation for the National Institutes of Health OA Biomarkers Consortium between the automated and previously reported manual expert segmentation, and we determined whether differences in progression rates between predefined cohorts can be detected by the fully automated approach.

Methods: The OA Initiative Biomarker Consortium was a nested case-control study. Progressor knees had both medial tibiofemoral radiographic joint space width loss (≥0.

Accuracy and longitudinal reproducibility of quantitative femorotibial cartilage measures derived from automated U-Net-based segmentation of two different MRI contrasts: data from the osteoarthritis initiative healthy reference cohort.

Objective: To evaluate the agreement, accuracy, and longitudinal reproducibility of quantitative cartilage morphometry from 2D U-Net-based automated segmentations for 3T coronal fast low angle shot (corFLASH) and sagittal double echo at steady-state (sagDESS) MRI.

Methods: 2D U-Nets were trained using manual, quality-controlled femorotibial cartilage segmentations available for 92 Osteoarthritis Initiative healthy reference cohort participants from both corFLASH and sagDESS (n = 50/21/21 training/validation/test-set). Cartilage morphometry was computed from automated and manual segmentations for knees from the test-set.

Rolling circle amplification of synthetic DNA accelerates biocatalytic determination of enzyme activity relative to conventional methods.

The ability to quickly and easily assess the activity of large collections of enzymes for a desired substrate holds great promise in the field of biocatalysis. Cell-free synthesis, although not practically amenable for large-scale enzyme production, provides a way to accelerate the timeline for screening enzyme candidates using small-scale reactions. However, because cell-free enzyme synthesis requires a considerable amount of template DNA, the preparation of high-quality DNA "parts" in large quantities represents a costly and rate-limiting prerequisite for high throughput screening.

Biocatalysis in Medicinal Chemistry: Challenges to Access and Drivers for Adoption.

The use of biocatalysis in the manufacture of small molecule active pharmaceutical ingredients has seen a marked increase over the past decade. Driven by academic and industrial interest in the application of enzymes as catalysts for transforming chemical routes, the biocatalytic toolbox available to a chemist has continued to expand. Despite this, the application of biocatalysis in early discovery chemistry has trailed in comparison to its use in manufacturing routes.

HLA-DRB4*01:14 is a null allele, and renamed HLA-DRB4*01:14N.

Full-length sequencing of HLA-DRB4*01:14 showed the same splice site mutation as in HLA-DRB4*01:03:01:02N.

Safety and feasibility of minocycline in treatment of acute traumatic brain injury.

Background: Minocycline is a pleomorphic neuroprotective agent well studied in animal models of traumatic brain injury (TBI) and brain ischemia.

Methods: To test the hypothesis that administration of minocycline in moderate to severe TBI (Glasgow Coma Score 3-12). Fifteen patients were enrolled in a two-dose escalation study of minocycline to evaluate the safety of twice the recommended antibiotic dosage; tier 1 n = 7 at a loading dose of 800 mg followed by 200 mg twice a day (BID) for 7 days; tier 2 n = 8 at a loading dose of 800 mg followed by 400 mg BID for 7 days.

Head Impact Burden and Change in Neurocognitive Function During a Season of Youth Football.

Objective: To determine the association of repetitive subconcussive head impacts with functional outcomes in primary and high school tackle football players.

Setting: Youth football fields and an outpatient sports neurology clinic.

Participants: A total of 112 primary school (n = 55, age 9-12 years) and high school (n = 57, age 15-18 years) football players.

Resequencing of four novel alleles with nanopore technology.

Long nanopore reads allow phasing of heterozygous positions but show limitations in sequencing of homopolymers.

Competing-risk outcomes after hematopoietic stem cell transplantation from the perspective of time-dependent effects.

The success of hematopoietic stem cell transplantation is determined by multiple factors. Additional complexity is conferred by covariables showing time-dependent effects. We evaluated the effect of predictors on competing-risk outcomes after hematopoietic stem cell transplantation in a time-dependent manner.

MICA-129 Dimorphism and Soluble MICA Are Associated With the Progression of Multiple Myeloma.

Natural killer (NK) cells are immune innate effectors playing a pivotal role in the immunosurveillance of multiple myeloma (MM) since they are able to directly recognize and kill MM cells. In this regard, among activating receptors expressed by NK cells, NKG2D represents an important receptor for the recognition of MM cells, being its ligands expressed by tumor cells, and being able to trigger NK cell cytotoxicity. The MHC class I-related molecule A (MICA) is one of the NKG2D ligands; it is encoded by highly polymorphic genes and exists as membrane-bound and soluble isoforms.

Intraoperative hippocampal electrocorticography frequently captures electrographic seizures and correlates with hippocampal pathology.

Objective: Relationship between electrographic seizures on hippocampal electrocorticography (IH-ECoG) and presence/type of hippocampal pathology remains unclear.

Methods: IH-ECoG was recorded for 10-20 min from the ventricular surface of the hippocampus following removal of the temporal neocortex in 40 consecutive patients. Correlation between intraoperative hippocampal seizures and preoperative MRI, hippocampal histopathology, and EEG from invasive monitoring was determined.

Enzymatic amidation for industrial applications.

Nature has developed a robust toolbox for the formation of amide bonds, enabling a variety of disconnections applicable to small molecule synthesis. In spite of this, the exploitation of biocatalytic techniques for industrial synthesis remains limited to a few very important cases. This review discusses previously demonstrated techniques for the biocatalytic synthesis of amide bonds, reviews examples of industrial scale-up of these techniques, and identifies a number of limitations to the scalability within the current state of the art.

Altered metabolomic-genomic signature: A potential noninvasive biomarker of epilepsy.

Objective: This study aimed to identify noninvasive biomarkers of human epilepsy that can reliably detect and localize epileptic brain regions. Having noninvasive biomarkers would greatly enhance patient diagnosis, patient monitoring, and novel therapy development. At the present time, only surgically invasive, direct brain recordings are capable of detecting these regions with precision, which severely limits the pace and scope of both clinical management and research progress in epilepsy.