Quick-reference criteria for identifying multivariate cognitive change in older adults with mild cognitive impairment and dementia: An ADNI study.

Objective: To establish quick-reference criteria regarding the frequency of statistically rare changes in seven neuropsychological measures administered to older adults.

Method: Data from 935 older adults examined over a two-year interval were obtained from the Alzheimer's Disease Neuroimaging Initiative. The sample included 401 cognitively normal older adults whose scores were used to determine the natural distribution of change scores for seven cognitive measures and to set change score thresholds corresponding to the 5 percentile.

Rapid and accurate remethylation of DNA in deficient hematopoietic cells with restoration of DNMT3A activity.

Here, we characterize the DNA methylation phenotypes of bone marrow cells from mice with hematopoietic deficiency of or (or both enzymes) or expressing the dominant-negative mutation [R882H in humans; the most common mutation found in acute myeloid leukemia (AML)]. Using these cells as substrates, we defined DNA remethylation after overexpressing wild-type (WT) DNMT3A1, DNMT3B1, DNMT3B3 (an inactive splice isoform of DNMT3B), or DNMT3L (a catalytically inactive "chaperone" for DNMT3A and DNMT3B in early embryogenesis). Overexpression of for 2 weeks reverses the hypomethylation phenotype of Dnmt3a-deficient cells or cells expressing the R878H mutation.

A draft human pangenome reference.

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels.

Can elderly patients regain their preoperative functional level after distal radius fracture type A? Results from a fracture register study using PROM.

Introduction: Although distal radius fractures (DRFs) are the most common fractures of the human body, there are still ongoing debates concerning the treatment for type A fractures, especially in elderly patients. In spite of good clinical outcomes, it remains unclear whether elderly patients, especially, could regain the preoperative functional level of the wrist. Therefore, we have quantified wrist function within a retrospective study design using patient-reported outcome measures (PROM) and we have analyzed the influence of age between control and patient collective and young vs.

Persistent Molecular Disease in Adult Patients With AML Evaluated With Whole-Exome and Targeted Error-Corrected DNA Sequencing.

Purpose: Persistent molecular disease (PMD) after induction chemotherapy predicts relapse in AML. In this study, we used whole-exome sequencing (WES) and targeted error-corrected sequencing to assess the frequency and mutational patterns of PMD in 30 patients with AML.

Materials And Methods: The study cohort included 30 patients with adult AML younger than 65 years who were uniformly treated with standard induction chemotherapy.

A study of environmental factors affecting nutritional status among students of primary schools at Ulanga district, Tanzania.

Background: The prime concern of a society is to ensure healthy growth and development particularly of students of primary school because they are the future of the nation. Normal growth and development takes place only if there is optimum nutrition and safe environment to live in. The World Health Organization estimates that there are 178 million children that are malnourished across the globe and malnutrition contributes to the deaths of over one half of children in developing countries and Tanzania included.

High-coverage whole-genome sequencing of the expanded 1000 Genomes Project cohort including 602 trios.

The 1000 Genomes Project (1kGP) is the largest fully open resource of whole-genome sequencing (WGS) data consented for public distribution without access or use restrictions. The final, phase 3 release of the 1kGP included 2,504 unrelated samples from 26 populations and was based primarily on low-coverage WGS. Here, we present a high-coverage 3,202-sample WGS 1kGP resource, which now includes 602 complete trios, sequenced to a depth of 30X using Illumina.

Results of a Retrospective Fracture Register of Distal Radius Fractures Built Up Using PROM.

Introduction: Although distal radius fractures (DRFs) are the most common fractures of the human body, the best treatment for every fracture type is still debatable. However, randomized controlled trials are difficult to perform. The quality of care can be determined primarily in the context of health care research using register studies.

Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci.

Few studies have explored the impact of rare variants (minor allele frequency < 1%) on highly heritable plasma metabolites identified in metabolomic screens. The Finnish population provides an ideal opportunity for such explorations, given the multiple bottlenecks and expansions that have shaped its history, and the enrichment for many otherwise rare alleles that has resulted. Here, we report genetic associations for 1391 plasma metabolites in 6136 men from the late-settlement region of Finland.

Somatic inactivation leads to slow, canonical DNA methylation loss in murine hematopoietic cells.

Mutations in the gene encoding DNA methyltransferase 3A () are the most common cause of clonal hematopoiesis and are among the most common initiating events of acute myeloid leukemia (AML). Studies in germline and somatic knockout mice have identified focal, canonical hypomethylation phenotypes in hematopoietic cells; however, the kinetics of methylation loss following acquired inactivation in hematopoietic cells is essentially unknown. Therefore, we evaluated a somatic, inducible model of hematopoietic loss, and show that inactivation of in murine hematopoietic cells results in a relatively slow loss of methylation at canonical sites throughout the genome; in contrast, remethylation of Dnmt3a deficient genomes in hematopoietic cells occurs much more quickly.

Functional and epigenetic phenotypes of humans and mice with DNMT3A Overgrowth Syndrome.

Germline pathogenic variants in DNMT3A were recently described in patients with overgrowth, obesity, behavioral, and learning difficulties (DNMT3A Overgrowth Syndrome/DOS). Somatic mutations in the DNMT3A gene are also the most common cause of clonal hematopoiesis, and can initiate acute myeloid leukemia (AML). Using whole genome bisulfite sequencing, we studied DNA methylation in peripheral blood cells of 11 DOS patients and found a focal, canonical hypomethylation phenotype, which is most severe with the dominant negative DNMT3A mutation.

Mitochondrial genome copy number measured by DNA sequencing in human blood is strongly associated with metabolic traits via cell-type composition differences.

Background: Mitochondrial genome copy number (MT-CN) varies among humans and across tissues and is highly heritable, but its causes and consequences are not well understood. When measured by bulk DNA sequencing in blood, MT-CN may reflect a combination of the number of mitochondria per cell and cell-type composition. Here, we studied MT-CN variation in blood-derived DNA from 19184 Finnish individuals using a combination of genome (N = 4163) and exome sequencing (N = 19034) data as well as imputed genotypes (N = 17718).

Association of structural variation with cardiometabolic traits in Finns.

The contribution of genome structural variation (SV) to quantitative traits associated with cardiometabolic diseases remains largely unknown. Here, we present the results of a study examining genetic association between SVs and cardiometabolic traits in the Finnish population. We used sensitive methods to identify and genotype 129,166 high-confidence SVs from deep whole-genome sequencing (WGS) data of 4,848 individuals.

Haplotype-resolved diverse human genomes and integrated analysis of structural variation.

Long-read and strand-specific sequencing technologies together facilitate the de novo assembly of high-quality haplotype-resolved human genomes without parent-child trio data. We present 64 assembled haplotypes from 32 diverse human genomes. These highly contiguous haplotype assemblies (average minimum contig length needed to cover 50% of the genome: 26 million base pairs) integrate all forms of genetic variation, even across complex loci.

Teleconsultations at a Pediatrics Outpatient Service in COVID-19 Pandemic: First Results.

Describe our experiences using teleconsultation approach to care for pediatric subspecialty follow-up patients during pandemic period. Synchronous teleconsultation solution was developed and implemented as a multiplatform/multimodality service, capable or running on desktop browsers and smartphones, and capable to handle chat, audio, and video. Term of consent was applied.

Mapping and characterization of structural variation in 17,795 human genomes.

A key goal of whole-genome sequencing for studies of human genetics is to interrogate all forms of variation, including single-nucleotide variants, small insertion or deletion (indel) variants and structural variants. However, tools and resources for the study of structural variants have lagged behind those for smaller variants. Here we used a scalable pipeline to map and characterize structural variants in 17,795 deeply sequenced human genomes.

Author Correction: Exome sequencing of Finnish isolates enhances rare-variant association power.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Exome sequencing of Finnish isolates enhances rare-variant association power.

Exome-sequencing studies have generally been underpowered to identify deleterious alleles with a large effect on complex traits as such alleles are mostly rare. Because the population of northern and eastern Finland has expanded considerably and in isolation following a series of bottlenecks, individuals of these populations have numerous deleterious alleles at a relatively high frequency. Here, using exome sequencing of nearly 20,000 individuals from these regions, we investigate the role of rare coding variants in clinically relevant quantitative cardiometabolic traits.

svtools: population-scale analysis of structural variation.

Summary: Large-scale human genetics studies are now employing whole genome sequencing with the goal of conducting comprehensive trait mapping analyses of all forms of genome variation. However, methods for structural variation (SV) analysis have lagged far behind those for smaller scale variants, and there is an urgent need to develop more efficient tools that scale to the size of human populations. Here, we present a fast and highly scalable software toolkit (svtools) and cloud-based pipeline for assembling high quality SV maps-including deletions, duplications, mobile element insertions, inversions and other rearrangements-in many thousands of human genomes.

Effects of drought-stressed temperate forage legumes on the degradation and the rumen microbial community in vitro.

According to climate change scenarios, central Europe may expect extending drought periods during summer. Lower water availability may influence the ruminal digestion of individual forage legume species differently. To test this hypothesis, Lotus corniculatus L.

Electrocardiographic Safety of Repeated Monthly Dihydroartemisinin-Piperaquine as a Candidate for Mass Drug Administration.

Mass drug administration (MDA) of sequential rounds of antimalarial drugs is being considered for use as a tool for malaria elimination. As an effective and long-acting antimalarial, dihydroartemisinin-piperaquine (DHA-PQP) appears to be suitable as a candidate for MDA. However, the absence of cardiac safety data following repeated administration hinders its use in the extended schedules proposed for MDA.