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Technical considerations for the use of CRISPR/Cas9 in hematology research

The hematopoietic system is responsible for transporting oxygen and nutrients, fighting infections, and repairing tissue damage. Hematopoietic system dysfunction therefore causes a range of serious health consequences. Lifelong hematopoiesis is maintained by repopulating multipotent hematopoietic stem cells (HSCs) that replenish shorter-lived, mature blood cell types. A prokaryotic mechanism of im

A Multi-Biomarker Disease Activity Score and the Choice of Second-Line Therapy in Early Rheumatoid Arthritis After Methotrexate Failure

Objective: To investigate whether the Multi-Biomarker Disease Activity (MBDA) score predicts optimal add-on treatment in patients with early rheumatoid arthritis (RA) who were inadequate responders to MTX (MTX-IRs). Methods: We analyzed data from 157 MTX-IRs (with a Disease Activity Score using the erythrocyte sedimentation rate [DAS28-ESR] >3.2) from the Swedish Pharmacotherapy (SWEFOT) trial who

Human Trials of Stem Cell-Derived Dopamine Neurons for Parkinson's Disease : Dawn of a New Era

Stem cell-based therapies for Parkinson's disease are moving into a new and exciting era, with several groups pursuing clinical trials with pluripotent stem cell (PSC)-derived dopamine neurons. As many groups have ongoing or completed GMP-level cell manufacturing, we highlight key clinical translation considerations from our recent fourth GForce-PD meeting. Stem cell-based therapies for Parkinson'

Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease

To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLADRB5 (odds ratio (

Inflammation and chronic colonization of Haemophilus influenzae in sputum in COPD patients related to the degree of emphysema and bronchiectasis in high-resolution computed tomography

The presence of bacteria in the lower airways in COPD results in inflammation, further airway structural damage, and might lead to repeated exacerbations. We have previously shown that chronic colonization of Haemophilus influenzae during stable disease is related to increased inflammation, and we now aimed to relate previous findings of bacterial colonization and inflammation to the degree of rad

Cancer risks and survival in patients with multiple primary melanomas : Association with family history of melanoma and germline CDKN2A mutation status

Background Worse outcomes have been noted in patients with multiple primary melanomas (MPMs) than in patients with single primary melanomas. Objective We investigated how family history of melanoma and germline CDKN2A mutation status of MPM patients affects risks of developing subsequent melanomas and other cancers and survival outcomes. Methods Comprehensive data on cancer diagnoses and deaths of

Simultaneous Control of Soot Emissions and Pressure Rise Rate in Gasoline PPC Engine

Partially Premixed Combustion (PPC) is an advanced combustion concept resulting in high efficiencies and low emission levels by the use of high levels of EGR and pilot injections. The main limitation of PPC to use in practice lies in the high pressure rise rate, which causes issues on engine noise and durability. In addition, soot emissions face with the overshoot problem during the transient oper

Constitutively Active SMAD2/3 Are Broad-Scope Potentiators of Transcription-Factor-Mediated Cellular Reprogramming

Reprogramming of cellular identity using exogenous expression of transcription factors (TFs) is a powerful and exciting tool for tissue engineering, disease modeling, and regenerative medicine. However, generation of desired cell types using this approach is often plagued by inefficiency, slow conversion, and an inability to produce mature functional cells. Here, we show that expression of constit

Identification of a Novel Autoimmune Peptide Epitope of Prostein in Prostate Cancer

There is a demand for novel targets and approaches to diagnose and treat prostate cancer (PCA). In this context, serum and plasma samples from a total of 609 individuals from two independent patient cohorts were screened for IgG reactivity against a sum of 3833 human protein fragments. Starting from planar protein arrays with 3786 protein fragments to screen 80 patients with and without PCA diagno

Legal Power: The Basic Definition

The concept of legal power (often called legal competence) is important in the law since, with regard to actions having legal effect, the “exercise of legal power” delimits those actions for which manifestation of intention to achieve a legal effect is essential for the effect to ensue. The paper proposes a definition that captures this feature of legal power and marks it off rom “direct effect,”

Effect of increased water intake on plasma copeptin in healthy adults

Purpose: Inter-individual variation in median plasma copeptin is associated with incident type 2 diabetes mellitus, progression of chronic kidney disease, and cardiovascular events. In this study, we examined whether 24-h urine osmolality was associated with plasma copeptin and whether increasing daily water intake could impact circulating plasma copeptin. Methods: This trial was a prospective stu

Direct Reprogramming of Resident NG2 Glia into Neurons with Properties of Fast-Spiking Parvalbumin-Containing Interneurons

Converting resident glia into functional and subtype-specific neurons in vivo by delivering reprogramming genes directly to the brain provides a step forward toward the possibility of treating brain injuries or diseases. To date, it has been possible to obtain GABAergic and glutamatergic neurons via in vivo conversion, but the precise phenotype of these cells has not yet been analyzed in detail. H

Inflammation and Stem Cell Therapy for Stroke

Ischemic stroke is a leading cause of death and disability worldwide. Currently, there is no treatment that can promote recovery in the chronic phase. It has been shown that neurogenesis occurs in ischemic striatum in rodents and probably also in humans. Moreover, blood-borne macrophages have been found to enhance spontaneous post- stroke recovery in mice. These findings have suggested potential n

Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia? : Findings From the GLACIER and the MDC Studies

BACKGROUND: Obesity is a major risk factor for dyslipidemia, but this relationship is highly variable. Recently published data from 2 Danish cohorts suggest that genetic factors may underlie some of this variability.METHODS AND RESULTS: We tested whether established triglyceride-associated loci modify the relationship of body mass index (BMI) and triglyceride concentrations in 2 Swedish cohorts (t

No evidence of increased breast cancer risk for proven noncarriers from BRCA1 and BRCA2 families.

In families screened for mutations in the BRCA1 or BRCA2 genes and found to have a segregating mutation the breast cancer risk for women shown not to carry the family-specific mutation might be at above "average" risk. We assessed the risk of breast cancer in a clinic based cohort of 725 female proven noncarriers in 239 BRCA1 and BRCA2 families compared with birth-matched controls from the Danish