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Direct neuronal reprogramming for disease modeling studies using patient-derived neurons : What have we learned?

Direct neuronal reprogramming, by which a neuron is formed via direct conversion from a somatic cell without going through a pluripotent intermediate stage, allows for the possibility of generating patient-derived neurons. A unique feature of these so-called induced neurons (iNs) is the potential to maintain aging and epigenetic signatures of the donor, which is critical given that many diseases o

Stellate cells and mesenchymal stem cells in benign mammary stroma are associated with risk factors for breast cancer - an observational study

Background: It is not known whether stromal cells in benign breast tissue can mediate risk of breast cancer. We recently described aldehyde dehydrogenase 1 A1 (ALDH1) positive (+) cells in morphologically normal breast stroma of premenopausal women, and the data indicated that their distribution is associated with clinical risk factors for breast cancer. The aim of the present study was to define

Endoplasmic reticulum, Golgi, and lysosomes are disorganized in lung fibroblasts from chronic obstructive pulmonary disease patients

Chronic Obstructive Pulmonary Disease (COPD) is often caused by smoking and other stressors. This causes oxidative stress, which induces numerous changes on both the transcriptome and proteome of the cell. We aimed to examine if the endomembrane pathway, including the endoplasmic reticulum (ER), Golgi, and lysosomes, was disrupted in fibroblasts from COPD patients as opposed to healthy ever-smoker

Elevated IL-27 in patients with acute coronary syndrome is associated with adverse ventricular remodeling and increased risk of recurrent myocardial infarction and cardiovascular death

Background and aims: IL-27 is an immunoregulatory cytokine belonging to the IL-6/IL-12 family that was found to be elevated in acute coronary syndrome (ACS) patients. We investigated whether IL-27 is related to post-ischemic cardiac remodeling and long-term prognosis in this patient group. Methods: We included 524 ACS patients, defined as acute myocardial infarction (AMI) or unstable angina (UA).

Evaluating Nutrient Reduction, Grazing and Barley Straw as Measures Against Algal Growth

The aim of our study was to experimentally investigate whether it is possible to reduce nuisance growth of filamentous algae in freshwater ecosystems. We used an experimental set-up mimicking a shallow pond system and performed a field investigation in the eutrophic moat of Krapperup castle (Southern Sweden), which exemplifies an extremely impaired ecosystem with ample growth of filamentous green

Prevalence and incidence of non-gout crystal arthropathy in southern Sweden

Objective: To estimate the prevalence and incidence of non-gout crystal arthropathy in relation to socioeconomic factors in southern Sweden. Methods: All patients (age ≥ 18 years) with at least one visit to a physician with the diagnosis of interest in the Skåne region (population of 1.3 million) in 1998-2014 were identified. Non-gout crystal arthropathy (ICD-10 codes M11.0-M11.9) was subclassifie

A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism

Adeno-associated virus (AAV) capsid modification enables the generation of recombinant vectors with tailored properties and tropism. Most approaches to date depend on random screening, enrichment, and serendipity. The approach explored here, called BRAVE (barcoded rational AAV vector evolution), enables efficient selection of engineered capsid structures on a large scale using only a single screen

Profiling of lincRNAs in human pluripotent stem cell derived forebrain neural progenitor cells

Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) can be differentiated into many different cell types of the central nervous system. One challenge when using pluripotent stem cells is to develop robust and efficient differentiation protocols that result in homogenous cultures of the desired cell type. Here, we have utilized the SMAD-inhibitors SB431542 and Noggin in a

Patients' and physicians' disagreement on patients' understanding of clinical cancer trial information : A pairwise pilot study of mirroring subjective assessments compared with objective measurements

Background: Informed consent is a prerequisite for patients included in clinical trials. Trial design, inclusion criteria and legal requirements are increasingly complex. This complexity challenges design and delivery of written and oral trial information to ensure understandable information. To evaluate the level of concordance between patients' and informing physicians' assessments regarding pat

The Aurora kinase/β-catenin axis contributes to dexamethasone resistance in leukemia

Glucocorticoids, such as dexamethasone and prednisolone, are widely used in cancer treatment. Different hematological malignancies respond differently to this treatment which, as could be expected, correlates with treatment outcome. In this study, we have used a glucocorticoid-induced gene signature to develop a deep learning model that can predict dexamethasone sensitivity. By combining gene expr

Type 1 diabetes, cognitive ability and incidence of cardiovascular disease and death over 60 years of follow-up time in men

AIMS: There are few cohorts of type 1 diabetes that follow individuals over more than half a century in terms of health outcomes. The aim of this study was to examine associations between type 1 diabetes, diagnosed before age 18, and long-term morbidity and mortality, and to investigate whether cognitive ability plays a role in long-term morbidity and mortality risk.METHODS: In a Swedish cohort, 1

Quantitative trait loci, G×E and G×G for glycemic traits : response to metformin and placebo in the Diabetes Prevention Program (DPP)

The complex genetic architecture of type-2-diabetes (T2D) includes gene-by-environment (G×E) and gene-by-gene (G×G) interactions. To identify G×E and G×G, we screened markers for patterns indicative of interactions (relationship loci [rQTL] and variance heterogeneity loci [vQTL]). rQTL exist when the correlation between multiple traits varies by genotype and vQTL occur when the variance of a trait

Surveillance of COVID-19 vaccine effectiveness : A real-time case-control study in southern Sweden

The extensive register infrastructure available for coronavirus disease 2019 surveillance in Scania county, Sweden, makes it possible to classify individual cases with respect to hospitalisation and disease severity, stratify on time since last dose and demographic factors, account for prior infection and extract data for population controls automatically. In the present study, we developed a case

Self-reported COVID-19 vaccine hesitancy and uptake among participants from different racial and ethnic groups in the United States and United Kingdom

Worldwide, racial and ethnic minorities have been disproportionately impacted by COVID-19 with increased risk of infection, its related complications, and death. In the initial phase of population-based vaccination in the United States (U.S.) and United Kingdom (U.K.), vaccine hesitancy may result in differences in uptake. We performed a cohort study among U.S. and U.K. participants who volunteere

Hemodynamic force analysis is not ready for clinical trials on HFpEF

Hemodynamic force analysis has been proposed as a novel tool for early detection of subclinical systolic dysfunction in heart failure with preserved ejection fraction (HFpEF). Here we investigated the ability of hemodynamic forces to discriminate between healthy subjects and heart failure patients with varying degrees of systolic dysfunction. We studied 34 controls, 16 HFpEF patients, and 25 heart

Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia

Dolutegravir-based antiretroviral therapy (ART) has been scaled up in many developing countries, including Ethiopia. However, subtype-dependent polymorphic differences might influence the occurrence of HIV-drug-resistance mutations (HIVDRMs). We analyzed the prevalence of pre-treatment integrase strand transfer inhibitor (INSTI) HIVDRMs and naturally occurring polymorphisms (NOPs) of the integrase

Antigen-Presenting B Cells Program the Efferent Lymph T Helper Cell Response

B cells interact with T follicular helper (Tfh) cells in germinal centers (GCs) to generate high-affinity antibodies. Much less is known about how cognate T–B-cell interactions influence Th cells that enter circulation and peripheral tissues. Therefore, we generated mice lacking MHC-II expressing B cells and, by thoracic duct cannulation, analyzed Th cells in the efferent lymph at defined interval

Human Embryonic Stem Cell-Derived Dopaminergic Grafts Alleviate L-DOPA Induced Dyskinesia

BACKGROUND: First-in-human studies to test the efficacy and safety of human embryonic stem cells (hESC)-derived dopaminergic cells in the treatment of Parkinson's disease (PD) are imminent. Pre-clinical studies using hESC-derived dopamine neuron transplants in rat models have indicated that the benefits parallel those shown with fetal tissue but have thus far failed to consider how ongoing L-DOPA