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Stem Cell-Derived Human Striatal Progenitors Innervate Striatal Targets and Alleviate Sensorimotor Deficit in a Rat Model of Huntington Disease

Huntington disease (HD) is an inherited late-onset neurological disorder characterized by progressive neuronal loss and disruption of cortical and basal ganglia circuits. Cell replacement using human embryonic stem cells may offer the opportunity to repair the damaged circuits and significantly ameliorate disease conditions. Here, we showed that in-vitro-differentiated human striatal progenitors u

Mammographic density changes during neoadjuvant breast cancer treatment : NeoDense, a prospective study in Sweden

Objectives: To assess if mammographic density (MD) changes during neoadjuvant breast cancer treatment and is predictive of a pathological complete response (pCR). Methods: We prospectively included 200 breast cancer patients assigned to neoadjuvant chemotherapy (NACT) in the NeoDense study (2014–2019). Raw data mammograms were used to assess MD with a fully automated volumetric method and radiolog

From Skin to Brain : A Parkinson's Disease Patient Transplanted with His Own Cells

In a pioneering study in New England Journal of Medicine, Schweitzer et al. (2020) report on a patient with Parkinson's disease who received a graft of dopamine neurons obtained from in vitro differentiated induced pluripotent stem cells, derived from the patient's own skin fibroblasts, showing the feasibility of autologous transplantation for dopamine cell replacement.

Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood

Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG c

Longitudinal association between housing accessibility and activities of daily living : The role of self-efficacy and control in people ageing with Parkinson's disease

Background: External housing-related control beliefs (HCB) and general self-efficacy (GSE) influence different health outcomes in the general ageing population, but there is no information of their role in people ageing with Parkinson's disease (PD). This study aimed to longitudinally assess the role of external HCB and GSE on the association between housing accessibility and activities of daily l

Induction of blood-circulating bile acids supports recovery from myelosuppressive chemotherapy

Chemotherapeutic agents can reduce bone marrow (BM) activity, causing myelosuppression, a common life-threatening complication of cancer treatment. It is challenging to predict the patients in whom prolonged myelosuppression will occur, resulting in a delay or discontinuation of the treatment protocol. An early indicator of recovery from myelosuppression would thus be highly beneficial in clinical

Grafted human pluripotent stem cell-derived cortical neurons integrate into adult human cortical neural circuitry

Several neurodegenerative diseases cause loss of cortical neurons, leading to sensory, motor, and cognitive impairments. Studies in different animal models have raised the possibility that transplantation of human cortical neuronal progenitors, generated from pluripotent stem cells, might be developed into a novel therapeutic strategy for disorders affecting cerebral cortex. For example, we have s

Variations in the Referral Pattern for Genetic Counseling of Patients with Early-Onset Breast Cancer : A Population-Based Study in Southern Sweden

Swedish national breast cancer guidelines recommend that all women diagnosed with breast cancer (BC) at the age of 35 years or younger should be referred to their regional oncogenetic clinic for genetic counseling and testing, regardless of family history of cancer. The main objective of this study was to evaluate whether place of residence at BC diagnosis and treating hospital were associated wit

GDNF and Parkinson's Disease : Where Next? A Summary from a Recent Workshop

The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily Parkinson's disease (PD) using glial cell line-derived neurotrophic factor (GDNF). This neurotrophic factor was discovered in 1993 and shown to have selective effects on promoting survival and regeneration of certain populations of neurons including

Neuronal Replacement as a Tool for Basal Ganglia Circuitry Repair : 40 Years in Perspective

The ability of new neurons to promote repair of brain circuitry depends on their capacity to re-establish afferent and efferent connections with the host. In this review article, we give an overview of past and current efforts to restore damaged connectivity in the adult mammalian brain using implants of fetal neuroblasts or stem cell-derived neuronal precursors, with a focus on strategies aimed t

Mortality and the business cycle : Evidence from individual and aggregated data

There has been much interest recently in the relationship between economic conditions and mortality, with some studies showing that mortality is pro-cyclical, while others find the opposite. Some suggest that the aggregation level of analysis (e.g. individual vs. regional) matters. We use both individual and aggregated data on a sample of 20–64 year-old Swedish men from 1993 to 2007. Our results s

Erectile Function and Oncologic Outcomes Following Open Retropubic and Robot-assisted Radical Prostatectomy : Results from the LAParoscopic Prostatectomy Robot Open Trial

Background: Whether surgeons perform better utilising a robot-assisted laparoscopic technique compared with an open approach during prostate cancer surgery is debatable. Objective: To report erectile function and early oncologic outcomes for both surgical modalities, stratified by prostate cancer risk grouping. Design, setting, and participants: In a prospective nonrandomised trial, we recruited 2

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