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Predicting and elucidating the etiology of fatty liver disease: A machine learning modeling and validation study in the IMI DIRECT cohorts

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD usin

An Artificial Intelligence-based Support Tool for Automation and Standardisation of Gleason Grading in Prostate Biopsies

BACKGROUND: Gleason grading is the standard diagnostic method for prostate cancer and is essential for determining prognosis and treatment. The dearth of expert pathologists, the inter- and intraobserver variability, as well as the labour intensity of Gleason grading all necessitate the development of a user-friendly tool for robust standardisation.OBJECTIVE: To develop an artificial intelligence

Agonistic targeting of TLR1/TLR2 induces p38 MAPK-dependent apoptosis and NFκB-dependent differentiation of AML cells

Acute myeloid leukemia (AML) is associated with poor survival, and there is a strong need to identify disease vulnerabilities that might reveal new treatment opportunities. Here, we found that Toll-like receptor 1 (TLR1) and TLR2 are upregulated on primary AML CD34+CD38-cells relative to corresponding normal bone marrow cells. Activating the TLR1/TLR2 complex by the agonist Pam3CSK4 inMLL-AF9-driv

Patient choice, entry, and the quality of primary care : Evidence from Swedish reforms

Policies aiming to spur quality competition among health care providers are ubiquitous, but their impact on quality is ex ante ambiguous, and credible empirical evidence is lacking in many contexts. This study contributes to the sparse literature on competition and primary care quality by examining recent competition enhancing reforms in Sweden. The reforms aimed to stimulate patient choice and en

X-Ray Dark-Field Imaging of Lung Cancer in Mice

Lung cancer accounts for 1.6 million deaths per year worldwide. The majority of patients are diagnosed at advanced stages of the disease and often present with metastasis. Thus, the 5-year survival rate of lung cancer remains around 15%. Early diagnosis of lung cancer allows for better control of the disease with 5-year survival rates up to around 70%. Chest radiography is the most common techniqu

Differential impedance spectra analysis reveals optimal actuation frequency in bulk mode acoustophoresis

This work reports a method to select the optimal working frequency in transversal bulk resonator acoustophoretic devices by electrical impedance measurements. The impedance spectra of acoustophoretic devices are rich in spurious resonance peaks originating from different resonance modes in the system not directly related to the channel resonance, why direct measurement of the piezoelectric transdu

Automated Bone Scan Index as an Imaging Biomarker to Predict Overall Survival in the Zometa European Study/SPCG11

BACKGROUND: Owing to the large variation in treatment response among patients with high-risk prostate cancer, it would be of value to use objective tools to monitor the status of bone metastases during clinical trials. Automated Bone Scan Index (aBSI) based on artificial intelligence has been proposed as an imaging biomarker for the quantification of skeletal metastases from bone scintigraphy.OBJE

A new genetic tool to improve immune-compromised mouse models : Derivation and CRISPR/Cas9-mediated targeting of NRG embryonic stem cell lines

Development of human hematopoietic stem cells and differentiation of embryonic stem (ES) cells/induced pluripotent stem (iPS) cells to hematopoietic stem cells are poorly understood. NOD (Non-obese diabetic)-derived mouse strains, such as NSG (NOD-Scid-il2Rg) or NRG (NOD-Rag1-il2Rg), are the best available models for studying the function of fetal and adult human hematopoietic cells as well as ES/

Improved acoustophoretic circulating tumor cell (CTC) separation for low target cell numbers in clinical volumes

We present an improved acoustophoretic system for circulating tumor cell separation from blood. The system is operated by pressure driven flow, including flow sensors and a feed-back loop for precise flow control. The pressure driven system provides a user interface that can be handled by a non-skilled operator, and most importantly full clinical samples of 7 mL can be processed in 70 minutes. The

Transcription Factor-Forced Astrocytic Differentiation Impairs Human Glioblastoma Growth In Vitro and In Vivo

Direct cellular reprogramming has recently gained attention of cancer researchers for the possibility to convert undifferentiated cancer cells into more differentiated, postmitotic cell types. While a few studies have attempted reprogramming of glioblastoma (GBM) cells toward a neuronal fate, this approach has not yet been used to induce differentiation into other lineages and in vivo data on redu

Charge Regulation during Amyloid Formation of α-Synuclein

Electrostatic interactions play crucial roles in protein function. Measuring pKa value perturbations upon complex formation or self-assembly of e.g. amyloid fibrils gives valuable information about the effect of electrostatic interactions in those processes. Site-specific pKa value determination by solution NMR spectroscopy is challenged by the high molecular weight of amyloid fibrils. Here we rep

Resonant X-ray photo-oxidation of light-harvesting iron (II/III) N-heterocyclic carbene complexes

Two photoactive iron N-heterocyclic carbene complexes [FeII(btz)2(bpy)]2+ and [FeIII(btz)3]3+, where btz is 3,3’-dimethyl-1,1’-bis(p-tolyl)-4,4’-bis(1,2,3-triazol-5-ylidene) and bpy is 2,2’-bipyridine, have been investigated by Resonant Photoelectron Spectroscopy (RPES). Tuning the incident X-ray photon energy to match core-valence excitations provides a site specific probe of the electronic struc