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Κυριακή 29 Μαρτίου 2020


Characterization of risk factors and efficacy of medical management of immune-related hepatotoxicity in real-world patients with metastatic melanoma treated with immune checkpoint inhibitors
Publication date: May 2020Source: European Journal of Cancer, Volume 130Author(s): Nicole A. Romanski, Rikke B. Holmstroem, Eva Ellebaek, Inge Marie Svane
European Journal of Cancer
1d
Safety and clinical efficacy of toripalimab, a PD-1 mAb, in patients with advanced or recurrent malignancies in a phase I study
Publication date: May 2020Source: European Journal of Cancer, Volume 130Author(s): Jianliang Yang, Lihou Dong, Sheng Yang, Xiaohong Han, Ying Han, Shiyu Jiang, Jiarui Yao, Zhishang Zhang, Shuxiang Zhang, Peng Liu, Yan Qin, Hai Wu, Hui Feng, Sheng Yao, Yan Sun, Haifeng Song, Yuankai Shi
European Journal of Cancer
1d
Emergency presentations in patients treated with immune checkpoint inhibitors
Publication date: May 2020Source: European Journal of Cancer, Volume 130Author(s): Tim Cooksley, Avinash Gupta, Tamer Al-Sayed, Paul Lorigan
European Journal of Cancer
1d
RON receptor tyrosine kinase in pancreatic ductal adenocarcinoma: Pathogenic mechanism in malignancy and pharmaceutical target for therapy
Publication date: Available online 29 March 2020Source: Biochimica et Biophysica Acta (BBA) - Reviews on CancerAuthor(s): Hang-Ping Yao, Rachel Hudson, Ming-Hai Wang
ScienceDirect Publication: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
10h
Stellate cells drive maturation of the entorhinal-hippocampal circuit
The neural representation of space relies on a network of entorhinal-hippocampal cell types with firing patterns tuned to different abstract features of the environment. To determine how this network is set up during early postnatal development, we monitored markers of structural maturation in developing mice, both in naïve animals and after temporally restricted pharmacogenetic silencing of specific cell populations. We found that entorhinal stellate cells provide an activity-dependent instructive...
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10h
Inter-rater agreement in evaluation of disability: systematic review of reproducibility studies
OBJECTIVES: To explore agreement among healthcare professionals assessing eligibility for work disability benefits. DESIGN: Systematic review and narrative synthesis of reproducibility studies. DATA SOURCES: Medline, Embase, and PsycINFO searched up to 16 March 2016, without language restrictions, and review of bibliographies of included studies. ELIGIBILITY CRITERIA: Observational studies investigating reproducibility among healthcare professionals performing disability evaluations using a global...
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10h
Return-to-work coordination programmes for improving return to work in workers on sick leave
BACKGROUND: To limit long-term sick leave and associated consequences, insurers, healthcare providers and employers provide programmes to facilitate disabled people's return to work. These programmes include a variety of coordinated and individualised interventions. Despite the increasing popularity of such programmes, their benefits remain uncertain. We conducted a systematic review to determine the long-term effectiveness of return-to-work coordination programmes compared to usual practice in workers...
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10h
Robust Single-Shot Spin Measurement with 99.5% Fidelity in a Quantum Dot Array
We demonstrate a new method for projective single-shot measurement of two electron spin states (singlet versus triplet) in an array of gate-defined lateral quantum dots in GaAs. The measurement has very high fidelity and is robust with respect to electric and magnetic fluctuations in the environment. It exploits a long-lived metastable charge state, which increases both the contrast and the duration of the charge signal distinguishing the two measurement outcomes. This method allows us to evaluate...
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10h
A systematic genomic screen implicates nucleocytoplasmic transport and membrane growth in nuclear size control
How cells control the overall size and growth of membrane-bound organelles is an important unanswered question of cell biology. Fission yeast cells maintain a nuclear size proportional to cellular size, resulting in a constant ratio between nuclear and cellular volumes (N/C ratio). We have conducted a genome-wide visual screen of a fission yeast gene deletion collection for viable mutants altered in their N/C ratio, and have found that defects in both nucleocytoplasmic mRNA transport and lipid synthesis...
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10h
Comprehensive Real-Time Analysis of the Yeast Volatilome
While yeast is one of the most studied organisms, its intricate biology remains to be fully mapped and understood. This is especially the case when it comes to capture rapid, in vivo fluctuations of metabolite levels. Secondary electrospray ionization-high resolution mass spectrometry SESI-HRMS is introduced here as a sensitive and noninvasive analytical technique for online monitoring of microbial metabolic activity. The power of this technique is exemplarily shown for baker's yeast fermentation,...
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11h
Protein structure determination by electron diffraction using a single three-dimensional nanocrystal
Three-dimensional nanometre-sized crystals of macromolecules currently resist structure elucidation by single-crystal X-ray crystallography. Here, a single nanocrystal with a diffracting volume of only 0.14 µm; 3; , i.e. no more than 6 × 10; 5; unit cells, provided sufficient information to determine the structure of a rare dimeric polymorph of hen egg-white lysozyme by electron crystallography. This is at least an order of magnitude smaller than was previously possible. The molecular-replacement...
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1d
Neutravidin-Mediated Extraction of Isolated Small Diameter Single Walled Carbon Nanotubes for Bio-Recognition
Electron-transparent substrate that can specifically capture tagged protein complexes prompted us to fabricate a template that allow capture and structural studies of biotinylated protein complexes by transmission electron microscopy (TEM) to understand protein-protein interactions. Here we present a novel method that allows the scalable extraction and individualization of the tiny fraction of small diameter SWNTs that is functionalized with neutravidin, which can be used to bind biotinylated species....
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1d
Purification of Biotinylated Proteins Using Single Walled Carbon Nanotube-Streptavidin Complexes
In this study, Single walled carbon nanotube (SWNT)-streptavidin complexes were used to capture and purify biotinylated proteins, including bio-GFP and bio-DBS using a pull-down method. The purification conditions were systematically studied, including surface blocking of SWNT using chicken egg albumin (CEA), the ratio of SWNT-streptavidin complexes to the cell lysate, as well as the centrifugation speed. Optimization of the protein purification using SWNT-streptavidin complexes shows the possibility...
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1d
Real-Time Monitoring of Tricarboxylic Acid Metabolites in Exhaled Breath
The tricarboxylic acid (TCA) cycle is one of the most important metabolic pathway for cellular respiration in aerobic organisms. It provides and collects intermediates for many other interconnecting pathways and acts as a hub connecting metabolism of carbohydrates, fatty acids, and amino acids. Alteration in intracellular levels of its intermediates has been linked with a wide range of illnesses ranging from cancer to cellular necrosis or liver cirrhosis. Therefore, there exists an intrinsic interest...
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1d
Effects of Birch Polypore Mushroom, Piptoporus betulinus (Agaricomycetes), the "Iceman's Fungus", on Human Immune Cells
Piptoporus betulinus, the mushroom that has been carried by Ötzi the "Iceman", has a long tradition of use in medicinal practice for its antiseptic, anticancer, and immune-enhancing properties. With this study, we aimed to investigate the immunomodulatory effects of P. betulinus on primary human immunocompetent cells. The influence of P. betulinus water and methanol extract on apoptosis and necrosis induction of T cells and monocytes was analyzed using annexin V/propidium iodide staining and proliferation...
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1d
Rosemary has immunosuppressant activity mediated through the STAT3 pathway
In Europe extracts of Rosmarinus officinalis were traditionally used for the treatment of rheumatic diseases. We investigated the capacity of standardized aqueous extracts of Rosmarinus officinalis on human primary lymphocyte function in vitro, as activated lymphocytes are an important mediator of rheumatic diseases.; Lymphocyte proliferation was measured using membrane-permeable dye carboxyfluorescein diacetate succinimidyl ester (CFSE). Apoptosis was analysed by surface staining of phosphatidylserine...
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1d
Impact of Green Tea Catechin ECG and Its Synthesized Fluorinated Analogue on Prostate Cancer Cells and Stimulated Immunocompetent Cells
Among the known or suspected risk factors, inflammation plays an important role in infectious and non-infectious pathways leading to cancer. Green tea polyphenols have been associated with reducing inflammation and protection against carcinogenesis, especially in prostate cancer. While most of the research in this field, so far, has focussed on epigallocatechin-3-; O; -gallate only, we studied epicatechin-3-; O; -gallate, the second most abundant green tea polyphenol with essential therapeutic potential,...
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1d
Investigations on the constitutional types under consideration of anthropometric data, autonomic regulation and immunological parameters
Over time different systems were developed for the characterization of individuals according to their physical and psycho-vegetative traits which until today play a role in complementary medicine. This pilot study aimed at investigating if the concepts of polar constitutional types of anthroposophic medicine and according to Kretschmer can be further clarified using empirical method.; 96 participants, preselected by two polar body mass index (BMI) ranges (17-19.5 kg/m; 2; and 27-31 kg/m; 2; ), were...
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1d
Chemoprevention with isothiocyanates - From bench to bedside
Isothiocyanates (ITCs) are naturally occurring hydrolization products from glucosinolates (GLSs) in brassicaceae and in epidemiological studies their intake has been weakly to moderately inversely correlated with the risk of colorectal cancer, prostate cancer and lung cancer. Numerous preclinical studies demonstrate chemopreventive mode of actions of ITCs, mainly related to a.) detoxification (induction of phase II enzymes), b.) anti-inflammatory properties by down-regulation of NFkappaB activity,...
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1d
In Vitro Anti-inflammatory Effects of Equisetum Arvense Are Not Solely Mediated by Silica
Equisetum arvense; , known as common horsetail, is used for the treatment of inflammatory diseases and is the plant with the highest concentration of silica. Yet it is unknown if the medicinal properties are mediated by its silica content. In the current study, optimal conditions for silica-rich horsetail preparations were identified. Bioactivity of the preparations was analyzed; in vitro; using flow cytometry-based activity and functionality profiling of primary human lymphocytes as well as cytokine...
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1d
Supercooling preservation technology in food and biological samples: a review focused on electric and magnetic field applications
Abstract Freezing has been widely recognized as the most common process for long-term preservation of perishable foods; however, unavoidable damages associated with ice crystal formation lead to unacceptable quality losses during storage. As an alternative, supercooling preservation has a great potential to extend the shelf-life and maintain quality attributes of fresh foods without freezing damage. Investigations for the application of external electric field (EF) and magnetic...
Latest Results for Food Science and Biotechnology
2d
Electron crystallography with the EIGER detector
Electron crystallography is a discipline that currently attracts much attention as method for inorganic, organic and macromolecular structure solution. EIGER, a direct-detection hybrid pixel detector developed at the Paul Scherrer Institut, Switzerland, has been tested for electron diffraction in a transmission electron microscope. EIGER features a pixel pitch of 75 × 75 µm; 2; , frame rates up to 23 kHz and a dead time between frames as low as 3 µs. Cluster size and modulation transfer functions...
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1d
The Neuronal Tau Protein Blocks in Vitro Fibrillation of the Amyloid-β (Aβ) Peptide at the Oligomeric Stage
In Alzheimer's disease, amyloid-β (Aβ) plaques and tau neurofibrillary tangles are the two pathological hallmarks. The co-occurrence and combined reciprocal pathological effects of Aβ and tau protein aggregation have been observed in animal models of the disease. However, the molecular mechanism of their interaction remain unknown. Using a variety of biophysical measurements, we here show that the native full-length tau protein solubilizes the Aβ; 40; peptide and prevents its fibrillation. The tau...
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1d
A Molecular Level Approach To Elucidate the Supramolecular Packing of Light-Harvesting Antenna Systems
The molecular geometry and supramolecular packing of two bichromophoric prototypic light harvesting compounds D1A2 and D2A2, consisting of two naphthylimide energy donors that were attached to the 1,7 bay positions of a perylene monoimide diester energy acceptor, have been determined by a hybrid approach using magic angle spinning NMR spectroscopy and electron nano-crystallography (ENC), followed by modelling. NMR shift constraints, combined with the P; 1; ‾; space group obtained from ENC, were used...
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1d
Electron diffraction data processing with DIALS
Electron diffraction is a relatively novel alternative to X-ray crystallography for the structure determination of macromolecules from three-dimensional nanometre-sized crystals. The continuous-rotation method of data collection has been adapted for the electron microscope. However, there are important differences in geometry that must be considered for successful data integration. The wavelength of electrons in a TEM is typically around 40 times shorter than that of X-rays, implying a nearly flat...
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1d
Electron diffraction and three-dimensional crystallography for structural biology
Electron crystallography is increasingly becoming a viable alternative for structure elucidation of three-dimensional, multi-nanometre sized crystals of beam-sensitive organics and macromolecules. Because electrons interact with matter strongly, crystals cannot be much more than 200nm thick. Diffracted volumes are therefore small, leading to a poor signal-to-noise ratio (SNR) as beam damage limits the total electron dose. Data can be collected in diffraction - and imaging mode. Imaging has the advantage...
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1d
CCDC 1817054: Experimental Crystal Structure Determination
An entry from the Cambridge Structural Database, the worlds repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
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1d
Mortariastempel von Vindonissa. Signierte Reibschüsseln aus dem römischen Windisch
Die vorliegende Arbeit verzeichnet die gestempelten mortaria aus Vindonissa und untersucht, aus welchen Töpfereien Legionäre wie Zivilisten ihre Reibschüsseln bezogen. Gegenwärtig liegen 121 beschriftete mortaria vor. Mehrheitlich wurden sie im Schutthügel und innerhalb des Legionslagers gefunden; aus den canabae legionis und aus Gräbern liegen nur wenige vor. Diese Unterschiede in der Fundmenge sprechen entweder für unterschiedliche Essgewohnheiten oder verweisen auf abweichende Vorlieben beim Erwerb...
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2d
Discovery of 4-((1-(1H-imidazol-2-yl)alkoxy)methyl)pyridines as a new class of Trypanosoma cruzi growth inhibitors
The identification of a new series of growth inhibitors of Trypanosoma cruzi, the causative agent of Chagas' disease, is described. In vitro screening of a subset of compounds from our in-house compound collection against the parasite led to the identification of hit compound 1 with low micromolar inhibition of T. cruzi growth. SAR exploration on the hit compound led to the identification of compounds that show nanomolar parasite growth inhibition (T. cruzi EC; 50; ≤ 100 nM) and no cytotoxicity in...
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2d
Preclinical antimalarial combination studies: the case of M5717, a P. falciparum elongation factor 2 inhibitor and pyronaridine, a hemozoin formation inhibitor
Antimalarial drug resistance in the; Plasmodium falciparum; parasite poses a constant challenge for drug development. To mitigate this risk, new antimalarial medicines should be developed as fixed-dose combinations. Assessing the pharmacodynamic interactions of potential antimalarial drug combination partners during early phases of development is essential in developing the targeted parasitological and clinical profile of the final drug product. Here, we have studied the combination of M5717, a;...
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2d
Long-term air pollution exposure is associated with increased severity of rhinitis in 2 European cohorts
Very few studies have examined the association between long-term outdoor air pollution and rhinitis severity in adults.; We sought to assess the cross-sectional association between individual long-term exposure to air pollution and severity of rhinitis.; Participants with rhinitis from 2 multicenter European cohorts (Epidemiological Study on the Genetics and Environment on Asthma and the European Community Respiratory Health Survey) were included. Annual exposure to NO; 2; , PM; 10; , PM; 2.5; ,...
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2d
Comparing the lung cancer burden of ambient particulate matter using scenarios of air quality standards versus acceptable risk levels
Ambient particulate matter (PM) is regulated with science-based air quality standards, whereas carcinogens are regulated with a number of "acceptable" cases. Given that PM is also carcinogenic, we identify differences between approaches.; We assessed the lung cancer deaths for Switzerland attributable to exposure to PM up to 10 µm (PM; 10; ) and to five particle-bound carcinogens. For PM; 10; , we used an epidemiological approach based on relative risks with four exposure scenarios compared to two...
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2d
Patients with severe schistosomiasis mekongi morbidity demonstrating ongoing transmission in Southern Lao People's Democratic Republic
Chronic infection with Schistosoma mekongi may result in severe hepatosplenic morbidity. We report on eight patients with severe morbidity due to S. mekongi infection. The patients were diagnosed, treated and followed-up between 2007 and 2010 in Khong district, Southern Lao People's Democratic Republic (Lao PDR), eight years after the end of a control intervention. S. mekongi control programmes aimed to prevent morbidity and mortality associated with infection. The patients were visited and interviewed...
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2d
High prevalence of Schistosoma haematobium × Schistosoma bovis hybrids in schoolchildren in Côte d'Ivoire
Schistosomiasis is a neglected tropical disease, though it is highly prevalent in many parts of sub-Saharan Africa. While Schistosoma haematobium-bovis hybrids have been reported in West Africa, no data about Schistosoma hybrids in humans are available from Côte d'Ivoire. This study aimed to identify and quantify S. haematobium-bovis hybrids among schoolchildren in four localities of Côte d'Ivoire. Urine samples were collected and examined by filtration to detect Schistosoma eggs. Eggs were hatched...
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2d
Atopy modifies the association between inhaled corticosteroid use and lung function decline in patients with asthma
Inhaled corticosteroids (ICSs) are the mainstay of asthma treatment, but response to medication is variable. Patients with allergic inflammation generally show a better short-term response to ICSs; however, studies on predictors of long-term response are few.; To assess whether allergic sensitization can modify the association between ICS use and lung function decline over 20 years in adult asthma.; We used data from the 3 clinical examinations of the European Community Respiratory Health Survey....
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2d
Multiplicity of asymptomatic Plasmodium falciparum infections and risk of clinical malaria: a systematic review and pooled analysis of individual participant data
The malaria parasite Plasmodium falciparum holds an extensive genetic polymorphism. In this pooled analysis, we investigate how the multiplicity in asymptomatic P. falciparum infections-that is, the number of coinfecting clones-affects the subsequent risk of clinical malaria in populations living under different levels of transmission.; A systematic search of the literature was performed to identify studies in which P. falciparum infections were genotyped in asymptomatic individuals who were followed...
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2d
Glycaemic control among patients with type 2 diabetes followed in a rural African primary care setting - a reality check in the Democratic Republic of Congo
The aim of this study was to assess diabetes control in adult patients with type II diabetes and to evaluate its association with socio-economic characteristics in rural the Democratic Republic Congo (DRC).; We recruited patients ≥18 years in care for type II diabetes in a hospital in rural DRC. Socio-economic status, medical history and diabetes control were assessed through a structured questionnaire, a physical examination and laboratory tests, such as fasting glucose, HbA1c, serum creatinine...
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2d
Prognostic accuracy of (sTREM-1)-based algorithms in febrile adults presenting to Tanzanian outpatient clinics
The inability to identify individuals with acute fever at risk of death is a barrier to effective triage and management of severe infections, especially in low-resource settings. Since endothelial and immune activation contribute to the pathogenesis of various distinct life-threatening infections, we hypothesized that measuring mediators of these pathways at clinical presentation would identify febrile adults at risk of death.; Plasma concentrations of markers of endothelial (angiopoetin-1/2, soluble...
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2d
Efficacy and safety of ascending dosages of moxidectin and moxidectin-albendazole against Trichuris trichiura in adolescents: a randomized controlled trial
Preventive chemotherapy is the main strategy to control soil-transmitted helminth (STH) infections. Albendazole and mebendazole are ubiquitously used, but they are not sufficiently effective against Trichuris trichiura. Moxidectin might be a useful addition to the small drug armamentarium. However, the optimal dosage of moxidectin alone and in combination with albendazole against T. trichiura and other STHs has not yet been determined.; A Phase II, randomized, placebo-controlled, dose-finding trial...
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2d

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