A feasibility study of zebrafish embryo irradiation with laser-accelerated protons.

The development from single shot basic laser plasma interaction research toward experiments in which repetition rated laser-driven ion sources can be applied requires technological improvements. For example, in the case of radio-biological experiments, irradiation duration and reproducible controlled conditions are important for performing studies with a large number of samples. We present important technological advancements of recent years at the ATLAS 300 laser in Garching near Munich since our last radiation biology experiment.

Using Bayesian Networks to Predict Long-Term Health-Related Quality of Life and Comorbidity after Bariatric Surgery: A Study Based on the Scandinavian Obesity Surgery Registry.

Previously published literature has identified a few predictors of health-related quality of life (HRQoL) after bariatric surgery. However, performance of the predictive models was not evaluated rigorously using real world data. To find better methods for predicting prognosis in patients after bariatric surgery, we examined performance of the Bayesian networks (BN) method in predicting long-term postoperative HRQoL and compared it with the convolution neural network (CNN) and multivariable logistic regression (MLR).

Mid-Infrared Imaging Is Able to Characterize and Separate Cancer Cell Lines.

Malignancies are still responsible for a large share of lethalities. Macroscopical evaluation of the surgical resection margins is uncertain. Big data based imaging approaches have emerged in the recent decade (mass spectrometry, two-photon microscopy, infrared and Raman spectroscopy).

A solid doxycycline HP-β-CD formulation for reconstitution (i.v. bolus) prepared by scaled-up electrospinning.

In this study a new intravenous (i.v.) bolus dosage form of doxycycline was prepared by electrospinning.

Spectral and spatial shaping of laser-driven proton beams using a pulsed high-field magnet beamline.

Intense laser-driven proton pulses, inherently broadband and highly divergent, pose a challenge to established beamline concepts on the path to application-adapted irradiation field formation, particularly for 3D. Here we experimentally show the successful implementation of a highly efficient (50% transmission) and tuneable dual pulsed solenoid setup to generate a homogeneous (laterally and in depth) volumetric dose distribution (cylindrical volume of 5 mm diameter and depth) at a single pulse dose of 0.7 Gy via multi-energy slice selection from the broad input spectrum.

Clinical and Genomic Characteristics of Small Cell Lung Cancer in Never Smokers: Results From a Retrospective Multicenter Cohort Study.

Background: Small cell lung cancer (SCLC) has the strongest association with smoking among lung cancers. The characteristics of never smokers with SCLC is not known.

Research Question: Are the clinical characteristics, prognostic factors, survival, genomic alterations, and tumor mutational burdens of SCLC in patients who have never smoked different from those who have smoked?

Study Design And Methods: A retrospective multicenter cohort study of patients with clinician-confirmed SCLC was performed with the use of a longitudinal and nationally representative electronic medical records database.

Stability Test of PACAP in Eye Drops.

PACAP is a neuropeptide with widespread distribution and diverse biological functions. It has strong cytoprotective effects mediated mainly through specific PAC1 receptors. Experimental data show protective effects of PACAP in the retina and cornea in several pathological conditions.

The Effect of Laparoscopic Gastric Bypass Surgery on Insulin Resistance and Glycosylated Hemoglobin A1c: a 2-Year Follow-up Study.

Background: Bariatric surgery improves insulin sensitivity and secretion in patients with type 2 diabetes, but the effect on patients with prediabetes or even normal glucose tolerance deserves further consideration.

Methods: Cohort study including patients operated with laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) between November 2012 and June 2017 at the Örebro University Hospital (n = 813) with follow-up of 742 patients 2 years after surgery. Fasting insulin, glucose, glycosylated hemoglobin (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR) were analyzed at baseline and 2 years after surgery for patients with overt type 2 diabetes, prediabetes, or non-diabetes.

Suppressive mechanisms by Heligmosomoides polygyrus-induced Tregs in C57BL/6 mice change over time and differ to that of naïve mice.

Disrupting or harnessing immune suppression is leading to new therapeutic avenues in a number of immune-related diseases. Understanding the suppressive functions of regulatory T cells (Tregs) in different environments is therefore key. Parasitic worms are strong inducers of Tregs and previous research has suggested that parasite-induced Tregs are stronger suppressors than naïve Tregs.

Current State of Understanding of the Role of PACAP in the Hypothalamo-Hypophyseal Gonadotropin Functions of Mammals.

PACAP was discovered 30 years ago in Dr. Akira Arimura's laboratory. In the past three decades since then, it has become evident that this peptide plays numerous crucial roles in mammalian organisms.

A validated UHPLC-MS method for tryptophan metabolites: Application in the diagnosis of multiple sclerosis.

The simultaneous quantitative estimation of tryptophan (TRP) and its metabolites represents a great challenge because of their diverse chemical properties, e.g., presence of acidic, basic, and nonpolar functional groups and their immensely different concentrations in biological matrices.

Precision-engineered reporter cell lines reveal ABCG2 regulation in live lung cancer cells.

Expression of the ABCG2 multidrug transporter is a marker of cancer stem cells and a predictor of recurrent malignant disease. Understanding how human ABCG2 expression is modulated by pharmacotherapy is crucial in guiding therapeutic recommendations and may aid rational drug development. Genome edited reporter cells are useful in investigating gene regulation and visualizing protein activity in live cells but require precise targeting to preserve native regulatory regions.

Digital UV/VIS imaging: A rapid PAT tool for crushing strength, drug content and particle size distribution determination in tablets.

The Process Analytical Technology (PAT) and the Quality-by-Design (QbD) approaches can efficiently facilitate the shift to the desired continuous manufacturing and real time release testing (RTRT). By this, it is vital to develop new, in-line analytical methods which fulfil the pharmaceutical requirements. The fast-developing digital imaging-based machine vision systems can provide revolutionary solutions not just in the automotive industry but in the pharmaceutical technology, as well.

Routing Nanomolar Protein Cargoes to Lipid Raft-Mediated/Caveolar Endocytosis through a Ganglioside GM1-Specific Recognition Tag.

There is a pressing need to develop ways to deliver therapeutic macromolecules to their intracellular targets. Certain viral and bacterial proteins are readily internalized in functional form through lipid raft-mediated/caveolar endocytosis, but mimicking this process with protein cargoes at therapeutically relevant concentrations is a great challenge. Targeting ganglioside GM1 in the caveolar pits triggers endocytosis.

Metabolic Labeling of RNAs Uncovers Hidden Features and Dynamics of the Arabidopsis Transcriptome.

Transcriptome analysis by RNA sequencing (RNA-seq) has become an indispensable research tool in modern plant biology. Virtually all RNA-seq studies provide a snapshot of the steady state transcriptome, which contains valuable information about RNA populations at a given time but lacks information about the dynamics of RNA synthesis and degradation. Only a few specialized sequencing techniques, such as global run-on sequencing, have been used to provide information about RNA synthesis rates in plants.

Real-world healthcare resource utilization in patients with indolent non-Hodgkin lymphoma: differences between patients treated with first-line ibrutinib or bendamustine + rituximab.

This study evaluated the real-world healthcare resource utilization (HCRU) and costs in patients diagnosed with an indolent non-Hodgkin lymphoma (iNHL) and treated with either first-line ibrutinib monotherapy (IbM) therapy or bendamustine plus rituximab combination therapy (BR). Treatment-naïve iNHL patients in the IBM MarketScan Research Databases were identified based on the first prescription of either IbM or BR therapy between 02/01/2014 and 08/30/2017. A greater proportion of IbM patients ( = 207) had at least one inpatient admission (IP) or emergency room visit (ER), both all-cause and iNHL-related, than BR ( = 1337) patients.

Attenuated total reflection fourier transform infrared spectroscopy based methods for identification of chromatography media formulations used in downstream processes.

Chromatographic media play a crucial role in the downstream processing of biotechnology products. The physical and chemical properties of these processing aids are mostly monitored by expensive and time-consuming preparative tests, but spectroscopic techniques may also be used to measure chromatographic media samples. In this study, chromatographic media formulations used in downstream processes were investigated using attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy.

Scale-up of electrospinning technology: Applications in the pharmaceutical industry.

Recently, electrospinning (ES) of fibers has been shown to be an attractive strategy for drug delivery. One of the main features of ES is that a wide variety of drugs can be loaded into the fibers to improve their bioavailability, to enhance dissolution, or to achieve controlled release. Besides, ES is a continuous technology with low energy consumption, which can make it a very economic production alternative to the widely used freeze drying and spray drying.

Cancer Prevention in Primary Care: Perception of Importance, Recognition of Risk Factors and Prescribing Behaviors.

Purpose: Acceptability and uptake of cancer preventive interventions is associated with physician recommendation, which is dependent on physician familiarity with available preventive options. The goal of this study is to evaluate cancer prevention perceptions, understanding of breast and ovarian cancer risk factors, and prescribing behaviors of primary care physicians.

Methods: We conducted cross-sectional.

A Phase IIa Trial of Metformin for Colorectal Cancer Risk Reduction among Individuals with History of Colorectal Adenomas and Elevated Body Mass Index.

Obesity is associated with risk of colorectal adenoma (CRA) and colorectal cancer. The signaling pathway activated by metformin (LKB1/AMPK/mTOR) is implicated in tumor suppression in Apc mice via metformin-induced reduction in polyp burden, increased ratio of pAMPK/AMPK, decreased pmTOR/mTOR ratio, and decreased pS6/S6 ratio in polyps. We hypothesized that metformin would affect colorectal tissue S6 among obese patients with recent history of CRA.

Continuous Formulation Approaches of Amorphous Solid Dispersions: Significance of Powder Flow Properties and Feeding Performance.

Preparation and formulation of amorphous solid dispersions (ASDs) are becoming more and more popular in the pharmaceutical field because the dissolution of poorly water-soluble drugs can be effectively improved this way, which can lead to increased bioavailability in many cases. During downstream processing of ASDs, technologists need to keep in mind both traditional challenges and the newest trends. In the last decade, the pharmaceutical industry began to display considerable interest in continuous processing, which can be explained with their potential advantages such as smaller footprint, easier scale-up, and more consistent product, better quality and quality assurance.

Duration of type 2 diabetes and remission rates after bariatric surgery in Sweden 2007-2015: A registry-based cohort study.

Background: Although bariatric surgery is an effective treatment for type 2 diabetes (T2D) in patients with morbid obesity, further studies are needed to evaluate factors influencing the chance of achieving diabetes remission. The objective of the present study was to investigate the association between T2D duration and the chance of achieving remission of T2D after bariatric surgery.

Methods And Findings: We conducted a nationwide register-based cohort study including all adult patients with T2D and BMI ≥ 35 kg/m2 who received primary bariatric surgery in Sweden between 2007 and 2015 identified through the Scandinavian Obesity Surgery Registry.

[Changes of lactate levels in diabetic ketoacidosis and in newly diagnosed type 1 diabetes mellitus].

It is known that lactate concentration is increased in diabetic ketoacidosis (DKA), however, the pathophysiology and kinetics of lactate changes are still unclear. Normally, L-lactate is the major form in the human body. According to previous data, also D- and L-lactate might be increased in hyperglycaemic disorders.

Predictive factors of complications in revisional gastric bypass surgery: results from the Scandinavian Obesity Surgery Registry.

Background: Roux-en-Y gastric bypass is the most common procedure for revisional bariatric surgery. This study is an analysis of revisional gastric bypass operations (rGBP) compared with primary gastric bypass (pGBP) performed in Sweden between 2007 and 2016.

Objective: The aim was to compare the incidence of adverse events in primary and revisional gastric bypass surgery and to identify predictive factors of intraoperative, early, and late complications in revisional gastric bypass surgery.