Variations of MRI-assessed peristaltic motions during radiation therapy.

Purpose: Understanding complex abdominal organ motion is essential for motion management in radiation therapy (RT) of abdominal tumors. This study investigates abdominal motion induced by respiration and peristalsis, during various time durations relevant to RT, using various CT and MRI techniques acquired under free breathing (FB) and breath hold (BH).

Methods: A series of CT and MRI images acquired with various techniques under free breathing and/or breath hold from 37 randomly-selected pancreatic or liver cancer patients were analyzed to assess the motion in various time frames.

Modelling predicts that soybean is poised to dominate crop production across Africa.

The superior agronomic and human nutritional properties of grain legumes (pulses) make them an ideal foundation for future sustainable agriculture. Legume-based farming is particularly important in Africa, where small-scale agricultural systems dominate the food production landscape. Legumes provide an inexpensive source of protein and nutrients to African households as well as natural fertilization for the soil.

Incremental Elevations in TNFα and IL6 in the Human Colon and Procancerous Changes in the Mucosal Transcriptome Accompany Adiposity.

Background: Obesity, a risk factor for colorectal cancer, raises systemic levels of proinflammatory mediators. Whether increased levels also reside in the colons of obese individuals and are accompanied by procancerous alterations in the mucosal transcriptome is unknown.

Methods: Concentrations of TNFα, IL1β, and IL6 in blood and colonic mucosa of 16 lean and 26 obese individuals were examined.

Exenatide corrects postprandial hyperglycaemia in young people with cystic fibrosis and impaired glucose tolerance: A randomized crossover trial.

Impaired glucose tolerance (IGT) in cystic fibrosis (CF) manifests as postprandial hyperglycaemia. Pancreatic enzyme supplementation reduces the latter; restoring incretin secretion and slowing gastric emptying. We aimed to determine the acute effect of exenatide on postprandial glycaemia in young people with CF and IGT.

Immune Checkpoint Inhibitor-Associated Colitis and Hepatitis.

Immune checkpoint inhibitors (ICPIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand PD-L1. ICPIs are now approved for the treatment of a wide array of malignancies, with rates of durable responses in the metastatic setting far exceeding what would be expected from conventional chemotherapy. ICPIs have also been associated with rare but serious immune-related adverse events due to over-activation of the immune system that can affect any organ, including the gastrointestinal tract and liver.

Random Insertional Mutagenesis of a Serotype 2 Dengue Virus Clone.

Protein tagging is a powerful method of investigating protein function. However, modifying positive-strand RNA virus proteins in the context of viral infection can be particularly difficult as their compact genomes and multifunctional proteins mean even small changes can inactivate or attenuate the virus. Although targeted approaches to functionally tag viral proteins have been successful, these approaches are time consuming and inefficient.

Whole genome sequencing reveals the emergence of a Pseudomonas aeruginosa shared strain sub-lineage among patients treated within a single cystic fibrosis centre.

Background: Chronic lung infections caused by Pseudomonas aeruginosa are a significant cause of morbidity and mortality in people with cystic fibrosis (CF). Shared P. aeruginosa strains, that can be transmitted between patients, are of concern and in Australia the AUST-02 shared strain is predominant in individuals attending CF centres in Queensland and Western Australia.

Bilateral osteomyelitis and liver abscess caused by hypervirulent Klebsiella pneumoniae- a rare clinical manifestation (case report).

Background: Hypervirulent strains of Klebsiella pneumoniae are a recognized cause of a distinct invasive syndrome that results in pyogenic liver abscesses and metastatic complications, particularly in the Asia Pacific region. Reports of hypervirulent K.pneumoniae in Europe, the Americas and Australia indicate worldwide spread.

Enhanced preservation of the human intestinal microbiota by ridinilazole, a novel Clostridium difficile-targeting antibacterial, compared to vancomycin.

Ridinilazole, a novel targeted antibacterial being developed for the treatment of C. difficile infection (CDI) and prevention of recurrence, was shown in a recent Phase 2 study to be superior to vancomycin with regard to the primary efficacy measure, sustained clinical response (SCR), with the superiority being driven primarily by marked reductions in the rates of CDI recurrence within 30 days. Tolerability of ridinilazole was comparable to that of vancomycin.

Feasibility of real-time lung tumor motion monitoring using intrafractional ultrasound and kV cone beam projection images.

Purpose: The ability to monitor intrafractional tumor motion is essential for radiation therapy of thoracic and abdominal tumors. This study aims to develop a method to track lung tumor motion using intrafractional continuous ultrasound (US) and periodic cone-beam projection images (CBPI).

Methods: Time-sequenced b-mode US and CBPI data were extracted from the data acquired with the Clarity and XVI platforms on an Elekta linac, respectively.

Droplet Digital PCR with EvaGreen Assay: Confirmational Analysis of Structural Variants.

DNA structural variants can be analyzed by droplet digital PCR (ddPCR), a water-oil microfluidics and fluorescence technology to quantify target nucleic acids with extreme precision and sensitivity. Traditional ddPCR uses expensive fluorescent oligonucleotide probes that require extensive optimization. Here we describe a variation of ddPCR using a DNA-binding dye (EvaGreen), whose properties allow target products to be effectively quantified at a significantly lower cost.

Inhibiting the integrated stress response pathway prevents aberrant chondrocyte differentiation thereby alleviating chondrodysplasia.

The integrated stress response (ISR) is activated by diverse forms of cellular stress, including endoplasmic reticulum (ER) stress, and is associated with diseases. However, the molecular mechanism(s) whereby the ISR impacts on differentiation is incompletely understood. Here, we exploited a mouse model of Metaphyseal Chondrodysplasia type Schmid (MCDS) to provide insight into the impact of the ISR on cell fate.

PET-based Treatment Response Assessment for Neoadjuvant Chemoradiation in Pancreatic Adenocarcinoma: An Exploratory Study.

Purpose: Performance of anatomical metrics of Response Evaluation Criteria in Solid Tumors (RECIST1.1) versus Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST1.0) for neoadjuvant chemoradiation (nCR) of pancreatic adenocarcinoma was evaluated based on the pathological treatment response (PTR) data.

Technical Note: Enhancing soft tissue contrast and radiation-induced image changes with dual-energy CT for radiation therapy.

Purpose: The purpose of this work is to investigate the use of low-energy monoenergetic decompositions obtained from dual-energy CT (DECT) to enhance image contrast and the detection of radiation-induced changes of CT textures in pancreatic cancer.

Methods: The DECT data acquired for 10 consecutive pancreatic cancer patients during routine nongated CT-guided radiation therapy (RT) using an in-room CT (Definition AS Open, Siemens Healthcare, Malvern, PA) were analyzed. With a sequential DE protocol, the scanner rapidly performs two helical acquisitions, the first at a tube voltage of 80 kVp and the second at a tube voltage of 140 kVp.

A global regulatory system links virulence and antibiotic resistance to envelope homeostasis in Acinetobacter baumannii.

The nosocomial pathogen Acinetobacter baumannii is a significant threat due to its ability to cause infections refractory to a broad range of antibiotic treatments. We show here that a highly conserved sensory-transduction system, BfmRS, mediates the coordinate development of both enhanced virulence and resistance in this microorganism. Hyperactive alleles of BfmRS conferred increased protection from serum complement killing and allowed lethal systemic disease in mice.

Deep Inspiration Breath Hold: Techniques and Advantages for Cardiac Sparing During Breast Cancer Irradiation.

Historically, heart dose from left-sided breast radiotherapy has been associated with a risk of cardiac injury. Data suggests that there is not a threshold for the deleterious effects from radiation on the heart. Over the past several years, advances in radiation delivery techniques have reduced cardiac morbidity due to treatment.

Robust identification of deletions in exome and genome sequence data based on clustering of Mendelian errors.

Multiple tools have been developed to identify copy number variants (CNVs) from whole exome (WES) and whole genome sequencing (WGS) data. Current tools such as XHMM for WES and CNVnator for WGS identify CNVs based on changes in read depth. For WGS, other methods to identify CNVs include utilizing discordant read pairs and split reads and genome-wide local assembly with tools such as Lumpy and SvABA, respectively.

Correlation of ADC With Pathological Treatment Response for Radiation Therapy of Pancreatic Cancer.

Purpose: To investigate the feasibility of using apparent diffusion coefficient (ADC) to assesspathological treatment response in pancreatic ductal adenocarcinoma (PDAC) following neoadjuvant chemoradiation (nCR).

Materials/methods: MRI and pathological data collected for 25patients with resectable and borderline resectable PDAC following nCR were retrospectively analyzed. Pre- and post-nCR mean ADC values in the tumors were compared using Wilcoxon matched pairs test.

Potential Antitumor Activity of 2-O-α-d-Glucopyranosyl-6-O-(2-Pentylheptanoyl)-l-Ascorbic Acid.

Intravenous administration of high-dose ascorbic acid (AA) has been reported as a treatment for cancer patients. However, cancer patients with renal failure cannot receive this therapy because high-dose AA infusion can have side effects. To solve this problem, we evaluated the antitumor activity of a lipophilic stable AA derivative, 2--α-d-glucopyranosyl-6--(2-pentylheptanoyl)-l-ascorbic acid (6-bOcta-AA-2G).

Robust identification of mosaic variants in congenital heart disease.

Mosaicism due to somatic mutations can cause multiple diseases including cancer, developmental and overgrowth syndromes, neurodevelopmental disorders, autoinflammatory diseases, and atrial fibrillation. With the increased use of next generation sequencing technology, multiple tools have been developed to identify low-frequency variants, specifically from matched tumor-normal tissues in cancer studies. To investigate whether mosaic variants are implicated in congenital heart disease (CHD), we developed a pipeline using the cancer somatic variant caller MuTect to identify mosaic variants in whole-exome sequencing (WES) data from a cohort of parent/affected child trios (n = 715) and a cohort of healthy individuals (n = 416).

A fast 4D IMRT/VMAT planning method based on segment aperture morphing.

Purpose: Four-dimensional volumetric modulated arc therapy (4D VMAT) and four-dimensional intensity-modulated radiotherapy (4D IMRT) are developing radiation therapy treatment strategies designed to maximize dose conformality, minimize normal tissue dose, and deliver the treatment as efficiently as possible. The patient's entire breathing cycle is captured through 4D imaging modalities and then separated into individual breathing phases for planning purposes. Optimizing multiphase VMAT and IMRT plans is computationally demanding and currently impractical for clinical application.

Structure-activity relationships of flavanones, flavanone glycosides, and flavones in anti-degranulation activity in rat basophilic leukemia RBL-2H3 cells.

The incidence of type I allergies, which are associated with mast cell degranulation and local inflammation, is increasing, and new treatments are needed. To date, structure-activity relationships of flavonoids in their degranulation-inhibiting activity have not been systematically characterized. In the current study, the degranulation-inhibiting activity of a series of flavonoids was evaluated.

Affinity resins as new tools for identifying target proteins of ascorbic acid.

l-Ascorbic acid (AA) has diverse physiological functions, but little is known about the functional mechanisms of AA. In this study, we synthesized two types of affinity resin on which AA is immobilized in a stable form to identify new AA-targeted proteins, which can provide important clues for elucidating unknown functional mechanisms of AA. To our knowledge, an affinity resin on which AA as a ligand is immobilized has not been prepared, because AA is very unstable and rapidly degraded in an aqueous solution.