Systematic application of UPLC-Q-ToF-MS/MS coupled with chemometrics for the identification of natural food pigments from Davidson plum and native currant.

This study investigates the potential of Australian Traditional foods as novel sources of natural colourants for food applications, employing untargeted metabolomics and chemometrics. Two native species were analysed: Davidson plum and native currant. The species were quantitatively assessed for colour properties using the CIELAB colour system in conjunction with Ultra Performance Liquid Chromatography-Quadrupole Time of Flight Tandem Mass Spectrometry (UPLC-Q-ToF-MS/MS).

Characteristics and Outcomes of Over a Million Patients with Inflammatory Bowel Disease in Seven Countries: Multinational Cohort Study and Open Data Resource.

Background And Aims: Observational healthcare data are an important tool for delineating patients' inflammatory bowel disease (IBD) journey in real-world settings. However, studies that characterize IBD cohorts typically rely on a single resource, apply diverse eligibility criteria, and extract variable sets of attributes, making comparison between cohorts challenging. We aim to longitudinally describe and compare IBD patient cohorts across multiple geographic regions, employing unified data and analysis framework.

Enhanced bacterial cancer therapy delivering therapeutic RNA interference of c-Myc.

Background: Bacterial cancer therapy was first trialled in patients at the end of the nineteenth century. More recently, tumour-targeting bacteria have been harnessed to deliver plasmid-expressed therapeutic interfering RNA to a range of solid tumours. A major limitation to clinical translation of this is the short-term nature of RNA interference in vivo due to plasmid instability.

Towards global model generalizability: independent cross-site feature evaluation for patient-level risk prediction models using the OHDSI network.

Background: Predictive models show promise in healthcare, but their successful deployment is challenging due to limited generalizability. Current external validation often focuses on model performance with restricted feature use from the original training data, lacking insights into their suitability at external sites. Our study introduces an innovative methodology for evaluating features during both the development phase and the validation, focusing on creating and validating predictive models for post-surgery patient outcomes with improved generalizability.

Conditional in vivo deletion of LYN kinase has little effect on a BRCA1 loss-of-function-associated mammary tumour model.

LYN kinase is expressed in BRCA1 loss-of-function-dependent mouse mammary tumours, in the cells of origin of such tumours, and in human breast cancer. Suppressing LYN kinase activity in BRCA1-defective cell lines as well as in in vitro cultures of Brca1-null mouse mammary tumours is deleterious to their growth. Here, we examined the interaction between LYN kinase and BRCA1 loss-of-function in an in vivo mouse mammary tumour model, using conditional knockout Brca1 and Lyn alleles.

NOTCH and AKT Signalling Interact to Drive Mammary Tumour Heterogeneity.

A better understanding of the mechanisms generating tumour heterogeneity will allow better targeting of current therapies, identify potential resistance mechanisms and highlight new approaches for therapy. We have previously shown that in genetically modified mouse models carrying conditional oncogenic alleles, mammary tumour histotype varies depending on the combination of alleles, the cell type to which they are targeted and, in some cases, reproductive history. This suggests that tumour heterogeneity is not a purely stochastic process; rather, differential activation of signalling pathways leads to reproducible differences in tumour histotype.

Machine learning for improving high-dimensional proxy confounder adjustment in healthcare database studies: An overview of the current literature.

Purpose: Supplementing investigator-specified variables with large numbers of empirically identified features that collectively serve as 'proxies' for unspecified or unmeasured factors can often improve confounding control in studies utilizing administrative healthcare databases. Consequently, there has been a recent focus on the development of data-driven methods for high-dimensional proxy confounder adjustment in pharmacoepidemiologic research. In this paper, we survey current approaches and recent advancements for high-dimensional proxy confounder adjustment in healthcare database studies.

Application of a high-resolution in vitro human MDR1-MDCK assay and in vivo studies in preclinical species to improve prediction of CNS drug penetration.

P-glycoprotein (P-gp, MDR1) is expressed at the blood-brain barrier (BBB) and restricts penetration of its substrates into the central nervous system (CNS). In vitro MDR1 assays are frequently used to predict the in vivo relevance of MDR1-mediated efflux at the BBB. It has been well established that drug candidates with high MDR1 efflux ratios (ERs) display poor CNS penetration.

pUL21 regulation of pUs3 kinase activity influences the nature of nuclear envelope deformation by the HSV-2 nuclear egress complex.

It is well established that the herpesvirus nuclear egress complex (NEC) has an intrinsic ability to deform membranes. During viral infection, the membrane-deformation activity of the NEC must be precisely regulated to ensure efficient nuclear egress of capsids. One viral protein known to regulate herpes simplex virus type 2 (HSV-2) NEC activity is the tegument protein pUL21.

Effects of sleepiness on clinical decision making among paramedic students: a simulated night shift study.

Objective: Paramedics are at the forefront of emergency healthcare. Quick and careful decision making is required to effectively care for their patients; however, excessive sleepiness has the potential to impact on clinical decision making. Studies investigating the effects of night shift work on sleepiness, cognitive function and clinical performance in the prehospital setting are limited.

Faecal diversion system usage in an adult intensive care unit.

Objective: To determine the frequency, indications and complications associated with the use of faecal diversion systems (rectal tubes) in critically ill patients.

Design: A single centre observational study over 15 months.

Setting: Intensive care unit (ICU).

How the weather affects the pain of citizen scientists using a smartphone app.

Patients with chronic pain commonly believe their pain is related to the weather. Scientific evidence to support their beliefs is inconclusive, in part due to difficulties in getting a large dataset of patients frequently recording their pain symptoms during a variety of weather conditions. Smartphones allow the opportunity to collect data to overcome these difficulties.

APC2 is critical for ovarian WNT signalling control, fertility and tumour suppression.

Background: Canonical WNT signalling plays a critical role in the regulation of ovarian development; mis-regulation of this key pathway in the adult ovary is associated with subfertility and tumourigenesis. The roles of Adenomatous polyposis coli 2 (APC2), a little-studied WNT signalling pathway regulator, in ovarian homeostasis, fertility and tumourigenesis have not previously been explored. Here, we demonstrate essential roles of APC2 in regulating ovarian WNT signalling and ovarian homeostasis.

Rapid activation of epithelial-mesenchymal transition drives PARP inhibitor resistance in -mutant mammary tumours.

Tumours defective in the DNA homologous recombination repair pathway can be effectively treated with poly (ADP-ribose) polymerase (PARP) inhibitors; these have proven effective in clinical trials in patients with gene function-defective cancers. However, resistance observed in both pre-clinical and clinical studies is likely to impact on this treatment strategy. Over-expression of phosphoglycoprotein (P-gp) has been previously suggested as a mechanism of resistance to the PARP inhibitor olaparib in mouse models of -mutant breast cancer.

The hospital-based evaluation of laxative prophylaxis in ICU (HELP-ICU): A pilot cluster-crossover randomized clinical trial.

Purpose: Prophylactic laxative regimens may prevent constipation but may increase diarrhea and subsequent rectal tube insertion. Our aim was to compare three prophylactic laxative regimens on the rate of rectal tube insertion (primary outcome) and major constipation- or diarrhea-associated complications.

Material And Methods: We conducted a cluster-crossover trial.

The aminoglycoside resistance-promoting AmgRS envelope stress-responsive two-component system in Pseudomonas aeruginosa is zinc-activated and protects cells from zinc-promoted membrane damage.

Exposure of wild-type (WT) Pseudomonas aeruginosa PAO1 to ZnCl2 (Zn) yielded a concentration-dependent increase in depolarization of the cytoplasmic membrane (CM), an indication that this metal is membrane-damaging. Consistent with this, Zn activated the AmgRS envelope stress-responsive two-component system (TCS) that was previously shown to be activated by and to protect P. aeruginosa from the membrane-damaging effects of aminoglycoside (AG) antibiotics.

Constipation, diarrhea, and prophylactic laxative bowel regimens in the critically ill: A systematic review and meta-analysis.

Introduction: Prophylactic laxative bowel regimens may prevent constipation in enterally-fed critically ill patients. However, their use may also increase diarrhea. We performed a systematic review to: 1.

Correction: Loss of tuberous sclerosis complex 2 sensitizes tumors to nelfinavir-bortezomib therapy to intensify endoplasmic reticulum stress-induced cell death.

This article was originally published under standard licence, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the paper have been modified accordingly.

Commentary: The Invention of Aboriginal Diabetes: The Role of the Thrifty Gene Hypothesis in Canadian Health Care Provision.

The purpose of this study was to analyze the extent to which the 'thrifty gene hypothesis' remains embedded within regimes of Canadian health care. The thrifty gene hypothesis, formulated by the American geneticist and travelling scientist James V. Neel in 1962, proposed that Indigenous peoples were genetically predisposed to Type 2 diabetes due to the foodways of their ancestors.

TGFβ inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence.

Liver injury results in rapid regeneration through hepatocyte proliferation and hypertrophy. However, after acute severe injury, such as acetaminophen poisoning, effective regeneration may fail. We investigated how senescence may underlie this regenerative failure.

Loss of tuberous sclerosis complex 2 sensitizes tumors to nelfinavir-bortezomib therapy to intensify endoplasmic reticulum stress-induced cell death.

Cancer cells lose homeostatic flexibility because of mutations and dysregulated signaling pathways involved in maintaining homeostasis. Tuberous Sclerosis Complex 1 (TSC1) and TSC2 play a fundamental role in cell homeostasis, where signal transduction through TSC1/TSC2 is often compromised in cancer, leading to aberrant activation of mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 hyperactivation increases the basal level of endoplasmic reticulum (ER) stress via an accumulation of unfolded protein, due to heightened de novo protein translation and repression of autophagy.

Retail food environments, shopping experiences, First Nations and the provincial Norths.

Introduction: This paper looks at the market food environments of First Nations communities located in the provincial Norths by examining the potential retail competition faced by the North West Company (NWC) and by reporting on the grocery shopping experiences of people living in northern Canada.

Methods: We employed two methodological approaches to assess northern retail food environments. First, we mapped food retailers in the North to examine the breadth of retail competition in the provincial Norths, focussing specifically on those communities without year-round road access.