Contact X-ray Brachytherapy as a Boost Therapy After Neoadjuvant (Chemo)Radiation in High-Risk Locally Advanced Rectal Cancer.

Purpose: Radical surgery following neoadjuvant therapy is the standard of care for locally advanced rectal cancer. A contact x-ray brachytherapy (CXB) boost can alternatively be used to treat residual disease postneoadjuvant (chemo)radiation, especially in patients who are not suitable for or do not wish to have surgery. Its role has mostly been studied to date in low- to intermediate-risk patients.

Contact X-ray Brachytherapy as a sole treatment in selected patients with early rectal cancer - Multi-centre study.

Background And Purpose: Radical surgery is the standard of care for early rectal cancer. However, alternative organ-preserving approaches are attractive, especially in frail or elderly patients as these avoid surgical complications. We have assessed the efficacy of sole Contact X-ray Brachytherapy (CXB) treatment in stage-1 rectal cancer patients who were unsuitable for or declined surgery.

Sequence of Contact X-ray Brachytherapy (CXB) and External Beam Radiation (EBRT) in organ-preserving treatment for small rectal cancer.

Background And Purpose: External Beam Radiotherapy (EBRT) followed by Contact X-ray Brachytherapy (CXB) and vice versa are viable alternatives to surgery for selected rectal cancer patients who have small tumours (≤3 cm). However, the optimal sequence of treatment needs to be established. We compared two approaches using Propensity Score (PS) matching and inverse probability treatment weighting (IPTW) analyses to investigate whether the sequence of treatment affected patient outcomes.

Contact X-ray brachytherapy (CXB) as a salvage treatment for rectal cancer patients who developed local tumor re-growth after watch-and-wait approach.

Purpose: A watch-and-wait approach is an alternative to surgery for rectal cancer patients who have achieved a clinical complete response (cCR) following neoadjuvant (chemo)radiotherapy. However, approximately 25-38% of patients experience subsequent local tumor re-growth that requires salvage surgery. We evaluated the effectiveness of contact X-ray brachytherapy (CXB) as an alternative method of salvage therapy for those patients who were either unfit for or refused surgery.

A novel model of the small intestinal epithelium in co-culture with 'gut-like' dendritic cells.

Cross-talk between dendritic cells (DCs) and the intestinal epithelium is important in the decision to mount a protective immune response to a pathogen or to regulate potentially damaging responses to food antigens and the microbiota. Failures in this decision-making process contribute to the development of intestinal inflammation, making the molecular signals that pass between DCs and intestinal epithelial cells potential therapeutic targets. Until now, models with sufficient complexity to understand these interactions have been lacking.

Characterising user engagement with mHealth for chronic disease self-management and impact on machine learning performance.

Mobile Health (mHealth) has the potential to be transformative in the management of chronic conditions. Machine learning can leverage self-reported data collected with apps to predict periods of increased health risk, alert users, and signpost interventions. Despite this, mHealth must balance the treatment burden of frequent self-reporting and predictive performance and safety.

EPR studies of ferredoxin in spinach and cyanobacterial thylakoids related to photosystem I-driven NADP reduction.

Photosynthetic light-dependent reactions occur in thylakoid membranes where embedded proteins capture light energy and convert it to chemical energy in the form of ATP and NADPH for use in carbon fixation. One of these integral membrane proteins is Photosystem I (PSI). PSI catalyzes light-driven transmembrane electron transfer from plastocyanin (Pc) to oxidized ferredoxin (Fd).

Homeostasis, injury, and recovery dynamics at multiple scales in a self-organizing mouse intestinal crypt.

The maintenance of the functional integrity of the intestinal epithelium requires a tight coordination between cell production, migration, and shedding along the crypt-villus axis. Dysregulation of these processes may result in loss of the intestinal barrier and disease. With the aim of generating a more complete and integrated understanding of how the epithelium maintains homeostasis and recovers after injury, we have built a multi-scale agent-based model (ABM) of the mouse intestinal epithelium.

Exploring the Validity of GOLD 2023 Guidelines: Should GOLD C and D Be Combined?

Introduction: The GOLD (Global Initiative for Chronic Obstructive Lung Disease) 2023 guidelines proposed important changes to the stratification of disease severity using the "ABCD" assessment tool. The highest risk groups "C" and "D" were combined into a single category "E" based on exacerbation history, no longer considering symptomology.

Purpose: We quantify the differential disease progression of individuals initially stratified by the GOLD 2022 "ABCD" scheme to evaluate these proposed changes.

A dynamic model of the intestinal epithelium integrates multiple sources of preclinical data and enables clinical translation of drug-induced toxicity.

We have built a quantitative systems toxicology modeling framework focused on the early prediction of oncotherapeutic-induced clinical intestinal adverse effects. The model describes stem and progenitor cell dynamics in the small intestinal epithelium and integrates heterogeneous epithelial-related processes, such as transcriptional profiles, citrulline kinetics, and probability of diarrhea. We fitted a mouse-specific version of the model to quantify doxorubicin and 5-fluorouracil (5-FU)-induced toxicity, which included pharmacokinetics and 5-FU metabolism and assumed that both drugs led to cell cycle arrest and apoptosis in stem cells and proliferative progenitors.

C1GalT1 expression reciprocally controls tumour cell-cell and tumour-macrophage interactions mediated by galectin-3 and MGL with double impact on cancer development and progression.

Although most cell membrane proteins are modified by glycosylation, our understanding of the role and actions of protein glycosylation is still very limited. β1,3galactosyltransferase (C1GalT1) is a key glycosyltransferase that controls the biosynthesis of the Core 1 structure of O-linked mucin type glycans and is overexpressed by many common types of epithelial cancers. This study reports that suppression of C1GalT1 expression in human colon cancer cells caused substantial changes of protein glycosylation of cell membrane proteins, many of which were ligands of the galactoside-binding galectin-3 and the macrophage galactose-type lectin (MGL).

Effect of ellagic acid and retinoic acid on collagen and elastin production by human dermal fibroblasts.

Background: Elastin is a fibrous protein key to the structure and support of skin as well as other organ tissues. Elastic fibers are located in the skin's dermal layer and make up approximately 2%-4% of the fat-free dry weight of the dermis in the skin of adults. Aging causes the progressive degradation of elastin fibers.

A brain flatmap data visualization tool for mouse, rat, and human.

Here we provide open-access brain data flatmap visualization and analysis tools for the mouse, rat, and human. The present work stems from a previous JCN Toolbox article that introduced a novel flatmap of the mouse brain and substantially enhanced flatmaps of the rat and human brain. These brain flatmap data visualization tools enable computer-generated graphical flatmap representation of tabulated user-entered data.

Galectin-2 in Health and Diseases.

Galectin-2 is a prototype member of the galactoside-binding galectin family. It is predominately expressed in the gastrointestinal tract but is also detected in several other tissues such as the placenta and in the cardiovascular system. Galectin-2 expression and secretion by epithelial cells has been reported to contribute to the strength of the mucus layer, protect the integrity of epithelia.

Interleukin-10 Deficiency Impacts on TNF-Induced NFκB Regulated Responses In Vivo.

Interleukin-10 (IL-10) is an anti-inflammatory cytokine that has a major protective role against intestinal inflammation. We recently revealed that intestinal epithelial cells in vitro regulate NFκB-driven transcriptional responses to TNF via an autocrine mechanism dependent on IL-10 secretion. Here in this study, we investigated the impact of IL-10 deficiency on the NFκB pathway and its downstream targets in the small intestinal mucosa in vivo.

Mouse organoids as an in vitro tool to study the in vivo intestinal response to cytotoxicants.

Cross-species comparison of drug responses at the organoid level could help to determine the human relevance of findings from animal studies. To this end, we first need to evaluate the in vitro to in vivo translatability of preclinical organoids. Here, we used 5-fluorouracil (5-FU) as an exemplar drug to test whether the in vivo gut response to this cytotoxicant was preserved in murine intestinal organoids.

deficiency and its impact on plasma cells and immunoglobulin expression in murine small intestinal mucosa.

The alternative (noncanonical) nuclear factor-κB (NF-κB) signaling pathway predominantly regulates the function of the p52/RelB heterodimer. Germline 2 deficiency in mice leads to loss of p100/p52 protein and offers protection against a variety of gastrointestinal conditions, including azoxymethane/dextran sulfate sodium (DSS)-induced colitis-associated cancer and lipopolysaccharide (LPS)-induced small intestinal epithelial apoptosis. However, the common underlying protective mechanisms have not yet been fully elucidated.

Explainable Machine Learning for Real-Time Hypoglycemia and Hyperglycemia Prediction and Personalized Control Recommendations.

Background: The occurrences of acute complications arising from hypoglycemia and hyperglycemia peak as young adults with type 1 diabetes (T1D) take control of their own care. Continuous glucose monitoring (CGM) devices provide real-time glucose readings enabling users to manage their control proactively. Machine learning algorithms can use CGM data to make ahead-of-time risk predictions and provide insight into an individual's longer term control.

COVID-19 Oximetry @home: evaluation of patient outcomes.

Background: COVID-19 has placed unprecedented demands on hospitals. A clinical service, COVID-19 Oximetry @home (CO@h) was launched in November 2020 to support remote monitoring of COVID-19 patients in the community. Remote monitoring through CO@h aims to identify early patient deterioration and provide timely escalation for cases of silent hypoxia, while reducing the burden on secondary care.

Higher Variability in Fungi Compared to Bacteria in the Foraging Honey Bee Gut.

Along with bacteria, fungi can represent a significant component of animal- and plant-associated microbial communities. However, we have only begun to describe these fungi, much less examine their effects on most animals and plants. Bacteria associated with the honey bee, Apis mellifera, have been well characterized across different regions of the gut.

Soluble Non-Starch Polysaccharides From Plantain ( L.) Diminish Epithelial Impact of .

infection (CDI) is a leading cause of antibiotic-associated diarrhoea. Adhesion of this Gram-positive pathogen to the intestinal epithelium is a crucial step in CDI, with recurrence and relapse of disease dependent on epithelial interaction of its endospores. Close proximity, or adhesion of, hypervirulent strains to the intestinal mucosa are also likely to be necessary for the release of toxins, which when internalized, result in intestinal epithelial cell rounding, damage, inflammation, loss of barrier function and diarrhoea.

Using explainable machine learning to characterise data drift and detect emergent health risks for emergency department admissions during COVID-19.

A key task of emergency departments is to promptly identify patients who require hospital admission. Early identification ensures patient safety and aids organisational planning. Supervised machine learning algorithms can use data describing historical episodes to make ahead-of-time predictions of clinical outcomes.

Identifying key regulators of the intestinal stem cell niche.

The intestinal tract is lined by a single layer of epithelium that is one of the fastest regenerating tissues in the body and which therefore requires a very active and exquisitely controlled stem cell population. Rapid renewal of the epithelium is necessary to provide a continuous physical barrier from the intestinal luminal microenvironment that contains abundant microorganisms, whilst also ensuring an efficient surface for the absorption of dietary components. Specialised epithelial cell populations are important for the maintenance of intestinal homeostasis and are derived from adult intestinal stem cells (ISCs).