The tumor microenvironment (TME) comprises all non-tumor elements of cancer and strongly influences disease progression and phenotype. To understand tumor biology and accurately test new therapeutic strategies, representative models should contain both tumor cells and normal cells of the TME. Here, we describe and characterize co-culture tumor-derived organoids and cancer-associated fibroblasts (CAFs), a major component of the TME, in matrix-embedded assembloid models of esophageal adenocarcinoma (EAC).
View Article and Find Full Text PDFAnn R Coll Surg Engl
November 2024
Introduction: Studies have demonstrated that prehabilitation in oesophagogastric cancer (OGC) improves body composition, physical fitness and quality of life, and can reduce surgical complications. However, it is not offered in all OGC centres. Furthermore, definitions, funding and access to services vary.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2024
The formation of mineral-associated organic matter (MAOM) is a key phenomenon that may explain the slow turnover rates of carbon in soil organic matter (SOM). Despite this, important details pertaining to the structure and dynamics of MAOM remain unknown. In the present study, we use replica-exchange molecular dynamics simulations to gain insight into the structure of MAOM on the surface of prototypical phyllosilicate clay and Fe-oxide minerals, montmorillonite and goethite, fine-grained minerals that strongly impact soil carbon dynamics in temperate and tropical regions, respectively.
View Article and Find Full Text PDFBackground: Prehabilitation is safe, feasible and may improve a range of outcomes in patients with oesophago-gastric cancer (OGC). Recent studies have suggested the potential of prehabilitation to improve body composition, sarcopenia and physical fitness, reduce surgical complications and improve quality of life. Despite this, prehabilitation services are not offered throughout all OGC centres in the UK.
View Article and Find Full Text PDFGenetic variation can alter brain structure and, consequently, function. Comparative statistical analysis of mouse brains across genetic backgrounds requires spatial, single-cell, atlas-scale data, in replicates-a challenge for current technologies. We introduce tlas-scale ranscriptome ocalization using ggregate ignatures (ATLAS), a scalable tissue mapping method.
View Article and Find Full Text PDFObjective: To understand the CD8+ tumour infiltrating lymphocyte (TIL) compartment of oesophageal adenocarcinoma (OAC) with regards to markers of lymphocyte exhaustion, tissue residency and to identify possible reasons behind differential responses to therapy.
Design: Tumour samples from 44 patients undergoing curative resection for OAC were assessed by flow cytometry for presence of antigen-experienced TILs and markers of activation and exhaustion. Populations of PD-1 and CD39 positive OAC TILs were sorted, and bulk RNA sequencing undertaken using a modified SmartSeq2 protocol.
Background: Clinician-led quality control into oncological decision-making is crucial for optimising patient care. Explainable artificial intelligence (XAI) techniques provide data-driven approaches to unravel how clinical variables influence this decision-making. We applied global XAI techniques to examine the impact of key clinical decision-drivers when mapped by a machine learning (ML) model, on the likelihood of receiving different oesophageal cancer (OC) treatment modalities by the multidisciplinary team (MDT).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2024
To test the hypothesis that an abiotic Earth and its inert atmosphere could form chemically reactive carbon- and nitrogen-containing compounds, we designed a plasma electrochemical setup to mimic lightning-induced electrochemistry under steady-state conditions of the early Earth. Air-gap electrochemical reactions at air-water-ground interfaces lead to remarkable yields, with up to 40 moles of carbon dioxide being reduced into carbon monoxide and formic acid, and 3 moles of gaseous nitrogen being fixed into nitrate, nitrite, and ammonium ions, per mole of transmitted electrons. Interfaces enable reactants (e.
View Article and Find Full Text PDFPromoting vaccine acceptance and demand is an essential, yet often underrecognized component of ensuring that everyone has access to the full benefits of immunization. Convened by the Sabin Vaccine Institute, the Vaccination Acceptance Research Network (VARN) is a global network of multidisciplinary stakeholders driving strengthened vaccination acceptance, demand, and delivery. VARN works to advance and apply social and behavioral science insights, research, and expertise to the challenges and opportunities facing vaccination decision-makers.
View Article and Find Full Text PDFCommunity engagement is vital to the development of people-centered, successful vaccination programs. The diverse Vaccination Acceptance Research Network (VARN) community brings together interdisciplinary professionals from across the immunization ecosystem who play a crucial role in vaccination acceptance, demand, and delivery. Over the course of the VARN2023 conference, researchers and practitioners alike shared ideas and experiences focused on strategies and approaches to building trust between communities and health systems to increase equity in vaccination.
View Article and Find Full Text PDFBackground: After two decades of extensive microbiome research, the current forefront of scientific exploration involves moving beyond description and classification to uncovering the intricate mechanisms underlying the coalescence of microbial communities. Deciphering microbiome assembly has been technically challenging due to their vast microbial diversity but establishing a synthetic community (SynCom) serves as a key strategy in unravelling this process. Achieving absolute quantification is crucial for establishing causality in assembly dynamics.
View Article and Find Full Text PDFIn a recent article, Wang (., 2020, , 10624) introduced a new class of interparticle potential for molecular simulations. The potential is defined by a single range parameter, eliminating the need to decide how to truncate truly long-range interactions like the Lennard-Jones (LJ) potential.
View Article and Find Full Text PDFThis learning solution shortens orientation times, reduces costs, and improves outcomes.
View Article and Find Full Text PDFMetal-organic framework (MOF) materials are a vast family of nanoporous solids with potential applications ranging from drug delivery to environmental remediation. Application of MOFs in these scenarios is hindered, however, by difficulties in MOF 'activation' after initial synthesis - removal of the synthesis solvent from the pores to make the pore space accessible - often leading to framework collapse if improperly performed. While experimental studies have correlated collapse to specific solvent properties and conditions, the mechanism of activation-collapse is currently unknown.
View Article and Find Full Text PDFAdenocarcinoma of the oesophagus and gastro-oesophageal junction represent a large burden of cancer death in the Western World with an increasing incidence. In the past two decades, the overall survival of patients on a potentially curative treatment pathway has more than doubled due to the addition of perioperative oncological therapies to surgery. However, patients often fail to respond to oncological treatment or struggle to complete their treatment after surgery.
View Article and Find Full Text PDFThe symptoms of pernicious anemia might resemble those of other common disorders and can be nonspecific, requiring extensive diagnostic workup. The provider must be aware of the harm pernicious anemia can do if undiagnosed and untreated and must understand that diligence and persistence are crucial for an accurate diagnosis.
View Article and Find Full Text PDFBackground: Rhabdomyosarcomas (RMS) are predominantly paediatric sarcomas thought to originate from muscle precursor cells due to impaired myogenic differentiation. Despite intensive treatment, 5-year survival for patients with advanced disease remains low (< 30%), highlighting a need for novel therapies to improve outcomes. Differentiation therapeutics are agents that induce differentiation of cancer cells from malignant to benign.
View Article and Find Full Text PDFFor external beam radiotherapy using photons or particles, upright patient positioning on a rotating, robotic chair (a gantry-less system) could offer substantial cost savings. In this study, we considered the feasibility of upright breast radiotherapy using a robotic radiotherapy chair, for (i) a cohort of 9 patients who received conventional supine radiotherapy using photons for a diagnosis of primary breast cancer, plus (ii) 7 healthy volunteers, selected to have relatively large bra cup sizes. We studied: overall body positioning, arm positioning, beam access, breast reproducibility, and comfort.
View Article and Find Full Text PDFThe first conference of the Vaccination Acceptance Research Network, VARN2022: Shaping Global Vaccine Acceptance with Localized Knowledge, was held virtually, from March 1 to 3 2022. This inaugural event brought together a global representation of experts to discuss key priorities and opportunities emerging across the ecosystem of vaccine acceptance and demand, from policies to programs and practice. Convened by the Sabin Vaccine Institute, VARN aims to support dialogue among multidisciplinary stakeholders to enhance the uptake of social and behavioral science-based solutions for vaccination decision-makers and implementers.
View Article and Find Full Text PDFThis study presents position changes of a few radiotherapy-relevant thoracic organs between upright and typical supine patient orientations. Using tools in a commercial treatment planning system (TPS), key anatomical distances were measured for four-dimensional CT data sets and analyzed for the two patient orientations. The uncertainty was calculated as the 95% confidence interval (CI) on the relative difference for each of the four analyzed changes for upright relative to supine, as follows: the distance of the bottom of the heart to the top of the sternum, it changed +2.
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