Publications by authors named "David Drew"

Background Waist circumference (WC) and its allometric counterpart, "a body shape index" (ABSI), are risk factors for colorectal cancer (CRC); however, it is uncertain whether associations with these body measurements are limited to specific molecular subtypes of the disease. Methods Data from 2,772 CRC cases and 3,521 controls were pooled from four cohort studies within the Genetics and Epidemiology of Colorectal Cancer Consortium. Four molecular markers (BRAF mutation, KRAS mutation, CpG island methylator phenotype, and microsatellite instability) were analysed individually and in combination (Jass-types).

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A polygenic risk score (PRS) is used to quantify the combined disease risk of many genetic variants. For complex human traits there is interest in determining whether the PRS modifies, i.e.

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plantations are a crucial global resource, offering raw materials for industries across five continents, including renewable energy sources, recyclable fibers, and eco-friendly wood products. To support sustainable management, ten wireless dendrometer and environmental sensor systems were deployed on trees-six in Stellenbosch, South Africa, and four in Leiria, Portugal. These systems measure tree stem growth, air and soil conditions, and transmit data via LoRaWAN to a cloud-based platform (ThingSpeak), with local SD-card backups.

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  • - Pregnancy may worsen the severity of SARS-CoV-2 and other respiratory infections, but the reasons behind this increased risk are not well understood.
  • - A study involving 226 women, including 152 pregnant and 74 non-pregnant, showed that pregnant women experience significant changes in T cell responses and immune functions after SARS-CoV-2 infection.
  • - The study found increased levels of interleukin-27 in pregnant women, which is linked to T cell exhaustion, suggesting that unique immune responses during pregnancy could make them more vulnerable to viral infections.
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Background: Metabolomic profiles may influence colorectal cancer (CRC) development. Few studies have performed prediagnostic metabolome-wide analyses with CRC risk.

Methods: We conducted a nested case-control study among women (Nurses' Health Study) and men (Health Professionals Follow-Up Study) who provided blood between 1989 and 1995.

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  • Colorectal cancer (CRC) is a major health concern, and understanding how genetic and environmental factors interact can help identify at-risk groups.
  • This study analyzed data from over 45,000 CRC cases to assess both multiplicative and additive interactions between genetic risk scores and various environmental factors, finding no multiplicative interactions but significant additive ones for high genetic susceptibility individuals.
  • Results suggest that individuals with high genetic risk could benefit more from lifestyle interventions like reducing alcohol intake or increasing fruit and fiber consumption, emphasizing the need for targeted prevention strategies in CRC care.
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Importance: Aspirin reduces the risk of colorectal cancer (CRC). Identifying individuals more likely to benefit from regular aspirin use for CRC prevention is a high priority.

Objective: To assess whether aspirin use is associated with the risk of CRC across different lifestyle risk factors.

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Introduction: Colorectal cancer (CRC) screening utilization is low among low-income, uninsured, and minority populations that receive care in community health centers (CHCs). There is a need for evidence-based interventions to increase screening and follow-up care in these settings.

Methods: A multilevel, multi-component pragmatic cluster randomized controlled trial is being conducted at 8 CHCs in two metropolitan areas (Boston and Los Angeles), with two arms: (1) Mailed FIT outreach with text reminders, and (2) Mailed FIT-DNA with patient support.

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  • Folate intake plays a crucial role in genetic and metabolic processes, and low levels are linked to higher cancer risk, specifically colorectal cancer (CRC).
  • The study analyzed dietary and supplemental folate intake among participants with CRC, investigating how this intake relates to specific genetic mutations using advanced sequencing techniques.
  • Results indicated that higher total folate intake generally reduced CRC risk, but the impact varied when considering mutation status in tumors, with a few specific gene mutations showing different associations with folate intake.
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Though artificial intelligence (AI) is being widely implemented in gastroenterology (GI) and hepatology and has the potential to be paradigm shifting for clinical practice, its pitfalls must be considered along with its advantages. Currently, although the use of AI is limited in practice to supporting clinical judgment, medicine is rapidly heading toward a global environment where AI will be increasingly autonomous. Broader implementation of AI will require careful ethical considerations, specifically related to bias, privacy, and consent.

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Background & Aims: Single-cell RNA sequencing (scRNA) has empowered many insights into gastrointestinal microenvironments. However, profiling human biopsies using droplet-based scRNA (D-scRNA) is challenging since it requires immediate processing to minimize epithelial cell damage. In contrast, picowell-based (P-scRNA) platforms permit short-term frozen storage before sequencing.

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Future climatic scenarios forecast increasingly frequent droughts that will pose substantial consequences on tree mortality. In light of this, drought-tolerant eucalypts have been propagated; however, the severity of these conditions will invoke adaptive responses, impacting the commercially valuable wood properties. To determine what mechanisms govern the wood anatomical adaptive response, highly controlled drought experiments were conducted in Eucalyptus grandis W.

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Intracellular potassium (K) homeostasis is fundamental to cell viability. In addition to channels, K levels are maintained by various ion transporters. One major family is the proton-driven K efflux transporters, which in gram-negative bacteria is important for detoxification and in plants is critical for efficient photosynthesis and growth.

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  • * Researchers analyzed data from 52 studies, including nearly 31,000 CRC cases and over 41,000 controls, to explore the genetic interactions with regular aspirin/NSAID use.
  • * They found significant interactions with genetic variants in two specific regions (6q24.1 and 5p13.1), which could help uncover new targets for understanding how aspirin provides its protective effects against colorectal cancer.
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  • Consumption of fiber, fruits, and vegetables may lower the risk of colorectal cancer (CRC), but genetic factors might influence this connection.
  • A large study involving nearly 70,000 participants identified two significant genetic variants linked to dietary intake and CRC risk using advanced statistical methods.
  • The findings suggest specific genetic loci (SLC26A3 and NEGR1) may affect how fiber and fruit consumption interacts with CRC risk, highlighting the need for more research on the underlying mechanisms.
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There is a high unmet need for early detection approaches for diffuse gastric cancer (DGC). We examined whether the stool proteome of mouse models of gastric cancer (GC) and individuals with hereditary diffuse gastric cancer (HDGC) have utility as biomarkers for early detection. Proteomic mass spectrometry of the stool of a genetically engineered mouse model driven by oncogenic KrasG12D and loss of p53 and Cdh1 in gastric parietal cells [known as Triple Conditional (TCON) mice] identified differentially abundant proteins compared with littermate controls.

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The number of patients with AKI receiving outpatient hemodialysis (AKI-D) is increasing. At present, on the basis of limited data, approximately one third of patients with AKI-D who receive outpatient dialysis after hospital discharge survive and regain sufficient kidney function to discontinue dialysis. Data to inform dialysis management strategies that promote kidney function recovery and processes of care among patients with AKI-D receiving outpatient dialysis are lacking.

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  • Menopausal hormone therapy (MHT) may lower the risk of colorectal cancer (CRC), especially in women with a higher genetic predisposition to the disease.
  • In a study of nearly 30,000 postmenopausal women, those in the highest genetic risk quartile saw a significantly greater reduction in CRC risk when using MHT compared to those in the lowest quartile.
  • The findings suggest that integrating genetic risk information could improve CRC risk predictions and inform the assessment of MHT benefits in postmenopausal women.
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Multidrug resistance-associated protein 2 (MRP2/ABCC2) is a polyspecific efflux transporter of organic anions expressed in hepatocyte canalicular membranes. MRP2 dysfunction, in Dubin-Johnson syndrome or by off-target inhibition, for example by the uricosuric drug probenecid, elevates circulating bilirubin glucuronide and is a cause of jaundice. Here, we determine the cryo-EM structure of rat Mrp2 (rMrp2) in an autoinhibited state and in complex with probenecid.

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Rationale & Objective: Kidney disease negatively affects cognition. We assessed the effect of kidney transplantation (KT) on different cognitive domains.

Study Design: Prospective cohort study.

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Transporting small molecules across cell membranes is an essential process in cell physiology. Many structurally diverse, secondary active transporters harness transmembrane electrochemical gradients of ions to power the uptake or efflux of nutrients, signalling molecules, drugs and other ions across cell membranes. Transporters reside in lipid bilayers on the interface between two aqueous compartments, where they are energized and regulated by symported, antiported and allosteric ions on both sides of the membrane and the membrane bilayer itself.

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Pregnancy is a risk factor for increased severity of SARS-CoV-2 and other respiratory infections. The mechanisms underlying this risk have not been well-established, partly due to a limited understanding of how pregnancy shapes immune responses. To gain insight into the role of pregnancy in modulating immune responses at steady state and upon perturbation, we collected peripheral blood mononuclear cells (PBMC), plasma, and stool from 226 women, including 152 pregnant individuals (n = 96 with SARS-CoV-2 infection and n = 56 healthy controls) and 74 non-pregnant women (n = 55 with SARS-CoV-2 and n = 19 healthy controls).

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  • Obesity is linked to various types of colorectal cancer (CRC), but the strength and cause of these links are not fully understood.
  • By using Mendelian randomization, researchers studied how body size traits like BMI, waist circumference, and body fat percentage affect risks for different CRC subtypes.
  • Results showed that higher BMI and body fat significantly increased the risks for serrated and alternate CRC pathways (Jass types 1, 2, and 3), while associations with the traditional pathway (Jass type 4) were weaker.
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Tripartite ATP-independent periplasmic (TRAP) transporters are secondary-active transporters that receive their substrates via a soluble-binding protein to move bioorganic acids across bacterial or archaeal cell membranes. Recent cryo-electron microscopy (cryo-EM) structures of TRAP transporters provide a broad framework to understand how they work, but the mechanistic details of transport are not yet defined. Here we report the cryo-EM structure of the -acetylneuraminate TRAP transporter (SiaQM) at 2.

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