Normal absolute neutrophil count (ANC) variations, as seen with Duffy-null associated neutrophil count (DANC), are not accounted for in trial eligibility, which may contribute to racial enrollment ...disparities. We describe ANC eligibility for pediatric oncology phase I/II clinical trials according to primary sponsorship from 2010 to 2023 using ClinicalTrials.gov. Out of 438 trials, 20% were industry-sponsored. Total 17% of trials required ANC ≥1500 cells/μL for enrollment; however, industry-sponsored trials were significantly more likely to require ANC ≥1500 cells/μL than non-industry-sponsored trials (odds ratio 2.53, 95% confidence interval: 1.39-4.62; p < .001). These data suggest laboratory exclusion criteria are one possible mechanism for pediatric clinical trial enrollment disparities.
Whole grain and fiber intakes may decrease the risk of colorectal cancer. The interplay between host genetic factors, colonization of specific bacteria, production of short-chain fatty acids (SCFA), ...and intake of whole grains and fiber could alter the protective role of carbohydrates against colorectal cancer. Here, we assessed intakes of types and sources of carbohydrates in 114,217 UK Biobank participants with detailed dietary data (2-5 24-hour dietary assessments), and a host polygenic score (PGS) was applied to categorize participants as high or low for intraluminal microbial SCFA production, namely, butyrate and propionate. Multivariable Cox proportional hazards models were used to determine the associations of carbohydrates and SCFA with colorectal cancer incidence. During a median follow-up of 9.4 years, 1,193 participants were diagnosed with colorectal cancer. Risk was inversely associated with intakes of non-free sugar and whole grain fiber. Evidence of heterogeneity was observed by the butyrate PGS; consuming higher amounts of whole grain starch was only associated with a lower risk of colorectal cancer in those with predicted high SCFA production. Similarly, in additional analyses utilizing the larger UK Biobank cohort (N = 343,621) with less detailed dietary assessment, only individuals with a high genetically predicted butyrate production had a lower risk of colorectal cancer per 5 g/day intake of bread and cereal fiber. This study suggests that colorectal cancer risk varies by intake of carbohydrate types and sources, and the impact of whole grain intake may be modified by SCFA production.
Prospective population-level analyses provide evidence supporting the importance of butyrate production in reduction of colorectal cancer risk by whole grain consumption.
Background: Significant mitigation efforts beyond the Nationally Determined Commitments (NDCs) coming out of the 2015 Paris Climate Agreement are required to avoid warming of 2 °C above ...pre-industrial temperatures. Health co-benefits represent selected near term, positive consequences of climate policies that can offset mitigation costs in the short term before the beneficial impacts of those policies on the magnitude of climate change are evident. The diversity of approaches to modeling mitigation options and their health effects inhibits meta-analyses and syntheses of results useful in policy-making. Methods/Design: We evaluated the range of methods and choices in modeling health co-benefits of climate mitigation to identify opportunities for increased consistency and collaboration that could better inform policy-making. We reviewed studies quantifying the health co-benefits of climate change mitigation related to air quality, transportation, and diet published since the 2009 Lancet Commission 'Managing the health effects of climate change' through January 2017. We documented approaches, methods, scenarios, health-related exposures, and health outcomes. Results/Synthesis: Forty-two studies met the inclusion criteria. Air quality, transportation, and diet scenarios ranged from specific policy proposals to hypothetical scenarios, and from global recommendations to stakeholder-informed local guidance. Geographic and temporal scope as well as validity of scenarios determined policy relevance. More recent studies tended to use more sophisticated methods to address complexity in the relevant policy system. Discussion: Most studies indicated significant, nearer term, local ancillary health benefits providing impetus for policy uptake and net cost savings. However, studies were more suited to describing the interaction of climate policy and health and the magnitude of potential outcomes than to providing specific accurate estimates of health co-benefits. Modeling the health co-benefits of climate policy provides policy-relevant information when the scenarios are reasonable, relevant, and thorough, and the model adequately addresses complexity. Greater consistency in selected modeling choices across the health co-benefits of climate mitigation research would facilitate evaluation of mitigation options particularly as they apply to the NDCs and promote policy uptake.
Evidence concerning intakes of protein or sources of dairy protein and risks of colorectal, breast, and prostate cancers is inconclusive.
Using a subsample of UK Biobank participants who completed ≥2 ...(maximum of 5) 24-h dietary assessments, we estimated intakes of total protein, protein from total dairy products, milk, and cheese, and dietary calcium in 114,217 participants. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using multivariable-adjusted Cox regression.
After a median of 9.4 years of follow-up, 1193 colorectal, 2024 female breast, and 2422 prostate cancer cases were identified. There were inverse associations of total dairy protein, protein from milk, and dietary calcium intakes with colorectal cancer incidence (HR
:0.80, 95% CI: 0.67-0.94; 0.79, 0.67-0.94; 0.71, 0.58-0.86, respectively). We also observed positive associations of milk protein and dietary calcium with prostate cancer risk (HR
:1.12, 1.00-1.26 and 1.16, 1.01-1.33, respectively). No significant associations were observed between intake of dairy protein and breast cancer risk. When insulin-like growth factor-I concentrations measured at recruitment were added to the multivariable-adjusted models, associations remained largely unchanged. Analyses were also similar when looking at total grams of dairy products, milk, and cheese.
Further research is needed to understand the mechanisms underlying the relationships of dairy products with cancer risk and the potential roles of dietary protein and calcium.
This study examines the reactivity of a series of copper(I) sulfide complexes stabilized by the expanded-ring N-heterocyclic carbene (NHC) ...1,3-bis(2,6-diisopropylphenyl)-4,5,6,7-tetrahydro-1,3-diazepin-2-ylidene (7Dipp) toward the nitrosonium ion (NO+). 7Dipp is shown to support neutral sulfide- and disulfide-bridged dicopper(I) complexes, as well as mononuclear copper(I) hydrosulfide. The addition of NO+ to each of these results in the formation of NHC-supported copper(I) cations and elemental sulfur. Reduction of copper(I) to copper(0) is observed upon reaction of NO+ with dicopper(I) sulfide or disulfide, whereas ammonium ion formation is observed upon reaction of copper(I) hydrosulfide with NO+. Ammonium ion formation is likewise observed upon reaction of NO+ with (7Dipp)copper(I) hydride.
The utility of lipid screening in pediatric settings for preventing adult atherosclerotic cardiovascular diseases partly depends on the lifelong tracking of lipid levels. This systematic review aimed ...to quantify the tracking of lipid levels from childhood and adolescence to adulthood.
We systematically searched MEDLINE, Embase, Web of Science, and Google Scholar in March 2022. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; ID: CRD42020208859). We included cohort studies that measured tracking of lipids from childhood or adolescence (<18 years) to adulthood (≥18) with correlation or tracking coefficients. We estimated pooled correlation and tracking coefficients using random-effects meta-analysis. Risk of bias was assessed with a review-specific tool.
Thirty-three studies of 19 cohorts (11,020 participants) were included. The degree of tracking from childhood and adolescence to adulthood differed among lipids. Tracking was observed for low-density lipoprotein cholesterol (pooled r = 0.55–0.65), total cholesterol (pooled r = 0.51–0.65), high-density lipoprotein cholesterol (pooled r = 0.46–0.57), and triglycerides (pooled r = 0.32–0.40). Only one study included tracking of non-high-density lipoprotein cholesterol (r = 0.42–0.59). Substantial heterogeneity was observed. Study risk of bias was moderate, mostly due to insufficient reporting and singular measurements at baseline and follow-up.
Early-life lipid measurements are important for predicting adult levels. However, further research is needed to understand the tracking of non-high-density lipoprotein cholesterol and the stability of risk classification over time, which may further inform pediatric lipid screening and assessment strategies.
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•Over 40 years of data from longitudinal studies inform lipid level tracking from childhood/adolescence to adulthood.•We performed meta-analysis of 33 studies (19 cohorts, 11,020 participants) meeting inclusion criteria.•Meta-analysis highlighted strongest tracking in LDL-C and total cholesterol, followed by HDL-C and triglycerides.•Our systematic review outlined a research gap in non-HDL cholesterol tracking.•Study risk of bias was moderate, mostly due to insufficient reporting.
The 2023 Marburg virus disease outbreaks in Equatorial Guinea and Tanzania highlighted the importance of better understanding this lethal pathogen. We did a systematic review (PROSPERO ...CRD42023393345) of peer-reviewed articles reporting historical outbreaks, modelling studies, and epidemiological parameters focused on Marburg virus disease. We searched PubMed and Web of Science from database inception to March 31, 2023. Two reviewers evaluated all titles and abstracts with consensus-based decision making. To ensure agreement, 13 (31%) of 42 studies were double-extracted and a custom-designed quality assessment questionnaire was used for risk of bias assessment. We present detailed information on 478 reported cases and 385 deaths from Marburg virus disease. Analysis of historical outbreaks and seroprevalence estimates suggests the possibility of undetected Marburg virus disease outbreaks, asymptomatic transmission, or cross-reactivity with other pathogens, or a combination of these. Only one study presented a mathematical model of Marburg virus transmission. We estimate an unadjusted, pooled total random effect case fatality ratio of 61·9% (95% CI 38·8–80·6; I2=93%). We identify epidemiological parameters relating to transmission and natural history, for which there are few estimates. This systematic review and the accompanying database provide a comprehensive overview of Marburg virus disease epidemiology and identify key knowledge gaps, contributing crucial information for mathematical models to support future Marburg virus disease epidemic responses.
In hypertrophic cardiomyopathy (HCM), myocyte disarray and microvascular disease (MVD) have been implicated in adverse events, and recent evidence suggests that these may occur early. As novel ...therapy provides promise for disease modification, detection of phenotype development is an emerging priority. To evaluate their utility as early and disease-specific biomarkers, we measured myocardial microstructure and MVD in 3 HCM groups-overt, either genotype-positive (G+LVH+) or genotype-negative (G-LVH+), and subclinical (G+LVH-) HCM-exploring relationships with electrical changes and genetic substrate.
This was a multicenter collaboration to study 206 subjects: 101 patients with overt HCM (51 G+LVH+ and 50 G-LVH+), 77 patients with G+LVH-, and 28 matched healthy volunteers. All underwent 12-lead ECG, quantitative perfusion cardiac magnetic resonance imaging (measuring myocardial blood flow, myocardial perfusion reserve, and perfusion defects), and cardiac diffusion tensor imaging measuring fractional anisotropy (lower values expected with more disarray), mean diffusivity (reflecting myocyte packing/interstitial expansion), and second eigenvector angle (measuring sheetlet orientation).
Compared with healthy volunteers, patients with overt HCM had evidence of altered microstructure (lower fractional anisotropy, higher mean diffusivity, and higher second eigenvector angle; all
<0.001) and MVD (lower stress myocardial blood flow and myocardial perfusion reserve; both
<0.001). Patients with G-LVH+ were similar to those with G+LVH+ but had elevated second eigenvector angle (
<0.001 after adjustment for left ventricular hypertrophy and fibrosis). In overt disease, perfusion defects were found in all G+ but not all G- patients (100% 51/51 versus 82% 41/50;
=0.001). Patients with G+LVH- compared with healthy volunteers similarly had altered microstructure, although to a lesser extent (all diffusion tensor imaging parameters;
<0.001), and MVD (reduced stress myocardial blood flow
=0.015 with perfusion defects in 28% versus 0 healthy volunteers
=0.002). Disarray and MVD were independently associated with pathological electrocardiographic abnormalities in both overt and subclinical disease after adjustment for fibrosis and left ventricular hypertrophy (overt: fractional anisotropy: odds ratio for an abnormal ECG, 3.3,
=0.01; stress myocardial blood flow: odds ratio, 2.8,
=0.015; subclinical: fractional anisotropy odds ratio, 4.0,
=0.001; myocardial perfusion reserve odds ratio, 2.2,
=0.049).
Microstructural alteration and MVD occur in overt HCM and are different in G+ and G- patients. Both also occur in the absence of hypertrophy in sarcomeric mutation carriers, in whom changes are associated with electrocardiographic abnormalities. Measurable changes in myocardial microstructure and microvascular function are early-phenotype biomarkers in the emerging era of disease-modifying therapy.
The Oxford WebQ is an online 24 h dietary assessment tool used by several large prospective studies. This study describes the creation of the new individual fatty acid (FA) dataset for the Oxford ...WebQ and reports intakes and sources of dietary individual FAs in the UK Biobank. Participants who completed ≥1 (maximum of five) 24 h dietary assessments were included (
= 207,997). Nutrient intakes were obtained from the average of all completed 24 h dietary assessments. Nutrient data from the UK McCance and Widdowson's The Composition of Foods and the US Department of Agriculture food composition tables were used to calculate intakes of 21 individual FAs. The individual FA dataset included 10 saturated fatty acids (SFAs), 4 monounsaturated fatty acids (MUFAs), and 7 polyunsaturated fatty acids (PUFAs; including alpha-linolenic (18:3), eicosapentaenoic (20:5), and docosahexaenoic (22:6) acids). Palmitic (16:0; mean ± standard deviation (SD): 13.5 ± 5.7 g/d) and stearic (18:0; 5.2 ± 2.5) acids were the main contributors to SFAs, and the main sources of these were cereals and cereal products (mostly desserts/cakes/pastries), milk and milk products (mostly cheese and milk), and meat and meat products. Oleic acid (18:1; 24.2 ± 9.8) was the main MUFA, derived mainly from cereals and cereal products, and meat and meat products. Linoleic acid (18:2; 9.7 ± 4.3) was the main PUFA, derived mostly from cereals and cereal products, and vegetables (including potatoes) and vegetable dishes. The individual FA dataset for the Oxford WebQ will allow future investigations on individual FAs and disease risk.
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