Supporting evidence-based analysis for modified risk tobacco products through a toxicology data-sharing infrastructure

Abstract

The US FDA defines modified risk tobacco products (MRTPs) as products that aim to reduce harm or the risk of tobacco-related disease associated with commercially marketed tobacco products. Establishing a product’s potential as an MRTP requires scientific substantiation including toxicity studies and measures of disease risk relative to those of cigarette smoking. Best practices encourage verification of the data from such studies through sharing and open standards. Building on the experience gained from the OpenTox project, a proof-of-concept database and website ( INTERVALS) has been developed to share results from both in vivo inhalation studies and in vitro studies conducted by Philip Morris International R&D to assess candidate MRTPs. As datasets are often generated by diverse methods and standards, they need to be traceable, curated, and the methods used well described so that knowledge can be gained using data science principles and tools. The data-management framework described here accounts for the latest standards of data sharing and research reproducibility. Curated data and methods descriptions have been prepared in ISA-Tab format and stored in a database accessible via a search portal on the INTERVALS website. The portal allows users to browse the data by study or mechanism (e.g., inflammation, oxidative stress) and obtain information relevant to study design, methods, and the most important results. Given the successful development of the initial infrastructure, the goal is to grow this initiative and establish a public repository for 21 st-century preclinical systems toxicology MRTP assessment data and results that supports open data principles.

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

“…[166][167][168] Therefore, in the case of mycobacteria, the importance of TLR2, TLR4, and TLR9 in the development of the microbicidal response is paramount since the regulation of the intracellular cascade involves the binding of MyD88 and Mal, also known as TIRAP, which recruits IRAK1/4, TRAF6, and TRICA1 to induce the production of mitogen-activated protein kinase (MAPK) and NF-κB. [169][170][171] As a final outcome, NF-kB is responsible for inducing the production of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-1β, and IL-6 that participate in the activation of macrophages and enzymes such as iNOS, which is responsible the generation of ROS and destruction of the microorganism. 126,172,173 However, the immune evasion strategies adopted by mycobacteria include a series of events aimed at inactivating this mechanism.…”

Parental knowledge gaps and barriers for children receiving human papillomavirus vaccine in the Rio Grande Valley of Texas

“…[1][2][3][4][5][6][7][8][9] There has been increasing evidence supporting the safety and effectiveness of HPV vaccination in reducing vaccine-type HPV infections at the population level. 10,11 The HPV vaccine provides the greatest benefit to those who receive the vaccine before they become sexually active. 12,13 Although routine HPV vaccination has been recommended in the United States (US) since 2006 for females and 2011 for males ages 9-26 years, 14 disparities in knowledge and awareness about HPV and the HPV vaccine persist, and vaccination rates remain suboptimal.…”

<p>Altered amplitude of low-frequency fluctuation and regional cerebral blood flow in females with primary dysmenorrhea: a resting-state fMRI and arterial spin labeling study</p>

“…Of patients 56.3–80.34% describe their menstrual pain as moderate or severe pain,2–4 which has negative effects on individual daily and academic activities, quality of life and so on 3–6. At present, the most widely accepted pathogenesis for PD is the overproduction of uterine prostaglandins that stimulate myometrial contractions and cause ischemia during endometrial sloughing 7. However, definite pathophysiology remains to be investigated.…”