Modeling and Simulation of Acetaminophen Pharmacokinetics and Hepatic Biomarkers After Overdoses of Extended-Release and Immediate-Release Formulations in Healthy Adults Using the Quantitative Systems Toxicology Software Platform DILIsym.

Acetaminophen (APAP) has been formulated as immediate-, modified-, and extended-release tablets (APAP-IR, -MR, and -ER, respectively). However, there was concern that APAP-MR previously available in Europe could form a bezoar after a large overdose, leading to delayed absorption and atypical pharmacokinetics (PK) compared to APAP-IR, and that current treatment guidelines developed for APAP overdose to prevent severe hepatotoxicity are inappropriate for APAP-MR. In contrast, APAP-ER caplets available in the United States are designed with an IR layer and an erodible ER layer.

Sodium arsenite induces aggresome formation by promoting PICK1 BAR domain homodimer formation.

The aggresome is a perinuclear structure that sequesters misfolded proteins. It is implicated in various neurodegenerative diseases. The perinuclear structure enriched with protein interacting with C kinase 1 (PICK1) was found to be inducible by cellular stressors, colocalizing with microtubule-organizing center markers and ubiquitin, hence classifying it as an aggresome.

Understanding the role of risk preferences and perceptions in vaccination decisions and post-vaccination behaviors among U.S. households.

COVID-19 vaccines play a critical role in protecting against infection and transmission of the virus. Therefore, understanding public perceptions of COVID-19 vaccines is essential for successful vaccine promotion. Previous literature reported strong associations between vaccination decisions and several sociodemographic variables.

Peripartum cardiomyopathy: a global effort to find the cause and cure for the rare and little understood disease.

In this review, we present our current understanding of peripartum cardiomyopathy (PPCM) based on reports of the incidence, diagnosis and current treatment options. We summarise opinions on whether PPCM is triggered by vascular and/or hormonal causes and examine the influence of comorbidities such as preeclampsia. Two articles published in 2021 strongly support the hypothesis that PPCM may be a familial disease.

Perception versus preference: The role of self-assessed risk measures on individual mitigation behaviors during the COVID-19 pandemic.

In the midst of a global pandemic, prevention methods stand as a crucial first step toward addressing the public health crisis and controlling the spread of the virus. However, slowing the spread of the virus hinges on the public's willingness to follow a combination of mitigation practices to avoid contracting and transmitting the disease. In this study, we investigate the factors related to individuals' risk perceptions associated with COVID-19 as well as their general self-assessed risk preferences.

Assessment of a Polygenic Risk Score for Colorectal Cancer to Predict Risk of Lynch Syndrome Colorectal Cancer.

It was not known whether the polygenic risk scores (PRSs) that predict colorectal cancer could predict colorectal cancer for people with inherited pathogenic variants in DNA mismatch repair genes-people with Lynch syndrome. We tested a PRS comprising 107 established single-nucleotide polymorphisms associated with colorectal cancer in European populations for 826 European-descent carriers of pathogenic variants in DNA mismatch repair genes (293 , 314 , 126 , 71 , and 22 ) from the Colon Cancer Family Registry, of whom 504 had colorectal cancer. There was no evidence of an association between the PRS and colorectal cancer risk, irrespective of which DNA mismatch repair gene was mutated, or sex (all 2-sided >.

A streamlined model for use in clinical breast cancer risk assessment maintains predictive power and is further improved with inclusion of a polygenic risk score.

Five-year absolute breast cancer risk prediction models are required to comply with national guidelines regarding risk reduction regimens. Models including the Gail model are under-utilized in the general population for various reasons, including difficulty in accurately completing some clinical fields. The purpose of this study was to determine if a streamlined risk model could be designed without substantial loss in performance.

Correction: Public preferences for ecological indicators used in Everglades restoration.

[This corrects the article DOI: 10.1371/journal.pone.

Revisiting the Digital Divide in the COVID-19 Era.

The digital divide limits opportunities for those without ready access to Internet. Movement online of essential activities during COVID-19 took inadequate Internet service from inconvenient to emergency/crisis for many households. A negative correlation between rurality and Internet speed was found at the county level, highlighting the struggle for rural areas.

Application of the DILIsym® Quantitative Systems Toxicology drug-induced liver injury model to evaluate the carcinogenic hazard potential of acetaminophen.

In 2019, the California Office of Environmental Health Hazard Assessment (OEHHA) initiated a review of the carcinogenic hazard potential of acetaminophen. The objective of the analysis herein was to inform this review by assessing whether variability in patient baseline characteristics (e.g.

#Eggs: social and online media-derived perceptions of egg-laying hen housing.

Enormous quantities of data are generated through social and online media in the era of Web 2.0. Understanding consumer perceptions or demand efficiently and cost effectively remains a focus for economists, retailer/consumer sciences, and production industries.

Public preferences for ecological indicators used in Everglades restoration.

The Everglades is one of the largest wetland ecosystems in the world covering almost 18,000 square miles from central Florida southward to Florida Bay. Over the 20th century, efforts to drain the Everglades for agriculture and development severely damaged the ecosystem so that today roughly 50% of the historic flow of water through the Everglades has been diverted elsewhere. In an attempt to restore the Everglades, the U.

Public Perceptions of Veterinarians from Social and Online Media Listening.

The public perception of the veterinary medicine profession is of increasing concern given the mounting challenges facing the industry, ranging from student debt loads to mental health implications arising from compassion fatigue, euthanasia, and other challenging aspects of the profession. This analysis employs social media listening and analysis to discern top themes arising from social and online media posts referencing veterinarians. Social media sentiment analysis is also employed to aid in quantifying the search results, in terms of whether they are positivity/negativity associated.

Author Correction: Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Gastroesophageal reflux GWAS identifies risk loci that also associate with subsequent severe esophageal diseases.

Gastroesophageal reflux disease (GERD) is caused by gastric acid entering the esophagus. GERD has high prevalence and is the major risk factor for Barrett's esophagus (BE) and esophageal adenocarcinoma (EA). We conduct a large GERD GWAS meta-analysis (80,265 cases, 305,011 controls), identifying 25 independent genome-wide significant loci for GERD.

Association Analysis of a Microsatellite Repeat in the Gene With Prostate Cancer Risk, Aggressiveness and Survival.

With an estimated 1.1 million men worldwide diagnosed with prostate cancer yearly, effective and more specific biomarkers for early diagnosis could lead to better patient outcome. As such, novel genetic markers are sought for this purpose.

Meat packaging, preservation, and marketing implications: Consumer preferences in an emerging economy.

Meat is a perishable food which appears in the market in a variety of forms. Using a choice experiment survey conducted across four Chinese cities, this paper studies consumers' preferences for packaging and preservation methods and place of origin for fresh pork. Results showed that Chinese consumers preferred chilled and locally produced pork packaged in plastic.

Impairment of Inhibitory Synapse Formation and Motor Behavior in Mice Lacking the NL2 Binding Partner LHFPL4/GARLH4.

Normal brain functions depend on the balanced development of excitatory and inhibitory synapses. Our knowledge of the molecular mechanisms underlying inhibitory synapse formation is limited. Neuroligin-2 (NL2), a transmembrane protein at inhibitory postsynaptic sites, is capable of initiating inhibitory synapse formation.

A novel tissue treatment to reduce mineralization of bovine pericardial heart valves.

Objective: With the increasing use of bioprostheses worldwide, continuous efforts have been made to improve tissue durability. We introduce a new treatment for bovine pericardium combining octanediol-ethanol based phospholipid removal with taurine-based glutaraldehyde neutralization and storage in an aldehyde-free solution (FREE).

Methods: Treated tissues were evaluated by mechanical and biochemical characterization, phospholipid content, aldehyde levels, cell cultures on pericardial samples (L929 fibroblasts and human umbilical vein endothelial cells), rat subcutaneous implantations, and long-term juvenile sheep mitral valve implantations (n = 3).

A microsatellite repeat in PCA3 long non-coding RNA is associated with prostate cancer risk and aggressiveness.

Short tandem repeats (STRs) are repetitive sequences of a polymorphic stretch of two to six nucleotides. We hypothesized that STRs are associated with prostate cancer development and/or progression. We undertook RNA sequencing analysis of prostate tumors and adjacent non-malignant cells to identify polymorphic STRs that are readily expressed in these cells.