The PubPeer conundrum: Administrative challenges in research misconduct proceedings.

The founders of PubPeer envisioned their website as an online form of a "journal club" that would facilitate post-publication peer review. Recently, PubPeer comments have led to a significant number of research misconduct proceedings - a development that could not have been anticipated when the current federal research misconduct regulations were developed two decades ago. Yet the number, frequency, and velocity of PubPeer comments identifying data integrity concerns, and institutional and government practices that treat all such comments as potential research misconduct allegations, have overwhelmed institutions and threaten to divert attention and resources away from other research integrity initiatives.

Assigning mutational signatures to individual samples and individual somatic mutations with SigProfilerAssignment.

Motivation: Analysis of mutational signatures is a powerful approach for understanding the mutagenic processes that have shaped the evolution of a cancer genome. To evaluate the mutational signatures operative in a cancer genome, one first needs to quantify their activities by estimating the number of mutations imprinted by each signature.

Results: Here we present SigProfilerAssignment, a desktop and an online computational framework for assigning all types of mutational signatures to individual samples.

Optimization of Culture and Aerosolization in a Murine Model of Inhalational Fungal Exposure.

is ubiquitous in the environment and is particularly abundant in damp indoor spaces. Exposure to species, as well as other environmental fungi, has been linked to respiratory health outcomes, including asthma, allergy, and even local or disseminated infection. However, the pulmonary immunological mechanisms associated with repeated exposure to have remained relatively uncharacterized.

Defining "recklessness" in research misconduct proceedings.

To find research misconduct in research that has been supported by federal funds, an institution must determine that the misconduct was committed intentionally, knowingly, or recklessly. "Intentional" and "knowing" are straightforward standards. Yet "reckless" often mystifies institutions, which struggle to assess whether a respondent's conduct should be deemed "reckless," or merely negligent.

Visualizing and exploring patterns of large mutational events with SigProfilerMatrixGenerator.

Background: All cancers harbor somatic mutations in their genomes. In principle, mutations affecting between one and fifty base pairs are generally classified as small mutational events. Conversely, large mutational events affect more than fifty base pairs, and, in most cases, they encompass copy-number and structural variants affecting many thousands of base pairs.

Topography of mutational signatures in human cancer.

The somatic mutations found in a cancer genome are imprinted by different mutational processes. Each process exhibits a characteristic mutational signature, which can be affected by the genome architecture. However, the interplay between mutational signatures and topographical genomic features has not been extensively explored.

Assigning mutational signatures to individual samples and individual somatic mutations with SigProfilerAssignment.

Analysis of mutational signatures is a powerful approach for understanding the mutagenic processes that have shaped the evolution of a cancer genome. Here we present SigProfilerAssignment, a desktop and an online computational framework for assigning all types of mutational signatures to individual samples. SigProfilerAssignment is the first tool that allows both analysis of copy-number signatures and probabilistic assignment of signatures to individual somatic mutations.

Visualizing and exploring patterns of large mutational events with SigProfilerMatrixGenerator.

Background: All cancers harbor somatic mutations in their genomes. In principle, mutations affecting between one and fifty base pairs are generally classified as small mutational events. Conversely, large mutational events affect more than fifty base pairs, and, in most cases, they encompass copy-number and structural variants affecting many thousands of base pairs.

Uncovering novel mutational signatures by extraction with SigProfilerExtractor.

Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for extraction of mutational signatures, and benchmark it against another 13 bioinformatics tools by using 34 scenarios encompassing 2,500 simulated signatures found in 60,000 synthetic genomes and 20,000 synthetic exomes. For simulations with 5% noise, reflecting high-quality datasets, SigProfilerExtractor outperforms other approaches by elucidating between 20% and 50% more true-positive signatures while yielding 5-fold less false-positive signatures.

Applying Civil Rights Law to Clinical Research: Title VI's Equal Access Mandate.

Title VI of the Civil Rights Act of 1964 and its implementing regulations prohibit federally-funded educational institutions and healthcare centers from engaging in disparate impact discrimination "on the ground of race, color, or national origin" in all of their operations.

Mapping clustered mutations in cancer reveals APOBEC3 mutagenesis of ecDNA.

Clustered somatic mutations are common in cancer genomes and previous analyses reveal several types of clustered single-base substitutions, which include doublet- and multi-base substitutions, diffuse hypermutation termed omikli, and longer strand-coordinated events termed kataegis. Here we provide a comprehensive characterization of clustered substitutions and clustered small insertions and deletions (indels) across 2,583 whole-genome-sequenced cancers from 30 types of cancer. Clustered mutations were highly enriched in driver genes and associated with differential gene expression and changes in overall survival.

CX3CR1-Expressing Myeloid Cells Regulate Host-Helminth Interaction and Lung Inflammation.

Many helminth life cycles, including hookworm, involve a mandatory lung phase, where myeloid and granulocyte subsets interact with the helminth and respond to infection-induced lung injury. To evaluate these innate subsets in Nippostrongylus brasiliensis infection, reporter mice for myeloid cells (CX3CR1 ) and granulocytes (PGRP ) are employed. Nippostrongylus infection induces lung infiltration of reporter cells, including CX3CR1 myeloid cells and PGRP eosinophils.

Cookstove Emissions and Performance Evaluation Using a New ISO Protocol and Comparison of Results with Previous Test Protocols.

In 2018, the International Organization for Standardization (ISO) 19867-1 "Harmonized laboratory test protocols" were released for establishing improved quality and comparability for data on cookstove air pollutant emissions, efficiency, safety, and durability. This is the first study that compares emissions [carbon dioxide, carbon monoxide, total hydrocarbons, methane, nitrogen oxides, fine particulate matter (PM), organic carbon, elemental carbon, and ultrafine particles] and efficiency data between the ISO protocol and the Water Boiling Test (WBT). The study examines six stove/fuel combinations [liquefied petroleum gas (LPG), pellet, wood fan, wood rocket, three stone fire, and charcoal] tested in the same US EPA laboratory.

Demystifying for the cross-border transfer of clinical research data.

The Courts of Justice of the European Union (CJEU) held in its July 2020 decision that, in order for entities in other countries to import personal data from the European Economic Area (EEA), the importer must be able to provide data protections 'essentially equivalent' to those the EEA offers under its General Data Protection Regulation. The CJEU expressed particular concern that United States' national security intelligence gathering laws prevent U.S.

Inhalation Triggers Neuroimmune, Glial, and Neuropeptide Transcriptional Changes.

Increasing evidence associates indoor fungal exposure with deleterious central nervous system (CNS) health, such as cognitive and emotional deficits in children and adults, but the specific mechanisms by which it might impact the brain are poorly understood. Mice were exposed to filtered air, heat-inactivated r (3 × 10 spores), or viable r (3 × 10 spores) via nose-only inhalation exposure 2 times per week for 1, 2, or 4 weeks. Analysis of cortex, midbrain, olfactory bulb, and cerebellum tissue from mice exposed to viable r spores for 1, 2, and 4 weeks revealed significantly elevated pro-inflammatory () and glial activity ( and ) gene expression in several brain regions when compared to filtered air control, with the most consistent and pronounced neuroimmune response 48H following the 4-week exposure in the midbrain and frontal lobe.

Morphology and quantification of fungal growth in residential dust and carpets.

Mold growth indoors is associated with negative human health effects, and this growth is limited by moisture availability. Dust deposited in carpet is an important source of human exposure due to potential elevated resuspension compared to hard floors. However, we need an improved understanding of fungal growth in dust and carpet to better estimate human exposure.

Ethical and Practical Concerns about IRB Restrictions on the Use of Research Data.

In response to researcher noncompliance with ethical and regulatory provisions governing research with humans, protocol deviations, and unanticipated problems with research, institutional review boards (IRBs) or institutions sometimes impose restrictions on the use of research data, although specific cases in which this happens are unlikely to be known publicly. We review IRB policies at top research institutions in the United States about restrictions on the use of research data and describe potential reasons for restricting the use of such data in the context of ensuring compliance with human subjects research standards. We also discuss ethical considerations related to restricting the use of research data and argue that IRBs have limited regulatory authority to take such actions.

Generating realistic null hypothesis of cancer mutational landscapes using SigProfilerSimulator.

Background: Performing a statistical test requires a null hypothesis. In cancer genomics, a key challenge is the fast generation of accurate somatic mutational landscapes that can be used as a realistic null hypothesis for making biological discoveries.

Results: Here we present SigProfilerSimulator, a powerful tool that is capable of simulating the mutational landscapes of thousands of cancer genomes at different resolutions within seconds.