Knowledge overconfidence is associated with anti-consensus views on controversial scientific issues

Public attitudes that are in opposition to scientific consensus can be disastrous and include rejection of vaccines and opposition to climate change mitigation policies. Five studies examine the interrelationships between opposition to expert consensus on controversial scientific issues, how much people actually know about these issues, and how much they think they know. Across seven critical issues that enjoy substantial scientific consensus, as well as attitudes toward COVID-19 vaccines and mitigation measures like mask wearing and social distancing, results indicate that those with the highest levels of opposition have the lowest levels of objective knowledge but the highest levels of subjective knowledge. Implications for scientists, policymakers, and science communicators are discussed

Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs

This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

A catchment-scale assessment of stream temperature response to contemporary forest harvesting in the Oregon Coast Range

Historical forest harvesting practices were reviewed in the original Alsea Watershed Study where they found increased energy loading to the stream and produced higher stream temperatures. This was an important early research site that led to the development of contemporary forest management practices to protect water quality and fish habitat in Oregon and elsewhere. Here we present an analysis of 6 years (3 years pre-harvest and 3 years post-harvest) of summer stream temperature data from a reference (Flynn Creek) and a harvested catchment (Needle Branch). The collected parameters include air temperature, the mean and max, stream temperature, mean and max, and the diel (daily) temperature fluctuations (max minus the minimum temperature)

The diagnostic impact of UK regional variations in age‐specific prostate‐specific antigen guidelines

The ideal prostate cancer diagnostic pathway would maximise detection of clinically-significant prostate cancer (csPCa) while avoiding unnecessary biopsies and other investigations. The introduction of pre-biopsy MRI has done much to aid this goal. However, referrals into the image-based diagnostic pathway still depends on prostate-specific antigen (PSA) testing performed in primary care and interpreted using referral guidelines. In the UK, the National Institute for Health and Care Excellence (NICE) only provides guidance on PSA thresholds for men aged 50-69 years (PSA ≥3.0 ng/mL) [1]. For other age groups, PSA thresholds are set by regional cancer networks without any national consensus. Here we explored if different regional guidelines impacted csPCa detection in modern image-based pathways

Clinical features of spinal and bulbar muscular atrophy

Spinal and bulbar muscular atrophy is an X-linked motor neuron disease caused by a CAG repeat expansion in the androgen receptor gene. To characterize the natural history and define outcome measures for clinical trials, we assessed the clinical history, laboratory findings and muscle strength and function in 57 patients with genetically confirmed disease. We also administered self-assessment questionnaires for activities of daily living, quality of life and erectile function. We found an average delay of over 5 years from onset of weakness to diagnosis. Muscle strength and function correlated directly with serum testosterone levels and inversely with CAG repeat length, age and duration of weakness. Motor unit number estimation was decreased by about half compared to healthy controls. Sensory nerve action potentials were reduced in nearly all subjects. Quantitative muscle assessment and timed 2 min walk may be useful as meaningful indicators of disease status. The direct correlation of testosterone levels with muscle strength indicates that androgens may have a positive effect on muscle function in spinal and bulbar muscular atrophy patients, in addition to the toxic effects described in animal models

Alsea watershed study revisited: unpublished temperature datasets from pre-harvest 2006 to 2010

These data contain temperature readings from dataloggers launched in Deer Creek, Flynn Creek, and Needle Branch from 2006 to 2010. These loggers were apart of the Alsea Watershed Revisisted Study Revisited articles, but the data was incomplete due to logging gaps, temperature spikes, or other issues. The "Thermistor Functionality" datasets indicate whether dataloggers launched in each stream have complete datasets or not. Despite these data not being complete, they help tell the data collection story for the Alsea Watershed Study Revisited

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches