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Background: People with HIV are at increased risk for lung cancer and multimorbidity, complicating the balance of risks and benefits of lung cancer screening. We previously adapted Decision Precision (screenlc.com) to guide shared decision-making for lung cancer screening in people with HIV., Research Question: Does an HIV-adapted and personally tailored decision aid improve shared decision-making regarding lung cancer screening in people with HIV as measured by knowledge, decisional conflict, and acceptability?, Study Design and Methods: This was a single-arm pilot trial of the decision aid in 40 participants with HIV eligible for lung cancer screening. The decision aid included personalized screening recommendations and HIV-specific, 5-year risk estimates of lung cancer and all-cause mortality. Participants reviewed the decision aid at shared decision-making visits and completed previsit and postvisit surveys with measures of knowledge about lung cancer screening, acceptability, and decisional conflict., Results: The 40 enrolled participants were a median age of 62 years, 60% currently smoked, and they had median 5-year risks of lung cancer and all-cause mortality of 2.0% (IQR, 1.4%-3.3%) and 4.1% (IQR, 3.3%-7.9%), respectively. Personalized recommendations included "Encourage Screening" for 53% of participants and "Preference Sensitive" recommendations for the remainder. Participants showed improvement in two validated knowledge measures with relative improvement of 60% (P < 0.001) on the 12-question lung cancer screening knowledge test and 27% (P < .001) on the seven-question lung cancer screening knowledge score, with significant improvement on questions regarding false-positive and false-negative findings, incidental findings, lung cancer-specific mortality benefit, and the possible harms of screening. Participants reported low scores on the decisional conflict scale (median score, 0; interquartile range, 0-5) and high acceptability. Ninety percent of patients ultimately underwent screening within 1 month of the visit., Interpretation: In our study, this HIV-adapted and personally tailored decision aid improved participants' knowledge of risks, benefits, and characteristics of screening with low decisional conflict and high acceptability. Our results indicate that this decision aid can enable high-quality shared decision-making in this high-risk population., Clinical Trial Registration: ClinicalTrials.gov; No.: NCT04682301; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: M. T. reports unrelated consultation fees from G02 Foundation. None declared (N. R. M., K. C., M. S., J. Z. B., M. C. B., B. J. W., N. G., T. C., K. Durette, K. DeCell)., (Copyright © 2024 American College of Chest Physicians. All rights reserved.)

Background: Adenoma detection rate and interval colon cancer rates are associated with bowel preparation quality. The US Multisociety Task Force recommends repeat colonoscopy for individuals with inadequate bowel preparation (IBP) within 1 year. However, little is known regarding the rate and associated factors of repeat colonoscopy after IBP., Methods: Individuals undergoing colonoscopy for screening, surveillance, positive fecal immunohistochemistry test, and virtual colonoscopy at the Minneapolis Veterans Affairs Medical Center from January 2016 to October 2021 were included. IBP was classified based on Boston Bowel Preparation Scale score or Aronchick scale., Results: A total of 10,466 individuals were included, of which 571 (5.5%) had IBP. Repeat colonoscopy within 1 year was recommended for 485 individuals (84.9%); 287 (59.2%) were completed within this time period and 126 (26.0%) never underwent repeat colonoscopy. Proximity to the endoscopy center was associated with a higher rate of repeat colonoscopy within 1 year (61.7% vs 51.0%, P = .02). Current smoking status was associated with a lower rate of repeat colonoscopy within 1 year (25.8% vs 35.9%, P = .02). There were no differences in age, sex, race, inflammatory bowel disease diagnosis, or opioid or anticoagulation use with adherence to repeat colonoscopy within 1 year. There was no difference in adherence to a timely repeat colonoscopy from 1 year before the COVID-19 pandemic (58.9%) vs 1 year postpandemic (59.9%)., Conclusions: The rate of IBP was 5.5%. Only 59.2% of those with IBP underwent recommended repeat colonoscopy within 1 year, and 26.0% never underwent repeat colonoscopy. Additional efforts are needed to ensure that individuals with IBP return for timely repeat colonoscopy., Competing Interests: Author disclosures: Brian Hanson is a consultant for Motus GI. Mohammad Bilal is a consultant for Boston Scientific. The other authors report no actual or potential conflicts of interest with regard to this article., (Copyright © 2024 Frontline Medical Communications Inc., Parsippany, NJ, USA.)

An estimated 1 in 10 000 people are born without the ability to smell, a condition known as congenital anosmia, and about one third of those people have non-syndromic, or isolated congenital anosmia (ICA). Despite the significant impact of olfaction for our quality of life, the underlying causes of ICA remain largely unknown. Using whole exome sequencing (WES) in 10 families and 141 individuals with ICA, we identified a candidate list of 162 rare, segregating, deleterious variants in 158 genes. We confirmed the involvement of CNGA2, a previously implicated ICA gene that is an essential component of the olfactory transduction pathway. Furthermore, we found a loss-of-function variant in SREK1IP1 from the family gene candidate list, which was also observed in 5% of individuals in an additional non-family cohort with ICA. Although SREK1IP1 has not been previously associated with olfaction, its role in zinc ion binding suggests a potential influence on olfactory signaling. This study provides a more comprehensive understanding of the spectrum of genetic alterations and their etiology in ICA patients, which may improve the diagnosis, prognosis, and treatment of this disorder and lead to better understanding of the mechanisms governing basic olfactory function., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In color vision, the quantitative rules for mixing lights to make a target color are well understood. By contrast, the rules for mixing odorants to make a target odor remain elusive. A solution to this problem in vision relied on characterizing receptor responses to different wavelengths of light and subsequently relating these responses to perception. In olfaction, experimentally measuring receptor responses to a representative set of complex mixtures is intractable due to the vast number of possibilities. To meet this challenge, we develop a biophysical model that predicts mammalian receptor responses to complex mixtures using responses to single odorants. The dominant nonlinearity in our model is competitive binding (CB): Only one odorant molecule can attach to a receptor binding site at a time. This simple framework predicts receptor responses to mixtures of up to 12 monomolecular odorants to within 15% of experimental observations and provides a powerful method for leveraging limited experimental data. Simple extensions of our model describe phenomena such as synergy, overshadowing, and inhibition. We demonstrate that the presence of such interactions can be identified via systematic deviations from the competitive-binding model., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Humans use a family of more than 400 olfactory receptors (ORs) to detect odors, but there is currently no model that can predict olfactory perception from receptor activity patterns. Genetic variation in human ORs is abundant and alters receptor function, allowing us to examine the relationship between receptor function and perception. We sequenced the OR repertoire in 332 individuals and examined how genetic variation affected 276 olfactory phenotypes, including the perceived intensity and pleasantness of 68 odorants at two concentrations, detection thresholds of three odorants, and general olfactory acuity. Genetic variation in a single OR was frequently associated with changes in odorant perception, and we validated 10 cases in which in vitro OR function correlated with in vivo odorant perception using a functional assay. In 8 of these 10 cases, reduced receptor function was associated with reduced intensity perception. In addition, we used participant genotypes to quantify genetic ancestry and found that, in combination with single OR genotype, age, and gender, we can explain between 10% and 20% of the perceptual variation in 15 olfactory phenotypes, highlighting the importance of single OR genotype, ancestry, and demographic factors in the variation of olfactory perception., Competing Interests: Conflict of interest statement: J.D.M is on the scientific advisory board of Aromyx and receives compensation for these activities.

The mouse olfactory sensory neuron (OSN) repertoire is composed of 10 million cells and each expresses one olfactory receptor (OR) gene from a pool of over 1000. Thus, the nose is sub-stratified into more than a thousand OSN subtypes. Here, we employ and validate an RNA-sequencing-based method to quantify the abundance of all OSN subtypes in parallel, and investigate the genetic and environmental factors that contribute to neuronal diversity. We find that the OSN subtype distribution is stereotyped in genetically identical mice, but varies extensively between different strains. Further, we identify cis -acting genetic variation as the greatest component influencing OSN composition and demonstrate independence from OR function. However, we show that olfactory stimulation with particular odorants results in modulation of dozens of OSN subtypes in a subtle but reproducible, specific and time-dependent manner. Together, these mechanisms generate a highly individualized olfactory sensory system by promoting neuronal diversity.

Background: Since late 2015, an epidemic of yellow fever has caused more than 7334 suspected cases in Angola and the Democratic Republic of the Congo, including 393 deaths. We sought to understand the spatial spread of this outbreak to optimise the use of the limited available vaccine stock., Methods: We jointly analysed datasets describing the epidemic of yellow fever, vector suitability, human demography, and mobility in central Africa to understand and predict the spread of yellow fever virus. We used a standard logistic model to infer the district-specific yellow fever virus infection risk during the course of the epidemic in the region., Findings: The early spread of yellow fever virus was characterised by fast exponential growth (doubling time of 5-7 days) and fast spatial expansion (49 districts reported cases after only 3 months) from Luanda, the capital of Angola. Early invasion was positively correlated with high population density (Pearson's r 0·52, 95% CI 0·34-0·66). The further away locations were from Luanda, the later the date of invasion (Pearson's r 0·60, 95% CI 0·52-0·66). In a Cox model, we noted that districts with higher population densities also had higher risks of sustained transmission (the hazard ratio for cases ceasing was 0·74, 95% CI 0·13-0·92 per log-unit increase in the population size of a district). A model that captured human mobility and vector suitability successfully discriminated districts with high risk of invasion from others with a lower risk (area under the curve 0·94, 95% CI 0·92-0·97). If at the start of the epidemic, sufficient vaccines had been available to target 50 out of 313 districts in the area, our model would have correctly identified 27 (84%) of the 32 districts that were eventually affected., Interpretation: Our findings show the contributions of ecological and demographic factors to the ongoing spread of the yellow fever outbreak and provide estimates of the areas that could be prioritised for vaccination, although other constraints such as vaccine supply and delivery need to be accounted for before such insights can be translated into policy., Funding: Wellcome Trust., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

A novel density barrier material, Phase Lock Gel, has been formulated and optimized for use in enhancing the separation between aqueous and organic phases during organic extraction/ centrifugation of nucleic acids. Phase Lock Gel is inert, stable to heating, compatible with most enzymatic reactions of nucleic acids without sacrificing subsequent downstream applications, and can be easily and conveniently used with most plasmid DNA, genomic DNA, phage DNA and RNA organic extraction protocols. Use of Phase Lock Gel as an aqueous/organic phase barrier material can decrease processing time and improve nucleic acid recovery from organic extraction purifications by as much as 30%, all while minimizing user exposure to volatile organics.

The performance characteristics of a potent new RNase inhibitor have been evaluated, as have applications for its use in molecular biology. PRIME Inhibitor is a protein, not related to the commonly available human placental RNase inhibitors (HPRI). It has a high specific activity, enhanced temperature stability, broad reaction pH range and significantly greater cost-effectiveness than commercial HPRI. PRIME Inhibitor is suitable for use in in vitro transcription, in vitro translation, first- and second-strand cDNA synthesis, preparation of RNA and mRNA, and reverse transcription-polymerase chain reaction.