To understand patient characteristics related to acceptability of returning individual research results via various modalities, focusing on electronic visits (e-visits).
Twelve hundred participants ...from the Mayo Clinic Biobank were selected using a stratified random sampling approach based on sex, age, and education level. Mailed surveys ascertained return of results preferences for 2 disease vignettes (cystic fibrosis and hereditary breast cancer) and a pharmacogenomics vignette. The study was conducted from October 1, 2013, through March 31, 2014.
In all, 685 patients (57%) responded, and 60% reported liking e-visits, although the option of receiving results in an office visit was liked most frequently. Multivariable logistic models showed that the odds of liking the use of e-visits for returning results for cystic fibrosis and hereditary breast cancer were higher among those with higher education and better genetic knowledge and among those not living in proximity to the Mayo Clinic (Rochester, Minnesota). Level of genetic knowledge was not considerably associated with accepting e-visits, whereas education level remained important. For all vignettes, those who are divorced were less likely to accept e-visits.
Researchers are faced with a difficult challenge of returning results with a method that is both acceptable to recipients and logistically feasible. This study implies that the use of e-visits may be a viable option for return of results to stratify the chasm between in-person genetic counseling and online portal receipt of results.
To report the design and implementation of the Right Drug, Right Dose, Right Time-Using Genomic Data to Individualize Treatment protocol that was developed to test the concept that prescribers can ...deliver genome-guided therapy at the point of care by using preemptive pharmacogenomics (PGx) data and clinical decision support (CDS) integrated into the electronic medical record (EMR).
We used a multivariate prediction model to identify patients with a high risk of initiating statin therapy within 3 years. The model was used to target a study cohort most likely to benefit from preemptive PGx testing among the Mayo Clinic Biobank participants, with a recruitment goal of 1000 patients. We used a Cox proportional hazards model with variables selected through the Lasso shrinkage method. An operational CDS model was adapted to implement PGx rules within the EMR.
The prediction model included age, sex, race, and 6 chronic diseases categorized by the Clinical Classifications Software for International Classification of Diseases, Ninth Revision codes (dyslipidemia, diabetes, peripheral atherosclerosis, disease of the blood-forming organs, coronary atherosclerosis and other heart diseases, and hypertension). Of the 2000 Biobank participants invited, 1013 (51%) provided blood samples, 256 (13%) declined participation, 555 (28%) did not respond, and 176 (9%) consented but did not provide a blood sample within the recruitment window (October 4, 2012, through March 20, 2013). Preemptive PGx testing included CYP2D6 genotyping and targeted sequencing of 84 PGx genes. Synchronous real-time CDS was integrated into the EMR and flagged potential patient-specific drug-gene interactions and provided therapeutic guidance.
This translational project provides an opportunity to begin to evaluate the impact of preemptive sequencing and EMR-driven genome-guided therapy. These interventions will improve understanding and implementation of genomic data in clinical practice.
Links between colorectal cancer (CRC) and the gut microbiome have been established, but the specific microbial species and their role in carcinogenesis remain an active area of inquiry. Our ...understanding would be enhanced by better accounting for tumor subtype, microbial community interactions, metabolism, and ecology.
We collected paired colon tumor and normal-adjacent tissue and mucosa samples from 83 individuals who underwent partial or total colectomies for CRC. Mismatch repair (MMR) status was determined in each tumor sample and classified as either deficient MMR (dMMR) or proficient MMR (pMMR) tumor subtypes. Samples underwent 16S rRNA gene sequencing and a subset of samples from 50 individuals were submitted for targeted metabolomic analysis to quantify amino acids and short-chain fatty acids. A PERMANOVA was used to identify the biological variables that explained variance within the microbial communities. dMMR and pMMR microbial communities were then analyzed separately using a generalized linear mixed effects model that accounted for MMR status, sample location, intra-subject variability, and read depth. Genome-scale metabolic models were then used to generate microbial interaction networks for dMMR and pMMR microbial communities. We assessed global network properties as well as the metabolic influence of each microbe within the dMMR and pMMR networks.
We demonstrate distinct roles for microbes in dMMR and pMMR CRC. Bacteroides fragilis and sulfidogenic Fusobacterium nucleatum were significantly enriched in dMMR CRC, but not pMMR CRC. These findings were further supported by metabolic modeling and metabolomics indicating suppression of B. fragilis in pMMR CRC and increased production of amino acid proxies for hydrogen sulfide in dMMR CRC.
Integrating tumor biology and microbial ecology highlighted distinct microbial, metabolic, and ecological properties unique to dMMR and pMMR CRC. This approach could critically improve our ability to define, predict, prevent, and treat colorectal cancers.
The Omicron variant of SARS-CoV-2 exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term ...durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron although the boosted titers decline rapidly within 2 months from the peak response compared to boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared to homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared to BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrial.gov# NCT04889209.
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•Vaccine boost substantially increases Omicron neutralizing antibody titers•Boosted neutralization titers to Omicron but not prototypic D614G decline rapidly•Ad26.COV2.S is better as prime or boost with mRNA vaccines than as homologous boost•Omicron sublineages exhibit 5-12 times reduced neutralization by mRNA-1273 boost sera
Following COVID-19 vaccine prime and boost, Lyke et al. find higher Omicron neutralization titers for homologous mRNA boost and heterologous mRNA and Ad26.COV2.S boost, compared to homologous Ad26.COV2.S boost. Omicron titers rapidly decline by Day 91 compared to prototypic D614G. Moderate differences in neutralization (<3-fold) was noted among Omicron sublineages.
As part of a multicenter study evaluating homologous and heterologous COVID-19 booster vaccines, we assessed the magnitude, breadth, and short-term durability of binding and pseudovirus-neutralizing ...antibody (PsVNA) responses following a single booster dose of NVX-CoV2373 in adults primed with either Ad26.COV2.S, mRNA-1273, or BNT162b2 vaccines. NVX-CoV2373 as a heterologous booster was immunogenic and associated with no safety concerns through Day 91. Fold-rises in PsVNA titers from baseline (Day 1) to Day 29 were highest for prototypic D614G variant and lowest for more recent Omicron sub-lineages BQ.1.1 and XBB.1. Peak humoral responses against all SARS-CoV-2 variants were lower in those primed with Ad26.COV2.S than with mRNA vaccines. Prior SARS CoV-2 infection was associated with substantially higher baseline PsVNA titers, which remained elevated relative to previously uninfected participants through Day 91. These data support the use of heterologous protein-based booster vaccines as an acceptable alternative to mRNA or adenoviral-based COVID-19 booster vaccines. This trial was conducted under ClinicalTrials.gov: NCT04889209.
Next generation electronics will be painted onto plastic substrates providing both functionality and physical flexibility. The corresponding manufacturing process will lead to significantly reduced ...cost; however the performance of the resulting circuits will not match many existing high-performance electronic circuits fabricated with traditional technology today. High performance is not always necessary, but when required, printed electronics may still be a viable solution. The future of printed electronics is bright and will eventually include sophisticated function, but until that time, a printed hybrid option will simultaneously provide the cost savings of printing and the high performance of silicon and printed circuit boards. An interim contribution is to use state-of-the-art silicon devices and print the supporting conductive patterns and passives on substrates for flexible systems integration. This paper describes and demonstrates a hybrid circuit technology, which can manufacture circuits more easily adapted to complex shapes and diverse sizes. Additionally, a number of printed components and devices are reviewed and a demonstration of two circuits is provided: an RF antenna and the supporting substrate design of a field programmable gate array.
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