American public opinion on artificial intelligence in healthcare.

Billions of dollars are being invested into developing medical artificial intelligence (AI) systems and yet public opinion of AI in the medical field seems to be mixed. Although high expectations for the future of medical AI do exist in the American public, anxiety and uncertainty about what it can do and how it works is widespread. Continuing evaluation of public opinion on AI in healthcare is necessary to ensure alignment between patient attitudes and the technologies adopted.

Quantifying Healthy Aging in Older Veterans Using Computational Audio Analysis.

Background: Researchers are increasingly interested in better methods for assessing the pace of aging in older adults, including vocal analysis. The present study sought to determine whether paralinguistic vocal attributes improve estimates of the age and risk of mortality in older adults.

Methods: To measure vocal age, we curated interviews provided by male U.

Explainable automated evaluation of the clock drawing task for memory impairment screening.

Introduction: The clock drawing task (CDT) is frequently used to aid in detecting cognitive impairment, but current scoring techniques are time-consuming and miss relevant features, justifying the creation of an automated quantitative scoring approach.

Methods: We used computer vision methods to analyze the stored scanned images ( = 7,109), and an intelligent system was created to examine these files in a study of aging World Trade Center responders. Outcomes were CDT, Montreal Cognitive Assessment (MoCA) score, and incidence of mild cognitive impairment (MCI).

Diet modulates brain network stability, a biomarker for brain aging, in young adults.

Epidemiological studies suggest that insulin resistance accelerates progression of age-based cognitive impairment, which neuroimaging has linked to brain glucose hypometabolism. As cellular inputs, ketones increase Gibbs free energy change for ATP by 27% compared to glucose. Here we test whether dietary changes are capable of modulating sustained functional communication between brain regions (network stability) by changing their predominant dietary fuel from glucose to ketones.

Latent human traits in the language of social media: An open-vocabulary approach.

Over the past century, personality theory and research has successfully identified core sets of characteristics that consistently describe and explain fundamental differences in the way people think, feel and behave. Such characteristics were derived through theory, dictionary analyses, and survey research using explicit self-reports. The availability of social media data spanning millions of users now makes it possible to automatically derive characteristics from behavioral data-language use-at large scale.

A codon-shuffling method to prevent reversion during production of replication-defective herpesvirus stocks: Implications for herpesvirus vaccines.

Herpesviruses establish life-long chronic infections that place infected hosts at risk for severe disease. Herpesvirus genomes readily undergo homologous recombination (HR) during productive replication, often leading to wild-type (WT) reversion during complementation of replication-defective and attenuated viruses via HR with the helper gene provided in trans. To overcome this barrier, we developed a synthetic-biology approach based on a technique known as codon shuffling.

Deliberate reduction of hemagglutinin and neuraminidase expression of influenza virus leads to an ultraprotective live vaccine in mice.

A long-held dogma posits that strong presentation to the immune system of the dominant influenza virus glycoprotein antigens neuraminidase (NA) and hemagglutinin (HA) is paramount for inducing protective immunity against influenza virus infection. We have deliberately violated this dogma by constructing a recombinant influenza virus strain of A/PR8/34 (H1N1) in which expression of NA and HA genes was suppressed. We down-regulated NA and HA expression by recoding the respective genes with suboptimal codon pair bias, thereby introducing hundreds of nucleotide changes while preserving their codon use and protein sequence.

Identification of two functionally redundant RNA elements in the coding sequence of poliovirus using computer-generated design.

Genomes of RNA viruses contain multiple functional RNA elements required for translation or RNA replication. We use unique approaches to identify functional RNA elements in the coding sequence of poliovirus (PV), a plus strand RNA virus. The general method is to recode large segments of the genome using synonymous codons, such that protein sequences, codon use, and codon pair bias are conserved but the nucleic acid sequence is changed.

Computationally designed adeno-associated virus (AAV) Rep 78 is efficiently maintained within an adenovirus vector.

Adeno-associated virus (AAV) is a single-stranded parvovirus retaining the unique capacity for site-specific integration into a transcriptionally silent region of the human genome, a characteristic requiring the functional properties of the Rep 78/68 polypeptide in conjunction with AAV terminal repeat integrating elements. Previous strategies designed to assemble these genetic elements into adenoviral (Ad) backbones have been limited by the general intolerability of AAV Rep sequences, prompting us to computationally reengineer the Rep gene by using synonymous codon pair recoding. Rep mutants generated by using de novo genome synthesis maintained the polypeptide sequence and endonuclease properties of Rep 78, while dramatically enhancing Ad replication and viral titer yields, characteristics indistinguishable from adenovirus lacking coexpressed Rep.

Live attenuated influenza virus vaccines by computer-aided rational design.

Despite existing vaccines and enormous efforts in biomedical research, influenza annually claims 250,000-500,000 lives worldwide, motivating the search for new, more effective vaccines that can be rapidly designed and easily produced. We applied the previously described synthetic attenuated virus engineering (SAVE) approach to influenza virus strain A/PR/8/34 to rationally design live attenuated influenza virus vaccine candidates through genome-scale changes in codon-pair bias. As attenuation is based on many hundreds of nucleotide changes across the viral genome, reversion of the attenuated variant to a virulent form is unlikely.

Crystallizing short-read assemblies around seeds.

Background: New short-read sequencing technologies produce enormous volumes of 25-30 base paired-end reads. The resulting reads have vastly different characteristics than produced by Sanger sequencing, and require different approaches than the previous generation of sequence assemblers. In this paper, we present a short-read de novo assembler particularly targeted at the new ABI SOLiD sequencing technology.

Virus attenuation by genome-scale changes in codon pair bias.

As a result of the redundancy of the genetic code, adjacent pairs of amino acids can be encoded by as many as 36 different pairs of synonymous codons. A species-specific "codon pair bias" provides that some synonymous codon pairs are used more or less frequently than statistically predicted. We synthesized de novo large DNA molecules using hundreds of over-or underrepresented synonymous codon pairs to encode the poliovirus capsid protein.

MultiPrimer: a system for microarray PCR primer design.

To construct full-genome spotted microarrays, a large number of PCR primers that amplify the required DNA need to be synthesized. We describe an algorithmic technique that allows one to use fewer primers to achieve this goal. This can reduce the expense of constructing full-genome spotted microarrays considerably.

Spatial analysis of news sources.

People in different places talk about different things. This interest distribution is reflected by the newspaper articles circulated in a particular area. We use data from our large-scale newspaper analysis system (Lydia) to make entity datamaps, a spatial visualization of the interest in a given named entity.

Reduction of the rate of poliovirus protein synthesis through large-scale codon deoptimization causes attenuation of viral virulence by lowering specific infectivity.

Exploring the utility of de novo gene synthesis with the aim of designing stably attenuated polioviruses (PV), we followed two strategies to construct PV variants containing synthetic replacements of the capsid coding sequences either by deoptimizing synonymous codon usage (PV-AB) or by maximizing synonymous codon position changes of the existing wild-type (wt) poliovirus codons (PV-SD). Despite 934 nucleotide changes in the capsid coding region, PV-SD RNA produced virus with wild-type characteristics. In contrast, no viable virus was recovered from PV-AB RNA carrying 680 silent mutations, due to a reduction of genome translation and replication below a critical level.

Copy correction and concerted evolution in the conservation of yeast genes.

The yeast Saccharomyces cerevisiae and other members of the genus Saccharomyces are descendants of an ancient whole-genome duplication event. Although most of the duplicate genes have since been deleted, many remain, and so there are many pairs of related genes. We have found that poorly expressed genes diverge rapidly from their paralog, while highly expressed genes diverge little, if at all.

Genomic sorting with length-weighted reversals.

Current algorithmic studies of genome rearrangement ignore the length of reversals (or inversions); rather, they only count their number. We introduce a new cost model in which the lengths of the reversed sequences play a role, allowing more flexibility in accounting for mutation phenomena. Our focus is on sorting unsigned (unoriented) permutations by reversals; since this problem remains difficult (NP-hard) in our new model, the best we can hope for are approximation results.

Deconvolving sequence variation in mixed DNA populations.

We present an original approach to identifying sequence variants in a mixed DNA population from sequence trace data. The heart of the method is based on parsimony: given a wildtype DNA sequence, a set of observed variations at each position collected from sequencing data, and a complete catalog of all possible mutations, determine the smallest set of mutations from the catalog that could fully explain the observed variations. The algorithmic complexity of the problem is analyzed for several classes of mutations, including block substitutions, single-range deletions, and single-range insertions.

Natural selection and algorithmic design of mRNA.

Messenger RNA (mRNA) sequences serve as templates for proteins according to the triplet code, in which each of the 4(3) = 64 different codons (sequences of three consecutive nucleotide bases) in RNA either terminate transcription or map to one of the 20 different amino acids (or residues) which build up proteins. Because there are more codons than residues, there is inherent redundancy in the coding. Certain residues (e.

Microarray synthesis through multiple-use PCR primer design.

A substantial percentage of the expense in constructing full-genome spotted microarrays comes from the cost of synthesizing the PCR primers to amplify the desired DNA. We propose a computationally-based method to substantially reduce this cost. Historically, PCR primers are designed so that each primer occurs uniquely in the genome.

Analysis techniques for microarray time-series data.

We address possible limitations of publicly available data sets of yeast gene expression. We study the predictability of known regulators via time-series analysis, and show that less than 20% of known regulatory pairs exhibit strong correlations in the Cho/Spellman data sets. By analyzing known regulatory relationships, we designed an edge detection function which identified candidate regulations with greater fidelity than standard correlation methods.