A Perspective on Protein Structure Prediction Using Quantum Computers.

Despite the recent advancements by deep learning methods such as AlphaFold2, in silico protein structure prediction remains a challenging problem in biomedical research. With the rapid evolution of quantum computing, it is natural to ask whether quantum computers can offer some meaningful benefits for approaching this problem. Yet, identifying specific problem instances amenable to quantum advantage and estimating the quantum resources required are equally challenging tasks. Here, we share our perspective on how to create a framework for systematically selecting protein structure prediction problems that are amenable for quantum advantage, and estimate quantum resources for such problems on a utility-scale quantum computer. As a proof-of-concept, we validate our problem selection framework by accurately predicting the structure of a catalytic loop of the Zika Virus NS3 Helicase, on quantum hardware.

"But for the blind spot": Accuracy and diagnostic performance of smart watch cardiac features in pediatric patients.

BACKGROUND: The Apple Watch™ (AW) offers heart rate (HR) tracking by photoplethysmography (PPG) and single-lead electrocardiographic (ECG) recordings. The accuracy of AW-HR and diagnostic performance of AW-ECGs among children during both sinus rhythm and arrhythmias have not been explored. OBJECTIVE: The purposes of this study were to assess the accuracy of AW-HR measurements compared to gold standard modalities in children during sinus rhythm and arrhythmias and to identify non-sinus rhythms using AW-ECGs. METHODS: Subjects ≤18 years wore an AW during (1) telemetry admission, (2) electrophysiological study (EPS), or (3) exercise stress test (EST). AW-HRs were compared to gold standard modality values. Recorded AW-ECGs were reviewed by 3 blinded pediatric electrophysiologists. RESULTS: Eighty subjects (median age 13 years; interquartile range 1.0-16.0 years; 50% female) wore AW (telemetry 41% [n = 33]; EPS 34% [n = 27]; EST 25% [n = 20]). A total of 1090 AW-HR measurements were compared to time-synchronized gold standard modality HR values. Intraclass correlation coefficient (ICC) was high 0.99 (0.98-0.99) for AW-HR during sinus rhythm compared to gold standard modalities. ICC was poor comparing AW-HR to gold standard modality HR in tachyarrhythmias (ICC 0.24-0.27) due to systematic undercounting of AW-HR values. A total of 126 AW-ECGs were reviewed. Identification of non-sinus rhythm by AW-ECG showed sensitivity of 89%-96% and specificity of 78%-87%. CONCLUSIONS: We found high levels of agreement for AW-HR values with gold standard modalities during sinus rhythm and poor agreement during tachyarrhythmias, likely due to hemodynamic effects of tachyarrhythmias on PPG-based measurements. AW-ECGs had good sensitivity and moderate specificity in identification of non-sinus rhythm in children.

Whole genome sequencing identifies etiology of recurrent male intrauterine fetal death.

OBJECTIVE: To identify the underlying genetic cause for recurrent intrauterine fetal death (IUFD) of males. METHODS: Whole genome sequencing was performed on DNA from five healthy obligatory carrier females and an unaffected male offspring of a multigenerational pedigree with recurrent second-trimester IUFD of males (n = 19). When documented, all deaths occurred at ≤20 weeks of gestation. Hydrops fetalis was diagnosed at death in the most recent case. RESULTS: Following variant filtering based on a recessive X-linked inheritance pattern, a rare FOXP3 frameshift mutation (p.D303fs*87) that results in a premature truncation of the protein was discovered. Sanger sequencing confirmed the mutation in the affected fetus. The FOXP3 gene encodes for a transcriptional regulator critical to the function of regulatory T cells. FOXP3 mutations are associated with immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome which exclusively affects males and may present with a potentially life-threatening complex autoimmune disorder in early childhood. CONCLUSIONS: Here, we demonstrate the utility of whole genome sequencing-based pedigree analysis to identify the genetic cause for recurrent IUFD when chromosome studies, including microarray analysis, are normal. Further studies are needed to determine the prevalence of FOXP3-mediated IUFD in males. © 2017 John Wiley & Sons, Ltd.

Evaluation and implementation of behavioral and educational tools that improves the patients' intentional and unintentional non-adherence to cardiovascular medications in family medicine clinics.

OBJECTIVE: There are limited number of studies describing the reasons and interventions of non-adherence to cardiovascular medications in United Arab Emirates (UAE). We aimed to implement and evaluate the behavioral and educational tools that indicate the reasons of non-adherence in patients with cardiovascular diseases and improve patient's adherence to their cardiovascular medications. METHODS: In this prospective interventional study, we recruited patients (n = 300) with cardiovascular diseases from three family medicine clinics in Al Ain, UAE in 2010. We assessed patients' responses to a validated brief medication questionnaire (BMQ). RESULTS: At the end of the study, we observed a significant improvement in adherence. When we compared pre- and post-interventions, the mean (± standard deviation, SD) score for non-adherence to current regimen were 4.1 ± 0.2 vs. 3.0 ± 0.3 (p = 0.034); indication of negative believes or motivational barriers scores was 1.8 ± 0.4 vs. 0.9 ± 0.1 (p = 0.027); the indication of recall barrier scores was 1.6 ± 0.1 vs. 0.8 ± 0.1 (p = 0.014); and the indication of access barrier scores was 1.6 ± 0.2 vs. 0.7 ± 0.2 (p = 0.019). Mean blood pressure, fasting blood glucose, glycosylated hemoglobin, low density lipoprotein and postprandial blood glucose decreased significantly (p < 0.01) post-intervention. CONCLUSION: We reported that implemented multifaceted tools targeting patients, provider and healthcare system have improved the adherence to cardiovascular medications. Our interventions managed to improve patients' clinical outcome via improving adherence to prescribed cardiovascular medications.

Experimental quantum annealing: case study involving the graph isomorphism problem.

Quantum annealing is a proposed combinatorial optimization technique meant to exploit quantum mechanical effects such as tunneling and entanglement. Real-world quantum annealing-based solvers require a combination of annealing and classical pre- and post-processing; at this early stage, little is known about how to partition and optimize the processing. This article presents an experimental case study of quantum annealing and some of the factors involved in real-world solvers, using a 504-qubit D-Wave Two machine and the graph isomorphism problem. To illustrate the role of classical pre-processing, a compact Hamiltonian is presented that enables a reduced Ising model for each problem instance. On random N-vertex graphs, the median number of variables is reduced from N(2) to fewer than N log2 N and solvable graph sizes increase from N = 5 to N = 13. Additionally, error correction via classical post-processing majority voting is evaluated. While the solution times are not competitive with classical approaches to graph isomorphism, the enhanced solver ultimately classified correctly every problem that was mapped to the processor and demonstrated clear advantages over the baseline approach. The results shed some light on the nature of real-world quantum annealing and the associated hybrid classical-quantum solvers.