Deep statistical modelling of nanopore sequencing translocation times reveals latent non-B DNA structures.

MOTIVATION: Non-canonical (or non-B) DNA are genomic regions whose three-dimensional conformation deviates from the canonical double helix. Non-B DNA play an important role in basic cellular processes and are associated with genomic instability, gene regulation, and oncogenesis. Experimental methods are low-throughput and can detect only a limited set of non-B DNA structures, while computational methods rely on non-B DNA base motifs, which are necessary but not sufficient indicators of non-B structures. Oxford Nanopore sequencing is an efficient and low-cost platform, but it is currently unknown whether nanopore reads can be used for identifying non-B structures. RESULTS: We build the first computational pipeline to predict non-B DNA structures from nanopore sequencing. We formalize non-B detection as a novelty detection problem and develop the GoFAE-DND, an autoencoder that uses goodness-of-fit (GoF) tests as a regularizer. A discriminative loss encourages non-B DNA to be poorly reconstructed and optimizing Gaussian GoF tests allows for the computation of P-values that indicate non-B structures. Based on whole genome nanopore sequencing of NA12878, we show that there exist significant differences between the timing of DNA translocation for non-B DNA bases compared with B-DNA. We demonstrate the efficacy of our approach through comparisons with novelty detection methods using experimental data and data synthesized from a new translocation time simulator. Experimental validations suggest that reliable detection of non-B DNA from nanopore sequencing is achievable. AVAILABILITY AND IMPLEMENTATION: Source code is available at https://github.com/bayesomicslab/ONT-nonb-GoFAE-DND.

Long-term safety and durability of novel intra-aortic percutaneous mechanical circulatory support device.

An unmet need exists for minimally invasive percutaneous mechanical circulatory support (pMCS) devices to provide partial support and promote cardiac rest and recovery in non-end-stage heart failure patients. This indication requires safe, long-term, ambulatory use with standard anticoagulation. The Aortix pump (Procyrion, Houston, Texas, USA) is a percutaneously deployed intra-aortic pump currently being clinically evaluated for subacute use and has the potential to provide extended therapy for non-end-stage heart failure patients. The device has demonstrated hemocompatibility and hemodynamic impact and has features well suited for home use. To evaluate the Aortix pump for long-term, ambulatory use, pumps were implanted in 4 untethered sheep. Pumps operated for 90 to 142 days and were stopped electively. Pump bearing components were found to have only superficial wear. No clinically significant hemolysis was observed and aorta and kidney histopathology showed no device-related findings or adhesions, suggesting Aortix is suitable for long-term (>6 months) ambulatory use.

Analysis of Mechanical Thrombectomy for Acute Ischemic Stroke on Nights and Weekends Versus Weekdays at Comprehensive Stroke Centers.

OBJECTIVE: The "weekend effect" has been shown to affect outcomes in acute ischemic stroke. We sought to compare metrics and outcomes of emergent stroke thrombectomy at three affiliated comprehensive stroke centers on weekdays versus nights/weekends for a three-year period beginning in 2015, when thrombectomy became common practice for large vessel occlusion acute ischemic stroke. METHODS: We performed a retrospective analysis of all stroke thrombectomy patients treated from 2015 to 2018 to compare standard thrombectomy metrics and outcomes in patients presenting during weekdays or nights/weekends. RESULTS: Two hundred-sixteen mechanical thrombectomy cases were evaluated, with 50.9% of patients presenting on weekdays and 49.1% presenting on nights/weekends. There were no statistical differences in baseline characteristics in demographics, stroke risk factors, or stroke severity, but patients presenting on nights/weekends had longer times from last known normal to presentation (130 versus 72.5 minutes, p=0.03). Door-to-groin times were delayed in patients presenting on nights/weekends compared to weekdays (median 104.5 versus 86 minutes, respectively; p=0.007) but groin-to-reperfusion times were similar (51.5 versus 48 minutes, respectively; p=0.4). Successful reperfusion was similar in both groups (90.6% nights/weekends versus 90% weekdays; p=1.0) as were the incidence of symptomatic intracerebral hemorrhage (10.4% nights/weekend versus 7.3% weekdays; p=0.48) and 90-day good functional outcomes based on the modified Rankin Scale did not differ between the two groups in a shift analysis (p=0.545). CONCLUSIONS: Despite delays in door-to-groin puncture times in acute ischemic stroke patients presenting on nights/weekends compared to weekdays, we did not identify significant differences in successful reperfusion or functional outcomes in this cohort. Further studies are warranted to continue to evaluate differences in stroke care on nights/weekends versus weekdays.

Bone Flap Resorption Associated with Indolent Propionibacterium acnes Infection After Cranioplasty: Case Report with Pathological Analysis.

BACKGROUND: Autologous bone resorption is a frequent complication of cranioplasty, often necessitating reoperation. The etiology of this phenomenon is unknown, although it has recently been associated with indolent Propionibacterium acnes infection. CASE DESCRIPTION: A 59-year-old man initially presented with a traumatic acute subdural hematoma treated with emergent decompressive hemicraniectomy and hematoma evacuation. His bone flap was cryopreserved. He underwent cranioplasty with autologous bone 3 months later. Over the subsequent 14 months, serial imaging demonstrated progressive bone flap resorption, ultimately requiring repeat cranioplasty with a custom allograft. Although there was no evidence of infection at the time of repeat cranioplasty, routine culture swabs were taken and grew P. acnes after the patient had been discharged home. Pathologic analysis of the fragments of the original bone flap that were removed demonstrated osteonecrosis with marrow fibrosis but no evidence of inflammation or infection. He was treated with 6 weeks of intravenous antibiotics and had no evidence of infection at 8-month follow-up. CONCLUSIONS: Indolent P. acnes infection can precipitate autologous bone flap resorption. While the mechanism of this is unknown, pathologic analysis of a partially resorbed bone flap in the setting of an indolent P. acnes infection found no evidence of an infectious process or inflammation within the bone. Further studies are needed to elucidate the mechanism of action of P. acnes in bone flap resorption.

VIGAN: Missing View Imputation with Generative Adversarial Networks.

In an era when big data are becoming the norm, there is less concern with the quantity but more with the quality and completeness of the data. In many disciplines, data are collected from heterogeneous sources, resulting in multi-view or multi-modal datasets. The missing data problem has been challenging to address in multi-view data analysis. Especially, when certain samples miss an entire view of data, it creates the missing view problem. Classic multiple imputations or matrix completion methods are hardly effective here when no information can be based on in the specific view to impute data for such samples. The commonly-used simple method of removing samples with a missing view can dramatically reduce sample size, thus diminishing the statistical power of a subsequent analysis. In this paper, we propose a novel approach for view imputation via generative adversarial networks (GANs), which we name by VIGAN. This approach first treats each view as a separate domain and identifies domain-to-domain mappings via a GAN using randomly-sampled data from each view, and then employs a multi-modal denoising autoencoder (DAE) to reconstruct the missing view from the GAN outputs based on paired data across the views. Then, by optimizing the GAN and DAE jointly, our model enables the knowledge integration for domain mappings and view correspondences to effectively recover the missing view. Empirical results on benchmark datasets validate the VIGAN approach by comparing against the state of the art. The evaluation of VIGAN in a genetic study of substance use disorders further proves the effectiveness and usability of this approach in life science.

Implantable device to monitor cardiac activity with sternal wires.

BACKGROUND: Sternal wires are used to close the thoracic cavity and facilitate healing after median sternotomy (MS). We invented an implantable device that uses these wires as sensors to monitor cardiac electrical activity and tested its utility in collecting electrocardiography (ECG) data in vivo. METHODS: The wafer-thin silicone device has grooves with embedded metal contacts that secure the sternal wires and connect them to an ECG sensor. We used radiofrequency telemetry to communicate with the implanted device, which was evaluated in three acute swine studies and one chronic-survival swine study. The device was implanted via MS in two acute studies and left thoracotomy in the other. In two acute studies, ECG data were collected with the pigs in four different positions for 2 minutes each; in the third study, we induced ischemia and collected ECG data. For the chronic study, we implanted the device via a left thoracotomy and obtained ECG data weekly until euthanasia on day 27. After each study, the sternum and device were removed and examined. RESULTS: The ECG tracings showed distinct P, QRS, and T waveforms with minimal positional or temporal variability. Our device captured signal changes during ischemia before the external control did. In the chronic study, necropsy showed appropriate healing, fibrous encapsulation, and no infection or adverse reactions. CONCLUSIONS: These initial results showed that our novel device can use sternal wires as electrodes in vivo to monitor cardiac electrical activity and safely capture physiologic signals after surgical placement.

Enhancing the care navigation model: potential roles for health sciences librarians.

This study analyzed the overlap between roles and activities that health care navigators perform and competencies identified by the Medical Library Association's (MLA's) educational policy statement.Roles and activities that health care navigators perform were gleaned from published literature. Once common roles and activities that health care navigators perform were identified, MLA competencies were mapped against those roles and activities to identify areas of overlap. The greatest extent of correspondence occurred in patient empowerment and support. Further research is warranted to determine the extent to which health sciences librarians might assume responsibility for roles and activities that health care navigators perform