Knowledges graphs (KGs) serve as a convenient framework for structuring knowledge. A number of computational methods have been developed to generate KGs from biomedical literature and use them for ...downstream tasks such as link prediction and question answering. However, there is a lack of computational tools or web frameworks to support the exploration and visualization of the KG themselves, which would facilitate interactive knowledge discovery and formulation of novel biological hypotheses.
We developed a web framework for Knowledge Graph Exploration and Visualization (KGEV), to construct and visualize KGs in five stages: triple extraction, triple filtration, metadata preparation, knowledge integration, and graph database preparation. The application has convenient user interface tools, such as node and edge search and filtering, data source filtering, neighborhood retrieval, and shortest path calculation, that work by querying a backend graph database. Unlike other KGs, our framework allows fast retrieval of relevant texts supporting the relationships in the KG, thus allowing human reviewers to judge the reliability of the knowledge extracted.
We demonstrated a case study of using the KGEV framework to perform research on COVID-19. The COVID-19 pandemic resulted in an explosion of relevant literature, making it challenging to make full use of the vast and heterogenous sources of information. We generated a COVID-19 KG with heterogenous information, including literature information from the CORD-19 dataset, as well as other existing knowledge from eight data sources. We showed the utility of KGEV in three intuitive case studies to explore and query knowledge on COVID-19. A demo of this web application can be accessed at http://covid19nlp.wglab.org . Finally, we also demonstrated a turn-key adaption of the KGEV framework to study clinical phenotypic presentation of human diseases by Human Phenotype Ontology (HPO), illustrating the versatility of the framework.
In an era of literature explosion, the KGEV framework can be applied to many emerging diseases to support structured navigation of the vast amount of newly published biomedical literature and other existing biological knowledge in various databases. It can be also used as a general-purpose tool to explore and query gene-phenotype-disease-drug relationships interactively.
Although brain-derived neurotrophic factor (BDNF) is known to regulate circuit development and synaptic plasticity, its exact role in neuronal network activity remains elusive. Using mutant mice ...(TrkB-PV-/-) in which the gene for the BDNF receptor, tyrosine kinase B receptor (trkB), has been specifically deleted in parvalbuminexpressing, fast-spiking GABAergic (PV+) interneurons, we show that TrkB is structurally and functionally important for the integrity of the hippocampal network. The amplitude of glutamatergic inputs to PV+ interneurons and the frequency of GABAergic inputs to excitatory pyramidal cells were reduced in the TrkB-PV-/- mice. Functionally, rhythmic network activity in the gamma-frequency band (30-80 Hz) was significantly decreased in hippocampal area CA1. This decrease was caused by a desynchronization and overall reduction in frequency of action potentials generated in PV+ interneurons of TrkB-PV-/- mice. Our results show that the integration of PV+ interneurons into the hippocampal microcircuit is impaired in TrkB-PV-/- mice, resulting in decreased rhythmic network activity in the gamma-frequency band.
Most previous studies about online product recommendation sources (recommendation agents RAs, consumers, and experts) have been limited to the evaluation by a single source on a website. Thus, the ...relative influence of convergent recommendations from different sources on consumers' acceptance of the advice remains largely unknown. We draw upon and extend the product uncertainty model to theorize how the convergence of recommendations from various sources differentially influences customers' acceptance of recommendations. Our experiments show that the recommendation convergence between RAs and experts leads to the greater recommendation acceptance of the jointly recommended products than the convergence between experts and consumers or convergence between RAs and consumers. The rationale is that RAs best reduce fit uncertainty, and experts best reduce description and performance uncertainties. Experts and RAs complement each other by reducing all three dimensions of product uncertainty. Online merchants are advised to incorporate multiple sources into their websites, including sources (i.e., RAs and experts) that play complementary roles in reducing product uncertainty.
OBJECTIVE The aim of this article is to review the authors' and published experience with deep brain stimulation (DBS) therapy for the treatment of patients with Alzheimer's disease (AD) and ...Parkinson's disease dementia (PDD). METHODS Two targets are current topics of investigation in the treatment of AD and PDD, the fornix and the nucleus basalis of Meynert. The authors reviewed the current published clinical experience with attention to patient selection, biological rationale of therapy, anatomical targeting, and clinical results and adverse events. RESULTS A total of 7 clinical studies treating 57 AD patients and 7 PDD patients have been reported. Serious adverse events were reported in 6 (9%) patients; none resulted in death or disability. Most studies were case reports or Phase 1/2 investigations and were not designed to assess treatment efficacy. Isolated patient experiences demonstrating improved clinical response after DBS have been reported, but no significant or consistent cognitive benefits associated with DBS treatment could be identified across larger patient populations. CONCLUSIONS PDD and AD are complex clinical entities, with investigation of DBS intervention still in an early phase. Recently published studies demonstrate acceptable surgical safety. For future studies to have adequate power to detect meaningful clinical changes, further refinement is needed in patient selection, metrics of clinical response, and optimal stimulation parameters.
Solid‐state single photon emitters (SPEs) within atomically thin transition metal dichalcogenides (TMDs) have recently attracted interest as scalable quantum light sources for quantum photonic ...technologies. Among TMDs, WSe2 monolayers (MLs) are promising for the deterministic fabrication and engineering of SPEs using local strain fields. The ability to reliably produce isolatable SPEs in WSe2 is currently impeded by the presence of numerous spectrally overlapping states that occur at strained locations. Here nanoparticle (NP) arrays with precisely defined positions and sizes are employed to deterministically create strain fields in WSe2 MLs, thus enabling the systematic investigation and control of SPE formation. Using this platform, electron beam irradiation at NP‐strained locations transforms spectrally overlapped sub‐bandgap emission states into isolatable, anti‐bunched quantum emitters. The dependence of the emission spectra of WSe2 MLs as a function of strain magnitude and exposure time to electron beam irradiation is quantified and provides insight into the mechanism for SPE production. Excitons selectively funnel through strongly coupled sub‐bandgap states introduced by electron beam irradiation, which suppresses spectrally overlapping emission pathways and leads to measurable anti‐bunched behavior. The findings provide a strategy to generate isolatable SPEs in 2D materials with a well‐defined energy range.
Spectrally overlapping mid‐gap emitters from deterministically positioned, nanoparticle‐strained WSe2 monolayers are converted into isolatable, anti‐bunched emitters using electron beam irradiation. The localized emission before and after irradiation are compared as a function of strain magnitude to assign the spectral transformation to the suppression of weakly coupled mid‐gap state‐strain pairs through strongly coupled mid‐gap state‐strain pairs introduced through electron beam irradiation.
Common-mode voltages (CMVs) can lead to premature failure of the motor insulation system in medium-voltage current-source-fed drives. By analyzing the CMV values at all switching states under ...different operating conditions of a current-source-inverter (CSI)-based motor drive, this paper first indicates that the CMV peaks are produced by the zero states in most of the cases. The nonzero-state (NZS) modulation techniques employed in voltage-source converters are adapted for use in a space-vector-modulated current-source converter (CSC) to reduce the CMV magnitude. For NZS modulation in CSCs, the nearest three-state (NTS) modulation sequences are designed with good low-order harmonic performances in their linear modulation region of m a ≥ 0.67 and with no increase in the device switching frequency. A combined active-zero-state (AZS) modulation technique is also proposed as compensation, for a lower modulation index in the range of 0.4-0.67, when a compromise is made between the dc-link current minimization and high input power factor control. The simulation and experimental results are provided to validate the CMV reduction effects and harmonic performances of the NTS and combined AZS modulation methods in CSI-fed drives.
Knowledge of the manufacturer of the previously implanted pedicle screw systems prior to revision spinal surgery may facilitate faster and safer surgery. Often, this information is unavailable ...because patients are referred by other centers or because of missing information in the patients' records. Recently, machine learning and computer vision have gained wider use in clinical applications. The authors propose a computer vision approach to classify posterior thoracolumbar instrumentation systems.
Lateral and anteroposterior (AP) radiographs obtained in patients undergoing posterior thoracolumbar pedicle screw implantation for any indication at the authors' institution (2015-2021) were obtained. DICOM images were cropped to include both the pedicle screws and rods. Images were labeled with the manufacturer according to the operative record. Multiple feature detection methods were tested (SURF, MESR, and Minimum Eigenvalues); however, the bag-of-visual-words technique with KAZE feature detection was ultimately used to construct a computer vision support vector machine (SVM) classifier for lateral, AP, and fused lateral and AP images. Accuracy was tested using an 80%/20% training/testing pseudorandom split over 100 iterations. Using a reader study, the authors compared the model performance with the current practice of surgeons and manufacturer representatives identifying spinal hardware by visual inspection.
Among the three image types, 355 lateral, 379 AP, and 338 fused radiographs were obtained. The five pedicle screw implants included in this study were the Globus Medical Creo, Medtronic Solera, NuVasive Reline, Stryker Xia, and DePuy Expedium. When the two most common manufacturers used at the authors' institution were binarily classified (Globus Medical and Medtronic), the accuracy rates for lateral, AP, and fused images were 93.15% ± 4.06%, 88.98% ± 4.08%, and 91.08% ± 5.30%, respectively. Classification accuracy decreased by approximately 10% with each additional manufacturer added. The multilevel five-way classification accuracy rates for lateral, AP, and fused images were 64.27% ± 5.13%, 60.95% ± 5.52%, and 65.90% ± 5.14%, respectively. In the reader study, the model performed five-way classification on 100 test images with 79% accuracy in 14 seconds, compared with an average of 44% accuracy in 20 minutes for two surgeons and three manufacturer representatives.
The authors developed a KAZE feature detector with an SVM classifier that successfully identified posterior thoracolumbar hardware at five-level classification. The model performed more accurately and efficiently than the method currently used in clinical practice. The relative computational simplicity of this model, from input to output, may facilitate future prospective studies in the clinical setting.
Previous anti-EGFR trials in unselected patients with gastroesophageal adenocarcinoma (GEA) were resoundingly negative. We identified
amplification in 5% (19/363) of patients at the University of ...Chicago, including 6% (8/140) who were prospectively screened with intention-to-treat using anti-EGFR therapy. Seven patients received ≥1 dose of treatment: three first-line FOLFOX plus ABT-806, one second-line FOLFIRI plus cetuximab, and three third/fourth-line cetuximab alone. Treatment achieved objective response in 58% (4/7) and disease control in 100% (7/7) with a median progression-free survival of 10 months. Pretreatment and posttreatment tumor next-generation sequencing (NGS), serial plasma circulating tumor DNA (ctDNA) NGS, and tumor IHC/FISH for EGFR revealed preexisting and/or acquired genomic events, including
-negative clones,
deletion,
amplification/mutation,
, and
amplification, and
mutations serving as mechanisms of resistance. Two evaluable patients demonstrated interval increase of CD3
infiltrate, including one who demonstrated increased NKp46
, and PD-L1 IHC expression from baseline, suggesting an immune therapeutic mechanism of action.
amplification predicted benefit from anti-EGFR therapy, albeit until various resistance mechanisms emerged.
This paper highlights the role of EGFR inhibitors in
-amplified GEA-despite negative results in prior unselected phase III trials. Using serial ctDNA and tissue NGS, we identified mechanisms of primary and acquired resistance in all patients, as well as potential contribution of antibody-dependent cell-mediated cytotoxicity to their clinical benefit.
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Strain‐engineering in atomically thin metal dichalcogenides is a useful method for realizing single‐photon emitters (SPEs) for quantum technologies. Correlating SPE position with local strain ...topography is challenging due to localization inaccuracies from the diffraction limit. Currently, SPEs are assumed to be positioned at the highest strained location and are typically identified by randomly screening narrow‐linewidth emitters, of which only a few are spectrally pure. In this work, hyperspectral quantum emitter localization microscopy is used to locate 33 SPEs in nanoparticle‐strained WSe2 monolayers with sub‐diffraction‐limit resolution (≈30 nm) and correlate their positions with the underlying strain field via image registration. In this system, spectrally pure emitters are not concentrated at the highest strain location due to spectral contamination; instead, isolable SPEs are distributed away from points of peak strain with an average displacement of 240 nm. These observations point toward a need for a change in the design rules for strain‐engineered SPEs and constitute a key step toward realizing next‐generation quantum optical architectures.
The positions of spectrally pure quantum emitters in nanoparticle‐strained WSe2 monolayers are mapped to the underlying strain field with a resolution below the diffraction limit (≈30 nm). The quantum emitters are displaced from the local strain maxima by an average distance of 240 nm, which contradicts the assumption that strain‐induced quantum emitters are concentrated at the local strain maxima.
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