Images Diagnosis and Emergent Endovascular Treatment of Acute Hemorrhagic Basilar Artery Dissection: A Case Report.

PURPOSE: Basilar artery dissection (BAD) is a rare but possibly fatal disease with specific neuroimage findings. The management of BAD varies. This report describes a case with hemorrhagic BAD treated by endovascular stent-assisted coil embolization. CASE REPORT: We report an 82-year-old case of acute mid basilar artery dissection complicated with acute subarachnoid hemorrhage (SAH), intraventricular hemorrhage (IVH) and hydrocephalus, which was diagnosed by complete neuroimage surveys including computed tomography angiography (CTA), magnetic resonance angiography (MRA), and digital subtraction angiography (DSA). She was then successfully treated by endovascular stent-assisted coil embolization. CONCLUSION: By modern sophisticated neuroimages, BAD could be diagnosed. Endovascular treatment with stent-assisted coil embolization can be a safe and efficacious choice for relatively poor surgical indicated patients with hemorrhagic BAD.

Efficacious CO2 Photoconversion to C2 and C3 Hydrocarbons on Upright SnS-SnS2 Heterojunction Nanosheet Frameworks.

In this work, SnS-SnS2 heterostructured upright nanosheet frameworks are constructed on FTO substrates, which demonstrate promising photocatalytic performances for the conversion of CO2 and water to C2 (acetaldehyde) and C3 (acetone) hydrocarbons without H2 formation. With post annealing in designated atmospheres, the photocatalytic activity of the SnS-SnS2 heterostructured nanosheet framework is critically enhanced by increasing the fraction of crystalline SnS in nanosheets through partial transformation of the SnS2 matrix to SnS but not obviously influenced by improving the crystallinity of the SnS2 matrix. DFT calculations indicate that transformed SnS possesses the CO2 adsorption sites with significantly lower activation energy for the rate-determining step to drive efficient CO2 conversion catalysis. The experimental results and DFT calculations suggest that the SnS-SnS2 heterojunction nanosheet framework photocatalyst experiences Z-scheme charge transfer dynamic to allow the water oxidation and CO2 reduction reactions occurring on the surfaces of SnS2 and SnS, respectively. The Z-scheme SnS-SnS2 heterostructured nanosheet framework photocatalyst exhibits not only efficient charge separation but also highly catalytic active sites to boost the photocatalytic activity for CO2 conversion to C2 and C3 hydrocarbons.

Spastic paraplegia preceding PSEN1-related familial Alzheimer's disease.

INTRODUCTION: We investigated the frequency, neuropathology, and phenotypic characteristics of spastic paraplegia (SP) that precedes dementia in presenilin 1 (PSEN1) related familial Alzheimer's disease (AD). METHODS: We performed whole exome sequencing (WES) in 60 probands with hereditary spastic paraplegia (HSP) phenotype that was negative for variants in known HSP-related genes. Where PSEN1 mutation was identified, brain biopsy was performed. We investigated the link between HSP and AD with PSEN1 in silico pathway analysis and measured in vivo the stability of PSEN1 mutant γ-secretase. RESULTS: We identified a PSEN1 variant (p.Thr291Pro) in an individual presenting with pure SP at 30 years of age. Three years later, SP was associated with severe, fast cognitive decline and amyloid deposition with diffuse cortical plaques on brain biopsy. Biochemical analysis of p.Thr291Pro PSEN1 revealed that although the mutation does not alter active γ-secretase reconstitution, it destabilizes γ-secretase-amyloid precursor protein (APP)/amyloid beta (Aßn) interactions during proteolysis, enhancing the production of longer Aß peptides. We then extended our analysis to all 226 PSEN1 pathogenic variants reported and show that 7.5% were associated with pure SP onset followed by cognitive decline later in the disease. We found that PSEN1 cases manifesting initially as SP have a later age of onset, are associated with mutations located beyond codon 200, and showed larger diffuse, cored plaques, amyloid-ring arteries, and severe CAA. DISCUSSION: We show that pure SP can precede dementia onset in PSEN1-related familial AD. We recommend PSEN1 genetic testing in patients presenting with SP with no variants in known HSP-related genes, particularly when associated with a family history of cognitive decline.

PGxCorpus, a manually annotated corpus for pharmacogenomics.

Pharmacogenomics (PGx) studies how individual gene variations impact drug response phenotypes, which makes PGx-related knowledge a key component towards precision medicine. A significant part of the state-of-the-art knowledge in PGx is accumulated in scientific publications, where it is hardly reusable by humans or software. Natural language processing techniques have been developed to guide experts who curate this amount of knowledge. But existing works are limited by the absence of a high quality annotated corpus focusing on PGx domain. In particular, this absence restricts the use of supervised machine learning. This article introduces PGxCorpus, a manually annotated corpus, designed to fill this gap and to enable the automatic extraction of PGx relationships from text. It comprises 945 sentences from 911 PubMed abstracts, annotated with PGx entities of interest (mainly gene variations, genes, drugs and phenotypes), and relationships between those. In this article, we present the corpus itself, its construction and a baseline experiment that illustrates how it may be leveraged to synthesize and summarize PGx knowledge.

Flunarizine and the risk of parkinsonism in a newly diagnosed type 2 diabetic population in Taiwan: A nested case-control study.

Previous studies demonstrated that both diabetes and flunarizine use can increase the risk of parkinsonism. The aim of the current study was to investigate the risk of developing parkinsonism after flunarizine treatment, in a cohort of patients newly diagnosed with type 2 diabetes. We conducted a nested case-control study of a type 2 diabetic cohort from the Taiwan Longitudinal Health Insurance Database 2005 (LHID 2005). Each incident case of parkinsonism, during the period from 2001 to 2013, was randomly matched with 3-10 controls, according to age, sex, calendar year of cohort entry, and the duration of follow-up. Conditional logistic regression was used to estimate the odds ratio (OR) of parkinsonism associated with flunarizine use. The cohort consisted of 44,644 patients with newly diagnosed type 2 diabetes from 2001 to 2013, of whom 464 patients had a parkinsonism event during the follow-up period. The adjusted OR of parkinsonism with relation to flunarizine use was 2.75 (95% confidence interval: 2.26-3.36). There were also duration- and dose-response effects. Compared to those who had not used it, the OR for developing parkinsonism was 1.77 for patients who used flunarizine for less than 1 month. When the exposure period expanded over 3 months, the OR increased to 7.03. Our findings suggested that flunarizine use is a potential risk factor for parkinsonism in patients with newly diagnosed type 2 diabetes, especially when the drug is persistently used for over 3 months.

A Knowledge-based System for Intelligent Support in Pharmacogenomics Evidence Assessment: Ontology-driven Evidence Representation and Retrieval.

Pharmacogenomics holds promise as a critical component of precision medicine. Yet, the use of pharmacogenomics in routine clinical care is minimal, partly due to the lack of efficient and effective use of existing evidence. This paper describes the design, development, implementation and evaluation of a knowledge-based system that fulfills three critical features: a) providing clinically relevant evidence, b) applying an evidence-based approach, and c) using semantically computable formalism, to facilitate efficient evidence assessment to support timely decisions on adoption of pharmacogenomics in clinical care. To illustrate functionality, the system was piloted in the context of clopidogrel and warfarin pharmacogenomics. In contrast to existing pharmacogenomics knowledge bases, the developed system is the first to exploit the expressivity and reasoning power of logic-based representation formalism to enable unambiguous expression and automatic retrieval of pharmacogenomics evidence to support systematic review with meta-analysis.

Usability evaluation of pharmacogenomics clinical decision support aids and clinical knowledge resources in a computerized provider order entry system: a mixed methods approach.

BACKGROUND: Pharmacogenomics (PGx) is positioned to have a widespread impact on the practice of medicine, yet physician acceptance is low. The presentation of context-specific PGx information, in the form of clinical decision support (CDS) alerts embedded in a computerized provider order entry (CPOE) system, can aid uptake. Usability evaluations can inform optimal design, which, in turn, can spur adoption. OBJECTIVES: The study objectives were to: (1) evaluate an early prototype, commercial CPOE system with PGx-CDS alerts in a simulated environment, (2) identify potential improvements to the system user interface, and (3) understand the contexts under which PGx knowledge embedded in an electronic health record is useful to prescribers. METHODS: Using a mixed methods approach, we presented seven cardiologists and three oncologists with five hypothetical clinical case scenarios. Each scenario featured a drug for which a gene encoding drug metabolizing enzyme required consideration of dosage adjustment. We used Morae(®) to capture comments and on-screen movements as participants prescribed each drug. In addition to PGx-CDS alerts, 'Infobutton(®)' and 'Evidence' icons provided participants with clinical knowledge resources to aid decision-making. RESULTS: Nine themes emerged. Five suggested minor improvements to the CPOE user interface; two suggested presenting PGx information through PGx-CDS alerts using an 'Infobutton' or 'Evidence' icon. The remaining themes were strong recommendations to provide succinct, relevant guidelines and dosing recommendations of phenotypic information from credible and trustworthy sources; any more information was overwhelming. Participants' median rating of PGx-CDS system usability was 2 on a Likert scale ranging from 1 (strongly agree) to 7 (strongly disagree). CONCLUSIONS: Usability evaluation results suggest that participants considered PGx information important for improving prescribing decisions; and that they would incorporate PGx-CDS when information is presented in relevant and useful ways.

A divide-and-conquer strategy to solve the out-of-memory problem of processing thousands of Affymetrix microarrays.

Out-of-memory problem was frequently encountered when processing thousands of CEL files using Bioconductor. We propose a divide-and-conquer strategy combined with randomised resampling to solve this problem. The CAMDA 2007 META-analysis data set which contains 5896 CEL files was used to test the approach on a typical commodity computer cluster by running established pre-processing algorithms for Affymetrix arrays in the Bioconductor package. The results were validated against a golden standard obtained by using a supercomputer. In addition to the performance improvement, the general divide-and-conquer strategy can be applied to any other normalisation algorithms without modifying the underlying implementation.