ColoWeb: a resource for analysis of colocalization of genomic features.

BACKGROUND: Next-generation sequencing techniques such as ChIP-seq allow researchers to investigate the genomic position of nuclear components and events. These experiments provide researchers with thousands of regions of interest to probe in order to identify biological relevance. As the cost of sequencing decreases and its robustness increases, more and more researchers turn to genome-wide studies to better understand the genomic elements they are studying. One way to interpret the output of sequencing studies is to investigate how the element of interest localizes in relationship to genome annotations and the binding of other nuclear components. Colocalization of genomic features could indicate cooperation and provide evidence for more detailed investigations. Although there are several existing tools for visualizing and analyzing colocalization, either they are difficult to use for experimental researchers, not well maintained, or without measurements for colocalization strength. Here we describe an online tool, ColoWeb, designed to allow experimentalists to compare their datasets to existing genomic features in order to generate hypotheses about biological interactions easily and quickly. RESULTS: ColoWeb is a web-based service for evaluating the colocation of genomic features. Users submit genomic regions of interest, for example, a set of locations from a ChIP-seq analysis. ColoWeb compares the submitted regions of interest to the location of other genomic features such as transcription factors and chromatin modifiers. To facilitate comparisons among various genomic features, the output consists of both graphical representations and quantitative measures of the degree of colocalization between user's genomic regions and selected features. Frequent colocation may indicate a biological relationship. CONCLUSION: ColoWeb is a biologist-friendly web service that can quickly provide an assessment of thousands of genomic regions to identify colocated genomic features. ColoWeb is freely available at: http://projects.insilico.us.com/ColoWeb .

Preemptive Impella 5.5 insertion to reduce operative risk in high-risk cardiac surgery: A case report.

INTRODUCTION AND IMPORTANCE: Society of thoracic surgery (STS) risk score has been used as a tool to gauge operative risk of cardiac surgery patients. High-risk patients, with STS risk score > 8 %, are considered as having prohibitive risk and are not offered surgery. There is no established strategy to minimize postoperative hemodynamic instability using mechanical circulatory support (MCS), despite growing interest in utilizing MCS prior to hemodynamic instability. The Impella 5.5 can provide enough perfusion and unload the left ventricle. CASE PRESENTATION: We managed a 75-year-old male with multiple comorbidities and a presumed Society of Thoracic Surgeons (STS) score higher than 9.8 %, who had redo coronary artery bypass grafting and aortic and mitral valve replacement with concomitant implantation of the Impella 5.5. Patient had a good recovery despite developing post-operative atrial fibrillation. DISCUSSION: Impella is used as a mechanical circulatory support device in patients with cardiogenic shock. It provides forward flow and effectively unloads the left ventricle. The concomitant placement of the Impella 5.5 in high-risk cardiac candidates may be associated with reduced operative risk. CONCLUSION: Placement of the device as part of surgical plan can potentially mitigate the perioperative risk by providing adequate endogean perfusion, decrease pressor support, unloading LV.

Essential requirements for establishing and operating data trusts: practical guidance co-developed by representatives from fifteen canadian organizations and initiatives.

INTRODUCTION: Increasingly, the label "data trust" is being applied to repeatable mechanisms or approaches to sharing data in a timely, fair, safe, and equitable way. However, there is an absence of practical guidance regarding how to establish and operate a data trust. AIM AND APPROACH: In December 2019, the Canadian Institute for Health Information and the Vector Institute for Artificial Intelligence convened a working meeting of 19 people representing 15 Canadian organizations/initiatives involved in data sharing, most of which focus on public sector health data. The objective was to identify essential requirements for the establishment and operation of data trusts in the Canadian context. Preliminary requirements were discussed during the meeting and then refined as authors contributed to this manuscript. RESULTS: Twelve minimum specification requirements ("min specs") for data trusts were identified. The foundational min spec is that data trusts must meet all legal requirements, including legal authority to collect, hold or share data. In addition, there was agreement that data trusts must have (i) an accountable governing body to ensure that the data trust achieves its stated purpose and is transparent, (ii) comprehensive data management including clear processes and qualified individuals responsible for the collection, storage, access, disclosure and use of data, (iii) training and accountability requirements for all data users and (iv) ongoing public and stakeholder engagement. CONCLUSIONS: Practical guidance for the establishment and operation of data trusts was articulated in the form of 12 min specs requirements. The 12 min specs are a starting point. Future work to refine and strengthen them with members of the public, companies, and additional research data stakeholders from within and outside of Canada, is recommended.

Expanding the Types of Lipids Amenable to Native Mass Spectrometry of Lipoprotein Complexes.

Native mass spectrometry (MS) has become an important tool for the analysis of membrane proteins. Although detergent micelles are the most commonly used method for solubilizing membrane proteins for native MS, nanoscale lipoprotein complexes such as nanodiscs are emerging as a promising complementary approach because they solubilize membrane proteins in a lipid bilayer environment. However, prior native MS studies of intact nanodiscs have employed only a limited set of phospholipids that are similar in mass. Here, we extend the range of lipids that are amenable to native MS of nanodiscs by combining lipids with masses that are simple integer multiples of each other. Although these lipid combinations create complex distributions, overlap between resonant peak series allows interpretation of nanodisc spectra containing glycolipids, sterols, and cardiolipin. We also investigate the gas-phase stability of nanodiscs with these new lipids towards collisional activation. We observe that negative ionization mode or charge reduction stabilizes nanodiscs and is essential to preserving labile lipids such as sterols. These new approaches to native MS of nanodiscs will enable future studies of membrane proteins embedded in model membranes that more accurately mimic natural bilayers. Graphical Abstract.

Protocol update and statistical analysis plan for CADENCE-BZ: a randomized clinical trial to assess the efficacy of sodium benzoate as an adjunctive treatment in early psychosis.

BACKGROUND: CADENCE-BZ is a multi-centre, parallel-group, double-blind randomized controlled trial designed to examine the clinical efficacy and safety of an accessible food preservative, sodium benzoate, as an add-on treatment for patients with early psychosis. The original study protocol was published in 2017. Here, we describe the updated protocol along with the Statistical Analysis Plan (SAP) for the CADENCE-BZ trial prior to study completion. METHODS AND MATERIALS: Two important changes were made to the original protocol: (1) improvements to our statistical analysis plan permitted a reduction in sample size; and (2) a revision in the secondary outcomes with the intent of reducing redundancy and excluding those measures that were not appropriate as outcomes. CONCLUSIONS: We provide the updated SAP prior to the completion of the study with the intent of increasing the transparency of the data analyses for CADENCE-BZ. The final participants are currently completing the study and the results will be published in the near future. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12615000187549 ). Registered on 26th February 2015.

The prevalence and treatment outcomes of antineuronal antibody-positive patients admitted with first episode of psychosis.

BACKGROUND: Antineuronal antibodies are associated with psychosis, although their clinical significance in first episode of psychosis (FEP) is undetermined. AIMS: To examine all patients admitted for treatment of FEP for antineuronal antibodies and describe clinical presentations and treatment outcomes in those who were antibody positive. METHOD: Individuals admitted for FEP to six mental health units in Queensland, Australia, were prospectively tested for serum antineuronal antibodies. Antibody-positive patients were referred for neurological and immunological assessment and therapy. RESULTS: Of 113 consenting participants, six had antineuronal antibodies (anti-N-methyl-D-aspartate receptor antibodies [n = 4], voltage-gated potassium channel antibodies [n = 1] and antibodies against uncharacterised antigen [n = 1]). Five received immunotherapy, which prompted resolution of psychosis in four. CONCLUSIONS: A small subgroup of patients admitted to hospital with FEP have antineuronal antibodies detectable in serum and are responsive to immunotherapy. Early diagnosis and treatment is critical to optimise recovery. DECLARATION OF INTEREST: None.

Acute intramural hematoma of the aorta as a cause of positive FDG PET/CT.

Type A acute intramural hematoma (IMH) of the ascending aorta is defined as hemorrhage in the aortic wall in the absence of intimal disruption. Proximity to the adventitia may explain the higher incidence of rupture in IMH. We present a case of IMH, diagnosed by the presence of linear intense uptake of FDG on PET/CT, in a 70-year-old woman undergoing staging for colorectal cancer. There is no current role for FDG-PET in the diagnosis of IMH. This case demonstrates that incidental focal FDG activity in the wall of the aorta may indicate the life-threatening diagnosis of IMH.

The efficacy of sodium benzoate as an adjunctive treatment in early psychosis - CADENCE-BZ: study protocol for a randomized controlled trial.

BACKGROUND: Psychotic disorders affect up to 3% of the population and are often chronic and disabling. Innovation in the pharmacological treatment of psychosis has remained stagnant in recent decades. In order to improve outcomes for those with psychotic disorders, we present a protocol for the trial of a common food preservative, sodium benzoate, as an adjunctive treatment in early psychosis. METHODS: Persons experiencing early psychosis (n = 160) will be recruited through hospitals and community mental health services in Queensland, Australia. Patients will be randomized to receive either 12-week treatment with 1000 mg (500 mg twice daily (BD)) sodium benzoate or placebo. Patients will undergo fortnightly outcome assessments, in addition to weekly ongoing capacity to consent, drug compliance and safety assessments. The primary outcome measure is the Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcomes are Global Assessment of Function (GAF), Assessment of Quality of Life Scale (AQOL), the Activity and Participation Questionnaire (APQ6), International Physical Activity Questionnaires (IPAQ), Simple Physical Activity Questionnaire (SIMPAQ), Physical Activity Questionnaire, Clinical Global Impression (CGI), Hamilton Depression rating Scale-17 items (HDRS), Opiate Treatment Index (OTI) and the Patients' Global Impression of Improvement (PGI-I). As a tertiary objective, changes from baseline to endpoint in to serum markers related to D-alanine, L-alanine, D-serine, L-serine, glycine and glutamate will be investigated. DISCUSSION: Consumers and clinicians are keen to help develop better treatments for those with psychosis. This study, part of the wider Cadence clinical trials platform will examine if a safe and accessible food preservative can help optimize outcomes in those with psychosis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials registry (ANZCTR), ACTRN12615000187549 . Registered on 26 February 2015.

Translational control of the cytosolic stress response by mitochondrial ribosomal protein L18.

In response to stress, cells attenuate global protein synthesis but permit efficient translation of mRNAs encoding heat-shock proteins (HSPs). Although decades have passed since the first description of the heat-shock response, how cells achieve translational control of HSP synthesis remains enigmatic. Here we report an unexpected role for mitochondrial ribosomal protein L18 (MRPL18) in the mammalian cytosolic stress response. MRPL18 bears a downstream CUG start codon and generates a cytosolic isoform in a stress-dependent manner. Cytosolic MRPL18 incorporates into the 80S ribosome and facilitates ribosome engagement on mRNAs selected for translation during stress. MRPL18 knockdown has minimal effects on mitochondrial function but substantially dampens cytosolic HSP expression at the level of translation. Our results uncover a hitherto-uncharacterized stress-adaptation mechanism in mammalian cells, which involves formation of a 'hybrid' ribosome responsible for translational regulation during the cytosolic stress response.

PET/CT Protocols and Artifacts in the Head and Neck.

Combined PET/CT has been in existence clinically for nearly 7 years since development and initial evaluation from 1998 to 2001. Combined PET/CT offers advantages over PET and CT acquired on separate devices, including consolidation of imaging studies, more accurate data coregistration, improved lesion localization, and benefits related to radiation therapy planning. This article discusses CT and PET protocols pertinent to PET/CT imaging in patients who have head and neck cancer, including a discussion of how the CT portion of a PET/CT scan can be performed and a description of common PET/CT artifacts that may be encountered secondary to CT protocols.