Giant Hemosiderotic Dermatofibroma: A Case Report and Review of the Literature

Dermatofibroma is a common benign fibrohistiocytic lesion that usually appears as a slow-growing, firm dermal nodule with a predilection for the legs of middle-aged women. They are usually smaller than 2 cm in diameter. Many histological variants have been described. Generally, the clinical and histological diagnosis is straightforward, but differentiating it from other cutaneous tumors can be difficult in atypical cases and rare variants. Giant dermatofibroma is a rare clinical variant of dermatofibroma and less than 25 cases have been reported. It is characterized essentially by its unusually large size, which often mimics malignant tumors clinically. We first present the case of a giant hemosiderotic dermatofibroma in a 54-year-old patient, who presented with a large ulcerated mass of the left foot which was excised, and then review the literature briefly

Identification of Frailty using EMR and Admin data: A complex issue

Introduction Frailty is a state of vulnerability to diverse stressors emphasizing the importance of identifying the frail to support them. The burden of frailty in Canada is steadily growing. Today, approximately 25% of people over age 65 and 50% past age 85 – over one million Canadians – are medically frail. Objectives and Approach To develop an administrative data definition of frailty to facilitate clinical and health system planning. We will validate the definition by linking the administrative data to electronic medical records (EMR) data. The EMR definition is based on a Machine Learning binarized frailty flag for patients with a Rockwood Clinical Frailty Score > 5 on physician chart audit. The sensitivity of the Machine Learning was disappointing: 28% (95% CI: 21% to 36%).specificity was: 94% (95% CI: 93% to 96%), positive predictive value: 53% (95% CI: 42% to 64%), negative predictive value: 86% (95% CI: 83% to 88%). Results There was little overlap between the EMR and administrative data definitions using the same population. Of the 29,382 eligible administrative data community dwelling patients over 65 years old, with a linkable EMR record, 2398 (8.15%) were identified as frail using the administrative data definition, but only 16.1% of these were frail according to the EMR definition. Of the 2396 who were identified as frail in EMR data, only 375 (15.7%) were identified as frail using the administrative data definition. Conclusion/Implications We are not yet able to develop a reliable administrative data definition of frailty to identify community living individuals to support health service planning. The lack of agreement between the results obtained from EMR and administrative data definitions suggests that further refinement is necessary. Identification of frailty remains complex

Cross-Jurisdictional Analysis of Administrative Health Data and Primary Care Electronic Medical Records in Canada

Over the last 30 years, public investments have created and supported administrative health data resources and repositories in Canada to support population health, health services and health policy research. Together, these repositories represent the building blocks of a world-class data platform that enables evidence-informed clinical, managerial and policy decisions. But because Canada’s universal health care system is managed at the provincial level, these repositories have limited capacity to share and use data across jurisdictional boundaries. Challenges with timely access to data remain and differences between jurisdictions affect the quality, scope, and impact of work that could be done. There are considerable benefits to be obtained from collaboration seeking to compare and/or combine health data across jurisdictional borders, despite the limitations in sharing the data. To ensure that Canadians continue to have access to high-quality health care and benefit from effective health policies, researchers and system planners must have access to and be able to make effective use of administrative health data. The purpose of this paper is to describe how we approached and addressed challenges in data access, data governance and data architecture in a Canadian cross-jurisdictional research study

Extensive pleiotropism and allelic heterogeneity mediate metabolic effects of IRX3 and IRX5

While coding variants often have pleiotropic effects across multiple tissues, non-coding variants are thought to mediate their phenotypic effects by specific tissue and temporal regulation of gene expression. Here, we dissected the genetic and functional architecture of a genomic region within the FTO gene that is strongly associated with obesity risk. We show that multiple variants on a common haplotype modify the regulatory properties of several enhancers targeting IRX3 and IRX5 from megabase distances. We demonstrate that these enhancers impact gene expression in multiple tissues, including adipose and brain, and impart regulatory effects during a restricted temporal window. Our data indicate that the genetic architecture of disease-associated loci may involve extensive pleiotropy, allelic heterogeneity, shared allelic effects across tissues, and temporally-restricted effects

Feedhorn-coupled TES polarimeter camera modules at 150 GHz for CMB polarization measurements with SPTpol

The SPTpol camera is a dichroic polarimetric receiver at 90 and 150 GHz. Deployed in January 2012 on the South Pole Telescope (SPT), SPTpol is looking for faint polarization signals in the Cosmic Microwave Background (CMB). The camera consists of 180 individual Transition Edge Sensor (TES) polarimeters at 90 GHz and seven 84-polarimeter camera modules (a total of 588 polarimeters) at 150 GHz. We present the design, dark characterization, and in-lab optical properties of the 150 GHz camera modules. The modules consist of photolithographed arrays of TES polarimeters coupled to silicon platelet arrays of corrugated feedhorns, both of which are fabricated at NIST-Boulder. In addition to mounting hardware and RF shielding, each module also contains a set of passive readout electronics for digital frequency-domain multiplexing. A single module, therefore, is fully functional as a miniature focal plane and can be tested independently. Across the modules tested before deployment, the detectors average a critical temperature of 478 mK, normal resistance R_N of 1.2 Ohm, unloaded saturation power of 22.5 pW, (detector-only) optical efficiency of ~ 90%, and have electrothermal time constants < 1 ms in transition.Comment: 15 pages, 11 figure

Human replication protein A unfolds telomeric G-quadruplexes

G-quadruplex structures inhibit telomerase activity and must be disrupted for telomere elongation during S phase. It has been suggested that the replication protein A (RPA) could unwind and maintain single-stranded DNA in a state amenable to the binding of telomeric components. We show here that under near-physiological in vitro conditions, human RPA is able to bind and unfold G-quadruplex structures formed from a 21mer human telomeric sequence. Analyses by native gel electrophoresis, cross-linking and fluorescence resonance energy transfer indicate the formation of both 1:1 and 2:1 complexes in which G-quadruplexes are unfolded. In addition, quadruplex opening by hRPA is much faster than observed with the complementary DNA, demonstrating that this protein efficiently unfolds G-quartets. A two-step mechanism accounting for the binding of hRPA to G-quadruplexes is proposed. These data point to the involvement of hRPA in regulation of telomere maintenance

Data management challenges for artificial intelligence in plant and agricultural research [version 2; peer review: 2 approved]

Artificial Intelligence (AI) is increasingly used within plant science, yet it is far from being routinely and effectively implemented in this domain. Particularly relevant to the development of novel food and agricultural technologies is the development of validated, meaningful and usable ways to integrate, compare and visualise large, multi-dimensional datasets from different sources and scientific approaches. After a brief summary of the reasons for the interest in data science and AI within plant science, the paper identifies and discusses eight key challenges in data management that must be addressed to further unlock the potential of AI in crop and agronomic research, and particularly the application of Machine Learning (AI) which holds much promise for this domain

The outcomes measured and reported in intracranial meningioma clinical trials: A systematic review

Background Meningioma clinical trials have assessed interventions including surgery, radiotherapy, and pharmacotherapy. However, agreement does not exist on what, how, and when outcomes of interest should be measured. To do so would allow comparative analysis of similar trials. This systematic review aimed to summarize the outcomes measured and reported in meningioma clinical trials. Methods Systematic literature and trial registry searches were performed to identify published and ongoing intracranial meningioma clinical trials (PubMed, Embase, Medline, CINAHL via EBSCO, and Web of Science, completed January 22, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were deduplicated and the resulting unique outcomes were grouped under standardized outcome terms. These were classified using the taxonomy proposed by the “Core Outcome Measures in Effectiveness Trials” (COMET) initiative. Results Thirty published articles and 18 ongoing studies were included, describing 47 unique clinical trials: Phase 2 n = 33, phase 3 n = 14. Common interventions included: Surgery n = 13, radiotherapy n = 8, and pharmacotherapy n = 20. In total, 659 verbatim outcomes were reported, of which 84 were defined. Following de-duplication, 415 unique verbatim outcomes remained and were grouped into 115 standardized outcome terms. These were classified using the COMET taxonomy into 29 outcome domains and 5 core areas. Conclusions Outcome measurement across meningioma clinical trials is heterogeneous. The standardized outcome terms identified will be prioritized through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a core outcome set for use in future meningioma clinical trials

The outcomes measured and reported in observational studies of incidental and untreated intracranial meningioma: A systematic review

Background The clinical management of patients with incidental intracranial meningioma varies markedly and is often based on clinician choice and observational data. Heterogeneous outcome measurement has likely hampered knowledge progress by preventing comparative analysis of similar cohorts of patients. This systematic review aimed to summarize the outcomes measured and reported in observational studies. Methods A systematic literature search was performed to identify published full texts describing active monitoring of adult cohorts with incidental and untreated intracranial meningioma (PubMed, EMBASE, MEDLINE, and CINAHL via EBSCO, completed January 24, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were de-duplicated and the resulting unique outcomes were grouped under standardized outcome terms. These were classified using the taxonomy proposed by the “Core Outcome Measures in Effectiveness Trials” (COMET) initiative. Results Thirty-three published articles and 1 ongoing study were included describing 32 unique studies: study designs were retrospective n = 27 and prospective n = 5. In total, 268 verbatim outcomes were reported, of which 77 were defined. Following de-duplication, 178 unique verbatim outcomes remained and were grouped into 53 standardized outcome terms. These were classified using the COMET taxonomy into 9 outcome domains and 3 core areas. Conclusions Outcome measurement across observational studies of incidental and untreated intracranial meningioma is heterogeneous. The standardized outcome terms identified will be prioritized through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a Core Outcome Set for use in future observational studies

Thermodynamic study of interactions between ZnO and ZnO binding peptides using isothermal titration calorimetry

Whilst material specific peptide binding sequences have been identified using a combination of combinato-rial methods and computational modelling tools, a deep molecular level understanding of the fundamental principles through which these interactions occur and in some instances modify the morphology of inorganic materials is far from being fully realized. Understanding the thermodynamic changes that occur during peptide-inorganic interactions and correlating these to structural modifications of the inorganic materials could be the key to achieving and mastering con-trol over material formation processes. This study is a detailed investigation applying isothermal titration calorimetry (ITC) to directly probe thermodynamic changes that occur during interaction of ZnO binding peptides (ZnO-BPs) and ZnO. The ZnO-BPs used are reported sequences G-12 (GLHVMHKVAPPR), GT-16 (GLHVMHKVAPPR-GGGC) and alanine mutants of G-12 (G-12A6, G-12A11 and G-12A12) whose interaction with ZnO during solution synthesis studies have been extensively investigated. The interactions of the ZnO-BPs with ZnO yielded biphasic isotherms comprising both an endo-thermic and an exothermic event. Qualitative differences were observed in the isothermal profiles of the different pep-tides and ZnO particles studied. Measured ΔG values were between -6 and -8.5 kcal/mol and high adsorption affinity val-ues indicated the occurrence of favourable ZnO-BP-ZnO interactions. ITC has great potential in its use to understand peptide-inorganic interactions and with continued development, the knowledge gained may be instrumental for simplifi-cation of selection processes of organic molecules for the advancement of material synthesis and design