Takotsubo Cardiomyopathy: A Case Series and Review of the Literature

Takotsubo cardiomyopathy (TCM) is an unusual form of acute cardiomyopathy showing left ventricular apical ballooning. It is often triggered by intense physical or emotional distress. We report here four cases of TCM and a review of the literature on the topic

The 1994 international transatlantic two-way satellite time and frequency transfer experiment: Preliminary results

The international transatlantic time and frequency transfer experiment was designed by participating laboratories and has been implemented during 1994 to test the international communications path involving a large number of transmitting stations. This paper will present empirically determined clock and time scale differences, time and frequency domain instabilities, and a representative power spectral density analysis. The experiments by the method of co-location which will allow absolute calibration of the participating laboratories have been performed. Absolute time differences and accuracy levels of this experiment will be assessed in the near future

Virtual Interviews for the Independent Plastic Surgery Match: A Modern Convenience or a Modern Misrepresentation?

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Objective: The virtual interview for residency and fellowship applicants has previously been utilized preliminarily in their respective processes. The COVID-19 pandemic forced many programs to switch to a virtual interview process on short notice. In the independent plastic surgery process, which was underway when the pandemic started, applicants had a heterogeneous experience of in-person and virtual interviews. The purpose of this study was to assess if applicants prefer a virtual interview experience to an in-person interview as well as determine if virtual interview applicants had a different opinion of a program compared to the in-person interview applicants. Design/Setting/Participants: The 2019 to 2020 applicants who interviewed at the Indiana University Independent Plastic Surgery program were administered an anonymous online survey about their interview experience at our program. Results: Our survey response was 60% (18/30). The in-person interview group (n = 10) rated their overall interview experience higher than the virtual interview group (n = 8) 8.8 vs 7.5 (p = 0.0314). The in-person interview group felt they became more acquainted with the program, the faculty, and the residents more than the virtual group (4.7 vs 3.25, p < 0.0001) (4.3 vs 3.25, p = 0.0194) (4.3 vs 2.75, p < 0.0001). The majority of applicants favored in-person interviews (16/18, 88.9%). The in-person interview group spent significantly more money on their interview at our program compared to the virtual interview group ($587 vs$0, p < 0.0001). Conclusion: Our study demonstrated that the virtual interview process was an efficient process for applicants from both a financial and time perspective. However, the virtual interview process left applicants less satisfied with their interview experience. The applicants felt they did not become as acquainted with the program as their in-person counterparts. The virtual interview process may play a large role in residency and fellowship applications in the future, and programs should spend time on how to improve the process

The Journal of Microelectronic Research 2005

https://scholarworks.rit.edu/meec_archive/1014/thumbnail.jp

Localized 4 Integrin Phosphorylation Directs Shear Stress-Induced Endothelial Cell Alignment

Vascular endothelial cells respond to laminar shear stress by aligning in the direction of flow, a process which may contribute to athero-protection. Here we report that localized α4 integrin phosphorylation is a mechanism for establishing the directionality of shear stress-induced alignment in microvascular endothelial cells. Within 5 minutes of exposure to a physiological level of shear stress, endothelial α4 integrins became phosphorylated on Ser988. In wounded monolayers, phosphorylation was enhanced at the downstream edges of cells relative to the source of flow. The shear-induced α4 integrin phosphorylation was blocked by inhibitors of cAMP-dependent protein kinase A (PKA), an enzyme involved in the alignment of endothelial cells under prolonged shear. Moreover, shear-induced localized activation of the small GTPase Rac1, which specifies the directionality of endothelial alignment, was similarly blocked by PKA inhibitors. Furthermore, endothelial cells bearing a non-phosphorylatable α4(S988A) mutation failed to align in response to shear stress, thus establishing α4 as a relevant PKA substrate. We thereby show that shear-induced PKA-dependent α4 integrin phosphorylation at the downstream edge of endothelial cells promotes localized Rac1 activation, which in turn directs cytoskeletal alignment in response to shear stress

Assessment of an in silico mechanistic model for proarrhythmia risk prediction under the CiPA initiative

International Council on Harmonization S7B and E14 regulatory guidelines are sensitive but not specific for predicting which drugs are proarrhythmic. In response, the Comprehensive In Vitro Proarrhythmia Assay (CiPA) was proposed that integrates multi-ion channel pharmacology data in vitro into a human cardiomyocyte model in silico for proarrhythmia risk assessment. Previously, we reported the model optimization and proarrhythmia metric selection based on CiPA training drugs. In this study, we report the application of the prespecified model and metric to independent CiPA validation drugs. Over two validation datasets, the CiPA model performance meets all pre-specified measures for ranking and classifying validation drugs, and outperforms alternatives, despite some in vitro data differences between the two datasets due to different experimental conditions and quality control procedures This suggests that the current CiPA model/metric is fit for regulatory use, and standard experimental protocols and quality control criteria could increase the model prediction accuracy even further

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment