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R code of our analysis for driver mutation discovery in Hodgkin lymphoma WGS and WES.

Supplementary Tables S1-S20

Background: Amniotic fluid index (AFI) is a key element in fetal biophysical profile that predicts pregnancy outcome especially near term in primigravidae. The objective of the study was to determine a reference range of AFI in primigravidae of a local population having gestational age from 37 to 42 weeks. Methodology: This study was carried out from January 2019 to December 2019 after approval from Institutional Review Board and Ethical Committee at Shifa International hospital, Islamabad, Pakistan. Applying inclusion and exclusion criteria, a sample of 272 was selected. AFI was calculated for each subject using ultrasound and recorded on a data collection sheet. For the sake of simplicity and clinical relevance, the population was further stratified as term pregnancy (gestational age 37-39 weeks) and postdates pregnancy (40-42 weeks). The reference range of AFI was then calculated using mean ±two standard deviations. Results: The reference range of AFI for gestational age of 37-42 weeks (population as a whole) was 6.8- 17.2 cm. For term pregnancy, it was 7.5- 17.5 cm, and for postdate pregnancy, it was 5.8 to 15.4 cm. Conclusion: The reference range of AFI for gestational age of 37 to 42 weeks in Primigravida women was 6.8 to 17.2 cm. There is a decreasing trend in AFI as pregnancy advances from term to postdate. Keywords: Amniotic Fluid Index, Gestational age, Primigravida, Reference Range.

Метою дослідження є окреслити принципи формування іншомовної комунікативної компетентності майбутніх фахівців ракетно-артилерійського озброєння та класифікувати їх на основі типових ознак. У процесі дослідження з’ясовано, що принципи навчання означає певні рекомендації, що здійснюють регуляцію педагогічною діяльністю викладача та освітнім процесом, з урахуванням особливостей професійної підготовки майбутніх військових фахівців. Доведено, що процес формування іншомовної комунікативної компетентності майбутніх офіцерів ракетно-артилерійського озброєння відбувається з урахуванням певних основоположних принципів, що визначають зміст, організаційні форми та методи освітнього процесу. Здійснено класифікацію принципів та виділено три групи – загально дидактичні, мовно-професійні та принципи методичного спрямування. З’ясовано їх взаємозв’язок та вплив на підвищення рівнів сформованості іншомовної комунікативної компетентності. Детально пояснено шляхи реалізації цих принципів. Доведено необхідність поєднання загально дидактичних, мовно-професійних та принципів методичного спрямування у процесі формування іншомовної комунікативної компетентності майбутніх фахівців ракетно-артилерійського озброєння.

We present a case report of a potentially lethal post-COVID complication. A 65-year-old male presented with shortness of breath and fever with chills. He had recently recovered from COVID pneumonia. Contrast enhanced CT scan chest gave the suspicion of pulmonary pseudoaneurysm. CT aortogram revealed a well-defined rounded mass in the right lung mainly occupying the lower lobe of right lung. Angiography through right common femoral vein was performed and it confirmed a huge pseudoaneurysm arising from the posteromedial branch of the right descending interlobar artery. As the artery was not found suitable for endovascular embolization, the patient was referred to thoracic surgeon.

ObjectivesContinuous hemodynamic monitoring offers the opportunity to individualize management in severe preeclampsia (PEC). We compared cardiac output (CO) and systemic vascular resistance (SVR) measured by bioreactance (NICOM), Clearsite™ Fingercuff [CS), and 3D-echocardiography (3DE).Study DesignThis prospective observational study included 12 pregnant patients with early PEC. CO and SVR were measured simultaneously by NICOM, CS, and 3DE antepartum and 1-2 days postpartum. Using 3DE as the standard, CS and NICOM interchangeability, precision, accuracy, and correlation were assessed.ResultsCompared to 3DE-CO, CS-CO was highly correlated (R2=0.70, p=2=0.81, p=5; LOA -580-18.4) these differences were unlikely to be clinically significant. Thus CS could be interchangeable with 3DE for CO and SVR. NICOM-CO had only moderate correlation with 3DE-CO (R2=0.29, p=0.01) with high PE (52%) above threshold for interchangeability. NICOM-CO had low mean bias (−1.2 +/-1.68 L/min) but wide 95% LOA (−4.41 - 2.14) suggesting adequate accuracy but low precision in relation to 3DE-CO. NICOM-SVR had poor correlation with 3DE-SVR (R2=0.32, p=0.001) with high PE (67%), relatively low mean bias (238 +/-256), and wide 95% LOA (– 655–1131). NICOM did not meet the criteria for interchangeable with 3DE for CO and SVR.ConclusionsClearsite Fingercuff, but not NICOM, has potential to be clinically useful for CO and SVR monitoring in severe preeclampsia.

A. Tumors were undetectable at 4 weeks by IVIS imaging when b-AP15 was administered from day 1 after injecting A673 cells expressing GFP-luciferase. NSG mice bearing A673 xenografts were treated with DMSO, bortezomib or b-AP15 after they reached 80-100mm3 and weekly tumor size measurements were taken. B. b-AP15 slowed the growth of the established A673 xenografts and C. prolonged survival of A673 tumor bearing mice compared to bortezomib. D. VLX-1570 and b-AP15 treatment did not cause significant weight loss in xenograft models. (two way Anova with Tukey's multiple comparison test).

Ewing sarcoma is a primitive round cell sarcoma with a peak incidence in adolescence that is driven by a chimeric oncogene created from the fusion of the EWSR1 gene with a member of the ETS family of genes. Patients with metastatic and recurrent disease have dismal outcomes and need better therapeutic options. We screened a library of 309,989 chemical compounds for growth inhibition of Ewing sarcoma cells to provide the basis for the development of novel therapies and to discover vulnerable pathways that might broaden our understanding of the pathobiology of this aggressive sarcoma. This screening campaign identified a class of benzyl-4-piperidone compounds that selectively inhibit the growth of Ewing sarcoma cell lines by inducing apoptosis. These agents disrupt 19S proteasome function through inhibition of the deubiquitinating enzymes USP14 and UCHL5. Functional genomic data from a genome-wide shRNA screen in Ewing sarcoma cells also identified the proteasome as a node of vulnerability in Ewing sarcoma cells, providing orthologous confirmation of the chemical screen findings. Furthermore, shRNA-mediated silencing of USP14 or UCHL5 in Ewing sarcoma cells produced significant growth inhibition. Finally, treatment of a xenograft mouse model of Ewing sarcoma with VLX1570, a benzyl-4-piperidone compound derivative currently in clinical trials for relapsed multiple myeloma, significantly inhibited in vivo tumor growth. Overall, our results offer a preclinical proof of concept for the use of 19S proteasome inhibitors as a novel therapeutic strategy for Ewing sarcoma. Cancer Res; 76(15); 4525–34. ©2016 AACR.

Cell lines were treated with the indicated compounds for 96 h and then growth determined. Results represent the mean {plus minus} SD of 2-4 experiments in which each condition was assayed in triplicate.

Results and analysis of a genome-wide functional genomic screen using the Sigma-Aldrich shRNA Human Genome Library consisting of 63,093 shRNAs targeting 11,748 human genes.

A. Pair�wise expression profile comparisons of EWS cell lines treated with the known proteasome inhibitors bortezomib and MG�262 demonstrated highly significant overlap with profiles treated with compounds EWS-P and EWS-W. B. Overlap included 13 core genes established through published studies as being upregulated by 20S inhibitors such as bortezomib and MG-262. C. EWS cell lines TC-71 and CHP100 show demonstrate an increase in polyubiquitinated proteins following treatment with proteasome inhibitors MG-262, bortezomib, EWS-P, and EWS-W.

Supplementary Tables

Supplementary Video

General Procedures for synthesis of 2,6-Bis-arylidenepiperidone scaffold

Ingenuity Pathway Analysis of positive hits identifies enrichment of genes involved in the ubiquitin-proteasome pathway.

72 hour IC50 growth inhibition levels (μM) of 23 compounds (labeled EWS-A through EWS-X) against five EWS cell lines and 11 non-EWS cell lines

Panel upper left: CHP100 cells exposed 3 hours to different concentrations of b-AP15. Extracts were labeled with HA-Ub-VS and subjected to western blot. Filters probed with HA antibody. Note the lack of inhibition of any of the DUBs labeled by HA-Ub-VS. Panel upper right: CHP100 cells exposed 3 hours to 1 uM b-AP15 Extracts were labeled with Ub-VS and subjected to western blot. Filters probed with USP14, UCHL5 or UCHL1 antibodies. b-AP15 treated extracts demonstrate inhibition of USP14, weak inhibition of UCHL5, and no inhibition of UCHL1. Middle Panels: Purified 26S proteasomes (5 nM) were treated with indicate concentrations for b-AP15 and DUB activity was determined by cleavage of Ub-AMC. Note the reduction in 26S associated proteasome activity following treatment with b-AP15. Lower Panels: Recombinant UCHL1 or UCHL3 was treated with b-AP15 and DUB activity was monitored using Ub-AMC cleavage as above. No inhibition of either UCHL1 or UCHL3 was observed.

To modernize the national system of education, to enhance teachers’ excellence or even to change the direction of professional teaching activity, it is important to upgrade pedagogical science and provide its practical orientation. In this regard, there is a necessity to look differently at the role and methods of experimental research in education. Accordingly, modern educator must fulfill the requirements of modern society; he/she be creative and learned, be able to analyze the experience and see prospects that means to be a researcher. The existing views on experimental research are developed under conditions of functioning of stable or standard programme in the unified state school. But currently, institutional diversity and a wide range of teaching methods can be considered the most significant features of educational system. These features suggest that pedagogical staff at the institution can design and implement their own educational technologies. Consequently, we observe a sharp increase in number of teaching approaches and methods within the educational process that leads to the explosive growth of pedagogical phenomena.

Dear Reader, It is a deep honour that I have been appointed as the Editor-in-Chief of newly-published journal titled EIKI Journal of Effective Teaching Methods. The journal features an exciting array of educational research and developments from experts in pedagogical field. First of all, I would like to extend my sincere thanks to the European Institute of Knowledge and Innovation, which publishes this journal, and which has entrusted me with this important duty. To be the Editor-in-Chief of a scientific journal is a very demanding and serious duty. It is not limited to performing editing tasks and supervising timely and thorough reviewing process of scientific papers. This duty also includes communication with the journal readers. And the editor must respond to their academic interests and needs. Moreover, this involves editor’s ability to respond to criticism and implement the applicable recommendations to improve the journal. Of course, editor is also required to make further plans for the journal, and especially to make sure it is recognized as an outstanding publication on an international plan. Our team constantly work to improve the journal and in nearly future it will get indexed in multiple databases to increase its visibility. Also, we are working on giving a new boost to regional and international cooperation on the journal platform. All these requirements oblige an editor to be ready for hard and long-lasting work, as only systematic attitudes may result in continuous publication of the journal, and constant quality improvements. At this point, please allow me to briefly introduce myself. My principal educational, scientific and professional activities have been focused on the field of linguistics and language education. My doctorate thesis dealt with comparative professional education of law-enforcement personnel in developing countries facing hybrid threats and counteracting proxy war. In addition to my lecturing activity, I am always trying to pursue the cooperation with research institutions, as this is the best way to obtain useful innovative ideas and exchange experience with outstanding scholars. I am currently heading an international project at the European Institute of Knowledge and Innovation. I am also in charge of several worshops for professional advancement in teaching methodology and educational discourse development. When considering various duties of editors-in-chief, then it can rightly be said that a great courage is needed to take on this position, especially if we are talking about newly-published journal that needs through efficient planning and management. In fact, already from the first issue I am editing, innovative features include an updated look of the journal website, easy-to-use journal platform, international experience of the editorial team and reviewers, and appointment of younger colleagues as members of the Editorial Board. As for me, I am thrilled to take on this important responsibility and contribute to the advancement of the scientific community through the publication of cutting-edge research. I am certainly very much interested in ensuring regular publication of the journal and hope it will become one of the leading journals in the sphere of pedagogical science. Also, I encourage newly appointed members of the board to publish papers in this journal to demonstrate their expertise and share innovative ideas as well as to promote the journal within their institutions and persuade their colleagues to present their findings in EIKI Journal of Effective Teaching Methods. Most importantly, I am grateful to the scientific community and the authors who have entrusted us with their research. As an editor-in-chief, I understand the importance of publishing high-quality research that advances our understanding of the world around us. I wish to extend my thanks in advance to all authors who are going to accept our journal as a proper platform for sharing and presenting their research results relating to all aspects of educational process and improvement of teaching methodology in particular. As the Editor-in-Chief of this journal, I am constantly inspired by the dedication and ingenuity of the scientific community, who work tirelessly to advance our understanding of the world around us. I will do everything in my power to ensure that this journal remains a respected and impactful platform for the dissemination of scientific knowledge. In this edition, you will find a diverse range of topics spanning various aspects of pedagogical science including professional training, innovative teaching and use of information and communication technologies, curriculum development, overcoming communication barriers in the educational process as well as organization of experimental research in education. I would like to express my gratitude to the authors, reviewers, and editorial staff who have contributed to the production of this journal. The peer review process is an integral part of our mission to publish high-quality scientific research, and I am grateful for the valuable insights and feedback provided by our reviewers. Finally, I hope that this edition of EIKI Journal of Effective Teaching Methods will serve as a valuable resource for researchers, academics, and practitioners in the scientific community, inspiring future investigations in education area of study and improving educational process in various educational institutions. Today, in times when education has a crucial role for society development, communication between educators from different countries would miraculously lead us to success and educational process modernization, in developing countries in particular. Therefore, I would also like to invite all persons connected with education studies and teaching to support development of the journal in the oncoming period. We promise to create comfortable and resourceful environment to make our cooperation efficient. Sincerely, Prof. Nataliya Bhinder, Doctor Pedagogical Sciences