scholarly journals miRNAtools: advanced training using the miRNA web of knowledge

2017 ◽  
Author(s):  
Francisco J. Enguita

ABSTRACTmiRNAs are small non-coding RNAs, that act as negative regulators of the genomic output. Their intrinsic importance within cell biology and human disease is well known. Their mechanism of action based on the base pairing binding to their cognate targets, have helped the development of many computer applications for the prediction of miRNA target recognition. More recently, many other computer applications have appeared with the objective of studying miRNA roles in many contexts, trying to dissect and predict their functions in a specific biological process. Learning about miRNA function needs a practical training in the use of specific computer and web-based applications that are complementary to the wet-lab studies. In the last seven years we have been involved in the organization of advanced training courses about thein silicofunctional analysis of miRNAs and non-coding RNAs, for students ranging from the postgraduate to the post-doctoral level. In order to guide the learning process about miRNAs, we have created miRNAtools (http://mirnatools.eu), a web repository of miRNA tools and tutorials. This page is a compilation of tools to analyze miRNAs and their regulatory action that intends to collect and organize the information that is dispersed in the web. The miRNAtools webpage is completed by a collection of tutorials that can be used by students and tutors engaged in advanced training courses. The tutorials follow the rationale of the analysis of the function of selected miRNAs, starting from their nomenclature and genomic localization and finishing by assessing their involvement in specific cellular functions.DESCRIPTION OF THE AUTHORFrancisco J. Enguita is assistant professor at the Faculty of Medicine, University of Lisbon and senior investigator at the Instituto de Medicina Molecular within the same University.KEY POINTS- We have designed a web-page, mIRNAtools3 (http://mirnatools.eu) specifically devoted for advanced teaching purposes within the miRNA field.- The webpage constitutes also a repository of web-tools for the analysis of miRNA function in several contexts.- The webpage contains tutorials that cover many aspects related with miRNAs including nomenclature, target prediction and validation, and functional analysis.

Author(s):  
Norina Forna ◽  
◽  
Gheorghe Tibirna ◽  
Claudiu Topoliceanu ◽  
Doriana Agop-Forna ◽  
...  

Theoretical and practical training program for complex cases in implantology, dento-alveolar surgery, OMF and complex oral rehabilitation. With Romania’s accession to the European Union, the opportunity arose to finance through non-reimbursable funds theoretical and practical training programs for teachers of Romanian dental faculties. Faculty of Dentistry, U.M.F. „Grigore T. Popa” Iași won, through POSDRU programs, a series of projects for obtaining European funds that allowed the initiation of training courses in the field of oral rehabilitation (prosthetics, implantology, dental-alveolar surgery, OMF surgery, oral rehabilitation complex). The courses included training and advanced training programs in the latest information and innovative technologies in the areas listed. Also, through these projects, the Faculty of Dentistry was equipped with a series of updated equipment and technologies.


Author(s):  
Larissa Familyarskaya

Updating the ways of interaction between the subjects of educational space, changing the formats of professional activity of a specialist requires a search for improvement of educational practices aimed at developing the digital competence of academic staff in postgraduate pedagogical education. The main challenges in distance educational interaction implementation at advanced training courses in an institution of postgraduate pedagogical education under the conditions of quarantine restrictions are investigated in the article. The approaches offered in the article implement educational communication using the possibilities of digital technologies in postgraduate pedagogical education. The advantages and limitations of distant interaction in the process of teaching adults are highlighted. The means of remote interaction organization in the process of professional development of teachers are systematized. The peculiarities of modern educational environment design in the institution of postgraduate pedagogical education are highlighted, which allows to create and implement a set of educational strategies aimed at implementing remote educational interaction. The definitions of the notions «distance learning», «online learning» are considered and the models of teachers professional development organization on the platform of distance learning of Communal institution «Zhytomyr Regional Institute of Postgraduate Pedagogical Education» of Zhytomyr Regional Council are characterized. The results of the research survey of teaching staff and teachers of advanced training prove that the use of learning environment, system of practical training courses requires adaptation of content, forms and means of teaching to the requirements of social demand, changes in the work of academic staff of postgraduate pedagogical education and improving the digital competence of subject teachers.


Author(s):  
Oksana Mironkina

Methods of training in advanced training groups formed from the staff of personnel divisions of the MIA of Russia, which involve the use of anti-corruption education at different stages of professional activity are discussed in the article. A comprehensive approach to the formation of anti-corruption behavior, which allows using various forms of training of police officers in their relation is described. The effectiveness of this approach in the system of professional development was shown. A comprehensive approach allows the training process to pay attention to the needs and difficulties in the field of corruption prevention without spending time on basic training information. Several stages in the organization and content of training are considered. Each of them corresponds to different stages of professional development of specialists of personnel divisions of internal affairs bodies. Described in detail every stage is aimed at a separate audience and has its own value. The possibilities of anti-corruption education are presented, starting with the selection of personnel for service in the internal affairs bodies and ending with the preparation for dismissal. The anti-corruption educational activities carried out at the present time are analyzed. Methods of intensifying each of them and the possibilities of optimal inclusion in the developed complex of content and forms are determined. The proposed approach can be used for majority posts. It is not limited to human resources units. In addition, the developed methodological material can be used by students in the course of their professional activities in the field after studying at advanced training courses.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ubiratan Cardinalli Adler ◽  
Maristela Schiabel Adler ◽  
Livia Mitchiguian Hotta ◽  
Ana Elisa Madureira Padula ◽  
Amarilys de Toledo Cesar ◽  
...  

Abstract Objectives To investigate the effectiveness and safety of homeopathic medicine Natrum muriaticum (LM2) for mild cases of COVID-19 in Primary Health Care. Trial design A randomized, two-armed (1:1), parallel, placebo-controlled, double-blind, clinical trial is being performed to test the following hypotheses: H0: homeopathic medicines = placebo (null hypothesis) vs. H1: homeopathic medicines ≠ placebo (alternative hypothesis) for mild cases of COVID-19 in Primary Care. Participants Setting: Primary Care of São Carlos – São Paulo – Brazil. One hundred participants aged 18 years or older, with Influenza-like symptoms and a positive RT-PCR for SARS-CoV-2. Willingness to give informed consent and to comply with the study procedures is also required. Exclusion criterium: severe acute respiratory syndrome. Intervention and comparator Homeopathy: 1 globule of Natrum muriaticum LM2 diluted in 20 mL of alcohol 30% and dispensed in a 30 ml bottle. Placebo: 20 mL of alcohol 30% dispensed in a 30 ml bottle. Posology: one drop taken orally every 4 hours (6 doses/day) while there is fever, cough, tiredness, or pain (headache, sore throat, muscle aches, chest pain, etc.) followed by one drop every 6 hours (4 doses/day) until the fourteenth day of use. The bottle of study medication should be submitted to 10 vigorous shakes (succussions) before each dose. Posology may be changed by telemedicine, with no break in blinding. Study medication should be maintained during home isolation. According to the Primary Care protocol, the home isolation period lasts until the 10th day after the appearance of the first symptom, or up to 72 hours without symptoms. Main outcomes The primary endpoint will be time to recovery, defined as the number of days elapsed before all COVID-19 Influenza-like symptoms are recorded as mild or absent during home isolation period. Secondary measures are recovery time for each COVID-19 symptom; score of the scale created for the study (COVID-Simile Scale); medicines used during follow-up; number of days of follow-up; number of visits to emergency services; number of hospitalizations; other symptoms and Adverse Events during home isolation period. Randomisation The study Statistician generated a block randomization list, using a 1:1 ratio of the two groups (denoted as A and B) and a web-based tool (http://www.random.org/lists). Blinding (masking) The clinical investigators, the statistician, the Primary Care teams, the study collaborators, and the participants will remain blinded from the identity of the two treatment groups until the end of the study. Numbers to be randomised (sample size) One hundred participants are planned to be randomized (1:1) to placebo (50) or homeopathy (50). Trial Status Protocol version/date May 21, 2020. Recruitment is ongoing. First participant was recruited/included on June 29,2020. Due to recruitment adaptations to Primary Care changes, the authors anticipate the trial will finish recruiting on April 10, 2021. Trial registration COVID-Simile Study was registered at the University Hospital Medical Information Network (UMIN - https://www.umin.ac.jp/ctr/index.htm) on June 1st, 2020, and the trial start date was June 15, 2020. Unique ID: UMIN000040602. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Merete Nørgaard Madsen ◽  
Maria Lange Kirkegaard ◽  
Thomas Martin Klebe ◽  
Charlotte Lorenzen Linnebjerg ◽  
Søren Martin Riis Villumsen ◽  
...  

Abstract Background Extended scope physiotherapists (ESP) are increasingly supplementing orthopaedic surgeons (OS) in diagnosing patients with musculoskeletal disorders. Studies have reported satisfactory diagnostic and treatment agreement between ESPs and OSs, but methodological study quality is generally low, and only few studies have evaluated inter-professional collaboration. Our aims were: 1) to evaluate agreement on diagnosis and treatment plan between ESPs and OSs examining patients with shoulder disorders, 2) to explore and evaluate their inter-professional collaboration. Methods In an orthopaedic outpatient shoulder clinic, 69 patients were examined independently twice on the same day by an ESP and an OS in random order. Primary and secondary diagnoses (nine categories) and treatment plan (five categories, combinations allowed) were registered by each professional and compared. Percentage of agreement and kappa-values were calculated. Two semi-structured focus-group interviews were performed with ESPs and OSs, respectively. Interviews were based on the theoretical concept of Relational Coordination, encompassing seven dimensions of communication and relationship among professionals. A thematic analysis was conducted. Results Agreement on primary diagnosis was 62% (95% CI: [50; 73]). ESPs and OSs agreed on the combination of diagnoses in 79% (95% CI: [70; 89]) of the cases. Partial diagnostic agreement (one professional’s primary diagnosis was also registered as either primary or secondary diagnosis by the other) was 96% (95% CI: [91; 100]). Across treatment categories, agreement varied between 68% (95% CI: [57; 79]) and 100%. In 43% (95% CI: [31; 54]) of the cases, ESP and OS had full concordance between treatment categories chosen, while they agreed on at least one recommendation in 96% (95% CI: [91; 100]). Positive statements of all dimensions of relational coordination were found. Three themes especially important in the inter-professional collaboration emerged: Close communication, equal and respectful relationship and professional skills. Conclusions In the majority of cases, the ESP and OS registered the same or partly the same diagnosis and treatment plan. Indications of a high relational coordination implying a good inter-professional collaboration were found. Our results support that ESPs and OSs can share the task of examining selected patients with shoulder disorders in an orthopaedic clinic. Trial registration ClinicalTrials.gov Identifier: NCT03343951. Registered 10 November 2017


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A372-A373
Author(s):  
Ira Winer ◽  
Lucy Gilbert ◽  
Ulka Vaishampayan ◽  
Seth Rosen ◽  
Christopher Hoimes ◽  
...  

BackgroundALKS 4230 is a novel engineered cytokine that selectively targets the intermediate-affinity interleukin-2 receptor complex to activate CD8+ T cells and natural killer cells.1 The ARTISTRY-1 trial (NCT02799095) has shown encouraging efficacy and acceptable tolerability of ALKS 4230 among patients with advanced solid tumors.2 We report a detailed analysis of ovarian cancer (OC) patients who received combination therapy in ARTISTRY-1.MethodsARTISTRY-1 is an ongoing multicohort phase 1/2 trial exploring intravenous ALKS 4230 as monotherapy and combined with pembrolizumab. OC patients were enrolled into a cohort with mixed anti PD 1/L1 unapproved tumor types who had progressed on prior chemotherapy. OC patients received ALKS 4230 (3 µg/kg) on days 1–5 and pembrolizumab (200 mg) on day 1 of a 21 day cycle. Outcomes presented include antitumor activity (RECIST v1.1) and safety as of 7/24/2020. To evaluate changes in tumor microenvironment (TME), baseline and on-treatment biopsies were collected.ResultsFourteen heavily pretreated patients with OC were enrolled. Patients received a median of 5 (range, 2 11) prior regimens and all were previously treated with platinum based therapy. Among 13 evaluable patients with ≥1 assessment, 9 experienced disease control and 4 experienced disease progression; median treatment duration was approximately 7 weeks. Three patients experienced an objective response, including 1 complete response, 1 partial response (PR), and 1 unconfirmed PR; all were platinum resistant and negative for BRCA mutations. Five patients experienced tumor burden reductions (table 1). Treatment-related adverse events at the doses tested have generally been transient and manageable, with the majority being grade 1 and 2 in severity. Overall, based on preliminary data, the combination with ALKS 4230 did not demonstrate any additive toxicity to that already established with pembrolizumab alone. Additional safety and efficacy data are being collected in ongoing cohorts. In the monotherapy dose escalation portion of the study, ALKS 4230 alone increased markers of lymphocyte infiltration in 1 paired melanoma biopsy (1 of 1; on treatment at cycle 2); CD8+ T cell density and PD-L1 tumor proportion score increased 5.2- and 11 fold, respectively, supporting evidence that ALKS 4230 has immunostimulatory impact on the TME and providing rationale for combining ALKS 4230 with pembrolizumab (figure 1).Abstract 347 Table 1Summary of response observations among patients with ovarian cancerAbstract 347 Figure 1Increased markers of lymphocyte tumor infiltrationAn increase in CD3+CD8+ T cells (A, red = CD3; blue = CD8; purple = CD3+CD8+; teal = tumor marker), GranzymeB (B, red = CD8; green = granzymeB; yellow = granzymeB+CD8+; teal = tumor marker), and PD-L1 (C, red = PD-L1; blue = tumor marker) in the tumor microenvironment of a single patient was observed after the patient received monotherapy ALKS 4230ConclusionsThe combination of ALKS 4230, an investigational agent, and pembrolizumab demonstrates an acceptable safety profile and provides some evidence of tumor shrinkage and disease stabilization in some patients with heavily pretreated OC. This regimen could represent a new therapeutic option for these patients.AcknowledgementsThe authors would like to thank all of the patients who are participating in this trial and their families. The trial is sponsored by Alkermes, Inc. Medical writing and editorial support was provided by Parexel and funded by Alkermes, Inc.Trial RegistrationClinicalTrials. gov NCT02799095Ethics ApprovalThis trial was approved by Ethics and Institutional Review Boards (IRBs) at all trial sites; IRB reference numbers 16–229 (Dana-Farber Cancer Institute), MOD00003422/PH285316 (Roswell Park Comprehensive Cancer Center), 20160175 (Western IRB), i15-01394_MOD23 (New York University School of Medicine), TRIAL20190090 (Cleveland Clinic), and 0000097 (ADVARRA).ReferencesLopes JE, Fisher JL, Flick HL, Wang C, Sun L, Ernstoff MS, et al. ALKS 4230: a novel engineered IL-2 fusion protein with an improved cellular selectivity profile for cancer immunotherapy. J Immunother Cancer 2020;8:e000673. doi: 10.1136/jitc-2020-000673.Vaishampayan UN, Muzaffar J, Velcheti V, Winer I, Hoimes CJ, Rosen SD, et al. ALKS 4230 monotherapy and in combination with pembrolizumab (pembro) in patients (pts) with refractory solid tumors (ARTISTRY-1). Oral presentation at: European Society for Medical Oncology Annual Meeting; September 2020; virtual.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Thierry Almont ◽  
Louis Bujan ◽  
Clarisse Joachim ◽  
Guillaume Joguet ◽  
Mylène Vestris ◽  
...  

Abstract Background In the French West-Indies, few studies have been performed on fertility and sexual problems in cancer survivors, which are frequent and recurring issues reported by surveys on unmet needs. Additionally, mutualizing human and material resources and promoting cooperation through a collaborative platform are the most appropriate response to complex health pathways in the Caribbean territories. Implementation of such a collaborative platform will help to launch a strategic Caribbean partnership to transfer theoretical and technical skills and care standards in oncofertility and oncosexuality. Methods We propose to set up a collaborative digital platform to strengthen, from the French expertise, Cuban health professionals’ knowledge, know-how, and skills in oncofertility and oncosexuality. The project will be coordinated by a coordinating, scientific, and supervisory committee, and the main activities will include: Theoretical training in e-learning adapted to low-speed Internet. Practical training in fertility preservation and sexual rehabilitation. Digital multidisciplinary consultation meetings for medical decisions to be taken for complex clinical cases. The platform will benefit from a recurrent evaluation, by the two cancer registries of Martinique and Cuba, with the following performance indicators: number of Cuban professionals trained, number of professionals sensitized, hourly volumes (or number of training courses provided), satisfaction of trained professionals, number of e-RCPs carried out online and number of missionaries supported. These indicators will be set up and analyzed by the registers. This project meets the Cuban and French health policies (cancer plans and national sexual health strategies) and will be implemented in liaison with the Health Agencies of both countries and the Embassy of France in Cuba. Discussion This project aims to provide support through bilateral exchanges to improve reproductive and sexual health in Cuba’s cancer patients. This collaboration will be based on a long-lasting French expertise and a solid Cuban health system. Consequently, this collaborative digital platform will contribute to data collection for cancer surveillance, and the two participating countries will ultimately be identified in the Caribbean as having centers of competence and excellence in oncofertility and oncosexuality with care standards.


2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A420-A420
Author(s):  
Timothy Yap ◽  
Deborah Wong ◽  
Siwen Hu-Lieskovan ◽  
Kyriakos Papadopoulos ◽  
Michelle Morrow ◽  
...  

BackgroundUpregulation of immune checkpoints, such as LAG-3, plays an important role in promoting resistance to anti-PD-(L)1 therapy. Targeting PD-L1 and LAG-3 using a bispecific antibody may overcome resistance to PD-(L)1 blockade.1 We report initial data from a first-in-human study evaluating FS118 in patients with advanced cancer and resistance to PD-(L)1 therapy.MethodsThe ongoing Phase I FIH study (NCT03440437) is being conducted to evaluate safety, tolerability, immunogenicity, PK/PD and clinical activity of FS118 administered IV weekly to heavily pre-treated patients who had previously received anti-PD-(L)1 therapy for a minimum of 12 weeks. Adverse events were assessed using CTCAEv4.03 and tumor responses assessed using RECISTv1.1 and iRECIST. Single subject dose escalation cohorts were followed by a 3+3 ascending dose design. Three cohorts (3, 10, 20 mg/kg) were expanded to evaluate PK, PD and clinical activity. Pharmacodynamic studies examined soluble LAG-3 production and peripheral T-cell expansion.ResultsForty-three patients (median 6 lines of prior therapy, including ICB) with solid tumors received FS118 at doses from 0.8 mg up to 20 mg/kg across 8 dose levels. Weekly administration of FS118 was well tolerated and did not result in dose- or treatment-limiting toxicities. An MTD was not reached. No safety signals unexpected for the drug class of immune-checkpoint inhibitors were identified in the early study population. The majority (95%) of treatment-emergent adverse events (TEAE) considered by the Safety Review Committee (SRC) to be treatment-related were Grade 1 and 2. Grade 3 TEAEs toxicities (elevated liver enzymes) were observed in 2 patients (5%). No SAEs or deaths were attributed to FS118 treatment. Anti-drug antibodies, observed in half of patients, were typically transient in nature. The pharmacokinetic profile confirmed preclinical predictions and PD parameters included a dose-dependent increase in serum soluble LAG-3 and expansion of peripheral T cells. Long-lasting disease stabilisation (>6 months) was observed in a subset of patients with acquired resistance (defined as a CR, PR or SD ≥3 months on previous PD-(L)1 treatment), but not in patients with primary resistance. Two patients remain on FS118 treatment as of 2 Jul 2020 (duration 10 and 16 months). Retrospective IHC analysis of PD-L1 and LAG-3 co-expression in the tumor was assessed as a potential biomarker associated with clinical outcome.ConclusionsWeekly treatment with FS118 was well tolerated up to 20 mg/kg and was associated with pharmacodynamic markers of FS118 activity. Encouraging signs of clinical activity were observed in highly pre-treated patients who had acquired resistance to prior PD-(L)1 therapy.Trial RegistrationRegistered at www.clinicaltrials.gov, NCT03440437ReferenceKraman M, Faroudi M, Allen N, Kmiecik K, Gliddon D, Seal C, Koers A, Wydro M, Winnewisser J, Young L, Tuna M, Doody J, Morrow M, Brewis N. FS118, a bispecific antibody targeting LAG-3 and PD-L1, Enhances T-Cell activation resulting in potent antitumor activity. Clin Cancer Res 2020; 26:3333–3344.


Author(s):  
Huihui Gong ◽  
Jun You ◽  
Xiurong Zhang ◽  
Yanzhong Liu ◽  
Fengtao Zhao ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 692
Author(s):  
Sweta Talyan ◽  
Samantha Filipów ◽  
Michael Ignarski ◽  
Magdalena Smieszek ◽  
He Chen ◽  
...  

Diseases of the renal filtration unit—the glomerulus—are the most common cause of chronic kidney disease. Podocytes are the pivotal cell type for the function of this filter and focal-segmental glomerulosclerosis (FSGS) is a classic example of a podocytopathy leading to proteinuria and glomerular scarring. Currently, no targeted treatment of FSGS is available. This lack of therapeutic strategies is explained by a limited understanding of the defects in podocyte cell biology leading to FSGS. To date, most studies in the field have focused on protein-coding genes and their gene products. However, more than 80% of all transcripts produced by mammalian cells are actually non-coding. Here, long non-coding RNAs (lncRNAs) are a relatively novel class of transcripts and have not been systematically studied in FSGS to date. The appropriate tools to facilitate lncRNA research for the renal scientific community are urgently required due to a row of challenges compared to classical analysis pipelines optimized for coding RNA expression analysis. Here, we present the bioinformatic pipeline CALINCA as a solution for this problem. CALINCA automatically analyzes datasets from murine FSGS models and quantifies both annotated and de novo assembled lncRNAs. In addition, the tool provides in-depth information on podocyte specificity of these lncRNAs, as well as evolutionary conservation and expression in human datasets making this pipeline a crucial basis to lncRNA studies in FSGS.


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