scholarly journals Apollo: Democratizing genome annotation

2019 ◽  
Author(s):  
Nathan Dunn ◽  
Deepak Unni ◽  
Colin Diesh ◽  
Monica Munoz-Torres ◽  
Nomi L. Harris ◽  
...  
Keyword(s):  
Genome Annotation ◽  
Genomic Analysis ◽  
List Type ◽  
Sources Of Information ◽  
Multiple Sources ◽  
Link Type ◽  
Open Source Software Package ◽  
Analytical Review ◽  
Graphical Browser ◽  
And Function

AbstractGenome annotation is the process of identifying the location and function of a genome’s encoded features. Improving the biological accuracy of annotation is a complex and iterative process requiring researchers to review and incorporate multiple sources of information such as transcriptome alignments, predictive models based on sequence profiles, and comparisons to features found in related organisms. Because rapidly decreasing costs are enabling an ever-growing number of scientists to incorporate sequencing as a routine laboratory technique, there is widespread demand for tools that can assist in the deliberative analytical review of genomic information. To this end, Apollo is an open source software package that enables researchers to efficiently inspect and refine the precise structure and role of genomic features in a graphical browser-based platform.In this paper we first outline some of Apollo’s newer user interface features, which were driven by the needs of this expanding genomics community. These include support for real-time collaboration, allowing distributed users to simultaneously edit the same encoded features while also instantly seeing the updates made by other researchers on the same region in a manner similar to Google Docs. Its technical architecture enables Apollo to be integrated into multiple existing genomic analysis pipelines and heterogeneous laboratory workflow platforms. Finally, we consider the implications that Apollo and related applications may have on how the results of genome research are published and made accessible. Source: https://github.com/GMOD/ApolloLicense (BSD-3): https://github.com/GMOD/Apollo/blob/master/LICENSE.mdDocker: https://hub.docker.com/r/gmod/apollo/tags/, https://github.com/GMOD/docker-apolloRequirements: JDK 1.8, Node v6.0+User guide: http://genomearchitect.org; technical guide: http://genomearchitect.readthedocs.io/en/latest/Mailing list: [email protected]

Supporting the Development of Clinical Reasoning of Preprofessional Novices in Dysphagia Management

2019 ◽  
Vol 40 (03) ◽  
pp. 151-161 ◽  
Author(s):  
Sebastian Doeltgen ◽  
Stacie Attrill ◽  
Joanne Murray
Keyword(s):  
Clinical Reasoning ◽  
Clinical Decision Making ◽  
Management Practice ◽  
Clinical Decision ◽  
Assessment Process ◽  
Evidence Based ◽  
Sources Of Information ◽  
Multiple Sources ◽  
Implicit Processing ◽  
Reasoning Skills

AbstractProficient clinical reasoning is a critical skill in high-quality, evidence-based management of swallowing impairment (dysphagia). Clinical reasoning in this area of practice is a cognitively complex process, as it requires synthesis of multiple sources of information that are generated during a thorough, evidence-based assessment process and which are moderated by the patient's individual situations, including their social and demographic circumstances, comorbidities, or other health concerns. A growing body of health and medical literature demonstrates that clinical reasoning skills develop with increasing exposure to clinical cases and that the approaches to clinical reasoning differ between novices and experts. It appears that it is not the amount of knowledge held, but the way it is used, that distinguishes a novice from an experienced clinician. In this article, we review the roles of explicit and implicit processing as well as illness scripts in clinical decision making across the continuum of medical expertise and discuss how they relate to the clinical management of swallowing impairment. We also reflect on how this literature may inform educational curricula that support SLP students in developing preclinical reasoning skills that facilitate their transition to early clinical practice. Specifically, we discuss the role of case-based curricula to assist students to develop a meta-cognitive awareness of the different approaches to clinical reasoning, their own capabilities and preferences, and how and when to apply these in dysphagia management practice.

scholarly journals The NALCN Channel Regulator UNC-80 Functions in a Subset of Interneurons To Regulate Caenorhabditis elegans Reversal Behavior

2019 ◽  
Vol 10 (1) ◽  
pp. 199-210 ◽  
Author(s):  
Chuanman Zhou ◽  
Jintao Luo ◽  
Xiaohui He ◽  
Qian Zhou ◽  
Yunxia He ◽  
...  
Keyword(s):  
Plant Hormone ◽  
Neuronal Excitability ◽  
Resting Membrane Potential ◽  
Loss Of Function ◽  
Wild Type ◽  
C Elegans ◽  
Link Type ◽  
Complex Functions ◽  
And Function ◽  
Multiple Loss

NALCN (Na+leak channel, non-selective) is a conserved, voltage-insensitive cation channel that regulates resting membrane potential and neuronal excitability. UNC79 and UNC80 are key regulators of the channel function. However, the behavioral effects of the channel complex are not entirely clear and the neurons in which the channel functions remain to be identified. In a forward genetic screen for C. elegans mutants with defective avoidance response to the plant hormone methyl salicylate (MeSa), we isolated multiple loss-of-function mutations in unc-80 and unc-79. C. elegans NALCN mutants exhibited similarly defective MeSa avoidance. Interestingly, NALCN, unc-80 and unc-79 mutants all showed wild type-like responses to other attractive or repelling odorants, suggesting that NALCN does not broadly affect odor detection or related forward and reversal behaviors. To understand in which neurons the channel functions, we determined the identities of a subset of unc-80-expressing neurons. We found that unc-79 and unc-80 are expressed and function in overlapping neurons, which verified previous assumptions. Neuron-specific transgene rescue and knockdown experiments suggest that the command interneurons AVA and AVE and the anterior guidepost neuron AVG can play a sufficient role in mediating unc-80 regulation of the MeSa avoidance. Though primarily based on genetic analyses, our results further imply that MeSa might activate NALCN by direct or indirect actions. Altogether, we provide an initial look into the key neurons in which the NALCN channel complex functions and identify a novel function of the channel in regulating C. elegans reversal behavior through command interneurons.

scholarly journals Homeopathy for Covid-19 in Primary Care: A structured summary of a study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ubiratan Cardinalli Adler ◽  
Maristela Schiabel Adler ◽  
Livia Mitchiguian Hotta ◽  
Ana Elisa Madureira Padula ◽  
Amarilys de Toledo Cesar ◽  
...  
Keyword(s):  
Primary Care ◽  
Alternative Hypothesis ◽  
University Hospital ◽  
List Type ◽  
Study Medication ◽  
Link Type ◽  
Care Protocol ◽  
Full Protocol ◽  
Isolation Period

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.

scholarly journals Task shifting in the care for patients with hand osteoarthritis. Protocol for a randomized controlled non-inferiority trial

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ingvild Kjeken ◽  
Kjetil Bergsmark ◽  
Ida K. Haugen ◽  
Toril Hennig ◽  
Merete Hermann-Eriksen ◽  
...  
Keyword(s):  
Health Care ◽  
Disease Activity ◽  
Primary Outcome ◽  
Hand Osteoarthritis ◽  
List Type ◽  
Specialist Care ◽  
Randomized Controlled ◽  
Number Of Patients ◽  
Specialist Health Care ◽  
And Function

Abstract Background Current health policy states that patients with osteoarthritis (OA) should mainly be managed in primary health care. Still, research shows that patients with hand OA have poor access to recommended treatment in primary care, and in Norway, they are increasingly referred to rheumatologist consultations in specialist care. In this randomized controlled non-inferiority trial, we will test if a new model, where patients referred to consultation in specialist health care receive their first consultation by an occupational therapy (OT) specialist, is as safe and effective as the traditional model, where they receive their first consultation by a rheumatologist. More specifically, we will answer the following questions: What are the characteristics of patients with hand OA referred to specialist health care with regards to joint affection, disease activity, symptoms and function? Is OT-led hand OA care as effective and safe as rheumatologist-led care with respect to treatment response, disease activity, symptoms, function and patient satisfaction? Is OT-led hand OA care equal to, or more cost effective than rheumatologist-led care? Which factors, regardless of hand OA care, predict improvement 6 and 12 months after baseline? Methods Participants will be patients with hand OA diagnosed by a general practitioner and referred for consultation at one of two Norwegian departments of rheumatology. Those who agree will attend a clinical assessment and report their symptoms and function in validated outcome measures, before they are randomly selected to receive their first consultation by an OT specialist (n = 200) or by a rheumatologist (n = 200). OTs may refer patients to a rheumatologist consultation and vice versa. The primary outcome will be the number of patients classified as OMERACT/OARSI-responders after six months. Secondary outcomes are pain, function and satisfaction with care over the twelve-month trial period. The analysis of the primary outcome will be done by logistic regression. A two-sided 95% confidence interval for the difference in response probability will be formed, and non-inferiority of OT-led care will be claimed if the upper endpoint of this interval does not exceed 15%. Discussion The findings will improve access to evidence-based management of people with hand OA. Trial registration ClinicalTrials.gov, NCT03102788. Registered April 6th, 2017, https://clinicaltrials.gov/ct2/show/NCT03102788?term=Kjeken&draw=2&rank=1 Date and version identifier: December 17th, 2020. First version.

scholarly journals Inter-professional agreement and collaboration between extended scope physiotherapists and orthopaedic surgeons in an orthopaedic outpatient shoulder clinic – a mixed methods study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Merete Nørgaard Madsen ◽  
Maria Lange Kirkegaard ◽  
Thomas Martin Klebe ◽  
Charlotte Lorenzen Linnebjerg ◽  
Søren Martin Riis Villumsen ◽  
...  
Keyword(s):  
Treatment Plan ◽  
Random Order ◽  
Primary Diagnosis ◽  
Diagnosis And Treatment ◽  
List Type ◽  
Professional Collaboration ◽  
Relational Coordination ◽  
Orthopaedic Surgeons ◽  
Link Type ◽  
Shoulder Disorders

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

scholarly journals Mobility Trends before and after the Pandemic Outbreak: Analyzing the Metropolitan Area of Barcelona through the Lens of Equality and Sustainability

2021 ◽  
Vol 13 (14) ◽  
pp. 7908
Author(s):  
Lucía Mejía-Dorantes ◽  
Lídia Montero ◽  
Jaume Barceló
Keyword(s):  
Metropolitan Area ◽  
Spatial Arrangement ◽  
Individual Characteristics ◽  
Sources Of Information ◽  
Mobility Patterns ◽  
Multiple Sources ◽  
Temporal Dimension ◽  
Population Groups ◽  
Highly Educated ◽  
Before And After

The spatial arrangement of a metropolis is of utmost importance to carry out daily activities, which are constrained by space and time. Accessibility is not only shaped by the spatial and temporal dimension, but it is also defined by individual characteristics, such as gender, impairments, or socioeconomic characteristics of the citizens living or commuting in this area. This study analyzes mobility trends and patterns in the metropolitan area of Barcelona before and after the COVID-19 pandemic outbreak, with special emphasis on gender and equality. The study draws on multiple sources of information; however, two main datasets are analyzed: two traditional travel surveys from the transport metropolitan area of Barcelona and two coming from smartphone data. The results show that gender plays a relevant role when analyzing mobility patterns, as already highlighted in other studies, but, after the pandemic outbreak, some population groups were more likely to change their mobility patterns, for example, highly educated population groups and those with higher income. This study also highlights that e-activities may shape new mobility patterns and living conditions for some population segments, but some activities cannot be replaced by IT technologies. For all these reasons, city and transport planning should foster sustainable development policies, which will provide the maximum benefit for society.

347 Clinical outcomes of ovarian cancer patients treated with ALKS 4230, a novel engineered cytokine, in combination with pembrolizumab: ARTISTRY-1 trial

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A372-A373
Author(s):  
Ira Winer ◽  
Lucy Gilbert ◽  
Ulka Vaishampayan ◽  
Seth Rosen ◽  
Christopher Hoimes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Tumor Marker ◽  
Solid Tumors ◽  
Cd8 T Cells ◽  
Comprehensive Cancer Center ◽  
List Type ◽  
Link Type ◽  
Heavily Pretreated

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.

395 A first-in-human study of FS118, a tetravalent bispecific antibody targeting LAG-3 and PD-L1, in patients with advanced cancer and resistance to PD-(L)1 therapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A420-A420
Author(s):  
Timothy Yap ◽  
Deborah Wong ◽  
Siwen Hu-Lieskovan ◽  
Kyriakos Papadopoulos ◽  
Michelle Morrow ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Advanced Cancer ◽  
Bispecific Antibody ◽  
Acquired Resistance ◽  
Human Study ◽  
Clinical Activity ◽  
List Type ◽  
Link Type ◽  
Antibody Targeting

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.

scholarly journals The proteome: structure, function and evolution

2006 ◽  
Vol 361 (1467) ◽  
pp. 441-451 ◽  
Author(s):  
Keiran Fleming ◽  
Lawrence A Kelley ◽  
Suhail A Islam ◽  
Robert M MacCallum ◽  
Arne Muller ◽  
...  
Keyword(s):  
Protein Function ◽  
Sequence Similarity ◽  
Structural Annotation ◽  
New Approach ◽  
Link Type ◽  
University College London ◽  
Automated Pipeline ◽  
3D Genomics ◽  
And Function ◽  
Structural Homologue

This paper reports two studies to model the inter-relationships between protein sequence, structure and function. First, an automated pipeline to provide a structural annotation of proteomes in the major genomes is described. The results are stored in a database at Imperial College, London (3D-GENOMICS) that can be accessed at www.sbg.bio.ic.ac.uk . Analysis of the assignments to structural superfamilies provides evolutionary insights. 3D-GENOMICS is being integrated with related proteome annotation data at University College London and the European Bioinformatics Institute in a project known as e-protein ( http://www.e-protein.org/ ). The second topic is motivated by the developments in structural genomics projects in which the structure of a protein is determined prior to knowledge of its function. We have developed a new approach PHUNCTIONER that uses the gene ontology (GO) classification to supervise the extraction of the sequence signal responsible for protein function from a structure-based sequence alignment. Using GO we can obtain profiles for a range of specificities described in the ontology. In the region of low sequence similarity (around 15%), our method is more accurate than assignment from the closest structural homologue. The method is also able to identify the specific residues associated with the function of the protein family.

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