scholarly journals Reducing complexity and unidentifiability when modelling human atrial cells

2020 ◽  
Vol 378 (2173) ◽  
pp. 20190339 ◽  
Author(s):  
C. Houston ◽  
B. Marchand ◽  
L. Engelbert ◽  
C. D. Cantwell
Keyword(s):  
Experimental Data ◽  
Clinical Decision Making ◽  
Cell Model ◽  
Sodium Current ◽  
Clinical Decision ◽  
Complex Model ◽  
Parameter Estimates ◽  
Gating Kinetics ◽  
Complex Formulation ◽  
Approximate Bayesian

Mathematical models of a cellular action potential (AP) in cardiac modelling have become increasingly complex, particularly in gating kinetics, which control the opening and closing of individual ion channel currents. As cardiac models advance towards use in personalized medicine to inform clinical decision-making, it is critical to understand the uncertainty hidden in parameter estimates from their calibration to experimental data. This study applies approximate Bayesian computation to re-calibrate the gating kinetics of four ion channels in two existing human atrial cell models to their original datasets, providing a measure of uncertainty and indication of potential issues with selecting a single unique value given the available experimental data. Two approaches are investigated to reduce the uncertainty present: re-calibrating the models to a more complete dataset and using a less complex formulation with fewer parameters to constrain. The re-calibrated models are inserted back into the full cell model to study the overall effect on the AP. The use of more complete datasets does not eliminate uncertainty present in parameter estimates. The less complex model, particularly for the fast sodium current, gave a better fit to experimental data alongside lower parameter uncertainty and improved computational speed. This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’.

scholarly journals Establishment and Preclinical Application of Conditional Reprogramming Culture System for Laryngeal and Hypopharyngeal Carcinoma

2021 ◽  
Author(s):  
Yanbo DONG ◽  
Jian WANG ◽  
Wei JI ◽  
Mengzhu ZHENG ◽  
Peng WANG ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
Drug Testing ◽  
Clinical Decision Making ◽  
Cell Model ◽  
Clinical Decision ◽  
Culture Technique ◽  
Hypopharyngeal Carcinoma ◽  
Molecular Characteristics ◽  
Drug Responses

Abstract Purpose Management of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) remains highly challenging due to their anatomic location and highly variable therapeutic responses. We aim to establish a new in vitro model for LHSCC based on conditional reprogramming (CR), a novel cell-culture technique, and investigate its potential value on personalized cancer therapies. Methods Primary LHSCC cells were isolated from tumor specimens and cultured under CR conditions. The characteristics and malignant potential of cells were evaluated by histological staining, whole-exome sequencing and heterotransplantation. The responses of CR tumor cells to anticancer drugs and radiotherapy were tested using cell proliferation assay. CR cells could form xenografts and organoids, which were used for drug testing respectively. Clinical responses for certain patients were also compared with in vitro responses. Results A panel of 28 human LHSCC CR cells were established from 50 tumor tissues. They retain tumorigenic potential upon xenotransplantation and recapitulate molecular characteristics of LHSCC. Differential responses to anticancer drugs and radiotherapy were detected in vitro. CR cells can be transformed to xenograft and organoid, shared comparable drug responses. The clinical drug responses were consistent with in vitro drug responses. Conclusions The patient-derived CR cell model could promisingly be utilized in clinical decision-making and assist in the selection of personalized therapies for LHSCC.

scholarly journals The Atlas of Inflammation-Resolution (AIR)

2020 ◽  
Author(s):  
Charles N. Serhan ◽  
Shailendra Gupta ◽  
Mauro Perretti ◽  
Catherine Godson ◽  
Eoin Brennan ◽  
...  
Keyword(s):  
Experimental Data ◽  
Acute Inflammation ◽  
Molecular Mechanisms ◽  
Clinical Decision Making ◽  
Interdisciplinary Approach ◽  
Clinical Decision ◽  
International Standards ◽  
Bioinformatics Analyses ◽  
Wide Range ◽  
Inflammation Resolution

AbstractAcute inflammation is a protective reaction by the immune system in response to invading pathogens or tissue damage. Ideally, the response should be localized, self-limited, and returning to homeostasis. If not resolved, acute inflammation can result in organ pathologies leading to chronic inflammatory phenotypes. Acute inflammation and inflammation resolution are complex coordinated processes, involving a number of cell types, interacting in space and time. The biomolecular complexity and the fact that several biomedical fields are involved, make a multi and interdisciplinary approach necessary.This Atlas of Inflammation Resolution (AIR) is a web-based resource capturing the state-of-the-art in acute inflammation and inflammation resolution research. The AIR provides an interface for users to search thousands of interactions, arranged in inter-connected multi-layers of process diagrams, covering a wide range of clinically relevant phenotypes. The AIR serves as an open access knowledgebase, including a gateway to numerous public databases. It is furthermore possible for the user to map experimental data onto the molecular interaction maps of the AIR, providing the basis for bioinformatics analyses and systems biology approaches. By mapping experimental data onto the Atlas, it can be used to elucidate drug action as well as molecular mechanisms underlying different disease phenotypes. For the visualization and exploration of information, the AIR uses the Minerva platform, which is a well-established tool for the presentation of disease maps. The molecular details of the AIR are encoded using international standards.The Atlas of Inflammation Resolution was created as a freely accessible resource, supporting research and education in the fields of acute inflammation and inflammation resolution. The AIR connects research communities, facilitates clinical decision making, and supports research scientists in the formulation and validation of hypotheses.

scholarly journals Preclinical Application of Conditional Reprogramming Culture System for Laryngeal and Hypopharyngeal Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Yanbo Dong ◽  
Jian Wang ◽  
Wei Ji ◽  
Mengzhu Zheng ◽  
Peng Wang ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Cell Model ◽  
Clinical Decision ◽  
Culture Technique ◽  
Hypopharyngeal Carcinoma ◽  
Molecular Characteristics ◽  
Cancer Therapies ◽  
Drug Responses ◽  
Personalized Cancer

Management of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) remains highly challenging due to highly variable therapeutic responses. By establishing an in vitro model for LHSCC based on conditional reprogramming (CR), a cell-culture technique, we aim to investigate its potential value on personalized cancer therapies. Herein, a panel of 28 human LHSCC CR cells were established from 50 tumor tissues using the CR method. They retained tumorigenic potential upon xenotransplantation and recapitulated molecular characteristics of LHSCC. Differential responses to anticancer drugs and radiotherapy were detected in vitro. CR cells could be transformed to xenograft and organoid, and they shared comparable drug responses. The clinical drug responses were consistent with in vitro drug responses. Collectively, the patient-derived CR cell model could promisingly be utilized in clinical decision-making and assisted in the selection of personalized therapies for LHSCC.

scholarly journals GLIOBLASTOMA MULTIFORME: A META-ANALYSIS OF DRIVER GENES, CURRENT DIAGNOSIS, AND TUMOR HETEROGENEITY

2020 ◽  
Author(s):  
Gabriel Emilio Herrera-Oropeza ◽  
Carla Angulo-Rojo ◽  
Santos Alberto Gástelum-López ◽  
Alfredo Varela-Echavarría ◽  
Maribel Hernández-Rosales ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Molecular Subtype ◽  
Cell Model ◽  
Meta Analysis ◽  
Adult Population ◽  
Young Patients ◽  
Clinical Decision ◽  
Significant Heterogeneity ◽  
Driver Genes ◽  
Molecular Events

AbstractGlioblastoma (GBM) is the most aggressive and common brain cancer in adults with the lowest life expectancy. The current neuro-oncology practice has incorporated genes involved in key molecular events that drive GBM tumorigenesis as biomarkers to guide diagnosis and design treatment. This study summarizes findings describing the significant heterogeneity of GBM at the transcriptional and genomic levels, emphasizing eighteen driver genes with clinical relevance. A pattern was identified fitting the stem cell model for GBM ontogenesis, with an up-regulation profile for MGMT and down-regulation for ATRX, H3F3A, TP53, and EGFR in the mesenchymal subtype. We also detected overexpression of EGFR, NES, VIM, and TP53 in the classical subtype and of MKi67 and OLIG2 genes in the proneural subtype. In keeping with this, we found a panel of nine biomarkers with a strong potential to determine the GBM molecular subtype. A unique distribution of somatic mutations was found for the young and adult population, particularly for genes related to DNA repair and chromatin remodeling, highlighting ATRX, MGMT, and IDH1. Our results also revealed that highly lesioned genes undergo differential regulation with particular biological pathways for young patients. This meta-analysis will help delineate future strategies related to the use of these molecular markers for clinical decision-making in the medical routine.

scholarly journals Glioblastoma multiforme: a multi-omics analysis of driver genes and tumour heterogeneity

2021 ◽  
Vol 11 (4) ◽  
pp. 20200072
Author(s):  
Gabriel Emilio Herrera-Oropeza ◽  
Carla Angulo-Rojo ◽  
Santos Alberto Gástelum-López ◽  
Alfredo Varela-Echavarría ◽  
Maribel Hernández-Rosales ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Molecular Subtype ◽  
Cell Model ◽  
Adult Population ◽  
Young Patients ◽  
Clinical Decision ◽  
Significant Heterogeneity ◽  
Driver Genes ◽  
Molecular Events ◽  
Differential Expression Pattern

Glioblastoma (GBM) is the most aggressive and common brain cancer in adults with the lowest life expectancy. The current neuro-oncology practice has incorporated genes involved in key molecular events that drive GBM tumorigenesis as biomarkers to guide diagnosis and design treatment. This study summarizes findings describing the significant heterogeneity of GBM at the transcriptional and genomic levels, emphasizing 18 driver genes with clinical relevance. A pattern was identified fitting the stem cell model for GBM ontogenesis, with an upregulation profile for MGMT and downregulation for ATRX, H3F3A, TP53 and EGFR in the mesenchymal subtype. We also detected overexpression of EGFR, NES, VIM and TP53 in the classical subtype and of MKi67 and OLIG2 genes in the proneural subtype. Furthermore, we found a combination of the four biomarkers EGFR, NES, OLIG2 and VIM with a remarkable differential expression pattern which confers them a strong potential to determine the GBM molecular subtype. A unique distribution of somatic mutations was found for the young and adult population, particularly for genes related to DNA repair and chromatin remodelling, highlighting ATRX, MGMT and IDH1. Our results also revealed that highly lesioned genes undergo differential regulation with particular biological pathways for young patients. This multi-omic analysis will help delineate future strategies related to the use of these molecular markers for clinical decision-making in the medical routine.

Preliminary Findings on the Use of Session Questionnaires to Improve Clinician-Client Alliance With Special Consideration to Clinical Education

2015 ◽  
Vol 25 (1) ◽  
pp. 50-60
Author(s):  
Anu Subramanian
Keyword(s):  
Graduate Students ◽  
Clinical Education ◽  
Clinical Decision Making ◽  
Rating Scale ◽  
Treatment Effectiveness ◽  
Clinical Decision ◽  
Added Value ◽  
Therapeutic Outcomes ◽  
Specific Feedback ◽  
Stakeholder Perspective

ASHA's focus on evidence-based practice (EBP) includes the family/stakeholder perspective as an important tenet in clinical decision making. The common factors model for treatment effectiveness postulates that clinician-client alliance positively impacts therapeutic outcomes and may be the most important factor for success. One strategy to improve alliance between a client and clinician is the use of outcome questionnaires. In the current study, eight parents of toddlers who attended therapy sessions at a university clinic responded to a session outcome questionnaire that included both rating scale and descriptive questions. Six graduate students completed a survey that included a question about the utility of the questionnaire. Results indicated that the descriptive questions added value and information compared to using only the rating scale. The students were varied in their responses regarding the effectiveness of the questionnaire to increase their comfort with parents. Information gathered from the questionnaire allowed for specific feedback to graduate students to change behaviors and created opportunities for general discussions regarding effective therapy techniques. In addition, the responses generated conversations between the client and clinician focused on clients' concerns. Involving the stakeholder in identifying both effective and ineffective aspects of therapy has advantages for clinical practice and education.

Clinical Decision-Making for Stroke and Aphasia in the Older Adult

2009 ◽  
Vol 14 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Jacqueline Hinckley
Keyword(s):  
Executive Function ◽  
Cerebrovascular Disease ◽  
Cognitive Abilities ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Cognitive Profile ◽  
Focal Lesion ◽  
Cognitive Profiles ◽  
Supportive Communication ◽  
Spaced Retrieval

Abstract A patient with aphasia that is uncomplicated by other cognitive abilities will usually show a primary impairment of language. The frequency of additional cognitive impairments associated with cerebrovascular disease, multiple (silent or diagnosed) infarcts, or dementia increases with age and can complicate a single focal lesion that produces aphasia. The typical cognitive profiles of vascular dementia or dementia due to cerebrovascular disease may differ from the cognitive profile of patients with Alzheimer's dementia. In order to complete effective treatment selection, clinicians must know the cognitive profile of the patient and choose treatments accordingly. When attention, memory, and executive function are relatively preserved, strategy-based and conversation-based interventions provide the best choices to target personally relevant communication abilities. Examples of treatments in this category include PACE and Response Elaboration Training. When patients with aphasia have co-occurring episodic memory or executive function impairments, treatments that rely less on these abilities should be selected. Examples of treatments that fit these selection criteria include spaced retrieval and errorless learning. Finally, training caregivers in the use of supportive communication strategies is helpful to patients with aphasia, with or without additional cognitive complications.

Debates in Dysphagia Management: How Do You Use Evidence-Based Practice in Your Dysphagia Patient Care?

2011 ◽  
Vol 20 (4) ◽  
pp. 121-123
Author(s):  
Jeri A. Logemann
Keyword(s):  
Decision Making ◽  
Patient Care ◽  
Clinical Outcomes ◽  
Clinical Judgment ◽  
Clinical Decision Making ◽  
Evidence Based Practice ◽  
Clinical Decision ◽  
Evidence Based ◽  
Clinical Method ◽  
Do So

Evidence-based practice requires astute clinicians to blend our best clinical judgment with the best available external evidence and the patient's own values and expectations. Sometimes, we value one more than another during clinical decision-making, though it is never wise to do so, and sometimes other factors that we are unaware of produce unanticipated clinical outcomes. Sometimes, we feel very strongly about one clinical method or another, and hopefully that belief is founded in evidence. Some beliefs, however, are not founded in evidence. The sound use of evidence is the best way to navigate the debates within our field of practice.

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