scholarly journals A Systematic Review of Published Physiologically based Kinetic Models and an Assessment of their Chemical Space Coverage

2021 ◽  
pp. 026119292110602
Author(s):  
Courtney V. Thompson ◽  
James W. Firman ◽  
Michael R. Goldsmith ◽  
Christopher M. Grulke ◽  
Yu-Mei Tan ◽  
...  
Keyword(s):  
Systematic Review ◽  
De Novo ◽  
Chemical Space ◽  
Life Stage ◽  
Chemical Information ◽  
Animal Testing ◽  
Data Set ◽  
Concentration Time ◽  
Physiologically Based ◽  
Pharmaceutical Industries

Across multiple sectors, including food, cosmetics and pharmaceutical industries, there is a need to predict the potential effects of xenobiotics. These effects are determined by the intrinsic ability of the substance, or its derivatives, to interact with the biological system, and its concentration–time profile at the target site. Physiologically based kinetic (PBK) models can predict organ-level concentration–time profiles — however, the models are time and resource intensive to generate de novo. Read-across is an approach used to reduce or replace animal testing, wherein information from a data-rich chemical is used to make predictions for a data-poor chemical. The recent increase in published PBK models presents the opportunity to use a read-across approach for PBK modelling, that is, to use PBK model information from one chemical to inform the development or evaluation of a PBK model for a similar chemical. Essential to this process, is identifying the chemicals for which a PBK model already exists. Herein, the results of a systematic review of existing PBK models, compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) format, are presented. Model information, including species, sex, life-stage, route of administration, software platform used and the availability of model equations, was captured for 7541 PBK models. Chemical information (identifiers and physico-chemical properties) has also been recorded for 1150 unique chemicals associated with these models. This PBK model data set has been made readily accessible, as a Microsoft Excel® spreadsheet, providing a valuable resource for those developing, using or evaluating PBK models in industry, academia and the regulatory sectors.

scholarly journals Liquid Biopsy for Small Cell Lung Cancer either De Novo or Transformed: Systematic Review of Different Applications and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2265
Author(s):  
Elio Gregory Pizzutilo ◽  
Martino Pedrani ◽  
Alessio Amatu ◽  
Lorenzo Ruggieri ◽  
Calogero Lauricella ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Liquid Biopsy ◽  
De Novo ◽  
Meta Analysis ◽  
Small Cell ◽  
Genomic Profiling ◽  
Small Cell Lung

Background: The potential added value of liquid biopsy (LB) is not well determined in the case of small cell lung cancer (SCLC), an aggressive tumor that can occur either de novo or from the histologic transformation of non-small cell lung cancer (NSCLC). Methods: A systematic review of studies adopting LB in patients with SCLC have been performed to assess the clinical utility of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs). Results: After a screening of 728 records, 62 studies (32 evaluating CTCs, 27 ctDNA, and 3 both) met predetermined eligibility criteria. Only four studies evaluated LB in the diagnostic setting for SCLC, while its prognostic significance was evaluated in 38 studies and prominently supported by both ctDNA and CTCs. A meta-analysis of 11 studies as for CTCs enumeration showed an HR for overall survival of 2.63 (1.71–4.05), with a potential publication bias. The feasibility of tumor genomic profiling and the predictive role of LB in terms of response/resistance to chemotherapy was assessed in 11 and 24 studies, respectively, with greater consistency for those regarding ctDNA. Intriguingly, several case reports suggest that LB can indirectly capture the transition to SCLC in NSCLC treated with EGFR tyrosine kinase inhibitors. Conclusions: While dedicated trials are needed, LB holds potential clinical roles in both de novo and transformed SCLC. CtDNA analysis appears the most valuable and practicable tool for both disease monitoring and genomic profiling.

scholarly journals Ever-increasing viral diversity associated with the red imported fire ant Solenopsis invicta (Formicidae: Hymenoptera)

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
César Augusto Diniz Xavier ◽  
Margaret Louise Allen ◽  
Anna Elizabeth Whitfield
Keyword(s):  
Solenopsis Invicta ◽  
De Novo ◽  
Rna Virus ◽  
Housekeeping Genes ◽  
Virus Genome ◽  
Single Strand ◽  
Viral Diversity ◽  
Red Imported Fire Ant ◽  
Sequence Comparisons ◽  
Data Set

Abstract Background Advances in sequencing and analysis tools have facilitated discovery of many new viruses from invertebrates, including ants. Solenopsis invicta is an invasive ant that has quickly spread worldwide causing significant ecological and economic impacts. Its virome has begun to be characterized pertaining to potential use of viruses as natural enemies. Although the S. invicta virome is the best characterized among ants, most studies have been performed in its native range, with less information from invaded areas. Methods Using a metatranscriptome approach, we further identified and molecularly characterized virus sequences associated with S. invicta, in two introduced areas, U.S and Taiwan. The data set used here was obtained from different stages (larvae, pupa, and adults) of S. invicta life cycle. Publicly available RNA sequences from GenBank’s Sequence Read Archive were downloaded and de novo assembled using CLC Genomics Workbench 20.0.1. Contigs were compared against the non-redundant protein sequences and those showing similarity to viral sequences were further analyzed. Results We characterized five putative new viruses associated with S. invicta transcriptomes. Sequence comparisons revealed extensive divergence across ORFs and genomic regions with most of them sharing less than 40% amino acid identity with those closest homologous sequences previously characterized. The first negative-sense single-stranded RNA virus genomic sequences included in the orders Bunyavirales and Mononegavirales are reported. In addition, two positive single-strand virus genome sequences and one single strand DNA virus genome sequence were also identified. While the presence of a putative tenuivirus associated with S. invicta was previously suggested to be a contamination, here we characterized and present strong evidence that Solenopsis invicta virus 14 (SINV-14) is a tenui-like virus that has a long-term association with the ant. Furthermore, based on virus sequence abundance compared to housekeeping genes, phylogenetic relationships, and completeness of viral coding sequences, our results suggest that four of five virus sequences reported, those being SINV-14, SINV-15, SINV-16 and SINV-17, may be associated to viruses actively replicating in the ant S. invicta. Conclusions The present study expands our knowledge about viral diversity associated with S. invicta in introduced areas with potential to be used as biological control agents, which will require further biological characterization.

scholarly journals Understanding the Needs of Australian Carers of Adults Receiving Palliative Care in the Home: A Systematic Review of the Literature

2021 ◽  
Vol 7 ◽  
pp. 237796082098568
Author(s):  
Elizabeth M. Miller ◽  
Joanne E. Porter
Keyword(s):  
Systematic Review ◽  
Palliative Care ◽  
Information Needs ◽  
Hospital Admissions ◽  
Positive Outcomes ◽  
Review Of The Literature ◽  
Data Set ◽  
Final Data ◽  
Perceived Impact ◽  
Meta Analyses

Introduction Caring for someone at home requiring palliative care is an ominous task. Unless the current support systems are better utilised and improved to meet the needs of those carers, the demand for acute hospital admissions will increase as the Australian population ages. The aim of this review was to examine the needs of unpaid carers who were caring for adults receiving palliative care in their home in Australia. Methods: A systematic review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines between 2008–2020. Results: Only Australian papers were selected due to the intent to understand carers’ needs in the Australian context and 17 papers made up the final data set. Four themes emerged: 1) Perceived factors influencing caregiving; 2) Perceived impact and responses to caregiving; 3) Communication and information needs; and 4) Perceptions of current palliative support services and barriers to uptake. Conclusion: Carers reported satisfaction and positive outcomes and also expressed feeling unprepared, unrecognised, stressed and exhausted.

scholarly journals Global production networks and the evolution of industrial capabilities: does production sharing warp the product space?

2020 ◽  
Vol 72 (3) ◽  
pp. 731-747
Author(s):  
Russell Thomson ◽  
Prema-Chandra Athukorala
Keyword(s):  
Product Space ◽  
Industrial Structure ◽  
De Novo ◽  
Trade Openness ◽  
Production Networks ◽  
Global Production Networks ◽  
Industrial Upgrading ◽  
Data Set ◽  
Production Sharing ◽  
Space Approach

Abstract Do production capabilities of countries evolve from existing capabilities or emerge de novo? The Product Space approach developed by Hidalgo, Klinger, Barabási and Hausmann postulates that a country’s existing industrial structure largely determines its opportunities for industrial upgrading. However, this is difficult to reconcile with the export dynamism of many developing countries such as Thailand, Malaysia, Costa Rica and Vietnam that transformed from primary commodity dependence to exporters of dynamic manufactured products. In each of these cases, global production sharing facilitated industrial transition. In this article, we advance the Product Space approach to accommodate the role of global production sharing. Using a newly constructed multi-country data set of manufacturing exports that distinguishes between trade within global production networks and traditional horizontal trade, we find that that existing industrial structure has a smaller impact, but trade openness has a greater impact, on industrial upgrading within vertically integrated global industries.

scholarly journals Physiologically Based Pharmacokinetic Models of Probenecid and Furosemide to Predict Transporter Mediated Drug-Drug Interactions

2020 ◽  
Vol 37 (12) ◽  
Author(s):  
Hannah Britz ◽  
Nina Hanke ◽  
Mitchell E. Taub ◽  
Ting Wang ◽  
Bhagwat Prasad ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Organic Anion ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Time Profiles ◽  
Pbpk Models ◽  
Physiologically Based Pharmacokinetic ◽  
Concentration Time ◽  
Anion Transporter ◽  
Physiologically Based

Abstract Purpose To provide whole-body physiologically based pharmacokinetic (PBPK) models of the potent clinical organic anion transporter (OAT) inhibitor probenecid and the clinical OAT victim drug furosemide for their application in transporter-based drug-drug interaction (DDI) modeling. Methods PBPK models of probenecid and furosemide were developed in PK-Sim®. Drug-dependent parameters and plasma concentration-time profiles following intravenous and oral probenecid and furosemide administration were gathered from literature and used for model development. For model evaluation, plasma concentration-time profiles, areas under the plasma concentration–time curve (AUC) and peak plasma concentrations (Cmax) were predicted and compared to observed data. In addition, the models were applied to predict the outcome of clinical DDI studies. Results The developed models accurately describe the reported plasma concentrations of 27 clinical probenecid studies and of 42 studies using furosemide. Furthermore, application of these models to predict the probenecid-furosemide and probenecid-rifampicin DDIs demonstrates their good performance, with 6/7 of the predicted DDI AUC ratios and 4/5 of the predicted DDI Cmax ratios within 1.25-fold of the observed values, and all predicted DDI AUC and Cmax ratios within 2.0-fold. Conclusions Whole-body PBPK models of probenecid and furosemide were built and evaluated, providing useful tools to support the investigation of transporter mediated DDIs.

scholarly journals DEELIG: A Deep Learning Approach to Predict Protein-Ligand Binding Affinity

2021 ◽  
Vol 15 ◽  
pp. 117793222110303
Author(s):  
Asad Ahmed ◽  
Bhavika Mam ◽  
Ramanathan Sowdhamini
Keyword(s):  
Deep Learning ◽  
Ligand Binding ◽  
Binding Affinity ◽  
Chemical Space ◽  
Biological Significance ◽  
Protein Crystal ◽  
Ligand Docking ◽  
Complex Data ◽  
Binding Prediction ◽  
Data Set

Protein-ligand binding prediction has extensive biological significance. Binding affinity helps in understanding the degree of protein-ligand interactions and is a useful measure in drug design. Protein-ligand docking using virtual screening and molecular dynamic simulations are required to predict the binding affinity of a ligand to its cognate receptor. Performing such analyses to cover the entire chemical space of small molecules requires intense computational power. Recent developments using deep learning have enabled us to make sense of massive amounts of complex data sets where the ability of the model to “learn” intrinsic patterns in a complex plane of data is the strength of the approach. Here, we have incorporated convolutional neural networks to find spatial relationships among data to help us predict affinity of binding of proteins in whole superfamilies toward a diverse set of ligands without the need of a docked pose or complex as user input. The models were trained and validated using a stringent methodology for feature extraction. Our model performs better in comparison to some existing methods used widely and is suitable for predictions on high-resolution protein crystal (⩽2.5 Å) and nonpeptide ligand as individual inputs. Our approach to network construction and training on protein-ligand data set prepared in-house has yielded significant insights. We have also tested DEELIG on few COVID-19 main protease-inhibitor complexes relevant to the current public health scenario. DEELIG-based predictions can be incorporated in existing databases including RSCB PDB, PDBMoad, and PDBbind in filling missing binding affinity data for protein-ligand complexes.

scholarly journals 9/11-related PTSD among highly exposed populations: a systematic review 15 years after the attack

2017 ◽  
Vol 48 (4) ◽  
pp. 537-553 ◽  
Author(s):  
A. Lowell ◽  
B. Suarez-Jimenez ◽  
L. Helpman ◽  
X. Zhu ◽  
A. Durosky ◽  
...  
Keyword(s):  
Systematic Review ◽  
Longitudinal Studies ◽  
Large Body ◽  
Health Impact ◽  
Time Frame ◽  
Post Traumatic Stress ◽  
Cross Sectional ◽  
Data Set ◽  
Prevalence Studies ◽  
Back Ground

BackgroundThe 11 September 2001 (9/11) attacks were unprecedented in magnitude and mental health impact. While a large body of research has emerged since the attacks, published reviews are few, and are limited by an emphasis on cross-sectional research, short time frame, and exclusion of treatment studies. Additionally, to date, there has been no systematic review of available longitudinal information as a unique data set. Consequently, knowledge regarding long-term trajectories of 9/11-related post-traumatic stress disorder (PTSD) among highly exposed populations, and whether available treatment approaches effectively address PTSD within the context of mass, man-made disaster, remains limited.MethodsThe present review aimed to address these gaps using a systematic review of peer-reviewed reports from October 2001 to May 2016. Eligible reports were of longitudinal studies of PTSD among highly exposed populations. We identified 20 reports of 9/11-related PTSD, including 13 longitudinal prevalence studies and seven treatment studies.ResultsFindings suggest a substantial burden of 9/11-related PTSD among those highly exposed to the attack, associated with a range of sociodemographic and back-ground factors, and characteristics of peri-event exposure. While most longitudinal studies show declining rates of prevalence of PTSD, studies of rescue/recovery workers have documented an increase over time. Treatment studies were few, and generally limited by methodological shortcomings, but support exposure-based therapies.ConclusionFuture directions for research, treatment, and healthcare policy are discussed.

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