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"systems biology"

These pubmed results were generated on 2018/03/13

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2018/03/13

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

CLC-Pred: A freely available web-service for in silico prediction of human cell line cytotoxicity for drug-like compounds.

PLoS One. 2018;13(1):e0191838

Authors: Lagunin AA, Dubovskaja VI, Rudik AV, Pogodin PV, Druzhilovskiy DS, Gloriozova TA, Filimonov DA, Sastry NG, Poroikov VV

Abstract
In silico methods of phenotypic screening are necessary to reduce the time and cost of the experimental in vivo screening of anticancer agents through dozens of millions of natural and synthetic chemical compounds. We used the previously developed PASS (Prediction of Activity Spectra for Substances) algorithm to create and validate the classification SAR models for predicting the cytotoxicity of chemicals against different types of human cell lines using ChEMBL experimental data. A training set from 59,882 structures of compounds was created based on the experimental data (IG50, IC50, and % inhibition values) from ChEMBL. The average accuracy of prediction (AUC) calculated by leave-one-out and a 20-fold cross-validation procedure during the training was 0.930 and 0.927 for 278 cancer cell lines, respectively, and 0.948 and 0.947 for cytotoxicity prediction for 27 normal cell lines, respectively. Using the given SAR models, we developed a freely available web-service for cell-line cytotoxicity profile prediction (CLC-Pred: Cell-Line Cytotoxicity Predictor) based on the following structural formula: http://way2drug.com/Cell-line/.

PMID: 29370280 [PubMed - indexed for MEDLINE]

Prediction of Novel Drugs for Hepatocellular Carcinoma Based on Multi-Source Random Walk.

IEEE/ACM Trans Comput Biol Bioinform. 2017 Jul-Aug;14(4):966-977

Authors: Yu L, Su R, Wang B, Zhang L, Zou Y, Zhang J, Gao L

Abstract
Computational approaches for predicting drug-disease associations by integrating gene expression and biological network provide great insights to the complex relationships among drugs, targets, disease genes, and diseases at a system level. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high rate of morbidity and mortality. We provide an integrative framework to predict novel d rugs for HCC based on multi-source random walk (PD-MRW). Firstly, based on gene expression and protein interaction network, we construct a gene-gene weighted i nteraction network (GWIN). Then, based on multi-source random walk in GWIN, we build a drug-drug similarity network. Finally, based on the known drugs for HCC, we score all drugs in the drug-drug similarity network. The robustness of our predictions, their overlap with those reported in Comparative Toxicogenomics Database (CTD) and literatures, and their enriched KEGG pathway demonstrate our approach can effectively identify new drug indications. Specifically, regorafenib (Rank = 9 in top-20 list) is proven to be effective in Phase I and II clinical trials of HCC, and the Phase III trial is ongoing. And, it has 11 overlapping pathways with HCC with lower p-values. Focusing on a particular disease, we believe our approach is more accurate and possesses better scalability.

PMID: 27076463 [PubMed - indexed for MEDLINE]

Canine and Feline Models of Human Genetic Diseases and Their Contributions to Advancing Clinical Therapies
.

Yale J Biol Med. 2017 Sep;90(3):417-431

Authors: Gurda BL, Bradbury AM, Vite CH

Abstract
For many lethal or debilitating genetic disorders in patients there are no satisfactory therapies. Several barriers exist that hinder the developments of effective therapies including the limited availability of clinically relevant animal models that faithfully recapitulate human genetic disease. In 1974, the Referral Center for Animal Models of Human Genetic Disease (RCAM) was established by Dr. Donald F. Patterson and continued by Dr. Mark E. Haskins at the University of Pennsylvania with the mission to discover, understand, treat, and maintain breeding colonies of naturally occurring hereditary disorders in dogs and cats that are orthologous to those found in human patients. Although non-human primates, sheep, and pig models are also available within the medical community, naturally occurring diseases are rarely identified in non-human primates, and the vast behavioral, clinicopathological, physiological, and anatomical knowledge available regarding dogs and cats far surpasses what is available in ovine and porcine species. The canine and feline models that are maintained at RCAM are presented here with a focus on preclinical therapy data. Clinical studies that have been generated from preclinical work in these models are also presented.

PMID: 28955181 [PubMed - indexed for MEDLINE]

Resilience to health challenges is related to different ways of thinking: mediators of physical and emotional quality of life in a heterogeneous rare-disease cohort.

Qual Life Res. 2017 Nov;26(11):3075-3088

Authors: Schwartz CE, Michael W, Rapkin BD

Abstract
BACKGROUND: We sought to understand what distinguishes people who confront health challenges but still manage to thrive. This study investigated whether resilience helps to explain the impact of health challenges on quality of life (QOL) outcomes, and how resilience relates to appraisal.
METHODS: A web-based survey of rare-disease panel participants included the Centers for Disease Control Healthy Days Core Module, the PROMIS-10, and comorbidities. The QOL Appraisal Profile-v2 assessed cognitive processes underlying QOL. Resilience was operationalized statistically using residual modeling, and hierarchical regressions tested the mediation hypothesis that resilience accounts for a significant amount of the relationship of appraisal to QOL.
RESULTS: The study sample (n = 3,324; mean age 50; 86% female; 90% White) represented a range of diagnostic codes, with cancer and diseases of the nervous system being the most prevalent health conditions. After adjusting for comorbidities (catalysts), resilience was associated with better physical and emotional functioning, and different appraisal processes were associated with better or worse physical or emotional functioning. After controlling for catalysts, 62% of the association of Physical Functioning and 23% of the association between Emotional Functioning and appraisal were mediated by resilience. Physical and emotional resilience comprised some of the same appraisal processes, but physically resilient people were characterized by more appraisal processes than their emotionally resilient counterparts.
CONCLUSIONS: Resilient people employ different appraisal processes than non-resilient people, and these processes differ for physical and emotional outcomes. Resilience was a stronger mediator of the relationship between physical rather than emotional functioning and appraisal.

PMID: 28660463 [PubMed - indexed for MEDLINE]

Sonographic and Magnetic Resonance Imaging Characteristics of Juvenile Papillomatosis: Three Cases With Different Manifestations.

Ultrasound Q. 2017 Jun;33(2):174-178

Authors: Yilmaz R, Bayramoglu Z, Bicen F, Kayhan A, Yesil S, Acunas G

Abstract
Juvenile papillomatosis (JP) is an infrequently seen benign proliferative lesion in women younger than 30 years. Herein, we present different clinical manifestations of histopathologically proven JP of the breast, in addition to magnetic resonance and sonographic imaging features of these cases. Patient 1 exhibited nipple discharge and papillary carcinoma accompanied after the operation. Patient 2 presented with a giant mass with cystic and numerous solid nodular components that filled the entire right breast. Patient 3 exhibited cystic areas in a well-circumscribed hypoechoic solid mass besides ahypoechoic mass with indistinct borders, which was evaluated as multifocal JP.

PMID: 28538449 [PubMed - indexed for MEDLINE]

Ovarian Artery Embolization as a Treatment for Persistent Ovarian Remnant Syndrome.

Cardiovasc Intervent Radiol. 2017 Aug;40(8):1278-1280

Authors: Chan TL, Singh H, Benton AS, Harkins GJ

Abstract
Ovarian remnant syndrome (ORS) is a rare condition in which ovarian tissue persists at the site of prior oophorectomy and often causes debilitating pelvic pain. Gold standard of treatment is surgical resection. We report a case of persistent ORS in a 44-year-old female who was successfully treated with ovarian artery embolization after failure of standard medical and gynecologic therapies. The ovarian tissue remnant was reduced by 75% in volume, and the patient was near symptom-free four months after the procedure.

PMID: 28280977 [PubMed - indexed for MEDLINE]

LAILAPS-QSM: A RESTful API and JAVA library for semantic query suggestions.

PLoS Comput Biol. 2018 Mar 12;14(3):e1006058

Authors: Chen J, Scholz U, Zhou R, Lange M

Abstract
In order to access and filter content of life-science databases, full text search is a widely applied query interface. But its high flexibility and intuitiveness is paid for with potentially imprecise and incomplete query results. To reduce this drawback, query assistance systems suggest those combinations of keywords with the highest potential to match most of the relevant data records. Widespread approaches are syntactic query corrections that avoid misspelling and support expansion of words by suffixes and prefixes. Synonym expansion approaches apply thesauri, ontologies, and query logs. All need laborious curation and maintenance. Furthermore, access to query logs is in general restricted. Approaches that infer related queries by their query profile like research field, geographic location, co-authorship, affiliation etc. require user's registration and its public accessibility that contradict privacy concerns. To overcome these drawbacks, we implemented LAILAPS-QSM, a machine learning approach that reconstruct possible linguistic contexts of a given keyword query. The context is referred from the text records that are stored in the databases that are going to be queried or extracted for a general purpose query suggestion from PubMed abstracts and UniProt data. The supplied tool suite enables the pre-processing of these text records and the further computation of customized distributed word vectors. The latter are used to suggest alternative keyword queries. An evaluated of the query suggestion quality was done for plant science use cases. Locally present experts enable a cost-efficient quality assessment in the categories trait, biological entity, taxonomy, affiliation, and metabolic function which has been performed using ontology term similarities. LAILAPS-QSM mean information content similarity for 15 representative queries is 0.70, whereas 34% have a score above 0.80. In comparison, the information content similarity for human expert made query suggestions is 0.90. The software is either available as tool set to build and train dedicated query suggestion services or as already trained general purpose RESTful web service. The service uses open interfaces to be seamless embeddable into database frontends. The JAVA implementation uses highly optimized data structures and streamlined code to provide fast and scalable response for web service calls. The source code of LAILAPS-QSM is available under GNU General Public License version 2 in Bitbucket GIT repository: https://bitbucket.org/ipk_bit_team/bioescorte-suggestion.

PMID: 29529024 [PubMed - as supplied by publisher]

New findings in pharmacogenetics of schizophrenia.

Curr Opin Psychiatry. 2018 Mar 09;:

Authors: Zai CC, Tiwari AK, Zai GC, Maes MS, Kennedy JL

Abstract
PURPOSE OF REVIEW: This review highlights recent advances in the investigation of genetic factors for antipsychotic response and side effects.
RECENT FINDINGS: Antipsychotics prescribed to treat psychotic symptoms are variable in efficacy and propensity for causing side effects. The major side effects include tardive dyskinesia, antipsychotic-induced weight gain (AIWG), and clozapine-induced agranulocytosis (CIA). Several promising associations of polymorphisms in genes including HSPG2, CNR1, and DPP6 with tardive dyskinesia have been reported. In particular, a functional genetic polymorphism in SLC18A2, which is a target of recently approved tardive dyskinesia medication valbenazine, was associated with tardive dyskinesia. Similarly, several consistent findings primarily from genes modulating energy homeostasis have also been reported (e.g. MC4R, HTR2C). CIA has been consistently associated with polymorphisms in the HLA genes (HLA-DQB1 and HLA-B). The association findings between glutamate system genes and antipsychotic response require additional replications.
SUMMARY: The findings to date are promising and provide us a better understanding of the development of side effects and response to antipsychotics. However, more comprehensive investigations in large, well characterized samples will bring us closer to clinically actionable findings.

PMID: 29528898 [PubMed - as supplied by publisher]

CYP Induction and Xeno-Sensing Receptors PXR, CAR, AHR and PPARα at the Crossroads of Toxicokinetics and Toxicodynamics.

Basic Clin Pharmacol Toxicol. 2018 Mar 12;:

Authors: Hakkola J, Bernasconi C, Coecke S, Richert L, Andersson TB, Pelkonen O

Abstract
Pregnane X receptor (PXR), constitutive androstane receptor (CAR), aryl hydrocarbon receptor (AHR) and peroxisome proliferator-activated receptor α (PPARα) are ligand-activated transcription factors that regulate expression of many xenobiotic metabolizing enzymes including several cytochrome P450 (CYP) enzymes. Many xenobiotics induce CYP enzymes through these intracellular receptors and consequently affect toxicokinetics and possible metabolic activation of the receptor ligands and other xenobiotics utilizing similar metabolic pathways. However, it is now apparent that the xenobiotic receptors regulate also many endogenous functions and signalling pathways, and xenobiotic exposure thus may dysregulate an array of fundamental cell functions. This MiniReview surveys and discusses the multi-faceted roles of xenobiotic receptors, for which CYP induction may serve as the first alert and possibly a biomarker for exposure to xenobiotics. With the current emergence of the Adverse Outcome Pathway (AOP) concept, these receptors are being and will be assigned as molecular initiating events or key events in numerous discrete toxicity pathways. This article is protected by copyright. All rights reserved.

PMID: 29527807 [PubMed - as supplied by publisher]