Literature Watch
pharmacogenomics; +14 new citations
14 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2018/05/22
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"systems biology"; +44 new citations
44 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2018/05/22
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.
Chloride and sodium ion concentrations in saliva and sweat as a method to diagnose cystic fibrosis.
Chloride and sodium ion concentrations in saliva and sweat as a method to diagnose cystic fibrosis.
J Pediatr (Rio J). 2018 May 18;:
Authors: Gonçalves AC, Marson FAL, Mendonça RMH, Bertuzzo CS, Paschoal IA, Ribeiro JD, Ribeiro AF, Levy CE
Abstract
OBJECTIVE: Cystic fibrosis diagnosis is dependent on the chloride ion concentration in the sweat test (≥60mEq/mL - recognized as the gold standard indicator for cystic fibrosis diagnosis). Moreover, the salivary glands express the CFTR protein in the same manner as sweat glands. Given this context, the objective was to verify the correlation of saliva chloride concentration (SaCl) and sweat chloride concentration (SwCl), and between saliva sodium concentration (SaNa) and sweat sodium concentration (SwNa), in patients with cystic fibrosis and healthy control subjects, as a tool for cystic fibrosis diagnosis.
METHODS: There were 160 subjects enrolled: 57/160 (35.7%) patients with cystic fibrosis and two known CFTR mutations and 103/160 (64.4%) healthy controls subjects. Saliva ion concentration was analyzed by ABL 835 Radiometer® equipment and, SwCl and SwNa, respectively, by manual titration using the mercurimetric procedure of Schales & Schales and flame photometry. Statistical analysis was performed by the chi-squared test, the Mann-Whitney test, and Spearman's correlation. Alpha=0.05.
RESULTS: Patients with cystic fibrosis showed higher values of SwCl, SwNa, SaCl, and SaNa than healthy controls subjects (p-value<0.001). The correlation between SaCl and SwCl showed a positive Spearman's Rho (correlation coefficient)=0.475 (95% CI=0.346-0.587). Also, the correlation between SaNa and SwNa showed a positive Spearman's Rho=0.306 (95% CI=0.158-0.440).
CONCLUSIONS: SaCl and SaNa are candidates to be used in cystic fibrosis diagnosis, mainly in cases where it is difficult to achieve the correct sweat amount, and/or CFTR mutation screening is difficult, and/or reference methods for sweat test are unavailable to implement or are not easily accessible by the general population.
PMID: 29782810 [PubMed - as supplied by publisher]
Identification of an Anti-inflammation Protein, Annexin A1, in Tendon Derived Stem Cells (TDSCs) of Cystic Fibrosis Mice: A Comparative Proteomic Analysis.
Identification of an Anti-inflammation Protein, Annexin A1, in Tendon Derived Stem Cells (TDSCs) of Cystic Fibrosis Mice: A Comparative Proteomic Analysis.
Proteomics Clin Appl. 2018 May 21;:e1700162
Authors: Liu Y, Feng L, Wang H, Wang YJ, Chan HC, Jiang XH, Fu WM, Li G, Zhang JF
Abstract
PURPOSE: Our previous study reported an elevated inflammation during tendon injury in mice with cystic fibrosis (CF), indicating the inadequate management of inflammation due to dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR). The objective of this study is to identify the targets of CFTR that contribute to the abnormal inflammation during tendon injury.
EXPERIMENTAL DESIGN: A two-dimensional gel electrophoresis and mass spectrometry-based comparative proteomics was performed to find the molecular targets of CFTR. And the targeted protein was further confirmed at both mRNA and protein levels.
RESULTS: It was identified that fourteen proteins were differentially expressed, with annexin A1 being one of the most significantly down-regulated protein. Further confirmation showed that annexin A1 was significantly decreased in TDSCs isolated from DF508 mice. As an essential anti-inflammation mediator, it was also down-regulated in the injured tendon tissue of DF508 mice when compared with WT mice.
CONCLUSIONS AND CLINICAL RELEVANCE: Decreased annexin A1 expression could contribute to the elevated inflammation in DF508 mice during tendon injury. Therefore, Annexin A1 could be considered as a new potential biomarker or drug target for a possible therapeutic approach in clinical practice. This article is protected by copyright. All rights reserved.
PMID: 29781578 [PubMed - as supplied by publisher]
Osteoporosis Is Associated with Deteriorating Clinical Status in Adults with Cystic Fibrosis.
Osteoporosis Is Associated with Deteriorating Clinical Status in Adults with Cystic Fibrosis.
Int J Endocrinol. 2018;2018:4803974
Authors: Mathiesen IH, Pressler T, Oturai P, Katzenstein TL, Skov M, Frikke-Schmidt R, Hitz MF
Abstract
Background: Cystic fibrosis (CF) patients are in increased risk of osteoporosis. We aimed to determine the osteoporosis prevalence in an adult CF cohort and investigate calcium metabolic parameters and clinical status' association with bone mineral density evaluated by dual X-ray absorptiometry scan.
Methods: We performed a cross section database study of adults at a tertiary CF Center. Z scores were applied for patients < 50 years of age and T scores for patients > 50 years of age.
Results: One hundred twenty-five patients were included. Compared to nonosteoporotic patients, osteoporotic patients (15%) had significantly lower percent predicted forced expiratory volume in 1 second (ppFEV1), lower body mass index, higher frequency of CF-related diabetes and chronic lung infection, and higher high-sensitive C-reactive protein and glycated hemoglobin levels. Vitamin D was not associated with any outcome. In multivariate analyses, only ppFEV1 and female gender were independently associated with Z scores.
Conclusions: Osteoporosis in CF occurs with deteriorating clinical status while the role of calcium metabolism seems minor. Gender specific and dysglycemic impact on bone status should be investigated further.
PMID: 29780417 [PubMed]
Challenges and Promises for Planning Future Clinical Research Into Bacteriophage Therapy Against Pseudomonas aeruginosa in Cystic Fibrosis. An Argumentative Review.
Challenges and Promises for Planning Future Clinical Research Into Bacteriophage Therapy Against Pseudomonas aeruginosa in Cystic Fibrosis. An Argumentative Review.
Front Microbiol. 2018;9:775
Authors: Rossitto M, Fiscarelli EV, Rosati P
Abstract
Although early aggressive and prolonged treatment with specific antibiotics can extend survival in patients with cystic fibrosis (CF) colonized by opportunistic Pseudomonas aeruginosa (PA), antibiotics fail to eradicate the infecting multidrug-resistant (MDR) PA strains in CF. Century-long research has suggested treating patients with bacteriophages (phages, prokaryotic viruses) naturally hosted by bacteria. Although the only phage types used in therapy, lytic phages, lyse PA aggregated in biofilm matrix by depolymerase degrading enzymes, how they can effectively, safely, and persistently do so in patients with CF is unclear. Even though advanced techniques for formulating phage cocktails, training phages and collecting phage libraries have improved efficacy in vitro, whether personalized or ready-to-use therapeutic approaches or phages and antibiotics combined are effective and safe in vivo, and can reduce PA biofilms, remains debatable. Hence, to advance clinical research on phage therapy in clinical trials, also involving mucoid and non-mucoid multidrug-resistant PA in CF, and overcome problems in Western international regulations, we need reliable and repeatable information from experiments in vitro and in vivo on phage characterization, cocktail selection, personalized approaches, and phages combined with antibiotics. These findings, challenges, and promises prompted us to undertake this argumentative review to seek up-to-date information from papers describing lytic phage activity tested in vitro on PA laboratory strains, and PA strains from chronic infections including CF. We also reviewed in vivo studies on phage activity on pulmonary and non-pulmonary animal host models infected by laboratory or CF PA strains. Our argumentative review provides essential information showing that future phage clinical research in CF should use well-characterized and selected phages isolated against CF PA, tested in vitro under dynamic conditions in cocktails or combined with antibiotics, and in vivo on non-pulmonary and pulmonary host models infected with mucoid and non-mucoid CF MDR PA. Our findings should encourage pharmaceutical industries to conduct clinical trials in vitro and in vivo testing patented genomic engineered phages from phage libraries combined with antibiotics to treat or even prevent multidrug-resistant PA in CF, thus helping international regulatory agencies to plan future clinical research on phage therapy in CF.
PMID: 29780361 [PubMed]
Identification of a mutation in CNNM4 by whole exome sequencing in an Amish family and functional link between CNNM4 and IQCB1.
Identification of a mutation in CNNM4 by whole exome sequencing in an Amish family and functional link between CNNM4 and IQCB1.
Mol Genet Genomics. 2018 Jun;293(3):699-710
Authors: Li S, Xi Q, Zhang X, Yu D, Li L, Jiang Z, Chen Q, Wang QK, Traboulsi EI
Abstract
We investigated an Amish family in which three siblings presented with an early-onset childhood retinal dystrophy inherited in an autosomal recessive fashion. Genome-wide linkage analysis identified significant linkage to marker D2S2216 on 2q11 with a two-point LOD score of 1.95 and a multi-point LOD score of 3.76. Whole exome sequencing was then performed for the three affected individuals and identified a homozygous nonsense mutation (c.C1813T, p.R605X) in the cyclin and CBS domain divalent metal cation transport mediator 4 (CNNM4) gene located within the 2p14-2q14 Jalili syndrome locus. The initial assessment and collection of the family were performed before the clinical delineation of Jalili syndrome. Another assessment was made after the discovery of the responsible gene and the dental abnormalities characteristic of Jalili syndrome were retrospectively identified. The p.R605X mutation represents the first probable founder mutation of Jalili syndrome identified in the Amish community. The molecular mechanism underlying Jalili syndrome is unknown. Here we show that CNNM4 interacts with IQCB1, which causes Leber congenital amaurosis (LCA) when mutated. A truncated CNNM4 protein starting at R605 significantly increased the rate of apoptosis, and significantly increased the interaction between CNNM4 and IQCB1. Mutation p.R605X may cause Jalili syndrome by a nonsense-mediated decay mechanism, affecting the function of IQCB1 and apoptosis, or both. Our data, for the first time, functionally link Jalili syndrome gene CNNM4 to LCA gene IQCB1, providing important insights into the molecular pathogenic mechanism of retinal dystrophy in Jalili syndrome.
PMID: 29322253 [PubMed - indexed for MEDLINE]
TCR Repertoire Intratumor Heterogeneity in Localized Lung Adenocarcinomas: An Association with Predicted Neoantigen Heterogeneity and Postsurgical Recurrence.
TCR Repertoire Intratumor Heterogeneity in Localized Lung Adenocarcinomas: An Association with Predicted Neoantigen Heterogeneity and Postsurgical Recurrence.
Cancer Discov. 2017 10;7(10):1088-1097
Authors: Reuben A, Gittelman R, Gao J, Zhang J, Yusko EC, Wu CJ, Emerson R, Zhang J, Tipton C, Li J, Quek K, Gopalakrishnan V, Chen R, Vence LM, Cascone T, Vignali M, Fujimoto J, Rodriguez-Canales J, Parra ER, Little LD, Gumbs C, Forget MA, Federico L, Haymaker C, Behrens C, Benzeno S, Bernatchez C, Sepesi B, Gibbons DL, Wargo JA, William WN, Swisher S, Heymach JV, Robins H, Lee JJ, Sharma P, Allison JP, Futreal PA, Wistuba II, Zhang J
Abstract
Genomic intratumor heterogeneity (ITH) may be associated with postsurgical relapse of localized lung adenocarcinomas. Recently, mutations, through generation of neoantigens, were shown to alter tumor immunogenicity through T-cell responses. Here, we performed sequencing of the T-cell receptor (TCR) in 45 tumor regions from 11 localized lung adenocarcinomas and observed substantial intratumor differences in T-cell density and clonality with the majority of T-cell clones restricted to individual tumor regions. TCR ITH positively correlated with predicted neoantigen ITH, suggesting that spatial differences in the T-cell repertoire may be driven by distinct neoantigens in different tumor regions. Finally, a higher degree of TCR ITH was associated with an increased risk of postsurgical relapse and shorter disease-free survival, suggesting a potential clinical significance of T-cell repertoire heterogeneity.Significance: The present study provides insights into the ITH of the T-cell repertoire in localized lung adenocarcinomas and its potential biological and clinical impact. The results suggest that T-cell repertoire ITH may be tightly associated to genomic ITH and disease relapse. Cancer Discov; 7(10); 1088-97. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 1047.
PMID: 28733428 [PubMed - indexed for MEDLINE]
Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy.
Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy.
Eur Urol. 2017 Oct;72(4):544-554
Authors: Seiler R, Ashab HAD, Erho N, van Rhijn BWG, Winters B, Douglas J, Van Kessel KE, Fransen van de Putte EE, Sommerlad M, Wang NQ, Choeurng V, Gibb EA, Palmer-Aronsten B, Lam LL, Buerki C, Davicioni E, Sjödahl G, Kardos J, Hoadley KA, Lerner SP, McConkey DJ, Choi W, Kim WY, Kiss B, Thalmann GN, Todenhöfer T, Crabb SJ, North S, Zwarthoff EC, Boormans JL, Wright J, Dall'Era M, van der Heijden MS, Black PC
Abstract
BACKGROUND: An early report on the molecular subtyping of muscle-invasive bladder cancer (MIBC) by gene expression suggested that response to neoadjuvant chemotherapy (NAC) varies by subtype.
OBJECTIVE: To investigate the ability of molecular subtypes to predict pathological downstaging and survival after NAC.
DESIGN, SETTING, AND PARTICIPANTS: Whole transcriptome profiling was performed on pre-NAC transurethral resection specimens from 343 patients with MIBC. Samples were classified according to four published molecular subtyping methods. We developed a single-sample genomic subtyping classifier (GSC) to predict consensus subtypes (claudin-low, basal, luminal-infiltrated and luminal) with highest clinical impact in the context of NAC. Overall survival (OS) according to subtype was analyzed and compared with OS in 476 non-NAC cases (published datasets).
INTERVENTION: Gene expression analysis was used to assign subtypes.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Receiver-operating characteristics were used to determine the accuracy of GSC. The effect of GSC on survival was estimated by Cox proportional hazard regression models.
RESULTS AND LIMITATIONS: The models generated subtype calls in expected ratios with high concordance across subtyping methods. GSC was able to predict four consensus molecular subtypes with high accuracy (73%), and clinical significance of the predicted consensus subtypes could be validated in independent NAC and non-NAC datasets. Luminal tumors had the best OS with and without NAC. Claudin-low tumors were associated with poor OS irrespective of treatment regimen. Basal tumors showed the most improvement in OS with NAC compared with surgery alone. The main limitations of our study are its retrospective design and comparison across datasets.
CONCLUSIONS: Molecular subtyping may have an impact on patient benefit to NAC. If validated in additional studies, our results suggest that patients with basal tumors should be prioritized for NAC. We discovered the first single-sample classifier to subtype MIBC, which may be suitable for integration into routine clinical practice.
PATIENT SUMMARY: Different molecular subtypes can be identified in muscle-invasive bladder cancer. Although cisplatin-based neoadjuvant chemotherapy improves patient outcomes, we identified that the benefit is highest in patients with basal tumors. Our newly discovered classifier can identify these molecular subtypes in a single patient and could be integrated into routine clinical practice after further validation.
PMID: 28390739 [PubMed - indexed for MEDLINE]
Identification of mutations through dominant screening for obesity using C57BL/6 substrains.
Identification of mutations through dominant screening for obesity using C57BL/6 substrains.
Sci Rep. 2016 09 02;6:32453
Authors: Hossain MS, Asano F, Fujiyama T, Miyoshi C, Sato M, Ikkyu A, Kanno S, Hotta N, Kakizaki M, Honda T, Kim SJ, Komiya H, Miura I, Suzuki T, Kobayashi K, Kaneda H, Kumar V, Takahashi JS, Wakana S, Funato H, Yanagisawa M
Abstract
The discovery of leptin substantiated the usefulness of a forward genetic approach in elucidating the molecular network regulating energy metabolism. However, no successful dominant screening for obesity has been reported, which may be due to the influence of quantitative trait loci between the screening and counter strains and the low fertility of obese mice. Here, we performed a dominant screening for obesity using C57BL/6 substrains, C57BL/6J and C57BL/6N, with the routine use of in vitro fertilization. The screening of more than 5000 mutagenized mice established two obese pedigrees in which single nucleotide substitutions in Mc4r and Sim1 genes were identified through whole-exome sequencing. The mutation in the Mc4r gene produces a premature stop codon, and the mutant SIM1 protein lacks transcriptional activity, showing that the haploinsufficiency of SIM1 and MC4R results in obesity. We further examined the hypothalamic neuropeptide expressions in the mutant pedigrees and mice with diet-induced obesity, which showed that each obesity mouse model has distinct neuropeptide expression profiles. This forward genetic screening scheme is useful and applicable to any research field in which mouse models work.
PMID: 27585985 [PubMed - indexed for MEDLINE]
Request for Information (RFI): Resources or Services to Enable Functional Interpretation of Sequence Variants of Heart, Lung, Blood, and Sleep Disorders
("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects"); +15 new citations
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 2018/05/22
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.
Enhancer identification and activity evaluation in the red flour beetle, Tribolium castaneum.
Enhancer identification and activity evaluation in the red flour beetle, Tribolium castaneum.
Development. 2018 04 05;145(7):
Authors: Lai YT, Deem KD, Borràs-Castells F, Sambrani N, Rudolf H, Suryamohan K, El-Sherif E, Halfon MS, McKay DJ, Tomoyasu Y
Abstract
Evolution of cis-regulatory elements (such as enhancers) plays an important role in the production of diverse morphology. However, a mechanistic understanding is often limited by the absence of methods for studying enhancers in species other than established model systems. Here, we sought to establish methods to identify and test enhancer activity in the red flour beetle, Tribolium castaneum To identify possible enhancer regions, we first obtained genome-wide chromatin profiles from various tissues and stages of Tribolium using FAIRE (formaldehyde-assisted isolation of regulatory elements)-sequencing. Comparison of these profiles revealed a distinct set of open chromatin regions in each tissue and at each stage. In addition, comparison of the FAIRE data with sets of computationally predicted (i.e. supervised cis-regulatory module-predicted) enhancers revealed a very high overlap between the two datasets. Second, using nubbin in the wing and hunchback in the embryo as case studies, we established the first universal reporter assay system that works in various contexts in Tribolium, and in a cross-species context. Together, these advances will facilitate investigation of cis-evolution and morphological diversity in Tribolium and other insects.
PMID: 29540499 [PubMed - indexed for MEDLINE]
"Rare Diseases"[Mesh] OR "orphan disease"; +8 new citations
8 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
"Rare Diseases"[Mesh] OR "orphan disease"
These pubmed results were generated on 2018/05/22
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.
pharmacogenomics; +14 new citations
14 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2018/05/22
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.
"systems biology"; +41 new citations
41 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2018/05/22
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.
AHRQ Small Research Grant Program (R03)
AHRQ Health Services Research Demonstration and Dissemination Grants (R18)
AHRQ Health Services Research Projects (R01)
Advancing Evidence into Practice through Shared, Interoperable Clinical Decision Support Resources (U18)
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