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

"Cystic Fibrosis"

These pubmed results were generated on 2016/10/16

PubMed comprises more than 24 million 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.

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

"Systems Biology"[Title/Abstract] AND ("2005/01/01"[PDAT] : "3000"[PDAT])

These pubmed results were generated on 2016/10/16

PubMed comprises more than 24 million 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.

Optimizing hydroxyurea therapy for sickle cell anemia.

Hematology Am Soc Hematol Educ Program. 2015;2015:436-43

Authors: Ware RE

Abstract
Hydroxyurea has proven efficacy in numerous clinical trials as a disease-modifying treatment for patients with sickle cell anemia (SCA) but is currently under-used in clinical practice. To improve the effectiveness of hydroxyurea therapy, efforts should be directed toward broadening the clinical treatment indications, optimizing the daily dosage, and emphasizing the benefits of early and extended treatment. Here, various issues related to hydroxyurea treatment are discussed, focusing on both published evidence and clinical experience. Specific guidance is provided regarding important but potentially unfamiliar aspects of hydroxyurea treatment for SCA, such as escalating to maximum tolerated dose, treating in the setting of cerebrovascular disease, switching from chronic transfusions to hydroxyurea, and using serial phlebotomy to alleviate iron overload. Future research directions to optimize hydroxyurea therapy are also discussed, including personalized dosing based on pharmacokinetic modeling, prediction of fetal hemoglobin responses based on pharmacogenomics, and the risks and benefits of hydroxyurea for non-SCA genotypes and during pregnancy/lactation. Another critical initiative is the introduction of hydroxyurea safely and effectively into global regions that have a high disease burden of SCA but limited resources, such as sub-Saharan Africa, the Caribbean, and India. Final considerations emphasize the long-term goal of optimizing hydroxyurea therapy, which is to help treatment become accepted as standard of care for all patients with SCA.

PMID: 26637755 [PubMed - indexed for MEDLINE]

PGWD: Integrating Personal Genome for Warfarin Dosing.

Interdiscip Sci. 2016 Mar;8(1):23-7

Authors: Pan Y, Cheng R, Li Z, Zhao Y, He J

Abstract
Warfarin is a drug normally used in the prevention of thrombosis and the formation of blood clots. The dosage of warfarin is strongly affected by genetic variants of CYP2C9 and VKORC1 genes. Current technologies for detecting the variants of these genes are mainly based on real-time PCR. In recent years, due to the rapidly dropping cost of whole genome sequencing and genotyping, more and more people get their whole genome sequenced or genotyped. However, current software for warfarin dosing prediction is based on low-throughput genetic information from either real-time PCR or melting curve methods. There is no bioinformatics tool available that can take the high-throughput genome sequencing data as input and determine the accurate dosage of warfarin. Here, we present PGWD, a web tool that analyzes personal genome sequencing data and integrates with clinical information for warfarin dosing.

PMID: 26267707 [PubMed - indexed for MEDLINE]

Text mining electronic hospital records to automatically classify admissions against disease: Measuring the impact of linking data sources.

J Biomed Inform. 2016 Oct 11;:

Authors: Kocbek S, Cavedon L, Martinez D, Bain C, Mac Manus C, Haffari G, Zukerman I, Verspoor K

Abstract
OBJECTIVE: Text and data mining play an important role in obtaining insights from Health and Hospital Information Systems. This paper presents a text mining system for detecting admissions marked as positive for several diseases: Lung Cancer, Breast Cancer, Colon Cancer, Secondary Malignant Neoplasm of Respiratory and Digestive Organs, Multiple Myeloma and Malignant Plasma Cell Neoplasms, Pneumonia, and Pulmonary Embolism. We specifically examine the effect of linking multiple data sources on text classification performance.
METHODS: Support Vector Machine classifiers are built for eight data source combinations, and evaluated using the metrics of Precision, Recall and F-Score. Sub-sampling techniques are used to address unbalanced datasets of medical records. We use radiology reports as an initial data source and add other sources, such as pathology reports and patient and hospital admission data, in order to assess the research question regarding the impact of the value of multiple data sources. Statistical significance is measured using the Wilcoxon signed-rank test. A second set of experiments explores aspects of the system in greater depth, focusing on Lung Cancer. We explore the impact of feature selection; analyse the learning curve; examine the effect of restricting admissions to only those containing reports from all data sources; and examine the impact of reducing the sub-sampling. These experiments provide better understanding of how to best apply text classification in the context of imbalanced data of variable completeness.
RESULTS: Radiology questions plus patient and hospital admission data contribute valuable information for detecting most of the diseases, significantly improving performance when added to radiology reports alone or to the combination of radiology and pathology reports.
CONCLUSION: Overall, linking data sources significantly improved classification performance for all the diseases examined. However, there is no single approach that suits all scenarios; the choice of the most effective combination of data sources depends on the specific disease to be classified.

PMID: 27742349 [PubMed - as supplied by publisher]

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/10/14

PubMed comprises more than 24 million 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.

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

"Systems Biology"[Title/Abstract] AND ("2005/01/01"[PDAT] : "3000"[PDAT])

These pubmed results were generated on 2016/10/14

PubMed comprises more than 24 million 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.

Bringing clinical pharmacogenomics information to pharmacists: A qualitative study of information needs and resource requirements.

Int J Med Inform. 2016 Feb;86:54-61

Authors: Romagnoli KM, Boyce RD, Empey PE, Adams S, Hochheiser H

Abstract
INTRODUCTION: As key experts in supporting medication-decision making, pharmacists are well-positioned to support the incorporation of pharmacogenomics into clinical care. However, there has been little study to date of pharmacists' information needs regarding pharmacogenomics. Understanding those needs is critical to design information resources that help pharmacists effectively apply pharmacogenomics information.
OBJECTIVES: We sought to understand the pharmacogenomics information needs and resource requirements of pharmacists.
METHODS: We conducted qualitative inquiries with 14 pharmacists representing 6 clinical environments, and used the results of those inquiries to develop a model of pharmacists' pharmacogenomics information needs and resource requirements.
RESULTS: The inquiries identified 36 pharmacogenomics-specific and pharmacogenomics-related information needs that fit into four information needs themes: background information, patient information, medication information, and guidance information. The results of the inquiries informed a model of pharmacists' pharmacogenomics resource requirements, with 3 themes: structure of the resource, perceptions of the resource, and perceptions of the information.
CONCLUSION: Responses suggest that pharmacists anticipate an imminently growing role for pharmacogenomics in their practice. Participants value information from trust-worthy resources like FDA product labels, but struggle to find relevant information quickly in labels. Specific information needs include clinically relevant guidance about genotypes, phenotypes, and how to care for their patients with known genotypes. Information resources supporting the goal of incorporating complicated genetic information into medication decision-making goals should be well-designed and trustworthy.

PMID: 26725696 [PubMed - indexed for MEDLINE]

Genetic polymorphisms of pharmacogenomic VIP variants in the lhoba population of southwest China.

Int J Clin Exp Pathol. 2015;8(10):13293-303

Authors: He Y, Yang H, Geng T, Feng T, Yuan D, Kang L, Luo M, Jin T

Abstract
BACKGROUND: It is well-established that differences among ethnic groups in drug responses are primarily due to the genetic diversity of pharmacogenes. A number of genes or variants that play a crucial role in drug responses have been designated Very Important Pharmacogenes (VIP) by the PharmGKB database. Clarifying the polymorphic distribution of VIPs in different ethnic groups will aid in personalized medicine for specific populations.
METHODS: We sequenced 85 VIP variants in the Lhoba population based on the PharmGKB database. The polymorphic distribution of the 85 VIP variants in 100 Lhoba subjects was determined and compared with that of 11 major HapMap populations, including ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI. We used χ(2) tests to identify significantly different loci between these populations. We downloaded SNP allele frequencies from the ALlele FREquency Database to observe the global genetic variation distribution for these specific loci. And then we used Structure software to perform the genetic structure analysis of 12 populations.
RESULTS: Based on comparisons of selected available loci, we found that 23, 28, 16, 10, 20, 16, 24, 19, 22, 21 and 36 of the selected VIP variant genotype frequencies in the Lhoba population differed from those of the ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI, and YRI populations, respectively. In addition, Pairwise FST values and clustering analyses also showed the VIP variants in Lhoba exhibited a close genetic affinity with CHD, CHB and JPT populations.
CONCLUSION: Our results complement pharmacogenomic data on the Lhoba ethnic group and may be helpful in the diagnosis of certain diseases in minorities.

PMID: 26722533 [PubMed - indexed for MEDLINE]

Physician perspectives of CYP2C19 and clopidogrel drug-gene interaction active clinical decision support alerts.

Int J Med Inform. 2016 Feb;86:117-25

Authors: Nishimura AA, Shirts BH, Salama J, Smith JW, Devine B, Tarczy-Hornoch P

Abstract
OBJECTIVE: To determine if physicians find clinical decision support alerts for pharmacogenomic drug-gene interactions useful and assess their perceptions of usability aspects that impact usefulness.
MATERIALS AND METHODS: 52 physicians participated in an online simulation and questionnaire involving a prototype alert for the clopidogrel and CYP2C19 drug-gene interaction.
RESULTS: Only 4% of participants stated they would override the alert. 92% agreed that the alerts were useful. 87% found the visual interface appropriate, 91% felt the timing of the alert was appropriate and 75% were unfamiliar with the specific drug-gene interaction. 80% of providers preferred the ability to order the recommended medication within the alert. Qualitative responses suggested that supplementary information is important, but should be provided as external links, and that the utility of pharmacogenomic alerts depends on the broader ecosystem of alerts.
PRINCIPAL CONCLUSIONS: Pharmacogenomic alerts would be welcomed by many physicians, can be built with minimalist design principles, and are appropriately placed at the end of the prescribing process. Since many physicians lack familiarity with pharmacogenomics but have limited time, information and educational resources within the alert should be carefully selected and presented in concise ways.

PMID: 26642939 [PubMed - indexed for MEDLINE]

Ventilatory limitation and dynamic hyperinflation during exercise testing in Cystic Fibrosis.

Pediatr Pulmonol. 2016 Oct 13;:

Authors: Karapanagiotis S, Gambazza S, Brivio A, D'Abrosca F, Colombo C

Abstract
OBJECTIVE: To investigate the presence of dynamic hyperinflation after the Modified Shuttle Test (MST) and its relationship with lung function, exercise tolerance, and clinical symptoms in Cystic Fibrosis (CF).
METHODS: Retrospective observational study. Subjects in clinically stable condition with a CF diagnosis based on a positive sweat test (chloride >60 mEq/L) and/or presence of two disease causing mutations, with available data on MST, spirometry, maximal voluntary ventilation, and inspiratory capacity manoeuvres were considered for the analysis. Breathing reserve was calculated and a threshold value of 0.7 was subsequently chosen as a value of pulmonary mechanical limit. Subjects were then categorized into two groups according to the change in the inspiratory capacity from rest to peak exercise. Unconditional logistic regression was used to estimate unadjusted odds ratios, 95% confidence intervals and P-values.
RESULTS: Twenty-two subjects demonstrated evidence of dynamic hyperinflation during the MST. Thirteen out of 22 subjects were ventilatory limited during exercise including 5 of those without evidence of dynamic hyperinflation (P = 0.24). No combination of variables resulted in a parsimonious regression model.
CONCLUSIONS: Dynamic hyperinflation is common in CF and it is not associated with traditionally defined ventilatory limitation parameters during the MST. Pediatr Pulmonol. © 2016 Wiley Periodicals, Inc.

PMID: 27736037 [PubMed - as supplied by publisher]

Inhalable Antimicrobials for Treatment of Bacterial Biofilm-Associated Sinusitis in Cystic Fibrosis Patients: Challenges and Drug Delivery Approaches.

Int J Mol Sci. 2016 Oct 09;17(10):

Authors: Kłodzińska SN, Priemel PA, Rades T, Mørck Nielsen H

Abstract
Bacterial biofilm-associated chronic sinusitis in cystic fibrosis (CF) patients caused by Pseudomonas aeruginosa infections and the lack of available treatments for such infections constitute a critical aspect of CF disease management. Currently, inhalation therapies to combat P. aeruginosa infections in CF patients are focused mainly on the delivery of antimicrobials to the lower respiratory tract, disregarding the sinuses. However, the sinuses constitute a reservoir for P. aeruginosa growth, leading to re-infection of the lungs, even after clearing an initial lung infection. Eradication of P. aeruginosa from the respiratory tract after a first infection has been shown to delay chronic pulmonary infection with the bacteria for up to two years. The challenges with providing a suitable treatment for bacterial sinusitis include: (i) identifying a suitable antimicrobial compound; (ii) selecting a suitable device to deliver the drug to the sinuses and nasal cavities; and (iii) applying a formulation design, which will mediate delivery of a high dose of the antimicrobial directly to the site of infection. This review highlights currently available inhalable antimicrobial formulations for treatment and management of biofilm infections caused by P. aeruginosa and discusses critical issues related to novel antimicrobial drug formulation design approaches.

PMID: 27735846 [PubMed - in process]

The cystic fibrosis transmembrane conductance regulator (CFTR) and its stability.

Cell Mol Life Sci. 2016 Oct 12;

Authors: Meng X, Clews J, Kargas V, Wang X, Ford RC

Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) is responsible for the disease cystic fibrosis (CF). It is a membrane protein belonging to the ABC transporter family functioning as a chloride/anion channel in epithelial cells around the body. There are over 1500 mutations that have been characterised as CF-causing; the most common of these, accounting for ~70 % of CF cases, is the deletion of a phenylalanine at position 508. This leads to instability of the nascent protein and the modified structure is recognised and then degraded by the ER quality control mechanism. However, even pharmacologically 'rescued' F508del CFTR displays instability at the cell's surface, losing its channel function rapidly and it is rapidly removed from the plasma membrane for lysosomal degradation. This review will, therefore, explore the link between stability and structure/function relationships of membrane proteins and CFTR in particular and how approaches to study CFTR structure depend on its stability. We will also review the application of a fluorescence labelling method for the assessment of the thermostability and the tertiary structure of CFTR.

PMID: 27734094 [PubMed - as supplied by publisher]

Identification of Burkholderia and Uncommon Glucose Non-fermenting Gram-Negative Bacilli Isolated from Patients with Cystic Fibrosis using Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS).

J Clin Microbiol. 2016 Oct 12;:

Authors: Plongla R, Panagea T, Pincus DH, Jones MC, Gilligan PH

Abstract
Environmental glucose non-fermenting Gram-negative bacilli other than Pseudomonas aeruginosa are frequently isolated from respiratory specimens of patients with cystic fibrosis (CF) (1).….

PMID: 27733629 [PubMed - as supplied by publisher]

Habitat-associated skew of clone abundance in the Pseudomonas aeruginosa population.

Environ Microbiol Rep. 2015 Dec;7(6):955-60

Authors: Wiehlmann L, Cramer N, Tümmler B

Abstract
The population structure of the cosmopolitan Pseudomonas aeruginosa was investigated by genotyping 2921 isolates from 1448 independent habitats with a custom-made 58 binary marker microarray. Of 323 identified clone types, 109 clones made up 82% of the population. The 20 most frequent clones had an absolute share of 44% indicating that the P. aeruginosa population is dominated by few epidemic clonal complexes. The frequency distribution of common clones was different between inanimate habitats and human niches. The three most abundant clones in the environment were rare among isolates from human infection. Conversely, disease-associated isolates either belonged to ubiquitous clones such as C and PA14 or to clones that were uncommon in the environment. The P. aeruginosa population consists of major clones that are just as versatile in their habitat and geographic origin as the whole species and of minor clones with preference for a peculiar niche.

PMID: 26419222 [PubMed - indexed for MEDLINE]

How users adopt healthcare information: An empirical study of an online Q&A community.

Int J Med Inform. 2016 Feb;86:91-103

Authors: Jin J, Yan X, Li Y, Li Y

Abstract
OBJECTIVES: The emergence of social media technology has led to the creation of many online healthcare communities, where patients can easily share and look for healthcare-related information from peers who have experienced a similar problem. However, with increased user-generated content, there is a need to constantly analyse which content should be trusted as one sifts through enormous amounts of healthcare information. This study aims to explore patients' healthcare information seeking behavior in online communities.
METHODS: Based on dual-process theory and the knowledge adoption model, we proposed a healthcare information adoption model for online communities. This model highlights that information quality, emotional support, and source credibility are antecedent variables of adoption likelihood of healthcare information, and competition among repliers and involvement of recipients moderate the relationship between the antecedent variables and adoption likelihood. Empirical data were collected from the healthcare module of China's biggest Q&A community-Baidu Knows. Text mining techniques were adopted to calculate the information quality and emotional support contained in each reply text. A binary logistics regression model and hierarchical regression approach were employed to test the proposed conceptual model.
RESULTS: Information quality, emotional support, and source credibility have significant and positive impact on healthcare information adoption likelihood, and among these factors, information quality has the biggest impact on a patient's adoption decision. In addition, competition among repliers and involvement of recipients were tested as moderating effects between these antecedent factors and the adoption likelihood. Results indicate competition among repliers positively moderates the relationship between source credibility and adoption likelihood, and recipients' involvement positively moderates the relationship between information quality, source credibility, and adoption decision.
CONCLUSIONS: In addition to information quality and source credibility, emotional support has significant positive impact on individuals' healthcare information adoption decisions. Moreover, the relationships between information quality, source credibility, emotional support, and adoption decision are moderated by competition among repliers and involvement of recipients.

PMID: 26616406 [PubMed - indexed for MEDLINE]

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/10/13

PubMed comprises more than 24 million 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.

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

"Cystic Fibrosis"

These pubmed results were generated on 2016/10/13

PubMed comprises more than 24 million 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.

Doxycycline is an NF-κB inhibitor that induces apoptotic cell death in malignant T-cells.

Oncotarget. 2016 Oct 6;:

Authors: Alexander-Savino CV, Hayden MS, Richardson C, Zhao J, Poligone B

Abstract
Cutaneous T-cell Lymphoma (CTCL) is a rare non-Hodgkin's lymphoma that can affect the skin, blood, and lymph nodes, and can metastasize at late stages. Novel therapies that target all affected disease compartments and provide longer lasting responses while being safe are needed. One potential therapeutic target is NF-κB, a regulator of immune responses and an important participant in carcinogenesis and cancer progression. As a transcription factor, NF-κB targets genes that promote cell proliferation and survival. Constitutive or aberrant activation of NF-κB is encountered in many types of cancer, including CTCL.Recently, while analyzing gene-expression profiles of a variety of small molecule compounds that target NF-κB, we discovered the tetracycline family of antibiotics, including doxycycline, to be potent inhibitors of the NF-κB pathway. Doxycycline is well-tolerated, safe, and inexpensive; and is commonly used as an antibiotic and anti-inflammatory for the treatment a multitude of medical conditions.In our current study, we show that doxycycline induces apoptosis in a dose dependent manner in multiple different cell lines from patients with the two most common subtypes of CTCL, Mycosis Fungoides (MF) and Sézary Syndrome (SS). Similar results were found using primary CD4+ T cells from a patient with SS. Doxycycline inhibits TNF induced NF-κB activation and reduces expression of NF-κB dependent anti-apoptotic proteins, such as BCL2α. Furthermore, we have identified that doxycycline induces apoptosis through reactive oxygen species.

PMID: 27732942 [PubMed - as supplied by publisher]

Identifying candidate agents for lung adenocarcinoma by walking the human interactome.

Onco Targets Ther. 2016;9:5439-5450

Authors: Sun Y, Zhang R, Jiang Z, Xia R, Zhang J, Liu J, Chen F

Abstract
Despite recent advances in therapeutic strategies for lung cancer, mortality is still increasing. Therefore, there is an urgent need to identify effective novel drugs. In the present study, we implement drug repositioning for lung adenocarcinoma (LUAD) by a bioinformatics method followed by experimental validation. We first identified differentially expressed genes between LUAD tissues and nontumor tissues from RNA sequencing data obtained from The Cancer Genome Atlas database. Then, candidate small molecular drugs were ranked according to the effect of their targets on differentially expressed genes of LUAD by a random walk with restart algorithm in protein-protein interaction networks. Our method identified some potentially novel agents for LUAD besides those that had been previously reported (eg, hesperidin). Finally, we experimentally verified that atracurium, one of the potential agents, could induce A549 cells death in non-small-cell lung cancer-derived A549 cells by an MTT assay, acridine orange and ethidium bromide staining, and electron microscopy. Furthermore, Western blot assays demonstrated that atracurium upregulated the proapoptotic Bad and Bax proteins, downregulated the antiapoptotic p-Bad and Bcl-2 proteins, and enhanced caspase-3 activity. It could also reduce the expression of p53 and p21(Cip1/Waf1) in A549 cells. In brief, the candidate agents identified by our approach may provide greater insights into improving the therapeutic status of LUAD.

PMID: 27729798 [PubMed - in process]