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

"systems biology"

These pubmed results were generated on 2018/07/20

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.

Funding Opportunity PA-18-863 from the NIH Guide for Grants and Contracts. The purpose of this funding announcement (FOA) issued by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of Health (NIH) is to encourage research grant applications that explore whether and how alcohol and other illicit drugs or illicitly used prescription drugs interact to contribute to unintentional injuries and poisonings and how to prevent and/or reduce simultaneous use of alcohol or drugs singly or in combination.

Funding Opportunity PA-18-861 from the NIH Guide for Grants and Contracts. The purpose of this funding announcement (FOA) issued by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of Health (NIH) is to encourage research grant applications that explore whether and how alcohol and other illicit drugs or illicitly used prescription drugs interact to contribute to unintentional injuries and poisonings and how to prevent and/or reduce simultaneous use of alcohol or drugs singly or in combination.

Funding Opportunity PA-18-862 from the NIH Guide for Grants and Contracts. The purpose of this funding announcement (FOA) issued by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of Health (NIH) is to encourage research grant applications that explore whether and how alcohol and other illicit drugs or illicitly used prescription drugs interact to contribute to unintentional injuries and poisonings and how to prevent and/or reduce simultaneous use of alcohol or drugs singly or in combination.

Funding Opportunity RFA-HL-19-025 from the NIH Guide for Grants and Contracts. This Funding Opportunity Announcement (FOA) invites applications to enhance the pool of highly trained investigators from diverse backgrounds underrepresented in research. It is targeted toward individuals whose basic, clinical, and translational research interests are grounded in the advanced methods and experimental approaches needed to solve problems related to cardiovascular, pulmonary, and hematologic diseases and sleep disorders in the general and health disparities populations. This FOA invites applications from institutions with eligible faculty members to undertake special study and supervised research under a mentor who is an accomplished investigator in the research area proposed and has experience in developing independent investigators. This FOA is designed specifically for applicants proposing to serve as the lead investigator of an independent clinical trial, a clinical trial feasibility study, or a separate ancillary study to an existing trial, as part of their research and career development. Applicants not planning an independent clinical trial, or proposing to gain research experience in a clinical trial led by another investigator, must apply to the companion FOA (see RFA-HL-19-026).

Funding Opportunity RFA-HL-19-026 from the NIH Guide for Grants and Contracts. This Funding Opportunity Announcement (FOA) invites applications to enhance the pool of of highly trained investigators from diverse backgrounds underrepresented in research. It is targeted toward individuals whose basic, clinical, and translational research interests are grounded in the advanced methods and experimental approaches needed to solve problems related to cardiovascular, pulmonary, and hematologic diseases and sleep disorders in the general and health disparities populations. This FOA invites applications from Institutions with eligible faculty members to undertake special study and supervised research under a mentor who is an accomplished investigator in the research area proposed and has experience in developing independent investigators. This FOA is designed specifically for applicants proposing research that does not involve leading an independent clinical trial, a clinical trial feasibility study, or an ancillary study to a clinical trial. Applicants to this FOA are permitted to propose research experience in a clinical trial led by a mentor or co-mentor. Applicants proposing a clinical trial or an ancillary study to an ongoing clinical trial as lead investigator, should apply to the companion FOA (see RFA-HL-19-025).

Funding Opportunity PAR-18-860 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to support short-term exploratory, developmental, and transdisciplinary research to understand the immunologic events that occur during blood feeding by hematophagous arthropods. The scientific objectives of this initiative are (1) to understand the immunological events in the vertebrate host, which occur during and after blood feeding by hematophagous arthropods, at the bite site (skin) and systemically; (2) to identify and characterize the immune modulatory properties of arthropod salivary components; and (3) to understand the immunological events in the hematophagous arthropods following a blood meal.

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

"drug repositioning" OR "drug repurposing"

These pubmed results were generated on 2018/07/19

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.

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

pharmacogenomics

These pubmed results were generated on 2018/07/19

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.

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

"systems biology"

These pubmed results were generated on 2018/07/19

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.

Related Articles

Osmoregulation in the Plotosidae Catfish: Role of the Salt Secreting Dendritic Organ.

Front Physiol. 2018;9:761

Authors: Malakpour Kolbadinezhad S, Coimbra J, Wilson JM

Abstract
Unlike other marine teleosts, the Plotosidae catfishes reportedly have an extra-branchial salt secreting dendritic organ (DO). Salinity acclimation [brackishwater (BW) 3aaa, seawater (SWcontrol) 34aaa, and hypersaline water (HSW) 60aaa] for 14 days was used to investigate the osmoregulatory abilities of Plotosus lineatus through measurements of blood chemistry, muscle water content (MWC), Na+/K+-ATPase (NKA) specific activity and ion transporter expression in gills, DO, kidney and intestine. Ion transporter expression was determined using immunoblotting, immunohistochemistry (IHC) and quantitative polymerase chain reaction (qPCR). HSW elevated mortality, plasma osmolality and ions, and hematocrit, and decreased MWC indicating an osmoregulatory challenge. NKA specific activity and protein levels were significantly higher in DO compared to gill, kidney and intestine at all salinities. NKA specific activity increased in kidney and posterior intestine with HSW but only kidney showed correspondingly higher NKA α-subunit protein levels. Since DO mass was greater in HSW, the total amount of DO NKA activity expressed per gram fish was greater indicating higher overall capacity. Gill NKA and V-ATPase protein levels were greater with HSW acclimation but this was not reflected in NKA activity, mRNA or ionocyte abundance. BW acclimation resulted in lower NKA activity in gill, kidney and DO. Cl- levels were better regulated and the resulting strong ion ratio in BW suggests a metabolic acidosis. Elevated DO heat shock protein 70 levels in HSW fish indicate a cellular stress. Strong NKA and NKCC1 (Na+:K+:2Cl- cotransporter1) co-localization was observed in DO parenchymal cells, which was rare in gill ionocytes. NKCC1 immunoblot expression was only detected in DO, which was highest at HSW. Cystic fibrosis transmembrane regulator Cl- channel (CFTR) localize apically to DO NKA immunoreactive cells. Taken together, the demonstration of high NKA activity in DO coexpressed with NKCC1 and CFTR indicates the presence of the conserved secondary active Cl- secretion mechanism found in other ion transporting epithelia suggesting a convergent evolution with other vertebrate salt secreting organs. However, the significant osmoregulatory challenge of HSW indicates that the DO may be of limited use under more extreme salinity conditions in contrast to the gill based ionoregulatory strategy of marine teleosts.

PMID: 30018560 [PubMed]

Related Articles

Nuclear Factor κB Activation in a Type V Pityriasis Rubra Pilaris Patient Harboring Multiple CARD14 Variants.

Front Immunol. 2018;9:1564

Authors: Danis J, Göblös A, Gál B, Sulák A, Farkas K, Török D, Varga E, Korom I, Kemény L, Széll M, Bata-Csörgö Z, Nagy N

Abstract
Pityriasis rubra pilaris (PRP) is a rare papulosquamous skin disorder, which is phenotypically related to psoriasis. Some familial PRP cases show autosomal dominant inheritance due to CARD14 mutations leading to increased nuclear factor κB (NFκB) activation. Moreover, CARD14 polymorphisms have also been implicated in sporadic PRP. A Hungarian PRP patient with childhood onset disease showing worsening of the symptoms in adulthood with poor therapeutic response underwent genetic screening for the CARD14 gene, revealing four genetic variants (rs117918077, rs2066964, rs28674001, and rs11652075). To confirm that the identified genetic variants would result in altered NFκB activity in the patient, functional studies were carried out. Immunofluorescent staining of the NFκB p65 subunit and NFκB-luciferase reporter assay demonstrated significantly increased NFκB activity in skin samples and keratinocytes from the PRP patient compared to healthy samples. Characterization of the cytokine profile of the keratinocytes and peripheral blood mononuclear cells demonstrated that the higher NFκB activation in PRP cells induces enhanced responses to inflammatory stimuli. These higher inflammatory reactions could not be explained solely by the observed CARD14 or other inflammation-related gene variants (determined by whole exome sequencing). Thus our study indicates the importance of investigations on other genetic factors related to PRP and their further functional characterization to bring us closer to the understanding of cellular and molecular background of disease pathogenesis.

PMID: 30018619 [PubMed]

Related Articles

Clinical Effects of Piribedil in Adjuvant Treatment of Parkinson's Disease: A Meta-Analysis.

Open Med (Wars). 2018;13:270-277

Authors: Peihua L, Jianqin W

Abstract
OBJECTIVE: To evaluate the clinical effects of piribedil in adjuvant treatment of Parkinson's Disease (PD) by pooling previously openly published studies.
METHODS: The related electronic databases of Medline (1960~2017.5), Cochrane central register of controlled trials (CENTRAL), EMBASE (1980~2017.5) and Wanfang (1986~20175.5) were searched by two reviewers (Lu Peihua and Wang Jianqian) independently for publications including the topic of prospective randomized controlled trials about clinical effects of piribedil in adjuvant treatment of PD. The data of each included study was extracted and pooled by Stata11.0 software (for meta-analysis). The statistical heterogeneity across the studies was evaluated by I2 test and the publication bias was calculated by begg's funnel plot and Egger's line regression test.
RESULTS: After searching the related electronic databases of Medline, CENTRAL, EMBSE and Wanfang databases, 11 clinical studies were included in this meta-analysis. The pooled RR (random effect model) of clinical efficacy was 1.29 (95%CI:1.18~1.41, P=4×10-3) indicating the clinical efficacy of piribedil group was signficat higher than those of control group. The standard mean difference (SMD) for UPDRS score changed before and after treatment was pooled by random effect model. The combined SMD was -0.41 (95%CI:-0.75~-0.06). For piribedil related side effects, the combined data indicated that there was no statistical difference for nausea and vomiting (RR=0.43, 95%CI:0.41~1.69, P=0.61), mental disorders (RR=0.85, 95%CI:0.45~1.59, P=0.61) and other toxicities (RR=0.32, 95%CI:0.09~1.16, P=0.08).
CONCLUSION: Piribedil combined with Levodopa in adjuvant treatment of PD is more effective than Levodopa alone without increasing the drug related toxicity.

PMID: 30019007 [PubMed]

Related Articles

Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours.

ESMO Open. 2018;3(4):e000381

Authors: Fiedler W, Stoeger H, Perotti A, Gastl G, Weidmann J, Dietrich B, Baumeister H, Danielczyk A, Goletz S, Salzberg M, De Dosso S

Abstract
Purpose: TrasGEX is a second-generation monoclonal antibody of trastuzumab, glyco-optimised to enhance antibody-dependent cellular cytotoxicity while fully retaining trastuzumab's antigen-binding properties to human epidermal growth factor receptor 2 (HER2). A phase I dose-escalation study was conducted to establish the optimal TrasGEX dose and regimen for phase II studies and to define the safety, pharmacokinetics (PK) and preliminary antitumour activity of TrasGEX.
Patients and methods: A total of 37 patients with advanced HER2-positive carcinomas and progressive disease received TrasGEX intravenously every 3 weeks until disease progression in doses of 12-720 mg in a three-plus-three dose escalation design, including an expansion cohort at the highest dose.
Results: No dose limiting toxicity was observed, and no maximum tolerated dose was reached. Drug-related adverse events were mainly infusion-related reactions occurring during the first infusion in 51% of patients; all but two were mild-to-moderate. Compared with trastuzumab, the PK parameters were dose dependent, with a mean terminal half-life (t1/2) of 263±99 hours for the 720 mg dose. Clinical benefit in 15 out of 30 (50%) evaluable patients included one ongoing complete response, two partial remissions lasting 16 and 77 weeks and disease stabilisation (SD) in 12 patients lasting a median (range) of 17 (7-26) weeks; three of them had SD of 24, 25 and 26 weeks, respectively.
Conclusion: TrasGEX was safe, well-tolerated and showed antitumour activity in 50% of evaluable patients, all with progressive disease at study entry. Infusions at an interval of 2-3 weeks should achieve clinically relevant trough levels for future studies (NCT01409343).

PMID: 30018811 [PubMed]

Related Articles

Linked Registries: Connecting Rare Diseases Patient Registries through a Semantic Web Layer.

Biomed Res Int. 2017;2017:8327980

Authors: Sernadela P, González-Castro L, Carta C, van der Horst E, Lopes P, Kaliyaperumal R, Thompson M, Thompson R, Queralt-Rosinach N, Lopez E, Wood L, Robertson A, Lamanna C, Gilling M, Orth M, Merino-Martinez R, Posada M, Taruscio D, Lochmüller H, Robinson P, Roos M, Oliveira JL

Abstract
Patient registries are an essential tool to increase current knowledge regarding rare diseases. Understanding these data is a vital step to improve patient treatments and to create the most adequate tools for personalized medicine. However, the growing number of disease-specific patient registries brings also new technical challenges. Usually, these systems are developed as closed data silos, with independent formats and models, lacking comprehensive mechanisms to enable data sharing. To tackle these challenges, we developed a Semantic Web based solution that allows connecting distributed and heterogeneous registries, enabling the federation of knowledge between multiple independent environments. This semantic layer creates a holistic view over a set of anonymised registries, supporting semantic data representation, integrated access, and querying. The implemented system gave us the opportunity to answer challenging questions across disperse rare disease patient registries. The interconnection between those registries using Semantic Web technologies benefits our final solution in a way that we can query single or multiple instances according to our needs. The outcome is a unique semantic layer, connecting miscellaneous registries and delivering a lightweight holistic perspective over the wealth of knowledge stemming from linked rare disease patient registries.

PMID: 29214177 [PubMed - indexed for MEDLINE]

Related Articles

Patient, disease, and treatment factors associated with overall survival in esthesioneuroblastoma.

Int Forum Allergy Rhinol. 2017 Dec;7(12):1186-1194

Authors: Carey RM, Godovchik J, Workman AD, Kuan EC, Parasher AK, Chen J, Palmer JN, Adappa ND, Newman JG, Brant JA

Abstract
BACKGROUND: Esthesioneuroblastomas (ENB) are uncommon and data regarding outcomes are often limited to single-institution series. The National Cancer Database (NCDB), which contains outcomes information from treatment centers across the United States, represents an opportunity to evaluate outcomes for rare diseases such as ENB across multiple institutions.
METHODS: The NCDB was queried for location codes corresponding to the nasal cavity and paranasal sinuses and the histology code for ENB. Multivariate analyses were performed to evaluate for contributing factors to overall survival.
RESULTS: A total of 1225 patients with ENB met the inclusion criteria. The 5-year overall survival was 76.2% (95% confidence interval [CI], 73.4-79.0%). Overall survival was associated with Kadish stage, grade, treatment sequence, margin status, Charlson/Deyo score, age, and gender (p < 0.05). Multivariate analysis demonstrated that, compared with surgery alone, surgery followed by radiation without chemotherapy had improved all-cause mortality (odds ratio [OR], 0.61; 95% CI, 0.40-0.95). Surgery with chemotherapy alone was associated with increased odds of all-cause mortality (OR, 4.86; 95% CI, 2.31-10.25). Multivariate subanalysis for Kadish stages A and B demonstrated no difference in survival between surgery and surgery followed by radiation, but surgery followed by chemoradiation had worse overall survival (OR, 3.03; 95% CI, 1.07-8.56). For Kadish stage C, surgery followed by radiation had improved overall survival compared with surgery alone (OR, 0.44; 95% CI, 0.24-0.81).
CONCLUSION: The most common treatment for ENB is surgery followed by radiation, which is associated with the highest overall survival. The role of adjunctive chemotherapy needs to be re-evaluated in further studies.

PMID: 29045018 [PubMed - indexed for MEDLINE]

Related Articles

Uncovering novel repositioning opportunities using the Open Targets platform.

Drug Discov Today. 2017 Dec;22(12):1800-1807

Authors: Khaladkar M, Koscielny G, Hasan S, Agarwal P, Dunham I, Rajpal D, Sanseau P

Abstract
The recently developed Open Targets platform consolidates a wide range of comprehensive evidence associating known and potential drug targets with human diseases. We have harnessed the integrated data from this platform for novel drug repositioning opportunities. Our computational workflow systematically mines data from various evidence categories and presents potential repositioning opportunities for drugs that are marketed or being investigated in ongoing human clinical trials, based on evidence strength on target-disease pairing. We classified these novel target-disease opportunities in several ways: (i) number of independent counts of evidence; (ii) broad therapy area of origin; and (iii) repositioning within or across therapy areas. Finally, we elaborate on one example that was identified by this approach.

PMID: 28919242 [PubMed - indexed for MEDLINE]

Related Articles

BioSearch: a semantic search engine for Bio2RDF.

Database (Oxford). 2017 Jan 01;2017:

Authors: Hu W, Qiu H, Huang J, Dumontier M

Abstract
Database URL: http://ws.nju.edu.cn/biosearch/.

PMID: 29220451 [PubMed - indexed for MEDLINE]

Case 260.

Radiology. 2018 Aug;288(2):621-623

Authors: Short RG, Tailor TD

Abstract
History A 31-year-old woman with a history of bilateral orthotopic lung transplantation performed 10 months earlier for cystic fibrosis presented for a routine follow-up appointment, with her chief symptom being a cough. The cough started approximately 1 month prior to this appointment and was minimally productive of clear to yellow phlegm. In addition to her cough, she reported increased sinus congestion and a sensation of "something in her upper chest." She denied shortness of breath, wheezing, hemoptysis, or cigarette smoking. Review of systems was negative for fever, chills, or night sweats. At physical examination, the patient was afebrile, borderline tachycardic (heart rate, 99 beats per minute), and mildly hypertensive (blood pressure, 138/99 mm Hg). Oxygen saturation was 96% on room air. Laboratory evaluation revealed a white blood cell count of 3.5 × 109/L (normal range, 3.2-9.8 × 109/L). Pulmonary function testing was notable for a newly decreased ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of 64% (2.0 and 3.4 L, respectively) (normal FEV1-to-FVC ratio, 80%), suggesting an obstructive lung process. One month prior to presentation, the patient's sputum cultures grew Pseudomonas and methicillin-resistant Staphylococcus aureus. The patient showed no evidence of active infection at the time of bronchoscopy. Thus, the bacteria were favored to reflect colonization, and antibiotic therapy was not administered at that time. The patient was taking an immunosuppression regimen of mycophenalate mofetil (CellCept; Genentech, San Francisco, Calif) (1 g twice daily), prednisone (10 mg daily), and tacrolimus (Prograf; Astellas Pharma US, Northbrook, Ill) (goal therapeutic range, 12-14 ng/mL). The patient was sent for posteroanterior and lateral chest radiography followed by chest CT ( Figs 1 - 3 ) and fluorine 18 fluorodeoxyglucose PET/CT ( Fig 4 ). [Figure: see text][Figure: see text][Figure: see text][Figure: see text].

PMID: 30020871 [PubMed - in process]

Gastrointestinal pathophysiology and nutrition in cystic fibrosis.

Expert Rev Gastroenterol Hepatol. 2018 Jul 18;:

Authors: Ratchford TL, Teckman JH, Patel DR

Abstract
INTRODUCTION: Cystic fibrosis (CF) is a severe, progressive, multi-systemic disease that is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Optimizing nutrition is critical, as higher growth parameters are associated with better pulmonary function and outcomes, but unfortunately patients with this disease are prone to malnutrition, growth failure, and vitamin deficiencies. The purpose of this review is to provide a timely highlight of the physiologic processes and outcome data to support today's management strategies, as well as review these principles themselves. Areas covered: This review covers the background of the importance of vigilant attention to nutrition and growth in these patients, the underlying physiology leading to an abnormal gastrointestinal tract and its role in CF malnutrition, and current evaluation and management strategies to address nutrition in CF. Analysis of up-to-date, relevant literature was performed using PubMed. Expert commentary: Advances in research and clinical developments over the years have improved knowledge of this disease as well as patient outcomes. Of particular importance is optimizing nutrition especially in the early stages of life, as well as accounting for the markedly abnormal CF intestinal milieu when addressing the gastrointestinal and nutritional needs of these patients.

PMID: 30019967 [PubMed - as supplied by publisher]