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"cystic fibrosis"

These pubmed results were generated on 2017/03/07

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.

Deep learning-based drug-target interaction prediction.

J Proteome Res. 2017 Mar 06;:

Authors: Wen M, Zhang Z, Niu S, Sha H, Yang R, Yun Y, Lu H

Abstract
Identifying interactions between known drugs and targets is a major challenge in drug repositioning. In silico prediction of drug target interaction (DTI) can speed up the experimental work which is expensive and time-consuming by providing most potent DTIs. In silico prediction of DTI can also provide insights about the potential drug-drug interaction and promote the exploration of drug side-effect. Traditionally, the performance of DTI prediction heavily depends on the descriptors used to represent the drugs and the target proteins. In this paper, to accurately predict new DTIs between approved drugs and targets without separating the target into different classes, we developed a deep learning-based algorithmic framework named DeepDTIs. It firstly abstracts representation from raw input descriptors using unsupervised pre-training, then applies known label pairs of interaction to build a classification model. Comparing with other methods, it is found that DeepDTIs reaches or outperforms other state-of-the-art methods. The DeepDTIs can be further used to predict whether a new drug targets to some existing targets or whether a new target interacts with some existing drugs.

PMID: 28264154 [PubMed - as supplied by publisher]

Lhermitte-Duclos disease associated to Cowden syndrome: de novo diagnosis and management of these extremely rare syndromes in a patient.

BMJ Case Rep. 2017 Jan 30;2017:

Authors: Gama I, Almeida L

Abstract
A 36-year-old woman, with history of cutaneous papilomatosis and thyroid carcinoma presented with headache, transitory visual blurring and nausea. Funduscopy showed papilloedema. MRI showed a tumour of the right cerebellar hemisphere with a striated, tigroid pattern, typical of Lhermitte-Duclos disease (LDD). Significant clinical and perimetric improvements were noted after surgery and the follow-up did not reveal recurrences of the tumour. LDD is an extremely rare differential diagnosis of posterior fossa tumours. LDD and the history of thyroid carcinoma permitted us to diagnose Cowden syndrome (CS). We present a clinical case that supports the possibility of performing a preoperative diagnosis of LDD based on MRI features. We review the diagnosis and management of LDD and CS. This report highlights the importance of excluding CS after LDD diagnosis, of monitoring the optic nerve postoperatively using optical coherence tomography and of prompt treatment that can potentially prevent visual function loss.

PMID: 28137902 [PubMed - indexed for MEDLINE]

TB or not to be? Kikuchi-Fujimoto disease: a rare but important differential for TB.

BMJ Case Rep. 2017 Jan 04;2017:

Authors: McKenna C, Whitfield T, Patel N, Bonington A

Abstract
A 29-year-old British Pakistani woman presented with a 2-month history of drenching fevers, night sweats, lethargy and tender cervical and axillary lymphadenopathy. Initial investigations, bloods and imaging were unremarkable. Fever persisted during her admission, and treatment for tuberculosis (TB) lymphadenitis was started postbiopsy until histology confirmed a diagnosis of Kikuchi-Fujimoto's disease (KFD). KFD has a non-specific presentation of fever, night sweats and lymphadenopathy and commonly raises a clinical suspicion of a number of other serious conditions such as TB, lymphoma, HIV, systemic lupus erythematous, toxoplasmosis and infectious mononucleosis. Although rare, KFD should be considered to be a differential diagnosis for fever of unknown origin and tender lymphadenopathy in otherwise well individuals. This case demonstrates the importance of a timely histological biopsy diagnosis to prevent an incorrect diagnosis and administration of unnecessary medications.

PMID: 28052948 [PubMed - indexed for MEDLINE]

Primitive neuroectodermal tumour of the cervix: a rare diagnosis.

BMJ Case Rep. 2017 Jan 04;2017:

Authors: Ahmad I, Chufal KS, Bhargava A, Bashir I

Abstract
A 48-year-old woman presented with symptoms of lower abdominal pain and vaginal discharge for 6 months. Clinical examination and pelvic ultrasound scan suggested a diagnosis of infected Gartner's cyst, for which she underwent vaginal cystectomy. However, histopathology and immunohistochemistry revealed a diagnosis of primitive neuroectodermal tumour of the cervix. Further investigations revealed the stage to be FIGO IIIB, which was inoperable. She received neoadjuvant chemotherapy (vincristine, adriamycin, cyclophosphamide alternating with ifosfamide, cisplatin and etoposide, every 21 days), but the tumour did not respond to treatment and she was started on radiotherapy with definitive intent (55.8 Gray in 31 fractions over 6.2 weeks). A PET-CT performed 2 months after completion of radiotherapy showed complete response, and she is now receiving adjuvant chemotherapy.

PMID: 28052947 [PubMed - indexed for MEDLINE]

Drug repositioning in sarcomas and other rare tumors.

EBioMedicine. 2016 Apr;6:4-5

Authors: Lee AT, Huang PH, Pollack SM, Jones RL

PMID: 27211532 [PubMed - indexed for MEDLINE]

BIOMedical Search Engine Framework: Lightweight and customized implementation of domain-specific biomedical search engines.

Comput Methods Programs Biomed. 2016 Jul;131:63-77

Authors: Jácome AG, Fdez-Riverola F, Lourenço A

Abstract
BACKGROUND AND OBJECTIVES: Text mining and semantic analysis approaches can be applied to the construction of biomedical domain-specific search engines and provide an attractive alternative to create personalized and enhanced search experiences. Therefore, this work introduces the new open-source BIOMedical Search Engine Framework for the fast and lightweight development of domain-specific search engines. The rationale behind this framework is to incorporate core features typically available in search engine frameworks with flexible and extensible technologies to retrieve biomedical documents, annotate meaningful domain concepts, and develop highly customized Web search interfaces.
METHODS: The BIOMedical Search Engine Framework integrates taggers for major biomedical concepts, such as diseases, drugs, genes, proteins, compounds and organisms, and enables the use of domain-specific controlled vocabulary. Technologies from the Typesafe Reactive Platform, the AngularJS JavaScript framework and the Bootstrap HTML/CSS framework support the customization of the domain-oriented search application. Moreover, the RESTful API of the BIOMedical Search Engine Framework allows the integration of the search engine into existing systems or a complete web interface personalization.
RESULTS: The construction of the Smart Drug Search is described as proof-of-concept of the BIOMedical Search Engine Framework. This public search engine catalogs scientific literature about antimicrobial resistance, microbial virulence and topics alike. The keyword-based queries of the users are transformed into concepts and search results are presented and ranked accordingly. The semantic graph view portraits all the concepts found in the results, and the researcher may look into the relevance of different concepts, the strength of direct relations, and non-trivial, indirect relations. The number of occurrences of the concept shows its importance to the query, and the frequency of concept co-occurrence is indicative of biological relations meaningful to that particular scope of research. Conversely, indirect concept associations, i.e. concepts related by other intermediary concepts, can be useful to integrate information from different studies and look into non-trivial relations.
CONCLUSIONS: The BIOMedical Search Engine Framework supports the development of domain-specific search engines. The key strengths of the framework are modularity and extensibilityin terms of software design, the use of open-source consolidated Web technologies, and the ability to integrate any number of biomedical text mining tools and information resources. Currently, the Smart Drug Search keeps over 1,186,000 documents, containing more than 11,854,000 annotations for 77,200 different concepts. The Smart Drug Search is publicly accessible at http://sing.ei.uvigo.es/sds/. The BIOMedical Search Engine Framework is freely available for non-commercial use at https://github.com/agjacome/biomsef.

PMID: 27265049 [PubMed - indexed for MEDLINE]

Intrahepatic Sampling for the Elucidation of Antiviral Clinical Pharmacology.

Clin Pharmacol Drug Dev. 2017 Mar;6(2):169-175

Authors: Venuto CS, Talal AH

Abstract
Although the importance of the liver in clinical pharmacology is widely recognized, little is known in humans concerning its function in vivo at the hepatocyte level and how pharmacological functions are altered in the setting of advanced liver disease. Several recent proof-of-principle studies with first-generation DAAs have demonstrated the feasibility of serial liver sampling for pharmacological studies. These studies have begun to describe the liver-to-plasma concentration ratio and how this ratio is altered in the setting of advanced liver disease. These data are particularly relevant to individuals with substance-use disorders because many have advanced liver disease as a consequence of long-standing viral hepatitis infection or continued use of hepatotoxins such as alcohol. Future research should attempt to develop standardized and reproducible methods to assess liver drug concentration, complex drug interactions, and pharmacogenomics in humans to permit elucidation of the clinical pharmacology within the liver.

PMID: 28263459 [PubMed - in process]

How gene polymorphisms can influence clinical response and toxicity following R-CHOP therapy in patients with diffuse large B cell lymphoma.

Blood Rev. 2017 Feb 27;:

Authors: Falduto A, Cimino F, Speciale A, Musolino C, Gangemi S, Saija A, Allegra A

Abstract
The treatment of diffuse large B cell lymphoma (DLBCL) is generally based on multidrug chemotherapy, for instance the therapy with rituximab together with cyclophosphamide, vincristine, doxorubicin, and prednisone (R-CHOP). A significant proportion of DLBCL patients benefit from rituximab-based chemoimmunotherapy. However, among patients with DLBCL toxic effects due to therapy treatment are still very frequent, as well as inter-individual differences in the outcomes of patients even having similar stage, histological grade and histopathological type of the tumor. The present paper reviews the actual status of pharmacogenomics studies concerning gene polymorphisms that may affect response and tolerability to R-CHOP therapeutic regimen used to treat DLBCL. There are clear evidences that polymorphisms of genes codifying for protein are involved in cytotoxicity induced by R-CHOP regimen. Moreover, polymorphisms in genes encoding TNF-superfamily cytokines and proteins involved in controlling cellular cycle and tumor growth may be related to variability in efficacy of R-CHOP therapy in DLBCL patients. This knowledge emphasizes the clinical meaning and importance of pharmacogenetics in oncology. The main merit of our study seems to have tried for the first time a comprehensive review of gene polymorphisms that are involved in the response to an entire therapeutic protocol, R-CHOP, in a specific disease, DLBCL, rather than examining polymorphisms referred to individual drugs among themselves not connected or used to treat different pathological conditions. Indeed, it seems clear that only the analysis of a constellation of polymorphisms can really be useful in clinical practice, while knowledge of a single polymorphism seems to give a limited contribution to our ability to use genetic analysis to the management of patients with malignant blood disorders.

PMID: 28262268 [PubMed - as supplied by publisher]

Cellular models to study schizophrenia: A systematic review.

Asian J Psychiatr. 2017 Feb;25:46-53

Authors: Seshadri M, Banerjee D, Viswanath B, Ramakrishnan K, Purushottam M, Venkatasubramanian G, Jain S

Abstract
BACKGROUND: Advancements in cellular reprogramming techniques have made it possible to directly study brain cells from patients with neuropsychiatric disorders. We have systematically reviewed the applications of induced pluripotent stem cells (IPSCs) and their neural derivatives in understanding the biological basis of schizophrenia.
METHOD: We searched the scientific literature published in MEDLINE with the following search strategy: (Pluripotent) AND (Schizophrenia OR Antipsychotic OR Psychosis). Studies written in English that used IPSCs derived from patients with schizophrenia were included.
RESULTS: Out of 23 articles, which had used IPSCs from patients with schizophrenia, neurons or neural stem cells had been derived from them in a majority. Several parameters had been studied; the key cellular phenotypes identified included those of synaptic pathology, neural migration/proliferation deficits, and abnormal oxidative phosphorylation.
CONCLUSION: Cellular modelling using IPSCs could improve the biological understanding of schizophrenia. Emerging findings are consistent with those of other study designs (post-mortem brain expression, animal studies, genome-wide association, brain imaging). Future studies should focus on refined study designs (family-based, pharmacogenomics, gene editing) and a combination of cellular studies with deep clinical phenotyping.

PMID: 28262173 [PubMed - in process]

[The pharmacogenomics of CFH Y402H and wet age-related macular degeneration].

Zhonghua Yan Ke Za Zhi. 2017 Feb 11;53(2):144-147

Authors: Chen LL, Chen YY

Abstract
Age-related macular degeneration(AMD) is one of the main leading causes of irreversible vision damage in patients over 50 years old. Genetic factors play an important role in the occurrence and development of AMD. Since the significant correlation between complement factor H (CFH) gene and AMD was found, the pharmacogenomics of CFH polymorphism was paid close attention by academic circles. Among which, studies concerning CFH Y402H were more deeply. Studies have found CFH Y402H genotypes might lead to differences toward the outcome of PDT and anti-VEGF treatment. In this article, we review the researches on the pharmacogenomics of CFH Y402H in wet AMD treatment. (Chin J Ophthalmol, 2017, 53: 144-147).

PMID: 28260367 [PubMed - in process]

Managing uncertainty in metabolic network structure and improving predictions using EnsembleFBA.

PLoS Comput Biol. 2017 Mar 06;13(3):e1005413

Authors: Biggs MB, Papin JA

Abstract
Genome-scale metabolic network reconstructions (GENREs) are repositories of knowledge about the metabolic processes that occur in an organism. GENREs have been used to discover and interpret metabolic functions, and to engineer novel network structures. A major barrier preventing more widespread use of GENREs, particularly to study non-model organisms, is the extensive time required to produce a high-quality GENRE. Many automated approaches have been developed which reduce this time requirement, but automatically-reconstructed draft GENREs still require curation before useful predictions can be made. We present a novel approach to the analysis of GENREs which improves the predictive capabilities of draft GENREs by representing many alternative network structures, all equally consistent with available data, and generating predictions from this ensemble. This ensemble approach is compatible with many reconstruction methods. We refer to this new approach as Ensemble Flux Balance Analysis (EnsembleFBA). We validate EnsembleFBA by predicting growth and gene essentiality in the model organism Pseudomonas aeruginosa UCBPP-PA14. We demonstrate how EnsembleFBA can be included in a systems biology workflow by predicting essential genes in six Streptococcus species and mapping the essential genes to small molecule ligands from DrugBank. We found that some metabolic subsystems contributed disproportionately to the set of predicted essential reactions in a way that was unique to each Streptococcus species, leading to species-specific outcomes from small molecule interactions. Through our analyses of P. aeruginosa and six Streptococci, we show that ensembles increase the quality of predictions without drastically increasing reconstruction time, thus making GENRE approaches more practical for applications which require predictions for many non-model organisms. All of our functions and accompanying example code are available in an open online repository.

PMID: 28263984 [PubMed - as supplied by publisher]

Remnants of an Ancient Metabolism without Phosphate.

Cell. 2017 Mar 02;:

Authors: Goldford JE, Hartman H, Smith TF, Segrè D

Abstract
Phosphate is essential for all living systems, serving as a building block of genetic and metabolic machinery. However, it is unclear how phosphate could have assumed these central roles on primordial Earth, given its poor geochemical accessibility. We used systems biology approaches to explore the alternative hypothesis that a protometabolism could have emerged prior to the incorporation of phosphate. Surprisingly, we identified a cryptic phosphate-independent core metabolism producible from simple prebiotic compounds. This network is predicted to support the biosynthesis of a broad category of key biomolecules. Its enrichment for enzymes utilizing iron-sulfur clusters, and the fact that thermodynamic bottlenecks are more readily overcome by thioester rather than phosphate couplings, suggest that this network may constitute a "metabolic fossil" of an early phosphate-free nonenzymatic biochemistry. Our results corroborate and expand previous proposals that a putative thioester-based metabolism could have predated the incorporation of phosphate and an RNA-based genetic system. PAPERCLIP.

PMID: 28262353 [PubMed - as supplied by publisher]

BIOMedical Search Engine Framework: Lightweight and customized implementation of domain-specific biomedical search engines.

Comput Methods Programs Biomed. 2016 Jul;131:63-77

Authors: Jácome AG, Fdez-Riverola F, Lourenço A

Abstract
BACKGROUND AND OBJECTIVES: Text mining and semantic analysis approaches can be applied to the construction of biomedical domain-specific search engines and provide an attractive alternative to create personalized and enhanced search experiences. Therefore, this work introduces the new open-source BIOMedical Search Engine Framework for the fast and lightweight development of domain-specific search engines. The rationale behind this framework is to incorporate core features typically available in search engine frameworks with flexible and extensible technologies to retrieve biomedical documents, annotate meaningful domain concepts, and develop highly customized Web search interfaces.
METHODS: The BIOMedical Search Engine Framework integrates taggers for major biomedical concepts, such as diseases, drugs, genes, proteins, compounds and organisms, and enables the use of domain-specific controlled vocabulary. Technologies from the Typesafe Reactive Platform, the AngularJS JavaScript framework and the Bootstrap HTML/CSS framework support the customization of the domain-oriented search application. Moreover, the RESTful API of the BIOMedical Search Engine Framework allows the integration of the search engine into existing systems or a complete web interface personalization.
RESULTS: The construction of the Smart Drug Search is described as proof-of-concept of the BIOMedical Search Engine Framework. This public search engine catalogs scientific literature about antimicrobial resistance, microbial virulence and topics alike. The keyword-based queries of the users are transformed into concepts and search results are presented and ranked accordingly. The semantic graph view portraits all the concepts found in the results, and the researcher may look into the relevance of different concepts, the strength of direct relations, and non-trivial, indirect relations. The number of occurrences of the concept shows its importance to the query, and the frequency of concept co-occurrence is indicative of biological relations meaningful to that particular scope of research. Conversely, indirect concept associations, i.e. concepts related by other intermediary concepts, can be useful to integrate information from different studies and look into non-trivial relations.
CONCLUSIONS: The BIOMedical Search Engine Framework supports the development of domain-specific search engines. The key strengths of the framework are modularity and extensibilityin terms of software design, the use of open-source consolidated Web technologies, and the ability to integrate any number of biomedical text mining tools and information resources. Currently, the Smart Drug Search keeps over 1,186,000 documents, containing more than 11,854,000 annotations for 77,200 different concepts. The Smart Drug Search is publicly accessible at http://sing.ei.uvigo.es/sds/. The BIOMedical Search Engine Framework is freely available for non-commercial use at https://github.com/agjacome/biomsef.

PMID: 27265049 [PubMed - indexed for MEDLINE]

Directed Regulation of Multienzyme Complexes of 2-Oxo Acid Dehydrogenases Using Phosphonate and Phosphinate Analogs of 2-Oxo Acids.

Biochemistry (Mosc). 2016 Dec;81(12):1498-1521

Authors: Artiukhov AV, Graf AV, Bunik VI

Abstract
2-Oxo acid dehydrogenase complexes are important metabolic checkpoints functioning at the intercept of sugar and amino acid degradation. This review presents a short summary of architectural, catalytic, and regulatory principles of the complexes structure and function, based on recent advances in studies of well-characterized family members. Special attention is given to use of synthetic phosphonate and phosphinate analogs of 2-oxo acids as selective and efficient inhibitors of the cognate complexes in biological systems of bacterial, plant, and animal origin. We summarize our own results concerning the application of synthetic analogs of 2-oxo acids in situ and in vivo to reveal functional interactions between 2-oxo acid dehydrogenase complexes and other components of metabolic networks specific to different cells and tissues. Based on our study of glutamate excitotoxicity in cultured neurons, we show how a modulation of metabolism by specific inhibition of its key reaction may be employed to correct pathologies. This approach is further developed in our study on the action of the phosphonate analog of 2-oxoglutarate in animals. The study revealed that upregulation of 2-oxoglutarate dehydrogenase complex is involved in animal stress response and may provide increased resistance to damaging effects, underlying so-called preconditioning. The presented analysis of published data suggests synthetic inhibitors of metabolic checkpoints as promising tools to solve modern challenges of systems biology, metabolic engineering, and medicine.

PMID: 28259128 [PubMed - in process]