Successful Recanalization of a Complete Lobar Bronchial Stenosis in a Lung Transplant Patient Using a Combined Percutaneous and Bronchoscopic Approach.

Cardiovasc Intervent Radiol. 2016 Mar;39(3):462-6

Authors: Miraglia R, Vitulo P, Maruzzelli L, Burgio G, Caruso S, Bertani A, Callari A, Luca A

Abstract
Airway stenosis is a major complication after lung transplantation that is usually managed with a combination of interventional endoscopic techniques, including endobronchial debridement, balloon dilation, and stent lacement. Herein, we report a successful case of recanalization of a complete stenosis of the right middle lobe bronchus in a lung transplant patient, by using a combined percutaneous–bronchoscopic approach after the failure of endobronchial debridement.

PMID: 26474580 [PubMed - indexed for MEDLINE]

A Circulating microRNA Signature Predicts Age-Based Development of Lymphoma.

PLoS One. 2017;12(1):e0170521

Authors: Beheshti A, Vanderburg C, McDonald JT, Ramkumar C, Kadungure T, Zhang H, Gartenhaus RB, Evens AM

Abstract
Extensive epidemiological data have demonstrated an exponential rise in the incidence of non-Hodgkin lymphoma (NHL) that is associated with increasing age. The molecular etiology of this remains largely unknown, which impacts the effectiveness of treatment for patients. We proposed that age-dependent circulating microRNA (miRNA) signatures in the host influence diffuse large B cell lymphoma (DLBCL) development. Our objective was to examine tumor development in an age-based DLBCL system using an inventive systems biology approach. We harnessed a novel murine model of spontaneous DLBCL initiation (Smurf2-deficient) at two age groups: 3 and 15 months old. All Smurf2-deficient mice develop visible DLBCL tumor starting at 15 months of age. Total miRNA was isolated from serum, bone marrow and spleen and were collected for all age groups for Smurf2-deficient mice and age-matched wild-type C57BL/6 mice. Using systems biology techniques, we identified a list of 10 circulating miRNAs being regulated in both the spleen and bone marrow that were present in DLBCL forming mice starting at 3 months of age that were not present in the control mice. Furthermore, this miRNA signature was found to occur circulating in the blood and it strongly impacted JUN and MYC oncogenic signaling. In addition, quantification of the miRNA signature was performed via Droplet Digital PCR technology. It was discovered that a key miRNA signature circulates throughout a host prior to the formation of a tumor starting at 3 months old, which becomes further modulated by age and yielded calculation of a 'carcinogenic risk score'. This novel age-based circulating miRNA signature may potentially be leveraged as a DLBCL risk profile at a young age to predict future lymphoma development or disease progression as well as for potential innovative miRNA-based targeted therapeutic strategies in lymphoma.

PMID: 28107482 [PubMed - in process]

Parenclitic Network Analysis of Methylation Data for Cancer Identification.

PLoS One. 2017;12(1):e0169661

Authors: Karsakov A, Bartlett T, Ryblov A, Meyerov I, Ivanchenko M, Zaikin A

Abstract
We make use of ideas from the theory of complex networks to implement a machine learning classification of human DNA methylation data, that carry signatures of cancer development. The data were obtained from patients with various kinds of cancers and represented as parenclictic networks, wherein nodes correspond to genes, and edges are weighted according to pairwise variation from control group subjects. We demonstrate that for the 10 types of cancer under study, it is possible to obtain a high performance of binary classification between cancer-positive and negative samples based on network measures. Remarkably, an accuracy as high as 93-99% is achieved with only 12 network topology indices, in a dramatic reduction of complexity from the original 15295 gene methylation levels. Moreover, it was found that the parenclictic networks are scale-free in cancer-negative subjects, and deviate from the power-law node degree distribution in cancer. The node centrality ranking and arising modular structure could provide insights into the systems biology of cancer.

PMID: 28107365 [PubMed - in process]

Selected proceedings of Machine Learning in Systems Biology: MLSB 2016.

BMC Bioinformatics. 2016 Dec 13;17(Suppl 16):437

Authors: van Dijk AD, Lähdesmäki H, de Ridder D, Rousu J

PMID: 28105910 [PubMed - in process]

Leveraging Electronic Health Care Record Information to Measure Pressure Ulcer Risk in Veterans With Spinal Cord Injury: A Longitudinal Study Protocol.

JMIR Res Protoc. 2017 Jan 19;6(1):e3

Authors: Luther SL, Thomason SS, Sabharwal S, Finch DK, McCart J, Toyinbo P, Bouayad L, Matheny ME, Gobbel GT, Powell-Cope G

Abstract
BACKGROUND: Pressure ulcers (PrUs) are a frequent, serious, and costly complication for veterans with spinal cord injury (SCI). The health care team should periodically identify PrU risk, although there is no tool in the literature that has been found to be reliable, valid, and sensitive enough to assess risk in this vulnerable population.
OBJECTIVE: The immediate goal is to develop a risk assessment model that validly estimates the probability of developing a PrU. The long-term goal is to assist veterans with SCI and their providers in preventing PrUs through an automated system of risk assessment integrated into the veteran's electronic health record (EHR).
METHODS: This 5-year longitudinal, retrospective, cohort study targets 12,344 veterans with SCI who were cared for in the Veterans Health Administration (VHA) in fiscal year (FY) 2009 and had no record of a PrU in the prior 12 months. Potential risk factors identified in the literature were reviewed by an expert panel that prioritized factors and determined if these were found in structured data or unstructured form in narrative clinical notes for FY 2009-2013. These data are from the VHA enterprise Corporate Data Warehouse that is derived from the EHR structured (ie, coded in database/table) or narrative (ie, text in clinical notes) data for FY 2009-2013.
RESULTS: This study is ongoing and final results are expected in 2017. Thus far, the expert panel reviewed the initial list of risk factors extracted from the literature; the panel recommended additions and omissions and provided insights about the format in which the documentation of the risk factors might exist in the EHR. This list was then iteratively refined through review and discussed with individual experts in the field. The cohort for the study was then identified, and all structured, unstructured, and semistructured data were extracted. Annotation schemas were developed, samples of documents were extracted, and annotations are ongoing. Operational definitions of structured data elements have been created and steps to create an analytic dataset are underway.
CONCLUSIONS: To our knowledge, this is the largest cohort employed to identify PrU risk factors in the United States. It also represents the first time natural language processing and statistical text mining will be used to expand the number of variables available for analysis. A major strength of this quantitative study is that all VHA SCI centers were included in the analysis, reducing potential for selection bias and providing increased power for complex statistical analyses. This longitudinal study will eventually result in a risk prediction tool to assess PrU risk that is reliable and valid, and that is sensitive to this vulnerable population.

PMID: 28104580 [PubMed - in process]

9 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 2017/01/20

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.

Continuous Suprascapular Nerve Block With a Perineural Catheter for Reverse Shoulder Arthroplasty Rescue Analgesia in a Patient With Severe Chronic Obstructive Pulmonary Disease.

A A Case Rep. 2016 Jul 15;7(2):37-40

Authors: Careskey M, Naidu R

Abstract
Reverse open shoulder arthroplasty requires a comprehensive analgesic plan involving regional anesthesia. The commonly performed interscalene brachial plexus blockade confers a high likelihood of diaphragmatic paralysis via phrenic nerve palsy, making this option riskier in patients with limited pulmonary reserve. Continuous blockade of the suprascapular nerve, a more distal branch of the C5 and C6 nerve roots, may be a viable alternative. We report a successful case of the use of a suprascapular nerve block with continuous programmed intermittent bolus perineural analgesia in a patient with severe chronic obstructive pulmonary disease who underwent reverse open shoulder arthroplasty.

PMID: 27258178 [PubMed - indexed for MEDLINE]

Extensions of indication throughout the drug product lifecycle: a quantitative analysis.

Drug Discov Today. 2016 Feb;21(2):348-55

Authors: Langedijk J, Whitehead CJ, Slijkerman DS, Leufkens HG, Schutjens MH, Mantel-Teeuwisse AK

Abstract
The marketing authorisation of the first generic product version is an important moment in a drug product lifecycle. The subsequently changed intellectual property protection prospects could affect the incentives for further drug development. We assessed the quantity and nature of extensions of indication of small molecule medicinal products authorised through the European Medicines Agency throughout the drug product lifecycle with special attention for the impact of the introduction of a first generic competitor. The majority (92.5%) of the extensions of indication was approved during the exclusivity period of the innovator product. Regulatory rethinking might be needed for a sustainable stimulation of extensions of indications in the post-generic period of a drug product lifecycle.

PMID: 26657087 [PubMed - indexed for MEDLINE]

Rare Cause of Acute Dysphagia Associated with Dysphonia.

Dysphagia. 2016 Feb;31(1):111-3

Authors: Demirhan E, Cukurova I, Tutuncu D, Gumussoy M

PMID: 26497805 [PubMed - indexed for MEDLINE]

McCune-Albright Syndrome: An Overview of Clinical Features.

J Pediatr Nurs. 2015 Sep-Oct;30(5):815-7

Authors: Brillante B, Guthrie L, Van Ryzin C

PMID: 26209174 [PubMed - indexed for MEDLINE]

Tissue is the issue and tissue competition. Re-biopsy for mutation T790: where and why?

Clin Transl Med. 2017 Dec;6(1):6

Authors: Zarogoulidis P, Gaga M, Huang H, Darwiche K, Rapti A, Hohenforst-Schmidt W

Abstract
Lung cancer is still the leading cause of death among all cancers. During the last 15 years, pharmacogenomics of lung cancer have established targeted therapy with tyrosine kinase inhibitors (TKIs) for epidermal growth factor receptor (EGFR) positive patients in adenocarcinoma or mixed adenosquamus lung cancer patients. However; while novel drugs are released in the market, at the same time novel mutations are observed after tyrosine kinase inhibitor administration. Recently the novel mutation T790 was observed and is highly prevalent in patients already treated with a TKI. A new drug targeting this mutation is already on the market, however; the most important factor for successful treatment in these patients, is adequate tissue re-sampling so that novel mutations can be detected.

PMID: 28101783 [PubMed - in process]

Exploring the Missing Links between Dietary Habits and Diseases.

IEEE Trans Nanobioscience. 2017 Jan 16;:

Authors: Bhattacharyya M, Maity S, Bandyopadhyay S

Abstract
Disease dietomics is an emerging area of systems biology that attempts to explore the connections between the dietary habits and diseases. Some of the topical studies highlight that foods might have different impacts over an organism either in progressing a disease (negative association) or in fighting against it (positive association). The association of foods with different diseases can be put together to build a network that might provide a global view of the entire system. Again, such disease-food networks might emerge in a more complex form while considering the disease subtypes individually. Some foods might have positive association with a particular subtype of a disease, whereas it might have no association or negative association with another subtype of the same disease. Therefore, the subtypes might have completely different network patterns. On the other hand, the same food may be helpful for a disease and harmful for another disease or even for a subtype. Analyzing such disease-food networks in different forms might give us important information about the relations between different diseases. In this study, we have analyzed a large-scale disease-food network comprising 162 different diseases and 455 types of foods for gaining knowledge about the connection between these diseases and their subtypes. We have measured the similarity between diseases based on their patterns of association with foods. In addition to observing a high similarity between several disease sub types, particularly for cancer, we have found strong relations between constipation-dysphagia and cancer-cardiovascular disease, which are rarely known. Tendency of occurrence of different diseases can be predicted based on such information.

PMID: 28103559 [PubMed - as supplied by publisher]

GIW and InCoB are advancing bioinformatics in the Asia-Pacific.

BMC Bioinformatics. 2015 Dec 18;16(Suppl 18):I1

Authors: Schönbach C, Horton P, Yiu SM, Tan TW, Ranganathan S

Abstract
GIW/InCoB2015 the joint 26th International Conference on Genome Informatics (GIW) and 14th International Conference on Bioinformatics (InCoB) held in Tokyo, September 9-11, 2015 was attended by over 200 delegates. Fifty-one out of 89 oral presentations were based on research articles accepted for publication in four BMC journal supplements and three other journals. Sixteen articles in this supplement and six articles in the BMC Systems Biology GIW/InCoB2015 Supplement are covered by this introduction. The topics range from genome informatics, protein structure informatics, image analysis to biological networks and biomarker discovery.

PMID: 28102114 [PubMed - in process]

Synthesis of human parainfluenza virus 4 nucleocapsid-like particles in yeast and their use for detection of virus-specific antibodies in human serum.

Appl Microbiol Biotechnol. 2017 Jan 19;:

Authors: Bulavaitė A, Lasickienė R, Tamošiūnas PL, Simanavičius M, Sasnauskas K, Žvirblienė A

Abstract
The aim of this study was to produce human parainfluenza virus type 4 (HPIV4) nucleocapsid (N) protein in yeast Saccharomyces cerevisiae expression system, to explore its structural and antigenic properties and to evaluate its applicability in serology. The use of an optimized gene encoding HPIV4 N protein amino acid (aa) sequence GenBank AGU90031.1 allowed high yield of recombinant N protein forming nucleocapsid-like particles (NLPs) in yeast. A substitution L332D disrupted self-assembly of NLPs, confirming the role of this position in the N proteins of Paramyxovirinae. Three monoclonal antibodies (MAbs) were generated against the NLP-forming HPIV4 N protein. They recognised HPIV4-infected cells, demonstrating the antigenic similarity between the recombinant and virus-derived N proteins. HPIV4 N protein was used as a coating antigen in an indirect IgG ELISA with serum specimens of 154 patients with respiratory tract infection. The same serum specimens were tested with previously generated N protein of a closely related HPIV2, another representative of genus Rubulavirus. Competitive ELISA was developed using related yeast-produced viral antigens to deplete the cross-reactive serum antibodies. In the ELISA either without or with competition using heterologous HPIV (2 or 4) N or mumps virus N proteins, the seroprevalence of HPIV4 N-specific IgG was, respectively, 46.8, 39.6 and 40.3% and the seroprevalence of HPIV2 N-specific IgG-47.4, 39.0 and 37.7%. In conclusion, yeast-produced HPIV4 N protein shares structural and antigenic properties of the native virus nucleocapsids. Yeast-produced HPIV4 and HPIV2 NLPs are prospective tools in serology.

PMID: 28102432 [PubMed - as supplied by publisher]

Developing timely insights into comparative effectiveness research with a text-mining pipeline.

Drug Discov Today. 2016 Mar;21(3):473-80

Authors: Chang M, Chang M, Reed JZ, Milward D, Xu JJ, Cornell WD

Abstract
Comparative effectiveness research (CER) provides evidence for the relative effectiveness and risks of different treatment options and informs decisions made by healthcare providers, payers, and pharmaceutical companies. CER data come from retrospective analyses as well as prospective clinical trials. Here, we describe the development of a text-mining pipeline based on natural language processing (NLP) that extracts key information from three different trial data sources: NIH ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP), and Citeline Trialtrove. The pipeline leverages tailored terminologies to produce an integrated and structured output, capturing any trials in which pharmaceutical products of interest are compared with another therapy. The timely information alerts generated by this system provide the earliest and most complete picture of emerging clinical research.

PMID: 26854423 [PubMed - indexed for MEDLINE]

Single embryo-resolution quantitative analysis of reporters permits multiplex spatial cis-regulatory analysis.

Dev Biol. 2017 Jan 15;:

Authors: Guay CL, McQuade ST, Nam J

Abstract
Cis-regulatory modules (CRMs) control spatiotemporal gene expression patterns in embryos. While measurement of quantitative CRM activities has become efficient, measurement of spatial CRM activities still relies on slow, one-by-one methods. To overcome this bottleneck, we have developed a high-throughput method that can simultaneously measure quantitative and spatial CRM activities. The new method builds profiles of quantitative CRM activities measured at single-embryo resolution in many mosaic embryos and uses these profiles as a 'fingerprint' of spatial patterns. We show in sea urchin embryos that the new method, Multiplex and Mosaic Observation of Spatial Information encoded in Cis-regulatory modules (MMOSAIC), can efficiently predict spatial activities of new CRMs and can detect spatial responses of CRMs to gene perturbations. We anticipate that MMOSAIC will facilitate systems-wide functional analyses of CRMs in embryos.

PMID: 28099870 [PubMed - as supplied by publisher]

Anthelmintic mebendazole enhances cisplatin's effect on suppressing cell proliferation and promotes differentiation of head and neck squamous cell carcinoma (HNSCC).

Oncotarget. 2017 Jan 16;:

Authors: Zhang F, Li Y, Zhang H, Huang E, Gao L, Luo W, Wei Q, Fan J, Song D, Liao J, Zou Y, Liu F, Liu J, Huang J, Guo D, Ma C, Hu X, Li L, Qu X, Chen L, Yu X, Zhang Z, Wu T, Luu HH, Haydon RC, Song J, He TC, Ji P

Abstract
Head and neck squamous cell carcinoma (HNSCC) is one of the most common and aggressive types of human cancers worldwide. Nearly a half of HNSCC patients experience recurrence within five years of treatment and develop resistance to chemotherapy. Thus, there is an urgent clinical need to develop safe and novel anticancer therapies for HNSCC. Here, we investigate the possibility of repurposing the anthelmintic drug mebendazole (MBZ) as an anti-HNSCC agent. Using the two commonly-used human HNSCC lines CAL27 and SCC15, we demonstrate MBZ exerts more potent anti-proliferation activity than cisplatin in human HNSCC cells. MBZ effectively inhibits cell proliferation, cell cycle progression and cell migration, and induces apoptosis of HNSCC cells. Mechanistically, MBZ can modulate the cancer-associated pathways including ELK1/SRF, AP1, STAT1/2, MYC/MAX, although the regulatory outcomes are context-dependent. MBZ also synergizes with cisplatin in suppressing cell proliferation and inducing apoptosis of human HNSCC cells. Furthermore, MBZ is shown to promote the terminal differentiation of CAL27 cells and keratinization of CAL27-derived xenograft tumors. Our results are the first to demonstrate that MBZ may exert its anticancer activity by inhibiting proliferation while promoting differentiation of certain HNSCC cancer cells. It's conceivable the anthelmintic drug MBZ can be repurposed as a safe and effective agent used in combination with other frontline chemotherapy drugs such as cisplatin in HNSCC treatment.

PMID: 28099902 [PubMed - as supplied by publisher]

Lysosomal Proteins as a Therapeutic Target in Neurodegeneration.

Annu Rev Med. 2017 Jan 14;68:445-458

Authors: Mc Donald JM, Krainc D

Abstract
Several proteins that are mutated in lysosomal storage diseases are linked to neurodegenerative disease. This review focuses on some of these lysosomal enzymes and transporters, as well as current therapies that have emerged from the lysosomal storage disease field. Given the deeper genetic understanding of lysosomal defects in neurodegeneration, we explore why some of these orphan disease drug candidates are also attractive targets in subpopulations of individuals with neurodegenerative disease.

PMID: 28099085 [PubMed - in process]

Managed care approach to the treatment of neurogenic orthostatic hypotension.

Am J Manag Care. 2015 Oct;21(13 Suppl):s258-68

Authors: Isaacson SH

Abstract
Neurogenic orthostatic hypotension (NOH) is an orphan disease that primarily affects patients with neurodegenerative disorders such as Parkinson's disease and multiple system atrophy. The first step in the management of NOH is to discontinue or minimize the use of drugs that lower blood pressure. Nonpharmacologic therapy for NOH includes physical countermaneuvers, compression abdominal binders and lower extremity stockings, recognition and avoidance of orthostatic stressors, hydration, and salt supplementation. The management of NOH should also include interventions to prevent falls. Pharmacotherapy for NOH includes the mineralocorticoid drug fludrocortisone to expand plasma volume and the sympathomimetic drugs midodrine and droxidopa. Clinical efficacy, tolerability, and the role of each drug in the treatment paradigm are reviewed here.

PMID: 26790110 [PubMed - indexed for MEDLINE]

Addressing the Crisis in the Treatment of Osteoporosis: A Path Forward.

J Bone Miner Res. 2016 Dec 29;:

Authors: Khosla S, Cauley JA, Compston J, Kiel DP, Rosen C, Saag KG, Shane E

Abstract
Considerable data and media attention have highlighted a potential "crisis" in the treatment of osteoporosis. Specifically, despite the availability of several effective drugs to prevent fractures, many patients who need pharmacological therapy are either not being prescribed these medications or if prescribed a medication, are simply not taking it. Although there are many reasons for this "gap" in the treatment of osteoporosis, a major factor is physician and patient concerns over the risk of side effects, especially atypical femur fractures (AFFs) related to bisphosphonate (and perhaps other antiresorptive) drug therapy. In this perspective, we review the current state of undertreatment of patients at increased fracture risk and suggest possible short-, intermediate-, and long-term approaches to address patient concerns, specifically those related to AFF risk. We suggest improved patient and physician education on prodromal symptoms, extended femur scans using dual-energy X-ray absorptiometry (DXA) to monitor patients on antiresorptive treatment, better identification of high-risk patients perhaps using geometrical parameters from DXA and other risk factors, and more research on pharmacogenomics to identify risk markers. Although not the only impediment to appropriate treatment of osteoporosis, concern over AFFs remains a major issue and one that needs to be resolved for effective dissemination of existing treatments to reduce fracture risk. © 2017 American Society for Bone and Mineral Research.

PMID: 28099754 [PubMed - as supplied by publisher]