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https://www.readbyqxmd.com/read/29342367/cystic-fibrosis-pulmonary-guidelines-use-of-cftr-modulator-therapy-in-patients-with-cystic-fibrosis
#1
Clement L Ren, Rebecca L Morgan, Christopher Oermann, Helaine E Resnick, Cynthia Brady, Annette Campbell, Richard DeNagel, Margaret Guill, Jeffrey Hoag, Andrew Lipton, Thomas Newton, Stacy Peters, Donna Beth Willey-Courand, Edward T Naureckas
BACKGROUND: CFTR modulators are a new class of medications that target the underlying defect in in cystic fibrosis (CF). Ivacaftor (IVA) and IVA combined with lumacaftor (IVA/LUM) have been approved by the FDA for use in CF patients. However, the FDA label for these medications encompasses patient groups that were not studied as part of the drug approval process. CF clinicians, patients, and their families have recognized a need for recommendations to guide the use of these medications...
January 17, 2018: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29341908/induction-of-au-methotrexate-conjugates-by-sugar-molecules-production-assembly-mechanism-and-bioassay-studies
#2
Wei-Yuan Wang, Xiu-Fen Zhao, Xiao-Han Ju, Ping Liu, Jing Li, Ya-Wen Tang, Shu-Ping Li, Xiao-Dong Li, Fu-Gui Song
Au-methotrexate (Au-MTX) conjugates induced by sugar molecules were produced by a simple, one-pot, hydrothermal growth method. Herein, the Au(III)-MTX complexes were used as the precursors to form Au-MTX conjugates. Addition of different types of sugar molecules with abundant hydroxyl groups resulted in the formation of Au-MTX conjugates featuring distinct characteristics that could be explained by the diverse capping mechanisms of sugar molecules. That is, the instant-capping mechanism of glucose favored the generation of peanut-like Au-MTX conjugates with high colloidal stability while the post-capping mechanism of dextran and sucrose resulted in the production of Au-MTX conjugates featuring excellent near-infrared (NIR) optical properties with a long-wavelength plasmon resonance near 630-760 nm...
January 13, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29341341/prediction-of-activation-patterns-preceding-hallucinations-in-patients-with-schizophrenia-using-machine-learning-with-structured-sparsity
#3
Amicie de Pierrefeu, Thomas Fovet, Fouad Hadj-Selem, Tommy Löfstedt, Philippe Ciuciu, Stephanie Lefebvre, Pierre Thomas, Renaud Lopes, Renaud Jardri, Edouard Duchesnay
Despite significant progress in the field, the detection of fMRI signal changes during hallucinatory events remains difficult and time-consuming. This article first proposes a machine-learning algorithm to automatically identify resting-state fMRI periods that precede hallucinations versus periods that do not. When applied to whole-brain fMRI data, state-of-the-art classification methods, such as support vector machines (SVM), yield dense solutions that are difficult to interpret. We proposed to extend the existing sparse classification methods by taking the spatial structure of brain images into account with structured sparsity using the total variation penalty...
January 16, 2018: Human Brain Mapping
https://www.readbyqxmd.com/read/29341222/89-zr-immunopet-companion-diagnostics-and-their-impact-in-clinical-drug-development
#4
REVIEW
Brooke N McKnight, Nerissa T Viola-Villegas
Therapeutic monoclonal antibodies (mAbs) have been used in cancer treatment for 30 years, with around 24 mAb and mAb:drug conjugates approved by the FDA to date. Despite their specificity, efficacy has remained limited, which, in part, derails nascent initiatives towards precision medicine. An image-guided approach to reinforce treatment decisions using immune positron emission tomography (immunoPET) companion diagnostic is warranted. This review provides a general overview of current translational research using Zr-89 immunoPET and opportunities for utilizing and harnessing this tool to its full potential...
January 17, 2018: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29341164/patient-derived-organoid-models-help-define-personalized-management-of-gastrointestinal-cancer
#5
REVIEW
M R Aberle, R A Burkhart, H Tiriac, S W M Olde Damink, C H C Dejong, D A Tuveson, R M van Dam
BACKGROUND: The prognosis of patients with different gastrointestinal cancers varies widely. Despite advances in treatment strategies, such as extensive resections and the addition of new drugs to chemotherapy regimens, conventional treatment strategies have failed to improve survival for many tumours. Although promising, the clinical application of molecularly guided personalized treatment has proven to be challenging. This narrative review focuses on the personalization of cancer therapy using patient-derived three-dimensional 'organoid' models...
January 2018: British Journal of Surgery
https://www.readbyqxmd.com/read/29340835/repurposed-fda-approved-drugs-targeting-genes-influencing-aging-can-extend-lifespan-and-healthspan-in-rotifers
#6
Terry W Snell, Rachel K Johnston, Amelia B Matthews, Hongyi Zhou, Mu Gao, Jeffrey Skolnick
Pharmaceutical interventions can slow aging in animals, and have advantages because their dose can be tightly regulated and the timing of the intervention can be closely controlled. They also may complement environmental interventions like caloric restriction by acting additively. A fertile source for therapies slowing aging is FDA approved drugs whose safety has been investigated. Because drugs bind to several protein targets, they cause multiple effects, many of which have not been characterized. It is possible that some of the side effects of drugs prescribed for one therapy may have benefits in retarding aging...
January 16, 2018: Biogerontology
https://www.readbyqxmd.com/read/29340321/randomized-clinical-trial-design-to-assess-abatacept-in-resistant-nephrotic-syndrome
#7
Howard Trachtman, Debbie S Gipson, Michael Somers, Cathie Spino, Sharon Adler, Lawrence Holzman, Jeffrey B Kopp, John Sedor, Sandra Overfield, Ayanbola Elegbe, Michael Maldonado, Anna Greka
Introduction: Treatment-resistant nephrotic syndrome is a rare form of glomerular disease that occurs in children and adults. No Food and Drug Administration-approved treatments consistently achieve remission of proteinuria and preservation of kidney function. CD80 (B7-1) can be expressed on injured podocytes, and administration of abatacept (modified CTLA4-Ig based on a natural ligand to CD80) has been associated with sustained normalization of urinary protein excretion and maintenance of glomerular filtration rate in experimental and clinical settings...
January 2018: KI Reports
https://www.readbyqxmd.com/read/29340111/effect-of-dihydropyrimidine-dehydrogenase-single-nucleotide-polymorphisms-on-prognosis-of-breast-cancer-patients-with-chemotherapy
#8
Fengxia Qin, Huikun Zhang, Yong Huang, Limin Yang, Feng Yu, Xiaoli Liu, Li Fu, Feng Gu, Yongjie Ma
Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate to guide patient selection for personalized cancer treatments. DPD (dihydropyrimidine dehydrogenase, encoded by DPYD gene) is the initial and rate-limiting enzyme of metabolic pathway of fluoropyrimidines, and fluoropyrimidines are common used drug therapies for breast cancer. Previous studies on DPYD polymorphism were mainly focused on its association with fluoropyrimidines toxicity. In our present study, 5 DPYD single nucleotide polymorphisms status was detected from tumor tissues of 331 invasive breast cancer patients using standard techniques...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339187/doxorubicin-loaded-dendritic-fe3o4-supramolecular-nanoparticles-for-magnetic-drug-targeting-and-tumor-regression-in-spheroid-murine-melanoma-model
#9
Saumya Nigam, D Bahadur
This work evaluates the magnetically-guided delivery of DOX-loaded dendritic-Fe3O4 nanoparticles and their tumor regression efficacy in subcutaneous melanoma in C57BL/6 mice. The hematological, biochemical and histopathological parameters were minimally affected. The nanoparticles localized in lungs, liver and spleen suggesting non-specific uptake. However, in tumor-bearing mice, substantially higher localization in magnetically-targeted tumor was observed when compared to passive localization in non-targeted tumor...
January 12, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29339127/the-basophil-activation-test-can-be-of-value-for-diagnosing-immediate-allergic-reactions-to%C3%A2-omeprazole
#10
Jose J Laguna, Gador Bogas, Maria Salas, Cristobalina Mayorga, Javier Dionicio, Rosario Gonzalez-Mendiola, Adriana Ariza, Ruben Fernández-Santamaría, Isabel Olazabal, Inmaculada Doña, Tahia D Fernandez, Maria J Torres
BACKGROUND: Proton pump inhibitors (PPIs) are commonly used to treat gastrointestinal diseases. Incidence of hypersensitivity reactions to PPIs has risen, likely because of increased consumption. Their diagnosis is difficult, with skin tests (STs) presenting low sensitivity, making it necessary to perform drug provocation tests (DPTs). The value of in vitro tests for the diagnosis of immediate reaction to PPI is unclear. OBJECTIVE: To analyze the diagnostic value of the basophil activation test (BAT) in a group of patients diagnosed with immediate allergy to omeprazole...
January 12, 2018: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/29337961/how-the-evolution-of-multicellularity-set-the-stage-for-cancer
#11
REVIEW
Anna S Trigos, Richard B Pearson, Anthony T Papenfuss, David L Goode
Neoplastic growth and many of the hallmark properties of cancer are driven by the disruption of molecular networks established during the emergence of multicellularity. Regulatory pathways and molecules that evolved to impose regulatory constraints upon networks established in earlier unicellular organisms enabled greater communication and coordination between the diverse cell types required for multicellularity, but also created liabilities in the form of points of vulnerability in the network that when mutated or dysregulated facilitate the development of cancer...
January 16, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29337600/developing-a-theoretical-foundation-to-change-road-user-behavior-and-improve-traffic-safety-driving-under-the-influence-of-cannabis-duic
#12
Nicholas J Ward, William Schell, Tara Kelley-Baker, Jay Otto, Kari Finley
OBJECTIVES: This study explored a theoretical model to assess the influence of culture on willingness and intention to drive under the influence of cannabis (DUIC). This model is expected to guide the design of strategies to change future DUIC behavior in road users. METHODS: This study used a survey methodology to obtain a nationally representative sample (n = 941) from the AmeriSpeak® Panel. Survey items were designed to measure aspects of a proposed definition of traffic safety culture and a predictive model of its relationship to DUIC...
January 16, 2018: Traffic Injury Prevention
https://www.readbyqxmd.com/read/29337578/physiologically-based-pharmacokinetic-modeling-in-lead-optimization-i-evaluation-and-adaptation-of-gastroplus-to-predict-bioavailability-of-medchem-series
#13
Pankaj R Daga, Michael B Bolger, Ian S Haworth, Robert Daniel Clark, Eric J Martin
When medicinal chemists need to improve bioavailability (%F) within a chemical series during lead optimization, they synthesize new series members with systematically modified properties mainly by following experience and general rules of thumb. More quantitative models that predict %F of proposed compounds from chemical structure alone have proven elusive. Global empirical %F quantitative structure-property (QSPR) models perform poorly and projects have too little data to train local %F QSPR models. Mechanistic oral absorption and physiologically-based pharmacokinetic (PBPK) models simulate the dissolution, absorption, systemic distribution, and clearance of a drug in preclinical species and humans...
January 16, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29336937/the-combination-of-stereo-eeg-and-radiofrequency-ablation
#14
Hélène Catenoix, Pierre Bourdillon, Marc Guénot, Jean Isnard
SEEG-guided radiofrequency thermocoagulation (SEEG-guided RFTC), a combination of Stereo-electroencephalography (SEEG) and radiofrequency thermocoagulation (RFTC), has been performed since 2001 in drug resistant epilepsy. The interest of this procedure is to aim at total or partial destruction of the epileptogenic zone, as tailored in each individual patient by the SEEG exploration. These multiple SEEG-guided RFTC lesions of epileptic foci are produced by using a radiofrequency generator connected to the electrode contacts...
January 9, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29336544/identification-of-collateral-sensitivity-to-dihydroorotate-dehydrogenase-inhibitors-in-i-plasmodium-falciparum-i
#15
Leila Saxby Ross, Maria Jose Lafuente-Monasterio, Tomoyo Sakata-Kato, Rebecca E K Mandt, Francisco-Javier Gamo, Dyann F Wirth, Amanda K Lukens
Drug resistance has been reported for every antimalarial in use highlighting the need for new strategies to protect the efficacy of therapeutics in development. We have previously shown that resistance can be suppressed with a population biology trap: by identifying situations where resistance to one compound confers hypersensitivity to another (collateral sensitivity), we can design combination therapies that not only kill the parasite, but also guide its evolution away from resistance. We applied this concept to the Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) enzyme, a well validated antimalarial target with inhibitors in the development pipeline...
January 16, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29336268/%C3%AE-naplastic-lymphoma-kinase-in-glioblastoma-detection-diagnostic-methods-and-therapeutic-options
#16
Theodosis Kalamatianos, Despoina Denekou, George Stranjalis, Evangelia Papadimitriou
BACKGROUND: Glioblastoma (GBM) is the most aggressive and common brain tumor in adults, currently lacking effective life-prolonging and recurrence-preventing therapy; median survival of GBM patients stands at only 14-16 months. Increasing lines of evidence indicate that Anaplastic lymphoma kinase (ALK), a druggable tyrosine kinase receptor over-expressed in GBM, represents a potential therapeutic target in this tumor. OBJECTIVE: An overview of the state of the art and the existing recent patents regarding potential exploitation of ALK as a therapeutic target and/or diagnostic/prognostic factor in GBM...
January 15, 2018: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29336139/smart-self-assembled-nanosystem-based-on-water-soluble-pillararene-and-rare-earth-doped-upconversion-nanoparticles-for-ph-responsive-drug-delivery
#17
Haihong Li, Ruoyan Wei, Guihua Yan, Ji Sun, Chunju Li, Haifang Wang, Liyi Shi, John A Capobianco, Lining Sun
Exploring novel drug delivery systems (DDSs) with good stability and new structure to integrate pillararene and upconversion nanoparticles (UCNPs) into one system continues to be an important challenge. Herein we report the novel preparation of a supramolecular upconversion nanosystem via the host-guest complexation based on carboxylate-based pillar[5]arene (WP5) and 15-carboxy-N,N,N-trialkylpentadecan-1-ammonium bromides (1) functionalized UCNPs to produce WP5⊃1-UCNPs that can be loaded with the chemotherapeutic drug doxorubicin (DOX)...
January 16, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29334287/efficacy-and-safety-of-alpha-blockers-in-medical-expulsive-therapy-for-ureteral-stones-a-mixed-treatment-network-meta-analysis-and-trial-sequential-analysis-of-randomized-controlled-clinical-trials
#18
Kannan Sridharan, Gowri Sivaramakrishnan
Alpha blockers (AB) are the main group of drugs used for medical expulsive therapy (MET) in patients with ureteral stones. However, there is no consensus on the relative efficacy and safety of individual AB in MET. Areas covered: The present work is a network meta-analysis of randomized controlled trials comparing AB with either placebo or standard of care in patients with ureteral stones. Electronic databases of Medline, Cochrane CENTRAL and Google Scholar were searched for eligible clinical studies. Inverse variance heterogeneity model was used for mixed treatment comparisons...
January 15, 2018: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/29334251/discussing-edaravone-with-the-als-patient-an-ethical-framework-from-a-u-s-perspective
#19
Crystal Jing Jing Yeo, Zachary Simmons
The recent approval of edaravone by the United States Food and Drug Administration has generated a mix of hope tempered by reality. The costs of the drug, both monetarily and with regard to intensity of treatment, are high. The benefits, while modest, will be viewed through a very different lens by individuals depending on their goals of care. By virtue of our training and experience, physicians are ideally suited to understand and explain new treatments to our patients. As healthcare providers with a fiduciary responsibility to our patients, we must make sure they are fully informed about both the costs and benefits of non-curative therapies such as edaravone, and be prepared to discuss these in the context of their goals of care and potential impact on quality of life...
January 15, 2018: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/29333748/near-infrared-light-sensitive-polyvinyl-alcohol-hydrogel-photoresist-for-spatiotemporal-control-of-cell-instructive-3d-microenvironments
#20
Xiao-Hua Qin, Xiaopu Wang, Markus Rottmar, Bradley J Nelson, Katharina Maniura-Weber
Advanced hydrogel systems that allow precise control of cells and their 3D microenvironments are needed in tissue engineering, disease modeling, and drug screening. Multiphoton lithography (MPL) allows true 3D microfabrication of complex objects, but its biological application requires a cell-compatible hydrogel resist that is sufficiently photosensitive, cell-degradable, and permissive to support 3D cell growth. Here, an extremely photosensitive cell-responsive hydrogel composed of peptide-crosslinked polyvinyl alcohol (PVA) is designed to expand the biological applications of MPL...
January 15, 2018: Advanced Materials
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