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https://www.readbyqxmd.com/read/28087566/application-of-whole-exome-sequencing-in-the-clinical-diagnosis-and-management-of-inherited-cardiovascular-diseases-in-adults
#1
Sara B Seidelmann, Emily Smith, Lakshman Subrahmanyan, Daniel Dykas, Maen D Abou Ziki, Bani Azari, Fady Hannah-Shmouni, Yuexin Jiang, Joseph G Akar, Mark Marieb, Daniel Jacoby, Allen E Bale, Richard P Lifton, Arya Mani
BACKGROUND: With the advent of high throughput sequencing, the identification of genetic causes of cardiovascular disease (CVD) has become an integral part of medical diagnosis and management and at the forefront of personalized medicine in this field. The use of whole exome sequencing for clinical diagnosis, risk stratification, and management of inherited CVD has not been previously evaluated. METHODS AND RESULTS: We analyzed the results of whole exome sequencing in first 200 adult patients with inherited CVD, who underwent genetic testing at the Yale Program for Cardiovascular Genetics...
February 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28079714/radiomic-phenotyping-in-brain-cancer-to-unravel-hidden-information-in-medical-images
#2
Srishti Abrol, Aikaterini Kotrotsou, Ahmed Salem, Pascal O Zinn, Rivka R Colen
Radiomics is a new area of research in the field of imaging with tremendous potential to unravel the hidden information in digital images. The scope of radiology has grown exponentially over the last two decades; since the advent of radiomics, many quantitative imaging features can now be extracted from medical images through high-throughput computing, and these can be converted into mineable data that can help in linking imaging phenotypes with clinical data, genomics, proteomics, and other "omics" information...
January 11, 2017: Topics in Magnetic Resonance Imaging: TMRI
https://www.readbyqxmd.com/read/28076445/emerging-bordetella-pertussis-strains-induce-enhanced-signaling-of-human-pattern-recognition-receptors-tlr2-nod2-and-secretion-of-il-10-by-dendritic-cells
#3
Elise S Hovingh, Marjolein van Gent, Hendrik-Jan Hamstra, Marc Demkes, Frits R Mooi, Elena Pinelli
Vaccines against pertussis have been available for more than 60 years. Nonetheless, this highly contagious disease is reemerging even in countries with high vaccination coverage. Genetic changes of Bordetella pertussis over time have been suggested to contribute to the resurgence of pertussis, as these changes may favor escape from vaccine-induced immunity. Nonetheless, studies on the effects of these bacterial changes on the immune response are limited. Here, we characterize innate immune recognition and activation by a collection of genetically diverse B...
2017: PloS One
https://www.readbyqxmd.com/read/28075457/high-resolution-melting-analysis-for-rapid-and-sensitive-notch1-screening-in-chronic-lymphocytic-leukemia
#4
Jing-Jing Xu, Fei-Rong Yao, Min Jiang, You-Tao Zhang, Feng Guo
Chronic lymphocytic leukemia (CLL) is a biological and clinical heterogeneous disease. Activating mutations of NOTCH1 have been implicated to be associated with adverse prognosis in CLL. The objective of the present study was to develop an effective high-resolution melting (HRM) assay for detecting NOTCH1 mutations. Genomic DNA (gDNA) extracted from 133 CLL patients was screened by HRM assay, and the results were compared with the data obtained using direct sequencing. The relative sensitivity of the HRM assay and direct sequencing was evaluated using diluted gDNA with different NOTCH1 mutational frequencies...
January 5, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28069180/investigation-of-the-microbiota-of-the-reproductive-tract-in-women-undergoing-a-total-hysterectomy-and-bilateral-salpingo-oopherectomy
#5
Shana M Miles, Britney L Hardy, D Scott Merrell
OBJECTIVE: To conduct a pilot study to investigate the possible presence of bacteria throughout the female reproductive tract and to make a preliminary assessment of whether there are differences in the composition of the microbial communities between these body sites and/or between patients. DESIGN: Prospective pilot study followed by 16S amplification and high-throughput sequencing. SETTING: Tertiary care military hospital. PATIENT(S): A total of 10 women underwent a total hysterectomy with bilateral salpingo-oopherectomy; tissue samples were collected from the vagina, resected cervix, uterus, fallopian tubes, and ovaries...
January 6, 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28068941/looking-beyond-the-brain-to-improve-the-pathogenic-understanding-of-parkinson-s-disease-implications-of-whole-transcriptome-profiling-of-patients-skin
#6
Anu Planken, Lille Kurvits, Ene Reimann, Liis Kadastik-Eerme, Külli Kingo, Sulev Kõks, Pille Taba
BACKGROUND: Parkinson's Disease is a progressive neurodegenerative disease, characterized by symptoms of motor impairment, resulting from the loss of dopaminergic neurons in the midbrain, however non-neuronal symptoms are also common. Although great advances have been made in the pathogenic understanding of Parkinson's Disease in the nervous system, little is known about the molecular alterations occurring in other non-neuronal organ systems. In addition, a higher rate of melanoma and non-melanoma skin cancer has been observed in the Parkinson's Disease population, indicating crosstalk between these diseases...
January 10, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28065690/medium-throughput-biochemical-compound-screening-identifies-novel-agents-for-pharmacotherapy-of-neurofibromatosis-type-i
#7
Galina Semenova, Dina Stepanova, Sergey M Deyev, Jonathan Chernoff
The variable manifestation of phenotypes that occur in patients with neurofibromatosis type 1 (NF1) includes benign and malignant neurocutaneous tumors for which no adequate treatment exists. Cell-based screening of known bioactive compounds library identified the protein phosphatase 2A (PP2A) inhibitor Cantharidin and the L-type calcium channel blocker Nifedipine as potential candidates for NF1 pharmacotherapy. Validation of screening results using human NF1-associated malignant peripheral nerve sheath tumor (MPNST) cells showed that Cantharidin effectively impeded MPNST cell growth, while Nifedipine treatment significantly decreased local tumor growth in an MPNST xenograft animal model...
January 5, 2017: Biochimie
https://www.readbyqxmd.com/read/28064117/differential-proteomic-and-oxidative-profiles-unveil-dysfunctional-protein-import-to-adipocyte-mitochondria-in-obesity-associated-aging-and-diabetes
#8
María Gómez-Serrano, Emilio Camafeita, Juan A López, Miguel A Rubio, Irene Bretón, Inés García-Consuegra, Eva García-Santos, Jesús Lago, Andrés Sánchez-Pernaute, Antonio Torres, Jesús Vázquez, Belén Peral
Human age-related diseases, including obesity and type 2 diabetes (T2DM), have long been associated to mitochondrial dysfunction; however, the role for adipose tissue mitochondria in these conditions remains unknown. We have tackled the impact of aging and T2DM on adipocyte mitochondria from obese patients by quantitating not only the corresponding abundance changes of proteins, but also the redox alterations undergone by Cys residues thereof. For that, we have resorted to a high-throughput proteomic approach based on isobaric labeling, liquid chromatography and mass spectrometry...
December 18, 2016: Redox Biology
https://www.readbyqxmd.com/read/28059958/future-technologies-for-monitoring-hiv-drug-resistance-and-cure
#9
Urvi M Parikh, Kevin McCormick, Gert van Zyl, John W Mellors
PURPOSE OF REVIEW: Sensitive, scalable and affordable assays are critically needed for monitoring the success of interventions for preventing, treating and attempting to cure HIV infection. This review evaluates current and emerging technologies that are applicable for both surveillance of HIV drug resistance (HIVDR) and characterization of HIV reservoirs that persist despite antiretroviral therapy and are obstacles to curing HIV infection. RECENT FINDINGS: Next-generation sequencing (NGS) has the potential to be adapted into high-throughput, cost-efficient approaches for HIVDR surveillance and monitoring during continued scale-up of antiretroviral therapy and rollout of preexposure prophylaxis...
January 5, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28057018/bioinformatic-analysis-of-microrna-and-mrna-regulation-in-peripheral-blood-mononuclear-cells-of-patients-with-chronic-obstructive-pulmonary-disease
#10
Xiaomin Dang, Xiaoyan Qu, Weijia Wang, Chongbing Liao, Ying Li, Xiaojin Zhang, Dan Xu, Carolyn J Baglole, Dong Shang, Ying Chang
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive, irreversible chronic inflammatory disorder typified by increased recruitment of monocytes, lymphocytes and neutrophils. Because of this, as well as the convenience of peripheral blood nuclear cells (PBMCs) assessments, miRNA profiling of PBMCs has drawn increasing attention in recent years for various disease. Therefore, we analyzed miRNA and mRNA profiles to understand their regulatory network between COPD subjects versus smokers without airflow limitation...
January 5, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28056055/hdac-and-proteasome-inhibitors-synergize-to-activate-pro-apoptotic-factors-in-synovial-sarcoma
#11
Aimée N Laporte, Jared J Barrott, Ren Jie Yao, Neal M Poulin, Bertha A Brodin, Kevin B Jones, T Michael Underhill, Torsten O Nielsen
Conventional cytotoxic therapies for synovial sarcoma provide limited benefit, and no drugs specifically targeting its driving SS18-SSX fusion oncoprotein are currently available. Patients remain at high risk for early and late metastasis. A high-throughput drug screen consisting of over 900 tool compounds and epigenetic modifiers, representing over 100 drug classes, was undertaken in a panel of synovial sarcoma cell lines to uncover novel sensitizing agents and targetable pathways. Top scoring drug categories were found to be HDAC inhibitors and proteasomal targeting agents...
2017: PloS One
https://www.readbyqxmd.com/read/28055301/autophagy-orchestrates-adaptive-responses-to-targeted-therapy-in-endometrial-cancer
#12
Núria Eritja, Bo-Juen Chen, Ruth Rodríguez-Barrueco, Maria Santacana, Sònia Gatius, August Vidal, Maria Dolores Martí, Jordi Ponce, Laura Bergadà, Andree Yeramian, Mario Encinas, Joan Ribera, Jaume Reventós, Jeff Boyd, Alberto Villanueva, Xavier Matias-Guiu, Xavier Dolcet, David Llobet-Navàs
Targeted therapies in endometrial cancer (EC) using kinase inhibitors rarely result in complete tumor remission and are frequently challenged by the appearance of refractory cell clones, eventually resulting in disease relapse. Dissecting adaptive mechanisms is of vital importance to circumvent clinical drug resistance and improve the efficacy of targeted agents in EC. Sorafenib is an FDA-approved multitarget tyrosine and serine/threonine kinase inhibitor currently used to treat hepatocellular carcinoma, advanced renal carcinoma and radioactive iodine-resistant thyroid carcinoma...
January 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28054367/development-of-an-uplc-ms-ms-method-for-routine-therapeutic-drug-monitoring-of-aripiprazole-amisulpride-olanzapine-paliperidone-and-ziprasidone-with-a-discussion-of-their-therapeutic-reference-ranges-for-chinese-patients
#13
Shao-Ting Wang, Yan Li
A highly feasible and reliable ultra-high performance liquid chromatography tandem mass spectrometry method was presented for therapeutic drug monitoring of five anti-schizophrenic drugs (amisulpride, olanzapine, aripiprazole, paliperidone and ziprasidone) simultaneously. To meet the requirements of practical clinical usage (easy-handling, high-throughput and cost effective), the pretreatment process has been especially simplified (only including protein precipitation and mobile phase dilution steps) and the UPLC separation cycle was set within 6 minutes...
January 5, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28053320/direct-measurement-of-b-cell-receptor-repertoire-s-composition-and-variation-in-systemic-lupus-erythematosus
#14
S Liu, X L Hou, W G Sui, Q J Lu, Y L Hu, Y Dai
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is known to be associated with polyclonal B-cell hyper-reactivity. B-cell receptor (BCR) has a central role in B-cell development, activation, survival and apoptosis, and thus is a critical component of the regulation of both protective and autoreactive B cells. In this study, we applied multiplex PCR and Illumina high-throughput sequencing to study the composition and variation of the BCRs in peripheral blood mononuclear cells from SLE patients and healthy donors (NC)...
January 5, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28053157/blockade-of-protease-activated-receptor-4-par4-provides-robust-antithrombotic-activity-with-low-bleeding
#15
Pancras C Wong, Dietmar Seiffert, J Eileen Bird, Carol A Watson, Jeffrey S Bostwick, Mary Giancarli, Nick Allegretto, Ji Hua, David Harden, Jocelyne Guay, Mario Callejo, Michael M Miller, R Michael Lawrence, Jacques Banville, Julia Guy, Brad D Maxwell, E Scott Priestley, Anne Marinier, Ruth R Wexler, Michel Bouvier, David A Gordon, William A Schumacher, Jing Yang
Antiplatelet agents are proven efficacious treatments for cardiovascular and cerebrovascular diseases. However, the existing drugs are compromised by unwanted and sometimes life-threatening bleeding that limits drug usage or dosage. There is a substantial unmet medical need for an antiplatelet drug with strong efficacy and low bleeding risk. Thrombin is a potent platelet agonist that directly induces platelet activation via the G protein (heterotrimeric guanine nucleotide-binding protein)-coupled protease-activated receptors PAR1 and PAR4...
January 4, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28048805/su-f-r-42-association-of-radiomic-and-metabolic-tumor-volumes-in-radiation-treatment-of-glioblastoma-multiforme
#16
C Lopez, N Nagornaya, N Parra, D Kwon, F Ishkanian, A Markoe, A Maudsley, R Stoyanova
PURPOSE: High-throughput extraction of imaging and metabolomic quantitative features from MRI and MR Spectroscopy Imaging (MRSI) of Glioblastoma Multiforme (GBM) results in tens of variables per patient. In radiotherapy (RT) of GBM, the relevant metabolic tumor volumes (MTVs) are related to aberrant levels of N-acetyl Aspartate (NAA) and Choline (Cho). Corresponding Clinical Target Volumes (CTVs) for RT planning are based on Contrast Enhancing T1-weighted MRI (CE-T1w) and T2-weighted/Fluid Attenuated Inversion Recovery (FLAIR) MRI...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28048698/tu-fg-bra-02-assure-the-quality-of-treatment-planning-when-time-is-constrained
#17
J Chang
Optimizing Radiation Therapy Process The radiotherapy (RT) process has evolved over the years with innovations in CT and MR simulations, treatment planning, and treatment delivery. Image-Guided Radiotherapy (IGRT) has been widely adopted for patient setup, leading to margin reduction and isocenter repositioning after simulation. Stereotactic Body Radiotherapy (SBRT) and Stereotactic Radiosurgery (SRS) have gradually become the standard of care for many treatment sites, which demand a higher throughput for the simulation/plan/treatment even if the number of treatments per day remains the same...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047314/tu-fg-bra-00-optimizing-the-treatment-planning-process
#18
Wenzheng Feng
Optimizing Radiation Therapy Process The radiotherapy (RT) process has evolved over the years with innovations in CT and MR simulations, treatment planning, and treatment delivery. Image-Guided Radiotherapy (IGRT) has been widely adopted for patient setup, leading to margin reduction and isocenter repositioning after simulation. Stereotactic Body Radiotherapy (SBRT) and Stereotactic Radiosurgery (SRS) have gradually become the standard of care for many treatment sites, which demand a higher throughput for the simulation/plan/treatment even if the number of treatments per day remains the same...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047234/tu-fg-bra-03-systems-engineering-and-treatment-planning-process-control-in-radiation-medicine
#19
A Kapur
Optimizing Radiation Therapy Process The radiotherapy (RT) process has evolved over the years with innovations in CT and MR simulations, treatment planning, and treatment delivery. Image-Guided Radiotherapy (IGRT) has been widely adopted for patient setup, leading to margin reduction and isocenter repositioning after simulation. Stereotactic Body Radiotherapy (SBRT) and Stereotactic Radiosurgery (SRS) have gradually become the standard of care for many treatment sites, which demand a higher throughput for the simulation/plan/treatment even if the number of treatments per day remains the same...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047194/su-f-t-501-dosimetric-comparison-of-single-arc-per-beam-and-two-arc-per-beam-vmat-optimization-in-the-monaco-treatment-planning-system
#20
A Kalet, H Richardson, N Cao, J Meyer, C Dempsey
PURPOSE: The purpose of this study was to evaluate the dosimetric and practical effects of the Monaco treatment planning system "max arcs-per-beam" optimization parameter in pelvic radiotherapy treatments. METHODS: A total of 17 previously treated patients were selected for this study with a range of pelvic disease site including prostate(9), bladder(1), uterus(3), rectum(3), and cervix(1). For each patient, two plans were generated, one using a arc-per-beam setting of '1' and another with setting of '2'...
June 2016: Medical Physics
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