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https://www.readbyqxmd.com/read/28749036/advantages-of-rna-seq-compared-to-rna-microarrays-for-transcriptome-profiling-of-anterior-cruciate-ligament-tears
#1
Muhammad Farooq Rai, Eric D Tycksen, Linda J Sandell, Robert H Brophy
Microarrays and RNA-seq are at the forefront of high throughput transcriptome analyses. Since these methodologies are based on different principles there are concerns about the concordance of data between the two techniques. The concordance of RNA-seq and microarrays for genome-wide analysis of differential gene expression has not been rigorously assessed in clinically derived ligament tissues. To demonstrate the concordance between RNA-seq and microarrays and to assess potential benefits of RNA-seq over microarrays, we assessed differences in transcript expression in anterior cruciate ligament (ACL) tissues based on time-from-injury...
July 27, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28747710/a-high-content-image-analysis-approach-for-quantitative-measurements-of-chemosensitivity-in-patient-derived-tumor-microtissues
#2
Ilmari Ahonen, Malin Åkerfelt, Mervi Toriseva, Eva Oswald, Julia Schüler, Matthias Nees
Organotypic, three-dimensional (3D) cancer models have enabled investigations of complex microtissues in increasingly realistic conditions. However, a drawback of these advanced models remains the poor biological relevance of cancer cell lines, while higher clinical significance would be obtainable with patient-derived cell cultures. Here, we describe the generation and data analysis of 3D microtissue models from patient-derived xenografts (PDX) of non-small cell lung carcinoma (NSCLC). Standard of care anti-cancer drugs were applied and the altered multicellular morphologies were captured by confocal microscopy, followed by automated image analyses to quantitatively measure phenotypic features for high-content chemosensitivity tests...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28746860/integrating-rna-sequencing-into-neuro-oncology-practice
#3
REVIEW
David S Rogawski, Nicholas A Vitanza, Angela C Gauthier, Vijay Ramaswamy, Carl Koschmann
Malignant tumors of the central nervous system (CNS) cause substantial morbidity and mortality, yet efforts to optimize chemo- and radiotherapy have largely failed to improve dismal prognoses. Over the past decade, RNA sequencing (RNA-seq) has emerged as a powerful tool to comprehensively characterize the transcriptome of CNS tumor cells in one high-throughput step, leading to improved understanding of CNS tumor biology and suggesting new routes for targeted therapies. RNA-seq has been instrumental in improving the diagnostic classification of brain tumors, characterizing oncogenic fusion genes, and shedding light on intratumor heterogeneity...
July 8, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28746207/integrating-nested-pcr-with-high-throughput-sequencing-to-characterize-mutations-of-hbv-genome-in-low-viral-load-samples
#4
Xianjun Wang, Lihui Xu, Yueming Chen, Anbing Liu, Liqian Wang, Peisong Xu, Yunhui Liu, Lei Li, Fei Meng
Due to the low viral load of hepatitis B virus (HBV) in plasma samples, conventional techniques have limitations to the detection of antiviral resistance mutations. To solve the problem, we developed a fast, highly sensitive, and accurate method to sequence the HBV whole-genome sequencing in plasma samples which had various viral loads from very low to high.Twenty-one plasma samples were collected from patients who were carriers of HBV from the Hangzhou First People's Hospital. Two pairs of conserved, overlapping, nested primers were used to amplify and sequence the whole HBV genome in 8 plasma samples with different viral loads...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28746071/toward-a-utopian-model-for-teaching-and-nonteaching-services-every-journey-begins-with-a-first-step
#5
Lisa M Bellini, Jack Ende
Nonteaching services are an imperfect step toward enabling inpatient teaching services to transition from an unregulated, natural state, driven solely by the exigencies of patient volume and throughput, to one that is more controlled and intends to achieve the proper balance between service and education. As career educators the authors prefer to view nonteaching services as critical components of an integrated system that enables the best possible patient care and learning, yet they acknowledge that, to meet the needs of patients and learners, teaching and nonteaching services alike must be truly complementary, collaborative, and integrated components of a single system...
July 25, 2017: Academic Medicine: Journal of the Association of American Medical Colleges
https://www.readbyqxmd.com/read/28743917/a-rapid-low-cost-and-microfluidic-chip-based-system-for-parallel-identification-of-multiple-pathogens-related-to-clinical-pneumonia
#6
Guoliang Huang, Qin Huang, Lan Xie, Guangxin Xiang, Lei Wang, Hui Xu, Li Ma, Xianbo Luo, Juan Xin, Xinying Zhou, Xiangyu Jin, Lei Zhang
An air-insulated microfluidic chip was designed for the automatic centrifugal distribution of samples to 24-test cells, enabling the parallel identification of multiple clinical pneumonia-related pathogens in 1.45-μL reactions without cross-contamination in 45 min. A portable nucleic acid analyzer that integrates mechanical, confocal optical, electronic, and software functions was also developed to collect fluorescence data in a Ø3 mm imaging field near the optical diffraction limit for highly sensitive fluorescence detection of nucleic acid amplification in real time...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28740226/multicomponent-high-throughput-drug-screening-via-inkjet-printing-to-verify-the-effect-of-immunosuppressive-drugs-on-immune-t-lymphocytes
#7
Moonhyun Choi, Jangsun Hwang, Jonghoon Choi, Jinkee Hong
High-throughput drug screening based on a multi-component array can be used to identify a variety of interaction between cells and drugs for suitable purposes. The signaling of immune cells is affected by specific proteins, diverse drug combinations, and certain immunosuppressive drugs. The effect of a drug on an organism is usually complex and involves interactions at multiple levels. Herein, we developed a multilayer fabricating system through the high-throughput assembly of nanofilms with inkjet printing to investigate the effects of immunosuppressive drugs...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28738563/urinary-volatile-fingerprint-based-on-mass-spectrometry-for-the-discrimination-of-patients-with-lung-cancer-and-controls
#8
Álvaro García Ramos, Ana Pérez Antón, Miguel Del Nogal Sánchez, José Luis Pérez Pavón, Bernardo Moreno Cordero
Profile signals of urine samples corresponding to patients with lung cancer and controls were obtained using a non-separative methodology. The method is based on the coupling of a headspace sampler, a programed temperature vaporizer and a mass spectrometer (HS-PTV-MS). With only a centrifugation step as prior sample treatment, the samples were subjected to the headspace generation process and the volatiles generated were introduced into the PTV where they were trapped in the Tenax® packed liner while the solvent was purged...
November 1, 2017: Talanta
https://www.readbyqxmd.com/read/28736626/molecular-landscape-and-sub-classification-of-gastrointestinal-cancers-a-review-of-literature
#9
REVIEW
Bita Fakhri, Kian-Huat Lim
The historical approach of diagnosing cancer types based entirely on anatomic origin and histologic features, and the "one-size-fit-all" therapeutic approach, are inadequate in modern cancer treatment. From decades of research we now know that cancer is a highly heterogeneous disease driven by complex genetic or epigenetic alterations. The advent of various high throughput molecular tools has now enabled us to view and sub-classify each cancer type based on their distinct molecular features, in addition to histologic classification, with the promise of individualized treatment strategies tailored towards each specific subtype to improve patient outcomes...
June 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28736238/the-pursuit-of-therapeutic-biomarkers-with-high-throughput-cancer-cell-drug-screens
#10
REVIEW
Steven P Williams, Ultan McDermott
In the last decade we have witnessed tremendous advances in our understanding of the landscape of the molecular alterations that underpin many of the most prevalent cancers, in the use of automated high-throughput platforms for high-throughput drug screens in cancer cells, in the creation of more clinically relevant cancer cell models, and lastly in the development of more useful computational approaches in the pursuit of biomarkers of drug response. Separately, each of these improvements will undoubtedly lead to improvements in the treatment of cancer patients but to fulfill the promise of truly personalized cancer medicine, we must bring these disciplines together in a truly multidisciplinary fashion...
July 12, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28735492/isolation-of-biologically-active-exosomes-from-plasma-of-patients-with-cancer
#11
Chang-Sook Hong, Sonja Funk, Theresa L Whiteside
A method for exosome isolation from human plasma was developed for rapid, high-throughput processing of plasma specimens obtained from patients with cancer. This method removes the bulk of plasma proteins associated with exosomes and can be used for comparative examinations of exosomes and their content in serial specimens of patients' plasma, allowing for monitoring changes in exosome numbers, profiles, and functions in the course of cancer progression or during therapy. The plasma-derived exosomes can be recovered in quantities sufficient for the characterization of their morphology by transmission electron microscopy (TEM), size and concentration by qNano, protein/lipid ratios, nucleic acid extraction, molecular profiling by Western blots or immune arrays, and functional assays...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28735360/navigating-the-future-of-cardiovascular-drug-development-leveraging-novel-approaches-to-drive-innovation-and-drug-discovery-summary-of-findings-from-the-novel-cardiovascular-therapeutics-conference
#12
REVIEW
Thomas J Povsic, Rob Scott, Kenneth W Mahaffey, Robert Blaustein, Jay M Edelberg, Martin P Lefkowitz, Scott D Solomon, Jonathan C Fox, Kevin E Healy, Aarif Y Khakoo, Douglas W Losordo, Fady I Malik, Brett P Monia, Rusty L Montgomery, Jeffrey Riesmeyer, Gregory G Schwartz, Steven L Zelenkofske, Joseph C Wu, Scott M Wasserman, Matthew T Roe
PURPOSE: The need for novel approaches to cardiovascular drug development served as the impetus to convene an open meeting of experts from the pharmaceutical industry and academia to assess the challenges and develop solutions for drug discovery in cardiovascular disease. METHODS: The Novel Cardiovascular Therapeutics Summit first reviewed recent examples of ongoing or recently completed programs translating basic science observations to targeted drug development, highlighting successes (protein convertase sutilisin/kexin type 9 [PCSK9] and neprilysin inhibition) and targets still under evaluation (cholesteryl ester transfer protein [CETP] inhibition), with the hope of gleaning key lessons to successful drug development in the current era...
July 22, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28733637/c26-ceramide-as-highly-sensitive-biomarker-for-the-diagnosis-of-farber-disease
#13
Claudia Cozma, Marius-Ionuț Iurașcu, Sabrina Eichler, Marina Hovakimyan, Oliver Brandau, Susanne Zielke, Tobias Böttcher, Anne-Katrin Giese, Jan Lukas, Arndt Rolfs
Farber disease (FD) is a rare autosomal recessive disease caused by mutations in the acid ceramidase gene (ASAH1). Low ceramidase activity results in the accumulation of fatty substances, mainly ceramides. Hallmark symptoms at clinical level are periarticular nodules, lipogranulomas, swollen and painful joints and a hoarse voice. FD phenotypes are heterogeneous varying from mild to very severe cases, with the patients not surviving past their first year of life. The diagnostic aspects of FD are poorly developed due to the rarity of the disease...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733468/management-impact-effects-on-quality-of-life-and-prognosis-in-men1
#14
Francesca Marini, Francesca Giusti, Francesco Tonelli, Maria Luisa Brandi
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant endocrine tumor syndrome, caused by inactivating mutations of the MEN1 tumor suppressor gene at 11q13 locus, which predisposes to develop tumors in target neuroendocrine tissues. Since the positional cloning and identification of the causative gene in 1997, genetic diagnosis, by the sequencing-based research of gene mutations, has become an important tool in the early and differential diagnosis of the disease. Application of the genetic test, in MEN1 index cases and in first degree relatives of mutated patients, has been constantly increasing during the last two decades, also thanks to the establishment of multidisciplinary referral centers and specific genetic counselling, and thanks to the wide availability of high throughput instruments for gene sequencing and gene mutation identification...
July 21, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28732184/high-throughput-identification-of-mir-596-inducing-p53-mediated-apoptosis-in-hela-and-hct116-cells-using-cell-microarray
#15
Ming Ma, Junyu Yang, Bolun Wang, Zhihua Zhao, Jianzhong Jeff Xi
miRNAs play a key role in the regulation of gene networks in mammalian cells. However, little is known about their roles and functions in the apoptosis pathway. Here, we conducted a whole-genome miRNA screening for apoptosis and identified more than 100 miRNAs as apoptosis inducers. To further explain the roles of these mRNAs in apoptosis, a second round of screening was conducted between p53 +/+ and -/- cells. Among the hits, miR-596 was identified as a regulator of p53. The overexpression of miR-596 significantly increased p53 at the protein level, thereby inducing apoptosis...
July 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/28731526/drug-discovery-and-development-for-rare-genetic-disorders
#16
REVIEW
Wei Sun, Wei Zheng, Anton Simeonov
Approximately 7,000 rare diseases affect millions of individuals in the United States. Although rare diseases taken together have an enormous impact, there is a significant gap between basic research and clinical interventions. Opportunities now exist to accelerate drug development for the treatment of rare diseases. Disease foundations and research centers worldwide focus on better understanding rare disorders. Here, the state-of-the-art drug discovery strategies for small molecules and biological approaches for orphan diseases are reviewed...
July 21, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28728565/identification-of-differential-co-expressed-gene-networks-in-early-rheumatoid-arthritis-achieving-sustained-drug-free-remission-after-treatment-with-a-tocilizumab-based-or-methotrexate-based-strategy
#17
Xavier M Teitsma, Johannes W G Jacobs, Michal Mokry, Michelle E A Borm, Attila Pethö-Schramm, Jacob M van Laar, Johannes W J Bijlsma, Floris P J Lafeber
BACKGROUND: Methotrexate is endorsed to be used as first-line treatment in rheumatoid arthritis (RA). However, a large proportion of patients need additional treatment with a biological disease-modifying anti-rheumatic drug (DMARD) to adequately suppress their disease activity. A better understanding of genotypes could help to distinguish between patients with different pathogenic mechanisms. The aim of this study was therefore to identify networks of genes within DMARD-naive early RA patients associated with achieving sustained drug-free remission (sDFR) after initiating tocilizumab plus methotrexate, tocilizumab, or methotrexate therapy...
July 20, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28726508/optimizing-mri-logistics-prospective-analysis-of-performance-efficiency-and-patient-throughput
#18
Kevin Beker, Alejandro Garces-Descovich, Jason Mangosing, Ines Cabral-Goncalves, Donna Hallett, Koenraad J Mortele
OBJECTIVE: The objective of this study is to optimize MRI logistics through evaluation of MRI workflow and analysis of performance, efficiency, and patient throughput in a tertiary care academic center. SUBJECTS AND METHODS: For 2 weeks, workflow data from two outpatient MRI scanners were prospectively collected and stratified by value added to the process (i.e., value-added time, business value-added time, or non-value-added time). Two separate time cycles were measured: the actual MRI process cycle as well as the complete length of patient stay in the department...
July 20, 2017: AJR. American Journal of Roentgenology
https://www.readbyqxmd.com/read/28725009/the-salivary-microbiome-as-an-indicator-of-carcinogenesis-in-patients-with-oropharyngeal-squamous-cell-carcinoma-a-pilot-study
#19
Axel Wolf, Christine Moissl-Eichinger, Alexandra Perras, Kaisa Koskinen, Peter V Tomazic, Dietmar Thurnher
This study aimed to undertake an initial, comparative analysis of the oral salivary microbiome of patients with oral and oropharyngeal squamous cell carcinoma versus healthy controls. This project, conceived as a pilot study, included 11 patients (1 female, 10 male, mean age 61.6 yrs., SD = 8.2 yrs.) and 11 healthy controls (1 female, 10 male, mean age 46.7 yrs., SD = 15.1 yrs.). Samples of saliva were analysed by high-throughput sequencing of the 16S rRNA gene using the MiSeq platform. Sequence data revealed microbial changes that may mirror disease progression and reflect clinical preconditions such as age, alcohol consumption, tumour size, lymph node status, smoking habit, and tumour HPV-positivity...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724801/tcr-ligand-dissociation-rate-is-a-robust-and-stable-biomarker-of-cd8-t-cell-potency
#20
Mathilde Allard, Barbara Couturaud, Laura Carretero-Iglesia, Minh Ngoc Duong, Julien Schmidt, Gwennaëlle C Monnot, Pedro Romero, Daniel E Speiser, Michael Hebeisen, Nathalie Rufer
Despite influencing many aspects of T cell biology, the kinetics of T cell receptor (TCR) binding to peptide-major histocompatibility molecules (pMHC) remain infrequently determined in patient monitoring or for adoptive T cell therapy. Using specifically designed reversible fluorescent pMHC multimeric complexes, we performed a comprehensive study of TCR-pMHC off-rates combined with various functional assays on large libraries of self/tumor- and virus-specific CD8+ T cell clones from melanoma patients and healthy donors...
July 20, 2017: JCI Insight
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