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https://www.readbyqxmd.com/read/28525563/omics-biomarkers-in-ophthalmology
#1
Susette Lauwen, Eiko K de Jong, Dirk J Lefeber, Anneke I den Hollander
"Omics" refers to high-throughput analyses of genes, proteins, or metabolites in a biological system, and is increasingly used for ophthalmic research. These system-based approaches can unravel disease-related processes and are valuable for biomarker discovery. Furthermore, potential therapeutic targets can be identified based on omics results, and targeted follow-up experiments can be designed to gain molecular understanding of the disease and to test new therapies. Here, we review the application of omics techniques in eye diseases, focusing on age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal detachment (RD), myopia, glaucoma, Fuchs' corneal dystrophy (FCD), cataract, keratoconus, and dry eyes...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28522750/inhibition-of-mitochondrial-matrix-chaperones-and-anti-apoptotic-bcl-2-family-proteins-empower-antitumor-therapeutic-responses
#2
Georg Karpel-Massler, Chiaki Tsuge Ishida, Elena Bianchetti, Chang Shu, Rolando Perez-Lorenzo, Basil Horst, Matei Banu, Kevin A Roth, Jeffrey N Bruce, Peter Canoll, Dario C Altieri, Markus D Siegelin
Rational therapeutic approaches based on synthetic lethality may improve cancer management. Based on a high-throughput drug screen, we provide preclinical proof of concept that targeting the mitochondrial Hsp90 chaperone network (mtHsp90) and inhibition of Bcl-2, Bcl-xL and Mcl-1 is sufficient to elicit synthetic lethality in tumors recalcitrant to therapy. Our analyses focused on BH3 mimetics that are broad acting (ABT263 and Obatoclax) or selective (ABT199, WEHI-539 and A1210477), along with the established mitochondrial matrix chaperone inhibitor Gamitrinib-TPP...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28522225/genetic-screening-of-spinal-muscular-atrophy-using-a-real-time-modified-cop-pcr-technique-with-dried-blood-spot-dna
#3
Mawaddah Ar Rochmah, Nur Imma Fatimah Harahap, Emma Tabe Eko Niba, Kenta Nakanishi, Hiroyuki Awano, Ichiro Morioka, Kazumoto Iijima, Toshio Saito, Kayoko Saito, Poh San Lai, Yasuhiro Takeshima, Atsuko Takeuchi, Yoshihiro Bouike, Maya Okamoto, Hisahide Nishio, Masakazu Shinohara
BACKGROUND: Spinal muscular atrophy (SMA) is a common neuromuscular disorder caused by mutations in SMN1. More than 95% of SMA patients carry homozygous SMN1 deletion. SMA is the leading genetic cause of infant death, and has been considered an incurable disease. However, a recent clinical trial with an antisense oligonucleotide drug has shown encouraging clinical efficacy. Thus, early and accurate detection of SMN1 deletion may improve prognosis of many infantile SMA patients. METHODS: A total of 88 DNA samples (37 SMA patients, 12 carriers and 39 controls) from dried blood spots (DBS) on filter paper were analyzed...
May 15, 2017: Brain & Development
https://www.readbyqxmd.com/read/28516436/the-growing-challenge-of-young-adults-with-colorectal-cancer
#4
REVIEW
Benjamin A Weinberg, John L Marshall, Mohamed E Salem
Although the incidence of colorectal cancer is declining in the overall US population, the rates of colorectal cancer are rising among adolescent and young adult (AYA) patients-defined as individuals under 45 years of age. This population includes patients deemed too young for routine colorectal cancer screening, which in the United States is typically initiated at age 50 for men and women at average risk. Clinicopathologic differences have long been observed between AYAs and older patients with colorectal cancer...
May 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28512194/ancient-antagonism-between-celf-and-rbfox-families-tunes-mrna-splicing-outcomes
#5
Matthew R Gazzara, Michael J Mallory, Renat Roytenberg, John Lindberg, Anupama Jha, Kristen W Lynch, Yoseph Barash
Over 95% of human multi-exon genes undergo alternative splicing, a process important in normal development and often dysregulated in disease. We sought to analyze the global splicing regulatory network of CELF2 in human T cells, a well-studied splicing regulator critical to T cell development and function. By integrating high-throughput sequencing data for binding and splicing quantification with sequence features and probabilistic splicing code models, we find evidence of splicing antagonism between CELF2 and the RBFOX family of splicing factors...
May 16, 2017: Genome Research
https://www.readbyqxmd.com/read/28507068/genome-wide-survey-of-pseudomonas-aeruginosa-pa14-reveals-a-role-for-the-glyoxylate-pathway-and-extracellular-proteases-in-the-utilization-of-mucin
#6
Jeffrey M Flynn, Chi Phan, Ryan C Hunter
Chronic airway infections by the opportunistic pathogen Pseudomonas aeruginosa are a major cause of mortality in cystic fibrosis (CF) patients. While this bacterium has been extensively studied for its virulence determinants, biofilm growth and immune evasion mechanisms, comparatively little is known about the nutrient sources that sustain its growth in vivo Respiratory mucins represent a potentially abundant bioavailable nutrient source, though we have recently shown that canonical pathogens inefficiently use these host glycoproteins as a growth substrate...
May 15, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28506344/-novel-phex-gene-mutations-in-patients-with-x-linked-hypophosphatemic-rickets-an-analysis-of-2-cases
#7
Qing Ran, Feng Xiong, Min Zhu, Lei-Li Deng, Pei-Yun Lei, Yan-Hong Luo, Yan Zeng, Gao-Hui Zhu, Cui Song
OBJECTIVE: To investigate PHEX gene mutations in 2 patients with X-linked hypophosphatemic rickets (XLH) and their families and to clarify the genetic etiology. METHODS: A retrospective analysis was performed for the clinical data of two patients with XLH. High-throughput sequencing was used to detect the PHEX gene, a pathogenic gene of XLH. PCR-Sanger sequencing was used to verify the distribution of mutations in families. RESULTS: Both patients had novel mutations in the PHEX gene; one patient had a frameshift mutation, c...
May 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28505414/quantitative-on-line-liquid-chromatography-surface-enhanced-raman-scattering-lc-sers-of-methotrexate-and-its-major-metabolites
#8
Abdu Subaihi, Drupad K Trivedi, Katherine Anne Hollywood, James Bluett, Yun Xu, Howbeer Muhamadali, David I Ellis, Royston Goodacre
The application of Raman spectroscopy as a detection method coupled with liquid chromatography (LC) has recently attracted considerable interest, although this has currently been limited to isocratic elution. The combination of LC with rapidly advancing Raman techniques, such as surface-enhanced Raman scattering (SERS), allows for the rapid separation, identification and quantification, leading to quantitative discrimination of closely eluting analytes. This study has demonstrated the utility of SERS in conjunction with reversed phase liquid chromatography (RP-LC), for the detection and quantification of the therapeutically relevant drug molecule methotrexate (MTX) and its metabolites 7-hydroxy methotrexate and 2,4-diamino-N(10)-methylpteroic acid (DAMPA) in pure solutions and mixtures, including spikes into human urine from a healthy individual...
May 15, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28505059/creation-of-an-adult-observation-unit-improving-outcomes
#9
Joy M Plamann, Judith Zedreck-Gonzalez, Laura Fennimore
A growing segment of patients in hospitals are considered outpatients, classified as observation. These patients neither have the severity of illness nor the intensity of service to qualify as inpatients, yet are not well enough to be discharged. Hospitals have created observation units to address the clinical needs of this growing patient type to provide care in the right setting by managing emergency department throughput and utilizing the most efficient staffing resources. This article describes the change processes and improvements in quality, length of stay, and patient satisfaction, which occurred following the implementation of an adult observation unit...
May 12, 2017: Journal of Nursing Care Quality
https://www.readbyqxmd.com/read/28502495/detection-of-common-sequence-variations-of-familial-hypercholesterolemia-in-taiwan-using-dna-mass-spectrometry
#10
Kuan-Rau Chiou, Min-Ji Charng
BACKGROUND: Familial hypercholesterolemia (FH) is a heterogeneous autosomal dominant disease. The genetic heterogeneity of FH requires low-cost, high-throughput, and rapid mutation detection technology to efficiently integrate genetic screening into clinical practice. OBJECTIVES: The aims of the study were to customize the MassARRAY assay to (1) establish an FH mutation assay panel, comprising known point mutations located on FH-causing genes and (2) test the feasibility of the assay for screening FH patients residing in Taiwan who fit the clinical criteria of FH diagnosis...
March 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28502004/somatic-dna-mutation-analysis
#11
Anthony O'Grady, Robert Cummins
Somatic mutations in patient tumor DNA samples can be readily detected based on mass spectrometry. The MassARRAY system is a high-throughput matrix-assisted laser desorption time-of-flight (MALDI) mass spectrometer for detection of nucleic acids. The technique is based on single-nucleotide base extension. A series of PCR assays amplify specific DNA regions of interest harboring mutations. A third primer is then introduced into the reaction which corresponds to the DNA template immediately in front of the mutation site...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28501851/implementing-liquid-biopsies-into-clinical-decision-making-for-cancer-immunotherapy
#12
REVIEW
Dagmar Quandt, Hans D Zucht, Arno Amann, Anne Wulf-Goldenberg, Carl Borrebaeck, Michael Cannarile, Diether Lambrechts, Herbert Oberacher, James Garrett, Tapan Nayak, Michael Kazinski, Charles Massie, Heidi Schwarzenbach, Michele Maio, Robert Prins, Björn Wendik, Richard Hockett, Daniel Enderle, Mikkel Noerholm, Hans Hendriks, Heinz Zwierzina, Barbara Seliger
During the last decade, novel immunotherapeutic strategies, in particular antibodies directed against immune checkpoint inhibitors, have revolutionized the treatment of different malignancies leading to an improved survival of patients. Identification of immune-related biomarkers for diagnosis, prognosis, monitoring of immune responses and selection of patients for specific cancer immunotherapies is urgently required and therefore areas of intensive research. Easily accessible samples in particular liquid biopsies (body fluids), such as blood, saliva or urine, are preferred for serial tumor biopsies...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28501667/update-and-new-insights-in-encephalitis
#13
REVIEW
Alexandra Mailles, Jean-Paul Stahl, Karen C Bloch
BACKGROUND: Encephalitis is a medical condition possibly caused by an unlimited number of infectious agents. AIMS: Our review aims at giving an overview of the recent discoveries and advances in encephalitis presentation, diagnosis and management, including in the field of emerging diseases. SOURCES: We search the literature using Pubmed and Embase to identify the most relevant new data published over the last years in the field of infectious encephalitis...
May 10, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28499138/human-pegivirus-1-in-the-csf-of-patients-with-hiv-associated-neurocognitive-disorder-hand-may-be-derived-from-blood-in-highly-viraemic-patients
#14
Diana Hardie, Heidi Smuts
BACKGROUND: Human pegivirus-1 (HPgV-1) infection in the brain has not been extensively examined and its association with disease remains unconfirmed. In a high throughput sequencing study to look for infectious agents that could play a role in HIV-associated neurocognitive disorder (HAND), this virus was detected in 3 of 8 CSF samples. OBJECTIVES: To determine the significance of this finding, additional patients were screened and the viral load and viral diversity in blood and CSF were examined...
April 6, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28498330/specific-microrna-pattern-in-colon-tissue-of-young-children-with-eosinophilic-colitis
#15
Zoltán Kiss, Nóra Judit Béres, Erna Sziksz, Bálint Tél, Katalin Borka, András Arató, Attila J Szabó, Gábor Veres
Eosinophilic colitis (EC) is a common cause of haematochezia in infants and young children. The exact pathomechanism is not understood, and the diagnosis is challenging. The role of microRNAs as key class of regulators of mRNA expression and translation in patients with EC has not been explored. Therefore, the aim of the present study was to explore the miRNA profile in EC with respect to eosinophilic inflammation. Patients enrolled in the study (n = 10) had persistent rectal bleeding, and did not respond to elimination dietary treatment...
May 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28497593/polymorphism-of-receptor-type-tyrosine-protein-phosphatase-delta-gene-in-the-development-of-non-alcoholic-fatty-liver-disease
#16
Shunsuke Nakajima, Hiroki Tanaka, Koji Sawada, Hidemi Hayashi, Takumu Hasebe, Masami Abe, Chitomi Hasebe, Mikihiro Fujiya, Toshikatsu Okumura
BACKGROUND AND AIM: Some single nucleotide polymorphisms (SNPs) are associated with the development of non-alcoholic fatty liver disease (NAFLD). As one of the genetic factors, PNPLA3 rs738409 (I148M) is important to associate with pathogenesis of NAFLD. Since other SNPs remain unclear in Japan, we performed high-throughput sequencing, which targeted more than 1,000 genes to identify a novel genetic variant in Japanese patients with NAFLD. METHODS: The present study in 36 NAFLD patients and 27 healthy volunteers (HVs) was performed...
May 11, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28497047/association-study-of-gut-flora-in-coronary-heart-disease-through-high-throughput-sequencing
#17
Li Cui, Tingting Zhao, Haibing Hu, Wen Zhang, Xiuguo Hua
Objectives. We aimed to explore the impact of gut microbiota in coronary heart disease (CHD) patients through high-throughput sequencing. Methods. A total of 29 CHD in-hospital patients and 35 healthy volunteers as controls were included. Nucleic acids were extracted from fecal samples, followed by α diversity and principal coordinate analysis (PCoA). Based on unweighted UniFrac distance matrices, unweighted-pair group method with arithmetic mean (UPGMA) trees were created. Results. After data optimization, an average of 121312 ± 19293 reads in CHD patients and 234372 ± 108725 reads in controls was obtained...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28496060/rapid-detection-of-small-molecule-metabolites-in-serum-of-hepatocellular-carcinoma-patients-using-ultrafast-liquid-chromatography-ion-trap-time-of-flight-tandem-mass-spectrometry
#18
Hui Li, Su-Fang Fan, Yan Wang, Shi-Gang Shen, Dian-Xing Sun
A method was developed for analyzing broad spectrum small molecule metabolites in the serum of hepatocellular carcinoma (HCC) patients based on ultrafast liquid chromatography-ion trap-time of flight tandem mass spectrometry (UFLC-IT-TOF MS). Serum samples were collected from 80 HCC patients and healthy persons. After pretreatment process for protein precipitation, the supernatant was analyzed with the UFLC-IT-TOF MS to obtain information on the metabonomics of small molecules. The eight compounds of glycocholic acid, choline glycerophosphate, acetyl-L-phenylalanine, oleamide, tetradecanamide, acetylcarnitine, lysolecithin and glycochenodeoxycholic acid in the HCC group were identified with significant differences from those in the health group (P <0...
2017: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
https://www.readbyqxmd.com/read/28495852/high-throughput-mrna-sequencing-of-stromal-cells-from-endometriomas-and-endometrium
#19
Kadri Rekker, Merli Saare, Elo Eriste, Tõnis Tasa, Viktorija Kukuškina, Anne Mari Roost, Kristi Anderson, Külli Samuel, Helle Karro, Andres Salumets, Maire Peters
The aetiology of endometriosis is still unclear and to find mechanisms behind the disease development it is important to study each cell type from endometrium and ectopic lesions independently. The objective of this study was to uncover complete mRNA profiles in uncultured stromal cells from paired samples of endometriomas and eutopic endometrium. High-throughput mRNA sequencing revealed over 1,300 dysregulated genes in stromal cells from ectopic lesions, including several novel genes in the context of endometriosis...
May 11, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28495399/evaluation-of-toll-like-receptor-gene-family-variants-as-prognostic-biomarkers-in-rheumatoid-arthritis
#20
Silvia Torices, Lorena Alvarez-Rodríguez, Ignacio Varela, Pedro Muñoz, Alejandro Balsa, M López-Hoyos, Víctor Martinez-Taboada, Jose L Fernández-Luna
Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main feature is persistent joint inflammation. Toll-like receptors (TLRs) play critical roles in the activation of innate and adaptive immune responses, and influence the activity of NFκB, a key player in chronic inflammation. We aimed at investigating the association of TLR allelic variants with susceptibility and severity of RA through a systematic, high-throughput, analysis of TLR genes. All coding exons and flanking regions of nine members of the TLR family (TLR1-9) were analyzed in 66 patients with RA and 30 healthy controls by next generation sequencing...
May 7, 2017: Immunology Letters
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