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Phenotypic heterogeneity

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https://www.readbyqxmd.com/read/28734132/high-dimensional-single-cell-mapping-of-cerium-distribution-in-the-lung-immune-microenvironment-of-an-active-smoker
#1
Adeeb H Rahman, Yonit Lavin, Soma Kobayashi, Andrew Leader, Miriam Merad
BACKGROUND: Mass cytometry leverages inductively coupled mass spectrometry to perform high dimensional single cell analyses using antibodies tagged with rare earth isotopes that are considered to be largely absent in biological samples. We have recently noted an unusual exception to this rule while analyzing tissue samples from patients undergoing surgical resection for early stage lung cancer, and here we present a detailed cytometric characterization of cerium in a clinical patient sample...
July 22, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28732379/integrative-analysis-of-novel-hypomethylation-and-gene-expression-signatures-in-glioblastomas
#2
Anan Yin, Amandine Etcheverry, Yalong He, Marc Aubry, Jill Barnholtz-Sloan, Luhua Zhang, Xinggang Mao, Weijun Chen, Bolin Liu, Wei Zhang, Jean Mosser, Xiang Zhang
Molecular and clinical heterogeneity critically hinders better treatment outcome for glioblastomas (GBMs); integrative analysis of genomic and epigenomic data may provide useful information for improving personalized medicine. By applying training-validation approach, we identified a novel hypomethylation signature comprising of three CpGs at non-CpG island (CGI) open sea regions for GBMs. The hypomethylation signature consistently predicted poor prognosis of GBMs in a series of discovery and validation datasets...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732178/reproductive-plasticity-in-the-nematode-gyrinicola-batrachiensis-does-an-intermediate-reproductive-strategy-exist-in-sexually-reproducing-didelphic-pinworms
#3
Jasmine N Childress, Sean C Rogers, Matthew G Bolek, Gabriel J Langford
Phenotypic plasticity is a process in which multiple phenotypes arise from one genotype due to environmental selection pressures. Gyrinicola batrachiensis has a heterogeneous reproductive strategy such that females reproduce either via parthogenesis with thick-shelled eggs in a single uterus or sexual reproduction with thick and thin-shelled eggs in separate uterine horns. No evidence exists that strains of G. batrachiensis are able to switch between parthenogenetic and sexual reproduction. Thin-shelled eggs are autoinfective while thick-shelled eggs act as transmission agents once shed into the aquatic environment...
July 21, 2017: Journal of Parasitology
https://www.readbyqxmd.com/read/28732051/cd4-is-expressed-on-a-heterogeneous-subset-of-hematopoietic-progenitors-which-persistently-harbor-cxcr4-and-ccr5-tropic-hiv-proviral-genomes-in-vivo
#4
Nadia T Sebastian, Thomas D Zaikos, Valeri Terry, Frances Taschuk, Lucy A McNamara, Adewunmi Onafuwa-Nuga, Ryan Yucha, Robert A J Signer, James Riddell, Dale Bixby, Norman Markowitz, Sean J Morrison, Kathleen L Collins
Latent HIV infection of long-lived cells is a barrier to viral clearance. Hematopoietic stem and progenitor cells are a heterogeneous population of cells, some of which are long-lived. CXCR4-tropic HIVs infect a broad range of HSPC subtypes, including hematopoietic stem cells, which are multi-potent and long-lived. However, CCR5-tropic HIV infection is limited to more differentiated progenitor cells with life spans that are less well understood. Consistent with emerging data that restricted progenitor cells can be long-lived, we detected persistent HIV in restricted HSPC populations from optimally treated people...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28731408/defining-the-biological-basis-of-radiomic-phenotypes-in-lung-cancer
#5
Patrick Grossmann, Olya Stringfield, Nehme El-Hachem, Marilyn M Bui, Emmanuel Rios Velazquez, Chintan Parmar, Ralph Th Leijenaar, Benjamin Haibe-Kains, Philippe Lambin, Robert Gillies, Hugo Jwl Aerts
Medical imaging can visualize characteristics of human cancer noninvasively. Radiomics is an emerging field that translates these medical images into quantitative data to enable phenotypic profiling of tumors. While radiomics has been associated with several clinical endpoints, the complex relationships of radiomics, clinical factors, and tumor biology are largely unknown. To this end, we analyzed two independent cohorts of respectively 262 North American and 89 European patients with lung cancer, and consistently identified previously undescribed associations between radiomic imaging features, molecular pathways, and clinical factors...
July 21, 2017: ELife
https://www.readbyqxmd.com/read/28729958/mutational-analysis-of-driver-genes-with-tumor-suppressive-and-oncogenic-roles-in-gastric-cancer
#6
Tianfang Wang, Yining Liu, Min Zhao
Gastric cancer (GC) is a complex disease with heterogeneous genetic mechanisms. Genomic mutational profiling of gastric cancer not only expands our knowledge about cancer progression at a fundamental genetic level, but also could provide guidance on new treatment decisions, currently based on tumor histology. The fact that precise medicine-based treatment is successful in a subset of tumors indicates the need for better identification of clinically related molecular tumor phenotypes, especially with regard to those driver mutations on tumor suppressor genes (TSGs) and oncogenes (ONGs)...
2017: PeerJ
https://www.readbyqxmd.com/read/28729668/novel-fam83h-mutations-in-patients-with-amelogenesis-imperfecta
#7
Wang Xin, Wang Wenjun, Qin Man, Zhao Yuming
Amelogenesis imperfecta (AI), characterized by a deficiency in the quantity and/or quality of dental enamel, is genetically heterogeneous and phenotypically variable. The most severe type, hypocalcified AI, is mostly caused by truncating mutations in the FAM83H gene. This study aimed to identify genetic mutations in four Chinese families with hypocalcified AI. We performed mutation analysis by sequencing the candidate FAM83H gene. Three novel mutations (c.931dupC, p.V311Rfs*13; c.1130_1131delinsAA, p.S377X; and c...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729471/hypoxic-vascular-response-and-ventilation-perfusion-matching-in-end-stage-copd-may-depend-on-p22phox
#8
Chandran Nagaraj, Christoph Tabeling, Bence M Nagy, Pritesh P Jain, Leigh M Marsh, Rita Papp, Michael Pienn, Martin Witzenrath, Bahil Ghanim, Walter Klepetko, E Kenneth Weir, Stefan Heschl, Grazyna Kwapiszewska, Andrea Olschewski, Horst Olschewski
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease in which the amount of emphysema and airway disease may be very different between individuals, even in end-stage disease. Emphysema formation may be linked to the involvement of the small pulmonary vessels. The NAPDH oxidase (Nox) family is emerging as a key disease-related factor in vascular diseases, but currently its role in hypoxia-induced pulmonary remodelling in COPD remains unclear.Here we investigate the role of p22phox, a regulatory subunit of Nox, in COPD lungs, hypoxic pulmonary vasoconstriction (HPV), hypoxia-induced pulmonary vascular remodelling and pulmonary hypertension...
July 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28729156/multivariate-pattern-analysis-utilizing-structural-or-functional-mri-in-individuals-with-musculoskeletal-pain-and-healthy-controls-a-systematic-review
#9
REVIEW
Ashley Smith, Marina López-Solà, Katie McMahon, Ashley Pedler, Michele Sterling
OBJECTIVE: The purpose of this systematic review is to systematically review the evidence relating to findings generated by multivariate pattern analysis (MVPA) following structural or functional magnetic resonance imaging (fMRI) to determine if this analysis is able to: a) Discriminate between individuals with musculoskeletal pain and healthy controls, b) Predict pain perception in healthy individuals stimulated with a noxious stimulus compared to those stimulated with a non-noxious stimulus...
June 15, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28728937/the-impact-of-machine-learning-techniques-in-the-study-of-bipolar-disorder-a-systematic-review
#10
REVIEW
Diego Librenza-Garcia, Bruno Jaskulski Kotzian, Jessica Yang, Benson Mwangi, Bo Cao, Luiza Nunes Pereira Lima, Mariane Bagatin Bermudez, Manuela Vianna Boeira, Flávio Kapczinski, Ives Cavalcante Passos
Machine learning techniques provide new methods to predict diagnosis and clinical outcomes at an individual level. We aim to review the existing literature on the use of machine learning techniques in the assessment of subjects with bipolar disorder. We systematically searched PubMed, Embase and Web of Science for articles published in any language up to January 2017. We found 757 abstracts and included 51 studies in our review. Most of the included studies used multiple levels of biological data to distinguish the diagnosis of bipolar disorder from other psychiatric disorders or healthy controls...
July 17, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28728016/location-location-location-microglia-are-where-they-live
#11
Margaret M McCarthy
A deep dive into microglia form and function reveals startling regional heterogeneity in number, morphology, activity, and transcriptomics in nuclei relevant to motor control and motivation (De Biase et al., 2017). Differences appear 2 weeks after birth, and depletion and recolonization in adulthood recapitulate the original phenotype, implicating local environment as mediators of microglial phenotype.
July 19, 2017: Neuron
https://www.readbyqxmd.com/read/28727142/genomic-and-transcriptomic-heterogeneity-of-colorectal-tumors-arising-in-lynch-syndrome
#12
Hans Binder, Lydia Hopp, Michal R Schweiger, Steve Hoffmann, Frank Jühling, Martin Kerick, Bernd Timmermann, Susann Siebert, Christina Grimm, Lilit Nersisyan, Arsen Arakelyan, Maria Herberg, Peter Buske, Henry Loeffler-Wirth, Maciej Rosolowski, Christoph Engel, Jens Przybilla, Martin Peifer, Nicolaus Friedrichs, Gabriela Moeslein, Margarete Odenthal, Michelle Hussong, Sophia Peters, Stefanie Holzapfel, Jacob Nattermann, Robert Hueneburg, Wolff Schmiegel, Brigitte Royer-Pokora, Stefan Aretz, Michael Kloth, Matthias Kloor, Reinhard Buettner, Jörg Galle, Markus Loeffler
Colorectal cancer (CRC) arising in Lynch Syndrome (LS) comprises tumors with constitutional mutations in DNA mismatch-repair genes. Whole-genome and transcriptome studies of LS-CRC are still missing to address questions about similarities and differences of mutation and gene expression characteristics between LS-CRC and sporadic CRC, about the molecular heterogeneity of LS-CRC and about specific mechanisms of LS-CRC genesis linked to dysfunctional mismatch-repair in LS colonic mucosa and the possible role of immune editing...
July 20, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28727138/partial-diel-migration-a-facultative-migration-underpinned-by-long-term-inter-individual-variation
#13
Philip M Harrison, Lee F G Gutowsky, Eduardo G Martins, David A Patterson, Steven J Cooke, Michael Power
The variations in migration that comprise partial diel migrations, putatively occur entirely as a consequence of behavioural flexibility. However, seasonal partial migrations are increasingly recognised to be mediated by a combination of reversible plasticity in response to environmental variation and individual variation due to genetic and environmental effects. Here, we test the hypothesis that while partial diel migration heterogeneity occurs primarily due to short-term within-individual flexibility in behaviour, long-term individual differences in migratory behaviour also underpin this migration variation...
June 14, 2017: Journal of Animal Ecology
https://www.readbyqxmd.com/read/28725641/mechanisms-mediating-pediatric-severe-asthma-and-potential-novel-therapies
#14
REVIEW
Aldara Martin Alonso, Sejal Saglani
Although a rare disease, severe therapy-resistant asthma in children is a cause of significant morbidity and results in utilization of approximately 50% of health-care resources for asthma. Improving control for children with severe asthma is, therefore, an urgent unmet clinical need. As a group, children with severe asthma have severe and multiple allergies, steroid resistant airway eosinophilia, and significant structural changes of the airway wall (airway remodeling). Omalizumab is currently the only add-on therapy that is licensed for use in children with severe asthma...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28724573/a-single-dose-of-peripherally-infused-egfrviii-directed-car-t-cells-mediates-antigen-loss-and-induces-adaptive-resistance-in-patients-with-recurrent-glioblastoma
#15
Donald M O'Rourke, MacLean P Nasrallah, Arati Desai, Jan J Melenhorst, Keith Mansfield, Jennifer J D Morrissette, Maria Martinez-Lage, Steven Brem, Eileen Maloney, Angela Shen, Randi Isaacs, Suyash Mohan, Gabriela Plesa, Simon F Lacey, Jean-Marc Navenot, Zhaohui Zheng, Bruce L Levine, Hideho Okada, Carl H June, Jennifer L Brogdon, Marcela V Maus
We conducted a first-in-human study of intravenous delivery of a single dose of autologous T cells redirected to the epidermal growth factor receptor variant III (EGFRvIII) mutation by a chimeric antigen receptor (CAR). We report our findings on the first 10 recurrent glioblastoma (GBM) patients treated. We found that manufacturing and infusion of CAR-modified T cell (CART)-EGFRvIII cells are feasible and safe, without evidence of off-tumor toxicity or cytokine release syndrome. One patient has had residual stable disease for over 18 months of follow-up...
July 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28724397/partial-uniparental-isodisomy-of-chromosome-16-unmasks-a-deleterious-biallelic-mutation-in-ift140-that-causes-mainzer-saldino-syndrome
#16
Benjamin M Helm, Jason R Willer, Azita Sadeghpour, Christelle Golzio, Eric Crouch, Samantha Schrier Vergano, Nicholas Katsanis, Erica E Davis
BACKGROUND: The ciliopathies represent an umbrella group of >50 clinical entities that share both clinical features and molecular etiology underscored by structural and functional defects of the primary cilium. Despite the advances in gene discovery, this group of entities continues to pose a diagnostic challenge, in part due to significant genetic and phenotypic heterogeneity and variability. We consulted a pediatric case from asymptomatic, non-consanguineous parents who presented as a suspected ciliopathy due to a constellation of retinal, renal, and skeletal findings...
July 19, 2017: Human Genomics
https://www.readbyqxmd.com/read/28724173/a-comparative-study-between-myo-inositol-and-metformin-in-the-treatment-of-insulin-resistant-women
#17
K Nas, L Tűű
OBJECTIVE: Insulin resistance (IR) is a common disorder, which can impair female fertility and is characterized by phenotypic heterogeneity. Life-style treatment and insulin sensitizers are commonly used in the management of women with IR and consequent hyperinsulinemia, in order to restore the normal endocrinological and clinical parameters. Metformin (MET) is considered one of the first approaches to this pathology but new evidences are showing promising results using myo-inositol (MYO) in the management of this pathology...
June 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28723940/modeling-the-dynamics-of-chromosomal-alteration-progression-in-cervical-cancer-a-computational-model
#18
Augusto Cabrera-Becerril, Cruz Vargas-De-León, Sergio Hernández, Pedro Miramontes, Raúl Peralta
Computational modeling has been applied to simulate the heterogeneity of cancer behavior. The development of Cervical Cancer (CC) is a process in which the cell acquires dynamic behavior from non-deleterious and deleterious mutations, exhibiting chromosomal alterations as a manifestation of this dynamic. To further determine the progression of chromosomal alterations in precursor lesions and CC, we introduce a computational model to study the dynamics of deleterious and non-deleterious mutations as an outcome of tumor progression...
2017: PloS One
https://www.readbyqxmd.com/read/28723629/stat3-mutation-impacts-biological-and-clinical-features-of-t-lgl-leukemia
#19
Antonella Teramo, Gregorio Barilà, Giulia Calabretto, Chiara Ercolin, Thierry Lamy, Aline Moignet, Mikael Roussel, Cédric Pastoret, Matteo Leoncin, Cristina Gattazzo, Anna Cabrelle, Elisa Boscaro, Sara Teolato, Elisa Pagnin, Tamara Berno, Elena De March, Monica Facco, Francesco Piazza, Livio Trentin, Gianpietro Semenzato, Renato Zambello
STAT3 mutations have been described in 30-40% of T-large granular lymphocyte (T-LGL) leukemia patients, leading to STAT3 pathway activation. Considering the heterogeneity of the disease and the several immunophenotypes that LGL clone may express, the aim of this work was to evaluate whether STAT3 mutations might be associated with a distinctive LGL immunophenotype and/or might be indicative for specific clinical features.Our series of cases included a pilot cohort of 101 T-LGL leukemia patients (68 CD8+/CD4- and 33 CD4+/CD8±) from Padua Hematology Unit (Italy) and a validation cohort of additional 20 patients from Rennes Hematology Unit (France)...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723472/human-prostate-tissue-derived-extracellular-matrix-as-a-model-of-prostate-microenvironment
#20
Walter Cazzaniga, Manuela Nebuloni, Erika Longhi, Irene Locatelli, Raffaele Allevi, Roberta Lucianò, Gelsomina Senatore, Eugenio Ventimiglia, Vito Cucchiara, Luca Genovese, Francesco Montorsi, Massimo Alfano, Andrea Salonia, Ilaria Cavarretta
BACKGROUND: Clinical experience highlights the wide heterogeneity of primary prostate cancer (PPCa), even when potentially related to the same grade and stage. Currently available prediction tools and biomarkers do not always allow for early recognition of PPCa aggressive phenotype, sometimes making it impossible to distinguish among men harbouring indolent tumours or life-threatening disease. OBJECTIVE: To establish a novel ex vivo/in vitro model suitable to estimate the invasive phenotype of PPCa cells (PPCaC)...
October 2016: European Urology Focus
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