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Clinical genomics

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https://www.readbyqxmd.com/read/28822887/the-changing-diagnostic-pathway-for-lung-cancer-patients-in-shanghai-china
#1
REVIEW
Tao Jiang, Shengxiang Ren, Xuefei Li, Chunxia Su, Caicun Zhou, Mary O'Brien
Accumulating evidence suggest that patients with advanced non-small-cell lung cancer (NSCLC) and specific genomic alterations including epidermal growth factor receptor and microtubule-associated protein-like 4 anaplastic lymphoma kinase could significantly benefit from molecular-targeted therapies compared with chemotherapy. Recently, immunotherapy based on programmed cell death 1 (PD-1) and its ligand (PD-L1) blockade prolong survival in patients with advanced NSCLC, especially in those patients with positive expression of PD-L1 and when used in the first-line setting...
August 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28822857/exploring-associations-of-clinical-and-social-parameters-with-violent-behaviors-among-psychiatric-patients
#2
Hong-Jie Dai, Emily Chia-Yu Su, Mohy Uddin, Jitendra Jonnagaddala, Chi-Shin Wu, Shabbir Syed-Abdul
Evidence has revealed interesting associations of clinical and social parameters with violent behaviors of patients with psychiatric disorders. Men are more violent preceding and during hospitalization, whereas women are more violent than men throughout the 3 days following a hospital admission. It has also been proven that mental disorders may be a consistent risk factor for the occurrence of violence. In order to better understand violent behaviors of patients with psychiatric disorders, it is important to investigate both the clinical symptoms and psychosocial factors that accompany violence in these patients...
August 16, 2017: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/28822354/3d-brain-organoids-derived-from-pluripotent-stem-cells-promising-experimental-models-for-brain-development-and-neurodegenerative-disorders
#3
REVIEW
Chun-Ting Lee, Raphael M Bendriem, Wells W Wu, Rong-Fong Shen
Three-dimensional (3D) brain organoids derived from human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), appear to recapitulate the brain's 3D cytoarchitectural arrangement and provide new opportunities to explore disease pathogenesis in the human brain. Human iPSC (hiPSC) reprogramming methods, combined with 3D brain organoid tools, may allow patient-derived organoids to serve as a preclinical platform to bridge the translational gap between animal models and human clinical trials...
August 20, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28822237/beyond-genomics-targeting-the-epigenome-in-diffuse-large-b-cell-lymphoma
#4
REVIEW
Andrea Kühnl, David Cunningham, Ian Chau
After decades of intense research on genetic alterations in cancer and successful implementation of genetically-based targeted therapies, the field of cancer epigenetics is only beginning to be fully recognized. The discovery of frequent mutations in genes modifying the epigenome in diffuse large B-cell lymphoma (DLBCL) has highlighted the outstanding role of epigenetic deregulation in this disease. Identification of epigenetically-driven DLBCL subgroups and development of novel epigenetic drugs have rapidly advanced...
August 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28822012/mtor-co-targeting-strategies-for-head-and-neck-cancer-therapy
#5
Zhiyong Wang, Juan Callejas Valera, Xuefeng Zhao, Qianming Chen, J Silvio Gutkind
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. There is an urgent need to develop effective therapeutic approaches to prevent and treat HNSCC. Recent deep sequencing of the HNSCC genomic landscape revealed a multiplicity and diversity of genetic alterations in this malignancy. Although a large variety of specific molecules were found altered in each individual tumor, they all participate in only a handful of driver signaling pathways. Among them, the PI3K/mTOR pathway is the most frequently activated, which plays a central role in cancer initiation and progression...
August 18, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28821607/two-plant-derived-aporphinoid-alkaloids-exert-their-antifungal-activity-by-disrupting-mitochondrial-iron-sulfur-cluster-biosynthesis
#6
Siddharth K Tripathi, Tao Xu, Qin Feng, Bharathi Avula, Xiaomin Shi, Xuewen Pan, Melanie M Mask, Scott R Baerson, Melissa R Jacob, Ranga Rao Ravu, Shabana I Khan, Xing-Cong Li, Ikhlas A Khan, Alice M Clark, Ameeta K Agarwal
Eupolauridine and liriodenine are plant-derived aporphinoid alkaloids that exhibit potent inhibitory activity against the opportunistic fungal pathogens Candida albicans and Cryptococcus neoformans However, the molecular mechanism of this antifungal activity is unknown. In this study, we show that eupolauridine 9591 (E9591), a synthetic analog of eupolauridine, and liriodenine methiodide (LMT), a methiodide salt of liriodenine, mediate their antifungal activities by disrupting mitochondrial iron-sulfur (Fe-S) cluster synthesis...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821546/a-supervised-statistical-learning-approach-for-accurate-legionella-pneumophila-source-attribution-during-outbreaks
#7
Andrew H Buultjens, Kyra Y L Chua, Sarah L Baines, Jason Kwong, Wei Gao, Zoe Cutcher, Stuart Adcock, Susan Ballard, Mark B Schultz, Takehiro Tomita, Nela Subasinghe, Glen P Carter, Sacha J Pidot, Lucinda Franklin, Torsten Seemann, Anders Gonçalves Da Silva, Benjamin P Howden, Timothy P Stinear
Public health agencies are increasingly relying on genomics during Legionnaires' disease investigations. However, the causative bacterium (Legionella pneumophila) has an unusual population structure with extreme temporal and spatial genome sequence conservation. Furthermore, Legionnaires' disease outbreaks can be caused by multiple L. pneumophila genotypes in a single source. These factors can confound cluster identification using standard phylogenomic methods. Here, we show that a statistical learning approach based onL...
August 18, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28821281/white-blood-cell-dna-methylation-and-risk-of-breast-cancer-in-the-prostate-lung-colorectal-and-ovarian-cancer-screening-trial-plco
#8
Susan R Sturgeon, J Richard Pilsner, Kathleen F Arcaro, Kaoru Ikuma, Haotian Wu, Soon-Mi Kim, Nayha Chopra-Tandon, Adam R Karpf, Regina G Ziegler, Catherine Schairer, Raji Balasubramanian, David A Reckhow
BACKGROUND: Several studies have suggested that global DNA methylation in circulating white blood cells (WBC) is associated with breast cancer risk. METHODS: To address conflicting results and concerns that the findings for WBC DNA methylation in some prior studies may reflect disease effects, we evaluated the relationship between global levels of WBC DNA methylation in white blood cells and breast cancer risk in a case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) cohort...
August 18, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28821273/a-practical-guide-to-single-cell-rna-sequencing-for-biomedical-research-and-clinical-applications
#9
REVIEW
Ashraful Haque, Jessica Engel, Sarah A Teichmann, Tapio Lönnberg
RNA sequencing (RNA-seq) is a genomic approach for the detection and quantitative analysis of messenger RNA molecules in a biological sample and is useful for studying cellular responses. RNA-seq has fueled much discovery and innovation in medicine over recent years. For practical reasons, the technique is usually conducted on samples comprising thousands to millions of cells. However, this has hindered direct assessment of the fundamental unit of biology-the cell. Since the first single-cell RNA-sequencing (scRNA-seq) study was published in 2009, many more have been conducted, mostly by specialist laboratories with unique skills in wet-lab single-cell genomics, bioinformatics, and computation...
August 18, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28821267/small-size-recombinant-adenoviral-hexon-protein-fragments-for-the-production-of-virus-type-specific-antibodies
#10
Martin Pacesa, Rodinde Hendrickx, Manuela Bieri, Justin W Flatt, Urs F Greber, Silvio Hemmi
BACKGROUND: Adenoviruses are common pathogens infecting animals and humans. They are classified based on serology, or genome sequence information. These methods have limitations due to lengthy procedures or lack of infectivity data. Adenoviruses are easy to produce and amenable to genetic and biochemical modifications, which makes them a powerful tool for biological studies, and clinical gene-delivery and vaccine applications. Antibodies directed against adenoviral proteins are important diagnostic tools for virus identification in vivo and in vitro, and are used to elucidate infection mechanisms, often in combination with genomic sequencing and type specific information from hyper-variable regions of structural proteins...
August 18, 2017: Virology Journal
https://www.readbyqxmd.com/read/28821231/novel-mutations-in-pank2-and-pla2g6-genes-in-patients-with-neurodegenerative-disorders-two-case-reports
#11
Hassan Dastsooz, Hamid Nemati, Mohammad Ali Farazi Fard, Majid Fardaei, Mohammad Ali Faghihi
BACKGROUND: Neurodegeneration with brain iron accumulation (NBIA) is a genetically heterogeneous group of disorders associated with progressive impairment of movement, vision, and cognition. The disease is initially diagnosed on the basis of changes in brain magnetic resonance imaging which indicate an abnormal brain iron accumulation in the basal ganglia. However, the diagnosis of specific types should be based on both clinical findings and molecular genetic testing for genes associated with different types of NBIA, including PANK2, PLA2G6, C19orf12, FA2H, ATP13A2, WDR45, COASY, FTL, CP, and DCAF17...
August 18, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28820946/proteogenomic-investigation-of-strain-variation-in-clinical-mycobacterium-tuberculosis-isolates
#12
Tiaan Heunis, Anzaan Dippenaar, Robin M Warren, Paul D van Helden, Ruben G van der Merwe, Nicolaas C Gey van Pittius, Arnab Pain, Samantha L Sampson, David L Tabb
Mycobacterium tuberculosis consists of a large number of different strains that display unique virulence characteristics. Whole-genome sequencing has revealed substantial genetic diversity among clinical M. tuberculosis isolates, and elucidating the phenotypic variation encoded by this genetic diversity will be of utmost importance to fully understand M. tuberculosis biology and pathogenicity. In this study we integrated whole-genome sequencing and mass spectrometry (GeLC-MS/MS) to reveal strain-specific characteristics in the proteomes of two clinical M...
August 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28820087/reinstating-mycobacterium-massiliense-and-mycobacterium-bolletii-as-species-of-the-mycobacterium-abscessus-complex
#13
Toidi Adekambi, Mohamed Sassi, Jakko van Ingen, Michel Drancourt
TheMycobacterium abscessus complex is a group of rapidly growing, multiresistant mycobacteria previously divided into three species. Proposal for the union of Mycobacterium bolletii and Mycobacterium massiliense into one subspecies, so-called M. abscessus subsp. massiliense, created much confusion about the routine identification and reporting of M. abscessus clinical isolates for clinicians. Results derived from multigene sequencing unambiguously supported the reinstatement of M. massiliense and M. bolletii as species, culminating in the presence of erm(41)-encoded macrolide resistance in M...
August 18, 2017: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/28820000/novel-combination-strategies-for-enhancing-efficacy-of-immune-checkpoint-inhibitors-in-the-treatment-of-metastatic-solid-malignancies
#14
Michael J Flynn, James M G Larkin
Immune-checkpoint inhibitor (ICPI) drugs, which include antibodies against CTLA-4, PD-1 and PD-L1, have been shown to induce durable complete responses in a proportion of patients with particular efficacy demonstrated in both the first line and refractory setting in advanced NSCLC and melanoma. However, these drugs remain effective only in a minority of unselected patients. Areas covered: This review will focus on mechanisms of resistance to ICPI and underline the importance of identification of novel predictive markers of responsiveness...
August 18, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28819821/anti-pd-1-antibodies-as-a-therapeutic-strategy-in-classical-hodgkin-lymphoma
#15
REVIEW
Michael D Jain, John Kuruvilla
Classical Hodgkin lymphoma (cHL) is defined by malignant Reed-Sternberg (RS) cells that recruit non-malignant immune cells into a supportive tumour microenvironment. In cHL, this is driven, in part, by genomic alterations of the 9p24.1 locus encoding the immune checkpoint ligands PD-L1 and PD-L2. Therapeutic anti-PD-1 antibodies have been developed that competitively inhibit the interaction between PD-1 and its ligands. Clinical trials of anti-PD-1 antibodies in cHL demonstrate high overall response rates but relapses still occur and new clinical challenges exist for toxicity management and response assessment...
August 17, 2017: Drugs
https://www.readbyqxmd.com/read/28819692/molecular-characterization-of-atypical-antigenic-variants-of-canine-rabies-virus-reveals-its-reintroduction-by-wildlife-vectors-in-southeastern-mexico
#16
Fabiola Garcés-Ayala, Nidia Aréchiga-Ceballos, Joanna M Ortiz-Alcántara, Elizabeth González-Durán, Sandra I Pérez-Agüeros, Alfonso Méndez-Tenorio, Belem Torres-Longoria, Irma López-Martínez, Lucía Hernández-Rivas, José Alberto Díaz-Quiñonez, José Ernesto Ramírez-González
Rabies is an infectious viral disease that is practically always fatal following the onset of clinical signs. In Mexico, the last case of human rabies transmitted by dogs was reported in 2006 and canine rabies has declined significantly due to vaccination campaigns implemented in the country. Here we report on the molecular characterization of six rabies virus strains found in Yucatan and Chiapas, remarkably, four of them showed an atypical reaction pattern when antigenic characterization with a reduced panel of eight monoclonal antibodies was performed...
August 17, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28819569/a-study-on-il8rb-gene-polymorphism-as-a-potential-immuno-compromised-adherent-in-exaggeration-of-parenteral-and-mammo-crine-oxidative-stress-during-mastitis-in-buffalo
#17
S M El Nahas, A H El Kasas, A A Abou Mossallem, M I Abdelhamid, Mohamad Warda
The genetic markers in inflammatory responses during mastitis afford a reasonable way for improving milk production in the Egyptian buffalo breed. Among them is the interleukin 8 Receptor Gene (IL8RB) (CXCR2); a chemokine receptor gene augments the neutrophil migration during infection. To understand its role better during mastitis in Egyptian buffalos, twenty-five dairy animals representing the normal, sub-clinically, clinically and chronically affected buffalos were randomly selected from different districts...
November 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/28819308/an-optimal-mean-based-block-robust-feature-extraction-method-to-identify-colorectal-cancer-genes-with-integrated-data
#18
Jian Liu, Yuhu Cheng, Xuesong Wang, Lin Zhang, Hui Liu
It is urgent to diagnose colorectal cancer in the early stage. Some feature genes which are important to colorectal cancer development have been identified. However, for the early stage of colorectal cancer, less is known about the identity of specific cancer genes that are associated with advanced clinical stage. In this paper, we conducted a feature extraction method named Optimal Mean based Block Robust Feature Extraction method (OMBRFE) to identify feature genes associated with advanced colorectal cancer in clinical stage by using the integrated colorectal cancer data...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819158/discovering-condition-specific-gene-co-expression-patterns-using-gaussian-mixture-models-a-cancer-case-study
#19
Stephen P Ficklin, Leland J Dunwoodie, William L Poehlman, Christopher Watson, Kimberly E Roche, F Alex Feltus
A gene co-expression network (GCN) describes associations between genes and points to genetic coordination of biochemical pathways. However, genetic correlations in a GCN are only detectable if they are present in the sampled conditions. With the increasing quantity of gene expression samples available in public repositories, there is greater potential for discovery of genetic correlations from a variety of biologically interesting conditions. However, even if gene correlations are present, their discovery can be masked by noise...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819111/community-outbreaks-of-group-a-streptococcus-revealed-by-genome-sequencing
#20
Claire E Turner, Luke Bedford, Nicholas M Brown, Kim Judge, M Estée Török, Julian Parkhill, Sharon J Peacock
The frequent occurrence of disease outbreaks in humans caused by group A Streptococcus (GAS) is an on-going public health threat. Conventional bacterial typing methods lack the discriminatory power to confidently confirm or refute outbreaks in hospital and community settings. Microbial whole genome sequencing (WGS) provides a potential solution to this, but, there has been limited population-based surveillance with accompanying sequence data. We performed retrospective genomic surveillance of 93 clinical GAS isolates from individuals in a defined geographic region...
August 17, 2017: Scientific Reports
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