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https://www.readbyqxmd.com/read/29682192/-atm-rb1-mutations-predict-shorter-overall-survival-in-urothelial-cancer
#1
Ming Yin, Petros Grivas, Hamid Emamekhoo, Prateek Mendiratta, Siraj Ali, JoAnn Hsu, Monali Vasekar, Joseph J Drabick, Sumanta Pal, Monika Joshi
Background: Mutations of DNA repair genes, e.g. ATM/RB1 , are frequently found in urothelial cancer (UC) and have been associated with better response to cisplatin-based chemotherapy. Further external validation of the prognostic value of ATM/RB1 mutations in UC can inform clinical decision making and trial designs. Results: In the discovery dataset, ATM/RB1 mutations were present in 24% of patients and were associated with shorter OS (adjusted HR 2.67, 95% CI, 1...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29675953/stimulus-presentation-order-in-receptive-identification-tasks-a-systematic-replication
#2
Kiley A Schneider, Bailey Devine, Gabriella Aguilar, Anna Ingeborg Petursdottir
Conflicting recommendations exist in the literature regarding the optimal order of stimulus presentation when teaching auditory-visual conditional discriminations. The present study examined the generality of a previously demonstrated advantage of presenting the auditory sample before visual comparisons (sample-first condition) over the reverse sequence (comparison-first condition). Participants were four typically developing 5- and 6-year-old boys. The procedures of Petursdottir and Aguilar (2016) were systematically replicated with the addition of a prompted error correction trial following each incorrect response...
April 19, 2018: Journal of Applied Behavior Analysis
https://www.readbyqxmd.com/read/29670758/remote-biomonitoring-of-temperatures-in-mothers-and-newborns-design-development-and-testing-of-a-wearable-sensor-device-in-a-tertiary-care-hospital-in-southern-india
#3
Prem K Mony, Prashanth Thankachan, Swarnarekha Bhat, Suman Rao, Maryann Washington, Sumi Antony, Annamma Thomas, Sheela C Nagarajarao, Hiteshwar Rao, Bharadwaj Amrutur
Objective: Newer technologies such as wearables, sensors, mobile telephony and computing offer opportunities to monitor vital physiological parameters and tackle healthcare problems, thereby improving access and quality of care. We describe the design, development and testing of a wearable sensor device for remote biomonitoring of body temperatures in mothers and newborns in southern India. Methods: Based on client needs and technological requirements, a wearable sensor device was designed and developed using principles of 'social innovation' design...
April 2018: BMJ Innovations
https://www.readbyqxmd.com/read/29670544/dynamic-alterations-in-salivary-microbiota-related-to-dental-caries-and-age-in-preschool-children-with-deciduous-dentition-a-2-year-follow-up-study
#4
Lei Xu, Xi Chen, Yuan Wang, Wen Jiang, Sa Wang, Zongxin Ling, Hui Chen
Dynamic alterations in oral microbiota are closely related to the development of dental caries;however, changes in salivary microbiota during this process have not been extensively studied. In addition, increasing evidence suggests that oral microbiome profiles differ according to dentition stages, but it is unclear whether they change with age during the same dentition, such as deciduous dentition. These two aspects were investigated in a 2-year follow-up study, and caries-free preschool children with complete deciduous dentition were enrolled...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29666338/identification-of-ssr-and-retrotransposon-based-molecular-markers-linked-to-morphological-characters-in-oily-sunfl-ower-helianthus-annuus-l-under-natural-and-water-limited-states
#5
Soleimani Gezeljeh Ali, Reza Darvishzadeh, Asa Ebrahimi, Mohammad Reza Bihamta
Sunflower is an important source of edible oil. Drought is known as an important factor limiting the growth and productivity of field crops in most parts of the world. Agricultural biotechnology mainly aims at developing crops with higher tolerance to the challenging environmental conditions, such as drought. This study examined a number of morphological characters, along with relative water content (RWC) in 100 inbred sunflower lines. A 10 × 10 simple lattice design with two replications was employed to measure the mentioned parameters under natural and water-limited states during two successive years...
March 2018: Journal of Genetics
https://www.readbyqxmd.com/read/29662167/sequencing-of-prostate-cancers-identifies-new-cancer-genes-routes-of-progression-and-drug-targets
#6
David C Wedge, Gunes Gundem, Thomas Mitchell, Dan J Woodcock, Inigo Martincorena, Mohammed Ghori, Jorge Zamora, Adam Butler, Hayley Whitaker, Zsofia Kote-Jarai, Ludmil B Alexandrov, Peter Van Loo, Charlie E Massie, Stefan Dentro, Anne Y Warren, Clare Verrill, Dan M Berney, Nening Dennis, Sue Merson, Steve Hawkins, William Howat, Yong-Jie Lu, Adam Lambert, Jonathan Kay, Barbara Kremeyer, Katalin Karaszi, Hayley Luxton, Niedzica Camacho, Luke Marsden, Sandra Edwards, Lucy Matthews, Valeria Bo, Daniel Leongamornlert, Stuart McLaren, Anthony Ng, Yongwei Yu, Hongwei Zhang, Tokhir Dadaev, Sarah Thomas, Douglas F Easton, Mahbubl Ahmed, Elizabeth Bancroft, Cyril Fisher, Naomi Livni, David Nicol, Simon Tavaré, Pelvender Gill, Christopher Greenman, Vincent Khoo, Nicholas Van As, Pardeep Kumar, Christopher Ogden, Declan Cahill, Alan Thompson, Erik Mayer, Edward Rowe, Tim Dudderidge, Vincent Gnanapragasam, Nimish C Shah, Keiran Raine, David Jones, Andrew Menzies, Lucy Stebbings, Jon Teague, Steven Hazell, Cathy Corbishley, Johann de Bono, Gerhardt Attard, William Isaacs, Tapio Visakorpi, Michael Fraser, Paul C Boutros, Robert G Bristow, Paul Workman, Chris Sander, Freddie C Hamdy, Andrew Futreal, Ultan McDermott, Bissan Al-Lazikani, Andrew G Lynch, G Steven Bova, Christopher S Foster, Daniel S Brewer, David E Neal, Colin S Cooper, Rosalind A Eeles
Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers...
April 16, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29659191/optimised-arid1a-immunohistochemistry-is-an-accurate-predictor-of-arid1a-mutational-status-in-gynaecological-cancers
#7
Saira Khalique, Kalnisha Naidoo, Ayoma D Attygalle, Divya Kriplani, Frances Daley, Anne Lowe, James Campbell, Thomas Jones, Michael Hubank, Kerry Fenwick, Nicholas Matthews, Alistair G Rust, Christopher J Lord, Susana Banerjee, Rachael Natrajan
ARID1A is a tumour suppressor gene that is frequently mutated in clear cell and endometrioid carcinomas of the ovary and endometrium and is an important clinical biomarker for novel treatment approaches for patients with ARID1A defects. However, the accuracy of ARID1A immunohistochemistry (IHC) as a surrogate for mutation status has not fully been established for patient stratification in clinical trials. Here we tested whether ARID1A immunohistochemistry could reliably predict ARID1A mutations identified by next-generation sequencing...
April 16, 2018: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/29658117/mapping-the-tumour-hla-ligandome-by-mass-spectrometry
#8
REVIEW
Lena Katharina Freudenmann, Ana Marcu, Stefan Stevanović
The entirety of HLA-presented peptides is referred to as the HLA ligandome of a cell or tissue, in tumours often termed immunopeptidome. Mapping the tumour immunopeptidome by mass spectrometry (MS) comprehensively views the pathophysiologically relevant antigenic signature of human malignancies. MS is an unbiased approach stringently filtering the candidates to be tested as opposed to epitope prediction algorithms. In the setting of peptide-specific immunotherapies, MS-based strategies significantly diminish the risk of lacking clinical benefit, as they yield highly enriched amounts of truly presented peptides...
April 15, 2018: Immunology
https://www.readbyqxmd.com/read/29657128/genomic-features-of-response-to-combination-immunotherapy-in-patients-with-advanced-non-small-cell-lung-cancer
#9
Matthew D Hellmann, Tavi Nathanson, Hira Rizvi, Benjamin C Creelan, Francisco Sanchez-Vega, Arun Ahuja, Ai Ni, Jacki B Novik, Levi M B Mangarin, Mohsen Abu-Akeel, Cailian Liu, Jennifer L Sauter, Natasha Rekhtman, Eliza Chang, Margaret K Callahan, Jamie E Chaft, Martin H Voss, Megan Tenet, Xue-Mei Li, Kelly Covello, Andrea Renninger, Patrik Vitazka, William J Geese, Hossein Borghaei, Charles M Rudin, Scott J Antonia, Charles Swanton, Jeff Hammerbacher, Taha Merghoub, Nicholas McGranahan, Alexandra Snyder, Jedd D Wolchok
Combination immune checkpoint blockade has demonstrated promising benefit in lung cancer, but predictors of response to combination therapy are unknown. Using whole-exome sequencing to examine non-small-cell lung cancer (NSCLC) treated with PD-1 plus CTLA-4 blockade, we found that high tumor mutation burden (TMB) predicted improved objective response, durable benefit, and progression-free survival. TMB was independent of PD-L1 expression and the strongest feature associated with efficacy in multivariable analysis...
April 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29643822/working-memory-and-reinforcement-schedule-jointly-determine-reinforcement-learning-in-children-potential-implications-for-behavioral-parent-training
#10
Elien Segers, Tom Beckers, Hilde Geurts, Laurence Claes, Marina Danckaerts, Saskia van der Oord
Introduction: Behavioral Parent Training (BPT) is often provided for childhood psychiatric disorders. These disorders have been shown to be associated with working memory impairments. BPT is based on operant learning principles, yet how operant principles shape behavior (through the partial reinforcement (PRF) extinction effect, i.e., greater resistance to extinction that is created when behavior is reinforced partially rather than continuously) and the potential role of working memory therein is scarcely studied in children...
2018: Frontiers in Psychology
https://www.readbyqxmd.com/read/29628515/state-of-the-antiretroviral-therapy-in-human-immunodeficiency-virus-drug-resistance-science-and-technology-knowledge-gap
#11
Charles A Boucher, Marina R Bobkova, Anna Maria Geretti, Chien-Ching Hung, Rolf Kaiser, Anne-Geneviève Marcelin, Adrian Streinu-Cercel, Jean van Wyk, Pat Dorr, Anne-Mieke Vandamme
Resistance to antiretroviral therapy (ART) threatens the efficacy of human immunodeficiency virus type 1 (HIV-1) treatment. We present a review of knowledge gaps in the science and technologies of acquired HIV-1 drug resistance (HIVDR) in an effort to facilitate research, scientific exchange, and progress in clinical management. The expert authorship of this review convened to identify data gaps that exist in the field of HIVDR and discuss their clinical implications. A subsequent literature review of trials and current practices was carried out to provide supporting evidence...
January 2018: AIDS Reviews
https://www.readbyqxmd.com/read/29626621/first-in-human-phase-i-study-of-ac0010-a-mutant-selective-egfr-inhibitor-in-non-small-cell-lung-cancer-safety-efficacy-and-potential-mechanism-of-resistance
#12
Yuxiang Ma, Xin Zheng, Hongyun Zhao, Wenfeng Fang, Yang Zhang, Jieying Ge, Lu Wang, Weicong Wang, Ji Jiang, Shaokun Chuai, Zhou Zhang, Wanhong Xu, Xiao Xu, Pei Hu, Li Zhang
INTRODUCTION: AC0010 is a mutation-selective, third-generation EGFR tyrosine kinase inhibitor (TKI). This first-in-human phase I trial determine the maximum tolerated dose (MTD), recommended phase II dose (RP2D), schedule, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of AC0010 in patients with advanced or recurrent NSCLC and acquired resistance to the first-generation EGFR-TKI. METHODS: Patients received escalating daily doses of AC0010 (50 to 600 mg) throughout 28-day cycles...
April 4, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29625879/tivantinib-for-second-line-treatment-of-met-high-advanced-hepatocellular-carcinoma-metiv-hcc-a-final-analysis-of-a-phase-3-randomised-placebo-controlled-study
#13
Lorenza Rimassa, Eric Assenat, Markus Peck-Radosavljevic, Marc Pracht, Vittorina Zagonel, Philippe Mathurin, Elena Rota Caremoli, Camillo Porta, Bruno Daniele, Luigi Bolondi, Vincenzo Mazzaferro, William Harris, Nevena Damjanov, Davide Pastorelli, María Reig, Jennifer Knox, Francesca Negri, Jörg Trojan, Carlos López López, Nicola Personeni, Thomas Decaens, Marie Dupuy, Wolfgang Sieghart, Giovanni Abbadessa, Brian Schwartz, Maria Lamar, Terri Goldberg, Dale Shuster, Armando Santoro, Jordi Bruix
BACKGROUND: Tivantinib (ARQ 197), a selective, oral MET inhibitor, improved overall survival and progression-free survival compared with placebo in a randomised phase 2 study in patients with high MET expression (MET-high) hepatocellular carcinoma previously treated with sorafenib. The aim of this phase 3 study was to confirm the results of the phase 2 trial. METHODS: We did a phase 3, randomised, double-blind, placebo-controlled study in 90 centres in Australia, the Americas, Europe, and New Zealand...
April 3, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29623931/associations-between-thromboxane-a-synthase-1-gene-polymorphisms-and-the-risk-of-ischemic-stroke-in-a-chinese-han-population
#14
Lei Li, Zhi-Yi He, Yan-Zhe Wang, Xu Liu, Li-Ying Yuan
Thromboxane A synthase 1 (TBXAS1) catalyses the synthesis of thromboxane A2 (TXA2), which plays an important role in the pathogenesis of ischemic stroke. Thus, the TBXAS1 gene was investigated as a candidate gene involved in the formation of atherosclerosis. This case-control study collected peripheral blood specimens and clinical data of 370 ischemic stroke patients and 340 healthy controls in the Northern Chinese Han population from October 2010 to May 2011. Two TBXAS1 single-nucleotide polymorphisms, rs2267682 and rs10487667, were analyzed using a SNaPshot Multiplex sequencing assay to explore the relationships between the single-nucleotide polymorphisms in TBXAS1 and ischemic stroke...
March 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29621994/the-pigeon-project-protocol-for-a-longitudinal-study-examining-psychosocial-behavioural-and-ethical-issues-and-outcomes-in-cancer-tumour-genomic-profiling
#15
Megan Best, Ainsley J Newson, Bettina Meiser, Ilona Juraskova, David Goldstein, Kathy Tucker, Mandy L Ballinger, Dominique Hess, Timothy E Schlub, Barbara Biesecker, Richard Vines, Kate Vines, David Thomas, Mary-Anne Young, Jacqueline Savard, Chris Jacobs, Phyllis Butow
BACKGROUND: Genomic sequencing in cancer (both tumour and germline), and development of therapies targeted to tumour genetic status, hold great promise for improvement of patient outcomes. However, the imminent introduction of genomics into clinical practice calls for better understanding of how patients value, experience, and cope with this novel technology and its often complex results. Here we describe a protocol for a novel mixed-methods, prospective study (PiGeOn) that aims to examine patients' psychosocial, cognitive, affective and behavioural responses to tumour genomic profiling and to integrate a parallel critical ethical analysis of returning results...
April 5, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29621291/fungal-community-profiles-in-agricultural-soils-of-a-long-term-field-trial-under-different-tillage-fertilization-and-crop-rotation-conditions-analyzed-by-high-throughput-its-amplicon-sequencing
#16
Loreen Sommermann, Joerg Geistlinger, Daniel Wibberg, Annette Deubel, Jessica Zwanzig, Doreen Babin, Andreas Schlüter, Ingo Schellenberg
Fungal communities in agricultural soils are assumed to be affected by soil and crop management. Our intention was to investigate the impact of different tillage and fertilization practices on fungal communities in a long-term crop rotation field trial established in 1992 in Central Germany. Two winter wheat fields in replicated strip-tillage design, comprising conventional vs. conservation tillage, intensive vs. extensive fertilization and different pre-crops (maize vs. rapeseed) were analyzed by a metabarcoding approach applying Illumina paired-end sequencing of amplicons generated by two recently developed primer pairs targeting the two fungal Internal Transcribed Spacer regions (ITS1, ITS2)...
2018: PloS One
https://www.readbyqxmd.com/read/29621254/il-13-receptors-as-possible-therapeutic-targets-in-diffuse-intrinsic-pontine-glioma
#17
Noah E Berlow, Matthew N Svalina, Michael J Quist, Teagan P Settelmeyer, Viktor Zherebitskiy, Mari Kogiso, Lin Qi, Yuchen Du, Cynthia E Hawkins, Esther Hulleman, Xiao-Nan Li, Sakir H Gultekin, Charles Keller
Diffuse intrinsic pontine glioma (DIPG) is a universally fatal childhood cancer of the brain. Despite the introduction of conventional chemotherapy and radiotherapy, improvements in survival have been marginal and long-term survivorship is uncommon. Thus, new targets for therapeutics are critically needed. Early phase clinical trials exploring molecularly-targeted therapies against the epidermal growth factor receptor (EGFR) and novel immunotherapies targeting interleukin receptor-13α2 (IL-13Rα2) have demonstrated activity in this disease...
2018: PloS One
https://www.readbyqxmd.com/read/29620007/ictal-spitting-in-non-dominant-temporal-lobe-epilepsy-an-anatomo-electrophysiological-correlation
#18
Marcos Quevedo-Diaz, Adrià Tauste Campo, Manel Vila-Vidal, Alessandro Principe, Miguel Ley, Rodrigo Rocamora
We report a patient presenting drug-resistant, non-dominant temporal lobe epilepsy with ictal spitting and prosopometamorphopsia, both extremely rare semiologies. Second-phase pre-surgical monitoring was performed using SEEG due to lesion-negative imaging and the rare semiology. The seizure onset zone was delimited to the right anterior hippocampus and the temporobasal cortex, with the propagation zone within the entorhinal cortex. Interestingly, direct electrical stimulation to the entorhinal cortex, which was reproduced in a number of trials, evoked spitting without leading to seizures or post-discharges...
April 5, 2018: Epileptic Disorders: International Epilepsy Journal with Videotape
https://www.readbyqxmd.com/read/29619799/low-carbohydrate-ketogenic-diet-impairs-anaerobic-exercise-performance-in-exercise-trained-women-and-men-a-randomized-sequence-crossover-trial
#19
Kymberly A Wroble, Morgan N Trott, George G Schweitzer, Rabia S Rahman, Patrick V Kelly, Edward P Weiss
BACKGROUND: Low-carbohydrate, ketogenic diets cause mild, sub-clinical systemic acidosis. Anaerobic exercise performance is limited by acidosis. Therefore, we evaluated the hypothesis that a low-carbohydrate, ketogenic diet impairs anaerobic exercise performance, as compared to a high-carbohydrate diet. METHODS: Sixteen men and women (BMI, 23±1 kg/m2, age 23±1 yr) participated in a randomized-sequence, counterbalanced crossover study in which they underwent exercise testing after four days of either a low-carbohydrate, ketogenic diet (LC; <50 g/day and <10% of energy from carbohydrates) or a high-carbohydrate diet (HC; 6-10 g/kg/day carbohydrate)...
April 4, 2018: Journal of Sports Medicine and Physical Fitness
https://www.readbyqxmd.com/read/29617755/soft-and-hard-tissue-changes-following-treatment-of-class-ii-division-1-malocclusion-with-activator-versus-trainer-a-randomized-controlled-trial
#20
Ghassan Idris, Mohammad Y Hajeer, Azzam Al-Jundi
Background: Increased awareness on the role of oral functions in the aetiology of Class II deformities has led to the wide spread of myofunctional training appliances as easy and possibly effective treatment for children with Class II malocclusion but their efficacy is yet to be proven. Objectives: To evaluate soft- and hard-tissue changes following 12 months of Class II division 1 treatment in growing patients with a conventional functional appliance (a modified Activator) versus a myofunctional Trainer system (T4K®)...
April 3, 2018: European Journal of Orthodontics
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