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https://www.readbyqxmd.com/read/29330206/evolution-of-cytogenetically-normal-acute-myeloid-leukemia-during-therapy-and-relapse-an-exome-sequencing-study-of-50-patients
#1
Philipp A Greif, Luise Hartmann, Sebastian Vosberg, Sophie Stief, Raphael Mattes, Ines Hellmann, Klaus H Metzeler, Tobias Herold, Stefanos Bamopoulos, Paul Kerbs, Vindi Jurinovic, Daniela Schumacher, Friederike Pastore, Kathrin Bräundl, Evelyn Zellmeier, Bianka Ksienzyk, Nikola Konstandin, Stephanie Schneider, Alexander Graf, Stefan Krebs, Helmut Blum, Martin Neumann, Claudia Baldus, Stefan K Bohlander, Stephan Wolf, Dennis Goerlich, Wolfgang E Berdel, Bernhard J Woermann, Wolfgang Hiddemann, Karsten Spiekermann
PURPOSE: To study mechanisms of therapy-resistance and disease progression, we analyzed the evolution of cytogenetically normal acute myeloid leukemia (CN-AML) based on somatic alterations. EXPERIMENTAL DESIGN: We performed exome-sequencing of matched diagnosis, remission and relapse samples from 50 CN-AML patients treated with intensive chemotherapy. Mutation patterns were correlated with clinical parameters. RESULTS: Evolutionary patterns correlated with clinical outcome...
January 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29328674/new-insights-on-ecosystem-mercury-cycling-revealed-by-stable-isotopes-of-mercury-in-water-flowing-from-a-headwater-peatland-catchment
#2
Glenn Woerndle, Martin Tsz-Ki Tsui, Stephen Sebestyen, Joel D Blum, Xiangping Nie, Randall K Kolka
Stable isotope compositions of mercury (Hg) were measured in the outlet stream and in soil cores at different landscape positions in a 9.7-ha boreal upland-peatland catchment in northern Minnesota. An acidic permanganate/persulfate digestion procedure was validated for water samples with high dissolved organic matter (DOM) concentrations and we verified the complete breakdown of DOM through Hg spike addition analysis. We report a relatively large variation in mass-dependent fractionation (δ202Hg; from -2.12 to -1...
January 12, 2018: Environmental Science & Technology
https://www.readbyqxmd.com/read/29327671/tissue-engineered-heart-valves-a-call-for-mechanistic-studies
#3
Kevin Blum, Joseph Drews, Christopher K Breuer
Heart valve disease carries a substantial risk of morbidity and mortality. Outcomes are significantly improved by valve replacement, but currently-available mechanical and biological replacement valves are associated with complications of their own. Mechanical valves have a high rate of thromboembolism and require lifelong anticoagulation. Biological prosthetic valves have a much shorter lifespan, and are prone to tearing and degradation. Both types of valves lack the capacity for growth, making them particularly problematic in pediatric patients...
January 12, 2018: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/29325054/dehydration-survival-of-crop-plants-and-its-measurement
#4
Abraham Blum, Roberto Tuberosa
Dehydration survival under drought stress is defined in this review as the transition from plant activity into a quiescent state of life preservation, which will be terminated by either recovery or death, depending on the stress regime and the plant's resilience. Dehydration survival is a popular phenotype by which functional genomics attempts to test gene function in drought resistance and survival. The available reports on phenotyping and genotyping of dehydration survival in genomic studies indicate that the measurement of this trait is often biased to the extent that misguided interpretations are likely to occur...
January 8, 2018: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29324475/bilateral-cochlear-implants-maximizing-expected-outcomes
#5
Kate E Willis, Nathan J Blum, Stephanie A Waryasz, Marilyn Augustyn
Sonia is a 4 1/12-year-old girl with Waardenburg syndrome and bilateral sensorineural hearing loss who had bilateral cochlear implants at 2 7/12 years of age. She is referred to Developmental-Behavioral Pediatrics by her speech/language pathologist because of concerns that her language skills are not progressing as expected after the cochlear implant. At the time of the implant, she communicated using approximately 20 signs and 1 spoken word (mama). At the time of the evaluation (18 months after the implant) she had approximately 70 spoken words (English and Spanish) and innumerable signs that she used to communicate...
January 10, 2018: Journal of Developmental and Behavioral Pediatrics: JDBP
https://www.readbyqxmd.com/read/29323558/optimizing-delivery-of-hiv-preexposure-prophylaxis-for-women-in-the-united-states
#6
Erika Aaron, Cori Blum, Dominika Seidman, Mary Jo Hoyt, Joanne Simone, Meg Sullivan, Dawn K Smith
Preexposure prophylaxis (PrEP) is a highly effective HIV prevention method; however, it is underutilized among women who are at risk for acquisition of HIV. Women comprise one in five HIV diagnoses in the United States, and significant racial disparities in new HIV diagnoses persist. The rate of new HIV diagnoses among black and African American women in 2015 was 16 times greater than that of white women. These disparities highlight the importance of HIV prevention strategies for women, including the use of PrEP...
January 2018: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/29317620/experimental-noise-cutoff-boosts-inferability-of-transcriptional-networks-in-large-scale-gene-deletion-studies
#7
C F Blum, N Heramvand, A S Khonsari, M Kollmann
Generating a comprehensive map of molecular interactions in living cells is difficult and great efforts are undertaken to infer molecular interactions from large-scale perturbation experiments. Here, we develop the analytical and numerical tools to quantify the fundamental limits for inferring transcriptional networks from gene knockout screens and introduce a network inference method that is unbiased with respect to measurement noise and scalable to large network sizes. We show that network asymmetry, knockout coverage and measurement noise are central determinants that limit prediction accuracy, whereas the knowledge about gene-specific variability among biological replicates can be used to eliminate noise-sensitive nodes and thereby boost the performance of network inference algorithms...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29316800/pro-dopamine-regulator-kb220z-attenuates-hoarding-and-shopping-behavior-in-a-female-diagnosed-with-sud-and-adhd
#8
Thomas McLaughlin, Kenneth Blum, Bruce Steinberg, Edward J Modestino, Lyle Fried, David Baron, David Siwicki, Eric R Braverman, Rajendra D Badgaiyan
Background Addictive-like behaviors (e.g., hoarding and shopping) may be the result of the cumulative effects of dopaminergic and other neurotransmitter genetic variants as well as elevated stress levels. We, therefore, propose that dopamine homeostasis may be the preferred goal in combating such challenging and unwanted behaviors, when simple dopaminergic activation through potent agonists may not provide any resolution. Case presentation C.J. is a 38-year-old, single, female, living with her mother. She has a history of substance use disorder as well as attention deficit hyperactivity disorder, inattentive type...
January 10, 2018: Journal of Behavioral Addictions
https://www.readbyqxmd.com/read/29315435/femtosecond-lenticule-extraction-flex-for-spherocylindrical-hyperopia-using-new-profiles
#9
Walter Sekundo, Anke Messerschmidt-Roth, Dan Z Reinstein, Timothy J Archer, Marcus Blum
PURPOSE: To investigate new lenticule profiles for the treatment of hyperopia by femtosecond lenticule extraction (FLEx) for spherocylindrical hyperopia using a modified laser scan sequence. METHODS: In this prospective 9-month study, 39 eyes of 22 patients with the mean age of 49 years (range: 27 to 56 years) underwent hyperopic FLEx. The mean optical zone was 6 mm (range: 5.75 to 6.75 mm) with keratometry readings and magnitude of correction adjusted mean transition zone of 2...
January 1, 2018: Journal of Refractive Surgery
https://www.readbyqxmd.com/read/29315423/impaired-ability-to-grow-colonies-of-endothelial-stem-cells-could-be-the-mechanism-explaining-the-high-cardiovascular-morbidity-and-mortality-of-patients-with-depression
#10
A Blum, N Pastukh, I Zaroura, J Rotem, F Kamal
No abstract text is available yet for this article.
January 5, 2018: QJM: Monthly Journal of the Association of Physicians
https://www.readbyqxmd.com/read/29313490/replication-study-transcriptional-amplification-in-tumor-cells-with-elevated-c-myc
#11
L Michelle Lewis, Meredith C Edwards, Zachary R Meyers, C Conover Talbot, Haiping Hao, David Blum, Elizabeth Iorns, Rachel Tsui, Alexandria Denis, Nicole Perfito, Timothy M Errington
As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Blum et al., 2015), that described how we intended to replicate selected experiments from the paper 'Transcriptional amplification in tumor cells with elevated c-Myc' (Lin et al., 2012). Here we report the results. We found overexpression of c-Myc increased total levels of RNA in P493-6 Burkitt's lymphoma cells; however, while the effect was in the same direction as the original study (Figure 3E; Lin et al., 2012), statistical significance and the size of the effect varied between the original study and the two different lots of serum tested in this replication...
January 9, 2018: ELife
https://www.readbyqxmd.com/read/29306762/microfluidic-platform-for-single-cell-analysis-under-dynamic-spatial-and-temporal-stimulation
#12
Jiyoung Song, Hyunryul Ryu, Minhwan Chung, Youngtaek Kim, Yannick Blum, Sung Sik Lee, Olivier Pertz, Noo Li Jeon
Recent research on cellular responses is shifting from static observations recorded under static stimuli to real-time monitoring in a dynamic environment. Since cells sense and interact with their surrounding microenvironment, an experimental platform where dynamically changing cellular microenvironments should be recreated in vitro. There has been a lack of microfluidic devices to support spatial and temporal stimulations in a simple and robust manner. Here, we describe a microfluidic device that generates dynamic chemical gradients and pulses in both space and time using a single device...
December 27, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29304333/tyrosine-1-of-rna-polymerase-ii-ctd-controls-global-termination-of-gene-transcription-in-mammals
#13
Nilay Shah, Muhammad Ahmad Maqbool, Yousra Yahia, Amal Zine El Aabidine, Cyril Esnault, Ignasi Forné, Tim-Michael Decker, David Martin, Roland Schüller, Stefan Krebs, Helmut Blum, Axel Imhof, Dirk Eick, Jean-Christophe Andrau
The carboxy-terminal domain (CTD) of RNA polymerase (Pol) II is composed of a repetition of YSPTSPS heptads and functions as a loading platform for protein complexes that regulate transcription, splicing, and maturation of RNAs. Here, we studied mammalian CTD mutants to analyze the function of tyrosine1 residues in the transcription cycle. Mutation of 3/4 of the tyrosine residues (YFFF mutant) resulted in a massive read-through transcription phenotype in the antisense direction of promoters as well as in the 3' direction several hundred kilobases downstream of genes...
January 4, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29299361/preoperative-accuracy-of-gastric-cancer-staging-in-patient-selection-for-preoperative-therapy-race-may-affect-accuracy-of-endoscopic-ultrasonography
#14
Naruhiko Ikoma, Jeffrey H Lee, Manoop S Bhutani, William A Ross, Brian Weston, Yi-Ju Chiang, Mariela A Blum, Tara Sagebiel, Catherine E Devine, Aurelio Matamoros, Keith Fournier, Paul Mansfield, Jaffer A Ajani, Brian D Badgwell
Background: Over the last 15 years, large randomized controlled studies have validated the benefit of preoperative therapy for patients with resectable gastric cancer. Computed tomography (CT) and endoscopic ultrasonography (EUS) are commonly used to select patients for preoperative treatment, but studies of preoperative staging accuracy that focus on patient selection for preoperative therapy are rare; therefore, whether CT or EUS can reliably identify patients eligible for preoperative therapy is still unclear...
December 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29299246/toward-a-methodical-framework-for-comprehensively-assessing-forest-multifunctionality
#15
Stefan Trogisch, Andreas Schuldt, Jürgen Bauhus, Juliet A Blum, Sabine Both, François Buscot, Nadia Castro-Izaguirre, Douglas Chesters, Walter Durka, David Eichenberg, Alexandra Erfmeier, Markus Fischer, Christian Geißler, Markus S Germany, Philipp Goebes, Jessica Gutknecht, Christoph Zacharias Hahn, Sylvia Haider, Werner Härdtle, Jin-Sheng He, Andy Hector, Lydia Hönig, Yuanyuan Huang, Alexandra-Maria Klein, Peter Kühn, Matthias Kunz, Katrin N Leppert, Ying Li, Xiaojuan Liu, Pascal A Niklaus, Zhiqin Pei, Katherina A Pietsch, Ricarda Prinz, Tobias Proß, Michael Scherer-Lorenzen, Karsten Schmidt, Thomas Scholten, Steffen Seitz, Zhengshan Song, Michael Staab, Goddert von Oheimb, Christina Weißbecker, Erik Welk, Christian Wirth, Tesfaye Wubet, Bo Yang, Xuefei Yang, Chao-Dong Zhu, Bernhard Schmid, Keping Ma, Helge Bruelheide
Biodiversity-ecosystem functioning (BEF) research has extended its scope from communities that are short-lived or reshape their structure annually to structurally complex forest ecosystems. The establishment of tree diversity experiments poses specific methodological challenges for assessing the multiple functions provided by forest ecosystems. In particular, methodological inconsistencies and nonstandardized protocols impede the analysis of multifunctionality within, and comparability across the increasing number of tree diversity experiments...
December 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/29296913/clinicopathologic-consensus-study-of-gray-zone-lymphoma-with-features-intermediate-between-dlbcl-and-classical-hl
#16
Monika Pilichowska, Stefania Pittaluga, Judith A Ferry, Jessica Hemminger, Hong Chang, Jennifer A Kanakry, Laurie H Sehn, Tatyana Feldman, Jeremy S Abramson, Athena Kritharis, Francisco J Hernandez-Ilizaliturri, Izidore S Lossos, Oliver W Press, Timothy S Fenske, Jonathan W Friedberg, Julie M Vose, Kristie A Blum, Deepa Jagadeesh, Bruce Woda, Gaurav K Gupta, Randy D Gascoyne, Elaine S Jaffe, Andrew M Evens
Gray zone lymphoma (GZL) is described as sharing features with classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). However, there remains complexity in establishing diagnosis, delineating prognosis, and determining optimum therapy. Sixty-eight cases diagnosed as GZL across 15 North American academic centers were evaluated by central pathology review to achieve consensus. Of these, only 26 (38%) were confirmed as GZL. Morphology was critical to GZL consensus diagnosis (eg, tumor cell richness); immunohistochemistry showed universal B-cell derivation, frequent CD30 expression, and rare Epstein-Barr virus (EBV) positivity (CD20+, 83%; PAX5+, 100%; BCL6+, 20%; MUM1+, 100%; CD30+, 92%; EBV+, 4%)...
December 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296820/cumulative-incidence-risk-factors-and-management-of-atrial-fibrillation-in-patients-receiving-ibrutinib
#17
Tracy E Wiczer, Lauren B Levine, Jessica Brumbaugh, Jessica Coggins, Qiuhong Zhao, Amy S Ruppert, Kerry Rogers, Anli McCoy, Luay Mousa, Avirup Guha, Nyla A Heerema, Kami Maddocks, Beth Christian, Leslie A Andritsos, Samantha Jaglowski, Steven Devine, Robert Baiocchi, Jennifer Woyach, Jeffrey Jones, Michael Grever, Kristie A Blum, John C Byrd, Farrukh T Awan
Atrial fibrillation (AF) has been reported in up to 16% of patients taking ibrutinib. Data regarding the management of AF in this patient population are limited, and stroke prevention poses a challenge because of increased risk of bleeding with ibrutinib treatment. Our study sought to describe the incidence of AF in adult patients treated with ibrutinib for a hematologic malignancy, assess management strategies, evaluate stroke and bleeding outcomes, and identify risk factors for occurrence. Of 582 patients treated with ibrutinib, 76 developed AF...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296799/near-tetraploidy-is-associated-with-richter-transformation-in-chronic-lymphocytic-leukemia-patients-receiving-ibrutinib
#18
Cecelia R Miller, Amy S Ruppert, Nyla A Heerema, Kami J Maddocks, Jadwiga Labanowska, Heather Breidenbach, Gerard Lozanski, Weiqiang Zhao, Amber L Gordon, Jeffrey A Jones, Joseph M Flynn, Samantha M Jaglowski, Leslie A Andritsos, Kristie A Blum, Farrukh T Awan, Kerry A Rogers, Michael R Grever, Amy J Johnson, Lynne V Abruzzo, Erin K Hertlein, James S Blachly, Jennifer A Woyach, John C Byrd
Ibrutinib is a highly effective targeted therapy for chronic lymphocytic leukemia (CLL). However, ibrutinib must be discontinued in a subset of patients due to progressive CLL or transformation to aggressive lymphoma (Richter transformation). Transformation occurs early in the course of therapy and has an extremely poor prognosis. Thus, identification of prognostic markers associated with transformation is of utmost importance. Near-tetraploidy (4 copies of most chromosomes within a cell) has been reported in various lymphomas, but its incidence and significance in CLL has not been described...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295989/amphiphilic-nanocarrier-induced-modulation-of-plk1-and-mir-34a-leads-to-improved-therapeutic-response-in-pancreatic-cancer
#19
Hadas Gibori, Shay Eliyahu, Adva Krivitsky, Dikla Ben-Shushan, Yana Epshtein, Galia Tiram, Rachel Blau, Paula Ofek, Joo Sang Lee, Eytan Ruppin, Limor Landsman, Iris Barshack, Talia Golan, Emmanuelle Merquiol, Galia Blum, Ronit Satchi-Fainaro
The heterogeneity of pancreatic ductal adenocarcinoma (PDAC) suggests that successful treatment might rely on simultaneous targeting of multiple genes, which can be achieved by RNA interference-based therapeutic strategies. Here we show a potent combination of microRNA and siRNA delivered by an efficient nanocarrier to PDAC tumors. Using proteomic-microRNA profiles and survival data of PDAC patients from TCGA, we found a novel signature for prolonged survival. Accordingly, we used a microRNA-mimic to increase miR-34a together with siRNA to silence PLK1 oncogene...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29282307/cutting-edge-low-affinity-tcrs-support-regulatory-t-cell-function-in-autoimmunity
#20
Maran L Sprouse, Ivan Shevchenko, Marissa A Scavuzzo, Faith Joseph, Thomas Lee, Samuel Blum, Malgorzata Borowiak, Matthew L Bettini, Maria Bettini
Regulatory T cells (Tregs) use a distinct TCR repertoire and are more self-reactive compared with conventional T cells. However, the extent to which TCR affinity regulates the function of self-reactive Tregs is largely unknown. In this study, we used a two-TCR model to assess the role of TCR affinity in Treg function during autoimmunity. We observed that high- and low-affinity Tregs were recruited to the pancreas and contributed to protection from autoimmune diabetes. Interestingly, high-affinity cells preferentially upregulated the TCR-dependent Treg functional mediators IL-10, TIGIT, GITR, and CTLA4, whereas low-affinity cells displayed increased transcripts for Areg and Ebi3, suggesting distinct functional profiles...
December 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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