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https://www.readbyqxmd.com/read/28894388/bone-anchored-annular-closure-following-lumbar-discectomy-reduces-risk-of-complications-and-reoperations-within-90-days-of-discharge
#1
Peter Douglas Klassen, Derek Thomas Bernstein, Hans-Peter Köhler, Mark P Arts, Bradley Weiner, Larry E Miller, Claudius Thomé
PURPOSE: The purpose of this study was to evaluate perioperative complications of lumbar discectomy with or without bone-anchored annular closure device (ACD) implant in patients at high risk of recurrent disc herniation. METHODS: This was a post hoc analysis of a randomized controlled trial that compared outcomes of lumbar discectomy with or without additional placement of an ACD. Patients presented with imaging evidence of lumbar disc herniation and radicular pain that was unresponsive to conservative care...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28891793/regulation-of-the-glucocorticoid-receptor-via-a-bet-dependent-enhancer-drives-antiandrogen-resistance-in-prostate-cancer
#2
Neel Shah, Ping Wang, John Wongvipat, Wouter R Karthaus, Wassim Abida, Joshua Armenia, Shira Rockowitz, Yotam Drier, Bradley E Bernstein, Henry W Long, Matthew L Freedman, Vivek K Arora, Deyou Zheng, Charles L Sawyers
In prostate cancer, resistance to the antiandrogen enzalutamide (Enz) can occur through bypass of androgen receptor (AR) blockade by the glucocorticoid receptor (GR). In contrast to fixed genomic alterations, here we show that GR-mediated antiandrogen resistance is adaptive and reversible due to regulation of GR expression by a tissue-specific enhancer. GR expression is silenced in prostate cancer by a combination of AR binding and EZH2-mediated repression at the GR locus, but is restored in advanced prostate cancers upon reversion of both repressive signals...
September 11, 2017: ELife
https://www.readbyqxmd.com/read/28818518/seladelpar-mbx-8025-a-selective-ppar-%C3%AE-agonist-in-patients-with-primary-biliary-cholangitis-with-an-inadequate-response-to-ursodeoxycholic-acid-a-double-blind-randomised-placebo-controlled-phase-2-proof-of-concept-study
#3
David Jones, Pol F Boudes, Mark G Swain, Christopher L Bowlus, Michael R Galambos, Bruce R Bacon, Yvonne Doerffel, Norman Gitlin, Stuart C Gordon, Joseph A Odin, David Sheridan, Markus-Alexander Wörns, Virginia Clark, Linsey Corless, Heinz Hartmann, Mark E Jonas, Andreas E Kremer, George F Mells, Peter Buggisch, Bradley L Freilich, Cynthia Levy, John M Vierling, David E Bernstein, Marek Hartleb, Ewa Janczewska, Fedja Rochling, Hemant Shah, Mitchell L Shiffman, John H Smith, Yun-Jung Choi, Alexandra Steinberg, Monika Varga, Harinder Chera, Robert Martin, Charles A McWherter, Gideon M Hirschfield
BACKGROUND: Many patients with primary biliary cholangitis have an inadequate response to first-line therapy with ursodeoxycholic acid. Seladelpar is a potent, selective agonist for the peroxisome proliferator-activated receptor-delta (PPAR-δ), which is implicated in bile acid homoeostasis. This first-in-class study evaluated the anti-cholestatic effects and safety of seladelpar in patients with an inadequate response to ursodeoxycholic acid. METHODS: The study was a 12-week, double-blind, placebo-controlled, phase 2 trial of patients with alkaline phosphatase of at least 1·67 times the upper limit of normal (ULN) despite treatment with ursodeoxycholic acid...
August 14, 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28753427/a-genetic-variant-associated-with-five-vascular-diseases-is-a-distal-regulator-of-endothelin-1-gene-expression
#4
Rajat M Gupta, Joseph Hadaya, Aditi Trehan, Seyedeh M Zekavat, Carolina Roselli, Derek Klarin, Connor A Emdin, Catharina R E Hilvering, Valerio Bianchi, Christian Mueller, Amit V Khera, Russell J H Ryan, Jesse M Engreitz, Robbyn Issner, Noam Shoresh, Charles B Epstein, Wouter de Laat, Jonathan D Brown, Renate B Schnabel, Bradley E Bernstein, Sekar Kathiresan
Genome-wide association studies (GWASs) implicate the PHACTR1 locus (6p24) in risk for five vascular diseases, including coronary artery disease, migraine headache, cervical artery dissection, fibromuscular dysplasia, and hypertension. Through genetic fine mapping, we prioritized rs9349379, a common SNP in the third intron of the PHACTR1 gene, as the putative causal variant. Epigenomic data from human tissue revealed an enhancer signature at rs9349379 exclusively in aorta, suggesting a regulatory function for this SNP in the vasculature...
July 27, 2017: Cell
https://www.readbyqxmd.com/read/28729483/epigenetic-plasticity-and-the-hallmarks-of-cancer
#5
REVIEW
William A Flavahan, Elizabeth Gaskell, Bradley E Bernstein
Chromatin and associated epigenetic mechanisms stabilize gene expression and cellular states while also facilitating appropriate responses to developmental or environmental cues. Genetic, environmental, or metabolic insults can induce overly restrictive or overly permissive epigenetic landscapes that contribute to pathogenesis of cancer and other diseases. Restrictive chromatin states may prevent appropriate induction of tumor suppressor programs or block differentiation. By contrast, permissive or "plastic" states may allow stochastic oncogene activation or nonphysiologic cell fate transitions...
July 21, 2017: Science
https://www.readbyqxmd.com/read/28678782/transcription-elongation-factors-represent-in-vivo-cancer-dependencies-in-glioblastoma
#6
Tyler E Miller, Brian B Liau, Lisa C Wallace, Andrew R Morton, Qi Xie, Deobrat Dixit, Daniel C Factor, Leo J Y Kim, James J Morrow, Qiulian Wu, Stephen C Mack, Christopher G Hubert, Shawn M Gillespie, William A Flavahan, Thomas Hoffmann, Rohit Thummalapalli, Michael T Hemann, Patrick J Paddison, Craig M Horbinski, Johannes Zuber, Peter C Scacheri, Bradley E Bernstein, Paul J Tesar, Jeremy N Rich
Glioblastoma is a universally lethal cancer with a median survival time of approximately 15 months. Despite substantial efforts to define druggable targets, there are no therapeutic options that notably extend the lifespan of patients with glioblastoma. While previous work has largely focused on in vitro cellular models, here we demonstrate a more physiologically relevant approach to target discovery in glioblastoma. We adapted pooled RNA interference (RNAi) screening technology for use in orthotopic patient-derived xenograft models, creating a high-throughput negative-selection screening platform in a functional in vivo tumour microenvironment...
July 5, 2017: Nature
https://www.readbyqxmd.com/read/28360267/decoupling-genetics-lineages-and-microenvironment-in-idh-mutant-gliomas-by-single-cell-rna-seq
#7
Andrew S Venteicher, Itay Tirosh, Christine Hebert, Keren Yizhak, Cyril Neftel, Mariella G Filbin, Volker Hovestadt, Leah E Escalante, McKenzie L Shaw, Christopher Rodman, Shawn M Gillespie, Danielle Dionne, Christina C Luo, Hiranmayi Ravichandran, Ravindra Mylvaganam, Christopher Mount, Maristela L Onozato, Brian V Nahed, Hiroaki Wakimoto, William T Curry, A John Iafrate, Miguel N Rivera, Matthew P Frosch, Todd R Golub, Priscilla K Brastianos, Gad Getz, Anoop P Patel, Michelle Monje, Daniel P Cahill, Orit Rozenblatt-Rosen, David N Louis, Bradley E Bernstein, Aviv Regev, Mario L Suvà
Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well as the composition of the tumor microenvironment (TME). We dissected these influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-cell RNA sequencing (RNA-seq) profiles from 16 patient samples with bulk RNA-seq profiles from 165 patient samples. Differences in bulk profiles between IDH-mutant astrocytoma and oligodendroglioma can be primarily explained by distinct TME and signature genetic events, whereas both tumor types share similar developmental hierarchies and lineages of glial differentiation...
March 31, 2017: Science
https://www.readbyqxmd.com/read/28175463/142%C3%A2-genetic-and-nongenetic-determinants-of-cellular-architecture-in-idh1-mutant-oligodendrogliomas-and-astrocytomas-using-single-cell-transcriptome-analysis
#8
Andrew Sean Venteicher, Itay Tirosh, Christine Hebert, Leah Escalante, Robert L Martuza, Brian V Nahed, William T Curry, Daniel P Cahill, Bradley Bernstein, David N Louis, Aviv Regev, Mario Suva
No abstract text is available yet for this article.
August 1, 2016: Neurosurgery
https://www.readbyqxmd.com/read/28137873/systematic-dissection-of-genomic-features-determining-transcription-factor-binding-and-enhancer-function
#9
Sharon R Grossman, Xiaolan Zhang, Li Wang, Jesse Engreitz, Alexandre Melnikov, Peter Rogov, Ryan Tewhey, Alina Isakova, Bart Deplancke, Bradley E Bernstein, Tarjei S Mikkelsen, Eric S Lander
Enhancers regulate gene expression through the binding of sequence-specific transcription factors (TFs) to cognate motifs. Various features influence TF binding and enhancer function-including the chromatin state of the genomic locus, the affinities of the binding site, the activity of the bound TFs, and interactions among TFs. However, the precise nature and relative contributions of these features remain unclear. Here, we used massively parallel reporter assays (MPRAs) involving 32,115 natural and synthetic enhancers, together with high-throughput in vivo binding assays, to systematically dissect the contribution of each of these features to the binding and activity of genomic regulatory elements that contain motifs for PPARγ, a TF that serves as a key regulator of adipogenesis...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28095557/the-photodynamic-therapy-experience-of-a-high-volume-laser-and-dermatologic-surgery-center
#10
David E Orbuch, Lauren Penn, Bradley S Bloom, Jeremy A Brauer, Daniel B Shin, Joshua Greenbaum, Leonard J Bernstein, Elliot T Weiss, Robert T Anolik, Roy G Geronemus
BACKGROUND: Photodynamic therapy (PDT) is an FDA approved treatment for actinic keratoses (AK's) although multiple off-label indi- cations are reported. Despite frequent use for AK's, no clear consensus exists regarding protocols for overall treatment parameters. METHODS: Retrospective chart review of 1,491 subjects who underwent PDT between 2007 and 2011 at a high volume laser surgery center. Demographic information, clinical history, treatment data, and subsequent diagnosis of skin cancers were recorded...
November 1, 2016: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/27989769/adaptive-chromatin-remodeling-drives-glioblastoma-stem-cell-plasticity-and-drug-tolerance
#11
Brian B Liau, Cem Sievers, Laura K Donohue, Shawn M Gillespie, William A Flavahan, Tyler E Miller, Andrew S Venteicher, Christine H Hebert, Christopher D Carey, Scott J Rodig, Sarah J Shareef, Fadi J Najm, Peter van Galen, Hiroaki Wakimoto, Daniel P Cahill, Jeremy N Rich, Jon C Aster, Mario L Suvà, Anoop P Patel, Bradley E Bernstein
Glioblastoma, the most common and aggressive malignant brain tumor, is propagated by stem-like cancer cells refractory to existing therapies. Understanding the molecular mechanisms that control glioblastoma stem cell (GSC) proliferation and drug resistance may reveal opportunities for therapeutic interventions. Here we show that GSCs can reversibly transition to a slow-cycling, persistent state in response to targeted kinase inhibitors. In this state, GSCs upregulate primitive developmental programs and are dependent upon Notch signaling...
February 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/27941797/smarcb1-mediated-swi-snf-complex-function-is-essential-for-enhancer-regulation
#12
Xiaofeng Wang, Ryan S Lee, Burak H Alver, Jeffrey R Haswell, Su Wang, Jakub Mieczkowski, Yotam Drier, Shawn M Gillespie, Tenley C Archer, Jennifer N Wu, Evgeni P Tzvetkov, Emma C Troisi, Scott L Pomeroy, Jaclyn A Biegel, Michael Y Tolstorukov, Bradley E Bernstein, Peter J Park, Charles W M Roberts
SMARCB1 (also known as SNF5, INI1, and BAF47), a core subunit of the SWI/SNF (BAF) chromatin-remodeling complex, is inactivated in nearly all pediatric rhabdoid tumors. These aggressive cancers are among the most genomically stable, suggesting an epigenetic mechanism by which SMARCB1 loss drives transformation. Here we show that, despite having indistinguishable mutational landscapes, human rhabdoid tumors exhibit distinct enhancer H3K27ac signatures, which identify remnants of differentiation programs. We show that SMARCB1 is required for the integrity of SWI/SNF complexes and that its loss alters enhancer targeting-markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers...
February 2017: Nature Genetics
https://www.readbyqxmd.com/read/27835623/gonorrhea-control-united-states-1972-2015-a-narrative-review
#13
Thomas A Peterman, Kevin O'Connor, Heather M Bradley, Elizabeth A Torrone, Kyle T Bernstein
Gonorrhea is the second most commonly reported infection. It can lead to pelvic inflammatory disease, ectopic pregnancy, and infertility. Rates of gonorrhea decreased after the National Gonorrhea Control Program began in 1972, but stabilized in the mid 1990s. The emergence of antimicrobial resistant strains increases the urgency for enhanced gonorrhea control efforts. To identify possible approaches for improving gonorrhea control, we reviewed historic protocols, reports, and other documents related to the activities of the National Gonorrhea Control Program using Centers for Disease Control and Prevention records and the published literature...
December 2016: Sexually Transmitted Diseases
https://www.readbyqxmd.com/read/27806376/single-cell-rna-seq-supports-a-developmental-hierarchy-in-human-oligodendroglioma
#14
Itay Tirosh, Andrew S Venteicher, Christine Hebert, Leah E Escalante, Anoop P Patel, Keren Yizhak, Jonathan M Fisher, Christopher Rodman, Christopher Mount, Mariella G Filbin, Cyril Neftel, Niyati Desai, Jackson Nyman, Benjamin Izar, Christina C Luo, Joshua M Francis, Aanand A Patel, Maristela L Onozato, Nicolo Riggi, Kenneth J Livak, Dave Gennert, Rahul Satija, Brian V Nahed, William T Curry, Robert L Martuza, Ravindra Mylvaganam, A John Iafrate, Matthew P Frosch, Todd R Golub, Miguel N Rivera, Gad Getz, Orit Rozenblatt-Rosen, Daniel P Cahill, Michelle Monje, Bradley E Bernstein, David N Louis, Aviv Regev, Mario L Suvà
Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures...
November 10, 2016: Nature
https://www.readbyqxmd.com/read/27565640/the-treatment-of-chronic-coccydynia-and-postcoccygectomy-pain-with-pelvic-floor-physical-therapy
#15
Kelly M Scott, Lauren W Fisher, Ira H Bernstein, Michelle H Bradley
BACKGROUND: Coccydynia is a challenging disorder that often is refractory to treatments such as medications and injections. Physical therapy for coccydynia rarely has been studied. OBJECTIVE: To evaluate the efficacy of pelvic floor physical therapy for reducing pain levels in patients with coccydynia. DESIGN: Retrospective chart review. SETTING: The pelvic floor rehabilitation clinic of a major university hospital. PATIENTS: A total of 124 consecutive patients over age 18 with a chief complaint of coccydynia between 2009 and 2012...
April 2017: PM & R: the Journal of Injury, Function, and Rehabilitation
https://www.readbyqxmd.com/read/27422298/appropriateness-criteria-for-active-surveillance-of-prostate-cancer
#16
Michael L Cher, Apoorv Dhir, Gregory B Auffenberg, Susan Linsell, Yuqing Gao, Bradley Rosenberg, S Mohammad Jafri, Laurence Klotz, David C Miller, Khurshid R Ghani, Steven J Bernstein, James E Montie, Brian R Lane
PURPOSE: The adoption of active surveillance varies widely across urological communities, which suggests a need for more consistency in the counseling of patients. To address this need we used the RAND/UCLA Appropriateness Method to develop appropriateness criteria and counseling statements for active surveillance. MATERIALS AND METHODS: Panelists were recruited from MUSIC urology practices. Combinations of parameters thought to influence decision making were used to create and score 160 theoretical clinical scenarios for appropriateness of active surveillance...
January 2017: Journal of Urology
https://www.readbyqxmd.com/read/27399421/142%C3%A2-genetic-and-nongenetic-determinants-of-cellular-architecture-in-idh1-mutant-oligodendrogliomas-and-astrocytomas-using-single-cell-transcriptome-analysis
#17
Andrew Sean Venteicher, Itay Tirosh, Christine Hebert, Leah Escalante, Robert L Martuza, Brian V Nahed, William T Curry, Daniel P Cahill, Bradley Bernstein, David N Louis, Aviv Regev, Mario Suva
INTRODUCTION: Gliomas are among the most lethal malignancies and their histogenesis in humans remains unresolved. IDH1 mutational status and co-occurring genetic alterations define major clinical and prognostic classes of gliomas that closely mirror their histologic classification into astrocytic or oligodendroglial tumors. This suggests that distinct progenitor cells give rise to different glioma types, or conversely, that genetic mutations influence cellular lineages, generating tumors of different cellular composition...
August 2016: Neurosurgery
https://www.readbyqxmd.com/read/27322055/rbpj-maintains-brain-tumor-initiating-cells-through-cdk9-mediated-transcriptional-elongation
#18
Qi Xie, Qiulian Wu, Leo Kim, Tyler E Miller, Brian B Liau, Stephen C Mack, Kailin Yang, Daniel C Factor, Xiaoguang Fang, Zhi Huang, Wenchao Zhou, Kareem Alazem, Xiuxing Wang, Bradley E Bernstein, Shideng Bao, Jeremy N Rich
Glioblastomas co-opt stem cell regulatory pathways to maintain brain tumor-initiating cells (BTICs), also known as cancer stem cells. NOTCH signaling has been a molecular target in BTICs, but NOTCH antagonists have demonstrated limited efficacy in clinical trials. Recombining binding protein suppressor of hairless (RBPJ) is considered a central transcriptional mediator of NOTCH activity. Here, we report that pharmacologic NOTCH inhibitors were less effective than targeting RBPJ in suppressing tumor growth. While NOTCH inhibitors decreased canonical NOTCH gene expression, RBPJ regulated a distinct profile of genes critical to BTIC stemness and cell cycle progression...
July 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27152786/results-on-the-spin-dependent-scattering-of-weakly-interacting-massive-particles-on-nucleons-from-the-run-3-data-of-the-lux-experiment
#19
D S Akerib, H M Araújo, X Bai, A J Bailey, J Balajthy, P Beltrame, E P Bernard, A Bernstein, T P Biesiadzinski, E M Boulton, A Bradley, R Bramante, S B Cahn, M C Carmona-Benitez, C Chan, J J Chapman, A A Chiller, C Chiller, A Currie, J E Cutter, T J R Davison, L de Viveiros, A Dobi, J E Y Dobson, E Druszkiewicz, B N Edwards, C H Faham, S Fiorucci, R J Gaitskell, V M Gehman, C Ghag, K R Gibson, M G D Gilchriese, C R Hall, M Hanhardt, S J Haselschwardt, S A Hertel, D P Hogan, M Horn, D Q Huang, C M Ignarra, M Ihm, R G Jacobsen, W Ji, K Kazkaz, D Khaitan, R Knoche, N A Larsen, C Lee, B G Lenardo, K T Lesko, A Lindote, M I Lopes, D C Malling, A Manalaysay, R L Mannino, M F Marzioni, D N McKinsey, D-M Mei, J Mock, M Moongweluwan, J A Morad, A St J Murphy, C Nehrkorn, H N Nelson, F Neves, K O'Sullivan, K C Oliver-Mallory, R A Ott, K J Palladino, M Pangilinan, E K Pease, P Phelps, L Reichhart, C Rhyne, S Shaw, T A Shutt, C Silva, V N Solovov, P Sorensen, S Stephenson, T J Sumner, M Szydagis, D J Taylor, W Taylor, B P Tennyson, P A Terman, D R Tiedt, W H To, M Tripathi, L Tvrznikova, S Uvarov, J R Verbus, R C Webb, J T White, T J Whitis, M S Witherell, F L H Wolfs, K Yazdani, S K Young, C Zhang
We present experimental constraints on the spin-dependent WIMP (weakly interacting massive particle)-nucleon elastic cross sections from LUX data acquired in 2013. LUX is a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility (Lead, South Dakota), which is designed to observe the recoil signature of galactic WIMPs scattering from xenon nuclei. A profile likelihood ratio analysis of 1.4×10^{4}  kg day of fiducial exposure allows 90% C.L. upper limits to be set on the WIMP-neutron (WIMP-proton) cross section of σ_{n}=9...
April 22, 2016: Physical Review Letters
https://www.readbyqxmd.com/read/27152785/improved-limits-on-scattering-of-weakly-interacting-massive-particles-from-reanalysis-of-2013-lux-data
#20
D S Akerib, H M Araújo, X Bai, A J Bailey, J Balajthy, P Beltrame, E P Bernard, A Bernstein, T P Biesiadzinski, E M Boulton, A Bradley, R Bramante, S B Cahn, M C Carmona-Benitez, C Chan, J J Chapman, A A Chiller, C Chiller, A Currie, J E Cutter, T J R Davison, L de Viveiros, A Dobi, J E Y Dobson, E Druszkiewicz, B N Edwards, C H Faham, S Fiorucci, R J Gaitskell, V M Gehman, C Ghag, K R Gibson, M G D Gilchriese, C R Hall, M Hanhardt, S J Haselschwardt, S A Hertel, D P Hogan, M Horn, D Q Huang, C M Ignarra, M Ihm, R G Jacobsen, W Ji, K Kazkaz, D Khaitan, R Knoche, N A Larsen, C Lee, B G Lenardo, K T Lesko, A Lindote, M I Lopes, D C Malling, A Manalaysay, R L Mannino, M F Marzioni, D N McKinsey, D-M Mei, J Mock, M Moongweluwan, J A Morad, A St J Murphy, C Nehrkorn, H N Nelson, F Neves, K O'Sullivan, K C Oliver-Mallory, R A Ott, K J Palladino, M Pangilinan, E K Pease, P Phelps, L Reichhart, C Rhyne, S Shaw, T A Shutt, C Silva, V N Solovov, P Sorensen, S Stephenson, T J Sumner, M Szydagis, D J Taylor, W Taylor, B P Tennyson, P A Terman, D R Tiedt, W H To, M Tripathi, L Tvrznikova, S Uvarov, J R Verbus, R C Webb, J T White, T J Whitis, M S Witherell, F L H Wolfs, K Yazdani, S K Young, C Zhang
We present constraints on weakly interacting massive particles (WIMP)-nucleus scattering from the 2013 data of the Large Underground Xenon dark matter experiment, including 1.4×10^{4}  kg day of search exposure. This new analysis incorporates several advances: single-photon calibration at the scintillation wavelength, improved event-reconstruction algorithms, a revised background model including events originating on the detector walls in an enlarged fiducial volume, and new calibrations from decays of an injected tritium β source and from kinematically constrained nuclear recoils down to 1...
April 22, 2016: Physical Review Letters
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