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https://www.readbyqxmd.com/read/29045844/a-b-cell-regulome-links-notch-to-downstream-oncogenic-pathways-in-small-b-cell-lymphomas
#1
Russell J H Ryan, Jelena Petrovic, Dylan M Rausch, Yeqiao Zhou, Caleb A Lareau, Michael J Kluk, Amanda L Christie, Winston Y Lee, Daniel R Tarjan, Bingqian Guo, Laura K H Donohue, Shawn M Gillespie, Valentina Nardi, Ephraim P Hochberg, Stephen C Blacklow, David M Weinstock, Robert B Faryabi, Bradley E Bernstein, Jon C Aster, Warren S Pear
Gain-of-function Notch mutations are recurrent in mature small B cell lymphomas such as mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), but the Notch target genes that contribute to B cell oncogenesis are largely unknown. We performed integrative analysis of Notch-regulated transcripts, genomic binding of Notch transcription complexes, and genome conformation data to identify direct Notch target genes in MCL cell lines. This B cell Notch regulome is largely controlled through Notch-bound distal enhancers and includes genes involved in B cell receptor and cytokine signaling and the oncogene MYC, which sustains proliferation of Notch-dependent MCL cell lines via a Notch-regulated lineage-restricted enhancer complex...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29032871/can-a-negative-high-sensitivity-troponin-result-rapidly-rule-out-acute-myocardial-infarction
#2
EDITORIAL
Nathan M Finnerty, Michael B Weinstock
No abstract text is available yet for this article.
October 9, 2017: Annals of Emergency Medicine
https://www.readbyqxmd.com/read/29029188/an-analysis-of-the-epidemic-of-kpc-producing-klebsiella-pneumoniae-convergence-of-two-evolutionary-mechanisms-creates-the-perfect-storm
#3
Laura J Rojas, George M Weinstock, Elsa De La Cadena, Lorena Diaz, Rafael Rios, Blake M Hanson, Joseph S Brown, Purva Vats, Daniel S Phillips, Hoan Nguyen, Kristine M Hujer, Adriana Correa, Mark D Adams, Federico Perez, Erica Sodergren, Apurva Narechania, Paul J Planet, Maria V Villegas, Robert A Bonomo, Cesar A Arias
Background: Carbapenem resistance is a critical health care challenge worldwide. Particularly concerning is the widespread dissemination of Klebsiella pneumoniae carbapenemase (KPC). K. pneumoniae harboring blaKPC (KPC-Kpn) is endemic in many areas including United States, where the epidemic was primarily mediated by the clonal dissemination of Kpn ST258. We postulated that the spread of blaKPC in other regions occurs by different and more complex mechanisms. To test this, we investigated the evolution and dynamics of spread of KPC-Kpn in Colombia, where KPC became rapidly endemic after emerging in 2005...
September 27, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29019863/bony-cartilaginous-mismatch-a-radiologic-investigation-into-the-etiology-of-tension-nose-deformity
#4
Michael S Weinstock, Howard D Stupak
BACKGROUND: Tension nose deformity is believed to be due to an "oversized" septal quadrangular cartilage. Prior studies have shown that quadrangular cartilage size is relatively consistent in size in populations. We hypothesize that the tension nose deformity is actually due to an external extrusion of a normal sized septal cartilage from an undersized bony septal encasement. METHODS: A retrospective case-control study of sagittal CT scans was conducted, measuring the perimeter and surface area of the quadrangular cartilage and bony septal aperture in tension nose cases and controls...
October 10, 2017: Plastic and Reconstructive Surgery
https://www.readbyqxmd.com/read/28993476/contribution-of-dietary-intake-to-relapse-rate-in-early-paediatric-multiple-sclerosis
#5
Saeedeh Azary, Teri Schreiner, Jennifer Graves, Amy Waldman, Anita Belman, Bianca Weinstock Guttman, Gregory Aaen, Jan-Mendelt Tillema, Soe Mar, Janace Hart, Jayne Ness, Yolanda Harris, Lauren Krupp, Mark Gorman, Leslie Benson, Moses Rodriguez, Tanuja Chitnis, John Rose, Lisa F Barcellos, Tim Lotze, Suzan L Carmichael, Shelly Roalstad, Charles T Casper, Emmanuelle Waubant
OBJECTIVE: The role of diet in multiple sclerosis (MS) course remains largely unknown. Children with MS have a higher relapse rate compared with MS in adults. Thus, studying the effect of diet on relapse rate in this age group is likely to provide more robust answers. METHODS: This is a multicentre study done at 11 paediatric MS centres in the USA. Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) with disease onset before 18 years of age and duration of less than 4 years were included in this study...
October 9, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28980494/genetic-risk-factors-for-pediatric-onset-multiple-sclerosis
#6
Milena A Gianfrancesco, Pernilla Stridh, Xiaorong Shao, Brooke Rhead, Jennifer S Graves, Tanuja Chitnis, Amy Waldman, Timothy Lotze, Teri Schreiner, Anita Belman, Benjamin Greenberg, Bianca Weinstock-Guttman, Gregory Aaen, Jan M Tillema, Janace Hart, Stacy Caillier, Jayne Ness, Yolanda Harris, Jennifer Rubin, Meghan Candee, Lauren Krupp, Mark Gorman, Leslie Benson, Moses Rodriguez, Soe Mar, Ilana Kahn, John Rose, Shelly Roalstad, T Charles Casper, Ling Shen, Hong Quach, Diana Quach, Jan Hillert, Anna Hedstrom, Tomas Olsson, Ingrid Kockum, Lars Alfredsson, Catherine Schaefer, Lisa F Barcellos, Emmanuelle Waubant
BACKGROUND: Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology. OBJECTIVE: We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS. METHODS: Cases with onset <18 years ( n = 569) and controls ( n = 16,251) were included from the United States and Sweden...
October 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28979265/impact-of-age-caloric-restriction-and-influenza-infection-on-mouse-gut-microbiome-an-exploratory-study-of-the-role-of-age-related-microbiome-changes-on-influenza-responses
#7
Jenna M Bartley, Xin Zhou, George A Kuchel, George M Weinstock, Laura Haynes
Immunosenescence refers to age-related declines in the capacity to respond to infections such as influenza (flu). Caloric restriction represents a known strategy to slow many aging processes, including those involving the immune system. More recently, some changes in the microbiome have been described with aging, while the gut microbiome appears to influence responses to flu vaccination and infection. With these considerations in mind, we used a well-established mouse model of flu infection to explore the impact of flu infection, aging, and caloric restriction on the gut microbiome...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28973793/the-relationship-between-gambling-severity-and-risk-of-criminal-recidivism
#8
Laura M April, Jeremiah Weinstock
Individuals involved with the criminal justice system have the highest prevalence of gambling disorder. Yet, this is an understudied area, especially in relation to postrelease functioning and recidivism risk. Participants (N = 100) were recruited from a local nonprofit organization and a federal probation office. Participants completed both self-report and interviewer-administered questionnaires assessing past-year and lifetime gambling behaviors and problems, legal history, health, and risk of recidivism...
October 3, 2017: Journal of Forensic Sciences
https://www.readbyqxmd.com/read/28973216/annals-graphic-medicine-every-little-bit
#9
Allison K Weinstock
No abstract text is available yet for this article.
October 3, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28967922/inhibition-of-usp10-induces-degradation-of-oncogenic-flt3
#10
Ellen L Weisberg, Nathan J Schauer, Jing Yang, Ilaria Lamberto, Laura Doherty, Shruti Bhatt, Atsushi Nonami, Chengcheng Meng, Anthony Letai, Renee Wright, Hong Tiv, Prafulla C Gokhale, Maria Stella Ritorto, Virginia De Cesare, Matthias Trost, Alexandra Christodoulou, Amanda Christie, David M Weinstock, Sophia Adamia, Richard Stone, Dharminder Chauhan, Kenneth C Anderson, Hyuk-Soo Seo, Sirano Dhe-Paganon, Martin Sattler, Nathanael S Gray, James D Griffin, Sara J Buhrlage
Oncogenic forms of the kinase FLT3 are important therapeutic targets in acute myeloid leukemia (AML); however, clinical responses to small-molecule kinase inhibitors are short-lived as a result of the rapid emergence of resistance due to point mutations or compensatory increases in FLT3 expression. We sought to develop a complementary pharmacological approach whereby proteasome-mediated FLT3 degradation could be promoted by inhibitors of the deubiquitinating enzymes (DUBs) responsible for cleaving ubiquitin from FLT3...
October 2, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28932270/repeat-treatment-with-rifaximin-improves-irritable-bowel-syndrome-related-quality-of-life-a-secondary-analysis-of-a-randomized-double-blind-placebo-controlled-trial
#11
Brooks D Cash, Mark Pimentel, Satish S C Rao, Leonard Weinstock, Lin Chang, Zeev Heimanson, Anthony Lembo
BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) impairs patient quality of life (QOL). Rifaximin is an oral, nonsystemic antibiotic indicated for IBS-D. The objective of this secondary analysis was to evaluate rifaximin retreatment on IBS-related QOL in patients with IBS-D. METHODS: Patients received open-label rifaximin 550 mg three times daily for 2 weeks. Clinical responders [simultaneously meeting weekly response criteria for abdominal pain (⩾30% improvement from baseline in mean weekly pain score) and stool consistency (⩾50% decrease from baseline in number of days/week with Bristol Stool Scale (BSS) type 6 or 7 stools) during ⩾2 of first 4 weeks posttreatment] who relapsed during an up to 18-week treatment-free observation phase were randomly assigned to receive two 2-week courses of double-blind rifaximin or placebo, separated by 10 weeks...
September 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28916537/reversibility-of-the-effects-of-natalizumab-on-peripheral-immune-cell-dynamics-in-ms-patients
#12
RANDOMIZED CONTROLLED TRIAL
Tatiana Plavina, Kumar Kandadi Muralidharan, Geoffrey Kuesters, Daniel Mikol, Karleyton Evans, Meena Subramanyam, Ivan Nestorov, Yi Chen, Qunming Dong, Pei-Ran Ho, Diogo Amarante, Alison Adams, Jerome De Sèze, Robert Fox, Ralf Gold, Douglas Jeffery, Ludwig Kappos, Xavier Montalban, Bianca Weinstock-Guttman, Hans-Peter Hartung, Bruce A C Cree
OBJECTIVE: To characterize the reversibility of natalizumab-mediated changes in pharmacokinetics/pharmacodynamics in patients with multiple sclerosis (MS) following therapy interruption. METHODS: Pharmacokinetic/pharmacodynamic data were collected in the Safety and Efficacy of Natalizumab in the Treatment of Multiple Sclerosis (AFFIRM) (every 12 weeks for 116 weeks) and Randomized Treatment Interruption of Natalizumab (RESTORE) (every 4 weeks for 28 weeks) studies...
October 10, 2017: Neurology
https://www.readbyqxmd.com/read/28891316/associations-of-the-abca1-and-lpl-gene-polymorphisms-with-lipid-levels-in-a-hyperlipidemic-population
#13
Fang Tao, Justin Weinstock, Scott A Venners, Jun Cheng, Yi-Hsiang Hsu, Yanfeng Zou, Faming Pan, Shanqun Jiang, Xiangdong Zha, Xiping Xu
We conducted a cross-sectional study to investigate the effects of the adenosine triphosphate-binding cassette transporter 1 (ABCA1) I883M and lipoprotein lipase (LPL) HindIII polymorphisms on lipid levels in patients with hyperlipidemia. A total of 533 patients were enrolled. Serum lipid parameters were determined by an automatic biochemistry analyzer. Genotyping of the ABCA1 I883M and LPL HindIII was carried out using the polymerase chain reaction-restriction fragment length polymorphism technique. Multiple linear regression analysis was used to estimate the associations between serum lipid levels and the genetic polymorphisms...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28881711/characterization-of-midostaurin-as-a-dual-inhibitor-of-flt3-and-syk-and-potentiation-of-flt3-inhibition-against-flt3-itd-driven-leukemia-harboring-activated-syk-kinase
#14
Ellen L Weisberg, Alexandre Puissant, Richard Stone, Martin Sattler, Sara J Buhrlage, Jing Yang, Paul W Manley, Chengcheng Meng, Michael Buonopane, John F Daley, Suzan Lazo, Renee Wright, David M Weinstock, Amanda L Christie, Kimberly Stegmaier, James D Griffin
Oncogenic FLT3 kinase is a clinically validated target in acute myeloid leukemia (AML), and both multi-targeted and selective FLT3 inhibitors have been developed. Spleen tyrosine kinase (SYK) has been shown to be activated and increased in FLT3-ITD-positive AML patients, and has further been shown to be critical for transformation and maintenance of the leukemic clone in these patients. Further, over-expression of constitutively activated SYK causes resistance to highly selective FLT3 tyrosine kinase inhibitors (TKI)...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877312/effect-of-topical-fluorouracil-cream-on-photodamage-secondary-analysis-of-a-randomized-clinical-trial
#15
Kaveri Korgavkar, Kachiu C Lee, Martin A Weinstock
Importance: Photoaging, which is premature skin aging caused by long-term UV exposure, is of aesthetic concern to many patients. Objective: To investigate the effect of topical fluorouracil, 5%, cream on photoaging using validated photonumeric scales. Design, Setting, and Participants: The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized clinical trial of 932 US veterans with a recent history of 2 or more keratinocyte carcinomas performed from September 30, 2011, through June 30, 2014, to assess the chemopreventive effects of a standard course of topical fluorouracil...
September 6, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28870390/how-do-we-balance-the-long-term-health-of-a-patient-with-the-short-term-risk-to-the-physician
#16
Michael B Weinstock, Amal Mattu, Erik P Hess
BACKGROUND: There is a wide variation in practice patterns among emergency medicine physicians; many factors weigh into the medical decision-making process including the health of the patient as well as short-term risk to the physician. OBJECTIVE: The objective of our discussion is to illustrate specific scenarios where medical decisions are focused on the physician's short-term risk, then to propose an approach to shifting the balance to the patient's long-term health...
September 1, 2017: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28864873/health-outcomes-in-individuals-with-problem-and-pathological-gambling-an-analysis-of-the-2014-north-carolina-behavioral-risk-factor-survey-system-brfss
#17
Ryan Van Patten, Jeremiah Weinstock, Andrew B McGrath
Problem and pathological gambling refers to subclinical and clinical levels of maladaptive gambling, respectively, and is associated with specific sociodemographic characteristics as well as a number of poor health outcomes. We examined such demographic, physical health, mental health, and health-related behaviors in a sample of 7045 low-risk gamblers and 244 problem/pathological gamblers. Participants completed the 2014 North Carolina Behavioral Risk Factor Surveillance System telephone survey. Using the National Opinion Research Center's Diagnostic Screen for Gambling Disorders-CLiP, participants were categorized as either "problem/pathological gamblers" or "low-risk gamblers...
September 1, 2017: Journal of Gambling Studies
https://www.readbyqxmd.com/read/28858936/pathologists-use-of-second-opinions-in-interpretation-of-melanocytic-cutaneous-lesions-policies-practices-and-perceptions
#18
Berta M Geller, Paul D Frederick, Stevan R Knezevich, Jason P Lott, Heidi D Nelson, Linda J Titus, Patricia A Carney, Anna N A Tosteson, Tracy L Onega, Raymond L Barnhill, Martin A Weinstock, David E Elder, Michael W Piepkorn, Joann G Elmore
BACKGROUND: Research examining the role of second opinions in pathology for diagnosis of melanocytic lesions is limited. OBJECTIVE: To assess current laboratory policies, clinical use of second opinions, and pathologists' perceptions of second opinions for melanocytic lesions. MATERIALS AND METHODS: Cross-sectional data collected from 207 pathologists in 10 US states who diagnose melanocytic lesions. The web-based survey ascertained pathologists' professional information, laboratory second opinion policy, use of second opinions, and perceptions of second opinion value for melanocytic lesions...
August 29, 2017: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/28854165/cancer-models-the-next-best-thing
#19
COMMENT
Mark A Murakami, David M Weinstock
No abstract text is available yet for this article.
September 7, 2017: Nature
https://www.readbyqxmd.com/read/28843292/more-than-many-how-to-manage-the%C3%A2-most-frequent-cancer
#20
REVIEW
Loes Hollestein, Martin Weinstock, Emma Le Roux, Catherine Olsen
Leiter et al. report on the increasing incidence of keratinocyte cancers in Germany. The true population burden is even larger then reported, because many of these new patients will develop multiple keratinocyte cancers. Keratinocyte cancer puts a large burden on health care systems worldwide. Prevention and management strategies are needed to maintain high quality of care for all patients.
September 2017: Journal of Investigative Dermatology
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