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James andrews

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https://www.readbyqxmd.com/read/28433513/ortho-group-activation-of-a-bromopyrrole-ester-in-suzuki-miyaura-cross-coupling-reactions-application-to-the-synthesis-of-new-microtubule-depolymerizing-agents-with-potent-cytotoxic-activities
#1
John T Gupton, Scott Yeudall, Nakul Telang, Megan Hoerrner, Ellis Huff, Evan Crawford, Katie Lounsbury, Michael Kimmel, William Curry, Andrew Harrison, Wen Juekun, Alex Shimozono, Joe Ortolani, Kristin Lescalleet, Jon Patteson, Veronica Moore-Stoll, Cristina C Rohena, Susan L Mooberry, Ahmad J Obaidullah, Glen E Kellogg, James A Sikorski
New microtubule depolymerizing agents with potent cytotoxic activities have been prepared with a 5-cyano or 5-oximino group attached to a pyrrole core. The utilization of ortho activation of a bromopyrrole ester to facilitate successful Suzuki-Miyaura cross-coupling reactions was a key aspect of the synthetic methodology. This strategy allows for control of regiochemistry with the attachment of four completely different groups at the 2, 3, 4 and 5 positions of the pyrrole scaffold. Biological evaluations and molecular modeling studies are reported for these examples...
April 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28432292/created-mangrove-wetlands-store-belowground-carbon-and-surface-elevation-change-enables-them-to-adjust-to-sea-level-rise
#2
Ken W Krauss, Nicole Cormier, Michael J Osland, Matthew L Kirwan, Camille L Stagg, Janet A Nestlerode, Marc J Russell, Andrew S From, Amanda C Spivak, Darrin D Dantin, James E Harvey, Alejandro E Almario
Mangrove wetlands provide ecosystem services for millions of people, most prominently by providing storm protection, food and fodder. Mangrove wetlands are also valuable ecosystems for promoting carbon (C) sequestration and storage. However, loss of mangrove wetlands and these ecosystem services are a global concern, prompting the restoration and creation of mangrove wetlands as a potential solution. Here, we investigate soil surface elevation change, and its components, in created mangrove wetlands over a 25 year developmental gradient...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432176/a-phase-i-study-of-the-cdk4-6-inhibitor-ribociclib-lee011-in-pediatric-patients-with-malignant-rhabdoid-tumors-neuroblastoma-and-other-solid-tumors
#3
Birgit Geoerger, Franck Bourdeaut, Steven G DuBois, Matthias Fischer, James I Geller, Nicholas G Gottardo, Aurélien Marabelle, Andrew D J Pearson, Shakeel Modak, Thomas Cash, Giles W Robinson, Marlyane Motta, Alessandro Matano, Suraj G Bhansali, Jason R Dobson, Sudha Parasuraman, Susan N Chi
Purpose: The cyclin-dependent kinase (CDK) 4/6 inhibitor, ribociclib (LEE011), displayed preclinical activity in neuroblastoma and malignant rhabdoid tumor (MRT) models. In this phase I study, the maximum tolerated dose (MTD) and recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of single-agent ribociclib were investigated in pediatric patients with neuroblastoma, MRT, or other cyclin D-CDK4/6-INK4-retinoblastoma pathway-altered tumors.Experimental Design: Patients (aged 1-21 years) received escalating once-daily oral doses of ribociclib (3-weeks-on/1-week-off)...
April 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28431554/a-need-to-accelerate-health-research-productivity-in-an-african-university-the-case-of-makerere-university-college-of-health-sciences
#4
Damalie Nakanjako, Dickens Akena, Dan K Kaye, James Tumwine, Elialilia Okello, Annettee Nakimuli, Andrew Kambugu, Hazel McCullough, Harriet Mayanja-Kizza, Moses R Kamya, Nelson K Sewankambo
BACKGROUND: In the last decade, Makerere University College of Health Sciences (MakCHS) has taken strides in research and training to improve healthcare through collaborative training and research programs. However, there is limited data on the trends of MakCHS faculty contributions to research and on faculty growth to take leading roles in health research. This paper reviews MakCHS faculty research publications over 15.5 years and outlines possible strategies to enhance faculty research outputs...
April 21, 2017: Health Research Policy and Systems
https://www.readbyqxmd.com/read/28430825/discovery-and-fine-mapping-of-adiposity-loci-using-high-density-imputation-of-genome-wide-association-studies-in-individuals-of-african-ancestry-african-ancestry-anthropometry-genetics-consortium
#5
Maggie C Y Ng, Mariaelisa Graff, Yingchang Lu, Anne E Justice, Poorva Mudgal, Ching-Ti Liu, Kristin Young, Lisa R Yanek, Mary F Feitosa, Mary K Wojczynski, Kristin Rand, Jennifer A Brody, Brian E Cade, Latchezar Dimitrov, Qing Duan, Xiuqing Guo, Leslie A Lange, Michael A Nalls, Hayrettin Okut, Salman M Tajuddin, Bamidele O Tayo, Sailaja Vedantam, Jonathan P Bradfield, Guanjie Chen, Wei-Min Chen, Alessandra Chesi, Marguerite R Irvin, Badri Padhukasahasram, Jennifer A Smith, Wei Zheng, Matthew A Allison, Christine B Ambrosone, Elisa V Bandera, Traci M Bartz, Sonja I Berndt, Leslie Bernstein, William J Blot, Erwin P Bottinger, John Carpten, Stephen J Chanock, Yii-Der Ida Chen, David V Conti, Richard S Cooper, Myriam Fornage, Barry I Freedman, Melissa Garcia, Phyllis J Goodman, Yu-Han H Hsu, Jennifer Hu, Chad D Huff, Sue A Ingles, Esther M John, Rick Kittles, Eric Klein, Jin Li, Barbara McKnight, Uma Nayak, Barbara Nemesure, Adesola Ogunniyi, Andrew Olshan, Michael F Press, Rebecca Rohde, Benjamin A Rybicki, Babatunde Salako, Maureen Sanderson, Yaming Shao, David S Siscovick, Janet L Stanford, Victoria L Stevens, Alex Stram, Sara S Strom, Dhananjay Vaidya, John S Witte, Jie Yao, Xiaofeng Zhu, Regina G Ziegler, Alan B Zonderman, Adebowale Adeyemo, Stefan Ambs, Mary Cushman, Jessica D Faul, Hakon Hakonarson, Albert M Levin, Katherine L Nathanson, Erin B Ware, David R Weir, Wei Zhao, Degui Zhi, Donna K Arnett, Struan F A Grant, Sharon L R Kardia, Olufunmilayo I Oloapde, D C Rao, Charles N Rotimi, Michele M Sale, L Keoki Williams, Babette S Zemel, Diane M Becker, Ingrid B Borecki, Michele K Evans, Tamara B Harris, Joel N Hirschhorn, Yun Li, Sanjay R Patel, Bruce M Psaty, Jerome I Rotter, James G Wilson, Donald W Bowden, L Adrienne Cupples, Christopher A Haiman, Ruth J F Loos, Kari E North
Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes...
April 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28429290/association-of-long-term-patterns-of-depressive-symptoms-and-attention-executive-function-among-older-men-with-and-without-human-immunodeficiency-virus
#6
Nicole M Armstrong, Pamela J Surkan, Glenn J Treisman, Ned C Sacktor, Michael R Irwin, Linda A Teplin, Ron Stall, Eileen M Martin, James T Becker, Cynthia Munro, Andrew J Levine, Lisa P Jacobson, Alison G Abraham
Older HIV-infected men are at higher risk for both depression and cognitive impairments, compared to HIV-uninfected men. We evaluated the association between longitudinal patterns of depressive symptoms and attention/executive function in HIV-infected and HIV-uninfected men aged 50+ years to understand whether HIV infection influenced the long-term effect of depression on attention/executive function. Responses to the Center for Epidemiologic Studies-Depression scale and attention/executive function tests (Trail Making Test Part B and Symbol Digit Modalities Test) were collected semiannually from May 1986 to April 2015 in 1611 men...
April 20, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28428369/single-cell-rna-seq-reveals-new-types-of-human-blood-dendritic-cells-monocytes-and-progenitors
#7
Alexandra-Chloé Villani, Rahul Satija, Gary Reynolds, Siranush Sarkizova, Karthik Shekhar, James Fletcher, Morgane Griesbeck, Andrew Butler, Shiwei Zheng, Suzan Lazo, Laura Jardine, David Dixon, Emily Stephenson, Emil Nilsson, Ida Grundberg, David McDonald, Andrew Filby, Weibo Li, Philip L De Jager, Orit Rozenblatt-Rosen, Andrew A Lane, Muzlifah Haniffa, Aviv Regev, Nir Hacohen
Dendritic cells (DCs) and monocytes play a central role in pathogen sensing, phagocytosis, and antigen presentation and consist of multiple specialized subtypes. However, their identities and interrelationships are not fully understood. Using unbiased single-cell RNA sequencing (RNA-seq) of ~2400 cells, we identified six human DCs and four monocyte subtypes in human blood. Our study reveals a new DC subset that shares properties with plasmacytoid DCs (pDCs) but potently activates T cells, thus redefining pDCs; a new subdivision within the CD1C(+) subset of DCs; the relationship between blastic plasmacytoid DC neoplasia cells and healthy DCs; and circulating progenitor of conventional DCs (cDCs)...
April 21, 2017: Science
https://www.readbyqxmd.com/read/28428158/mobile-application-to-promote-adherence-to-oral-chemotherapy-and-symptom-management-a-protocol-for-design-and-development
#8
Joel Nathan Fishbein, Lauren Ellen Nisotel, James John MacDonald, Nicole Amoyal Pensak, Jamie Michele Jacobs, Clare Flanagan, Kamal Jethwani, Joseph Andrew Greer
BACKGROUND: Oral chemotherapy is increasingly used in place of traditional intravenous chemotherapy to treat patients with cancer. While oral chemotherapy includes benefits such as ease of administration, convenience, and minimization of invasive infusions, patients receive less oversight, support, and symptom monitoring from clinicians. Additionally, adherence is a well-documented challenge for patients with cancer prescribed oral chemotherapy regimens. With the ever-growing presence of smartphones and potential for efficacious behavioral intervention technology, we created a mobile health intervention for medication and symptom management...
April 20, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28427826/suvorexant-in-elderly-patients-with-insomnia-pooled-analyses-of-data-from-phase-iii-randomized-controlled-clinical-trials
#9
W Joseph Herring, Kathryn M Connor, Ellen Snyder, Duane B Snavely, Ying Zhang, Jill Hutzelmann, Deborah Matzura-Wolfe, Ruth M Benca, Andrew D Krystal, James K Walsh, Christopher Lines, Thomas Roth, David Michelson
OBJECTIVE: Suvorexant is an orexin receptor antagonist approved for treating insomnia at doses of 10-20 mg. Previously reported phase III results showed that suvorexant was effective and well-tolerated in a combined-age population (elderly and nonelderly adults). The present analysis evaluated the clinical profile of suvorexant specifically in the elderly. METHODS: Prespecified subgroup analyses of pooled 3-month data from two (efficacy) and three (safety) randomized, double-blind, placebo-controlled, parallel-group trials...
March 8, 2017: American Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28424091/investigations-into-the-association-between-soil-transmitted-helminth-infections-haemoglobin-and-child-development-indices-in-manufahi-district-timor-leste
#10
Suzy J Campbell, Susana V Nery, Catherine A D'Este, Darren J Gray, James S McCarthy, Rebecca J Traub, Ross M Andrews, Stacey Llewellyn, Andrew J Vallely, Gail M Williams, Archie C A Clements
BACKGROUND: Timor-Leste has a high prevalence of soil-transmitted helminth (STH) infections. High proportions of the population have been reported as being anaemic, and extremely high proportions of children as stunted or wasted. There have been no published analyses of the contributions of STH to these morbidity outcomes in Timor-Leste. METHODS: Using baseline cross-sectional data from 24 communities (18 communities enrolled in a cluster randomised controlled trial, and identically-collected data from six additional communities), analyses of the association between STH infections and community haemoglobin and child development indices were undertaken...
April 19, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28423342/a-broadly-neutralizing-antibody-targets-the-dynamic-hiv-envelope-trimer-apex-via-a-long-rigidified-and-anionic-%C3%AE-hairpin-structure
#11
Jeong Hyun Lee, Raiees Andrabi, Ching-Yao Su, Anila Yasmeen, Jean-Philippe Julien, Leopold Kong, Nicholas C Wu, Ryan McBride, Devin Sok, Matthias Pauthner, Christopher A Cottrell, Travis Nieusma, Claudia Blattner, James C Paulson, Per Johan Klasse, Ian A Wilson, Dennis R Burton, Andrew B Ward
Broadly neutralizing antibodies (bnAbs) to HIV delineate vaccine targets and are prophylactic and therapeutic agents. Some of the most potent bnAbs target a quaternary epitope at the apex of the surface HIV envelope (Env) trimer. Using cryo-electron microscopy, we solved the atomic structure of an apex bnAb, PGT145, in complex with Env. We showed that the long anionic HCDR3 of PGT145 penetrated between glycans at the trimer 3-fold axis, to contact peptide residues from all three Env protomers, and thus explains its highly trimer-specific nature...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28423301/risankizumab-versus-ustekinumab-for-moderate-to-severe-plaque-psoriasis
#12
Kim A Papp, Andrew Blauvelt, Michael Bukhalo, Melinda Gooderham, James Krueger, Jean-Philippe Lacour, Alan Menter, Sandra Philipp, Howard Sofen, Stephen Tyring, Beate R Berner, Sudha Visvanathan, Chandrasena Pamulapati, Nathan Bennett, Mary Flack, Paul Scholl, Steven J Padula
Background Interleukin-23 is thought to be critical to the pathogenesis of psoriasis. We compared risankizumab (BI 655066), a humanized IgG1 monoclonal antibody that inhibits interleukin-23 by specifically targeting the p19 subunit and thus prevents interleukin-23 signaling, and ustekinumab, an interleukin-12 and interleukin-23 inhibitor, in patients with moderate-to-severe plaque psoriasis. Methods We randomly assigned a total of 166 patients to receive subcutaneous injections of risankizumab (a single 18-mg dose at week 0 or 90-mg or 180-mg doses at weeks 0, 4, and 16) or ustekinumab (45 or 90 mg, according to body weight, at weeks 0, 4, and 16)...
April 20, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28422916/beware-of-the-interval-cholecystectomy
#13
James Ackerman, Ryan Abegglen, Mark Scaife, Andrew Peitzman, Matthew Rosengart, Wallis Marsh, Kurt Stahlfeld
BACKGROUND *: Despite limited data regarding the indications and effectiveness of percutaneous cholecystostomy (PC) in the treatment of acute cholecystitis (AC), usage has increased by over 500% since 1994. Many of these patients subsequently undergo interval cholecystectomy (IC), a procedure that has not been rigorously evaluated. This aim of this study was to quantify the morbidity and mortality associated with the IC. METHODS *: We included all consecutive adult patients (>18 years old) who underwent PC and IC from January 2008 to December 2013...
April 18, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28422755/%C3%AE-klotho-deficiency-protects-against-obesity-through-a-crosstalk-between-liver-microbiota-and-brown-adipose-tissue
#14
Emmanuel Somm, Hugues Henry, Stephen J Bruce, Sébastien Aeby, Marta Rosikiewicz, Gerasimos P Sykiotis, Mohammed Asrih, François R Jornayvaz, Pierre Damien Denechaud, Urs Albrecht, Moosa Mohammadi, Andrew Dwyer, James S Acierno, Kristina Schoonjans, Lluis Fajas, Gilbert Greub, Nelly Pitteloud
β-Klotho (encoded by Klb) is the obligate coreceptor mediating FGF21 and FGF15/19 signaling. Klb-/- mice are refractory to beneficial action of pharmacological FGF21 treatment including stimulation of glucose utilization and thermogenesis. Here, we investigated the energy homeostasis in Klb-/- mice on high-fat diet in order to better understand the consequences of abrogating both endogenous FGF15/19 and FGF21 signaling during caloric overload. Surprisingly, Klb-/- mice are resistant to diet-induced obesity (DIO) owing to enhanced energy expenditure and BAT activity...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28420692/an-improved-assembly-and-annotation-of-the-allohexaploid-wheat-genome-identifies-complete-families-of-agronomic-genes-and-provides-genomic-evidence-for-chromosomal-translocations
#15
Bernardo J Clavijo, Luca Venturini, Christian Schudoma, Gonzalo Garcia Accinelli, Gemy Kaithakottil, Jonathan Wright, Philippa Borrill, George Kettleborough, Darren Heavens, Helen Chapman, James Lipscombe, Tom Barker, Fu-Hao Lu, Neil McKenzie, Dina Raats, Ricardo H Ramirez-Gonzalez, Aurore Coince, Ned Peel, Lawrence Percival-Alwyn, Owen Duncan, Josua Trösch, Guotai Yu, Dan M Bolser, Guy Namaati, Arnaud Kerhornou, Manuel Spannagl, Heidrun Gundlach, Georg Haberer, Robert P Davey, Christine Fosker, Federica Di Palma, Andrew Phillips, A Harvey Millar, Paul J Kersey, Cristobal Uauy, Ksenia V Krasileva, David Swarbreck, Michael W Bevan, Matthew D Clark
Advances in genome sequencing and assembly technologies are generating many high-quality genome sequences, but assemblies of large, repeat-rich polyploid genomes, such as that of bread wheat, remain fragmented and incomplete. We have generated a new wheat whole-genome shotgun sequence assembly using a combination of optimized data types and an assembly algorithm designed to deal with large and complex genomes. The new assembly represents >78% of the genome with a scaffold N50 of 88.8 kb that has a high fidelity to the input data...
April 18, 2017: Genome Research
https://www.readbyqxmd.com/read/28419686/gastrointestinal-mucormycosis-in-an-immunocompromised-host
#16
Michael Kwok, Andrew Maurice, James Carroll, Jason Brown, Carl Lisec, Leo Francis, Bhavik Patel
No abstract text is available yet for this article.
April 16, 2017: ANZ Journal of Surgery
https://www.readbyqxmd.com/read/28419032/formal-physical-therapy-after-total-hip-arthroplasty-is-not-required-a-randomized-controlled-trial
#17
Matthew S Austin, Brian T Urbani, Andrew N Fleischman, Navin D Fernando, James J Purtill, William J Hozack, Javad Parvizi, Richard H Rothman
BACKGROUND: The value of formal physical therapy after total hip arthroplasty is unknown. With substantial changes that have occurred in surgical and anesthesia techniques, self-directed therapy may be efficacious in restoring function to patients undergoing total hip arthroplasty. METHODS: We conducted a single-center, randomized trial of 120 patients undergoing primary, unilateral total hip arthroplasty who were eligible for direct home discharge. The experimental group followed a self-directed home exercise program for 10 weeks...
April 19, 2017: Journal of Bone and Joint Surgery. American Volume
https://www.readbyqxmd.com/read/28418656/informing-the-selection-of-screening-hit-series-with-in-silico-absorption-distribution-metabolism-excretion-and-toxicity-profiles
#18
John M Sanders, Douglas C Beshore, J Chris Culberson, James I Fells, Jason E Imbriglio, Hakan Gunaydin, Andrew M Haidle, Marc Labroli, Brian E Mattioni, Nunzio Sciammetta, William D Shipe, Robert P Sheridan, Linda M Suen, Andreas Verras, Abbas M Walji, Elizabeth M Joshi, Tjerk Bueters
High-throughput screening (HTS) has enabled millions of compounds to be assessed for biological activity, but challenges remain in the prioritization of hit series. While biological, absorption, distribution, metabolism, excretion, and toxicity (ADMET), purity, and structural data are routinely used to select chemical matter for further follow-up, the scarcity of historical ADMET data for screening hits limits our understanding of early hit compounds. Herein, we describe a process that utilizes a battery of in-house quantitative structure activity relationship (QSAR) models to generate in silico ADMET profiles for hit series to enable more complete characterizations of HTS chemical matter...
April 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28418294/exposure-risk-for-infection-and-lack-of-human-to-human-transmission-of-mycobacterium-ulcerans-disease-australia
#19
Daniel P O'Brien, James W Wynne, Andrew H Buultjens, Wojtek P Michalski, Timothy P Stinear, N Deborah Friedman, Andrew Hughes, Eugene Athan
We conducted epidemiologic and genetic analyses of family clusters of Mycobacterium ulcerans (Buruli ulcer) disease in southeastern Australia. We found that the incidence of M. ulcerans disease in family members was increased. However, the risk for exposure appeared short-term and not related to human-human transmission.
May 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28416613/hypoxia-inducible-factor-1%C3%AE-activates-insig-2-transcription-for-degradation-of-hmg-coa-reductase-in-the-liver
#20
Seonghwan Hwang, Andrew D Nguyen, Youngah Jo, Luke J Engelking, James Brugarolas, Russell A DeBose-Boyd
Cholesterol synthesis is a highly oxygen-consuming process. As such, oxygen deprivation (hypoxia) limits cholesterol synthesis through incompletely understood mechanisms mediated by the oxygen-sensitive transcription factor hypoxia-inducible factor (HIF)-1α. We show here that HIF-1α links pathways for oxygen sensing and feedback control of cholesterol synthesis in human fibroblasts by directly activating transcription of the INSIG-2 gene. Insig-2 is one of two endoplasmic reticulum (ER) membrane proteins that inhibit cholesterol synthesis by mediating sterol-induced ubiquitination and subsequent ER-associated degradation of the rate-limiting enzyme in the pathway, HMG CoA reductase (HMGCR)...
April 17, 2017: Journal of Biological Chemistry
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