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Jeffrey Miller

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https://www.readbyqxmd.com/read/28635286/utilization-of-an-active-site-mutant-receptor-for-the-identification-of-potent-and-selective-atypical-5-ht2c-receptor-agonists
#1
Joseph Carpenter, Ying Wang, Gang Wu, Jianxin Feng, Xiang-Yang Ye, Christian L Morales, Matthias Broekema, Karen A Rossi, Keith J Miller, Brian J Murphy, Ginger Yingzhe Wu, Sarah E Malmstrom, Anthony V Azzara, Philip M Sher, John M Fevig, Andrew Alt, Robert L Bertekap, Mary Jane Cullen, Timothy M Harper, Kimberly A Foster, Chiuwa Emily Luk, Qian Xiang, Mary F Grubb, Jeffrey A Robl, Dean A Wacker
Agonism of the 5-HT2C receptor represents one of the most well-studied and clinically-proven mechanisms for pharmacological weight reduction. Selectivity over the closely related 5-HT2A and 5-HT2B receptors is critical as their activation has been shown to lead to undesirable side-effects and major safety concerns. In this communication, we report the development of a new screening paradigm which utilizes an active site mutant D134A 5-HT2C receptor to identify atypical agonist structures. We additionally report the discovery and optimization of a novel class of non-basic heterocyclic amide agonists of 5-HT2C...
June 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28617917/genomic-profiling-of-small-bowel-adenocarcinoma
#2
Alexa B Schrock, Craig E Devoe, Robert McWilliams, James Sun, Thomas Aparicio, Philip J Stephens, Jeffrey S Ross, Richard Wilson, Vincent A Miller, Siraj M Ali, Michael J Overman
Importance: Small-bowel adenocarcinomas (SBAs) are rare cancers with a significantly lower incidence, later stage at diagnosis, and worse overall survival than other intestinal-derived cancers. To date, comprehensive genomic analysis of SBA is lacking. Objective: To perform in-depth genomic characterization of a large series of SBAs and other gastrointestinal tumors to draw comparisons and identify potentially clinically actionable alterations. Design, Setting, and Participants: Prospective analysis was performed of clinical samples from patients with SBA (n = 317), colorectal cancer (n = 6353), and gastric carcinoma (n = 889) collected between August 24, 2012, and February 3, 2016, using hybrid-capture-based genomic profiling, at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions...
June 15, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28613108/a-novel-phylogroup-of-pseudomonas-cichorii-identified-following-an-unusual-disease-outbreak-on-tomato
#3
Sujan Timilsina, Heather Adkison, Anna Louise Testen, Eric A Newberry, Sally A Miller, Mathews Lal Paret, Gerald V Minsavage, Erica M Goss, Jeffrey B Jones, Gary E Vallad
Recently, in Central Florida tomato production fields, tomato foliage and fruit were observed with symptoms similar to bacterial speck. Fluorescent pseudomonads were consistently isolated and the strains were characterized by standard LOPAT tests, pathogenicity tests and genetic characterization using 16S rRNA sequences and multilocus sequence analysis of conserved housekeeping genes. LOPAT test results indicated the strains were likely P. cichorii. These strains were pathogenic on tomato and were also pathogenic on lettuce, the host for the type strain of P...
June 14, 2017: Phytopathology
https://www.readbyqxmd.com/read/28602834/cns-disease-diminishes-the-therapeutic-functionality-of-bone-marrow-mesenchymal-stem-cells
#4
Alex Sargent, Lianhua Bai, Genevieve Shano, Molly Karl, Eric Garrison, Lahiru Ranasinghe, Sarah M Planchon, Jeffrey Cohen, Robert H Miller
Mesenchymal stem cells (MSCs) have emerged as a potentially powerful cellular therapy for autoimmune diseases including multiple sclerosis (MS). Based on their success in treating animal models of MS like experimental autoimmune encephalomyelitis (EAE), MSCs have moved rapidly into clinical trials for MS. The majority of these trials use autologous MSCs derived from MS patients, although it remains unclear how CNS disease may affect these cells. Here, we report that bone marrow MSCs derived from EAE mice lack therapeutic efficacy compared to naïve MSCs in their ability to ameliorate EAE...
June 9, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28592970/lps-from-p-gingivalis-negatively-alters-gingival-cell-mitochondrial-bioenergetics
#5
Kiran Napa, Andrea C Baeder, Jeffrey E Witt, Sarah T Rayburn, Madison G Miller, Blake W Dallon, Jonathan L Gibbs, Shalene H Wilcox, Duane R Winden, Jared H Smith, Paul R Reynolds, Benjamin T Bikman
OBJECTIVE: Oral inflammatory pathologies are linked to increased oxidative stress, thereby partly explaining their relevance in the etiology of systemic disorders. The purpose of this work was to determine the degree to which LPS from Porphyromonas gingivalis, the primary pathogen related to oral inflammation, altered gingival mitochondrial function and reactive oxygen species generation. METHODS: Human gingival fibroblast (HGF-1) cells were treated with lipopolysaccharide of P...
2017: International Journal of Dentistry
https://www.readbyqxmd.com/read/28592388/characterization-of-clinical-cases-of-advanced-papillary-renal-cell-carcinoma-via-comprehensive-genomic-profiling
#6
Sumanta K Pal, Siraj M Ali, Evgeny Yakirevich, Daniel M Geynisman, Jose A Karam, Julia A Elvin, Garrett M Frampton, Xuan Huang, Douglas I Lin, Mark Rosenzweig, Doron Lipson, Philip J Stephens, Jeffrey S Ross, Vincent A Miller, Neeraj Agarwal, Brian Shuch, Toni K Choueiri, Jon H Chung
BACKGROUND: Papillary renal cell carcinoma (PRCC) is a rare subset of RCC. The Cancer Genome Atlas (TCGA) data largely reflect localized disease, and there are limited data for advanced PRCC. OBJECTIVE: To characterize the frequency of genomic alterations (GAs) in patients with advanced PRCC for whom comprehensive genomic profiling (CGP) was performed in the context of routine clinical care. DESIGN, SETTING, AND PARTICIPANTS: Formalin-fixed, paraffin-embedded tissue was obtained for 169 consecutive patients with confirmed PRCC...
May 30, 2017: European Urology
https://www.readbyqxmd.com/read/28588151/in-vivo-imaging-of-the-programmed-death-ligand-1-by-18-f-positron-emission-tomography
#7
Dinko E Gonzalez Trotter, Xiangjun Meng, Paul McQuade, Daniel Rubins, Michael Klimas, Zhizhen Zhang, Brett M Connolly, Patricia J Miller, Stacey S O'Malley, Shu-An Lin, Krista L Getty, Laurence Fayadat-Dilman, Linda Liang, Elisabet Wahlberg, Olof Widmark, Caroline Ekblad, Fredrik Y Frejd, Eric D Hostetler, Jeffrey L Evelhoch
Introduction: PD-L1 (Programmed Death Ligand 1) is an immune regulatory ligand that binds to the T-cell immune check point PD-1 (Programmed Death 1). Tumor expression of PD-L1 is correlated with immune suppression and poor prognosis. It is also correlated with therapeutic efficacy of PD-1 and PD-L1 inhibitors. In vivo imaging may enable real-time follow-up of changing PD-L1 expression and heterogeneity evaluation of PD-L1 expression across tumors in the same subject. We have radiolabeled the PD-L1 binding Affibody® molecule NOTA-ZPD-L1_1 with (18)F and evaluated its in vitro and in vivo binding affinity, targeting and specificity...
June 6, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28581676/comprehensive-genomic-profiling-of-different-subtypes-of-nasopharyngeal-carcinoma-reveals-similarities-and-differences-to-guide-targeted-therapy
#8
Siraj M Ali, Ming Yao, Jicheng Yao, Jing Wang, Yuwei Cheng, Alexa B Schrock, Gung-Wei Chirn, Hui Chen, Shuo Mu, Laurie Gay, Julia A Elvin, James Suh, Vincent A Miller, Philip J Stephens, Jeffrey S Ross, Kai Wang
BACKGROUND: To date, no targeted therapy has been approved for nasopharyngeal carcinoma (NPC), and this underscores the need for an in-depth understanding of clinically relevant genomic alterations (CRGAs). METHODS: Comprehensive genomic profiling was performed for 190 NPC patients, including 20 patients with nasopharyngeal adenocarcinoma (NPAC), 62 patients with nasopharyngeal squamous cell carcinoma (NPSCC), and 108 patients with nasopharyngeal undifferentiated carcinoma (NPUC)...
June 5, 2017: Cancer
https://www.readbyqxmd.com/read/28581512/structural-basis-for-the-cooperative-allosteric-activation-of-the-free-fatty-acid-receptor-gpr40
#9
Jun Lu, Noel Byrne, John Wang, Gerard Bricogne, Frank K Brown, Harry R Chobanian, Steven L Colletti, Jerry Di Salvo, Brande Thomas-Fowlkes, Yan Guo, Dawn L Hall, Jennifer Hadix, Nicholas B Hastings, Jeffrey D Hermes, Thu Ho, Andrew D Howard, Hubert Josien, Maria Kornienko, Kevin J Lumb, Michael W Miller, Sangita B Patel, Barbara Pio, Christopher W Plummer, Bradley S Sherborne, Payal Sheth, Sarah Souza, Srivanya Tummala, Clemens Vonrhein, Maria Webb, Samantha J Allen, Jennifer M Johnston, Adam B Weinglass, Sujata Sharma, Stephen M Soisson
Clinical studies indicate that partial agonists of the G-protein-coupled, free fatty acid receptor 1 GPR40 enhance glucose-dependent insulin secretion and represent a potential mechanism for the treatment of type 2 diabetes mellitus. Full allosteric agonists (AgoPAMs) of GPR40 bind to a site distinct from partial agonists and can provide additional efficacy. We report the 3.2-Å crystal structure of human GPR40 (hGPR40) in complex with both the partial agonist MK-8666 and an AgoPAM, which exposes a novel lipid-facing AgoPAM-binding pocket outside the transmembrane helical bundle...
June 5, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28570277/epithelial-gpr116-regulates-pulmonary-alveolar-homeostasis-via-gq-11-signaling
#10
Kari Brown, Alyssa Filuta, Marie-Gabrielle Ludwig, Klaus Seuwen, Julian Jaros, Solange Vidal, Kavisha Arora, Anjaparavanda P Naren, Kathirvel Kandasamy, Kaushik Parthasarathi, Stefan Offermanns, Robert J Mason, William E Miller, Jeffrey A Whitsett, James P Bridges
Pulmonary function is dependent upon the precise regulation of alveolar surfactant. Alterations in pulmonary surfactant concentrations or function impair ventilation and cause tissue injury. Identification of the molecular pathways that sense and regulate endogenous alveolar surfactant concentrations, coupled with the ability to pharmacologically modulate them both positively and negatively, would be a major therapeutic advance for patients with acute and chronic lung diseases caused by disruption of surfactant homeostasis...
June 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/28557557/subsequent-surgery-after-revision-anterior-cruciate-ligament-reconstruction-rates-and-risk-factors-from-a-multicenter-cohort
#11
David Y Ding, Alan L Zhang, Christina R Allen, Allen F Anderson, Daniel E Cooper, Thomas M DeBerardino, Warren R Dunn, Amanda K Haas, Laura J Huston, Brett Brick A Lantz, Barton Mann, Kurt P Spindler, Michael J Stuart, Rick W Wright, John P Albright, Annunziato Ned Amendola, Jack T Andrish, Christopher C Annunziata, Robert A Arciero, Bernard R Bach, Champ L Baker, Arthur R Bartolozzi, Keith M Baumgarten, Jeffery R Bechler, Jeffrey H Berg, Geoffrey A Bernas, Stephen F Brockmeier, Robert H Brophy, Charles A Bush-Joseph, J Brad Butler, John D Campbell, James L Carey, James E Carpenter, Brian J Cole, Jonathan M Cooper, Charles L Cox, R Alexander Creighton, Diane L Dahm, Tal S David, David C Flanigan, Robert W Frederick, Theodore J Ganley, Elizabeth A Garofoli, Charles J Gatt, Steven R Gecha, James Robert Giffin, Sharon L Hame, Jo A Hannafin, Christopher D Harner, Norman Lindsay Harris, Keith S Hechtman, Elliott B Hershman, Rudolf G Hoellrich, Timothy M Hosea, David C Johnson, Timothy S Johnson, Morgan H Jones, Christopher C Kaeding, Ganesh V Kamath, Thomas E Klootwyk, Bruce A Levy, C Benjamin Ma, G Peter Maiers, Robert G Marx, Matthew J Matava, Gregory M Mathien, David R McAllister, Eric C McCarty, Robert G McCormack, Bruce S Miller, Carl W Nissen, Daniel F O'Neill, Brett D Owens, Richard D Parker, Mark L Purnell, Arun J Ramappa, Michael A Rauh, Arthur C Rettig, Jon K Sekiya, Kevin G Shea, Orrin H Sherman, James R Slauterbeck, Matthew V Smith, Jeffrey T Spang, Steven J Svoboda, Timothy N Taft, Joachim J Tenuta, Edwin M Tingstad, Armando F Vidal, Darius G Viskontas, Richard A White, James S Williams, Michelle L Wolcott, Brian R Wolf, James J York
BACKGROUND: While revision anterior cruciate ligament reconstruction (ACLR) can be performed to restore knee stability and improve patient activity levels, outcomes after this surgery are reported to be inferior to those after primary ACLR. Further reoperations after revision ACLR can have an even more profound effect on patient satisfaction and outcomes. However, there is a current lack of information regarding the rate and risk factors for subsequent surgery after revision ACLR. PURPOSE: To report the rate of reoperations, procedures performed, and risk factors for a reoperation 2 years after revision ACLR...
May 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/28550065/exceptional-durable-response-to-everolimus-in-a-patient-with-biphenotypic-breast-cancer-harboring-an-stk11-variant
#12
Christine A Parachoniak, Andrew Rankin, Bernadette Gaffney, Ryan Hartmaier, Dan Spritz, Rachel L Erlich, Vincent A Miller, Deborah Morosini, Phil Stephens, Jeffrey S Ross, John Keech, Juliann Chmielecki
Metastatic triple negative breast cancer comprises 12-17% of breast cancers and carries a poor prognosis relative to other breast cancer subtypes. Treatment options in this disease are largely limited to systemic chemotherapy. A majority of clinical studies assessing efficacy of targeted therapeutics (e.g. the mTOR inhibitor everolimus) in advanced breast cancer patients have not utilized predictive genomic biomarker-based selection and have reported only modest improvement in clinical outcome relative to standard of care...
May 26, 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28539475/the-brain-microenvironment-mediates-resistance-in-luminal-breast-cancer-to-pi3k-inhibition-through-her3-activation
#13
David P Kodack, Vasileios Askoxylakis, Gino B Ferraro, Qing Sheng, Mark Badeaux, Shom Goel, Xiaolong Qi, Ram Shankaraiah, Z Alexander Cao, Rakesh R Ramjiawan, Divya Bezwada, Bhushankumar Patel, Yongchul Song, Carlotta Costa, Kamila Naxerova, Christina S F Wong, Jonas Kloepper, Rita Das, Angela Tam, Jantima Tanboon, Dan G Duda, C Ryan Miller, Marni B Siegel, Carey K Anders, Melinda Sanders, Monica V Estrada, Robert Schlegel, Carlos L Arteaga, Elena Brachtel, Alan Huang, Dai Fukumura, Jeffrey A Engelman, Rakesh K Jain
Although targeted therapies are often effective systemically, they fail to adequately control brain metastases. In preclinical models of breast cancer that faithfully recapitulate the disparate clinical responses in these microenvironments, we observed that brain metastases evade phosphatidylinositide 3-kinase (PI3K) inhibition despite drug accumulation in the brain lesions. In comparison to extracranial disease, we observed increased HER3 expression and phosphorylation in brain lesions. HER3 blockade overcame the resistance of HER2-amplified and/or PIK3CA-mutant breast cancer brain metastases to PI3K inhibitors, resulting in marked tumor growth delay and improvement in mouse survival...
May 24, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28537348/a-cadaver-study-to-evaluate-the-accuracy-of-a-new-3d-mini-optical-navigation-tool-for-total-hip-arthroplasty
#14
Jonathan M Vigdorchik, Michael B Cross, Eric A Bogner, Theodore T Miller, Jeffrey M Muir, Ran Schwarzkopf
BACKGROUND: Accurate measurement of acetabular cup position (CP), changes in leg length (LL), and offset (OS) are paramount in ensuring proper sizing and implantation of components during total hip arthroplasty (THA). LL/OS inaccuracies can cause low back pain, neurological deficits, and patient dissatisfaction, while inaccurate positioning of the acetabular cup can lead to instability, dislocation, and, ultimately, revision surgery. The objective of this study was to evaluate the accuracy of a mini-navigation tool in measuring CP and LL/OS differential during THA...
May 24, 2017: Surgical Technology International
https://www.readbyqxmd.com/read/28533303/cardiopulmonary-resuscitation-in-adults-and-children-with-mechanical-circulatory-support-a-scientific-statement-from-the-american-heart-association
#15
REVIEW
Mary Ann Peberdy, Jason A Gluck, Joseph P Ornato, Christian A Bermudez, Russell E Griffin, Vigneshwar Kasirajan, Richard E Kerber, Eldrin F Lewis, Mark S Link, Corinne Miller, Jeffrey J Teuteberg, Ravi Thiagarajan, Robert M Weiss, Brian O'Neil
Cardiac arrest in patients on mechanical support is a new phenomenon brought about by the increased use of this therapy in patients with end-stage heart failure. This American Heart Association scientific statement highlights the recognition and treatment of cardiovascular collapse or cardiopulmonary arrest in an adult or pediatric patient who has a ventricular assist device or total artificial heart. Specific, expert consensus recommendations are provided for the role of external chest compressions in such patients...
May 22, 2017: Circulation
https://www.readbyqxmd.com/read/28530141/decisions-around-long-term-ventilation-for-children-perspectives-of-directors-of-pediatric-home-ventilation-programs
#16
Jeffrey D Edwards, Marilyn C Morris, Judith E Nelson, Howard B Panitch, Rachel L Miller
RATIONALE: The decision of whether to initiate or forgo long-term ventilation for children with life-limiting conditions can be complex and impactful. Providers are responsible for helping families to understand the consequences of their options and guiding them through shared decision-making, but little has been published on how to do this. OBJECTIVES: To assess how directors of pediatric home ventilation programs facilitate shared decision-making with families facing decisions of whether to initiate or forgo long-term ventilation for their children with life-limiting conditions...
May 21, 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28516848/the-role-of-psychopathic-traits-in-female-sexual-coercion
#17
Holly A Miller, Jeffrey A Bouffard, Cassidy A DeHaan
Researchers have consistently found a relationship between psychopathy and the use of sexual coercion in samples of males with and without previous sexual arrests (Abbey, Jacques-Tiura, & LeBreton, 2011; Hare, 1991; Hersh & Gray-Little, 1998; Seto & Lalumiere, 2000). Although there is growing recognition that females also engage in sexually coercive behavior, current understanding of female coercion is limited (Bouffard, Bouffard, & Miller, 2015; Cortoni, Hanson, & Coache, 2010; Muñoz, Khan, & Cordwell, 2011)...
May 17, 2017: Violence and Victims
https://www.readbyqxmd.com/read/28516158/a-management-algorithm-for-mitomycin-c-induced-cystitis
#18
Amy N Luckenbaugh, Rory M Marks, David C Miller, Alon Z Weizer, John T Stoffel, Jeffrey S Montgomery
Background/Objective: A post-bladder tumor resection dose of MMC can reduce non-invasive papillary (pTa) bladder cancer recurrences by up to 40%; this treatment is recommended in both the AUA and EUA non-muscle-invasive bladder cancer guidelines. A common complication of this treatment is eosinophilic cystitis. Symptoms range from mild urinary frequency and urgency to debilitating pain and dysuria. Currently, there is no established treatment algorithm for MMC-induced cystitis. Methods: Members of the Urologic Surgery Quality Collaborative (USQC), a group composed of over 160 private and academic urologists, met to discuss the management of patients with cystitis following MMC therapy...
April 27, 2017: Bladder Cancer
https://www.readbyqxmd.com/read/28507204/detection-of-an-alk-fusion-in-colorectal-carcinoma-by-hybrid-capture-based-assay-of-circulating-tumor-dna
#19
Andrea Z Lai, Alexa B Schrock, Rachel L Erlich, Jeffrey S Ross, Vincent A Miller, Evgeny Yakirevich, Siraj M Ali, Fadi Braiteh
ALK rearrangements have been observed in 0.05%-2.5% of patients with colorectal cancers (CRCs) and are predicted to be oncogenic drivers largely mutually exclusive of KRAS, NRAS, or BRAF alterations. Here we present the case of a patient with metastatic CRC who was treatment naïve at the time of molecular testing. Initial ALK immunohistochemistry (IHC) staining was negative, but parallel genomic profiling of both circulating tumor DNA (ctDNA) and tissue using similar hybrid capture-based assays each identified an identical STRN-ALK fusion...
May 15, 2017: Oncologist
https://www.readbyqxmd.com/read/28504123/erythropoietin-and-small-molecule-agonists-of-the-tissue-protective-erythropoietin-receptor-increase-fxn-expression-in-neuronal-cells-in%C3%A2-vitro-and-in-fxn-deficient-kiko-mice-in%C3%A2-vivo
#20
James L Miller, Myriam Rai, Normand L Frigon, Massimo Pandolfo, Juha Punnonen, Jeffrey R Spencer
Friedreich's ataxia (FA) is a progressive neurodegenerative disease caused by reduced levels of the mitochondrial protein frataxin (FXN). Recombinant human erythropoietin (rhEPO) increased FXN protein in vitro and in early clinical studies, while no published reports evaluate rhEPO in animal models of FA. STS-E412 and STS-E424 are novel small molecule agonists of the tissue-protective, but not the erythropoietic EPO receptor. We find that rhEPO, STS-E412 and STS-E424 increase FXN expression in vitro and in vivo...
May 11, 2017: Neuropharmacology
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