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https://www.readbyqxmd.com/read/28439809/site-selection-a-case-study-in-the-identification-of-optimal-cysteine-engineered-antibody-drug-conjugates
#1
L Nathan Tumey, Fengping Li, Brian Rago, Xiaogang Han, Frank Loganzo, Sylvia Musto, Edmund I Graziani, Sujiet Puthenveetil, Jeffrey Casavant, Kimberly Marquette, Tracey Clark, Jack Bikker, Eric M Bennett, Frank Barletta, Nicole Piche-Nicholas, Amy Tam, Christopher J O'Donnell, Hans Peter Gerber, Lioudmila Tchistiakova
As the antibody drug conjugate (ADC) community continues to shift towards site-specific conjugation technology, there is a growing need to understand how the site of conjugation impacts the biophysical and biological properties of an ADC. In order to address this need, we prepared a carefully selected series of engineered cysteine ADCs and proceeded to systematically evaluate their potency, stability, and PK exposure. The site of conjugation did not have a significant influence on the thermal stability and in vitro cytotoxicity of the ADCs...
April 24, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28437289/congenital-pseudarthrosis-of-the-tibia
#2
Courtney O'Donnell, James Foster, Ryan Mooney, Corey Beebe, Nathan Donaldson, Travis Heare
No abstract text is available yet for this article.
April 21, 2017: JBJS Reviews
https://www.readbyqxmd.com/read/28436458/development-of-a-fluorescent-asfv-strain-that-retains-the-ability-to-cause-disease-in-swine
#3
Manuel V Borca, Vivian O'Donnell, Lauren G Holinka, Brent Sanford, Paul A Azzinaro, Guillermo R Risatti, Douglas P Gladue
African swine fever is a contagious and often lethal disease for domestic pigs with a significant economic impact for the swine industry. The etiological agent, African swine fever virus (ASFV), is a highly structurally complex double stranded DNA virus. No effective vaccines or antiviral treatment are currently commercially available. We present here the development of a strain of ASFV that has been shown to retain its ability to cause disease in swine, efficiently replicate in swine macrophage and that is fluorescently tagged...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28435344/development-of-performance-and-error-metrics-for-ultrasound-guided-axillary-brachial-plexus-block
#4
Osman M Ahmed, Brian D O'Donnell, Anthony G Gallagher, George D Shorten
PURPOSE: Change in the landscape of medical education coupled with a paradigm shift toward outcome-based training mandates the trainee to demonstrate specific predefined performance benchmarks in order to progress through training. A valid and reliable assessment tool is a prerequisite for this process. The objective of this study was to characterize ultrasound-guided axillary brachial plexus block to develop performance and error metrics and to verify face and content validity using a modified Delphi method...
2017: Advances in Medical Education and Practice
https://www.readbyqxmd.com/read/28435153/human-rhinovirus-induced-inflammatory-responses-are-inhibited-by-phosphatidylserine-containing-liposomes
#5
C A Stokes, R Kaur, M R Edwards, M Mondhe, D Robinson, E C Prestwich, R D Hume, C A Marshall, Y Perrie, V B O'Donnell, J L Harwood, I Sabroe, L C Parker
No abstract text is available yet for this article.
May 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28435047/histological-and-cognitive-alterations-in-adult-diabetic-rats-following-an-episode-of-juvenile-diabetic-ketoacidosis-evidence-of-permanent-cerebral-injury
#6
Nicole Glaser, Jennifer Sasaki-Russell, Michael Cohen, Christopher Little, Martha O'Donnell, Jeffrey Sall
Evidence suggests that diabetic ketoacidosis (DKA) may cause subtle cognitive alterations in children but the mechanisms are poorly understood. Acute DKA is associated with reactive astrogliosis and microglial activation in a rat model. Whether these inflammatory changes permanently alter brain histology is unknown. We aimed to determine whether DKA results in permanent alterations in brain histology and whether these changes are associated with cognitive deficits in a rat model. We induced diabetes in juvenile rats with streptozotocin at 4 weeks of age...
April 20, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28432403/bone-marrow-fat-content-in-70-adolescent-girls-with-anorexia-nervosa-magnetic-resonance-imaging-and-magnetic-resonance-spectroscopy-assessment
#7
Kirsten Ecklund, Sridhar Vajapeyam, Robert V Mulkern, Henry A Feldman, Jennifer M O'Donnell, Amy D DiVasta, Catherine M Gordon
BACKGROUND: Adolescents and women with anorexia nervosa have increased bone marrow fat and decreased bone formation, at least in part due to hormonal changes leading to preferential stem cell differentiation to adipocytes over osteoblasts. OBJECTIVE: The purpose of this study was to evaluate marrow fat content and correlate with age and disease severity using knee MRI with T1 relaxometry (T1-R) and MR spectroscopy (MRS) in 70 adolescents with anorexia nervosa. MATERIALS AND METHODS: We enrolled 70 girls with anorexia nervosa who underwent 3-T knee MRI with coronal T1-W images, T1-R and single-voxel proton MRS at 30 and 60 ms TE...
April 22, 2017: Pediatric Radiology
https://www.readbyqxmd.com/read/28431058/additional-electrodes-on-the-quartet%C3%A2-lv-lead-provide-more-programmable-pacing-options-than-bipolar-and-tripolar-equivalents
#8
David O'Donnell, Johannes Sperzel, Bernard Thibault, Christopher A Rinaldi, Carlo Pappone, Klaus-Jürgen Gutleben, Christopher Leclercq, Hedi Razavi, Kyungmoo Ryu, Luke C Mcspadden, Avi Fischer, Gery Tomassoni
Aims: The aim of this study was to evaluate any benefits to the number of viable pacing vectors and maximal spatial coverage with quadripolar left ventricular (LV) leads when compared with tripolar and bipolar equivalents in patients receiving cardiac resynchronization therapy (CRT). Methods and Results: A meta-analysis of five previously published clinical trials involving the Quartet™ LV lead (St Jude Medical, St Paul, MN, USA) was performed to evaluate the number of viable pacing vectors defined as capture thresholds ≤2...
April 1, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28427541/long-term-safety-and-efficacy-of-glycopyrrolate-formoterol-metered-dose-inhaler-using-novel-co-suspension%C3%A2-delivery-technology-in-patients-with-chronic-obstructive-pulmonary-disease
#9
Nicola A Hanania, Donald P Tashkin, Edward M Kerwin, James F Donohue, Michael Denenberg, Denis E O'Donnell, Dean Quinn, Shahid Siddiqui, Chad Orevillo, Andrea Maes, Colin Reisner
BACKGROUND: The long-term safety and efficacy of a novel Co-Suspension™ Delivery Technology glycopyrrolate (GP)/formoterol fumarate (FF) 18/9.6 μg fixed-dose combination metered dose inhaler (GFF MDI) were investigated in a 28-week safety extension study (PINNACLE-3, NCT01970878) of two randomized controlled Phase III trials (PINNACLE-1 and -2; NCT01854645 and NCT01854658) in subjects with moderate-to-very severe chronic obstructive pulmonary disease (COPD). METHODS: Subjects completing 24 weeks' treatment with GFF MDI, GP MDI, FF MDI (all twice-daily) or open-label tiotropium 18 μg (once-daily) in PINNACLE-1 or -2 were randomly selected to continue treatment for 28 weeks...
May 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28426940/prospective-assessment-of-virtual-screening-heuristics-derived-using-a-novel-fusion-score
#10
Dante A Pertusi, Gregory O'Donnell, Michelle F Homsher, Kelli Solly, Amita Patel, Shannon L Stahler, Daniel Riley, Michael F Finley, Eleftheria N Finger, Gregory C Adam, Juncai Meng, David J Bell, Paul D Zuck, Edward M Hudak, Michael J Weber, Jennifer E Nothstein, Louis Locco, Carissa Quinn, Adam Amoss, Brian Squadroni, Michelle Hartnett, Mee Ra Heo, Tara White, S Alex May, Evelyn Boots, Kenneth Roberts, Patrick Cocchiarella, Alex Wolicki, Anthony Kreamer, Peter S Kutchukian, Anne Mai Wassermann, Victor N Uebele, Meir Glick, Andrew Rusinko, J Christopher Culberson
High-throughput screening (HTS) is a widespread method in early drug discovery for identifying promising chemical matter that modulates a target or phenotype of interest. Because HTS campaigns involve screening millions of compounds, it is often desirable to initiate screening with a subset of the full collection. Subsequently, virtual screening methods prioritize likely active compounds in the remaining collection in an iterative process. With this approach, orthogonal virtual screening methods are often applied, necessitating the prioritization of hits from different approaches...
April 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28424418/the-aryl-hydrocarbon-receptor-is-required-for-induction-of-p21cip1-waf1-expression-and-growth-inhibition-by-su5416-in-hepatoma-cells
#11
Edmond F O'Donnell, Hyo Sang Jang, Martin Pearce, Nancy I Kerkvliet, Siva Kumar Kolluri
The aryl hydrocarbon receptor (AhR) is a potential clinical target for cancer and autoimmune dysfunction. Identifying selective AhR modulators that produce desirable clinical outcomes represents an opportunity for developing new anti-cancer agents. Repurposing clinically-used drugs with established safety profiles that activate the AhR represents a good starting place to pursue this goal. In this study, we characterized the AhR-dependent effects of SU5416 (Semaxanib) following its identification in a small-molecule library screen...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424359/effects-of-combined-tiotropium-olodaterol-on-inspiratory-capacity-and-exercise-endurance-in-copd
#12
Denis E O'Donnell, Richard Casaburi, Peter Frith, Anne Kirsten, Dorothy De Sousa, Alan Hamilton, Wenqiong Xue, François Maltais
Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler...
April 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28424332/improving-genetic-diagnosis-in-mendelian-disease-with-transcriptome-sequencing
#13
Beryl B Cummings, Jamie L Marshall, Taru Tukiainen, Monkol Lek, Sandra Donkervoort, A Reghan Foley, Veronique Bolduc, Leigh B Waddell, Sarah A Sandaradura, Gina L O'Grady, Elicia Estrella, Hemakumar M Reddy, Fengmei Zhao, Ben Weisburd, Konrad J Karczewski, Anne H O'Donnell-Luria, Daniel Birnbaum, Anna Sarkozy, Ying Hu, Hernan Gonorazky, Kristl Claeys, Himanshu Joshi, Adam Bournazos, Emily C Oates, Roula Ghaoui, Mark R Davis, Nigel G Laing, Ana Topf, Peter B Kang, Alan H Beggs, Kathryn N North, Volker Straub, James J Dowling, Francesco Muntoni, Nigel F Clarke, Sandra T Cooper, Carsten G Bönnemann, Daniel G MacArthur
Exome and whole-genome sequencing are becoming increasingly routine approaches in Mendelian disease diagnosis. Despite their success, the current diagnostic rate for genomic analyses across a variety of rare diseases is approximately 25 to 50%. We explore the utility of transcriptome sequencing [RNA sequencing (RNA-seq)] as a complementary diagnostic tool in a cohort of 50 patients with genetically undiagnosed rare muscle disorders. We describe an integrated approach to analyze patient muscle RNA-seq, leveraging an analysis framework focused on the detection of transcript-level changes that are unique to the patient compared to more than 180 control skeletal muscle samples...
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28424146/excess-all-cause-and-influenza-attributable-mortality-in-europe-december-2016-to-february-2017
#14
Lasse S Vestergaard, Jens Nielsen, Tyra G Krause, Laura Espenhain, Katrien Tersago, Natalia Bustos Sierra, Gleb Denissov, Kaire Innos, Mikko J Virtanen, Anne Fouillet, Theodore Lytras, Anna Paldy, Janos Bobvos, Lisa Domegan, Joan O'Donnell, Matteo Scortichini, Annamaria de Martino, Kathleen England, Neville Calleja, Liselotte van Asten, Anne C Teirlinck, Ragnhild Tønnessen, Richard A White, Susana P Silva, Ana P Rodrigues, Amparo Larrauri, Inmaculada Leon, Ahmed Farah, Christoph Junker, Mary Sinnathamby, Richard G Pebody, Arlene Reynolds, Jennifer Bishop, Diane Gross, Cornelia Adlhoch, Pasi Penttinen, Kåre Mølbak
Since December 2016, excess all-cause mortality was observed in many European countries, especially among people aged ≥ 65 years. We estimated all-cause and influenza-attributable mortality in 19 European countries/regions. Excess mortality was primarily explained by circulation of influenza virus A(H3N2). Cold weather snaps contributed in some countries. The pattern was similar to the last major influenza A(H3N2) season in 2014/15 in Europe, although starting earlier in line with the early influenza season start...
April 6, 2017: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/28423310/c-myb-regulates-the-t-bet-dependent-differentiation-program-in-b-cells-to-coordinate-antibody-responses
#15
Dana Piovesan, Jessica Tempany, Andrea Di Pietro, Inge Baas, Callisthenis Yiannis, Kristy O'Donnell, Yunshun Chen, Victor Peperzak, Gabrielle T Belz, Charles R Mackay, Gordon K Smyth, Joanna R Groom, David M Tarlinton, Kim L Good-Jacobson
Humoral immune responses are tailored to the invading pathogen through regulation of key transcription factors and their networks. This is critical to establishing effective antibody-mediated responses, yet it is unknown how B cells integrate pathogen-induced signals to drive or suppress transcriptional programs specialized for each class of pathogen. Here, we detail the key role of the transcription factor c-Myb in regulating the T-bet-mediated anti-viral program. Deletion of c-Myb in mature B cells significantly increased serum IgG2c and CXCR3 expression by upregulating T-bet, normally suppressed during Th2-cell-mediated responses...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28421763/synthetic-approaches-to-new-drugs-approved-during-2015
#16
Andrew C Flick, Hong Xia Ding, Carolyn A Leverett, Robert E Kyne, Kevin K-C Liu, Sarah J Fink, Christopher J O'Donnell
New drugs introduced to the market every year represent privileged structures for particular biological targets. These new chemical entities (NCEs) provide insight into molecular recognition while serving as leads for designing future new drugs. This annual review describes the most likely process-scale synthetic approaches to twenty nine new chemical entities (NCEs) that were approved for the first time in 2015.
April 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28413382/angiomyolipoma-with-epithelial-cysts-masquerading-as-a-cystic-renal-cell-carcinoma
#17
Andrew Wood, Fiona Young, Marie O'Donnell
Angiomyolipoma with epithelial cysts (AMLEC) is a very uncommon renal tumor. AMLEC has a characteristic histological appearance and immunohistochemical staining pattern, knowledge of which should preclude misdiagnosis by pathologists. We present a rare case of an AMLEC which was suspected to be a cystic renal cell carcinoma radiologically. We describe the characteristic immunological staining pattern and ultrastructural features of this lesion and discuss the potential differential diagnoses.
January 2017: Current Urology
https://www.readbyqxmd.com/read/28411706/report-of-the-society-for-vascular-surgery-and-the-american-venous-forum-on-the-july-20-2016-meeting-of-the-medicare-evidence-development-and-coverage-advisory-committee-panel-on-lower-extremity-chronic-venous-disease
#18
Peter Gloviczki, Michael C Dalsing, Peter Henke, Brajesh K Lal, Thomas F O'Donnell, Cynthia K Shortell, Ying Huang, Jovan Markovic, Thomas W Wakefield
On July 20, 2016, a Medicare Evidence Development and Coverage Advisory Committee panel assessed the benefits and risks of currently used lower extremity chronic venous disease (CVD) treatments and their effects on health outcome of the American adult population. The main purpose of the meeting was to advise the Centers for Medicare & Medicaid Services on coverage determination for interventions used for treatment of CVD. A systematic review of the Agency for Healthcare Research and Quality was presented, followed by lectures of invited experts and a public hearing of representatives of professional societies and the industry...
May 2017: Journal of Vascular Surgery. Venous and Lymphatic Disorders
https://www.readbyqxmd.com/read/28408159/brain-mrs-glutamine-as-a-biomarker-to-guide-therapy-of-hyperammonemic-coma
#19
Anne H O'Donnell-Luria, Alexander P Lin, Sai K Merugumala, Frances Rohr, Susan E Waisbren, Rebecca Lynch, Vatche Tchekmedyian, Aaron D Goldberg, Andrew Bellinger, J Ricardo McFaline-Figueroa, Tracey Simon, Esteban F Gershanik, Bruce D Levy, David E Cohen, Martin A Samuels, Gerard T Berry, Natasha Y Frank
Acute idiopathic hyperammonemia in an adult patient is a life-threatening condition often resulting in a rapid progression to irreversible cerebral edema and death. While ammonia-scavenging therapies lower blood ammonia levels, in comparison, clearance of waste nitrogen from the brain may be delayed. Therefore, we used magnetic resonance spectroscopy (MRS) to monitor cerebral glutamine levels, the major reservoir of ammonia, in a gastric bypass patient with hyperammonemic coma undergoing therapy with N-carbamoyl glutamate and the ammonia-scavenging agents, sodium phenylacetate and sodium benzoate...
March 10, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28406883/characteristics-of-fentanyl-overdose-massachusetts-2014-2016
#20
Nicholas J Somerville, Julie O'Donnell, R Matthew Gladden, Jon E Zibbell, Traci C Green, Morgan Younkin, Sarah Ruiz, Hermik Babakhanlou-Chase, Miranda Chan, Barry P Callis, Janet Kuramoto-Crawford, Henry M Nields, Alexander Y Walley
Opioid overdose deaths in Massachusetts increased 150% from 2012 to 2015 (1). The proportion of opioid overdose deaths in the state involving fentanyl, a synthetic, short-acting opioid with 50-100 times the potency of morphine, increased from 32% during 2013-2014 to 74% in the first half of 2016 (1-3). In April 2015, the Drug Enforcement Agency (DEA) and CDC reported an increase in law enforcement fentanyl seizures in Massachusetts, much of which was believed to be illicitly manufactured fentanyl (IMF) (4)...
April 14, 2017: MMWR. Morbidity and Mortality Weekly Report
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