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John Martin

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https://www.readbyqxmd.com/read/28431230/structural-basis-for-guide-rna-processing-and-seed-dependent-dna-targeting-by-crispr-cas12a
#1
Daan C Swarts, John van der Oost, Martin Jinek
The CRISPR-associated protein Cas12a (Cpf1), which has been repurposed for genome editing, possesses two distinct nuclease activities: endoribonuclease activity for processing its own guide RNAs and RNA-guided DNase activity for target DNA cleavage. To elucidate the molecular basis of both activities, we determined crystal structures of Francisella novicida Cas12a bound to guide RNA and in complex with an R-loop formed by a non-cleavable guide RNA precursor and a full-length target DNA. Corroborated by biochemical experiments, these structures reveal the mechanisms of guide RNA processing and pre-ordering of the seed sequence in the guide RNA that primes Cas12a for target DNA binding...
April 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28431024/radiosurgery-for-unruptured-brain-arteriovenous-malformations-an-international-multicenter-retrospective-cohort-study
#2
Dale Ding, Robert M Starke, Hideyuki Kano, John Y K Lee, David Mathieu, John Pierce, Paul Huang, Symeon Missios, Caleb Feliciano, Rafael Rodriguez-Mercado, Luis Almodovar, Inga S Grills, Danilo Silva, Mahmoud Abbassy, Douglas Kondziolka, Gene H Barnett, L Dade Lunsford, Jason P Sheehan
BACKGROUND: The role of intervention in the management of unruptured brain arteriovenous malformations (AVM) is controversial. OBJECTIVE: To analyze in a multicenter, retrospective cohort study, the outcomes following radiosurgery for unruptured AVMs and determine predictive factors. METHODS: We evaluated and pooled AVM radiosurgery data from 8 institutions participating in the International Gamma Knife Research Foundation. Patients with unruptured AVMs and ≥12 mo of follow-up were included in the study cohort...
April 20, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28427598/computed-tomography-based-oversizing-degrees-and-incidence-of-paravalvular-regurgitation-of-a-new-generation-transcatheter-heart-valve
#3
Philipp Blanke, Philippe Pibarot, Rebecca Hahn, Neil Weissman, Susheel Kodali, Vinod Thourani, Rupa Parvataneni, Danny Dvir, Christopher Naoum, Bjarne L Nørgaard, Pamela Douglas, Wael Jaber, Omar K Khalique, Hasan Jilaihawi, Michael Mack, Craig Smith, Martin Leon, John Webb, Jonathon Leipsic
OBJECTIVES: The aim of the study was to investigate the influence of the extent of computed tomography (CT)-based area and perimeter oversizing on the incidence and severity of paravalvular aortic regurgitation (PAR) for the Edwards SAPIEN 3 (Edwards Lifesciences, Irvine, California) device, using CT data and echocardiographic outcome data of the PARTNER II (Placement of AoRTic TraNscathetER Valves Trial II) SAPIEN 3 intermediate-risk cohort. BACKGROUND: Transcatheter heart valve (THV) sizing algorithms are device specific, requiring refinements for new valve designs...
April 24, 2017: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/28427464/accuracy-of-low-density-lipoprotein-cholesterol-estimation-at-very-low-levels
#4
Renato Quispe, Aditya Hendrani, Mohamed B Elshazly, Erin D Michos, John W McEvoy, Michael J Blaha, Maciej Banach, Krishnaji R Kulkarni, Peter P Toth, Josef Coresh, Roger S Blumenthal, Steven R Jones, Seth S Martin
BACKGROUND: As the approach to low-density lipoprotein cholesterol (LDL-C) lowering becomes increasingly intensive, accurate assessment of LDL-C at very low levels warrants closer attention in individualized clinical efficacy and safety evaluation. We aimed to assess the accuracy of LDL-C estimation at very low levels by the Friedewald equation, the de facto clinical standard, and compare its accuracy with a novel, big data-derived LDL-C estimate. METHODS: In 191,333 individuals with Friedewald LDL-C < 70 mg/dL, we compared the accuracy of Friedewald and novel LDL-C values in relation to direct measurements by Vertical Auto Profile ultracentrifugation...
April 20, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28426697/perceived-conflict-of-interest-in-health-science-partnerships
#5
John C Besley, Aaron M McCright, Nagwan R Zahry, Kevin C Elliott, Norbert E Kaminski, Joseph D Martin
University scientists conducting research on topics of potential health concern often want to partner with a range of actors, including government entities, non-governmental organizations, and private enterprises. Such partnerships can provide access to needed resources, including funding. However, those who observe the results of such partnerships may judge those results based on who is involved. This set of studies seeks to assess how people perceive two hypothetical health science research collaborations...
2017: PloS One
https://www.readbyqxmd.com/read/28426371/optimization-of-preculture-conditions-to-maximize-the-in-vivo-performance-of-cell-seeded-engineered-intervertebral-discs
#6
John T Martin, Sarah E Gullbrand, Bhavana Mohanraj, Beth G Ashinsky, Dong Hwa Kim, Kensuke Ikuta, Dawn M Elliott, Lachlan J Smith, Robert L Mauck, Harvey E Smith
The development of engineered tissues has progressed over the past 20 years from in vitro characterization to in vivo implementation. For musculoskeletal tissue engineering in particular, the emphasis of many of these studies was to select conditions that maximized functional and compositional gains in vitro. However, the transition from the favorable in vitro culture environment to a less favorable in vivo environment has proven difficult, and, in many cases, engineered tissues do not retain their preimplantation phenotype after even short periods in vivo...
April 19, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28424684/modulation-of-human-leukocyte-antigen-c-by-human-cytomegalovirus-stimulates-kir2ds1-recognition-by-natural-killer-cells
#7
Kattria van der Ploeg, Chiwen Chang, Martin A Ivarsson, Ashley Moffett, Mark R Wills, John Trowsdale
The interaction of inhibitory killer cell Ig-like receptors (KIRs) with human leukocyte antigen (HLA) class I molecules has been characterized in detail. By contrast, activating members of the KIR family, although closely related to inhibitory KIRs, appear to interact weakly, if at all, with HLA class I. KIR2DS1 is the best studied activating KIR and it interacts with C2 group HLA-C (C2-HLA-C) in some assays, but not as strongly as KIR2DL1. We used a mouse 2B4 cell reporter system, which carries NFAT-green fluorescent protein with KIR2DS1 and a modified DAP12 adaptor protein...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28422912/vascular-complications-from-resuscitative-endovascular-balloon-occlusion-of-the-aorta-reboa-life-over-limb
#8
John R Taylor, John A Harvin, Clay Martin, John B Holcomb, Laura J Moore
BACKGROUND: Vascular complications from resuscitative endovascular balloon occlusion of the aorta (REBOA) have been reported as high as 13% with some patients requiring lower extremity amputation. We sought to review our institutions series of REBOA and assess our vascular complications. METHODS: Retrospective review of all patients undergoing REBOA from October 2011 through July 2016. Data was gathered from the Memorial Hermann Trauma registry and the hospital electronic medical records...
April 18, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28422909/multi-institutional-prospective-observational-study-comparing-the-gastrografin-challenge-versus-standard-treatment-in-adhesive-small-bowel-obstruction
#9
Martin D Zielinski, Nadeem N Haddad, Asad J Choudhry, Daniel C Cullinane, Kenji Inaba, Agustin Escalante, D Dante Yeh, Salina Wydo, David Turay, Andrea Pakula, Therese M Duane, Jill Watras, Kenneth A Widom, John Cull, Carlos J Rodriguez, Eric A Toschlog, Valerie G Sams, Joshua P Hazelton, John Christopher Graybill
INTRODUCTION: Existing trials studying the use of Gastrografin for management of adhesive small bowel obstruction (SBO) are limited by methodological flaws and small sample sizes. We compared institutional protocols with and without Gastrografin (GG), hypothesizing that a SBO management protocol utilizing GG is associated with lesser rates of exploration, shorter length of stay, and fewer complications. METHODS: A multi-institutional, prospective, observational study was performed on patients appropriate for GG with adhesive SBO...
April 18, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28422043/real-world-efficacy-and-safety-of-ritonavir-boosted-paritaprevir-ombitasvir-dasabuvir-%C3%A2-ribavirin-for-hepatitis-c-genotype-1-final-results-of-the-rev1tal-study
#10
John Lubel, Simone Strasser, Katherine A Stuart, Gregory Dore, Alexander Thompson, Stephen Pianko, Steven Bollipo, Joanne L Mitchell, Vincenzo Fragomeli, Tracey Jones, Sarah Chivers, Paul Gow, David Iser, Miriam Levy, Edmund Tse, Alessia Gazzola, Wendy Cheng, Saroj Nazareth, Sam Galhenage, Amanda Wade, Martin Weltman, Alan Wigg, Gerry MacQuillan, Joe Sasadeusz, Jacob George, Amany Zekry, Stuart K Roberts
BACKGROUND: Limited data exist on the outcomes of ritonavir-boosted paritaprevir with ombitasvir and dasabuvir (PrOD) ± ribavirin in a real-world setting. The aim of this study was to compare the efficacy and safety of PrOD-based therapy in hepatitis C genotype 1 patients with and without cirrhosis, and to explore pre-treatment factors predictive of sustained viral response (SVR) and serious adverse events (SAEs) on treatment. METHODS: 451 patients with hepatitis C genotype 1 treated in 20 centres across Australia were included...
April 19, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28421039/population-structure-of-sclerotinia-subarctica-and-sclerotinia-sclerotiorum-in-england-scotland-and-norway
#11
John P Clarkson, Rachel J Warmington, Peter G Walley, Matthew Denton-Giles, Martin J Barbetti, Guro Brodal, Berit Nordskog
Sclerotinia species are important fungal pathogens of a wide range of crops and wild host plants. While the biology and population structure of Sclerotinia sclerotiorum has been well-studied, little information is available for the related species S. subarctica. In this study, Sclerotinia isolates were collected from different crop plants and the wild host Ranuculus ficaria (meadow buttercup) in England, Scotland, and Norway to determine the incidence of Sclerotinia subarctica and examine the population structure of this pathogen for the first time...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28419413/long-term-outcomes-secondary-malignancies-and-stem-cell-collection-following-bendamustine-in-patients-with-previously-treated-non-hodgkin-lymphoma
#12
Peter Martin, Zhengming Chen, Bruce D Cheson, Katherine S Robinson, Michael Williams, Saurabh A Rajguru, Jonathan W Friedberg, Richard H van der Jagt, Ann S LaCasce, Robin Joyce, Kristen N Ganjoo, Nancy L Bartlett, Bernard Lemieux, Ari VanderWalde, Jordan Herst, Jeffrey Szer, Michael H Bar, Fernando Cabanillas, Anthony J Dodds, Paul G Montgomery, Bryn Pressnail, Tricia Ellis, Mitchell R Smith, John P Leonard
Despite the long history of bendamustine as treatment for indolent non-Hodgkin lymphoma, long-term efficacy and toxicity data are minimal. We reviewed long-term data from three clinical trials to characterize the toxicity and efficacy of patients receiving bendamustine. Data were available for 149 subjects at 21 sites. The median age was 60 years at the start of bendamustine (range 39-84), and patients had received a median of 3 prior therapies. The histologies included grades 1-2 follicular lymphoma (FL; n = 73), grade 3 FL (n = 23), small lymphocytic lymphoma (n = 20), marginal zone lymphoma (n = 15), mantle cell lymphoma (n = 9), transformed lymphomas (n = 5), lymphoplasmacytic lymphoma (n = 2) and not reported (n = 2)...
April 17, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28418520/rapid-rule-out-of-acute-myocardial-infarction-with-a-single-high-sensitivity-cardiac-troponin-t-measurement-below-the-limit-of-detection-a-collaborative-meta-analysis
#13
John W Pickering, Martin P Than, Louise Cullen, Sally Aldous, Ewoud Ter Avest, Richard Body, Edward W Carlton, Paul Collinson, Anne Marie Dupuy, Ulf Ekelund, Kai M Eggers, Christopher M Florkowski, Yonathan Freund, Peter George, Steve Goodacre, Jaimi H Greenslade, Allan S Jaffe, Sarah J Lord, Arash Mokhtari, Christian Mueller, Andrew Munro, Sebbane Mustapha, William Parsonage, W Frank Peacock, Christopher Pemberton, A Mark Richards, Juan Sanchis, Lukas P Staub, Richard Troughton, Raphael Twerenbold, Karin Wildi, Joanna Young
Background: High-sensitivity assays for cardiac troponin T (hs-cTnT) are sometimes used to rapidly rule out acute myocardial infarction (AMI). Purpose: To estimate the ability of a single hs-cTnT concentration below the limit of detection (<0.005 µg/L) and a nonischemic electrocardiogram (ECG) to rule out AMI in adults presenting to the emergency department (ED) with chest pain. Data Sources: EMBASE and MEDLINE without language restrictions (1 January 2008 to 14 December 2016)...
April 18, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28417945/one-pot-phosphate-mediated-synthesis-of-novel-1-3-5-trisubstituted-pyridinium-salts-a-new-family-of-s-aureus-inhibitors
#14
Thomas Pesnot, Markus C Gershater, Martin Edwards, John M Ward, Helen C Hailes
Polysubstituted pyridinium salts are valuable pharmacophores found in many biologically active molecules. Their synthesis typically involves the use of multistep procedures or harsh reaction conditions. Here, we report water-based phosphate mediated reaction conditions that promote the condensation of arylacetaldehydes with amines to give 1,3,5-pyridinium salts. The reaction, carried out at pH 6, provides conditions suitable for the use of less stable aldehydes and amines in this Chichibabin pyridine condensation...
April 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28416744/real-time-near-infrared-fluorescence-imaging-using-crgd-zw800-1-for-intraoperative-visualization-of-multiple-cancer-types
#15
Henricus J M Handgraaf, Martin C Boonstra, Hendrica A J M Prevoo, Joeri Kuil, Mark W Bordo, Leonora S F Boogerd, Babs G Sibinga Mulder, Cornelis F M Sier, Maaike L Vinkenburg-van Slooten, A Rob P M Valentijn, Jacobus Burggraaf, Cornelis J H van de Velde, John V Frangioni, Alexander L Vahrmeijer
Incomplete resections and damage to critical structures increase morbidity and mortality of patients with cancer. Targeted intraoperative fluorescence imaging aids surgeons by providing real-time visualization of tumors and vital structures. This study evaluated the tumor-targeted zwitterionic near-infrared fluorescent peptide cRGD-ZW800-1 as tracer for intraoperative imaging of multiple cancer types. cRGD-ZW800-1 was validated in vitro on glioblastoma (U-87 MG) and colorectal (HT-29) cell lines. Subsequently, the tracer was tested in orthotopic mouse models with HT-29, breast (MCF-7), pancreatic (BxPC-3), and oral (OSC-19) tumors...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416122/patients-with-a-resected-pancreatic-mucinous-cystic-neoplasm-have-a-better-prognosis-than-patients-with-an-intraductal-papillary-mucinous-neoplasm-a-large-single-institution-series
#16
James F Griffin, Andrew J Page, Georges J Samaha, Adrienne Christopher, Feriyl Bhaijee, Maryam K Pezhouh, Niek A Peters, Ralph H Hruban, Jin He, Martin A Makary, Anne Marie Lennon, John L Cameron, Christopher L Wolfgang, Matthew J Weiss
BACKGROUND/OBJECTIVES: Mucinous cystic neoplasms (MCNs) are rare pancreas tumors distinguished from intraductal papillary mucinous neoplasms (IPMNs) by the presence of ovarian-type stroma. Historical outcomes for MCNs vary due to previously ambiguous diagnostic criteria resulting in confusion with IPMNs. This study seeks to characterize and clarify the clinical features and long-term outcomes of MCNs versus IPMNs in the largest single-institution series of pathology-confirmed MCNs to date...
April 11, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28414270/human-biallelic-mfn2-mutations-induce-mitochondrial-dysfunction-upper-body-adipose-hyperplasia-and-suppression-of-leptin-expression
#17
Nuno M Rocha, David A Bulger, Andrea Frontini, Hannah Titheradge, Sigrid Bjerge Gribsholt, Rachel Knox, Matthew Page, Julie Harris, Felicity Payne, Claire Adams, Alison Sleigh, John Crawford, Anette Prior Gjesing, Jette Bork-Jensen, Oluf Pedersen, Inês Barroso, Torben Hansen, Helen Cox, Mary Reilly, Alex Rossor, Rebecca J Brown, Simeon I Taylor, Duncan McHale, Martin Armstrong, Elif A Oral, Vladimir Saudek, Stephen I O'Rahilly, Eamonn R Maher, Bjørn Richelsen, David B Savage, Robert K Semple
MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth. We describe similar massive adipose overgrowth with suppressed leptin expression in four further patients with biallelic MFN2 mutations and at least one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1-negative unilocular adipocytes, with mitochondrial network fragmentation, disorganised cristae, and increased autophagosomes...
April 17, 2017: ELife
https://www.readbyqxmd.com/read/28413860/distribution-and-characterisation-of-cck-containing-enteroendocrine-cells-of-the-mouse-small-and-large-intestine
#18
Josiane Fakhry, Joyce Wang, Patricia Martins, Linda J Fothergill, Billie Hunne, Pierre Prieur, Arthur Shulkes, Jens F Rehfeld, Brid Callaghan, John B Furness
There is general consensus that enteroendocrine cells, EEC, containing the enteric hormone cholecystokinin (CCK) are confined to the small intestine and predominate in the duodenum and jejunum. Contrary to this, EEC that express the gene for CCK have been isolated from the large intestine of the mouse and there is evidence for EEC that contain CCK-like immunoreactivity in the mouse colon. However, the human and rat colons do not contain CCK cells. In the current study, we use immunohistochemistry to investigate CCK peptide presence in endocrine cells, PCR to identify cck transcripts and chromatography to identify CCK peptide forms in the mouse small and large intestine...
April 17, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28412746/kr%C3%A3-ppel-like-factor-4-klf4-regulates-the-mir-183-96-182-cluster-under-physiologic-and-pathologic-conditions
#19
Miguel F Segura, Luz Jubierre, SiDe Li, Aroa Soriano, Lisa Koetz, Avital Gaziel-Sovran, Marc Masanas, Kevin Kleffman, John F Dankert, Martin J Walsh, Eva Hernando
MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs that post-transcriptionally control the translation and stability of target mRNAs in a sequence-dependent manner. MiRNAs are essential for key cellular processes including proliferation, differentiation, cell death and metabolism, among others. Consequently, alterations of miRNA expression contribute to developmental defects and a myriad of diseases.The expression of miRNAs can be altered by several mechanisms including gene copy number alterations, aberrant DNA methylation, defects of the miRNA processing machinery or unscheduled expression of transcription factors...
February 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412565/the-use-of-a-novel-perfusion-based-cadaveric-simulation-model-with-cerebrospinal-fluid-reconstitution-comparing-dural-repair-techniques-a-pilot-study
#20
Joshua Bakhsheshian, Ben A Strickland, Neil N Patel, Andre M Jakoi, Michael Minneti, Gabriel Zada, Frank L Acosta, Patrick C Hsieh, Jeffrey C Wang, John C Liu, Martin H Pham
BACKGROUND CONTEXT: Watertight dural repair is crucial for both incidental durotomy and closure after intradural surgery. PURPOSE: To describe a perfusion-based cadaveric simulation model with cerebrospinal-fluid (CSF) reconstitution and to compare spine dural repair techniques. STUDY DESIGN/SETTING: Fresh Tissue Dissection Laboratory. SAMPLE SIZE: 8 fresh human cadavers. OUTCOME MEASURES: A watertight closure was achieved when pressurized saline up to 40 mm Hg did not cause further CSF leakage beyond the suture lines...
April 12, 2017: Spine Journal: Official Journal of the North American Spine Society
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