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https://www.readbyqxmd.com/read/28922466/blinatumomab-pharmacodynamics-and-exposure-response-relationships-in-relapsed-refractory-acute-lymphoblastic-leukemia
#1
Min Zhu, Andrea Kratzer, Jessica Johnson, Chris Holland, Christian Brandl, Indrajeet Singh, Andreas Wolf, Sameer Doshi
We evaluated blinatumomab pharmacokinetics, pharmacodynamics (CD3+ T-cell, CD19+ B-cell, and cytokine levels), and their associations with efficacy or safety in relapsed/refractory acute lymphoblastic leukemia. Blinatumomab pharmacokinetics (continuous intravenous infusion) from a phase 2 study (n = 189; NCT01466179) were assessed noncompartmentally. Associations between steady-state concentration (Css ) and efficacy (complete remission [CR] or CR with partial hematologic recovery [CRh]) or safety (cytokine release syndrome [CRS] and neurologic events [NEs]) were evaluated with statistical models...
September 18, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28921874/polaronic-charge-carrier-lattice-interaction-in-lead-halide-perovskites
#2
Christoph Wolf, Young-Hoon Kim, Himchan Cho, Tae-Woo Lee
Almost ten years after the renaissance of the popular perovskite-type semiconductors based on lead-salts with general formula AMX3 (A=organic or inorganic cation, M=divalent metal, X=halide), many facets of photophysics continue to puzzle researchers. In this review, we shed some light on the low mobilities of charge carriers in lead-halide perovskites with special focus on the lattice properties at non-zero temperature. The polar and soft lattice leads to pronounced electron-phonon coupling, limiting carrier mobility and retarding recombination...
September 18, 2017: ChemSusChem
https://www.readbyqxmd.com/read/28921806/a-large-area-spatially-continuous-assessment-of-land-cover-map-error-and-its-impact-on-downstream-analyses
#3
Lyndon Estes, Peng Chen, Stephanie Debats, Tom Evans, Stefanus Ferreira, Tobias Kuemmerle, Gabrielle Ragazzo, Justin Sheffield, Adam Wolf, Eric Wood, Kelly Caylor
Land cover maps increasingly underlie research into socioeconomic and environmental patterns and processes, including global change. It is known that map errors impact our understanding of these phenomena, but quantifying these impacts is difficult because many areas lack adequate reference data. We used a highly accurate, high-resolution map of South African cropland to assess 1) the magnitude of error in several current generation land cover maps, and 2) how these errors propagate in downstream studies. We first quantified pixel-wise errors in the cropland classes of four widely used land cover maps at resolutions ranging from 1 to 100 km, then calculated errors in several representative "downstream" (map-based) analyses, including assessments of vegetative carbon stocks, evapotranspiration, crop production, and household food security...
September 16, 2017: Global Change Biology
https://www.readbyqxmd.com/read/28921505/nfatc1-activation-by-dna-hypomethylation-in-chronic-lymphocytic-leukemia-correlates-with-clinical-staging-and-can-be-inhibited-by-ibrutinib
#4
Christine Wolf, Angela Garding, Katharina Filarsky, Jasmin Bahlo, Sandra Robrecht, Natalia Becker, Manuela Zucknick, Arefeh Rouhi, Anja Weigel, Rainer Claus, Dieter Weichenhan, Barbara Eichhorst, Kirsten Fischer, Michael Hallek, Florian Kuchenbauer, Christoph Plass, Hartmut Döhner, Stephan Stilgenbauer, Peter Lichter, Daniel Mertens
B cell receptor (BCR) signaling is key for survival of chronic lymphocytic leukemia (CLL) cells, and BCR signaling inhibitors are clinically active. However, relapse and resistance to treatment require novel treatment options. In order to detect novel candidate therapeutic targets, we performed a genome-wide DNA methylation screen with custom arrays and identified aberrant promoter DNA methylation in 2192 genes. The transcription factor NFATC1 that is a downstream effector of BCR signaling was among the top hypomethylated genes and was concomitantly transcriptionally upregulated in CLL...
September 18, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28920936/dopamine-induces-soluble-%C3%AE-synuclein-oligomers-and-nigrostriatal-degeneration
#5
Danielle E Mor, Elpida Tsika, Joseph R Mazzulli, Neal S Gould, Hanna Kim, Malcolm J Daniels, Shachee Doshi, Preetika Gupta, Jennifer L Grossman, Victor X Tan, Robert G Kalb, Kim A Caldwell, Guy A Caldwell, John H Wolfe, Harry Ischiropoulos
Parkinson's disease (PD) is defined by the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy body inclusions containing aggregated α-synuclein. Efforts to explain dopamine neuron vulnerability are hindered by the lack of dopaminergic cell death in α-synuclein transgenic mice. To address this, we manipulated both dopamine levels and α-synuclein expression. Nigrally targeted expression of mutant tyrosine hydroxylase with enhanced catalytic activity increased dopamine levels without damaging neurons in non-transgenic mice...
September 18, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28920093/pyrazine-analogues-from-wolf-urine-induced-unlearned-fear-in-rats
#6
Makoto Kashiwayanagi, Sadaharu Miyazono, Kazumi Osada
Urine excreted from the common grey wolf (Canis lupus) contains a kairomone, inducing fear-related behaviors in various mammals. Numerous fear-inducing substances activate neurons at the main and/or accessory olfactory bulb (AOB), medial and central amygdala, and hypothalamus. Our previous study showed that the mixture of pyrazine analogues (P-mix) contained in wolf urine induced avoidance and fear-related behaviors in laboratory mice and Hokkaido deer (Cervus nippon yesoensis), a species native to Japan. Exposure to wolf urine or P-mix induced expression of Fos, a marker of neuronal excitation, in the AOB of mice...
August 2017: Heliyon
https://www.readbyqxmd.com/read/28918356/what-is-the-price-for-the-duchenne-gait-pattern-in-patients-with-cerebral-palsy
#7
Firooz Salami, Mirjam Niklasch, Britta K Krautwurst, Thomas Dreher, Sebastian I Wolf
Duchenne gait is characterized by trunk lean towards the affected stance limb with the pelvis stable or elevated on the swinging limb side during single limb stance phase. We assessed the relationship between hip abduction moments and trunk kinetics in patients with cerebral palsy showing excessive lateral trunk motion. Data of 18 subjects with bilateral spastic cerebral palsy (CP) and 20 aged matched typically developing subjects (TD) were collected retrospectively. Criteria for patient selection were barefoot walking without aid presenting with excessive lateral trunk motion...
September 7, 2017: Gait & Posture
https://www.readbyqxmd.com/read/28918146/short-communication-automated-detection-of-behavioral-changes-from-respiratory-disease-in-pre-weaned-calves
#8
T H Swartz, A N Findlay, C S Petersson-Wolfe
Group housing of calves can pose a challenge in identifying respiratory disease; therefore, it is necessary to develop tools that can identify these disease events. In this experiment, pre-weaned calves (n = 30) were housed in groups with an automatic calf feeder and were fitted with an accelerometer. Step activity, lying behaviors, and feeding behaviors were recorded to determine the effect of respiratory disease. All calves were health scored twice daily, and calves with respiratory scores ≥5 were diagnosed with respiratory disease (n = 10)...
September 13, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28918089/urinary-incontinence-and-indwelling-urinary-catheters-as-predictors-of-death-after-new-onset-stroke-a-report-of-the-south-london-stroke-register
#9
Gregor John, Steve Primmaz, Siobhan Crichton, Charles Wolfe
OBJECTIVE: To explore the relationship between indwelling urinary catheters (IUCs), urinary incontinence (UI), and death in the poststroke period and to determine when, after the neurological event, UI has the best ability to predict 1-year mortality. METHODS: In a prospective observational study, 4477 patients were followed up for 1 year after a first-ever stroke. The impact of UI or urinary catheters on time to death was adjusted in a Cox model for age, sex, Glasgow Coma Scale, prestroke and poststroke Barthel Index, swallow test, motor deficit, diabetes, and year of inclusion...
September 13, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28917858/a-structural-study-of-acacia-nilotica-and-acacia-modesta-gums
#10
Shazma Massey, William MacNaughtan, Huw E L Williams, Bettina Wolf, Mohammad S Iqbal
Superficially similar carbohydrate polymers from similar sources can have dramatically different characteristics. This work seeks to examine the molecular properties responsible for these differences. Protons responsible for cross-polarization in the anomeric region of Acacia nilotica (AN) were replaced easily by deuterium, but not for Acacia modesta (AM). Time constants describing the mobility and cross-polarization transfer were both found to be lower for AM. Variable contact time experiments showed poorer fits and more heterogeneity for AN...
November 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28917639/protein-oxidation-involved-in-cys-tyr-post-translational-modification
#11
Susan E Hromada, Adam M Hilbrands, Elysa M Wolf, Jackson L Ross, Taylor R Hegg, Andrew G Roth, Matthew T Hollowell, Carolyn E Anderson, David E Benson
Some post-translationally modified tyrosines can perform reversible redox chemistry similar to metal cofactors. The most studied of these tyrosine modifications is the intramolecular thioether-crosslinked 3'-(S-cysteinyl)-tyrosine (Cys-Tyr) in galactose oxidase. This Cu-mediated tyrosine modification in galactose oxidase involves direct electron transfer (inner-sphere) to the coordinated tyrosine. Mammalian cysteine dioxygenase enzymes also contain a Cys-Tyr that is formed, presumably, through outer-sphere electron transfer from a non-heme iron center ~6Å away from the parent residues...
September 14, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28916789/whole-body-and-hematopoietic-adam8-deficiency-does-not-influence-advanced-atherosclerotic-lesion-development-despite-its-association-with-human-plaque-progression
#12
Kosta Theodorou, Emiel P C van der Vorst, Marion J Gijbels, Ine M J Wolfs, Mike Jeurissen, Thomas L Theelen, Judith C Sluimer, Erwin Wijnands, Jack P Cleutjens, Yu Li, Yvonne Jansen, Christian Weber, Andreas Ludwig, Jacob F Bentzon, Jörg W Bartsch, Erik A L Biessen, Marjo M P C Donners
Although A Disintegrin And Metalloproteinase 8 (ADAM8) is not crucial for tissue development and homeostasis, it has been implicated in various inflammatory diseases by regulating processes like immune cell recruitment and activation. ADAM8 expression has been associated with human atherosclerosis development and myocardial infarction, however a causal role of ADAM8 in atherosclerosis has not been investigated thus far. In this study, we examined the expression of ADAM8 in early and progressed human atherosclerotic lesions, in which ADAM8 was significantly upregulated in vulnerable lesions...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916293/is-there-ever-a-role-for-the-unilateral-do-not-attempt-resuscitation-order-in-pediatric-care
#13
Jonathan M Marron, Emma Jones, Joanne Wolfe
Care for children as they near the end of life is difficult and very complex. More difficult still are the decisions regarding what interventions are and are not indicated during these trying times. Occasionally, families of children who are nearing the end of life disagree with the assessment of the medical team regarding these interventions. In rare cases, the medical team can be moved to enact a do not attempt resuscitation (DNAR) order against the wishes of the patient's parents. This manuscript presents one such illustrative case and discusses the ethical issues relevant to such challenging clinical scenarios...
September 12, 2017: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28915316/plate-pattern-clarification-of-the-marine-dinophyte-heterocapsa-triquetra-sensu-stein-dinophyceae-collected-at-the-kiel-fjord-germany
#14
Urban Tillmann, Mona Hoppenrath, Marc Gottschling, Kusber Wolf-Henning, Malte Elbrächter
One of the most common marine dinophytes is a species known as Heterocapsa triquetra. When Stein introduced the taxon Heterocapsa he formally based the type species H. triquetra on the basionym Glenodinium triquetrum. The latter was described by Ehrenberg and is most likely a species of Kryptoperidinium. In addition to that currently unresolved nomenclatural situation, the thecal plate composition of H. triquetra sensu Stein (1883) was controversial in the past. In order to clarify the debate, we collected material and established the strain UTKG7 from the Baltic Sea off Kiel (Germany, the same locality as Stein had studied), which was investigated using light and electron microscopy, and whose systematic position was inferred using molecular phylogenetics...
September 15, 2017: Journal of Phycology
https://www.readbyqxmd.com/read/28915221/metformin-exerts-beneficial-effects-in-hemorrhagic-shock-in-an-ampk%C3%AE-1-independent-manner
#15
Paul Kim, Giovanna Piraino, Michael O'Connor, Paul W Hake, Vivian Wolfe, Patrick Lahni, Basilia Zingarelli
Despite therapeutic advances in hemorrhagic shock, mortality from multiple organ failure remains high. AMP-activated protein kinase (AMPK) is involved in cellular energy homeostasis. Two catalytic subunits, α1 and α2, have been identified, with α1 subunit largely expressed in major organs. Here, we hypothesized that genetic deficiency of AMPKα1 worsens hemorrhage-induced multiple organ failure. We also investigated whether treatment with metformin, a clinically used drug for metabolic homeostasis, affords beneficial effects...
September 14, 2017: Shock
https://www.readbyqxmd.com/read/28915219/intrabronchial-catheter-resuscitation-for-respiratory-and-cardiorespiratory-arrest
#16
Jeffrey S Wolf, Andrea Hebert, Pablo Sanchez, Marniker Wijesinha, Scott Shapiro, Robert Morales, Aldo T Iacono
INTRODUCTION: We sought to determine whether intrabronchial oxygenation would provide adequate gas exchange during both anesthesia induced apneic and cardiopulmonary arrest and cardiac massage (CPR). METHODS: Ten pigs underwent general anesthesia with mechanical ventilation. Blood gases were measured in each animal at 4 min intervals for up to 28 min. An intrabronchial catheter (4 L/min O2) was inserted through an endotracheal tube after respirator cessation. Group A animals (6) were resuscitated with the catheter but without CPR...
September 14, 2017: Shock
https://www.readbyqxmd.com/read/28915045/identification-and-validation-of-reaction-coordinates-describing-protein-functional-motion-hierarchical-dynamics-of-t4-lysozyme
#17
Matthias Ernst, Steffen Wolf, Gerhard Stock
While adequately chosen reaction coordinates are expected to reveal the mechanism of a dynamical process, it proves to be notoriously difficult to model the complex structural rearrangement of a macromolecule by a low-dimensional collective coordinate. Adopting the hinge-bending motion of T4 lysozyme (T4L) as a prominent example and performing a 50 microsecond long unbiased molecular dynamics (MD) simulation of T4L, a general strategy to identify reaction coordinates of protein functional dynamics is developed...
September 15, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28913830/ontogenesis-of-opercular-deformities-in-gilthead-sea-bream-sparus-aurata-a-histological-description
#18
N P Thuong, B Verstraeten, B D Kegel, J Christiaens, T D Wolf, P Sorgeloos, D Bonte, D Adriaens
The aim of this study was to characterize histological changes during opercular osteogenesis in farmed gilthead sea bream Sparus aurata larvae from 7 to 69 days post hatching (dph) and compare normal osteogenesis with that of deformed opercles. Mild opercular deformities were first detected in 19 dph larvae by folding of the opercle's distal edge into the gill chamber. Here, the variation in the phenotype and the irregular bone structure at the curled part of the opercles is described and compared with the histology of normal opercles...
September 15, 2017: Journal of Fish Biology
https://www.readbyqxmd.com/read/28913715/oxidized-low-density-lipoprotein-oxldl-affects-load-free-cell-shortening-of-cardiomyocytes-in-a-proprotein-convertase-subtilisin-kexin-9-pcsk9-dependent-way
#19
Klaus-Dieter Schlüter, Annemarie Wolf, Martin Weber, Rolf Schreckenberg, Rainer Schulz
Recent studies have documented that oxidized low-density lipoprotein cholesterol (oxLDL) levels directly impact myocardial structure and function. However, the molecular mechanisms by which oxLDL affects cardiac myocytes are not well established. We addressed the question whether oxLDL modifies load-free cell shortening, a standardized readout of cardiac cellular function, and investigated whether proprotein convertase subtilisin/kexin-9 (PCSK9) is involved on oxLDL-dependent processes. Adult rat ventricular cardiomyocytes were isolated and incubated for 24 h with oxLDL...
September 14, 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28913674/prognostic-significance-of-corticotroph-staining-in-radiosurgery-for-non-functioning-pituitary-adenomas-a-multicenter-study
#20
Or Cohen-Inbar, Zhiyuan Xu, Cheng-Chia Lee, Chin-Chun Wu, Tomáš Chytka, Danilo Silva, Mayur Sharma, Hesham Radwan, Inga S Grills, Brandon Nguyen, Zaid Siddiqui, David Mathieu, Christian Iorio-Morin, Amparo Wolf, Christopher P Cifarelli, Daniel T Cifarelli, L Dade Lunsford, Douglas Kondziolka, Jason P Sheehan
Silent corticotroph staining pituitary adenoma (SCA) represents an uncommon subset of Non-Functioning adenomas (NFAs), hypothesized to be more locally aggressive. In this retrospective multicenter study, we investigate the safety and effectiveness of Stereotactic Radiosurgery (SRS) in patients with SCA compared with other non-SCA NFA's. Eight centers participating in the International Gamma-Knife Research Foundation (IGKRF) contributed to this study. Outcomes of 50 patients with confirmed SCAs and 307 patients with confirmed non-SCA NFA's treated with SRS were evaluated...
September 14, 2017: Journal of Neuro-oncology
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