bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non–small cell lung cancer clinical trials requiring biopsies with biomarker‐specific results for enrollment provide unique challenges
Authors: Spiegel Marshall L. , Goldman Jonathan W. , Wolf Brian R. , Nameth Danielle J. , Grogan Tristan R. , Lisberg Aaron E. , Wong Deborah J. L. , Ledezma Blanca A. , Mendenhall Melody A. , Genshaft Scott J. , Gutierrez Antonio J. , Abtin Fereidoun , Wallace W. Dean , Adame Carlos R. , McKenzie Jordan R. , Abarca Phillip A. , Li Alice J. , Strunck Jennifer L. , Famenini Sina , Carroll James M. , Tucker D. Andrew , Sauer Lauren M. , Moghadam Nima M. , Elashoff David A. , Abaya Christina D. , Brennan Meghan B. , Garon Edward B. 
Published: November 2017

BACKGROUNDClinical trials in lung cancer increasingly require patients to provide fresh tumor tissue as a prerequisite to enrollment. The effects of this requirement on enrollment rates, enrollment durations, and patient selection have not been fully elucidated.METHODSThe authors retrospectively reviewed data generated by patients who consented to 1 or more interventional lung cancer clinical trials at the University of California‐Los Angeles Jonsson Comprehensive Cancer Center between January 2013 and December 2014. Trials were considered to require a biopsy when enrollment was conditional on the procurement of tissue without intervening therapy between procurement and enrollment.RESULTSIn total, 311 patients underwent 368 screening incidents for 1 or more of 19 trials. Trials that required a new biopsy had a longer median screening duration (34 vs 14 days) than trials that did not require a biopsy (P < .001). Trials that required a biopsy had a greater screen failure rate (49.1% vs 26.5%; P < .001), which was largely driven by patients who did not undergo the required biopsy or lacked the required biomarker. Worsening performance status led to the majority of screen failures (56.5%) among biomarker‐eligible patients.CONCLUSIONSAlthough the scientific benefits of obtaining a new biopsy and requiring specific results for trial enrollment are clear, these requirements lead to a lengthening of the screening period, which, in some patients, is associated with clinical decline before enrollment. Implications for the interpretation of data from studies of this design should be explored. Cancer 2017;123:4800‐7. © 2017 American Cancer Society.
Relationship between the left ventricular size and the amount of trabeculations
Authors: Paun Bruno , Bijnens Bart , Butakoff Constantine 
Published: November 2017

AbstractContemporary imaging modalities offer noninvasive quantification of myocardial deformation; however, they make gross assumptions about internal structure of the cardiac walls. Our aim is to study the possible impact of the trabeculations on the stroke volume, strain, and capacity of differently sized ventricles. The cardiac left ventricle is represented by an ellipsoid and the trabeculations by a tissue occupying a fixed volume. The ventricular contraction is modeled by scaling the ellipsoid whereupon the measurements of longitudinal strain, end‐diastolic, end‐systolic, and stroke volumes are derived and compared. When the trabeculated and nontrabeculated ventricles, having the same geometry and deformation pattern, contain the same amount of blood and contract with the same strain, we observed an increased stroke volume in our model of the trabeculated ventricle. When these ventricles contain and eject the same amount of blood, we observed a reduced strain in the trabeculated case. We identified that a trade‐off between the strain and the amount of trabeculations could be reached with a 0.35‐ to 0.41‐cm dense trabeculated layer, without blood filled recesses (for a ventricle with end‐diastolic volume of about 150 mL). A trabeculated ventricle can work at lower strains compared to a nontrabeculated ventricle to produce the same stroke volume, which could be a possible explanation why athletes and pregnant women develop reversible signs of left ventricular noncompaction, since the trabeculations could help generating extra cardiac output. This knowledge might help to assess heart failure patients with dilated cardiomyopathies who often show signs of noncompaction.
Two Phase 1, Open‐Label, Single‐Dose, Randomized, Crossover Studies to Assess the Pharmacokinetics, Safety, and Tolerability of Orally Administered Granules of Secnidazole (2 g) in Healthy Female Volunteers Under Different Administration Conditions
Authors: Pentikis Helen S. , Adetoro Nikki 
Published: November 2017

AbstractBacterial vaginosis (BV) is the most common vaginal infection in reproductive‐age women and a significant risk factor for sexually transmitted diseases and pregnancy complications. Standard 5‐ to 7‐day antimicrobial treatments for BV are associated with high rates of recurrence and adverse events. SYM‐1219 is a novel granule formulation containing 2 g of secnidazole, developed as an oral, single‐dose BV treatment. Two phase 1, open‐label, single‐center, randomized, crossover trials (studies 102 and 103) assessed the pharmacokinetics and safety of SYM‐1219 single doses (≥7‐day washout between doses) in healthy, nonpregnant women aged 18 to 65 years inclusive. Study 102 compared SYM‐1219 in applesauce in fasted vs fed states. Study 103 compared SYM‐1219 (fasted) in pudding and yogurt vs applesauce. Studies 102 and 103 each dosed 24 subjects (mean [standard deviation] ages, 36 [1.8] and 40 [11.6] years, respectively). In both studies the 90% confidence intervals for all treatment comparisons of maximum plasma concentration, area under the concentration‐time curve from 0 to last measurable concentration and to infinity, geometric mean ratios were within 80% to 125%, demonstrating bioequivalence. In both studies median fasted time to maximum plasma concentration was 4 hours (6 hours fed in study 102), and mean half‐life ranged from 17 to 19 hours. Treatment‐emergent adverse events occurred in 70.8% and 83.3% subjects in studies 102 and 103, respectively, most commonly headache (41.7% and 50.0%) and gastrointestinal treatment‐emergent adverse events. The pharmacokinetics of SYM‐1219 were similar in fed and fasted states and when administered in different foods.
Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans
Authors: Nagy Christa F. , Leach Timothy S. , King Alex , Guttendorf Robert 
Published: November 2017

AbstractInhalational anthrax is a highly lethal infection caused by Bacillus anthracis and a serious bioterrorism threat. Protective antigen (PA) is a critical component required for the virulence of Bacillus anthracis. Obiltoxaximab, a high‐affinity monoclonal antibody that neutralizes PA, is approved in the United States for intravenous use for the treatment of inhalational anthrax in combination with appropriate antibacterial drugs and for prophylaxis of inhalational anthrax when alternative therapies are not available or appropriate. Here, we explored the safety, pharmacokinetics (PK), and immunogenicity of obiltoxaximab administered by intramuscular injection at doses of 4, 8, 16, 20, and 24 mg/kg in healthy humans. Systemic exposures were approximately dose proportional, maximum serum concentrations were observed after 6–9 days, and terminal half‐life ranged from 16 to 23 days. Average absolute intramuscular bioavailability was 64%. Obiltoxaximab was well tolerated, and local tolerability was acceptable up to 24 mg/kg intramuscularly, up to 6 injections per dose, and up to 5 mL per injection. No injection‐site abscesses or hypersensitivity reactions occurred; no subjects developed treatment‐emergent antitherapeutic antibodies over the study period of 71 days.
Bioavailability and Pharmacokinetics of TRPV1 Antagonist Mavatrep (JNJ‐39439335) Tablet and Capsule Formulations in Healthy Men: Two Open‐Label, Crossover, Single‐Dose Phase 1 Studies
Authors: Manitpisitkul Prasarn , Shalayda Kevin , Russell Lucille , Sanga Panna , Williams Yinka , Solanki Bhavna , Caruso Joseph , Moyer John A. 
Published: November 2017

AbstractTo improve room temperature stability and oral bioavailability of mavatrep (JNJ‐39439335, a transient receptor potential vanilloid subtype‐1 antagonist), various formulations were initially developed and evaluated in 2 phase 1 open‐label, randomized, 3‐way crossover studies in healthy participants. Study 1 evaluated 2 new overencapsulated tablet formulations (formulations B and C) relative to an overencapsulated early tablet formulation (formulation A), using mavatrep HCl salt form. Because these tablets were still not room‐temperature stable, in study 2: two free‐base solid dispersion amorphous formulations (formulations D and E) were evaluated relative to the best encapsulated formulation from study 1 (formulation C) and also food effect. Both studies had screening (∼4 weeks), treatment (study 1: n = 18, 6‐sequenced; formulations B and C [2 × 25 mg] versus A [2 × 25 mg]; study 2, part 1: n = 24, formulations D and E [2 × 12.5 mg] versus C [1 × 25 mg]; study 2, part 2: n = 16, best formulation from part 1 fed versus fasted, 2 × 12.5 mg) with a 21‐day washout period and a follow‐up. Mavatrep exhibited consistent pharmacokinetics across formulations. Following rapid absorption (median tmax, 1.5–6.5 hours), plasma concentrations declined multiexponentially (mean t1/2, 67–104 hours). The new encapsulated tablet formulation (formulation C, capsule filler: poloxamer 407) was the best formulation (Cmax and AUC values 2‐3‐fold > than the other 2) from study 1. Using this as a reference in study 2, part 1, only small (<20%) differences in mean Cmax and AUC were observed between the 3 formulations (C, D, and E). Formulation E (gelatin capsule with amorphous solid dispersion [12.5 mg free base], hydroxypropyl methylcellulose, vitamin E polyethylene glycol succinate, silicified microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide) showed improved room‐temperature stability and provided the best overall bioavailability with small variability. Small effects of a high‐fat meal on oral bioavailability were observed for formulation E, but were not clinically meaningful. Mavatrep safety profiles were similar across formulations and under fasted and fed conditions. No new safety concerns were reported.
The Stabilization of Glycosyl Cations Through Cooperative Noncovalent Interactions: A Theoretical Perspective
Authors: Franconetti Antonio , Jiménez‐Barbero Jesús , Cabrera‐Escribano Francisca 
Published: November 2017

AbstractA systematic study of the stabilization of glycosyl cations on aromatic rings is reported at the B3LYP, M06‐2X and M11 levels of theory. In particular, π‐acidic arenes such as fluorobenzenes or naphthalenediimides efficiently stabilize these cations acting cooperatively as sandwich‐type ternary cation–π–anion systems. The stabilization and cooperativity in polar (both protic and aprotic) and non‐polar solvents has been also evaluated by using the polarizable continuum model. In addition, the role of the protecting group at the C‐2 position (methyl, acetyl, benzyl, and pivaloyl) for this noncovalent stabilization has been explored, as well as the behaviour of the corresponding 2‐deoxy glycosyl cation.
Electrochemistry of Metalloproteins Attached through Functional Self‐Assembled Monolayers on Gold and Ferromagnetic Electrodes
Authors: Mondal Prakash Chandra , Fontanesi Claudio 
Published: November 2017

AbstractWe report the experimental results of a study of the electron‐transfer processes of redox‐active metalloproteins bound to mixed self‐assembled monolayers (SAMs) on magnetic (nickel or ultrathin gold‐coated nickel) or nonmagnetic (gold) electrodes. Metalloproteins, such as hemoglobin (Hb), Cytochrome C (Cyt C), and Cyt C oxidase, are attached through electrostatic interactions to the free carboxylate or imidazole groups present in the mixed SAMs. The formation of both mixed SAMs and SAM/metalloprotein heterostructures were confirmed by using advanced surface analysis techniques, such as polarization modulation infrared reflection absorption spectroscopy and aqueous contact angle measurements. Electrochemical measurements indicated a stronger electronic coupling between Hb and Cyt C oxidase and the mixed‐SAM‐coated gold or gold‐coated‐nickel electrodes, whereas a weaker coupling was found between the protein and the pure nickel electrode. Surface coverage and the electron‐transfer rate constant were estimated from the cyclic voltammetry data.
Image analysis of neural stem cell division patterns in the zebrafish brain
Authors: Lupperger Valerio , Buggenthin Felix , Chapouton Prisca , Marr Carsten 
Published: November 2017

AbstractProliferating stem cells in the adult body are the source of constant regeneration. In the brain, neural stem cells (NSCs) divide to maintain the stem cell population and generate neural progenitor cells that eventually replenish mature neurons and glial cells. How much spatial coordination of NSC division and differentiation is present in a functional brain is an open question. To quantify the patterns of stem cell divisions, one has to (i) identify the pool of NSCs that have the ability to divide, (ii) determine NSCs that divide within a given time window, and (iii) analyze the degree of spatial coordination. Here, we present a bioimage informatics pipeline that automatically identifies GFP expressing NSCs in three‐dimensional image stacks of zebrafish brain from whole‐mount preparations. We exploit the fact that NSCs in the zebrafish hemispheres are located on a two‐dimensional surface and identify between 1,500 and 2,500 NSCs in six brain hemispheres. We then determine the position of dividing NSCs in the hemisphere by EdU incorporation into cells undergoing S‐phase and calculate all pairwise NSC distances with three alternative metrics. Finally, we fit a probabilistic model to the observed spatial patterns that accounts for the non‐homogeneous distribution of NSCs. We find a weak positive coordination between dividing NSCs irrespective of the metric and conclude that neither strong inhibitory nor strong attractive signals drive NSC divisions in the adult zebrafish brain. © 2017 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of ISAC.
Artificial noise–aided secure communication in a bidirectional relaying network
Authors: Li An , Xu Yizhu , Wang Yuhao , Sun Lihua 
Published: November 2017

SummaryAn artificial noise strategy is proposed for amplify‐and‐forward bi‐directional relay network where the eavesdropper can wiretap the relay channels in both hops. Artificial noise is used to confuse the eavesdropper and improve its secrecy. Specifically, the source and the relay are allowed to split their available transmit power into 2 parts: a useful information portion and a jamming portion to transmit a jamming signal. The mathematical model is established for 2‐way relay network with an eavesdropper. The secrecy rate achieved by using artificial jamming is derived from the above model. The optimal power allocation with individual power constraint is obtained via sequential quadratic programming to maximize the secrecy sum rate, and 2 special cases are investigated. Furthermore, the benchmark is provided for the purpose of performance comparison. Simulation results show that the proposed strategy can significantly improve the secrecy sum rate by using artificial noise to jam the eavesdropper.
Detailed characterization of human Mycobacterium tuberculosis specific HLA‐E restricted CD8+ T cells
Authors: Prezzemolo Teresa , van Meijgaarden Krista E. , Franken Kees L.M.C. , Caccamo Nadia , Dieli Francesco , Ottenhoff Tom H.M. , Joosten Simone A. 
Published: November 2017

AbstractHLA‐E presented antigens are interesting targets for vaccination given HLA‐Es’ essentially monomorphic nature. We have shown previously that Mycobacterium tuberculosis (Mtb) peptides are presented by HLA‐E to CD8+ effector T cells, but the precise phenotype and functional capacity of these cells remains poorly characterized. We have developed and utilized in this study a new protocol combining HLA‐E tetramer with intracellular staining for cytokines, transcription factors and cytotoxic molecules to characterize these cells in depth. We confirm in this study the significantly increased ex vivo frequency of Mtb‐peptide/HLA‐E‐TM+ CD8+ T cells in the circulation of patients with active tuberculosis (TB). HLA‐E restricted CD8+ T cells from TB patients produced more IL‐13 than cells from controls or subjects with latent tuberculosis infection (LTBI). Compared to total CD8+ T cells, HLA‐E restricted cells produced more IFNγ, IL‐4, IL‐10, and granulysin but less granzyme‐A. Moreover, compared to “classical” Mtb specific HLA‐A2 restricted CD8+ T cells, HLA‐E restricted CD8+ T cells produced less TNFα and perforin, but more IL‐4. In conclusion, HLA‐E restricted‐ Mtb specific cells can produce Th2 cytokines directly.
A mechanically strengthened polyacrylamide gel matrix fully compatible with electrophoresis of proteins and nucleic acids
Authors: Pushparajan Charlotte , Goswami Shailesh K. , McAdam C. John , Hanton Lyall R. , Dearden Peter K. , Moratti Stephen C. , Cridge Andrew G. 
Published: November 2017

AbstractPolyacrylamide gel electrophoresis is a universal tool in a biochemist's toolkit for protein and nucleic acid separation and subsequent visualisation and analysis. The standard formulation of polyacrylamide gels consists of acrylamide (ACM) monomer crosslinked with bisacrylamide (MBA) which creates a gel with excellent sieving properties but which is mechanically fragile and prone to tearing during post‐electrophoresis manipulations involved in visualisation and analysis. By adding a poly(ethylene oxide) macro‐crosslinker to the standard gel formulation, we have created a tough gel matrix that can be used to fractionate proteins and nucleic acids by polyacrylamide gel electrophoresis. The protein and nucleic acid resolving capabilities and performance during staining and electroblotting of the tough gel matrix rivals that of conventional acrylamide/bisacrylamide gels. The tough gel matrix is resistant to tear and remarkably elastic, capable of stretching to over four times its original length before breaking, and represents a significant improvement over standard polyacrylamide gel formulations.
Evaluation of MESSAGE communication strategy combined with group reminiscence therapy on elders with mild cognitive impairment in long‐term care facilities
Authors: Zhang Huan‐huan , Liu Peng‐cheng , Ying Jie , Shi Ying , Wang Shou‐qi , Zhang Mei‐ling , Sun Jiao 
Published: November 2017

ObjectiveThis study aims to evaluate combined effects of MESSAGE communication strategy and group reminiscence therapy (GRT) on elders with mild cognitive impairment (MCI) in long‐term care facilities in Changchun, China.MethodsThis study is a nonrandomized controlled trial. Subjects included 60 elders with MCI. Participants were divided into intervention (MESSAGE communication strategy combined with GRT) and control groups (without any intervention). Primary outcomes comprised cognitive function and quality of life of elderly people, as measured by the Beijing version of the Montreal Cognitive Assessment and the Chinese (mainland) version of Short‐Form 36 Health Survey assessment.ResultsWe observed significant changes in cognitive function with mean difference of 1.962 after 12 weeks (P = .000; 95% confidence interval [CI] = 1.341, 2.582), delayed memory dimension of 1.115 (P = .003; 95% CI = 0.417, 1.813). The intervention group exhibited the following improvements: general health of 14.731 (P = .000; 95% CI = 8.511, 20.951), mental health of 21.038 (P = .000; 95% CI = 17.301, 24.776), role‐emotional of 26.925 (P = .003; 95% CI = 10.317, 45.533), and vitality of 14.231 (P = .000; 95% CI = 10.084, 18.377).ConclusionsUsing a sample of Chinese elderly people with MCI and residing in long‐term care facilities, we concluded that application of MESSAGE communication strategy combined with GRT resulted in improved cognitive function and quality of life.
Evaluation of energy balance closure adjustment methods by independent evapotranspiration estimates from lysimeters and hydrological simulations
Authors: Mauder Matthias , Genzel Sandra , Fu Jin , Kiese Ralf , Soltani Mohsen , Steinbrecher Rainer , Zeeman Matthias , Banerjee Tirtha , De Roo Frederik , Kunstmann Harald 
Published: November 2017

AbstractNon‐closure of the surface energy balance is a frequently observed phenomenon of hydrometeorological field measurements, when using the eddy‐covariance method, which can be ascribed to an underestimation of the turbulent fluxes. Several approaches have been proposed in order to adjust the measured fluxes for this apparent systematic error. However, there are uncertainties about partitioning of the energy balance residual between the sensible and latent heat flux and whether such a correction should be applied on 30‐min data or longer time scales. The data for this study originate from two grassland sites in southern Germany, where measurements from weighable lysimeters are available as reference. The adjusted evapotranspiration rates are also compared with joint energy and water balance simulations using a physically based distributed hydrological model. We evaluate two adjustment methods: the first one preserves the Bowen ratio and the correction factor is determined on a daily basis. The second one attributes a smaller portion of the residual energy to the latent heat flux than to the sensible heat flux for closing the energy balance for every 30‐min flux integration interval. Both methods lead to an improved agreement of the eddy‐covariance based fluxes with the independent lysimeter estimates and the physically based model simulations. The first method results in a better comparability of evapotranspiration rates, and the second method leads to a smaller overall bias. These results are similar between both sites despite considerable differences in terrain complexity and grassland management. Moreover, we found that a daily adjustment factor leads to less scatter than a complete partitioning of the residual for every half‐hour time interval. The vertical temperature gradient in the surface layer and friction velocity were identified as important predictors for a potential future parameterisation of the energy balance residual.