bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved stratification of ALS clinical trials using predicted survival
Authors: Berry James D. , Taylor Albert A. , Beaulieu Danielle , Meng Lisa , Bian Amy , Andrews Jinsy , Keymer Mike , Ennist David L. , Ravina Bernard 
Published: March 2018

AbstractIntroductionIn small trials, randomization can fail, leading to differences in patient characteristics across treatment arms, a risk that can be reduced by stratifying using key confounders. In ALS trials, riluzole use (RU) and bulbar onset (BO) have been used for stratification. We hypothesized that randomization could be improved by using a multifactorial prognostic score of predicted survival as a single stratifier.MethodsWe defined a randomization failure as a significant difference between treatment arms on a characteristic. We compared randomization failure rates when stratifying for RU and BO (“traditional stratification”) to failure rates when stratifying for predicted survival using a predictive algorithm. We simulated virtual trials using the PRO‐ACT database without application of a treatment effect to assess balance between cohorts. We performed 100 randomizations using each stratification method – traditional and algorithmic. We applied these stratification schemes to a randomization simulation with a treatment effect using survival as the endpoint and evaluated sample size and power.ResultsStratification by predicted survival met with fewer failures than traditional stratification. Stratifying predicted survival into tertiles performed best. Stratification by predicted survival was validated with an external dataset, the placebo arm from the BENEFIT‐ALS trial. Importantly, we demonstrated a substantial decrease in sample size required to reach statistical power.ConclusionsStratifying randomization based on predicted survival using a machine learning algorithm is more likely to maintain balance between trial arms than traditional stratification methods. The methodology described here can translate to smaller, more efficient clinical trials for numerous neurological diseases.
Biopebbles: DNA‐Functionalized Core–Shell Silica Nanospheres for Cellular Uptake and Cell Guidance Studies
Authors: Leidner Arnold , Weigel Simone , Bauer Jens , Reiber Jens , Angelin Alessandro , Grösche Maximilian , Scharnweber Tim , Niemeyer Christof M. 
Published: March 2018

AbstractThe development of a versatile class of silica nanoparticles for cell studies is reported. The particles contain a fluorescent dye‐encoded core and a single‐stranded DNA oligonucleotide‐displaying shell. They are accessible in arbitrary size and color through robust protocols for Stöber‐based colloidal synthesis and sturdy chemical surface functionalization. Silica particles in the size range of 100 nm to 1.5 µm diameter containing fluorescein, Cy3 oder Cy5 dye‐encoded cores are synthesized and functionalized with DNA oligonucleotides. These silica biopebbles are conveniently traceable by microscopy and have a high affinity to live cells, which makes them ideal for cell uptake studies, as demonstrated for MCF7 and A431 cancer cells. The biopebbles can be utilized as building blocks for the self‐assembled formation of arbitrary surface patterns on glass substrates. With these architectures, the privileged internalization of the biopebbles can be exploited for improved adhesion and guidance of cells because the particles are no longer ingested by adhered cells due to their physical connection with the solid support. It is believed that the biopebble approach will be useful for a variety of applications, fundamental studies in cell biology and tissue engineering.
The effect of polyploidization on tree hydraulic functioning
Authors: De Baerdemaeker Niels J. F. , Hias Niek , Van den Bulcke Jan , Keulemans Wannes , Steppe Kathy 
Published: March 2018

Premise of the StudyRecent research has highlighted the importance of living tissue in wood. Polyploidization can impact amounts and arrangements of living cells in wood, potentially leading to increased drought tolerance. Tetraploid variants were created from the apple cultivar Malus ×domestica ‘Gala’ (Gala‐4x), and their vulnerability to drought‐induced cavitation and their hydraulic capacitance were compared to those of their diploid predecessors (Gala‐2x). Assuming a positive correlation between polyploidy and drought tolerance, we hypothesized lower vulnerability and higher capacitance for the tetraploid.MethodsVulnerability to drought‐induced cavitation and the hydraulic capacitance were quantified through acoustic emission and continuous weighing of shoots during a bench‐top dehydration experiment. To underpin the hydraulic trait results, anatomical variables such as vessel area, conduit diameter, cell wall reinforcement, and ray and vessel‐associated parenchyma were measured.Key ResultsVulnerability to drought‐induced cavitation was intrinsically equal for both ploidy variants, but Gala‐4x proved to be more vulnerable than Gala‐2x during the early phase of desiccation as was indicated by its significantly lower air entry value. Higher change in water content of the leafy shoot, higher amount of parenchyma, and larger vessel area and size resulted in a significantly higher hydraulic capacitance and efficiency for Gala‐4x compared to Gala‐2x.ConclusionsBoth ploidy variants were typified as highly sensitive to drought‐induced cavitation, with no significant difference in their overall drought vulnerability. But, when water deficit is short and moderate, Gala‐4x may delay a drought‐induced decrease in performance by trading hydraulic safety for increased release of capacitively stored water from living tissue.
Effects of the Addition of Spray‐Dried Whey on the Stability of Fat‐Reduced Mayonnaise‐Type Emulsions During Storage
Authors: Biller Elżbieta , Waszkiewicz‐Robak Bożena , Longo Edoardo , Boselli Emanuele , Obiedziński Mieczysław , Siwek Adam , Stachelska Milena A. 
Published: March 2018

AbstractThe applicability of the spray‐dried whey for the production of reduced‐calorie mayonnaise‐type emulsions was studied. Whey was used as a stabilizing/emulsifying agent and as a fat‐replacement component. Whey powder was spray‐dried at 130, 140, and 180 °C. As control sample, 80% w/w standard fat emulsion was prepared. Mayonnaise‐like fat‐reduced emulsions contained 65% w/w of fat and 15% w/w of three distinct types of whey. The destabilization of the emulsions was investigated within 7 days of storage by scanning the samples with laser light. Backscattering, Turbiscan stability index, elasticity index, and macroscopic viscosity index were determined. The most stable emulsion contained whey powder spray‐dried at 180 °C. The emulsion made with whey powder spray‐dried at 130 °C was less stable than that with 180 °C spray‐dried whey, but it was more stable than the control and the one with whey spray‐dried at 140 °C.
Fabricating durable, fluoride‐free, water repellency cotton fabrics with CPDMS
Authors: Ma Yue , Zhu Danjie , Si Yang , Sun Gang 
Published: March 2018

ABSTRACTThe demand for fluoride‐free and durable hydrophobic cotton fabric is dramatically increasing due to environmental and human safety concerns. The current approach to produce water repellent cotton fabrics is applying fluorocarbon compounds in topical treatments. However, the fluorocarbons employed in the water repellent treatments on cotton fabrics have environmental concerns and environmentally friendly technologies are desperately sought. Herein, we report a new approach of fabricating water repellent cotton fabrics with proper washing durability by using poly{dimethylsiloxane‐co‐[2‐(3,4‐epoxycyclohexyl)ethyl]methylsiloxane} (CPDMS) as a hydrophobic agent. Benefiting from formation of robust ether bonds between CPDMS and celluloses, the cotton fabrics could gain promising durability for daily laundry. The resultant cotton fabrics demonstrated simultaneously desired waterproofness (hydrostatic pressure up to 22 mbar), durability (hydrostatic pressure stabled at 12 mbar after five laundry cycles), and breathability. Moreover, the CPDMS modified cotton fabrics also exhibited robust physical property with tensile strength retention up to 73%. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46396.
Pyridine‐substituted thiazolylphenol derivatives: Synthesis, modeling studies, aromatase inhibition, and antiproliferative activity evaluation
Authors: Ertas Merve , Sahin Zafer , Berk Barkin , Yurttas Leyla , Biltekin Sevde N. , Demirayak Seref 
Published: March 2018

AbstractDrugs used in breast cancer treatments target the suppression of estrogen biosynthesis. During this suppression, the main goal is to inhibit the aromatase enzyme that is responsible for the cyclization and structuring of estrogens either with steroid or non‐steroidal‐type inhibitors. Non‐steroidal derivatives generally have a planar aromatic structure attached to the triazole ring system in their structures, which inhibits hydroxylation reactions during aromatization by coordinating the heme group. Bioisosteric replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase the selectivity for aromatase enzyme inhibition. In this study, pyridine‐substituted thiazolylphenol derivatives, which are non‐steroidal triazole bioisosteres, were synthesized using the Hantzsch method, and physical analysis and structural determination studies were performed. The IC50 values of the compounds were determined by a fluorescence‐based aromatase inhibition assay. Then, their antiproliferative activities on the MCF7 and HEK 293 cell lines were evaluated with the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. Furthermore, the crystal structure of human placental aromatase was subjected to a series of docking experiments to identify the possible interactions between the most active structure and the active site. Lastly, an in silico technique was performed to analyze and predict the drug‐likeness, molecular and ADME properties of the synthesized molecules.
Nano Trek Beyond: Driving Nanocars/Molecular Machines at Interfaces
Authors: Ariga Katsuhiko , Mori Taizo , Nakanishi Waka 
Published: March 2018

AbstractIn 2016, the Nobel Prize in Chemistry was awarded for pioneering work on molecular machines. Half a year later, in Toulouse, the first molecular car race, a “nanocar race”, was held by using the tip of a scanning tunneling microscope as an electrical remote control. In this Focus Review, we discuss the current state‐of‐the‐art in research on molecular machines at interfaces. In the first section, we briefly explain the science behind the nanocar race, followed by a selection of recent examples of controlling molecules on surfaces. Finally, motion synchronization and the functions of molecular machines at liquid interfaces are discussed. This new concept of molecular tuning at interfaces is also introduced as a method for the continuous modification and optimization of molecular structure for target functions.
Cover Image, Volume 12, Issue 2
Authors: de Assis Camilla Abbati , Iglesias Maria Celeste , Bilodeau Michael , Johnson Donna , Phillips Richard , Peresin Maria Soledad , Bilek E.M. (Ted) , Rojas Orlando J. , Venditti Richard , Gonzalez Ronalds 
Published: March 2018

The cover image, by Camilla Abbati de Assis et al., is based on the Modeling and Analysis Cellulose micro‐ and nanofibrils (CMNF) manufacturing ‐ financial and risk assessment, DOI: 10.1002/bbb.1835.
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Differentially expressed and survival‐related proteins of lung adenocarcinoma with bone metastasis
Authors: Yang Mengdi , Sun Yi , Sun Jing , Wang Zhiyu , Zhou Yiyi , Yao Guangyu , Gu Yifeng , Zhang Huizhen , Zhao Hui 
Published: March 2018

AbstractDespite recent advances in targeted and immune‐based therapies, the poor prognosis of lung adenocarcinoma (LUAD) with bone metastasis (BM) remains a challenge. First, two‐dimensional gel electrophoresis (2‐DE) was used to identify proteins that were differentially expressed in LUAD with BM, and then matrix‐assisted laser desorption/ionization time of flight mass spectrometry (MALDI‐TOF‐MS) was used to identify these proteins. Second, the Cancer Genome Atlas (TCGA) was used to identify mutations in these differentially expressed proteins and Kaplan–Meier plotter (KM Plotter) was used to generate survival curves for the analyzed cases. Immunohistochemistry (IHC) was used to check the expression of proteins in 28 patients with BM and nine patients with LUAD. Lastly, the results were analyzed with respect to clinical features and patient's follow‐up. We identified a number of matched proteins from 2‐DE. High expression of enolase 1 (ENO1) (HR = 1.67, logrank P = 1.9E‐05), ribosomal protein lateral stalk subunit P2 (RPLP2) (HR = 1.77, logrank P = 2.9e‐06), and NME/NM23 nucleoside diphosphate kinase 2 (NME1‐NME2) (HR = 2.65, logrank P = 3.9E‐15) was all significantly associated with poor survival (P < 0.05). Further, ENO1 was upregulated (P = 0.0004) and calcyphosine (CAPS1) was downregulated (P = 5.34E‐07) in TCGA LUAD RNA‐seq expression data. IHC revealed that prominent ENO1 staining (OR = 7.5, P = 0.034) and low levels of CAPS1 (OR = 0.01, P < 0.0001) staining were associated with BM incidence. Finally, we found that LUAD patients with high expression of ENO1 and RPLP2 had worse overall survival. This is the first instance where the genes ENO1, RPLP2, NME1‐NME2 and CAPS1 were associated with disease severity and progression in LUAD patients with BM. Thus, with this study, we have identified potential biomarkers and therapeutic targets for this disease.
Emergence of nasal chondrosarcoma in a dog with nasal polyposis
Authors: Sumner Judd A. , Witham Adrian I. , Stent Andrew W. , Wightman Paul F. , Mansfield Caroline S. 
Published: March 2018

Key Clinical MessageWhilst the malignant transformation of nasal polyps or secondary development of nasal neoplasia after chronic inflammation is likely to be relatively rare, this potential complication should be considered, and the clinician should be vigilant for evidence of malignant transformation.
Characterization of two familial cases presenting with a syndromic specific learning disorder and carrying (17q;21q) unbalanced translocations
Authors: Coton Julie , Labalme Audrey , Till Marianne , Bussy Gerald , Krifi Papoz Sonia , Lesca Gaetan , Heron Delphine , Sanlaville Damien , Edery Patrick , des Portes Vincent , Rossi Massimiliano 
Published: March 2018

Key Clinical MessageChromosomal microarray (CMA) can detect pathogenic copy number variations in 15–20% of individuals with intellectual disability and in 10% of patients with autism spectrum disorders. The diagnostic rate in specific learning disorders (SLD) is unknown. Our study emphasizes the usefulness of CMA in the diagnostic workout assessment of familial SLD.
Photocatalytic Regulation of an Autocatalytic Wave of Spatially Propagating Enzymatic Reactions
Authors: Lanchuk Yulia , Nikitina Anna , Brezhneva Nadzeya , Ulasevich Sviatlana A. , Semenov Sergey N. , Skorb Ekaterina V. 
Published: March 2018

AbstractBioinspiration is an attractive way to develop new robust chemistry. In biological cell, chemical reactions form complex networks (e.g. signaling and metabolic) that communicate with each other and control cell division, growth, and interaction with environment. Thus, combining multiple chemical subsystems into a single network is an attractive way to design a chemical system with new functions. In this paper, we combined two chemical networks: i) a photocatalytic oxidation/ reduction on TiO2particles, and ii) an autocatalytic formation of enzyme trypsin (Tr) from its precursor trypsinogen (Tg). Moreover, we put the combined network in hydrogel media, where all reactions are coupled to diffusion, to achieve a photocatalytic regulation of an autocatalytic wave. We showed that TiO2particles affected the fluorescence quenching ofTr, but, without irradiation, had no effect on the autocatalytic formation ofTr. With irradiation, however, a cascade of photocatalytic reactions causes media acidification that suppress the autocatalytic formation ofTrand propagation of the autocatalytic wave.
In Situ Incorporation Strategy for Bimetallic FeCo‐Doped Carbon as Highly Efficient Bifunctional Oxygen Electrocatalysts
Authors: Shui Hengxin , Jin Tian , Hu Jun , Liu Honglai 
Published: March 2018

AbstractHighly efficient bifunctional oxygen reduction reaction/oxygen evolution reaction (ORR/OER) electrocatalysts are of great significance for developing rechargeable metal–air batteries. A facile in situ incorporation strategy was proposed to introduce an iron‐based complex into a cobalt‐based ZIF‐67 framework. The resultant FeCo−N/C exhibited an excellent ORR activity with a high half‐wave potential of 0.84 V and simultaneous outstanding OER activity with a low overpotential of 370 mV at a current density of 10 mA cm−2 in 0.1 M KOH. The overall oxygen electrode activity was calculated to be as low as 0.77 V. This work provides new opportunities for the development of highly efficient bifunctional electrocatalysts.
Oriented MoS2 Nanoflakes on N‐Doped Carbon Nanosheets Derived from Dodecylamine‐Intercalated MoO3 for High‐Performance Lithium‐Ion Battery Anodes
Authors: Liao Zhenhua , Li Qingwei , Zhang Jiabao , Xu Juan , Gao Biao , Chu Paul K. , Huo Kaifu 
Published: March 2018

AbstractMoS2 is a promising anode material for lithium‐ion batteries (LIBs) because of its layered structure, analogous to that of graphite, and high lithium storage capacity of 670 mAh g−1. However, its practical implementation in LIBs is hindered by poor conductivity, large volume change, and possible polysulfide shuttling during cycling. In this work, oriented MoS2 nanoflakes grown on N‐doped carbon nanosheets (MoS2/NC) are investigated as high‐performance anodes in LIBs. The materials are prepared by annealing dodecylamine‐intercalated MoO3 nanosheets under Ar at 400 °C, followed by a hydrothermal treatment in the thiourea (CH4N2S) solution at 220 °C for 30 h. In the MoS2/NC structure, the NC nanosheets constitute a long‐range conductive network for fast electron transfer, whereas the oriented MoS2 nanoflakes provide sufficient active sites for Li+ storage and fast Li+ diffusion along the a–b plane. Consequently, the MoS2/NC electrode shows a remarkable capacity of 803 mAh g−1 at a current density of 100 mA g−1, a high rate capability of 554 mAh g−1 at 2000 mA g−1, and excellent cycle stability. Our results reveal a facile and general method to produce high‐performance heterostructured MoS2/NC anodes and the process can be extended to other metal dichalcogenides for future high‐performance LIBs.
Subnaphthalocyanines as Electron Acceptors in Polymer Solar Cells: Improving Device Performance by Modifying Peripheral and Axial Substituents
Authors: Duan Chunhui , Guzmán David , Colberts Fallon J. M. , Janssen René A. J. , Torres Tomás 
Published: March 2018

AbstractA new class of subnaphthalocyanines bearing various peripheral and axial substituents have been synthesized for use as electron acceptors in solution‐processed bulk‐heterojunction polymer solar cells. The resulting solar cells exhibit modest photovoltaic performance with contributions from both the polymer donor and subnaphthalocyanine acceptor to the photocurrent.
The Physico‐Chemical Basis of DNA Radiosensitization: Implications for Cancer Radiation Therapy
Authors: Schürmann Robin , Vogel Stefanie , Ebel Kenny , Bald Ilko 
Published: March 2018

AbstractHigh‐energy radiation is used in combination with radiosensitizing therapeutics to treat cancer. The most common radiosensitizers are halogenated nucleosides and cisplatin derivatives, and recently also metal nanoparticles have been suggested as potential radiosensitizing agents. The radiosensitizing action of these compounds can at least partly be ascribed to an enhanced reactivity towards secondary low‐energy electrons generated along the radiation track of the high‐energy primary radiation, or to an additional emission of secondary reactive electrons close to the tumor tissue. This is referred to as physico‐chemical radiosensitization. In this Concept article we present current experimental methods used to study fundamental processes of physico‐chemical radiosensitization and discuss the most relevant classes of radiosensitizers. Open questions in the current discussions are identified and future directions outlined, which can lead to optimized treatment protocols or even novel therapeutic concepts.
Fluorinated GluN2B Receptor Antagonists with a 3‐Benzazepine Scaffold Designed for PET Studies
Authors: Szermerski Marina , Börgel Frederik , Schepmann Dirk , Haider Achi , Betzel Thomas , Ametamey Simon M. , Wünsch Bernhard 
Published: March 2018

AbstractTo analyze the N‐methyl‐d‐aspartate (NMDA) receptor distribution in the central nervous system, fluorinated ligands that selectively address the ifenprodil binding site of GluN2B‐subunit‐containing NMDA receptors were developed. Various strategies to introduce a fluorine atom into the potent GluN2B ligand 2 (3‐(4‐phenylbutyl)‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepin‐1,7‐diol) were pursued, including replacement of the benzylic OH moiety with a fluorine atom (13) and introduction of fluoroethoxy moieties at various positions (14 (7‐position), 17 (9‐position), 18a–c (1‐position)). With respect to GluN2B affinity and selectivity over related receptors, the fluoroethoxy derivatives 14 and 18a are the most promising ligands. Radiosynthesis of fluoroethoxy derivative [18F]14 was performed by nucleophilic substitution of the phenol 2 with 2‐[18F]fluoroethyl tosylate. On rat brain slices the fluorinated PET tracer [18F]14 accumulated in regions with high density of NMDA receptors containing GluN2B subunits. The bound radioactivity could not be replaced by (S)‐glutamate. However, the GluN2B ligands eliprodil, Ro 25‐6981, and the non‐labeled 3‐benzazepine 14 were able to abolish the specific binding of [18F]14.
Structural Determinants of the Stability of Enzyme‐Responsive Polyion Complex Nanoparticles Targeting Pseudomonas aeruginosa’s Elastase
Authors: Insua Ignacio , Petit Marion , Blackman Lewis D. , Keogh Robert , Pitto‐Barry Anaïs , O'Reilly Rachel K. , Peacock Anna F. A. , Krachler Anne Marie , Fernandez‐Trillo Francisco 
Published: March 2018

AbstractHere, we report how the stability of polyion complex (PIC) particles containing Pseudomonas aeruginosa’s elastase (LasB) degradable peptides and antimicrobial poly(ethylene imine) is significantly improved by careful design of the peptide component. Three LasB‐degradable peptides are reported herein, all of them carrying the LasB‐degradable sequence −GLA− and for which the number of anionic amino acids and cysteine units per peptide were systematically varied. Our results suggest that while net charge and potential to cross‐link via disulfide bond formation do not have a predictable effect on the ability of LasB to degrade these peptides, a significant effect of these two parameters on particle preparation and stability is observed. A range of techniques has been used to characterize these new materials and demonstrates that increasing the charge and cross‐linking potential of the peptides results in PIC particles with better stability in physiological conditions and upon storage. These results highlight the importance of molecular design for the preparation of PIC particles and should underpin the future development of these materials for responsive drug delivery.