bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design, Synthesis and Pharmacological Evaluation of Novel Hsp90N‐terminal Inhibitors Without Induction of Heat Shock Response
Authors: Liu Peng , Chen Xiangling , Zhu Jianming , Li Bo , Chen Zhaoqiang , Wang Guimin , Sun Haiguo , Xu Zhijian , Zhao Zhixin , Zhou Chen , Xie Chengying , Lou Liguang , Zhu Weiliang 
Published: March 2019

AbstractHeat shock protein 90 (Hsp90) is a potential oncogenic target. However, Hsp90 inhibitors in clinical trial induce heat shock response, resulting in drug resistance and inefficiency. In this study, we designed and synthesized a series of novel triazine derivatives (A1‐26, B1‐13, C1‐23) as Hsp90 inhibitors. Compound A14 directly bound to Hsp90 in a different manner from traditional Hsp90 inhibitors, and degraded client proteins, but did not induce the concomitant activation of Hsp72. Importantly, A14 exhibited the most potent anti‐proliferation ability by inducing autophagy, with the IC50 values of 0.1 μM and 0.4 μM in A549 and SK‐BR‐3 cell lines, respectively. The in vivo study demonstrated that A14 could induce autophagy and degrade Hsp90 client proteins in tumor tissues, and exhibit anti‐tumor activity in A549 lung cancer xenografts. Therefore, the compound A14 with potent antitumor activity and unique pharmacological characteristics is a novel Hsp90 inhibitor for developing anticancer agent without heat shock response.
Dextramabs: A Novel Format of Antibody‐Drug Conjugates Featuring a Multivalent Polysaccharide Scaffold
Authors: Schneider Hendrik , Deweid Lukas , Pirzer Thomas , Yanakieva Desislava , Englert Simon , Becker Bastian , Avrutina Olga , Kolmar Harald 
Published: March 2019

AbstractAntibody‐drug conjugates (ADCs) are multicomponent biomolecules that have emerged as a powerful tool for targeted tumor therapy. Combining specific binding of an immunoglobulin with toxic properties of a payload, they however often suffer from poor hydrophilicity when loaded with a high amount of toxins. To address these issues simultaneously, we developed dextramabs, a novel class of hybrid antibody‐drug conjugates. In these architectures, the therapeutic antibody trastuzumab is equipped with a multivalent dextran polysaccharide that enables efficient loading with a potent toxin in a controllable fashion. Our modular chemoenzymatic approach provides an access to synthetic dextramabs bearing monomethyl auristatin as releasable cytotoxic cargo. They possess high drug‐to‐antibody ratios, remarkable hydrophilicity, and high toxicity in vitro.
SFCE METRO‐01 four‐drug metronomic regimen phase II trial for pediatric extracranial tumor
Authors: Heng‐Maillard Marie‐Amélie , Verschuur Arnauld , Aschero Audrey , Dabadie Alexia , Jouve Elisabeth , Chastagner Pascal , Leblond Pierre , Aerts Isabelle , De Luca Bénédicte , André Nicolas 
Published: March 2019

AbstractObjectiveTo investigate the antitumor activity of a four‐drug metronomic chemotherapy (MC) regimen in relapsed/progressing pediatric extracranial solid tumors (EST). The primary objective was clinical benefit (complete response /partial response/stable disease [SD]) after two cycles of therapy (four months).MethodsPatients aged ≥4 to 25 years with progressing EST and adequate organ function were eligible. Treatment consisted of an eight‐week cycle of oral celecoxib b.i.d., weekly vinblastine, and oral cyclophosphamide for three weeks alternating with oral methotrexate for three weeks, with a two‐week rest. The Kepner–Chang two‐stage model was used with 10 patients in the first stage. If primary objective was reached in two or more patients, eight additional patients were included according to four groups: neuroblastoma (NBL), soft‐tissue sarcoma (STS), bone sarcoma (BS), and miscellaneous (Misc.).ResultsForty‐four patients were evaluable. The NBL cohort could be expanded to 18 patients: 4 of 18 patients stabilized with MC treatment for 6 (n = 1) and 12 (n = 3) months. In STS, two of seven patients (metastatic hemangioendothelioma and angiosarcoma) had SD for > 2 cycles. One of nine Misc. (metastatic myoepithelial carcinoma) had SD for one year. All patients with BS had progressive disease. One‐year progression‐free survival of the whole cohort was 6.8% and one‐year overall survival was 55.3%. Grade 3 toxicity occurred in 18 patients and grade 4 in 15 patients. The most frequent toxicity was hematologic, predominantly neutropenia.ConclusionsThis MC has no activity in BS and limited though interesting activity in NBL with some patients being stable for > 1 year. It is not possible to conclude activity in STS and Misc.
Outcome of localized liver‐bile duct rhabdomyosarcoma according to local therapy: A report from the European Paediatric Soft‐Tissue Sarcoma Study Group (EpSSG)‐RMS 2005 study
Authors: Guérin Florent , Rogers Timothy , Minard‐Colin Véronique , Gaze Mark N. , Terwisscha Sheila , Van Noesel Max , De Corti Federica , Guillén Burrieza Gabriela , De Salvo Gian Luca , Kelsey Anna , Orbach Daniel , Ferrari Andrea , Bergeron Christophe , Bisogno Gianni , Martelli Hélène 
Published: March 2019

AbstractObjectivesTo evaluate the impact of local therapies on the outcome of patients with liver‐bile duct rhabdomyosarcoma (LBDRMS).MethodsData of 30 patients included in the EpSSG‐RMS 2005 study were analyzed.ResultsThe median age at diagnosis was 3 years (11 months–8 years). All patients had non‐alveolar histology. Fifteen patients had a tumor > 5 cm and six had enlarged regional lymph nodes on imaging. Eight patients (27%) had primary surgery (1 R0). Six of them received external beam radiotherapy (EBRT). All are in first complete remission (CR1) except one (R1, EBRT+, local relapse, death). Six patients (20%) received EBRT without surgery: one had local relapse and died. Sixteen patients (53%) underwent delayed surgery, with 12 achieving R0 margins, which were higher than those in the primary surgery group (P = 0.003). Three patients with R0 margins received EBRT; one had a metastatic relapse and died. Nine patients with R0 resection did not receive EBRT, three relapsed locally (two deaths). Four R1 patients received additional EBRT without relapses. Local relapse occurred in two among 19 patients with EBRT and three among 11 without EBRT (P = 0.326). At a median follow‐up of 61 months (48–84 months), five patients died; all had a tumor size > 5 cm (P = 0.01). The five‐year overall survival was 85% (95% CI, 65–94), and event‐free survival was 76% (95% CI, 54–89).ConclusionThis analysis did not show any significant difference in outcome between irradiated and nonirradiated patients. Local relapse in LBDRMS is related to initial tumor size and is often fatal.
Impact of a prescription drug monitoring program use mandate on potentially problematic patterns of opioid analgesic prescriptions in New York City
Authors: Bachhuber Marcus A. , Tuazon Ellenie , Nolan Michelle L. , Kunins Hillary V. , Paone Denise 
Published: March 2019

AbstractPurposeTo evaluate New York State's mandate that prescribers query the prescription drug monitoring program (PDMP) prior to prescribing Schedule II‐IV medications.MethodsWe conducted an interrupted time series analysis of opioid analgesic prescriptions dispensed to adult New York City (NYC) residents using data from New York State's PDMP. Our main outcomes were the rate of (a) greater than or equal to five prescriber episodes, (b) greater than or equal to five prescriber and greater than or equal to five pharmacy episodes, and (c) paying for prescriptions with both cash and insurance, per quarter, per 100 000 NYC residents. We defined three periods: (a) the baseline period (January 2011 to July 2012), (b) the anticipatory period (September 2012 to July 2013) after mandate law enactment but before mandate implementation, and (c) the postmandate period (September 2013 to December 2015). For each outcome, we used autoregressive linear regression models to account for correlation in outcomes over time.ResultsAt the end of the postmandate period, the rate of greater than or equal to five prescriber episodes was 58% lower than expected (absolute difference: −17.2 per 100 000 NYC residents; 95% CI, −31.2 to −3.1), the rate of greater than or equal to five prescriber and greater than or equal to five pharmacy episodes was 88% lower than expected (absolute difference: −8.6; 95% CI, −11.0 to −6.3), and the rate of cash and insurance payment episodes was 50% lower than expected (absolute difference: −145.4; 95% CI, −279.4 to −11.6).ConclusionsWhile outcomes were relatively rare, New York State's PDMP mandate was associated with significant decreases in rates of potentially problematic patterns of opioid analgesic prescriptions.
Calcium Channel Blocker Use and the Risk for Prostate Cancer: A Population‐Based Nested Case‐Control Study
Authors: Rotshild Victoria , Azoulay Laurent , Feldhamer Ilan , Perlman Amichai , Muszkat Mordechai , Matok Ilan 
Published: March 2019

IntroductionCalcium channels play a significant role in the regulation of cell proliferation and apoptosis. This study investigates associations between calcium channel blocker (CCB) use and the incidence of prostate cancer (PCa).MethodsA nested case‐control study was conducted using the Clalit Health Services database. We formed a population‐based cohort of patients who were prescribed their first antihypertensive agent between 2000 and 2014. For each newly diagnosed PCa case in the cohort, 10 controls were matched by age, calendar year of cohort entry, and duration of follow‐up. Multivariate conditional logistic regression analyses were used to evaluate the odds ratios (ORs) of PCa among CCB users compared with users of other antihypertensive drugs.ResultsWe identified 4346 patients with newly diagnosed PCa during the median follow‐up of 5.3 years. The exposure to CCBs was associated with a slight increase in risk for PCa (OR 1.10, 95% confidence interval [CI] 1.02–1.18) when compared with non‐CCB antihypertensive drugs. In secondary analyses, evidence was found of a duration‐response relationship, with the association for PCa increasing by 27% for every 10‐year increment of CCB use (OR 1.27, 95% CI 1.04–1.56).ConclusionsThe results of this large population‐based study indicate a modest but significant increase in the risk of PCa among CCB users, and the risk increases with duration of use.
Enhancing performance of nonvolatile transistor memories via electron‐accepting composition in triphenylamine‐based random copolymers
Authors: Chen Chun‐Kai , Hsieh Hui‐Ching , Shih Chien‐Chung , Wu Chien‐Hsin , Fu Mao‐Chun , Higashihara Tomoya , Jeng Ru‐Jong , Chen Wen‐Chang 
Published: March 2019

ABSTRACTWith the rapid advances in organic memory, organic field‐effect transistor (OFET) memory has been recognition of the value over the past few years. Although the functional polymer with the Donor‐Acceptor (D‐A) structure has been widely investigated, little research has been carried out to clarify the relationships among D‐A structure of the polymer, capability of charge‐transfer, and memory performance. Here, we report the nonvolatile memory characteristics of pentacene‐based OFET memory using random copolyimides, poly[4,4′‐diaminotriphenylamine‐hexafluoroisopropylidenediphthalimide‐co‐4‐(N,N‐bis(p‐aminophenyl)amino)‐4′‐nitroazobenzene‐hexafluoroisopropylidenediphthalimide) (PI(TPA‐6FDA‐DACx)), with feeding ratios of DAC to TPA set as x (where x = 0,10, 30,50,70,100). The OFET memory performance based on the molar ratio of DAC to TPA equal to 30:70 represents the best results with the proper charge mobility, on/off current ratio, and memory window. Intriguingly, the memory performance can be enhanced by introducing more D‐A monomer in polymer electrets, yet the concomitant inferior growth of pentacene decreases the charge mobility, attributed to the intrinsically destructive arrangement of polymer backbone. Our conclusion points out the importance of polymer arrangement and capability of charge‐transfer to the OFET performance and memory characteristics. The comparable results can also be applied for advanced OFET memory devices. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1113–1121
Suicidal germination as a control strategy for Striga hermonthica (Benth.) in smallholder farms of sub‐Saharan Africa
Authors: Kountche Boubacar A. , Jamil Muhammad , Yonli Djibril , Nikiema Minimassom P. , Blanco‐Ania Daniel , Asami Tadao , Zwanenburg Binne , Al‐Babili Salim 
Published: March 2019

Societal Impact StatementInfestation by the parasitic plant Striga hermonthica is a severe threat to food security in sub‐Saharan Africa, impacting the production of the major staple crops pearl millet and sorghum, equating to 7–10 billion $ losses. Using Striga seed dependency on host‐released germination stimulants, we have developed and validated a method for addressing the problem of accumulated parasite seedbanks—the major obstacle in combating Striga infestation in African rain‐fed fields. Application of our method promises to alleviate the problem posed by this pernicious weed by increasing crop production for smallholder farmers.
Summary

The root parasitic plant Striga hermonthica is a major threat to global food security, causing enormous losses in yields of the main staple crops in sub‐Saharan Africa, which include pearl millet, sorghum, maize and rice.

Sustainable Striga control should ideally lead to the depletion of the vast, long‐lived Striga seedbank, and this can be achieved by inducing suicidal seed germination through application of strigolactone (SL) analogs in the absence of host plants. However, this “suicidal germination” strategy has not been evaluated under the natural rain‐fed conditions that prevail in Striga‐prone regions.

We have developed and validated a protocol for suicidal germination in laboratory and natural conditions in Striga‐infested rain‐fed African fields. Three SL analogs were tested and these resulted to between 65% and 55% reduction in Striga emergence in pearl millet and sorghum fields, respectively.

We conclude that suicidal germination is an effective method for reducing the Striga seedbank. Moreover, the minimal demands of our protocol, in terms of water consumption and amount of selected SL analogs, make it affordable and applicable at a large scale in African rain‐fed agriculture, holding promise for sustainable cleaning of heavily Striga‐infested fields in sub‐Saharan Africa.
Decrease the flow setting to improve trans‐nasal pulmonary aerosol delivery via “high‐flow nasal cannula” to infants and toddlers
Authors: Li Jie , Gong Lingyue , Ari Arzu , Fink James B. 
Published: March 2019

AbstractObjectivesTrans‐nasal pulmonary aerosol delivery for infants and toddlers has recently gained popularity, however, the reported lung deposition is low. We aimed to investigate the influential factors to improve the delivery.MethodsAnatomic airway manikins simulating infant (5 kg) and toddler (15 kg) with collecting filter connected the trachea and breath simulator, were set to represent quiet and distressed breathing. Nasal cannula flow was set at 0.125, 0.25, 0.5, 1, and 2 L/kg/min. A mesh nebulizer (Aerogen) was placed at the inlet of humidifier (Fisher & Paykel) and proximal to patient. Albuterol (5 mg in 1 mL) was nebulized for each condition (n = 3). Drug was eluted from the filter and assayed with UV spectrophotometry (276 nm).ResultsInhaled dose was higher with nebulizer placed at the inlet of humidifier than proximal to patient in all settings, except the infant model at low gas flow settings (0.125 and 0.25 L/kg/min). When nebulizer was placed at the inlet of humidifier, inhaled dose was higher when gas flow was below patient's inspiratory flow than when gas flow exceeded patient's inspiratory flow (8.77 ± 3.84 vs 2.16 ± 1.29%, P < 0.001); aerosol deposition increased as gas flow decreased, with greatest deposition at gas flow of 0.25 L/kg/min (11.29 ± 2.15%). A multiple linear regression identified gas flow as the primary predictor of aerosol delivery.ConclusionsTrans‐nasal pulmonary aerosol delivery was significantly improved when gas flow was below patient's inspiratory flow, aerosol deposition increased with decreased nasal cannula flow, with greatest deposition at 0.25 L/kg/min.
OPUS‐SSF: A side‐chain‐inclusive scoring function for ranking protein structural models
Authors: Xu Gang , Ma Tianqi , Wang Qinghua , Ma Jianpeng 
Published: March 2019

AbstractWe introduce a side‐chain‐inclusive scoring function, named OPUS‐SSF, for ranking protein structural models. The method builds a scoring function based on the native distributions of the coordinate components of certain anchoring points in a local molecular system for peptide segments of 5, 7, 9, and 11 residues in length. Differing from our previous OPUS‐CSF [Xu et al., Protein Sci. 2018; 27: 286–292], which exclusively uses main chain information, OPUS‐SSF employs anchoring points on side chains so that the effect of side chains is taken into account. The performance of OPUS‐SSF was tested on 15 decoy sets containing totally 603 proteins, and 571 of them had their native structures recognized from their decoys. Similar to OPUS‐CSF, OPUS‐SSF does not employ the Boltzmann formula in constructing scoring functions. The results indicate that OPUS‐SSF has achieved a significant improvement on decoy recognition and it should be a very useful tool for protein structural prediction and modeling.
Small binary iron‐carbon clusters with persistent high magnetic moments. A theoretical characterization
Authors: Limon Patricio , Miralrio Alan , Castro Miguel 
Published: March 2019

AbstractCharacterization of the structural and electronic properties of binary iron‐carbon clusters composed by six iron atoms and with up to nine carbon atoms was carried out with density functional theory calculations. Neutral, cations (q = +1), and anions (q = −1), some of them experimentally detected, were studied. The formation of dimers and trimers of carbon atoms over the iron surface were preferred. Moreover, some large carbon chains, with up to five atoms, were determined. High spin states emerged for the ground states, with multiplicities above 16, for all clusters independently of the number of carbon atoms attached to the iron core. All neutral clusters were stable because fragmentation (into carbon chains), dissociation (of a single carbon atom), and detachment of all carbons need high amounts of energy. Reactive species were defined by small HOMO‐LUMO gaps. Charge transfer, to the carbon atoms, increased as the carbon content increased, producing, for some cases, an even‐odd behavior for the magnetic moment of the Fe6Cn particles.
On the nature of ion‐stabilized cytosine pairs in DNA i‐motifs: The importance of charge transfer processes
Authors: Kohagen Miriam , Uhlig Frank , Smiatek Jens 
Published: March 2019

AbstractRecent experimental results indicate that the stability of non‐Watson‐Crick DNA i‐motif structures can be influenced by the presence of various metal cations. Whereas Au+, Cu+, and Ag+ are stabilizing agents, alkali metal ions like Na+ or Li+ are known to destabilize the i‐motif. In terms of reduced ion‐cytosine complexes, we rationalize the experimental observations with the help of standard and conceptual density functional theory (DFT) calculations. Our results highlight the importance of coordinating electrostatic bonds with partially covalent character for the stability of the ion‐cytosine complex. The occurrence of these bonds can be mainly attributed to charge transfer processes between two cytosines and the transition metal ions, which can be either explained by frontier molecular orbital theory in combination with a bond critical point analysis, or by the concept of chemical reactivity indices within a conceptual DFT approach. The results of our calculations establish a consistent theoretical framework to understand the experimentally observed behavior, and are also important in order to achieve more detailed insights into nucleobase pairing mechanisms in general.
Contribution of the Centrifugal Partition Chromatography (CPC) to the Purification of Zincke Reaction Products
Authors: Lachaise Isabelle , Zeghbib Narimane , Asskar Ghada , Rivard Michael , Martens Thierry 
Published: March 2019

AbstractThe Zincke reaction poses a difficulty when attempting to purify the crude mixtures and isolate reaction products in analytically pure form. This paper introduces the successful method of using the centrifugal partition chromatography (CPC) to isolate pyridinium salts garnered by this reaction returning good yields and high degrees of purity. Efficient purifications were obtained by using (n‐BuOH/MeOH/H2O) biphasic solvent systems. The CPC confirmed its suitability for isolating compounds prone to decompose during purification on solid stationary phases. It has also proved to be an efficient method for valorizing incomplete Zincke reactions.
Well‐Defined Cu2O/Cu3(BTC)2 Sponge Architecture as Efficient Phenolics Scavenger: Synchronous Etching and Reduction of MOFs in confined‐pH NH3⋅H2O
Authors: Jia Kai , Ye Jiahua , Zhuang Guoxin , Zhuang Zanyong , Yu Yan 
Published: March 2019

AbstractFabrication of low‐dimensional nano‐MOFs as well as nanoparticles/metal‐organic frameworks (MOFs) hybrids has sparked new scientific interests but remains a challenging task. Taking Cu3(BTC)2 as a proof of concept, it is demonstrated thats NH3⋅H2O solution of a confined pH value can readily shape the bulk Cu3(BTC)2 into nanoscale Cu3(BTC)2, beyond the need to control the crystal growth kinetics of MOFs. Adjusting the pH of NH3⋅H2O within a much small range (10–11) allows fine tuning over the size and shape of nanoscale Cu3(BTC)2. Particularly at pH = 11, NH3⋅H2O exhibits weak reducibility that triggers a reduction of part of Cu3(BTC)2 into Cu2O, while shaping the other into Cu3(BTC)2 nanowires. Benefiting from the coincidence of reduction and etching effects, the newly generated Cu2O dots can in situ anchor onto adjacent Cu3(BTC)2 nanowires at highly dispersive state, forming a well‐defined sponge‐like architecture built of Cu2O dots and nano‐Cu3(BTC)2. The CuOx
derived from annealing of the Cu2O dots/nano‐Cu3(BTC)2 hybrid preserves the sophisticated sponge architecture and high porosity, and exhibits promising applications in phenol scavenging, with efficiency outperforming its counterparts and many other Cu‐based catalysts reported in literature. It is anticipated that the findings here pave the way for the rational design of intricate nano‐MOFs in a more efficient way.
Integration of properties of virtual reality, artificial neural networks, and artificial intelligence in the automation of software tests: A review
Authors: Serna M. Edgar , Acevedo M. Eder , Serna A. Alexei 
Published: March 2019

AbstractThe complete automation of software tests has been considered to be an unattainable goal. This article discusses the potential to achieve this goal with recent discoveries and innovations in the areas of virtual reality (VR), artificial neural networks (ANNs), and artificial intelligence (AI). In this study, a theoretical proposal is described to integrate the properties of each of these areas using a process of automation of software tests. This process is based on a classification and description of the properties after consulting the literature, interviews, and dialogs with specialists from Australia, the United States, Germany, and Colombia. In addition to the experiences of the researchers, the construction of two tools is proposed: (1) a robot to design and apply functional tests, and (2) a virtual machine to identify errors in the logical structure of the code. Both tools are expected to replace human factors; the advantage is that the first tool identifies procedural flaws and the second errors of operation.