bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concentrating Immiscible Molecules at Solid@MOF Interfacial Nanocavities to Drive an Inert Gas–Liquid Reaction at Ambient Conditions
Authors: Sim Howard Yi Fan , Lee Hiang Kwee , Han Xuemei , Koh Charlynn Sher Lin , Phan‐Quang Gia Chuong , Lay Chee Leng , Kao Ya‐Chuan , Phang In Yee , Yeow Edwin K. L. , Ling Xing Yi 
Published: November 2018

AbstractGas–liquid reactions form the basis of our everyday lives, yet they still suffer poor reaction efficiency and are difficult to monitor in situ, especially at ambient conditions. Now, an inert gas–liquid reaction between aniline and CO2 is driven at 1 atm and 298 K by selectively concentrating these immiscible reactants at the interface between metal–organic framework and solid nanoparticles (solid@MOF). Real‐time reaction SERS monitoring and simulations affirm the formation of phenylcarbamic acid, which was previously undetectable because they are unstable for post‐reaction treatments. The solid@MOF ensemble gives rise to a more than 28‐fold improvement to reaction efficiency as compared to ZIF‐only and solid‐only platforms, emphasizing that the interfacial nanocavities in solid@MOF are the key to enhance the gas–liquid reaction. Our strategy can be integrated with other functional materials, thus opening up new opportunities for ambient‐operated gas–liquid applications.
Asymmetric Total Synthesis of Brasilicardins
Authors: Yoshimura Fumihiko , Itoh Ryusei , Torizuka Makoto , Mori Genki , Tanino Keiji 
Published: November 2018

AbstractBrasilicardins, bacterial diterpenoid natural products that display highly potent immunosuppressive activity, are promising immunosuppressant drug candidates. Structurally, they can be described as hybrids of terpenoids, amino acids, and saccharides, and share a characteristic highly strained anti‐syn‐anti‐fused perhydrophenanthrene terpenoid scaffold (ABC‐ring system) with two quaternary asymmetric carbon atoms. A unified and stereoselective total synthesis of all four brasilicardins has been designed based on the strategic use of an intramolecular conjugate addition. The ABC‐ring system was initially constructed with high stereocontrol by novel intramolecular conjugate additions of Weinreb amides and in situ generated (Z)‐vinyl copper species. The late‐stage common intermediate was subjected to stereoselective installation of the amino acid component, followed by introduction of the saccharide unit via glycosylation to accomplish the total synthesis of brasilicardins A–D. Our synthesis offers opportunities to synthesize various brasilicardin analogues for biological and pharmacological investigations.
Resolution of unexpected pregnancy‐related findings in a rat embryofetal development and toxicokinetic study of monoclonal antibodies specific for hCMV
Authors: Katavolos Paula , Prell Rodney , Zane Doris , Deng Rong , Halpern Wendy 
Published: November 2018

BackgroundDevelopmental and reproductive toxicity testing is not uniformly warranted for biopharmaceuticals that lack relevant targets in test species. However, RG7667, consisting of two monoclonal antibodies specific for human cytomegalovirus (hCMV), was intended for administration to pregnant women to prevent transmission of CMV to the developing fetus.MethodsConsidering the target indication, a Pilot Embryo Fetal Development/Toxicokinetic study was conducted to assess toxicokinetics in the dam and fetuses and general tolerability.ResultsRG7667 administered intravenously to presumed pregnant Sprague–Dawley rats was well tolerated with no clinical signs in any dam and comparable litter sizes and viability across groups. However, at cesarean section, hepatic necrosis and pancreatic edema were identified in two dams administered RG7667, with no clear dose relationship. Investigation of total protein, albumin, and transaminase activity in residual serum from TK samples demonstrated striking hypoproteinemia and elevated transaminases limited to these two dams. Overall, these pathology findings in dams were considered of uncertain relationship to RG7667; therefore, a subsequent Pivotal EFD study was conducted, which did not repeat the liver or pancreatic findings.ConclusionsThe results of the Pivotal study confirmed the lack of overt toxicity, teratogenicity, or effects on litter size and viability when human or humanized monoclonal antibodies that lack an endogenous target are administered IV to rats during pregnancy. With these additional data, we concluded that the unexpected pathology findings in the Pilot study were not specific to RG7667, but rather highlight some clinical pathology and macroscopic/microscopic findings that can occur during pregnancy in rats.
ABOUND.2L+: A randomized phase 2 study of nanoparticle albumin‐bound paclitaxel with or without CC‐486 as second‐line treatment for advanced nonsquamous non‐small cell lung cancer (NSCLC)
Authors: Morgensztern Daniel , Cobo Manuel , Ponce Aix Santiago , Postmus Pieter E. , Lewanski Conrad R. , Bennouna Jaafar , Fischer Jürgen R. , Juan‐Vidal Oscar , Stewart David J. , Fasola Gianpiero , Ardizzoni Andrea , Bhore Rafia , Wolfsteiner Marianne , Talbot Denis C. , Jin Ong Teng , Govindan Ramaswamy , on behalf of the ABOUND.2L+ Investigators  
Published: November 2018

BackgroundThis randomized phase 2 trial compared the efficacy and safety of second‐line nanoparticle albumin‐bound paclitaxel (nab‐paclitaxel) with or without the addition of CC‐486 (an oral formulation of 5‐azacytidine) in patients with advanced‐stage, nonsquamous non‐small cell lung cancer.MethodsPatients were randomized to receive either nab‐paclitaxel 100 mg/m2 on days 8 and 15 plus CC‐486 200 mg daily on days 1 to 14 or single‐agent nab‐paclitaxel 100 mg/m2 on days 1 and 8, with both regimens administered every 21 days until tumor progression or unacceptable toxicity. The primary endpoint was progression‐free survival. Secondary endpoints included the overall response rate, the disease control rate, and overall survival.ResultsBetween January 2015 and August 2016, 161 patients were randomized (81 to the combination arm and 80 to the single‐agent nab‐paclitaxel arm). There was no benefit from the addition of CC‐486 to nab‐paclitaxel. The median progression‐free survival was 3.2 months for the combination and 4.2 months for single‐agent nab‐paclitaxel (hazard ratio, 1.3; 95% confidence interval, 0.9‐1.9). The median overall survival was 8.1 months in the combination arm and 17 months in the single‐agent nab‐paclitaxel arms (hazard ratio, 1.7; 95% confidence interval, 1.08‐2.57). Grade 3 or greater treatment‐related, emergent adverse events were reported by 40.5% of patients in the combination arm and by 31.6% of those in the single‐agent nab‐paclitaxel arm.ConclusionsSingle‐agent nab‐paclitaxel was associated with promising outcomes and a tolerable safety profile as second‐line treatment for patients with advanced‐stage, nonsquamous non‐small cell lung cancer. There was no benefit from the addition of CC‐486 to nab‐paclitaxel.
Estimating child mortality associated with maternal mortality from breast and cervical cancer
Authors: Mailhot Vega Raymond B. , Balogun Onyinye D. , Ishaq Omar F. , Bray Freddie , Ginsburg Ophira , Formenti Silvia C. 
Published: November 2018

BackgroundLarge‐scale population studies demonstrate an association between mothers’ deaths and child mortality in both lower and higher income countries. The authors estimated children’s deaths in association with mothers’ deaths from breast or cervical cancer, 2 common cancers in low‐income and middle‐income countries affecting women of reproductive age, to develop a comprehensive assessment of the death burden of these cancers.MethodsA Monte Carlo simulation model was devised whereby women were at risk of dying from breast cancer, cervical cancer, or another cause. Compared with children who have living mothers, children of women who die before they reached age 10 years have an elevated risk of death from all causes. Therefore, simulations were conducted, and the impact of mothers’ deaths from cervical and breast cancer on associated child mortality was quantified for Bangladesh, Burkina Faso, and Denmark (benchmark analysis), then the analyses were extended to all African countries.ResultsBenchmark estimates of child deaths associated with mothers’ deaths from breast and cervical cancer resulted in an increment in cancer‐related mortality of approximately 2% in Bangladesh, 14% in Burkina Faso, and less than 1% in Denmark. The model predicted an increment in comprehensive cancer deaths when including child death estimates by as high as 30% in certain African countries.ConclusionsTo the authors’ knowledge, this is the first study to estimate the impact of a mother’s death from cancer on child mortality. The model’s estimates call for further investigation into this correlation and underscore the relevance of adequate access to prevention and treatment among women of childbearing age.
2H and 13C NMR‐Based Enantiodetection Using Polyacetylene versus Polypeptide Aligning Media: Versatile and Complementary Tools for Chemists
Authors: Lesot Philippe , Berdagué Philippe , Meddour Abdelkrim , Kreiter Alexander , Noll Markus , Reggelin Michael 
Published: November 2018

AbstractIn this work, the practical/analytical potential of an L‐valine‐derived polyacetylene (PLA) lyotropic liquid crystal (LLC) is examined to spectrally discriminate enantiomers (racemic mixture) or enantiotopic directions of a large collection (23) of (pro)chiral model compounds (from rigid to flexible and polar to apolar ones), thus covering various important aspects of enantiomorphism. Experimental 2H‐{1H} (deuterated analytes and at natural abundance level) and 13C‐{1H} NMR results are discussed in terms of the difference of 2H‐RQCs or 13C‐RCSAs and compared to those obtained in polypeptide‐type LLCs (PBLG). The analysis of the NMR results provides an overview of the enantiodifferentiation capabilities of PLA and gives useful/practical hints for the chemist to select the most appropriate chiral oriented system. Astonishing NAD NMR results were obtained in the case of one of the simplest, chiral alkanes, 3‐methylhexane. From a theoretical viewpoint, the data collected highlight the key molecular factors involved in orientation/discrimination processes, as a basis for optimizing computational prediction (molecular dynamics simulation), as well as designing novel helically chiral polymers as new enantiodiscriminating aligning media. In addition, a new, robust and efficient protocol to synthesize PLA and its enantiomer (PDA) on a large scale and with small polydispersities is proposed.
The first complete mitochondrial genome of the Mariana Trench Freyastera benthophila (Asteroidea: Brisingida: Brisingidae) allows insights into the deep‐sea adaptive evolution of Brisingida
Authors: Mu Wendan , Liu Jun , Zhang Haibin 
Published: November 2018

AbstractStarfish (phylum Echinodermata) are ecologically important and diverse members of marine ecosystems in all of the world's oceans, from the shallow water to the hadal zone. The deep sea is recognized as an extremely harsh environment on earth. In this study, we present the mitochondrial genome sequence of Mariana Trench starfish Freyastera benthophila, and this study is the first to explore in detail the mitochondrial genome of a deep‐sea member of the order Brisingida. Similar to other starfish, it contained 13 protein‐coding genes, two ribosomal RNA genes, and 22 transfer RNA genes (duplication of two tRNAs: trnL and trnS). Twenty‐two of these genes are encoded on the positive strand, while the other 15 are encoded on the negative strand. The gene arrangement was identical to those of sequenced starfish. Phylogenetic analysis showed the deep‐sea Brisingida as a sister taxon to the traditional members of the Asteriidae. Positive selection analysis indicated that five residues (8 N and 16 I in atp8, 47 D and 196 V in nad2, 599 N in nad5) were positively selected sites with high posterior probabilities. Compared these features with shallow sea starfish, we predict that variation specifically in atp8, nad2, and nad5 may play an important role in F. benthophila's adaptation to deep‐sea environment.
Hyperbolic normal stochastic volatility model
Authors: Choi Jaehyuk , Liu Chenru , Seo Byoung Ki 
Published: November 2018

AbstractFor option pricing models and heavy‐tailed distributions, this study proposes a continuous‐time stochastic volatility model based on an arithmetic Brownian motion: a one‐parameter extension of the normal stochastic alpha‐beta‐rho (SABR) model. Using two generalized Bougerol's identities in the literature, the study shows that our model has a closed‐form Monte Carlo simulation scheme and that the transition probability for one special case follows Johnson's distribution—a popular heavy‐tailed distribution originally proposed without stochastic process. It is argued that the distribution serves as an analytically superior alternative to the normal SABR model because the two distributions are empirically similar.
Cancer diagnosis and immunotherapy in the age of CRISPR
Authors: Cook Peter J. , Ventura Andrea 
Published: November 2018

AbstractThe explosion in genome editing technologies that has occurred in the past decade has revolutionized cancer research and promises to improve cancer diagnosis and therapy. Ongoing efforts include engineering of chimeric antigen receptor‐T cells using clustered regularly interspaced short palindromic repeats (CRISPR) to generate a safer, more effective therapy with improved performance in immunologically “cold” tumors, as well as clever adaptations of CRISPR enzymes to allow fast, simple, and sensitive detection of specific nucleotide sequences. While still in their infancy, CRISPR‐based cancer therapeutics and diagnostics are developing at an impressive speed and it is likely they will soon impact clinical practice. Here, we summarize their history and the most recent developments.
Long noncoding RNA DLEU1 aggravates pancreatic ductal adenocarcinoma carcinogenesis via the miR‐381/CXCR4 axis
Authors: Gao Song , Cai Yunyun , Zhang Hu , Hu Fei , Hou Lengchen , Xu Qing 
Published: November 2018

AbstractRecent evidence has highlighted that long noncoding RNAs (lncRNA) are associated with many diseases, particularly cancer. However, current understanding of the lncRNA deleted in lymphocytic leukemia 1 (DLEU1) in pancreatic ductal adenocarcinoma (PDAC) remains limited. Our studies indicated that the DLEU1 expression level was upregulated in PDAC tissue samples compared with adjacent normal tissue. Moreover, the aberrant overexpression of DLEU1 indicated poor prognosis of patients with PDAC. Loss‐of‐function experiments revealed that DLEU1 knockdown inhibited the proliferation, migration, and invasion of PDAC cells in vitro and decreased tumor growth in vivo. Bioinformatics analysis predicted that miR‐381 potentially targeted the DLEU1 3′‐untranslated region (UTR), suggesting an interaction between miR‐381 and DLEU1. Furthermore, miR‐381 also targeted the chemokine receptor‐4 (CXCR4) messenger RNA 3′‐UTR, which was validated by luciferase reporter assay. Taken together, our study demonstrated the oncogenic role of DLEU1 in clinical PDAC specimens and cellular experiments, showing the potential involvement of DLEU1/miR‐381/CXCR4 pathway. These results provide novel insight into PDAC tumorigenesis.
OCT4&SOX2‐specific cytotoxic T lymphocytes plus programmed cell death protein 1 inhibitor presented with synergistic effect on killing lung cancer stem‐like cells in vitro and treating drug‐resistant lung cancer mice in vivo
Authors: Zhang Xueyan , Hu Fang , Li Changhui , Zheng Xiaoxuan , Zhang Bo , Wang Huimin , Tao Guangyu , Xu Jianlin , Zhang Yanwei , Han Baohui 
Published: November 2018

AbstractThis study aimed to investigate the synergistic effect of octamer‐binding transcription factor 4 and sex determining region Y‐box 2 (OCT4&SOX2)‐specific cytotoxic T lymphocytes (CTLs) and programmed cell death protein 1 (PD‐1) inhibitor on killing lung cancer stem‐like cells (LCSCs) and their efficacy in treating drug‐resistant lung cancer (DRLC) mice. OCT4&SOX2‐specific CTLs and PD‐1 inhibitor with differed doses were applied to treat PC9 cells and PC9 LCSCs. Cell counting kit‐8 (CCK8) assay and flow cytometry (FCM) assay with carboxyfluorescein diacetate/succinimidyl ester staining target cells before treatment and propidium iodide (PI) staining dead cells after treatment were conducted to detect the cytotoxic activity. DRLC mice were constructed by injection of PC9 LCSCs suspension and Matrigel into left lung of SD mice. DRLC mice were randomly divided into five groups: control group, cytomegalovirus (CMV) pp65 CTLs group, OCT4&SOX2 CTLs group, PD‐1 inhibitor group, and OCT4&SOX2 CTLs + PD‐1 inhibitor group. In vitro, both CCK8 assay and FCM assay disclosed that OCT4&SOX2‐specific CTLs plus PD‐1 inhibitor presented with elevated cytotoxic activity on PC9 cells and PC9 LCSCs. In vivo, tumor volume and tumor weight were decreased, while tumor necrosis and tumor apoptosis were increased in OCT4&SOX2 CTLs group than CMV pp65 CTLs group and control group, and in OCT4&SOX2 CTLs + PD‐1 inhibitor group than OCT4&SOX2 CTLs group and PD‐1 inhibitor group. In addition, CD8 expression was increased while OCT4&SOX2 expressions were decreased in OCT4&SOX2 CTLs + PD‐1 inhibitor group than OCT4&SOX2 CTLs group and PD‐1 inhibitor group. In conclusion, OCT4&SOX2‐specific CTLs and PD‐1 inhibitor presented with the synergistic effect on killing LCSCs in vitro and treating DRLC mice in vivo.
Gas phase reaction between chromones and solvent in an electrospray ionization source
Authors: Liu Zhen , Shao Yunlong , Zhu Guizhen , Wang Xiayan , Chai Yunfeng , Wang Lin 
Published: November 2018

AbstractChromones were measured by using electrospray ionization mass spectrometry in negative mode. Interestingly, in addition to the deprotonated ion ([M − H]−), unexpected [M + 17]− and [M + 31]− ions were observed in high intensity when water and methanol were used as the solvent. Chromones with different substitutes were tested. Compared with the deprotonated ion, [M + 17]− and [M + 31]− ions were observed with higher abundances when the C‐3 site of chromones was substituted by electron withdrawing groups. Based on high performance liquid chromatography‐mass spectrometry (LC‐MS), deuterium‐labeling and collisional‐induced dissociation experiments, a covalent gas‐phase nucleophilic addition reaction between chromone and water, and the formation of a noncovalent complex between chromone and methanol were proposed as the mechanism for the observed [M + 17]− and [M + 31]− ions, respectively. Understanding and using these unique gas phase reactions can avoid misannotation when analyzing chromones and their metabolites.
Virulence behavior of uropathogenic Escherichia coli strains in the host model Caenorhabditis elegans
Authors: Schifano Emily , Marazzato Massimiliano , Ammendolia Maria Grazia , Zanni Elena , Ricci Marta , Comanducci Antonella , Goldoni Paola , Conte Maria Pia , Uccelletti Daniela , Longhi Catia 
Published: November 2018

AbstractUrinary tract infections (UTIs) are among the most common bacterial infections in humans. Although a number of bacteria can cause UTIs, most cases are due to infection by uropathogenic Escherichia coli (UPEC). UPEC are a genetically heterogeneous group that exhibit several virulence factors associated with colonization and persistence of bacteria in the urinary tract. Caenorhabditis elegans is a tiny, free‐living nematode found worldwide. Because many biological pathways are conserved in C. elegans and humans, the nematode has been increasingly used as a model organism to study virulence mechanisms of microbial infections and innate immunity. The virulence of UPEC strains, characterized for antimicrobial resistance, pathogenicity‐related genes associated with virulence and phylogenetic group belonging was evaluated by measuring the survival of C. elegans exposed to pure cultures of these strains. Our results showed that urinary strains can kill the nematode and that the clinical isolate ECP110 was able to efficiently colonize the gut and to inhibit the host oxidative response to infection. Our data support that C. elegans, a free‐living nematode found worldwide, could serve as an in vivo model to distinguish, among uropathogenic E. coli, different virulence behavior.
Pigmented Rice‐Derived Phenolic Compounds Reduce Biomarkers of Oxidative Stress and Inflammation in Human Umbilical Vein Endothelial Cells
Authors: Callcott Esther T. , Blanchard Christopher L. , Oli Prakash , Santhakumar Abishek B. 
Published: November 2018

ScopeEndothelial dysfunction pathogenesis is significantly associated with increased oxidative stress (OS) and inflammation. Rice‐derived phenolic compounds have been demonstrated to have antioxidant and anti‐inflammatory potential. This study aims to determine if phenolic extracts (PE) from pigmented rice varieties (Purple, Yunlu29–red, and Reiziq–brown) at varying concentrations modulate biomarkers of OS and inflammation in human umbilical vein endothelial cells under induced OS conditions.Methods and results2,7‐dichlorofluorescein diacetate and superoxide dismutase‐1 (SOD‐1) enzyme‐linked immuno‐sorbent assay quantification demonstrate that Purple PE significantly decreases reactive oxygen species and increases SOD‐1 by 27% and 226%, respectively. Yunlu29 PE (50 µg mL−1) is the most effective in reducing (p < 0.0001) interleukin‐8 (61%) and interleukin‐6 (57.2%). Yunlu29 (50 µg mL−1) reduces intracellular‐adhesion molecule‐1 (p < 0.0001) expression by 34%, followed by Reiziq (31.9%) and Purple (30.2%). Flow cytometric analysis demonstrates that vascular cell‐adhesion molecule‐1 expression is reduced (p < 0.0001) by 53.5% by Yunlu29 followed by Purple (46.8%) and Reiziq (46.7%). Yunlu29 is the most effective in reducing nuclear factor kappa‐B expression by 50.1%, followed by purple (48.8%) and Reiziq (38.6%).ConclusionThis study indicates that colored rice PE may potentially target OS and inflammatory pathways associated with the pathogenesis of endothelial dysfunction.