bluuebunny/crossref_metadata_2025_split huggingface dataset:
A system‐based intervention to reduce Black‐White disparities in the treatment of early stage lung cancer: A pragmatic trial at five cancer centers
Authors: Cykert Samuel , Eng Eugenia , Walker Paul , Manning Matthew A. , Robertson Linda B. , Arya Rohan , Jones Nora S. , Heron Dwight E. 
Published: February 2019

AbstractBackgroundAdvances in early diagnosis and curative treatment have reduced high mortality rates associated with non‐small cell lung cancer. However, racial disparity in survival persists partly because Black patients receive less curative treatment than White patients.MethodsWe performed a 5‐year pragmatic, trial at five cancer centers using a system‐based intervention. Patients diagnosed with early stage lung cancer, aged 18‐85 were eligible. Intervention components included: (1) a real‐time warning system derived from electronic health records, (2) race‐specific feedback to clinical teams on treatment completion rates, and (3) a nurse navigator. Consented patients were compared to retrospective and concurrent controls. The primary outcome was receipt of curative treatment.ResultsThere were 2841 early stage lung cancer patients (16% Black) in the retrospective group and 360 (32% Black) in the intervention group. For the retrospective baseline, crude treatment rates were 78% for White patients vs 69% for Black patients (P < 0.001); difference by race was confirmed by a model adjusted for age, treatment site, cancer stage, gender, comorbid illness, and income‐odds ratio (OR) 0.66 for Black patients (95% CI 0.51‐0.85, P = 0.001). Within the intervention cohort, the crude rate was 96.5% for Black vs 95% for White patients (P = 0.56). Odds ratio for the adjusted analysis was 2.1 (95% CI 0.41‐10.4, P = 0.39) for Black vs White patients. Between group analyses confirmed treatment parity for the intervention.ConclusionA system‐based intervention tested in five cancer centers reduced racial gaps and improved care for all.
Recognition of HER2 expression in hepatocellular carcinoma and its significance in postoperative tumor recurrence
Authors: Shi Ji‐Hua , Guo Wen‐Zhi , Jin Yang , Zhang Hua-Peng , Pang Chun , Li Jie , Line Pål‐Dag , Zhang Shui‐Jun 
Published: February 2019

AbstractBackgroundThe ERBB2 oncogene hypothesis is challenged in hepatocellular carcinoma (HCC) with the conflicting evidences of human epidermal growth factor receptor 2 (HER2) overexpression. HER2 could be a new target as a treatment option for HCC as well as tumor recurrence after surgery. HER2 in HCC biology needs further explorations.MethodsClinical and mRNA data of HCC patients were obtained from TCGA HCC cohort, GSE89377 and GSE115018. Western Blotting and immunohistochemistry were employed to test expression of HER2, E‐cadherin, and Vimentin. In HepG2, JM1, HER2‐transfected McA cells, and TGF‐β cocultured JM1 cells, HCC biology, including cell survival, proliferation, and epithelial‐to‐mesenchymal transition (EMT) phenotypes were evaluated.ResultsERBB2 mRNA amplification was found in HCC datasets, and its expression was downregulated in high grade HCC with a worse overall survival. HER2 overexpression was identified in H4IIE, HepG2, JM1 cells, and 82% (14/17) HCC samples, and tumor stage was correlated with expression of HER2, E‐cadherin, and Vimentin (P < 0.05). Trastuzumab with the high concentrations suppressed proliferation of HER2‐positive hepatoma cells (P < 0.05); in the coculture model to induce EMT of JM1 cells, HER2 expression increased with downregulated E‐cadherin and upregulated Vimentin. Trastuzumab intravenous injection inhibited in vivo tumor size and metastases (P < 0.05). Signal analysis revealed that HER2 functioned through upregulation of β‐catenin and inhibition of SMAD3.ConclusionHER2 expression pattern is linked with tumor stage and overall survival; the transforming function of HER2 is found more relevant through β‐catenin and SMAD3. HER2‐targeted treatment is recommended to suppress the HER2‐mediated tumor growth during postoperative liver regeneration.
Optimal Substrate‐Trapping Mutants to Discover Substrates of HDAC1
Authors: Gomes Inosha D. , Pflum Mary Kay H. 
Published: January 2019

AbstractHistone deacetylase 1 (HDAC1) regulates transcription by deacetylating histones. In addition to histones, several non‐histone proteins are HDAC1 substrates, which suggests a role for HDAC1 beyond epigenetics. Unfortunately, the identification of non‐histone substrates has been largely serendipitous, which makes full characterization of HDAC1 functions difficult. To overcome this challenge, inactive “trapping” mutants were recently developed to identify HDAC1 substrates. To optimize substrate trapping, the relative trapping abilities of 17 inactive HDAC1 mutants was assessed. HDAC1 H141A, F150A, and C151A showed strong binding to substrates LSD1 and p53. Interestingly, each mutant preferentially trapped a different substrate. By combining several inactive mutants, the trapping strategy will facilitate the discovery of new HDAC1 substrates and shed light on the variety of HDAC1‐related functions in cell biology.
Numerical Simulation of Sterilization Processes for Shear‐Thinning Food in Taylor‐Couette Flow Systems
Authors: Masuda Hayato , Hubacz Robert , Shimoyamada Makoto , Ohmura Naoto 
Published: February 2019

AbstractThe performance of the Taylor‐Couette flow apparatus as a heat sterilizer is numerically investigated. The destruction of Clostridium botulinum and thiamine (vitamin B1) was selected as model reaction. When Taylor vortices were formed in the annular space, the heat transfer significantly enhanced as compared to the case without vortex flow. As a result, the equivalent lethality calculated from the temperature field increased, which is regarded as a quantum leap. Conversely, the improvement of heat transfer induced destruction of thiamine. These results suggest that there is a trade‐off relationship between the enhancement of heat transfer and the avoidance of thermal destruction of nutritional components. In conclusion, the Taylor‐Couette flow sterilizer has the potential for process intensification in heat sterilization processes.
Ionic Conductivity of the NASICON‐Related Thiophosphate Na1+xTi2−xGax(PS4)3
Authors: Schlem Roman , Till Paul , Weiss Manuel , Krauskopf Thorben , Culver Sean P. , Zeier Wolfgang G. 
Published: January 2019

AbstractInspired by the recent interest in fast ionic conducting solids for electrolytes, the ionic conductivity of a novel ionic conductor Na1+xTi2−xGax(PS4)3 has been investigated. Using X‐ray diffraction and impedance spectroscopy the sodium ionic conductivity in this compound was demonstrated, in which bond valence sum analysis suggests a tunnel diffusion for Na+. Substitution with Ga3+ leads to an increasing Na+ content, an expansion of the lattice and an increasing conductivity with increasing x in Na1+xTi2−xGax(PS4)3. Given the relation to the NASICON family, upon replacement of the phosphate by a thiophosphate group, a rich structural chemistry can be expected in this class of materials. This work demonstrates the potential for making NaTi2(PS4)3 an ideal system to study structure‐property relationships in ionic conductors.
Direct Conversion of Benzothiadiazole to Benzimidazole: New Benzimidazole‐Derived Metal–Organic Frameworks with Adjustable Honeycomb‐Like Cavities
Authors: Zhao Yingnan , Han Xiao , Yu Feihu , Wei Donghui , Cheng Qing , Meng Xiangru , Ding Jie , Hou Hongwei 
Published: February 2019

AbstractUp to now, the direct conversion of the thiadiazole ring to other heterocyclic rings has been a very challenging task. Herein, a CdII‐mediated alcohol‐substitution strategy for direct conversion from benzothiadiazole to benzimidazole is reported. Experimental and molecular modeling studies on the role of the chelated metal ion in this in situ alcohol‐substitution reaction revealed that it serves as an all‐rounder that is involved in the insertion of alcohol, activation of the thiadiazole ring by coordinative interaction, and the sulfur‐extrusion process. Interestingly, the insertion of alcohol occurs much earlier than the sulfur‐extrusion process, supported by a water‐mediated proton‐transfer process. This strategy also is suitable for constructing new benzimidazole‐derived MOFs [Cd2(HMBIDC2−)2]⋅4 H2O (Cd‐BID‐MOF‐1, HMBIDC2−=2‐methyl‐1H‐benzimidazole‐4,7‐dicarboxylate) and [Cd2(HPBIDC2−)2]⋅1/3 H2O (Cd‐BID‐MOF‐2, HPBIDC2−=2‐(3‐hydroxypropyl)‐2H‐benzimidazole‐4,7‐dicarboxylate). Because the terminal hydroxyl group on the imidazole ring protrudes into the circular channel in rhombohedral Cd‐BID‐MOF‐2, the cavity is closer to hydrophilic than the honeycomb‐like cavity in Cd‐BID‐MOF‐1 with similar 3D structure. This rare observation will provide a new strategy to develop in situ ligand‐reaction synthesis of functional MOFs and useful chelation‐assisted catalytic reactions in heteroaromatic chemistry.
Boosting Molecular Complexity with O2: Iron‐Catalysed Oxygenation of 1‐Arylisochromans through Dehydrogenation, Csp3−O Bond Cleavage and Hydrogenolysis
Authors: Gonzalez‐de‐Castro Angela , Robertson Craig M. , Xiao Jianliang 
Published: February 2019

AbstractOxidative cleavage of the Csp3−O bond in 1‐arylisochromans with stoichiometric oxidants, such as CrO3/H2SO4, has been practiced for decades in synthetic chemistry. Herein, we report that a structurally well‐defined FeII–pyridyl(bis‐imidazolidine) catalyst promotes the aerobic oxygenation of 1‐arylisochromans, affording highly selectively 2‐(hydroxyethyl)benzophenones, compounds of potential for neuroprotective agents. Key intermediates have been isolated, indicating that the reaction proceeds through dehydrogenative oxygenation of the isochromans at the 1‐position, Csp3−O bond cleavage at the iron centre and hydrogenolysis of the resulting Fe−O bond with the H2generated from the dehydrogenation step. In the absence of H2but under iron catalysis, the peroxide intermediate is converted into an unexpected ketal compound, which transfers into a 2‐(hydroxyethyl)benzophenone when both O2and H2are admitted. The unique ability of the iron catalyst for oxygenation and hydrogenation in the same catalytic process under mild conditions allows for the stepwise preparation of a variety of isolable oxygenated products on a preparative scale, circumventing the need for using wasteful and/or toxic oxidants.
Chemoenzymatic Cascade Synthesis of Optically Pure Alkanoic Acids by Using Engineered Arylmalonate Decarboxylase Variants
Authors: Enoki Junichi , Mügge Carolin , Tischler Dirk , Miyamoto Kenji , Kourist Robert 
Published: January 2019

AbstractArylmalonate decarboxylase (AMDase) catalyzes the cofactor‐free asymmetric decarboxylation of prochiral arylmalonic acids and produces the corresponding monoacids with rigorous R selectivity. Alteration of catalytic cysteine residues and of the hydrophobic environment in the active site by protein engineering has previously resulted in the generation of variants with opposite enantioselectivity and improved catalytic performance. The substrate spectrum of AMDase allows it to catalyze the asymmetric decarboxylation of small methylvinylmalonic acid derivatives, implying the possibility to produce short‐chain 2‐methylalkanoic acids with high optical purity after reduction of the nonactivated C=C double bond. Use of diimide as the reductant proved to be a simple strategy to avoid racemization of the stereocenter during reduction. The developed chemoenzymatic sequential cascade with use of R‐ and S‐selective AMDase variants produced optically pure short‐chain 2‐methylalkanoic acids in moderate to full conversion and gave both enantiomers in excellent enantiopurity (up to 83 % isolated yield and 98 % ee).
Rare‐Earth‐Metal Pentadienyl Half‐Sandwich and Sandwich Tetramethylaluminates–Synthesis, Structure, Reactivity, and Performance in Isoprene Polymerization
Authors: Barisic Damir , Buschmann Dennis A. , Schneider David , Maichle‐Mössmer Cäcilia , Anwander Reiner 
Published: February 2019

AbstractTargeting the synthesis of rare‐earth‐metal pentadienyl half‐sandwich tetramethylaluminate complexes, homoleptic [Ln(AlMe4)3] (Ln=Y, La, Ce, Pr, Nd, Lu) were treated with equimolar amounts of the potassium salts K(2,4‐dmp) (2,4‐dmp=2,4‐dimethylpentadienyl), K(2,4‐dipp) (2,4‐dipp=2,4‐diisopropylpentadienyl), and K(2,4‐dtbp) (2,4‐dtbp=2,4‐di‐tert‐butylpentadienyl). The reactions involving the larger rare‐earth‐metal centers lanthanum, cerium, praseodymium, and neodymium gave selectively the desired half‐sandwich complexes [(2,4‐dmp)La(AlMe4)2], [(2,4‐dipp)La(AlMe4)2], and [(2,4‐dtbp)Ln(AlMe4)2] (Ln=La, Ce, Pr, Nd) in high crystalline yields. Smaller rare‐earth‐metal centers yielded preferentially the sandwich complexes [(2,4‐dmp)2Ln(AlMe4)] (Ln=Y, Lu) and [(2,4‐dipp)2Y(AlMe4)]. Activation with fluorinated borate/borane co‐catalysts gave highly active catalyst systems for the fabrication of polyisoprene, displaying molecular weight distributions as low asMw/Mn=1.09 and a maximumcis‐1,4 selectivity of 90.4 %. The equimolar reaction of half‐sandwich complex [(2,4‐dtbp)La(AlMe4)2] with B(C6F5)3led to the isolation and full characterization of the single‐component catalyst {{(2,4‐dtbp)La[(μ‐Me)2AlMe(C6F5)]}[Me2Al(C6F5)2]}2. The reaction of the latter complex with 10 equivalents of isoprene could be monitored by1H NMR spectroscopy. Also, a donor‐induced aluminato/gallato exchange was achieved with [(2,4‐dtbp)La(AlMe4)2] and GaMe3(OEt2) leading to [(2,4‐dtbp)La(GaMe4)2].
Enantioselective Synthesis of the Platensimycin Core by Silver(I)‐Promoted Cyclization of Δ6‐α‐Iodoketone
Authors: Trajkovic Milos , Ferjancic Zorana , Saicic Radomir N. , Bihelovic Filip 
Published: February 2019

AbstractA chiral‐pool‐based synthesis of the platensimycin core was achieved using (S)‐lactic acid as an inexpensive starting material. The cyclohexenone ring was closed in a Mukaiyama–Michael domino sequence, while the quaternary stereocenter was created by a highly stereoselective decarboxylative allylation. The spirobicyclic skeleton was constructed by a RCM reaction. A new silver(I)‐promoted cyclization reaction of Δ6‐ and Δ7‐α‐iodoketones was developed and applied for the pivotal carbon–carbon bond formation. The scope and limitations of this methodology are also presented.
Design, synthesis and application of chiral tetraoxacalix[2]arene[2]triazine‐based organocatalysts in asymmetric Michael addition reactions
Authors: Genc Hayriye Nevin , Ozgun Ummu , Sirit Abdulkadir 
Published: January 2019

AbstractA novel type of oxacalix[2]arene[2]triazine‐based organocatalysts for asymmetric Michael reactions are reported for the first time. Chiral subunits were attached to the heteroatom‐bridged calixaromatic platform by a reaction of (R)‐ and (S)‐1‐aminotetraline with tetraoxacalix[2]arene[2]triazine in both enantiomeric forms. To evaluate the catalytic efficiency of the novel organocatalysts, isobutyraldehyde reacted with various substituted and unsubstituted aromatic trans‐β‐nitrostyrenes in tetrahydrofuran (THF), leading to Michael adducts in excellent yields and enantioselectivites (up to 97% yield and 99% ee).
Rigidity and Edge Universality of Discrete β‐Ensembles
Authors: Guionnet Alice , Huang Jiaoyang 
Published: February 2019

AbstractWe study discrete β‐ensembles as introduced in [17]. We obtain rigidity estimates on the particle locations; i.e., with high probability, the particles are close to their classical locations with an optimal error estimate. We prove the edge universality of the discrete β‐ensembles; i.e., for β ≥ 1, the distribution of extreme particles converges to the Tracy‐Widom β‐distribution. As far as we know, this is the first proof of general Tracy‐Widom β‐distributions in the discrete setting. A special case of our main results implies that under the Jack deformation of the Plancherel measure, the distribution of the lengths of the first few rows in Young diagrams converges to the Tracy‐Widom β‐distribution, which answers an open problem in [38]. Our proof relies on Nekrasov's (or loop) equations, a multiscale analysis, and a comparison argument with continuous β‐ensembles. © 2019 Wiley Periodicals, Inc.
pH Controlled Intersystem Crossing and Singlet Oxygen Generation of 8‐Azaadenine in Aqueous Solution
Authors: Zhou Zhongneng , Hu Zhubin , Zhang Xianwang , Jia Menghui , Wang Xueli , Su Hongmei , Sun Haitao , Chen Jinquan , Xu Jianhua 
Published: January 2019

AbstractAzabases are intriguing DNA and RNA analogues and have been used as effective antiviral and anticancer medicines. However, photosensitivity of these drugs has also been reported. Here, pH‐controlled intersystem crossing (ISC) process of 9H 8‐azaadenine (8‐AA) in aqueous solution is reported. Broadband transient absorption measurements reveal that the hydrogen atom at N9 position can greatly affect ISC of 8‐AA and ISC is more favorable when 8‐AA is in its neutral form in aqueous solution. The initial excited ππ* (S2) state evolves through ultrafast internal conversion (IC) (4.2 ps) to the lower‐lying nπ* state (S1), which further stands as a door way state for ISC with a time constant of 160 ps. The triplet state has a lifetime of 6.1 μs. On the other hand, deprotonation at N9 position promotes the IC from the ππ* (S2) state to the ground state (S0) and the lifetime of the S2 state is determined to be 10 ps. The experimental results are further supported by time‐dependent density functional theory (TDDFT) calculations. Singlet oxygen generation yield is measured to be 13.8 % for the neutral 8‐AA while the deprotonated one exhibit much lower yield (<2 %), implying that this compound could be a potential pH‐sensitized photodynamic therapy agent.
Ion Mobility Mass Spectrometric Investigation on the Photoisomerization of a 4,4’‐Diamidoazobenzene Model
Authors: Wollschläger Jan M. , Schalley Christoph A. 
Published: February 2019

AbstractThe photoisomerization of a new 4,4′‐diamidoazobenzene model is investigated with ion mobility mass spectrometry. Taking observations of previous studies and new control experiments into consideration, a mechanism for a fast thermal (Z)→(E) isomerization of azobenzenes during ionization is proposed. The experiments clearly show that a fast (Z)→(E) isomerization is operative when the azo group is protonated, while it can be prevented when another protonation site remote from the azo group is offered. Besides this, the peak integration ratio in the ion mobilogram is shown to closely correlate with the photoisomer ratio in solution. Future prospects for applications in photocatalysis and systems chemistry are discussed.
Inducing a Mucosal Barrier–Sparing Inflammatory Response in Laboratory‐Grown Primary Human Nasal Epithelial Cells
Authors: Ramezanpour Mahnaz , Bolt Harrison , Psaltis Alkis , Wormald Peter‐John , Vreugde Sarah 
Published: February 2019

AbstractHere we use the toll‐like receptor (TLR) 3 agonist poly I:C (LMW) to induce an inflammatory response in cells of submerged and/or air‐liquid interface (ALI) cultures of human nasal epithelial cells (HNECs). The inflammatory response is determined by measuring interleukin‐6 (IL‐6) protein levels by enzyme‐linked immunosorbent assay (ELISA). The mucosal barrier integrity is determined by measuring transepithelial electrical resistance (TEER) and passage of fluorescently labeled dextrans. Stimulation with poly (I:C) LMW induces a 15‐ to 17‐fold increase in IL‐6 production by HNEC‐ALI cells. © 2019 by John Wiley & Sons, Inc.
FxCycle™ Based Ploidy Correlates with Cytogenetic Ploidy in B‐Cell Acute Lymphoblastic Leukemia and Is Able to Detect the Aneuploid Minimal Residual Disease Clone
Authors: Gupta Nishit , Parihar Mayur , Banerjee Sambhunath , Brahma Subhajit , Pawar Ravikiran , Rath Asish , Shewale Sundar , Singh Manish , Sasikumaran Nair Remani Arun , Krishnan Shekhar , Bhatacharyya Arpita , Das Anirban , Kumar Jeevan , Bhave Saurabh , Radhakrishnan Vivek , Nair Reena , Chandy Mammen , Mishra Deepak , Arora Neeraj 
Published: February 2019

BackgroundFlow cytometry (FCM) is a simple, sensitive, and specific technique that can potentially determine DNA ploidy in B‐cell precursor ALL (BCP‐ALL) and is complementary to cytogenetics.MethodsA prospective FCM DNA ploidy analysis using FxCycle™ Violet (assay sensitivity 0.01%) was done in 125 consecutive new cases of BCP‐ALL (90 cases <15 years of age) and compared with corresponding cytogenetic ploidy (karyotyping and/or FISH) data wherever available. This assay was also subsequently evaluated for detection of residual aneuploid clone in few BCP‐ALL cases.ResultsOf the total 125 BCP‐ALL cases evaluated, flow ploidy analysis revealed diploidy (DI 0.96–1.05) in 44.8% (n= 56), low‐hyperdiploidy (DI 1.06 to 1.15) in 13.6% (n= 17), high‐hyperdiploidy (DI 1.16–1.39) in 32.8% (n= 41) and near‐tetraploidy (DI ≥ 1.80) in 2.4% (n= 3) cases. The high risk sub‐group of low‐hypodiploidy (DI 0.70 to 0.88)/near‐triploidy (DI 1.40 to 1.79) constituted 5.6% (n= 7) cases while there was only one case with haploidy (DI 0.58). Overall, high concordance of 90.4% (n= 113) was noted between the combined cytogenetics ploidy and FCM ploidy. Of the total discordant cases (n= 12), the maximum discordance was seen in the low‐hyperdiploid DI subgroup (n= 10), which included seven cases with low DNA index high hyperdiploidy (LDI‐HHD). FCM DNA ploidy assay was able to detect the residual clone in all six MRD positive aneuploid cases evaluated.ConclusionsFxCycle™ based DNA ploidy ascertains strong correlation with cytogenetic profiles and yields complementary information that can be used by the cytogenetics laboratories or otherwise. © 2019 International Clinical Cytometry Society
Obesity and its cardiovascular effects
Authors: Ortega‐Loubon Christian , Fernández‐Molina Manuel , Singh Gauri , Correa Ricardo 
Published: February 2019

SummaryObesity is described in terms of body fat percentage or body mass index (BMI), despite the fact that these measures do not give full insight about the body fat distribution. It is presently a consistently growing universal challenge since it has tripled in the last 10 years, killing approximately 28 million people each year. In this review, we aim to clarify the different results of obesity on the working and physiology of the cardiovascular system and to reveal changes in the obesity “paradox”—a variety of cardiovascular outcomes in typical/overweight people. Central fat build‐up in ordinary/overweight populaces has been related to expanded occurrences of myocardial infarction, heart failure, or all‐cause mortality when contrasted with the obese populace. These discoveries are additionally clarified as the abundance and prolonged vulnerability to free fatty acids (FFAs) in obesity. This has been believed to cause the myocardial substrate to move from glucose to FFAs digestion, which causes lipid gathering in cardiomyocytes, spilling over to other lean tissues, and prompting a general atherogenic impact. This cardiomyocyte lipid aggregation has been demonstrated to cause insulin resistance and cardiovascular hypertrophy, and to lessen the heart functions in general. There is a proof backing the fact that fat tissue is not only an energy reservoir, it also coordinates hormones and proinflammatory cytokines and deals with the energy transition of the body by putting away abundant lipids in diverse tissues.