bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic risk of dementia mitigated by cognitive reserve: A cohort study
Authors: Dekhtyar Serhiy , Marseglia Anna , Xu Weili , Darin‐Mattsson Alexander , Wang Hui‐Xin , Fratiglioni Laura 
Published: May 2019

ObjectiveWe investigated whether cognitive reserve modifies the risk of dementia attributable to apolipoprotein ε4 (APOE‐ε4), a well‐known genetic risk factor for dementia.MethodsWe followed 2,556 cognitively intact participants aged ≥60 years from the ongoing prospective community‐based Swedish National Study on Aging and Care in Kungsholmen (SNAC‐K). Dementia was ascertained through clinical and neuropsychological assessments and diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. Structural equation modeling was used to generate a cognitive reserve indicator from 4 previously validated contributors: early life education, midlife substantive work complexity, late life leisure activities, and late life social networks. Cox proportional hazard models estimated dementia risk in relation to cognitive reserve indicator. The interaction between the cognitive reserve indicator and APOE‐ε4 was assessed on multiplicative and additive scales.ResultsAfter an average of 6.3 years (range = 2.1–10.7) of follow‐up, 232 dementia cases were ascertained. Relative to individuals in the lowest tertile of cognitive reserve indicator, those with moderate and high reserve were at a reduced risk of dementia. There was no multiplicative interaction between APOE‐ε4 status and cognitive reserve indicator (p = 0.113). Additive interaction was statistically significant. Relative to APOE‐ε4 carriers with low cognitive reserve, ε4 carriers with high reserve had a reduced risk of dementia (hazard ratio [HR] = 0.28, 95% confidence interval [CI] = 0.13–0.59). The magnitude of risk reduction was similar in ε4 noncarriers with a high cognitive reserve indicator (HR = 0.24, 95% CI = 0.15–0.40).InterpretationLifelong engagement in reserve‐enhancing activities attenuates the risk of dementia attributable to APOE‐ε4. Promoting cognitive reserve might be especially effective in subpopulations with high genetic risk of dementia. ANN NEUROL 2019
Atomic‐Scale Observation of the Metal–Promoter Interaction in Rh‐Based Syngas‐Upgrading Catalysts
Authors: Huang Xing , Teschner Detre , Dimitrakopoulou Maria , Fedorov Alexey , Frank Benjamin , Kraehnert Ralph , Rosowski Frank , Kaiser Harry , Schunk Stephan , Kuretschka Christiane , Schlögl Robert , Willinger Marc‐Georg , Trunschke Annette 
Published: May 2019

AbstractThe direct conversion of syngas to ethanol, typically using promoted Rh catalysts, is a cornerstone reaction in CO2 utilization and hydrogen storage technologies. A rational catalyst development requires a detailed structural understanding of the activated catalyst and the role of promoters in driving chemoselectivity. Herein, we report a comprehensive atomic‐scale study of metal–promoter interactions in silica‐supported Rh, Rh–Mn, and Rh–Mn–Fe catalysts by aberration‐corrected (AC) TEM. While the catalytic reaction leads to the formation of a Rh carbide phase in the Rh–Mn/SiO2 catalyst, the addition of Fe results in the formation of bimetallic Rh–Fe alloys, which further improves the selectivity and prevents the carbide formation. In all promoted catalysts, Mn is present as an oxide decorating the metal particles. Based on the atomic insight obtained, structural and electronic modifications induced by promoters are revealed and a basis for refined theoretical models is provided.
Synthesis of a Strained Spherical Carbon Nanocage by Regioselective Alkyne Cyclotrimerization
Authors: Hayase Norihiko , Nogami Juntaro , Shibata Yu , Tanaka Ken 
Published: May 2019

AbstractThe smallest spherical carbon nanocage so far, [2.2.2]carbon nanocage, has been synthesized by the cationic rhodium(I)/H8‐binap complex‐catalyzed regioselective intermolecular cyclotrimerization of a cis‐1‐ethynyl‐4‐arylcyclohexadiene derivative followed by the triple Suzuki–Miyaura cross‐couplings with 1,3,5‐triborylbenzene and reductive aromatization. This cage molecule is highly strained, and its ring strain is between those of [6] and [5]cycloparaphenylenes. A significant red‐shift of an emission maximum was observed, compared with that of known [4.4.4]carbon nanocage. The sequential cyclotrimerizations of a cis‐1,4‐diethynylcyclohexadiene derivative with the same rhodium(I) catalyst followed by reductive aromatization failed to afford [1.1.1]carbon nanocage; instead, a β‐graph‐shaped cage molecule was generated.
Targeting HIV‐TB coinfection by developing novel piperidin‐4‐substituted imines: Design, synthesis, in vitro and in silico studies
Authors: Kumar Avinash , Revathi Rajappan , Sriram Dharmarajan , Curreli Francesca , Debnath Asim K. , Pai K. Sreedhara , Kini Suvarna G. 
Published: May 2019

AbstractTuberculosis is the “Achilles heel” of the human immunodeficiency (HIV) ministration. HIV‐positive people are 16–27 times more prone to contract tuberculosis. But the adverse interaction between antiretroviral drugs and antitubercular drugs has made it necessary to look for a single drug regimen for HIV‐TB coinfection. Piperidine derivatives have been reported as anti‐HIV and anti‐TB agents. This inspired us to design, synthesize, and characterize a series of 3,5‐bis(furan‐2‐ylmethylidene)‐piperidin‐4‐substituted imines (R1‐R25) and these were further screened for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv and anti‐HIV activity. Molecular docking studies showed energetically favorable binding interactions with both EACP reductase (1ZID.pdb) and reverse‐transcriptase (1REV.pdb) targets. The compounds R7, R12, R17, R18, R19, R20 were found to be more potent as anti‐TB agents than ethambutol (MIC 3.125 μg/ml). Compound R7 was found to be moderately active with an IC50 of 2.1 ± 0.04 μM in multicycle infection assays, in comparison with the standard drug, zidovudine (IC50 = 5.7 ± 0.04 nM), used as anti‐HIV drug. The cytotoxicity assay was done on Vero, MT‐2, and TZM‐bl cells to assess the safety of these compounds and they were found to be safe. From the above results, R7 seems to be a promising lead for anti‐HIV and anti‐TB activity.
Synthesis, characterization, and in vitro effect of the Cu(II) complex with niflumic acid and 3‐picoline on paraoxanase‐I
Authors: Dilek Esra , Caglar Sema , Çardak Seda , Karakoç Barış , Caglar Bülent , Sahin Onur 
Published: May 2019

AbstractNiflumic acid is used to treat inflammatory rheumatoid diseases, pain, and fever. The present study reports the experimental, spectroscopic, thermal, structural analyses, and biological activities of this complex. The nonsteroidal anti‐inflammatory drug niflumic acid, 3‐picoline, and copper(II) chloride were utilized to synthesize a new complex: [Cu2Cl
2(nif)
2(3‐pic)
4]. The crystal structure of [Cu
2Cl
2(nif)
2(3‐pic)
4] was determined by X‐ray crystallography. The complex crystallizes in the triclinic space group P‐1 and each Cu(II) center displayed six‐coordinated distorted octahedral geometry. Two Cu(II) centers are connected by a chloro‐bridge to form the binuclear metal core. Finally, the in vitro effects of the synthesized new complex and free niflumic acid were evaluated on the human serum paraoxonase 1 enzyme. At low doses, both the new complex and free niflumic acid showed very good inhibition activity with different inhibition mechanisms. In addition, the results showed that the new complex has more inhibition activity than free niflumic acid.
Multi‐omics profiling of CHO parental hosts reveals cell line‐specific variations in bioprocessing traits
Authors: Lakshmanan Meiyappan , Kok Yee Jiun , Lee Alison P. , Kyriakopoulos Sarantos , Lim Hsueh Lee , Teo Gavin , Poh Swan Li , Tang Wen Qin , Hong Jongkwang , Tan Andy Hee‐Meng , Bi Xuezhi , Ho Ying Swan , Zhang Peiqing , Ng Say Kong , Lee Dong‐Yup 
Published: May 2019

AbstractChinese hamster ovary (CHO) cells are the most prevalent mammalian cell factories for producing recombinant therapeutic proteins due to their ability to synthesize human‐like post‐translational modifications and ease of maintenance in suspension cultures. Currently, a wide variety of CHO host cell lines has been developed; substantial differences exist in their phenotypes even when transfected with the same target vector. However, relatively less is known about the influence of their inherited genetic heterogeneity on phenotypic traits and production potential from the bioprocessing point of view. Herein, we present a global transcriptome and proteome profiling of three commonly used parental cell lines (CHO‐K1, CHO‐DXB11, and CHO‐DG44) in suspension cultures and further report their growth‐related characteristics, and N‐ and O‐glycosylation patterns of host cell proteins (HCPs). The comparative multi‐omics and subsequent genome‐scale metabolic network model‐based enrichment analyses indicated that some physiological variations of CHO cells grown in the same media are possibly originated from the genetic deficits, particularly in the cell‐cycle progression. Moreover, the dihydrofolate reductase deficient DG44 and DXB11 possess relatively less active metabolism when compared to K1 cells. The protein processing abilities and the N‐ and O‐glycosylation profiles also differ significantly across the host cell lines, suggesting the need to select host cells in a rational manner for the cell line development on the basis of recombinant protein being produced.
How to choose proper local treatment in men aged ≥75 years with cT2 localized prostate cancer?
Authors: Jin Kun , Qiu Shi , Li Jiakun , Zheng Xiaonan , Tu Xiang , Liao Xinyang , Yang Yan , Yang Lu , Wei Qiang 
Published: May 2019

AbstractBackgroundFor localized prostate cancer (PCa), radical prostatectomy (RP) and radiotherapy (RT) are two standard interventions to decrease PCa mortality. Contemporary studies contained the elderly people; analyses focusing on patients over 75 years of age were still lacking.MethodIn the Surveillance Epidemiology and End Results (SEER) database (2004‐2015), people over 75 years of age with cT2 stage were selected in our research. Multivariable Cox proportional hazard models were used to analyze cancer‐specific mortality (CSM) and overall mortality (OM) after adjustment. The propensity score matching was performed to assume the randomization. An instrument variate (IVA) was used to calculate the unmeasured confounders.ResultsRadical prostatectomy is superior to RT in OM and CSM after adjustment for covariates (HR = 0.54, 95% CI = 0.47‐0.62, P < 0.001 and HR = 0.30, 95% CI = 0.20‐0.45, P < 0.001, respectively). The cox model after matching indicated similar consequence (OM: HR = 0.53, 95% CI = 0.46‐0.62, P < 0.001; CSM: HR = 0.27, 95% CI = 0.17‐0.43, P < 0.001). In the IVA‐adjusted model, the effect of treatment changed slightly (OM: HR = 0.65, 95% CI = 0.54‐0.78, P < 0.001; CSM: HR = 0.21, 95% CI = 0.12‐0.37, P < 0.001). Subgroup analyses showed that for patients with GS = 7, those received RP obtained the highest risk decline for overall death (HR = 0.41, 95% CI = 0.32‐0.52); and for patients with younger age, those received RP obtained the highest risk decline for CSM (HR = 0.11, 95% CI = 0.01‐0.52).ConclusionPatients over 75 years of age with cT2 stage will obtain more benefit from RP compared with RT, especially for patients with GS = 7 and younger age.
Single‐step Conversion of Methyl Ethyl Ketone to Olefins over ZnxZryOz Catalysts in Water
Authors: Dagle Vanessa L. , Dagle Robert A. , Kovarik Libor , Baddour Frederick , Habas Susan E. , Elander Richard 
Published: May 2019

AbstractIn this study we investigated the conversion of aqueous methyl‐ethyl‐ketone (MEK) to olefin fuel precursors over ZnxZryOz mixed oxide catalysts. Experiments were carried out in water as MEK is intended to be produced from the dehydration of 2,3‐butanediol in fermentation broth which is highly diluted in water. We demonstrated that ZnxZryOz catalysts are highly effective for converting aqueous MEK to C4−C5 olefins. High selectivity to olefins equal to 85 % was reached at 92 % per pass conversion when under H2 atmosphere. Catalyst stability was demonstrated for 60 hours’ time on stream, highlighting the potential for upgrading 2,3‐butanediol contained in fermentation broth without the need for energy‐intensive water separation. Increased concentration of MEK in the aqueous feed results in increased activity towards olefin production. However, water inhibits catalyst deactivation from coking. A mechanistic investigation revealed the impact of the reaction environment (inert or reducing atmosphere) on the reaction pathways. In an inert environment, the mechanism involves consecutive aldol condensation of MEK and 3‐pentanone intermediate. Under reducing conditions two reaction pathways compete with each other as MEK hydrogenation to butenes occurs concurrently with the aldol condensation/decomposition.
First Bis(σ)‐borane Complexes of Group 6 Transition Metals: Experimental and Theoretical Studies
Authors: Lenczyk Carsten , Roy Dipak Kumar , Ghosh Bijoy , Schwarzmann Johannes , Phukan Ashwini K. , Braunschweig Holger 
Published: May 2019

AbstractA series of bis(σ)‐borane complexes of Group 6 transition metals were prepared by direct dihydroborane coordination to the metal center. Reaction of [M(CO)3(PCy3)2] and two dihydroboranes [DurBH2] and [(Me3Si)2NBH2] (Dur=2,3,5,6‐Me4C6H) yielded bis(σ)‐borane complexes fac‐[M(CO)3(PCy3){η2‐(H2BR)}] (R=Dur; 1: M=Cr, 2: M=W; R=N(SiMe3)2; 3: M=Cr, 4: M=W). In the case of molybdenum, we have isolated an arene complex (5) with [DurBH2] in which the Dur group acts as a η6‐bound ligand, and with [(Me3Si)2NBH2] a similar bis(σ)‐borane complex was isolated, cis,trans‐[Mo(CO)2(PCy3)2{η2‐(H2BN(SiMe3)2}] (6), with a different pattern of auxiliary ligands. The complexes were investigated by multinuclear NMR spectroscopy, mass spectrometry, X‐ray diffraction analysis, and computational methods. Quantum theory of atoms in molecules (QTAIM) calculations demonstrated that the borane complexes may be described as pure bis(σ)‐borane complexes rather than elongated or stretched examples given that the calculations do not show the presence of a ring‐critical point (RCP) at the ring formed by the interactions of the B−H with metal center.
Visible‐Light‐Promoted Ring‐Opening Alkynylation, Alkenylation, and Allylation of Cyclic Hemiacetals through β‐Scission of Alkoxy Radicals
Authors: Shi Jiang‐Ling , Wang Zixuan , Zhang Rui , Wang Yuankai , Wang Jianbo 
Published: May 2019

AbstractThe alkoxy radicals that are derived from cyclic hemiacetals have been generated through the visible‐light‐promoted reaction of the corresponding N‐alkoxyphthalimides with Hantzsch ester as the reductant. The alkoxy radicals subsequently undergo β‐scission of the C−C bond to generate carbon‐centered radicals, which are trapped by alkynyl‐, alkenyl‐, or allylsulfones.
Synthesis of Air‐stable, Odorless Thiophenol Surrogates via Ni‐Catalyzed C−S Cross‐Coupling
Authors: Magné Valentin , Ball Liam T. 
Published: May 2019

AbstractThiophenols are versatile synthetic intermediates whose practical appeal is marred by their air sensitivity, toxicity and extreme malodor. Herein we report an efficient catalytic method for the preparation of S‐aryl isothiouronium salts, and demonstrate that these air‐stable, odorless solids serve as user‐friendly sources of thiophenols in synthesis. Diverse isothiouronium salts featuring synthetically useful functionality are readily accessible by nickel‐catalyzed C−S cross‐coupling of (hetero)aryl iodides and thiourea. Convenient, chromatography‐free isolation of these salts is achieved by precipitation, allowing the methodology to be applied directly to large scales. Thiophenols are liberated from the corresponding isothiouronium salts upon treatment with a weak base, enabling an in situ release/S‐functionalization strategy that entirely negates the need to isolate, purify or manipulate these noxious reagents.
Catalytic Hydrogenation of Acetic Acid to Acetaldehyde: Synergistic Effect of Bifunctional Co/Ce‐Fe Oxide Solid Solution Catalysts
Authors: Li Naixu , Zhang Qi , Bibi Rehana , Shen Quanhao , Ngulube Richard , Liu Yunyi , Zhou Jiancheng 
Published: May 2019

Summary of main observation and conclusionThe large‐scale industrial production of acetic acid (HAc) from carbonylation of methanol has enabled intense research interest from direct hydrogenation of HAc to acetaldehyde (AA). Herein, a series of cerium‐iron oxide solid solution supported metallic cobalt catalysts were prepared by modified sol‐gel method and were applied in gas‐phase hydrogenation of HAc to AA. A synergistic effect between the hydrogenation metal cobalt and Ce‐Fe oxide solid solution is revealed. Specifically, oxygen vacancies provide the active sites for adsorption of HAc, while highly uniformly dispersed metallic Co adsorbs H2 and activates the reduction of HAc into AA. Moreover, the metallic Co can also assist the cyclical conversion between Fe3+/Fe2+ and Ce3+/Ce4+ on the surface of Ce1‐xFexO2‐δ supports. The unique effect substantially enhances the ability of the support material to rapidly capture oxygen atoms from HAc. It is found that the catalyst of 5% Co/Ce0.8Fe0.2O2‐δ with the highest concentration of oxygen vacancy presents the best catalytic performance (i.e. acetaldehyde yield reaches 49.9%) under the optimal reaction conditions (i.e. 623 K and H2 flow rate = 10 mL/min). This work indicates that the Co/Ce‐Fe oxide solid solution catalyst can be potentially used for the selective hydrogenation from HAc to AA. The synergy between the metallic Co and Ce1‐xFexO2‐δ revealed can be extended to the design of other composite catalysts.
Structural States of Hdm2 and HdmX: X‐ray Elucidation of Adaptations and Binding Interactions for Different Chemical Compound Classes
Authors: Kallen Joerg , Izaac Aude , Chau Suzanne , Wirth Emmanuelle , Schoepfer Joseph , Mah Robert , Schlapbach Achim , Stutz Stefan , Vaupel Andrea , Guagnano Vito , Masuya Keiichi , Stachyra Therese‐Marie , Salem Bahaa , Chene Patrick , Gessier Francois , Holzer Philipp , Furet Pascal 
Published: May 2019

AbstractHdm2 (human MDM2, human double minute 2 homologue) counteracts p53 function by direct binding to p53 and by ubiquitin‐dependent p53 protein degradation. Activation of p53 by inhibitors of the p53–Hdm2 interaction is being pursued as a therapeutic strategy in p53 wild‐type cancers. In addition, HdmX (human MDMX, human MDM4) was also identified as an important therapeutic target to efficiently reactivate p53, and it is likely that dual inhibition of Hdm2 and HdmX is beneficial. Herein we report four new X‐ray structures for Hdm2 and five new X‐ray structures for HdmX complexes, involving different classes of synthetic compounds (including the worldwide highest resolutions for Hdm2 and HdmX, at 1.13 and 1.20 Å, respectively). We also reveal the key additive 18‐crown‐ether, which we discovered to enable HdmX crystallization and show its stabilization of various Lys residues. In addition, we report the previously unpublished details of X‐ray structure determinations for eight further Hdm2 complexes, including the clinical trial compounds NVP‐CGM097 and NVP‐HDM201. An analysis of all compound binding modes reveals new and deepened insight into the possible adaptations and structural states of Hdm2 (e.g., flip of F55, flip of Y67, reorientation of H96) and HdmX (e.g., flip of H55, dimer induction), enabling key binding interactions for different compound classes. To facilitate comparisons, we used the same numbering for Hdm2 (as in Q00987) and HdmX (as in O15151, but minus 1). Taken together, these structural insights should prove useful for the design and optimization of further selective and/or dual Hdm2/HdmX inhibitors.
An updated analysis of 4 randomized ECOG trials of high‐dose interferon in the adjuvant treatment of melanoma
Authors: Najjar Yana G. , Puligandla Maneka , Lee Sandra J. , Kirkwood John M. 
Published: May 2019

BackgroundThe pivotal E1684, E1690, E1694, and E2696 trials of adjuvant high‐dose interferon‐α (HDI) enrolled nearly 2000 patients, and established HDI as the standard of care in adjuvant therapy for patients with resected high‐risk melanoma. Herein, the authors present an updated analysis of these 4 trials.MethodsSurvival and disease status were updated in September 2016. These data represent a median follow‐up of 17.9 years for the E1684 trial, 12.2 years for the E1690 trial, 16.0 years for the E1694 trial, and 16.5 years for the E2696 trial.ResultsThe current analysis confirmed the benefit to recurrence‐free survival (RFS) of HDI in the E1684 trial at a median follow‐up of 17.9 years. The RFS benefit in the E1694 trial remained evident at a median follow‐up of 16 years. Furthermore, the results of the current study confirmed the RFS benefit of adjuvant HDI compared with observation in a pooled analysis of the E1684 and E1690 trials. No overall survival benefit was apparent in this pooled analysis. Updated results for the E1690 and E2696 trials did not differ from those previously reported. In addition, to the authors’ knowledge, the current study is the first to report a significant difference in melanoma‐specific survival (MSS) between patients treated with HDI compared with the ganglioside GM2/keyhole limpet hemocyanin (GMK) vaccine in the E1694 trial.ConclusionsIn patients with resected high‐risk melanoma, adjuvant HDI demonstrated improved RFS in the E1684 and E1694 trials, and improved MSS in a pooled analysis of HDI in the E1694 trial. To the authors’ knowledge, these findings represent the most mature level of evidence for the benefit of HDI with respect to RFS and MSS. HDI is the only approved adjuvant treatment for which there are data available in patients with resected stage IIB/IIC melanoma, and remains a reasonable treatment option in this population.
Dependence of the Properties of 2D Nanocomposites Generated by Covalent Crosslinking of Nanosheets on the Interlayer Separation: A Combined Experimental and Theoretical Study
Authors: Singh Reetendra , Gupta Uttam , Kumar V. Sampath , Ayyub Mohd Monis , Waghmare Umesh V. , Rao C. N. R. 
Published: May 2019

AbstractCovalently cross‐linked heterostructures of 2D materials are a new class of materials which possess electrochemical and photochemical hydrogen evolution properties. It was of considerable interest to investigate the role of interlayer spacing in the nanocomposites involving MoS2 and graphene sheets and its control over electronic structures and catalytic properties. We have investigated this problem with emphasis on the hydrogen evolution properties of these structures by a combined experimental and theoretical study. We have linked MoS2 based nanocomposites with other 2D materials with varying interlayer spacing by changing the linker and studied their hydrogen evolution properties. The hydrogen evolution activity for these composites decreases with increasing linker length, which we can link to a decrease in magnitude of charge transfer across the layers with increasing interlayer spacing. Factors such as the nature of the sheets, interlayer distance as well as the nature of the linker provide pathways to tune the properties of covalently cross‐linked 2D material rendering this new class of materials highly interesting.