bluuebunny/crossref_metadata_2025_split huggingface dataset:
Denosumab Versus Risedronate in Glucocorticoid‐Induced Osteoporosis: Final Results of a Twenty‐Four–Month Randomized, Double‐Blind, Double‐Dummy Trial
Authors: Saag Kenneth G. , Pannacciulli Nicola , Geusens Piet , Adachi Jonathan D. , Messina Osvaldo D. , Morales‐Torres Jorge , Emkey Ronald , Butler Peter W. , Yin Xiang , Lems Willem F. 
Published: February 2019

ObjectiveClinical trial results have shown that, in glucocorticoid‐treated patients, treatment with denosumab 60 mg subcutaneously once every 6 months (Q6M) increased spine and hip bone mineral density (BMD) at month 12 significantly more than treatment with risedronate 5 mg orally once daily (QD). The present analysis was performed to compare efficacy and characterize safety through month 24.MethodsThis phase III study enrolled men and women ≥18 years old who had received ≥7.5 mg daily prednisone or equivalent for <3 months (glucocorticoid‐initiating) or for ≥3 months (glucocorticoid‐continuing) before screening. All patients <50 years old had a history of osteoporotic fracture. Glucocorticoid‐continuing patients ≥50 years old had T scores of −2.0 or less (or −1.0 or less with fracture history). Patients were randomized (1:1) to receive denosumab 60 mg subcutaneously Q6M or risedronate 5 mg orally QD for 24 months, with daily calcium and vitamin D.ResultsOf 795 patients, 590 (74.2%) completed the study (in the glucocorticoid‐initiating group, 109 of 145 patients treated with denosumab and 117 of 145 patients treated with risedronate; in the glucocorticoid‐continuing group, 186 of 253 patients treated with denosumab and 178 of 252 patients treated with risedronate). Denosumab was superior to risedronate in increasing lumbar spine and total hip BMD at all time points assessed, among glucocorticoid‐initiating patients (24‐month lumbar spine: BMD increase of 6.2% versus 1.7%, respectively [P < 0.001]; 24‐month total hip: BMD increase of 3.1% versus 0.0% [P < 0.001]) and among glucocorticoid‐continuing patients (24‐month lumbar spine: BMD increase of 6.4% versus 3.2% [P < 0.001]; 24‐month total hip: BMD increase of 2.9% versus 0.5% [P < 0.001]). Adverse events, serious adverse events (including infections), and fractures were similar between treatment groups.ConclusionDenosumab was superior to risedronate in terms of increases in spine and hip BMD through month 24, and the safety profile was similar between treatment groups. Denosumab may offer a new osteoporosis treatment option for glucocorticoid‐treated patients.
Novel CaO/polylactic acid nanoscaffold as dental resin nanocomposites and the investigation of physicochemical properties
Authors: Ranjbar Mehdi , Pardakhty Abbas , Tahmipour Batool , Mohamadzadeh Iman 
Published: February 2019

AbstractIn this study, for the first time, calcium oxide (CaO)/polylactic acid nanoscaffolds were synthesized by co‐precipitation assistant reverse micelles method. The physical and chemical (physicochemical) properties of the structures as dental resin composites were also studied. Nanocomposite materials as primary and basic dental compounds can be conveniently applied as dental filling materials with a high esthetic quality. In this research nanoscaffolds act as a bed for nanoparticles and improve the mechanical and chemical (mechanochemical) properties, CaO nanoparticles were loading in polylactic acid nanoscaffold as a bioactivity polymer for usage in the dental resin composites. Mechanical properties of the dental resin composite containing CaO/polylactic acid nanoscaffold were calculated: the flexural strength (137.2 MPa), modulus (12.9GPa) and compressive strength (344.2 MPa). Potential of the basic nanoparticle and the products were characterized by X‐ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), dynamic light scattering (DLS), ultraviolet‐visible spectroscopy (UV‐visible) and atomic force microscopy (AFM) showed the size of the optimized nanostructures was about 85 to 120 nm. According to TGA results of polylactic acid nanofibers with thermal stability below 300°C these high thermal stability materials can be used as dental resin composites.
Prospective cohort study of ultrasound surveillance of regional lymph nodes in patients with intermediate-risk cutaneous melanoma
Authors: Hayes A J , Moskovic E , O'Meara K , Smith H G , Pope R J E , Larkin J , Thomas J M 
Published: February 2019

Abstract

Background
For patients with intermediate-thickness melanoma, surveillance of regional lymph node basins by clinical examination alone has been reported to result in a larger number of lymph nodes involved by melanoma than if patients had initial sentinel node biopsy and completion dissection. This may result in worse regional control. A prospective study of both regular clinical examination and ultrasound surveillance was conducted to assess the effectiveness of these modalities.

Methods
Between 2010 and 2014, patients with melanoma of thickness 1·2–3·5 mm who had under-gone wide local excision but not sentinel node biopsy were recruited to a prospective observational study of regular clinical and ultrasound nodal surveillance. The primary endpoint was nodal burden within a dissected regional lymph node basin. Secondary endpoints included locoregional or distant relapse, progression-free and overall survival.

Results
Ninety patients were included in the study. After a median follow-up of 52 months, ten patients had developed nodal relapse as first recurrence, four had locoregional disease outside of an anatomical nodal basin as the first site of relapse and six had relapse with distant disease. None of the patients who developed relapse within a nodal basin presented with unresectable nodal disease. The median number of involved lymph nodes in patients undergoing lymphadenectomy for nodal relapse was 1 (range 1–2; mean 1·2).

Conclusion
This study suggests that ultrasound surveillance of regional lymph node basins is safe for patients with melanoma who undergo a policy of nodal surveillance.
Exploring the association between Cerebral small‐vessel diseases and motor symptoms in Parkinson's disease
Authors: Wan Ying , Hu Wenjian , Gan Jing , Song Lu , Wu Na , Chen Yuzhen , Liu Zhenguo 
Published: February 2019

AbstractObjectivesto explore the association between cerebral small‐vessel diseases (CSVDs) and motor symptoms in Parkinson's disease (PD).Methods137 PD patients were recruited into the study. Detailed motor symptoms, including tremor, rigidity, bradykinesia, and axial impairment, were evaluated using Unified Parkinson's disease Rating Scale (UPDRS). Non‐motor symptoms, including cognition, anxiety, and depression, were evaluated using Montreal Cognitive Assessment (MoCA), Hamilton anxiety scale (HAMA), and Hamilton depression scale (HAMD). Brain MRI was used to assess the subtypes of CSVDs, including lacunes, enlarged perivascular spaces (EPVS), and white matter hyperintensities (WMH). WMH were furtherly divided into deep WMH (DWMH) and periventricular hyperintensities (PVH). The association between CSVDs and motor symptoms was analyzed. Patients were divided into the postural instability and gait disability (PIGD) group and non‐PIGD group. Demographic, clinical and CSVDs variables were compared between the two groups.ResultsCSVDs subtypes were all detected in the participants with different prevalence rates and severity degrees. We found a close association between EPVS in basal ganglia and the tremor score (p = 0.032), and between DWMH in the frontal and occipital lobes and the axial motor score (p < 0.05) through the spearman and multivariate liner regression analysis. Compared with the non‐PIGD group, the PIGD group demonstrated more serious cognitive impairment and DWMH in the frontal and occipital lobes (p < 0.05). The demographic characteristics and vascular risk factors of the PIGD group were not different from those of the non‐PIGD group. Cognitive impairment and DWMH in the frontal lobe were identified to be independent risk factors of PIGD motor phenotype.ConclusionsWe identified a close association between the CSVDs and motor symptoms in PD and DWMH in the frontal lobe was a risk factor of PIGD motor phenotype, which supports the contribution of vascular pathology in PD.
Heterologous expression of Neurospora crassa cbh1 gene in Pichia pastoris resulted in production of a neutral cellobiohydrolase I
Authors: Yang Jie , Deng Lu , Zhao Chen , Fang Hao 
Published: February 2019

AbstractThe high production cost of cellulase is one of the limitations that hinder the commercialization of lignocellulose‐based biorefineries. As one of the important cellulases, Neurospora crassa cellulase is not so intensively investigated as T. reesei cellulase. In this study, the cbh1gene (NCU07340) cloned from N. crassa was expressed in Pichia pastoris under the control of alcohol oxidase 1 (AOX1) promotor. Six transformants with the highest resistance to G418 were selected by two rounds of transformant screening, among which the most robust producer of the recombinant cellobiohydrolase I (CBHI) has an Avicelase activity of 0.22 U/mL. After fermentation optimization, it was improved to 0.30 U/mL. Interestingly, the optimal temperature and pH of the recombinant CBHI were 60°C and 7.2, respectively, and it was quite stable within the wide ranges of temperature and pH. This work is a good example for the future improvement and optimization of N. crassa cellulase.
The effect of acetate on population heterogeneity in different cellular characteristics of Escherichia coli in aerobic batch cultures
Authors: Heins Anna‐Lena , Lundin Luisa , Nunes Inês , Gernaey Krist V. , Sørensen Søren J. , Lantz Anna Eliasson 
Published: February 2019

AbstractAcetate as the major by‐product in industrial‐scale bioprocesses with Escherichia coli is found to decrease process efficiency as well as to be toxic to cells, which has several effects like a significant induction of cellular stress responses. However, the underlying phenomena are poorly explored. Therefore, we studied time‐resolved population heterogeneity of the E. coli growth reporter strain MG1655/pGS20PrrnBGFPAAV expressing destabilized green fluorescent protein during batch growth on acetate and glucose as sole carbon sources. Additionally, we applied five fluorescent stains targeting different cellular properties (viability as well as metabolic and respiratory activity). Quantitative analysis of flow cytometry data verified that bacterial populations in the bioreactor are more heterogeneous in growth as well as stronger metabolically challenged during growth on acetate as sole carbon source, compared to growth on glucose or acetate after diauxic shift. Interestingly, with acetate as sole carbon source, significant subpopulations were found with some cells that seem to be more robust than the rest of the population. In conclusion, following batch cultures population heterogeneity was evident in all measured parameters. Our approach enabled a deeper study of heterogeneity during growth on the favored substrate glucose as well as on the toxic by‐product acetate. Using a combination of activity fluorescent dyes proved to be an accurate and fast alternative as well as a supplement to the use of a reporter strain. However, the choice of combination of stains should be well considered depending on which population traits to aim for.
Competency‐based education and higher education enterprise systems
Authors: Boyer Naomi , Bucklew Kathy 
Published: February 2019

AbstractBackgroundCompetency‐based education (CBE) as a means of awarding degrees and credentials in higher education has emerged as a student‐centric, personalized academic design with the potential to transform learning; however, the variety that currently exists in program design and delivery has limited the development opportunities for systemic enterprise solutions. To scale, expand, and enhance the delivery of these programs, new technological systems and administrative processes are required, as existing enterprise systems do not support flexible configurations of automated business processes that respond to institutions that deliver both traditional and CBE programs.AimsThe research presented explores the basic system design and configuration elements that are necessary to electronically facilitate the student, academic, and business functions in higher education CBE programs.MethodA national survey was conducted collecting data on CBE program design and practices as it relates to enterprise system elements.DiscussionBased on the results of the survey, it is recommended that future efforts in the next‐generation enterprise technology, specifically student information systems, focus on three foundational building blocks: course/program catalogs, class/schedule building, and term/subterm timeframes. By integrating key configuration options into these three areas, the variety across institutional design can be accounted for, and flexibility for future innovative instructional models can be addressed.ConclusionAdditional consideration, in future research, should be given to the interplay between systems to create a technological ecosystem responsive to the individual student with the educational process.
Cell Profiling Based on Sugar‐Chain–Cell Binding Interaction and Its Application to Typing and Quality Verification of Cells
Authors: Shinchi Hiroyuki , Nakamura Tomoya , Ota Hayato , Nishihara Shoko , Wakao Masahiro , Suda Yasuo 
Published: February 2019

AbstractDeveloping methods to determine cell type and cell state has been a significant challenge in the field of cancer diagnosis as well as in typing and quality verification for cultured cells. Herein, we report a cell profiling method based on binding interactions between cell‐surface sugar‐chain‐binding proteins and sugar‐chain‐immobilized fluorescent nanoparticles (SFNPs), together with a method for cell typing and cell quality verification. Binding profiles of cells against sugar chains were analyzed by performing flow cytometry analysis with SFNPs. Discrimination analysis based on binding profiles could classify cell type and evaluate the quality of cultured cells. By applying our method to differentiated cells originating from conventional cell lines and also to mouse embryotic stem cells, we could detect the cells before and after differentiation. Our method can be utilized not only for the biofunctional analysis of cells but also for diagnosis of cancer cells and quality verification of cultured cells.
Transcatheter tricuspid valve‐in‐valve replacement: Making it simpler
Authors: Capretti Giuliana , Urena Marina , Bouleti Claire , Himbert Dominique 
Published: February 2019

AbstractTranscatheter tricuspid valve‐in‐valve replacement (TTVR) represents an attractive therapeutic option in very high surgical risk patients with degenerated tricuspid bioprostheses. However, the procedural management of these patients might be challenging due to their comorbidities, long lasting heart valve disease and the presence of left‐sided mechanical prostheses. Thus, a more “minimally disruptive” procedure would have several potential benefits in such a frail population. We present the cases of four patients admitted for congestive heart failure due to severe degeneration of their tricuspid bioprostheses who were treated with a minimalist TTVR. The protocol combined continuation of the oral anticoagulant treatment with no bridging therapy, the use of a single venous access with local anesthesia, rapid pacing via the stiff right ventricular wire, and transthoracic echocardiographic guidance and assessment, with no need for contrast injection.Our protocol aims at simplifying the TTVR procedure and might be a useful tool to avoid procedural complications and reduce hospital stay.
Nitrogen‐Rich, Well‐Dispersed Nanoporous Carbon Materials for Super‐Efficient Oxygen Reduction Reaction
Authors: Wu Qi , Wang Zhichang , Li Yibing , Wang Zheng , Liang Yan , Hu Yaoxin , Ou Ranwen , Wang Jianshe , Lu Tianliang , Wang Jianfeng , Wang Huanting , Zhao Chuan , Han Li 
Published: February 2019

AbstractNitrogen‐doped carbon with a well‐dispersed and three‐dimensional porous network structure has been fabricated for efficient oxygen reduction reaction (ORR) by using polyacrylamide (PAM) and graphene oxide (GO) as well as a zeolitic imidazolate framework (ZIF) as raw materials. The PAM is favorable for the formation of three‐dimensional porous structures, while high‐temperature carbonization of the ZIF results in well‐dispersed microporous carbon. Among them, Zn‐Z/P0.6/G‐T calcined at 800 °C with a PAM concentration of 60 % shows the largest specific surface area (1,458 m2/g) and best ORR performance in 0.1 M KOH, giving an onset potential of 0.918 V (vs. RHE), which is even more positive than Pt/C (0.902 V vs. RHE), demonstrating its superior ORR capability. The ORR performance can be further improved by incorporating cobalt into the composite (denoted Co‐Z/P0.6/G‐T), and this can be prepared by using cobalt nitrate as a metal source. As an ORR catalyst, it exhibits a more positive onset potential (0.935 V vs. RHE) than Zn‐Z/P0.6/G‐T (0.918 V vs. RHE). The good ORR performance together with its long‐term stability and better methanol tolerance make it a promising non‐noble catalyst for fuel cell applications.
Diselenolane‐Mediated Cellular Uptake: Efficient Cytosolic Delivery of Probes, Peptides, Proteins, Artificial Metalloenzymes and Protein‐Coated Quantum Dots
Authors: Bartolami Eline , Basagiannis Dimitris , Zong Lili , Martinent Rémi , Okamoto Yasunori , Laurent Quentin , Ward Thomas R. , Gonzalez‐Gaitan Marcos , Sakai Naomi , Matile Stefan 
Published: February 2019

AbstractCyclic oligochalcogenides are emerging as powerful tools to penetrate cells. With disulfide ring tension maximized, selenium chemistry had to be explored next to enhance speed and selectivity of dynamic covalent exchange on the way into the cytosol. We show that diseleno lipoic acid (DiSeL) delivers a variety of relevant substrates. DiSeL‐driven uptake of artificial metalloenzymes enables bioorthogonal fluorophore uncaging within cells. Binding of a bicyclic peptide, phalloidin, to actin fibers evinces targeted delivery to the cytosol. Automated tracking of diffusive compared to directed motility and immobility localizes 79 % of protein‐coated quantum dots (QDs) in the cytosol, with little endosomal capture (0.06 %). These results suggest that diselenolanes might act as molecular walkers along disulfide tracks in locally denatured membrane proteins, surrounded by adaptive micellar membrane defects. Miniscule and versatile, DiSeL tags are also readily available, stable, soluble, and non‐toxic.
The Construction of Molecular Complexity from Functionalized Alkylidenecyclopropanes (FACPs)
Authors: Yu Liu‐Zhu , Shi Min 
Published: February 2019

AbstractAs a special family of cyclopropanes, alkylidenecyclopropanes (ACPs), exhibit outstanding physical and chemical activities, which provide opportunities to participate in fascinating chemical transformations to access cyclopropane‐containing units without ring‐opening processes and other unavailable compounds through conventional routes with ring‐opening processes owing to their strain‐driven reactivity and synthetic accessibility. Nowadays, intramolecular reactions of methylenecyclopropanes (MCPs) or ACPs with adjacent functionalities have emerged as a powerful synthetic protocol for the construction of a variety of polycyclic and heterocyclic compounds with different sized skeletons through catalytic methods. Recently, we put forward the concept of functional alkylidenecyclopropanes (FACPs) and in this Minireview, we will summarize the reactions of FACPs after 2016 including several important early works from three aspects: 1) reactions with distal C−C bond cleavage, 2) reactions with proximal C−C bond cleavage (including ring‐expansion reactions), and 3) reactions without C−C bond cleavage.
Development of Chiral Spiro Phosphoramidites for Rhodium‐Catalyzed Enantioselective Reactions
Authors: Zheng Zhiyao , Cao Yuxi , Zhu Dongsheng , Wang Zheng , Ding Kuiling 
Published: February 2019

AbstractA series of 1,1′‐spirobiindane‐7,7′‐diol (SPINOL) analogues bearing a 2,2′‐dimethyl‐, cyclopentyl‐, or cyclohexyl‐fused ring were synthesized, and their distinct structural features were elucidated by X‐ray crystallography. On the basis of these scaffolds, chiral monophosphoramidite ligands 6 a–m were synthesized, which demonstrated excellent enantioselectivity in RhI‐catalyzed asymmetric hydrogenation of a dehydro amino acid methyl ester. Ligands 6 a–m were also successfully applied in the RhI‐catalyzed enantioselective [4+2] cycloaddition of α,β‐unsaturated imines with isocyanates, which afforded the corresponding pyrimidinones in good yields (60–92 %) with high enantioselectivities (75–92 % ee).
Copper‐Catalyzed Carbotrifluoromethylation of Unactivated Alkenes Driven by Trifluoromethylation of Alkyl Radicals
Authors: Zhang Zhenzhen , Zhu Lin , Li Chaozhong 
Published: February 2019

Summary of main observation and conclusionWe report herein an unprecedented protocol for radical carbotrifluoromethylation of unactivated alkenes. With Cu(OTf)2 as the catalyst, the reaction of unactivated alkenes, TMSCF3 and activated alkyl chlorides at room temperature provides the corresponding carbotrifluoromethylation products in satisfactory yields. Directed by trifluoromethylation of alkyl radicals, the method exhibits an excellent regioselectivity that is opposite to those driven by CF3 radical addition.
Novel Approaches to Access Arylfluorosulfates and Sulfamoyl Fluorides Based on Sulfur (VI) Fluoride Exchange
Authors: Liu Zilei , Meng Genyi , Guo Taijie , Dong Jiajia , Wu Peng 
Published: February 2019

AbstractSulfur (VI) fluoride exchange (SuFEx) is a new family of click chemistry reactions that relies on readily available sulfuryl fluoride (SO2F2) and ethenesulfonyl fluoride to build diverse chemical structures bearing the SVI‐F motif, such as fluorosulfate (‐OSO2F) and sulfonyl fluoride (‐SO2F). These motifs could be useful functional groups and connective linkers in organic synthesis. This unit describes two protocols for performing SuFEx. The first protocol describes an in situ method for rapid generation of arylfluorosulfates in 96‐well plates for high‐throughput screening. The second protocol outlines use of a shelf‐stable fluorosulfuryl imidazolium salt for generating arylfluorosulfates and sulfamoyl fluorides. © 2019 by John Wiley & Sons, Inc.