bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of protein cryoconcentration and processing conditions on kinetics of dimer formation for a monoclonal antibody: A case study on bioprocessing
Authors: Mehta Shyam B. , Subramanian Srishty , D'Mello Rowena , Brisbane Charlene , Roy Shouvik 
Published: May 2019

AbstractMonoclonal antibodies (mAbs) may be prone to self‐association leading to formation of dimers, trimers, or other high molecular weight species during bio‐processing. In order to implement appropriate manufacturing control strategies during bio‐processing, it is important to understand various real life bio‐processing conditions where such self‐associations may manifest. One such case study is presented here of increase in dimer content for an mAb during scale‐up bio‐processing and the approach taken to understand the under‐lying mechanism. In this example, a therapeutic mAb demonstrated a consistently higher dimer values (~0.5% higher) in the drug product (DP) during release when compared to the same value measured in the corresponding drug substance (DS) lot. This observation was interesting since the DS was supplied frozen, and the DS and DP share the same formulation composition and therefore investigation of this dimer change was the scope of the characterization study. Variable path length spectroscopy and size exclusion chromatography was used for protein quantification and to monitor %dimer respectively during characterization of fill‐finish unit operations. At the start of DP manufacturing process, immediately after thaw of bulk DS, a protein concentration gradient was observed and the concentration ranged from 90 mg/mL (top of container) to 210 mg/mL (bottom of container). The dimerization kinetics in the same DS container was dependent on concentration with higher concentrations demonstrating higher rates of dimerization. After the bulk DS was mixed for further processing, %dimer in purified bulk DS was quantitated to be approximately 1.4% which is identical to levels observed during scale‐up manufacturing of DP. After each unit operation, the in‐process samples tested for %dimer showed a gradual increase in dimer as a function of time over the next 7 days accumulating to 1.8% dimer at the end of DP manufacturing process. Samples subjected to static incubation at 2–8°C and room temperature (RT; 15–25°C) showed a gradual increase in dimer over the same time frame; however, the rate of increase in dimer at RT was higher compared to samples stored at 2–8°C. The results from this demonstrate two important key findings: self‐association kinetics of mAbs could be exacerbated by protein cryoconcentration and temperature conditions during bioprocessing. Since these two parameters are commonly encountered during manufacturing, the proposed mitigation strategy is to ensure homogeneity of the bulk DP during processing. The temperature dependent self‐association kinetics of mAb could be mitigated by processing at lower temperature (e.g., 2–8°C) and by storing the finished DP at lower temperature after manufacturing. The results from this study also highlight the criticality of setting slightly wider specifications for DP compared to DS following ICH Q6B guidelines.
Establishment of epithelial and fibroblast cell cultures and cell lines from primary renal cancer nephrectomies
Authors: Yap Ning Yi , Ong Teng Aik , Morais Christudas , Pailoor Jayalakshmi , Gobe Glenda C. , Rajandram Retnagowri 
Published: May 2019

AbstractRenal cell carcinoma (RCC) is one of the most lethal urogenital cancers and effective treatment of metastatic RCC remains an elusive target. Cell lines enable the in vitro investigation of molecular and genetic changes leading to renal carcinogenesis and are important for evaluating cellular drug response or toxicity. This study details a fast and easy protocol of establishing epithelial and fibroblast cell cultures or cell lines concurrently from renal cancer nephrectomy tissue. The protocol involves mechanical disaggregation, collagenase digestion and cell sieving for establishing epithelial cells while fibroblast cells were grown from explants. This protocol has been modified from previous published reports with additional antibiotics and washing steps added to eliminate microbial contamination from the surgical source. Cell characterisation was carried out using immunofluorescence and quantitative polymerase chain reaction. Eleven stable epithelial renal tumour cell lines of various subtypes, including rare subtypes, were established with a spontaneous immortalisation rate of 21.6% using this protocol. Eight fibroblast cell cultures grew successfully but did not achieve spontaneous immortalisation. Cells of epithelial origin expressed higher expressions of epithelial markers such as pan‐cytokeratin, cytokeratin 8 and E‐cadherin whereas fibroblast cells expressed high α‐smooth muscle actin. Further mutational analysis is needed to evaluate the genetic or molecular characteristics of the cell lines.
X‐ray fused with MRI guidance of pre‐selected transcatheter congenital heart disease interventions
Authors: Grant Elena K. , Kanter Joshua P. , Olivieri Laura J. , Cross Russell R. , Campbell‐Washburn Adrienne , Faranesh Anthony Z. , Cronin Ileen , Hamann Karin S. , O'Byrne Michael L. , Slack Michael C. , Lederman Robert J. , Ratnayaka Kanishka 
Published: May 2019

AbstractObjectivesTo determine whether X‐ray fused with MRI (XFM) is beneficial for select transcatheter congenital heart disease interventions.BackgroundComplex transcatheter interventions often require three‐dimensional (3D) soft tissue imaging guidance. Fusion imaging with live X‐ray fluoroscopy can potentially improve and simplify procedures.MethodsPatients referred for select congenital heart disease interventions were prospectively enrolled. Cardiac MRI data was overlaid on live fluoroscopy for procedural guidance. Likert scale operator assessments of value were recorded. Fluoroscopy time, radiation exposure, contrast dose, and procedure time were compared to matched cases from our institutional experience.ResultsForty‐six patients were enrolled. Pre‐catheterization, same day cardiac MRI findings indicated intervention should be deferred in nine patients. XFM‐guided cardiac catheterization was performed in 37 (median age 8.7 years [0.5–63 years]; median weight 28 kg [5.6–110 kg]) with the following prespecified indications: pulmonary artery (PA) stenosis (n = 13), aortic coarctation (n = 12), conduit stenosis/insufficiency (n = 9), and ventricular septal defect (n = 3). Diagnostic catheterization showed intervention was not indicated in 12 additional cases. XFM‐guided intervention was performed in the remaining 25. Fluoroscopy time was shorter for XFM‐guided intervention cases compared to matched controls. There was no significant difference in radiation dose area product, contrast volume, or procedure time. Operator Likert scores indicated XFM provided useful soft tissue guidance in all cases and was never misleading.ConclusionsXFM provides operators with meaningful three‐dimensional soft tissue data and reduces fluoroscopy time in select congenital heart disease interventions.
Multiple Covalent Triazine Frameworks with Strong Polysulfide Chemisorption for Enhanced Lithium‐Sulfur Batteries
Authors: Wang De‐Gao , Tan Lei , Wang Huan , Song Min , Wang Jiexi , Kuang Gui‐Chao 
Published: May 2019

AbstractEndowed with high theoretical energy density, low cost, and environmental friendliness, lithium‐sulfur batteries have a promising future in energy storage. The volume expansion of the sulfur cathode, shuttle effects, and the insulating nature of polysulfide result in poor cycling stability and limit practical applications of lithium‐sulfur batteries. In this work, these matters are relieved by physically and chemically restricting sulfur species in highly fluorinated sulfur‐rich multiple covalent triazine frameworks synthesized through nucleophilic aromatic substitution reaction chemistry. It exhibits a specific capacity of 681 mAh g−1 and capacity retention of 62.6 % after 400 cycles, indicating a 0.09 % degradation per cycle. The superiority in cycle performance is attributed to the homogeneous distribution of sulfur, covalent bonding of sulfur, and affinity for polysulfide of triazine rings.
Layered Crystalline and Amorphous Platinum Disulfide (PtS2): Contrasting Electrochemistry
Authors: Wang Yong , Szokolova Katerina , Nasir Muhammad Zafir Mohamad , Sofer Zdenek , Pumera Martin 
Published: May 2019

AbstractGroup 6 transition metal dichalcogenides (TMDs), such as MoS2 and WS2 have been extensively studied for various applications while few studies have delved into other TMDs such as platinum dichalcogenides. In this work, layered crystalline and amorphous platinum disulfide (PtS2) were synthesized, characterised and their fundamental electrochemical properties were investigated. Both materials exhibited inherent oxidation and reduction reactions which would limit their operating potential window for sensing applications. Amorphous phase materials are considered to be promising electrocatalysts due to the porous, and nanostructured morphology with high concentration of unsaturated active sites. The electrocatalytic performances towards oxygen reduction (ORR) and hydrogen evolution reactions (HER) of crystalline and amorphous PtS2 were analysed. Amorphous PtS2 was found to exhibit superior electrocatalytic performances towards ORR and HER as compared to crystalline PtS2. For HER, amorphous and crystalline PtS2 have overpotential values of 0.30 V and 0.70 V (vs. RHE) at current density of 10 mA cm−2, respectively. The influence of electrochemical reduction pre‐treatment on their catalytic behaviours was also investigated. Electrochemical reduction pre‐treatment on both crystalline and amorphous PtS2 removed the oxidized sulfate groups and increased the proportion of Pt0 oxidation state which exposed more catalytic sites. As such, these materials were activated and displayed improved ORR and HER performances. Electrochemically reduced amorphous PtS2 outperformed the untreated counterparts and exhibited the best HER performance with overpotential of 0.17 V (vs. RHE) at current density of −10 mA cm−2. These findings provide insights into the electrochemical properties of noble metal PtS2 in both crystalline and amorphous states which can be activated by electrochemical reduction pre‐treatment.
Chiral Symmetry Breaking of Spiropyrans and Spirooxazines by Dynamic Enantioselective Crystallization
Authors: Ishikawa Hiroki , Uemura Naohiro , Saito Rei , Yoshida Yasushi , Mino Takashi , Kasashima Yoshio , Sakamoto Masami 
Published: May 2019

AbstractDynamic enantioselective crystallization enabled the chiral symmetry breaking of two spiropyrans and one spirooxazine. The three spiro compounds afforded racemic conglomerate crystals, and easily racemized in alcoholic solution without irradiation. Optically pure enantiomorphic crystals were obtained by vapor‐diffusion crystallization or attrition‐enhanced deracemization (Viedma ripening). Their absolute configurations were determined by single‐crystal X‐ray analysis and each enantiomorphic crystal was correlated with its solid‐state circular dichroism (CD) spectrum.
Pd‐Catalyzed Synthesis of Vinyl Arenes from Aryl Halides and Acrylic Acid
Authors: Gao Yang , Ou Yang , Gooßen Lukas J. 
Published: May 2019

AbstractAcrylic acid is presented as an inexpensive, non‐volatile vinylating agent in a palladium‐catalyzed decarboxylative vinylation of aryl halides. The reaction proceeds through a Heck reaction of acrylic acid, immediately followed by protodecarboxylation of the cinnamic acid intermediate. The use of the carboxylate group as a deciduous directing group ensures high selectivity for monoarylated products. The vinylation process is generally applicable to diversely substituted substrates. Its utility is shown by the synthesis of drug‐like molecules and the gram‐scale preparation of key intermediates in drug synthesis.
Uranyl‐Bound Tetra‐Dentate Non‐Innocent Ligands: Prediction of Structure and Redox Behaviour Using Density Functional Theory
Authors: Arumugam Krishnamoorthy , Burton Neil A. 
Published: May 2019

AbstractComputational methods have been applied to understand the reduction potentials of [UO2‐salmnt‐L] complexes (L=pyridine, DMSO, DMF and TPPO), and their redox behavior is compared with previous experiments in dichloromethane solution. Since the experimental results were inconclusive regarding the influence of the uranyl‐bound tetra‐dentate ‘salmnt’ ligand, here we will show that salmnt acts as a redox‐active ligand and exhibits non‐innocent behavior to interfere with the otherwise expected one‐electron metal (U) reduction. We have employed two approaches to determine the uranyl (VI/V) reduction potentials, using a direct study of one‐electron reduction processes and an estimation of the overall reduction using isodesmic reactions. Hybrid density functional theory (DFT) methods were combined with the Conductor‐like Polarizable Continuum Model (CPCM) to account for solvation effects. The computationally predicted one‐electron reduction potentials for the range of [UO2‐salmnt‐L] complexes are in excellent agreement with shoulder peaks (∼1.4 eV) observed in the cyclic voltammetry experiments and clearly correlate with ligand reduction. Highly conjugated pi‐bonds stabilize the ligand based delocalized orbital relative to the localized U f‐orbitals, and as a consequence, the ligand traps the incoming electron. A second reduction step results in metal U(VI) to U(V) reduction, in good agreement with the experimentally assigned uranyl (VI/V) reduction potentials.
Decreased heart rate variability as a predictor for diabetes—A prospective study of the Brazilian longitudinal study of adult health
Authors: Hoshi Rosangela A. , Santos Itamar S. , Dantas Eduardo M. , Andreão Rodrigo V. , Schmidt Maria Inês , Duncan Bruce B. , Mill José G. , Lotufo Paulo A. , Bensenor Isabela 
Published: May 2019

AbstractAimTo investigate whether heart rate variability (HRV) is a predictor for the incidence of diabetes in a 4‐year follow‐up.Materials and methodsThe HRV of 9192 participants free of diabetes was analysed in time and frequency domains and stratified based on the reference values presented in the literature. The participants were then allocated to one of three groups, according to age‐specific value distributions for each HRV domain: lower than the 25th percentile, between the 25th and 75th percentiles, and higher than the 75th percentile. The association between HRV and diabetes incidence at 4‐year follow‐up was analysed using Poisson regression models with robust estimator.ResultsSix hundred thirty‐four participants (6.90%) developed diabetes within 4 years and five out of six HRV analysed indices showed increased relative risk of developing diabetes associated with low HRV: SDNN (RR = 1.29; 95% CI, 1.09‐1.52; .003), pNN50 (RR = 1.33; 95% CI, 1.11‐1.58; .001), RMSSD (RR = 1.29; 95% CI, 1.09‐1.53; .004), LF (RR = 1.25; 95% CI, 1.05‐1.48; .012), and HF (RR = 1.39; 95% CI, 1.16‐1.63; .001).ConclusionsThis study suggests that both overall variability and changes in parasympathetic modulation precede the incidence of diabetes. For four HRV indices below the 25th percentile, the risk for incident diabetes was 68% higher than for those participants who presented none. We concluded that HRV is an independent risk predictor of diabetes in a 4‐year period.
A feasibility study comparing a web‐based intervention to a workshop intervention for caregivers of adults with eating disorders
Authors: Dimitropoulos Gina , Landers Ashley , Freeman Victoria , Novick Jason , Schmidt Ulrike , Olmsted Marion 
Published: May 2019

AbstractObjectiveTo assess for the validity of a future trial, the current feasibility study aimed to compare the feasibility and efficacy of a web‐ and workshop‐based education intervention for caregivers of adults with eating disorders.MethodsPsychoeducation was provided to caregivers, who were randomly assigned to a web or workshop condition. Independent samples t tests were conducted to analyse the between‐group effect sizes for intervention condition with regard to change over time. A random selection of participants from each intervention provided qualitative feedback about their experiences.ResultsOverall, participants reported positive experiences in both education interventions. From baseline to the end of intervention, small between‐group effect sizes were observed for changes in caregiver accommodation, problem‐solving abilities, the quality of psychological health, and the quality of social relationships, favouring the web‐based intervention, and changes in expressed emotion in the family context, caregiver burden, perceived stress, and the quality of the environment, supporting the workshop intervention.ConclusionsThere was a difference in initial feasibility of the web intervention. A future large‐scale trial of these interventions is supported by the results of this feasibility study.
Gastrointestinal alterations in anorexia nervosa — A systematic review
Authors: Schalla Martha A. , Stengel Andreas 
Published: May 2019

AbstractObjectiveAnorexia nervosa (AN) is an eating disorder characterized by body schema disruptions, underweight (>15% reduction of the ideal body weight or a body mass index <17.5 kg/m2), self‐induced weight reduction, and endocrine impairments. The three latter features greatly impact on most physiological functions including the cardiovascular, skeletal, reproductive, and the gastrointestinal system, which results in an increased mortality rate in affected individuals. Especially, gastrointestinal alterations are described as particularly bothersome by patients.MethodsTo address the need for a better understanding of the interplay between AN and the gastrointestinal (GI) tract, a systematic data search in the databases Medline, Embase, and PsycINFO was conducted.ResultsOver 1,235 studies were identified, out of these, 107 appropriate articles were selected and discussed in the present review.ConclusionAN has large impact on GI alterations and symptoms; conversely, GI symptoms may also affect the manifestation and course of AN as discussed in the present review. Despite increasing data, several gaps in knowledge exist especially on the pathophysiology underlying the changes described.
Multimodal [18F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNFα Transgenic Mice
Authors: Hayer Silvia , Zeilinger Markus , Weiss Volker , Dumanic Monika , Seibt Markus , Niederreiter Birgit , Shvets Tetyana , Pichler Florian , Wadsak Wolfgang , Podesser Bruno K , Helbich Thomas H , Hacker Marcus , Smolen Josef S , Redlich Kurt , Mitterhauser Markus 
Published: May 2019

ABSTRACTIn rheumatoid arthritis (RA), chronic joint inflammation leading to bone and cartilage damage is the major cause of functional impairment. Whereas reduction of synovitis and blockade of joint damage can be successfully achieved by disease modifying antirheumatic therapies, bone repair upon therapeutic interventions has only been rarely reported. The aim of this study was to use fluorodeoxyglucose ([18F]FDG) and [18F]fluoride µPET/CT imaging to monitor systemic inflammatory and destructive bone remodeling processes as well as potential bone repair in an established mouse model of chronic inflammatory, erosive polyarthritis. Therefore, human tumor necrosis factor transgenic (hTNFtg) mice were treated with infliximab, an anti-TNF antibody, for 4 weeks. Before and after treatment period, mice received either [18F]FDG, for detecting inflammatory processes, or [18F]fluoride, for monitoring bone remodeling processes, for PET scans followed by CT scans. Standardized uptake values (SUVmean) were analyzed in various joints and histopathological signs of arthritis, joint damage, and repair were assessed. Longitudinal PET/CT scans revealed a significant decrease in [18F]FDG SUVs in affected joints demonstrating complete remission of inflammatory processes due to TNF blockade. In contrast, [18F]fluoride SUVs could not discriminate between different severities of bone damage in hTNFtg mice. Repeated in vivo CT images proved a structural reversal of preexisting bone erosions after anti-TNF therapy. Accordingly, histological analysis showed complete resolution of synovial inflammation and healing of bone at sites of former bone erosion. We conclude that in vivo multimodal [18F]FDG µPET/CT imaging allows to quantify and monitor inflammation-mediated bone damage and reveals not only reversal of synovitis but also bone repair upon TNF blockade in experimental arthritis. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
The clinical significance of neutrophil gelatinase‐associated lipocalin in ischemic stroke patients with acute kidney injury
Authors: Xiao Wei , Chen Wei , Hu Hanning , Huang Xiaomei , Luo Yi 
Published: May 2019

AbstractBackgroundAcute kidney injury (AKI) has become a common complication of acute ischemic stroke (AIS) and may have a significant impact on the clinical outcomes. Neutrophil gelatinase‐associated lipocalin (NGAL), an acute phase protein, has been identified as a novel biomarker for acute kidney impairment. Here, we studied the early expression of NGAL in AIS patients with AKI and its clinic value in predicting and diagnosis of AKI after stroke.MethodsA total of 205 subjects diagnosed as first‐ever AIS were recruited in this study, including 40 AIS with AKI and 165 AIS without AKI defined using the KDIGO guidelines. The serum and urine levels of NGAL were measured with ELISA. To evaluate the clinic value of NGAL, we also detected creatinine, urea nitrogen and cystatin C and microalbumin (mALB) in serum or urine using chemiluminescence or immunoturbidimetry method, and then the receiver operating characteristic (ROC) curve and correlation was analyzed. The severity of AIS patients was evaluated based on the National Institutes of Health Stroke Scale (NIHSS) score.ResultsThe serum and urine NGAL levels were significantly increased in AIS patients with AKI, and line regression analysis indicated that there was a positive correlation between the serum NGAL and creatinine level in AIS patients accompanied AKI. Additionally, the concentration of serum NGAL in AIS patients with AKI increased with the severity of stroke.ConclusionThe increased serum NGAL may be used as a valuable complementary marker for the diagnoses and prediction of AKI in the early stage of AIS patients.