bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of a Serum Protein Signature With Rheumatoid Arthritis Development
Authors: O’Neil Liam J. , Spicer Victor , Smolik Irene , Meng Xiaobo , Goel Rishi R. , Anaparti Vidyanand , Wilkins John , El‐Gabalawy Hani S. 
Published: August 2020

ObjectiveThe pathophysiologic events that precede the onset of rheumatoid arthritis (RA) remain incompletely understood. This study was undertaken to identify changes in the serum proteome that precede the onset of RA, with the aim of providing new insights into the pathogenic mechanisms that lead to its development.MethodsIn a cohort of first‐degree relatives of Indigenous North American RA patients, the SomaScan proteomics platform was used to determine the levels of 1,307 proteins in multiple longitudinal serum samples from 17 individuals who were followed up prospectively to the time of disease onset. Proteomic signatures from this group of individuals (designated the progressor group) were compared to those in a group of individuals who were considered at risk of developing RA, stratified as either positive (n = 63) or negative (n = 47) for anti–citrullinated protein antibodies (ACPAs) (designated the at‐risk group). Machine learning was used to identify a protein signature that could accurately classify those individuals at highest risk of future RA development.ResultsA preclinical proteomic signature that differentiated RA progressors from at‐risk individuals, irrespective of ACPA status, was identified (area under the curve 0.913, accuracy 91.2%). Importantly, the predictive preclinical proteomic signature was present not only in serum samples obtained close to the onset of RA, but also in serum samples obtained a median of 30.9 months prior to onset. Network analysis implicated the activation of Toll‐like receptor 2 and production of tumor necrosis factor and interleukin‐1 as key events that precede RA progression.ConclusionAlterations in the serum proteome in the preclinical phase of RA can emerge years prior to the onset of disease. Our findings suggest that the serum proteome provides a rich source of proteins serving both to classify at‐risk individuals and to identify molecular pathways involved in the development of clinically detectable RA.
B(C6F5)3‐Catalyzed Tandem Friedel‐Crafts and C−H/C−O Coupling Reactions of Dialkylanilines
Authors: Zhai Gaowen , Liu Xueting , Ma Wentao , Wang Guoqiang , Yang Liu , Li Shuhua , Wu Youting , Hu Xingbang 
Published: August 2020

AbstractTandem Friedel‐Crafts (FC) and C−H/C−O coupling reactions catalyzed by tris(pentafluorophenyl) borane (B(C6F5)3) were achieved without using any other additive in the absence of solvent. This process can be used for the reactions between a series of dialkylanilines and vinyl ethers with good isolated yields of bis(4‐dialkylaminophenyl) compounds. Based on combined theoretical and experimental studies, the possible reaction mechanism was proposed. B(C6F5)3 can activate the C=C and C−O bond for FC and C−H/C−O coupling reactions respectively. The FC reaction is slow, which is followed by a fast C−H/C−O coupling.
Engineered Live Biotherapeutics: Progress and Challenges
Authors: Tan Yang , Shen Juntao , Si Tong , Ho Chun Loong , Li Yinqing , Dai Lei 
Published: August 2020

AbstractThe human microbiome plays an important role in human health, from metabolism to immunity. In the last few decades, advances in synthetic biology have enabled scientists to design and engineer live microorganisms for therapeutic purposes. In this review, major strategies for manipulating the microbiome are outlined, which include three emerging areas with promising therapeutic applications: engineered commensal bacteria, synthetic microbial consortia, and targeted modulation by phages. Furthermore, the applications of engineered live biotherapeutics in treating a variety of human diseases, including pathogenic infections, metabolic disorders, inflammatory bowel disease, and colorectal cancer, are highlighted. Finally, an overview of the challenges and opportunities in the future development of engineered live biotherapeutics is provided.
Metabolically engineered Caldicellulosiruptor bescii as a platform for producing acetone and hydrogen from lignocellulose
Authors: Straub Christopher T. , Bing Ryan G. , Otten Jonathan K. , Keller Lisa M. , Zeldes Benjamin M. , Adams Michael W. W. , Kelly Robert M. 
Published: August 2020

AbstractThe production of volatile industrial chemicals utilizing metabolically engineered extreme thermophiles offers the potential for processes with simultaneous fermentation and product separation. An excellent target chemical for such a process is acetone (Tb = 56°C), ideally produced from lignocellulosic biomass. Caldicellulosiruptor bescii (Topt 78°C), an extremely thermophilic fermentative bacterium naturally capable of deconstructing and fermenting lignocellulose, was metabolically engineered to produce acetone. When the acetone pathway construct was integrated into a parent strain containing the bifunctional alcohol dehydrogenase from Clostridium thermocellum, acetone was produced at 9.1 mM (0.53 g/L), in addition to minimal ethanol 3.3 mM (0.15 g/L), along with net acetate consumption. This demonstrates that C. bescii can be engineered with balanced pathways in which renewable carbohydrate sources are converted to useful metabolites, primarily acetone and H2, without net production of its native fermentation products, acetate and lactate.
An in situ collagen‐HA hydrogel system promotes survival and preserves the proangiogenic secretion of hiPSC‐derived vascular smooth muscle cells
Authors: Dash Biraja C. , Duan Kaiti , Xing Hao , Kyriakides Themis R. , Hsia Henry C. 
Published: August 2020

AbstractHuman‐induced pluripotent stem cell‐derived vascular smooth muscle cells (hiPSC‐VSMCs) with proangiogenic properties have huge therapeutic potential. While hiPSC‐VSMCs have already been utilized for wound healing using a biomimetic collagen scaffold, an in situ forming hydrogel mimicking the native environment of skin offers the promise of hiPSC‐VSMC mediated repair and regeneration. Herein, the impact of a collagen type‐I‐hyaluronic acid (HA) in situ hydrogel cross‐linked using a polyethylene glycol‐based cross‐linker on hiPSC‐VSMCs viability and proangiogenic paracrine secretion was investigated. Our study demonstrated increases in cell viability, maintenance of phenotype and proangiogenic growth factor secretion, and proangiogenic activity in response to the conditioned medium. The optimally cross‐linked and functionalized collagen type‐I/HA hydrogel system developed in this study shows promise as an in situ hiPSC‐VSMC carrier system for wound regeneration.
Irisin ameliorates high glucose‐induced cardiomyocytes injury via AMPK/mTOR signal pathway
Authors: Deng Jingyu , Zhang Ning , Chen Feng , Yang Chao , Ning Hongjuan , Xiao Chun , Sun Ke , Liu Yongfei , Yang Ming , Hu Taohong , Zhang Zheng , Jiang Wei 
Published: August 2020

AbstractHigh glucose (HG)‐induced cardiomyocytes (CMs) injury is a leading cause of diabetic cardiomyopathy with little treatment options. Irisin, a new myokine, which is cleaved from its precursor fibronectin type III domain‐containing protein 5 (FNDC5), has aroused great attention as an essential cardioprotective factor and glucose metabolism regulator but little was known on diabetic cardiomyopathy yet. Here, we aim to clarify the role of irisin in the HG‐induced CMs injury. Neonatal Sprague–Dawley rat CMs were cultured in a normal or HG medium for 12, 24, and 48 hr, respectively before exposing to irisin. The apoptosis level was determined by terminal‐deoxynucleotidyl transferase‐mediated‐dUTP nick end‐labeling assay. Cell viability was measured with the conventional methyl thiazolyl tetrazolium assay. Moreover, reactive oxygen species production was evaluated by dihydroethidium staining. Inflammatory factors, namely tumor necrosis factor‐α, interleukin‐6, interleukin‐1β were determined by enzyme‐linked immunosorbent assay kits. Furthermore, protein and messenger RNA (mRNA) expressions were measured by western blot and quantitative real‐time polymerase chain reaction, respectively. HG increases the apoptosis of CMs and activated the inflammatory responses and oxidative stress in CMs. Meanwhile, the mRNA and protein expressions of FNDC5 are decreased after HG exposure. Nevertheless, the increased apoptosis is alleviated by irisin treatment. Notably, irisin suppresses the inflammatory responses and oxidative stress in injured CMs. Mechanically, after the administration of Compound C, AMP‐activated protein kinase (AMPK) inhibitor, these cardioprotective effects resulting from irisin are reversed. Irisin plays a significant role in antiapoptosis, anti‐inflammation, antioxidative stress in HG‐induced CMs via AMPK/mammalian target of the rapamycin signaling pathway.
MAPRE1 promotes cell cycle progression of hepatocellular carcinoma cells by interacting with CDK2
Authors: Liang Xing‐hua , Feng Zheng‐ping , Liu Fo‐qiu , Yan Rong , Yin Liang‐yu , Shen Hao , Lu Hai‐lin 
Published: August 2020

AbstractTargeting cyclin‐dependent kinases (CDKs) is a promising method of therapy for cancer. Unfortunately, the efficacy of CDK inhibitors in hepatocellular carcinoma (HCC) is limited, due in part to incomplete understanding of cell cycle progression and a lack of specific biomarkers to adequately identify which patients may be responsive to CDK inhibitors. In the present study, we report that microtubule‐associated protein RP/EB family member 1 (MAPRE1), a gene involved in cell cycle and microtubule regulation, is significantly increased in HCC tissue, promotes HCC cell proliferation, enhances in vitro tumorigenesis, and associates with poor prognosis of HCC. We demonstrate that MAPRE1 binds with CDK2, resulting in the hyperphosphorylation of the CDK2 Thr161 residue in HCC cells. Our findings reveal that targeting MAPRE1 might be an effective therapeutic strategy in HCC, and suggest that MAPRE1 expression might provide a promising biomarker to stratify patients with HCC who may benefit from treatment with CDK inhibitors.
A Modified Four‐Probe Method to Separate Ionic Conductance from Composite Conductors
Authors: Fu Xudong , Xia Zhangxun , Liu Qingting , Wang Suli , Sun Gongquan 
Published: August 2020

AbstractAs one of the most important phenomena in electrochemistry and biosystems, ion transport often suffers from the difficulty of effective measurement in electron‐/ion‐conductive composite components. Hence, by modifying the testing probes with an ion‐conductive polymer, a new four‐probe method is invented to separate ion transport within composite materials. By adopting this method, the ionic conductance of the electronic conductors could be precisely measured and the ion migration behaviors in various environments could also be investigated.
Nucleation of Tiny Silver Nanoparticles by Using a Tetrafacial Organic Molecular Barrel: Potential Use in Visible‐Light‐Triggered Photocatalysis
Authors: Mondal Bijnaneswar , Bhandari Pallab , Mukherjee Partha Sarathi 
Published: August 2020

AbstractCoordination‐driven self‐assembly of discrete molecular architectures of diverse shapes and sizes has been well studied in the last three decades. Use of dynamic imine bonds for designing analogous metal‐free architectures has become a growing challenge recently. This article reports an organic molecular barrel (OB4R) as a potential template for nucleation and stabilization of very tiny (<1.5 nm) Ag nanoparticles (AgNPs). Imine bond condensation of a rigid tetra‐aldehyde with a flexible diamine followed by imine‐bond reduction yielded the discrete tetragonal organic barrel (OB4R). The presence of a molecular pocket ornamented with eight diamine moieties gives the potential for encapsulation of silver(I). The organic barrel was finally used as a molecular vessel for the controlled nucleation of silver nanoparticles (AgNPs) with fine size tuning through binding of AgI ions in the confined space of the barrel followed by reduction. Transmission electron microscopy (TEM) analysis of the Ag0@OB4R composite revealed that the mean particle size is 1.44±0.16 nm. The composite material has approximately 52 wt % silver loading. The barrel‐supported ultrafine AgNPs [Ag0@OB4R] are found to be an efficient photocatalyst for facile Ullmann‐type aryl‐amination coupling of haloarenes at ambient temperature without using any additives. The catalyst was stable for several cycles of reuse without any agglomeration. The new composite Ag0@OB4R represents the first example of discrete organic barrel‐supported AgNPs employed as a photocatalyst in Ullmann‐type coupling reactions at room temperature.
Low participation rates and disparities in participation in interventional clinical trials for myelodysplastic syndromes
Authors: Brierley Charlotte K. , Zabor Emily C. , Komrokji Rami S. , DeZern Amy E. , Roboz Gail J. , Brunner Andrew M. , Stone Richard M. , Sekeres Mikkael A. , Steensma David P. 
Published: August 2020

BackgroundThe development of novel therapies for the myelodysplastic syndromes (MDS) is hampered by inadequate trial recruitment. Factors contributing to low trial accrual are incompletely understood.MethodsThis study analyzed a pooled patient database from institutions of the US MDS Clinical Research Consortium to compare the characteristics of participants in interventional trials with those of patients who did not enroll in a trial.ResultsData were identified for 1919 patients with MDS, and 449 of these patients (23%) participated in an interventional clinical trial. The median age of all patients was 68 years, and 64% were male. Patients who participated in trials were significantly younger than nonparticipants (P = .014), and men were more likely to participate in a trial (71% of trial participants were male, whereas 61% of nonparticipants were; P < .001). Race and ethnicity were not associated with trial enrollment. Patients in more affluent ZIP codes had a higher participation rate (P < .001). Patients with intermediate‐ and high‐risk disease according to the revised International Prognostic Scoring System were overrepresented (P = .004), and trial participants less frequently had treatment‐related disease (P < .001). In multivariable analyses, participation in a clinical trial was associated with a reduced hazard of death (P = .004). Even at large referral centers, only a minority of patients with MDS enrolled in interventional trials.ConclusionsRestrictive trial eligibility criteria that exclude patients with MDS on account of age, comorbidities, or a history of another cancer are limit enrollment of MDS patients to clinical trials. Gaining insight into the barriers to trial accrual may help investigators and study sponsors to design trials that will accrue more rapidly and augment treatment options for patients with MDS.
Efficacy and Safety of Ticagrelor vs. Clopidogrel in East Asian Patients with Acute Myocardial Infarction: A Nationwide Cohort Study
Authors: Chang Chi‐Jen , Tung Ying‐Chang , Liu Jia‐Rou , Chang Shu‐Hao , Kuo Chi‐Tai , See Lai‐Chu 
Published: August 2020

Ticagrelor improves clinical outcomes in patients with acute myocardial infarction (AMI). This study aimed to compare the efficacy and safety of ticagrelor vs. clopidogrel in East Asian patients with AMI. Between July 2013 and December 2015, patients with AMI prescribed dual antiplatelet therapy were identified from the National Health Insurance Research Database of Taiwan. Using propensity score weighting, ticagrelor was compared with clopidogrel for the primary efficacy end point (a composite of all‐cause death, myocardial infarction (MI), and stroke) and bleeding. A total of 32,442 patients with AMI (ticagrelor: 10,057; clopidogrel: 22,385) were eligible for analysis. After propensity score weighting, ticagrelor was comparable to clopidogrel in the incidence rate of the primary efficacy end point (23.6 vs. 22.76/100 patient‐years; hazard ratio (HR) 0.97; 95% confidence interval (CI) 0.89–1.06; P = 0.513). Ticagrelor was associated with a lower risk of stroke (1.78 vs. 2.66/100 patient‐years; HR 0.64; 95% CI 0.49–0.85; P = 0.002) and higher risks of overall (21.59 vs. 18.35/100 patient‐years; HR 1.16; 95% CI 1.06–1.27; P = 0.002) and Bleeding Academic Research Consortium (BARC) type 2 bleeding (18.67 vs. 15.08/100 patient‐years; HR 1.22; 95% CI 1.11–1.36; P < 0.001). The risks of death, MI, and BARC 3 or 5 bleeding were comparable between ticagrelor and clopidogrel. In the present study, ticagrelor was comparable to clopidogrel in the composite of death, MI, and stroke, but had an increased risk of BARC type 2 bleeding. Ticagrelor may be beneficial in preventing post‐MI stroke in East Asian patients.
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C19 and Proton Pump Inhibitor Dosing
Authors: Lima John J. , Thomas Cameron D. , Barbarino Julia , Desta Zeruesenay , Van Driest Sara L. , El Rouby Nihal , Johnson Julie A. , Cavallari Larisa H. , Shakhnovich Valentina , Thacker David L. , Scott Stuart A. , Schwab Matthias , Uppugunduri Chakradhara Rao S. , Formea Christine M. , Franciosi James P. , Sangkuhl Katrin , Gaedigk Andrea , Klein Teri E. , Gammal Roseann S. , Furuta Takahisa 
Published: August 2020

Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, Helicobacter pylori infection, and pathological hypersecretory conditions. Most PPIs are metabolized primarily by cytochrome P450 2C19 (CYP2C19) into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy, and adverse effects. We summarize the evidence from the literature and provide therapeutic recommendations for PPI prescribing based on CYP2C19 genotype (updates at www.cpicpgx.org). The potential benefits of using CYP2C19 genotype data to guide PPI therapy include (i) identifying patients with genotypes predictive of lower plasma exposure and prescribing them a higher dose that will increase the likelihood of efficacy, and (ii) identifying patients on chronic therapy with genotypes predictive of higher plasma exposure and prescribing them a decreased dose to minimize the risk of toxicity that is associated with long‐term PPI use, particularly at higher plasma concentrations.
Cannabidivarin for HIV‐Associated Neuropathic Pain: A Randomized, Blinded, Controlled Clinical Trial
Authors: Eibach Luca , Scheffel Simone , Cardebring Madeleine , Lettau Marie , Özgür Celik M. , Morguet Andreas , Roehle Robert , Stein Christoph 
Published: August 2020

HIV remains a major burden to the health care system and neuropathic pain is the most common neurological complication of HIV infection. Because current treatment strategies often lack satisfying pain relief, cannabinoids (CBs) are discussed as a new option. We investigated cannabidivarin (CBDV) as treatment for HIV‐associated neuropathic pain. We conducted a randomized, double‐blind, placebo‐controlled crossover study. Patients underwent two successive treatment phases (4 weeks each) and were treated with CBDV (400 mg/day) or placebo in a randomized order. A 3‐week washout phase was designed to eliminate potential carry‐over effects. Patients were followed up for 3 weeks after the end of the second treatment phase. The primary end point was pain intensity on an 11‐point numeric rating scale, recorded in a diary. Secondary end points were additional pain medication, pain characteristics, and quality of life. We included 32 patients. The mean pain intensity under CBDV was 0.62 points higher compared with placebo (P = 0.16, 95% confidence interval −0.27 to 1.51). CBDV did not influence the amount of additional pain medication, pain characteristics, or quality of life. The incidence of adverse events was similar during both treatments. No suspected unexpected adverse reactions occurred during either treatment. CBDV was safe but failed to reduce neuropathic pain in patients with HIV. This may be explained by a lack of CB receptor activation, as indicated by preclinical experiments. Although a larger patient number might be desirable, we would not expect a change in the conclusions because the present differences are far from statistical significance. Therefore, we would currently not consider CBDV as a clinically meaningful treatment option for neuropathic pain.
The use of 5‐aminolevulinic acid to reduce heat‐stress‐related damages in tall fescue
Authors: Katuwal Krishna B , Rowe Somerville , Jespersen David 
Published: August 2020

AbstractHeat stress is a major abiotic stress that damages cool‐season turfgrasses, such as tall fescue (Festuca arundinacea Schreb.), during summer months. Heat stress results in oxidative damage, reductions in photosynthesis, and ultimately can cause plant death. Exogenous applications of 5‐aminolevulinic acid (ALA) have previously been demonstrated to improve abiotic stress tolerance in a number of crops by improving chlorophyll levels and reducing oxidative damage, two major indicators of heat stress in plants. Experiments were conducted in growth chamber conditions to determine the effect of ALA application on heat stress in tall fescue plants and to confirm if ALA could alleviate damage related to inhibited photosynthesis or oxidative damages associated with high temperature. A rate of 100 mg L−1 ALA was determined to be effective in eliciting positive tall fescue responses during heat stress with plants maintaining better visual characteristics. Plants treated with ALA had greater levels of chlorophyll as well as photosynthetic performance under heat stress than plants that were not treated with ALA. Additionally, ALA plants had reduced oxidative damage associated with greater antioxidant activities of the enzymes catalase (CAT), ascorbate peroxidase (APX), and glutathione reductase (GR). The use of ALA was demonstrated to be effective in reducing heat stress related damages in tall fescue.
Effect of single operator cholangioscopy on accuracy of bile duct cytology
Authors: Aly Fatima Zahra , Mostofizadeh Sayedamin , Jawaid Salmaan , Knapik Jacquelyn , Mukhtar Faisal , Klein Robert 
Published: August 2020

AbstractIntroductionThis is the first study to evaluate the accuracy of bile duct brushings since the introduction of single operator cholangioscopy SpyGlass DS system in 2015. The primary aim of our study was to compare the accuracy of cytology brushings against biopsies obtained at endoscopic retrograde cholangiopancreatography (ERCP) and cholangioscopy.MethodA retrospective search for bile duct brushing specimens was performed and the charts reviewed. The gold standard for definitive diagnosis of malignancy was surgical tissue or compelling clinical evidence of malignancy. Definite negative diagnosis relied on lack of clinical/imaging features of malignancy on follow‐up.ResultsThere was no significant difference in diagnostic accuracy of cytology specimens obtained at different procedures. Overall sensitivity for all methods was 59%, specificity 90% and accuracy of 82%. Notably, all four false‐positive cases except for one were from patients with primary sclerosing cholangitis or primary biliary sclerosis. There was no significant difference in sensitivity or specificity between biopsies procured by the two methods. The combined biopsy sensitivity for all modalities was 44% with a specificity of 100%. There was 70% concordance between cytology and biopsy cases. The overall specificity and sensitivity of the combined cytology and biopsy result was 85% and 65.3%, respectively. Ranking of factors that predict clinical diagnosis shows cytology results to surpass other parameters including pancreatic mass, age and stenosis length. Similarly, the presence of two cell populations and three‐dimensional clusters was not nearly as predictive of malignancy as single malignant cells.ConclusionBiliary brush cytology specimens performed better than biopsies irrespective of whether they are procured during ERCP or cholangioscopy. The combination of cytology and biopsy had the best accuracy than either one alone.