bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of Hedgehog Signaling by Kappa Opioids to Attenuate Osteoarthritis
Authors: Weber Alexander E. , Jalali Omid , Limfat Sean , Shkhyan Ruzanna , Van Der Horst Robert , Lee Siyoung , Lin Yucheng , Li Liangliang , Mayer Erik N. , Wang Liming , Liu Nancy Q. , Petrigliano Frank A. , Lieberman Jay R. , Evseenko Denis 
Published: April 2020

ObjectiveInhibition of hedgehog (HH) signaling prevents cartilage degeneration and promotes repair in animal models of osteoarthritis (OA). This study, undertaken in OA models and in human OA articular cartilage, was designed to explore whether kappa opioid receptor (KOR) modulation via the inhibition of HH signaling may have therapeutic potential for achieving disease‐modifying activity in OA.MethodsPrimary human articular cartilage and synovial tissue samples from patients with knee OA undergoing total joint replacement and from healthy human subjects were obtained from the National Disease Research Interchange. For in vivo animal studies, a partial medial meniscectomy (PMM) model of knee OA in rats was used. A novel automated 3‐dimensional indentation tester (Mach‐1) was used to quantify the thickness and stiffness properties of the articular cartilage.ResultsInhibition of HH signaling through KOR activation was achieved with a selective peptide agonist, JT09, which reduced HH signaling via the cAMP/CREB pathway in OA human articular chondrocytes (P = 0.002 for treated versus untreated OA chondrocytes). Moreover, JT09 markedly decreased matrix degeneration induced by an HH agonist, SAG, in pig articular chondrocytes and cartilage explants (P = 0.026 versus untreated controls). In vivo application of JT09 via intraarticular injection into the rat knee joint after PMM surgery significantly attenuated articular cartilage degeneration (60% improvement in the tibial plateau; P = 0.021 versus vehicle‐treated controls). In JT09‐treated rats, cartilage content, structure, and functional properties were largely maintained, and osteophyte formation was reduced by 70% (P = 0.005 versus vehicle‐treated controls).ConclusionThe results of this study define a novel mechanism for the role of KOR in articular cartilage homeostasis and disease, providing a potential unifying mechanistic basis for the overlap in disease processes and features involving opioid and HH signaling. Moreover, this study identifies a potential novel therapeutic strategy in which KOR modulation can improve outcomes in patients with OA.
High‐throughput protein precipitation method with 96‐well plate for determination of doxepin and nordoxepin in human plasma using LC–MS/MS
Authors: Margaryan Tigran , Sargsyan Mariam , Gevorgyan Arpine , Zakaryan Hasmik , Aleksanyan Armine , Harutyunyan Armen , Armoudjian Yeghig , Mikayelyan Astghik 
Published: April 2020

AbstractThe aim of this study was to establish a high‐throughput and sensitive LC–MS/MS method for the determination of doxepin and its major active metabolite nordoxepin in human plasma. It has been designed for bioequivalence study for formulations containing 25 mg of doxepin. Doxepin and nordoxepin were extracted from human plasma samples by protein precipitation with acetonitrile by using protein precipitation 96‐well plates. The analyte was separated using a Phenomenex Kinetex Biphenyl column (100 × 2.1 mm, 2.6 μm) using isocratic elution with a mobile phase of 20 mM ammonium formate (30%) and acetonitrile:methanol 3:7 v:v (70%) at a flow rate of 0.5 mL/min and an injection volume of 10 μL. The detection was performed using a triple quadrupole mass spectrometer by multiple reaction monitoring mode to monitor the precursor‐to‐product ion transitions ofm/z280.4 → 107.0 and 283.4 → 235.0 for doxepin and doxepin‐D3, respectively, and 266.3 → 106.9 and 269.3 → 235.0 for nordoxepin and nordoxepin‐D3, respectively, in positive electrospray ionization mode. The total run time was 3.5 min. The method was validated over a concentration range of 50–10,000 pg/mL using a Triple Quad 4500 MS System (Sciex) for both analytes. The developed and validated method can be successfully used to study the bioequivalence/pharmacokinetics of doxepin and nordoxepin.
Downregulated hsa_circ_0077837 and hsa_circ_0004826, facilitate bladder cancer progression and predict poor prognosis for bladder cancer patients
Authors: Shen Chong , Wu Zhouliang , Wang Yujie , Gao Shen , Da La , Xie Linguo , Qie Yunkai , Tian Dawei , Hu Hailong 
Published: April 2020

AbstractGrowing evidence has indicated that circular RNAs (circRNAs) play crucial roles in multiple biological processes. However, alterations in circRNA profiles during bladder cancer progression and the clinical significance thereof remain unclear. Therefore, high‐throughput RNA sequencing was conducted to identify circRNA and mRNA profiles in five pairs of bladder cancer tissues and adjacent noncancerous tissues. A total of 87 differentially expressed circRNAs and 2756 mRNAs were detected in above bladder cancer samples compared with paired noncancerous samples. Functional enrichment analyses, circRNA‐microRNA‐mRNA, and protein‐protein interaction networks revealed that these dysregulated circRNAs were potentially involved in carcinogenesis and evolution of bladder cancer. Subsequently, the differential expression of eight circRNAs was detected by real‐time qPCR. Hsa_circ_0003141 and hsa_circ_0008039 were significantly upregulated as well as hsa_circ_0026782, hsa_circ_0077837, hsa_circ_0004826, and hsa_circ_0001946 were significantly downregulated among validation of 70 matched bladder cancer tissues (≥75%). Moreover, hsa_circ_0077837 and hsa_circ_0004826 were also verified as markedly downregulated in four bladder cancer cells (100%). Naturally, hsa_circ_0077837 and hsa_circ_0004826 were also demonstrated using RNase‐R+ resistance experiments. In addition, Fisherʹs exact test, Kaplan‐Meier plots, Cox regression analyses, and receiver operating characteristic curve was performed to assess their clinical value. Downregulation of hsa_circ_0077837 and hsa_circ_0004826 all was significantly correlated with worse clinicopathological features and poor prognosis of bladder cancer patients. The area under the receiver operating characteristic curve of them was 0.775 (P < .0001) and 0.790 (P < .0001), respectively. Not surprisingly, in vitro functional experiments also demonstrated that the overexpression of hsa_circ_0077837 and hsa_circ_0004826 significantly weakened the proliferation, migration, and invasion of bladder cancer cells. Overall, hsa_circ_0077837 and hsa_circ_0004826 might act as tumor suppressors in the bladder cancer progression and serve as a potential biomarker for the diagnosis, prognosis, and therapy of bladder cancer.
Toxicity and efficacy of Gamma Knife radiosurgery for brain metastases in melanoma patients treated with immunotherapy or targeted therapy—A retrospective cohort study
Authors: Gatterbauer Brigitte , Hirschmann Dorian , Eberherr Nadine , Untersteiner Helena , Cho Anna , Shaltout Abdallah , Göbl Philipp , Fitschek Fabian , Dorfer Christian , Wolfsberger Stefan , Kasprian Gregor , Höller Christoph , Frischer Josa M. 
Published: April 2020

AbstractBackgroundFew safety data of concurrent stereotactic radiosurgery and targeted therapy (TT) or immunotherapy (IT) are available. The aim of the study was to evaluate the outcome of melanoma patients with brain metastases (MBM) after Gamma Knife Radiosurgery (GKRS) in relation to IT/TT.MethodsWe evaluated 182 MBM patients, who were treated with GKRS in the modern radiosurgical and oncological era.ResultsThe median time between the initial melanoma diagnosis and occurrence of MBM was 2.4 years. The median overall survival time was 5.4 years after melanoma diagnosis. The estimated median survival after the initial diagnosis of MBM was 1.0 year (95% CI = 0.7‐1.2 years). Patients treated with anti‐PD‐1 or a combination of anti‐CTLA‐4/PD‐1 showed a significantly longer survival after first GKRS compared to all other forms of treatment. In addition, patients treated with anti‐PD‐1, anti‐CTLA‐4, or a combination of anti‐CTLA‐4/PD‐1 showed a significantly longer time to new MBM after GKRS1 compared to patients treated with other forms and combinations of the oncological therapy. The occurrence of hemorrhage or radiation reaction/necrosis after GKRS did not show any statistically significant differences in relation to IT/TT.ConclusionIn MBM patients, complications after GKRS are not significantly increased if IT/TT treatment is performed at the time of or after radiosurgery. Further, a clear benefit in distant control and survival is seen in MBM patients treated with GKRS and checkpoint inhibitors. Thus, concomitant treatment of MBM with GKRS and IT/TT seems to be a safe and powerful treatment option although further prospective studies should be conducted.
Reflective‐verbal language and reverie in a qualitative interview
Authors: McVey Lynn , Lees John , Nolan Greg 
Published: April 2020

AbstractBackgroundIn contrast to dominant approaches to therapy research that look at outcomes and focus on large samples, another primary strand of research considers microphenomenal processes and focuses on small samples. This study contributes to the latter genre in regard to the implicit impact of language.AimThis study aims to apply relational psychotherapeutic thinking about empathic dialogue, specifically the concepts of reflective‐verbal language and reverie, to qualitative interviewing.MethodologyAn example from a small‐scale study about emotionally evocative language is reviewed in detail, focusing on the interviewer's phenomenological experience of her conversation with a participant in a qualitative interview.FindingsThe authors argue that the interviewer's reflexive awareness of her reveries and the reflective‐verbal nature of the research dialogue gave her an alternative perspective on the participant's (and her own) experience.ImplicationsThe study highlights the value within research and practice of maintaining awareness of language at a microphenomenal level, using techniques based on the principles of psychological therapy.
Mindsets, shopping motivations and compulsive buying: Insights from China
Authors: Japutra Arnold , Song Zening 
Published: April 2020

AbstractThis study investigates how mindsets (i.e., the beliefs that individuals have about the nature of human characteristics) are associated with compulsive buying behavior (i.e., the tendency to buy impulsively and obsessively). In particular, we test the relationships between consumer mindsets, three shopping motivations (deal proneness, social comparison, and hedonic motives) and compulsive buying. Based on a survey of 421 respondents conducted in China, our findings reveal the mechanism through which mindsets affect compulsive buying. The results show that when consumers believe in the consistency of personal traits (fixed mindset), they tend to be more vulnerable to deal offers and social comparison. These motivations increase the desire to seek hedonic pleasure, which is associated with a greater propensity for compulsive buying. However, when consumers believe that personal traits can be changed and developed (growth mindset), they seek hedonic pleasure in shopping, which result in a greater tendency to engage in compulsive buying. The present study adds to the existing body of knowledge by unveiling how different mindsets are associated with compulsive buying. In terms of practical implications, this study provides policy makers and marketers with a better understanding of the different motivations that lead to compulsive buying.
Triage considerations for patients referred for structural heart disease intervention during the COVID‐19 pandemic: An ACC/SCAI position statement
Authors: Shah Pinak B. , Welt Frederick G. P. , Mahmud Ehtisham , Phillips Alistair , Kleiman Neal S. , Young Michael N. , Sherwood Matthew , Batchelor Wayne , Wang Dee Dee , Davidson Laura , Wyman Janet , Kadavath Sabeeda , Szerlip Molly , Hermiller James , Fullerton David , Anwaruddin Saif 
Published: April 2020

AbstractThe coronavirus disease‐2019 (COVID‐19) pandemic has strained health care resources around the world, causing many institutions to curtail or stop elective procedures. This has resulted in an inability to care for patients with valvular and structural heart disease in a timely fashion, potentially placing these patients at increased risk for adverse cardiovascular complications, including CHF and death. The effective triage of these patients has become challenging in the current environment, as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID‐19 pandemic against the risk of delaying a needed procedure. In this document, the authors suggest guidelines for how to triage patients in need of structural heart disease interventions and provide a framework for how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, the authors address the triage of patients in need of transcatheter aortic valve replacement and percutaneous mitral valve repair. The authors also address procedural issues and considerations for the function of structural heart disease teams during the COVID‐19 pandemic.
Antioxidant, anti‐inflammatory, and antitumor activities of phenolic compounds from white, red, and black Chenopodium quinoa seed
Authors: Liu Mengjie , Zhu Kaili , Yao Yang , Chen Yinhuan , Guo Huimin , Ren Guixing , Yang Xiushi , Li Jincai 
Published: April 2020

AbstractBackground and objectivesQuinoa (Chenopodium quinoa Willd.) is a promising nutritious cereal known for its rich nutrition and diverse physiological activities. In order to further investigate the profiles and physiological activities of phenolic compounds from quinoa, the composition of free and bound phenolic extracts from white, red, and black quinoa were analyzed, as well as their antioxidant, anti‐inflammatory, and antitumor activities.FindingsTotal phenolic content (TPC) and total flavonoid content (TFC) ranged from 514.03 to 1,409.54 mg gallic acid equivalent (GAE)/100g and 177.49 to 407.75 mg rutin equivalent (RE)/100 g, respectively. TPC existed mainly in bound form in red and black quinoa, but free form in white quinoa. Eight individual phenolic acids were detected, with the total acids amount ranging from 86.21 to 188.76 µg/g. Protocatechuic acid was the dominant phenolic acid both in red and black quinoa. Red quinoa showed the highest TPC and TFC, while black quinoa had the highest phenolic acids concentration. Red quinoa also showed the best ABTS and DPPH radical scavenging activities. Positive correlations were found among antioxidant activity and phenolic components. Besides, phenolics from red and black quinoa showed better anti‐inflammatory and antitumor activity by down‐regulating the NO production and inhibiting the proliferation of MCF‐7 cells.ConclusionsQuinoa seed is rich in phenolic components, especially the red and black one. Higher phenolic contents in red and black quinoa can be responsible for their superior antioxidant, anti‐inflammatory, and antitumor activities. With potential health benefits, quinoa phenolics may be used as ingredients for functional food.Significance and noveltyFindings of this study revealed useful information on phenolics and bioactivity of quinoa for its cultivation and breeding with functional oriented purpose. The results could be also applied in health food industry for quinoa material selection and processing.
Spray‐Flame‐Prepared LaCo1–xFexO3 Perovskite Nanoparticles as Active OER Catalysts: Influence of Fe Content and Low‐Temperature Heating
Authors: Alkan Baris , Medina Danea , Landers Joachim , Heidelmann Markus , Hagemann Ulrich , Salamon Soma , Andronescu Corina , Wende Heiko , Schulz Christof , Schuhmann Wolfgang , Wiggers Hartmut 
Published: April 2020

AbstractSpray‐flame synthesis was used to produce high‐surface‐area perovskite electrocatalysts with high phase purity, minimum surface contamination, and high electrochemical stability. In this study, as‐prepared LaCo1–xFexO3 perovskite nanoparticles (x=0.2, 0.3, and 0.4) were found to contain a high degree of combustion residuals, and mostly consist of both, stoichiometric and oxygen‐deficient perovskite phases. Heating them at moderate temperature (250 °C) in oxygen could remove combustion residuals and increases the content of stoichiometric perovskite while preventing particle growth. A higher surface crystallinity was observed with increasing iron content coming along with a rise in oxygen deficient phases. With heat treatment, OER activity and stability of perovskites improved at 30 and 40 at.% Fe while deteriorating at 20 at.% Fe. This study highlights spray‐flame synthesis as a promising technique to synthesize highly active nanoscale perovskite catalysts with improved OER activity.
Chemistry of NOx and HNO3 Molecules with Gas‐Phase Hydrated O.− and OH− Ions
Authors: Lengyel Jozef , Ončák Milan , Beyer Martin K. 
Published: April 2020

AbstractThe gas‐phase reactions of O.−(H2O)n and OH−(H2O)n, n=20–38, with nitrogen‐containing atmospherically relevant molecules, namely NOx and HNO3, are studied by Fourier transform ion cyclotron resonance (FT‐ICR) mass spectrometry and theoretically with the use of DFT calculations. Hydrated O.− anions oxidize NO. and NO2. to NO2− and NO3− through a strongly exothermic reaction with enthalpy of −263±47 kJ mol−1 and −286±42 kJ mol−1, indicating a covalent bond formation. Comparison of the rate coefficients with collision models shows that the reactions are kinetically slow with 3.3 and 6.5 % collision efficiency. Reactions between hydrated OH− anions and nitric oxides were not observed in the present experiment and are most likely thermodynamically hindered. In contrast, both hydrated anions are reactive toward HNO3 through proton transfer from nitric acid, yielding hydrated NO3−. Although HNO3 is efficiently picked‐up by the water clusters, forming (HNO3)0–2(H2O)mNO3− clusters, the overall kinetics of nitrate formation are slow and correspond to an efficiency below 10 %. Combination of the measured reaction thermochemistry with literature values in thermochemical cycles yields ΔHf(O−(aq.))=48±42 kJ mol−1 and ΔHf(NO2−(aq.))=−125±63 kJ mol−1.
A Single‐Dose, Open‐Label, Randomized, Two‐Way Crossover Study in Healthy Japanese Participants to Evaluate the Bioequivalence and the Food Effect on the Pharmacokinetics of Daprodustat
Authors: Yamada Masanori , Osamura Minori , Ogura Hirofumi , Onoue Tomohiro , Wakamatsu Akira , Numachi Yotaro , Caltabiano Stephen , Mahar Kelly M. 
Published: April 2020

AbstractDaprodustat is a prolyl hydroxylase inhibitor that stimulates erythropoiesis in a manner similar to the natural response to hypoxia, whereby inhibition of hypoxia inducible factor (HIF) prolyl‐4‐hydroxylases by daprodustat ultimately results in increased levels of HIF‐responsive genes. Daprodustat is under development as an emerging new class of agents for the treatment of anemia associated with chronic kidney disease (CKD). This was a single‐center, single‐dose, open‐label, randomized, 2‐way crossover study in healthy Japanese male participants consisting of 2 parts. The primary objective was to evaluate the bioequivalence (BE) between daprodustat tablet strengths (part 1) and to evaluate the food effect on the pharmacokinetics (PK) of daprodustat (part 2). A total of 64 healthy Japanese male participants were enrolled; 52 participants were included in part 1 and 12 in part 2. BE was demonstrated between the daprodustat 2‐mg tablet and the daprodustat 4‐mg tablet. A standard CKD meal did not have a large effect on the PK parameters of daprodustat after a single oral dose of daprodustat 4 mg. Administration of single oral doses of daprodustat 4 mg was generally well tolerated in the healthy Japanese participants, and no new safety signals were identified without regard to food.
Influence of TMAO as co‐solvent on the gelation of silica‐PNIPAm core‐shell nanogels at intermediate volume fractions
Authors: Frenzel Lara , Lokteva Irina , Koof Michael , Narayanan Suresh , Grübel Gerhard , Lehmkühler Felix 
Published: April 2020

AbstractWe study the structure and dynamics of poly(N‐isopropylacrylamide) (PNIPAm) core‐shell nanogels dispersed in aqueous trimethylamine N‐oxide (TMAO) solutions by means of small‐angle X‐ray scattering and X‐ray photon correlation spectroscopy (XPCS). Upon increasing the temperature above the lower critical solution temperature of PNIPAm at 33 °C, a colloidal gel is formed as identified by an increase of I(q) at small q as well as a slowing down of sample dynamics by various orders of magnitude. With increasing TMAO concentration the gelation transition shifts linearly to lower temperatures. Above a TMAO concentration of approximately 0.40 mol/L corresponding to a 1 : 1 ratio of TMAO and NIPAm groups, collapsed PNIPAm states are found for all temperatures without any gelation transition. This suggests that reduction of PNIPAm‐water hydrogen bonds due to the presence of TMAO results in a stabilisation of the collapsed PNIPAm state and suppresses gelation of the nanogel.
The Decay Mechanism Related to Structural and Morphological Evolution in Lithium‐Rich Cathode Materials for Lithium‐Ion Batteries
Authors: Liu Qiong , Zheng Wei , Lu Zhouguang , Zhang Xuan , Wan Kai , Luo Jiangshui , Fransaer Jan 
Published: April 2020

AbstractLi‐rich oxides have garnered intense interest recently for their excellent capacity in rechargeable lithium‐ion batteries (LIBs). However, poor cycling stability and capacity degradation during the cycling process impede their practical application. Herein, two ball‐shaped cobalt‐free oxide materials, Li1.1Mg0.05Ni0.3Mn0.55O2 and Li1.1Zn0.05Ni0.3Mn0.55O2, which exhibit excellent cycling performance at a high current between 2 V and 4.8 V, are demonstrated. The two Li‐rich materials are prepared from hydrothermally synthesized carbonated precursors. Both oxides exhibit high reversible capacities of 237 and 231 mAh g−1 at 20 mA g−1, respectively, originating from the redox of Ni2+/Ni4+ and O2−/(O2)n−. Li1.1Mg0.05Ni0.3Mn0.55O2 presents excellent cycling stability after 200 cycles with 90 % capacity retention. Studies of the structural evolution upon electrochemical cycling implies the cathodes undergo a volume expansion, which results in continuous expanding, cracking, and crushing of the spherical particles, which further induces capacity fading in the cathodes.