bluuebunny/crossref_metadata_2025_split huggingface dataset:
Private debt overhang and the government spending multiplier: Evidence for the United States
Authors: Bernardini Marco , Peersman Gert 
Published: April 2018

SummaryUsing state‐dependent local projections and historical US data, we find that government spending multipliers are considerably larger in periods of private debt overhang. In particular, while multipliers are below or close to one in low private debt states, we find significant crowding‐in of private spending in periods of debt overhang, resulting in multipliers that are much larger than one. In high private debt episodes, more government purchases even reduce the ratio of government debt to gross domestic product. These results are robust for the type of shocks, and when we control for the business cycle, financial crises, deleveraging episodes, government debt overhang, and the zero‐lower‐bound.
Chondrogenic response in presence of cartilage extracellular matrix nanoparticles
Authors: Zahiri Saeed , Masaeli Elahe , Poorazizi Elahe , Nasr‐Esfahani Mohammad Hossein 
Published: April 2018

AbstractCurrent studies based on regenerative medicine suggest, decellularized extracellular matrix (DC‐ECM) components can regulate cell phenotype. In this regard, it is believed, presence of cartilage extracellular matrix particles in culture condition could produce physical and biochemical supportive cues for chondrogenesis. In this study, DC‐ECM nanoparticles with average size of 61.5± 22.4 nm were produced by decellularization and mechanical processing. Homogenous distribution and nanoscale size of yield particles were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) microscopy imaging. Chemical structure preservation of cartilage ECM after decellularization was also confirmed by typical Fourier transform infrared (FTIR) spectrum mapping. The influence these nanoparticles on chondrogenic response of chondrocyte cells was investigated by direct and indirect addition of nanoparticles to culture medium. A clinical devitalized cartilage powder (DV‐ECM) was also used as a positive control. Totally, MTS results showed that direct and indirect presence of both DC‐ECM and DV‐ECM particles in culture medium enhanced cellular metabolic activity except on day one of culture. Furthermore, on day 21, SOX9 and COL2 expression of cultured chondrocytes in the medium containing DC‐ECM nanoparticles were up‐regulated in comparison to negative control, which was further confirmed by presence more frequent number of larger size lacunae in micromass spheroids. Our findings support the use of ECM nanoparticles as condition supplement in culture medium and injectable biomaterials, especially for cell‐based therapies for cartilage regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2463–2471, 2018.
Healing bone lesion defects using injectable CaSO4/CaPO4‐TCP bone graft substitute compared to cancellous allograft bone chips in a canine model
Authors: Hall Deborah J. , Turner Thomas M. , Urban Robert M. 
Published: April 2018

AbstractCaSO4/CaPO4‐TCP bone graft substitute has been shown to be effective for treatment of bone lesion defects, but its mechanical, histological, and radiographic characteristics have not been studied in direct comparison with a conventional treatment such as cancellous allograft bone. Thirteen canines had a critical‐size axial defect created bilaterally into the proximal humerus. CaSO4/CaPO4‐TCP bone graft substitute (PRO‐DENSE™, Wright Medical Technology) was injected into the defect in one humerus, and an equal volume of freeze‐dried cancellous allograft bone chips was placed in the contralateral defect. The area fraction of new bone, residual graft, and fibrous tissue and the compressive strength and elastic modulus of bone within the defects were determined after 6, 13, or 26 weeks and correlated with radiographic changes. The data were analyzed using Friedman and Mann–Whitney tests. There was more bone in defects treated with the CaSO4/CaPO4‐TCP bone graft substitute compared to defects treated with cancellous bone allograft at all three time points, and the difference at 13 weeks was significant (p = 0.025). The new bone was significantly stronger and stiffer in defects treated with the CaSO4/CaPO4‐TCP bone graft substitute compared to defects treated with cancellous bone allograft at 13 (p = 0.046) and 26 weeks (p = 0.025). At 26 weeks, all defects treated with CaSO4/CaPO4‐TCP bone graft substitute demonstrated complete healing with new bone, whereas healing was incomplete in all defects treated with cancellous allograft chips. The CaSO4/CaPO4‐TCP bone graft substitute could provide faster and significantly stronger healing of bone lesions compared to the conventional treatment using freeze‐dried cancellous allograft bone. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 408–414, 2019.
Retracted: Protective effects of Progranulin against focal cerebral ischemia‐reperfusion injury in rats by suppressing endoplasmic reticulum stress and NF‐κB activation in reactive astrocytes
Authors: Shu Qing , Fan Hua , Li Shi‐Jun , Zhou Dan , Ma Wei , Zhao Xiao‐Yan , Yan Jun‐Qiang , Wu Gang 
Published: April 2018

AbstractThe aim of this study is to explore the effect progranulin (PGRN) has on endoplasmic reticulum (ER) stress and the NF‐κB activation in reactive astrocytes found in rat models with focal cerebral ischemia‐reperfusion (I/R) injury. Sprague‐Dawley (SD) rats were grouped into the sham, I/R, PGRN‐high dose, PGRN‐low dose, and negative control (NC) groups. TTC staining was applied in order to detect the cerebral infarction volume, a TUNEL assay to detect the apoptosis rate of neurons, an ELISA to measure MDA, SOD, iNOS, LDH, TNF‐α, IL‐1β, IL‐6, and IL‐10 levels, and both RT‐qPCR and western blotting methods in order to detect PGRN, GFAP, GRP78, CHOP, and NF‐κB p65 expressions. The astrocytes (AST) cells were then assigned into the normal, I/R, negative control (NC), PGRN‐high dose, and PGRN‐low dose groups. After completing the transfection process, the proliferative capacity of AST cells was detected by use of the CCK‐8 assay. Both the in vivo and in vitro results, in comparison with the I/R and the NC groups, the PGRN‐high dose and PGRN‐low dose groups both presented a decrease in cerebral infarction volume, apoptosis rate of neurons, MDA, LDH, iNOS, TNF‐α, IL‐1β, IL‐6 levels, and GFAP, GRP78, CHOP, NF‐κB p65 expressions, and an increase in SOD, IL‐10, and PGRN levels as well as cell proliferation depending on dosage. Based on our results, we came to the confirmation that PGRN can reduce neuronal apoptosis by mitigating ER stress in the reactive astrocytes as well as downregulating the inflammatory levels by suppressing the NF‐κB signaling pathway.
The role of high‐mobility group protein box 1 in lung cancer
Authors: Wu Xiao‐Jin , Chen Yuan‐Yuan , Gong Chan‐Chan , Pei Dong‐Sheng 
Published: April 2018

AbstractHigh‐mobility group protein box 1(HMGB1)is a ubiquitous highly conserved nuclear protein. Acting as a chromatin‐binding factor, HMGB1 binds to DNA and plays an important role in stabilizing nucleosome formation, facilitating gene transcription, DNA repairing, inflammation, cell differentiation, and regulating the activity of steroid hormone receptors. Currently, HMGB1 is discovered to be related to development, progression, and targeted therapy of lung cancer, which makes it an attractive biomarker, and therapeutic target. This review aims to encapsulate the relationship between HMGB1 and lung cancer, suggesting that HMGB1 plays a pivotal role in initiation, development, invasion, metastasis, and prognosis of lung cancer.
S6K1 controls epigenetic plasticity for the expression of pancreatic α/β cell marker genes
Authors: Yi Sang Ah , Lee Jieun , Park Jong Woo , Han Jihoon , Lee Min Gyu , Nam Ki Hong , Park Jee Hun , Oh Hwamok , Ahn Sung Jin , Kim Saetbyul , Kwon So Hee , Jo Dong‐Gyu , Han Jeung‐Whan 
Published: April 2018

AbstractThe failure of insulin production by pancreatic β cells is a common hallmark of type 1 diabetes mellitus (T1DM). Because administration of exogenous insulin is associated with diabetes‐derived complications, endogenous α to β cell transition can be an attractive alternative. Although decreased β cell size and hypoinsulinaemia have been observed in S6K1‐deficient mice, the molecular mechanism underlying the involvement of S6K1 in the transcriptional regulation of insulin remains elusive. Here, we show that the hypoinsulinaemic phenotype of S6K1‐deficient mice stems from the dysregulated transcription of a set of genes required for insulin and glucagon production. First, we observed that increased expression of α cell marker genes and decreased expression of β cell marker genes in pancreas tissues from S6K1‐deficient mice. Furthermore, S6K1 was highly activated in murine β cell line, βTC6, compared to murine α cell line αTC1. In both α and β cells, active S6K1 promoted the transcription of β cell marker genes, including insulin, whereas S6K1 inhibition increased the transcription of α cell marker genes. Moreover, S6K1 mediated pancreatic gene regulation by modifying two histone marks (activating H3K4me3 and repressing H3K27me3) on gene promoters. These results suggest that S6K1 drives the α to β transition through the epigenetic regulation of cell‐specific genes, including insulin and glucagon. This novel role of S6K1 in islet cells provides basic clues to establish therapeutic strategies against T1DM.
Hyperbaric oxygen treatment sensitizes gastric cancer cells to melatonin‐induced apoptosis through multiple pathways
Authors: Wei Xiang , Qi Yinliang , Jia Ning , Zhou Qing , Zhang Sumei , Wang Yuan 
Published: April 2018

AbstractAlthough extensive efforts have been made in recent decades to treat advanced gastric cancer with comprehensive therapy based on chemotherapy, effective anti‐gastric cancer therapeutics are still lacking in the clinics. Therefore, potent novel anti‐gastric cancer ways are greatly needed. Here, we explored hyperbaric oxygen treatment as a novel and effective adjuvant treatment method which has anti‐gastric cancer effects when used together with melatonin. When performed together with MLT, HBO effectively inhibited tumorigenicity of gastric cancer through selectively inducing a robust tumor suppressive apoptosis response. Mechanistic studies revealed that the sensitizing effect of hyperbaric oxygen is due to decreased ratio of Bcl‐2/Bax, increased level of p53, cleaved Caspase3, GRP78, CHOP, and LC3. These results give a vivid picture that classic apoptosis pathways including mitochondrial pathway, tumor suppressive endoplasmic reticulum stress (ERS), and autophagy are all involved in the process. From the preliminary results got from the current study, we identified that HBO sensitizes human gastric cancer cells to MLT‐induced apoptosis through a variety of complicated molecular mechanisms. HBO may provide a novel candidate supplemental treatment method for further development of potential anti‐gastric cancer therapeutics. The combination of HBO and MLT could be a promising treatment for advanced gastric cancer.
Dual Targeting Autoimmunity and Cancer: From Biology to Medicine
Authors: Chen Daohong 
Published: April 2018

AbstractCancer is known to be often associated with autoimmunity/inflammation epidemically and pathologically. Although comprehensive mechanisms behind the link of these 2 medical conditions are yet to be elucidated, cumulated biological evidence has pointed to an array of molecular pathways that are shared in the pathogenesis of cancer and autoimmunity. Herein, this article presents the representative druggable cellular proteins that substantially contribute to the development of the 2 medical conditions, in particular highlighting the recently approved medications that target these molecular pathways to corroborate the link between autoimmunity and cancer from the therapeutic perspective. It will ideally help to minimize a knowledge gap, not only regarding mechanistic information across these biomedical fields but also for clinicians and pharmaceutical innovation to deal with the challenges of preventing or managing patients with concomitant cancer and autoimmunity taking advantage of an optimally efficient medication.
Bidirectional Pharmacokinetic Interaction Between Amodiaquine and Pioglitazone in Healthy Subjects
Authors: Edema Opeyemi , Adeagbo Babatunde A. , Adehin Ayorinde , Olugbade Tiwalade A. 
Published: April 2018

AbstractAmodiaquine (AQ) and pioglitazone (PGZ) are both metabolized by CYP2C8, an enzyme also inhibited by PGZ. These drugs are likely to be administered in instances of comorbidity of malaria with type 2 diabetes. This study, hence, evaluated the possibility of a drug interaction resulting from the concurrent use of both drugs. A 3‐period crossover design in 10 healthy subjects, that assessed the disposition of AQ and PGZ alone and when coadministered, was implemented with the administration of single oral doses of AQ and PGZ. Whole‐blood samples collected between 0 and 24 hours on protein saver cards across the study periods were processed and analyzed for AQ and PGZ contents. Pharmacokinetic parameters were derived by a noncompartmental analysis. Geometric mean ratios for the Cmax, area under the concentration‐time curve for 24 hours (AUC0‐24h), and AUC0‐∞, alongside their corresponding 90%CIs, were compared across the study periods to infer clinically significant changes in disposition. The coadministration of AQ and PGZ resulted in decreases of about 38% and 54% in the Cmax and AUC0‐24h of AQ, respectively. For PGZ, the Cmax increased by about 50%, and AUC0‐24 rose by 48%. The 90%CIs of geometric mean ratios for the Cmax, AUC0‐24h, and AUC0‐∞ were all outside the expected bioequivalence interval of 80% to 125% for both drugs, implying significant interactions. These findings suggest that a bidirectional interaction between AQ and PGZ, with likely implications for the therapy and toxicity of both drugs, may occur in the event of their coadministration.
Phase 1 First‐in‐Human, Single‐ and Multiple‐Ascending Dose, and Food Effect Studies to Assess the Safety, Tolerability, and Pharmacokinetics of Presatovir for the Treatment of Respiratory Syncytial Virus Infection
Authors: German Polina , Xin Yan , Chien Jason W. , Weng Winnie , Mackman Richard , Lewis Sandra A. , Meng Amy , Ling John , Mathias Anita 
Published: April 2018

AbstractRespiratory syncytial virus (RSV)‐associated respiratory tract infection is a leading cause of hospitalizations in infants for which no effective treatment exists. RSV infection is also an important cause of respiratory disease in adults and immunocompromised patients. Presatovir (GS‐5806) is an orally bioavailable antiviral agent that inhibits fusion of RSV with host cell membranes. Here, results from 2 phase 1 studies that evaluated safety, tolerability, and pharmacokinetics of presatovir in healthy adults following administration of single and multiple (7 days) once‐ or twice‐daily ascending doses (first‐in‐human study) and in the presence or absence of food (food effect study) are described. Presatovir exhibited favorable safety and pharmacokinetic profiles that supported once‐daily dosing. Presatovir exposure increased in an approximately dose‐proportional manner across the evaluated dose range (single doses 25‐300 mg; multiple doses 10‐75 mg once daily for 7 days). Administration of presatovir with a high‐fat meal did not alter exposure, supporting administration without regard to a meal in further clinical studies. These data were subsequently used to inform presatovir dosing regimens in a phase 2a challenge study of adults experimentally infected with RSV. Collectively, results from phase 1 evaluations and a phase 2a challenge study support further clinical investigation of presatovir for the treatment of RSV infection.
Midazolam Single Time Point Concentrations to Estimate Exposure and Cytochrome P450 (CYP) 3A Constitutive Activity Utilizing Limited Sampling Strategy With a Population Pharmacokinetic Approach
Authors: Yang Jincheng , Patel Maulik , Nikanjam Mina , Capparelli Edmund V. , Tsunoda Shirley M. , Greenberg Howard E. , Penzak Scott R. , Aubrey Stoch S. , Bertino Joseph S. , Nafziger Anne N. , Ma Joseph D. 
Published: April 2018

AbstractMidazolam is the preferred probe to phenotype cytochrome P450 (CYP) 3A activity. This study evaluated a single‐concentration, midazolam limited sampling strategy utilizing a population pharmacokinetic (PK) approach to estimate area under the curve, and thus CYP3A activity. Midazolam concentrations from adults during CYP3A constitutive conditions were obtained from previous studies after single, oral or intravenous administration. Population PK modeling was conducted by nonlinear mixed‐effects modeling. Potential covariates of clearance, volume of distribution, and bioavailability were evaluated. A limited sampling model at 1, 2, 4, or 6 hours was selected and fitted with post hoc estimation with the final population PK model. Preset criterion for the limited sampling model selection was a coefficient of determination ≥0.9. Bias and precision were also evaluated. The studies provided 2122 observations from 152 healthy adults. Midazolam concentrations were adequately described by a two‐compartment model with first order absorption. Age and sex were significant covariates of central volume (V2) and were retained in the final model. An estimate (interindividual variability) of midazolam clearance was 32.5 L/hr (52.9%), covariate of central volume was 67 L (39.1%), and oral bioavailability was 0.33 (45.5%). The final population parameter estimates were within the 95% confidence intervals and were similar to the median bootstrap estimates. Upon comparison to the population PK model, the 4‐hour limited sampling model estimated area under the curve had an acceptable coefficient of determination and acceptable bias and precision limits. A 4‐hour, but not the 1‐, 2‐, and 6‐hour, single concentration accurately estimated midazolam area under the curve during constitutive CYP3A conditions in healthy adults.
The Effects of Linguistic Devices on Consumer Information Processing and Persuasion: A Language Complexity × Processing Mode Framework
Authors: Pogacar Ruth , Shrum L. J. , Lowrey Tina M. 
Published: April 2018

People—be they politicians, marketers, job candidates, product reviewers, or romantic interests—often use linguistic devices to persuade others, and there is a sizeable literature that has documented the effects of numerous linguistic devices. However, understanding the implications of these effects is difficult without an organizing framework. To this end, we introduce a Language Complexity × Processing Mode Framework for classifying linguistic devices based on two continuous dimensions: language complexity, ranging from simple to complex, and processing mode, ranging from automatic to controlled. We then use the framework as a basis for reviewing and synthesizing extant research on the effects of the linguistic devices on persuasion, determining the conditions under which the effectiveness of the linguistic devices can be maximized, and reconciling inconsistencies in prior research.
Physiological and biochemical responses of Dosinia corrugata to different thermal and salinity stressors
Authors: Nie Hongtao , Zuo Shuqi , Li Long , Tian Cun , Cao Chen , Yan Xiwu 
Published: April 2018

AbstractTemperature and salinity are major factors affecting geographic distribution, reproduction, and physiological processes of marine and estuarine organisms. In this study, the effects of different temperatures and salinity on the respiratory metabolism and physiological response were evaluated in D. corrugata by measuring oxygen consumption rate (OCR), ammonia excretion rate (AER), and glycolytic enzyme activity. An increase in the OCR of D. corrugata with increasing temperature was observed. No peak of oxygen consumption was observed in D. corrugata over the temperature range evaluated. There was an increase in AERs with increasing temperature and salinity, respectively. With increasing salinity, the enzyme activity increased until it reached a peak at a salinity of 30 ppt, while the highest HK and LDH activity was observed at a salinity of 25 ppt. Our results may be used to optimize the temperature and salinity conditions for optimal growth and survival of D. corrugata and to provide basic information for conservation management and fishing moratorium of this economically important bivalve species. The enzyme activity decreased slightly from 15 to 20°C, but when the temperature exceeded 20°C, enzyme activity increased, reaching a maximum at 30°C (tested range of 10–30°C). With increasing salinity, the enzyme activity increased until it reached a peak at a salinity of 30 ppt, but once the salinity was greater than 30 ppt, the enzyme activity began to decrease up to salinity of 35 ppt.
Design, Synthesis, and Evaluation of the Anticancer Properties of Novel Quinone Bearing Carbamyl β‐Lactam Hybrids
Authors: Payili Nagaraju , Yennam Satyanarayana , Rekula Santhosh Reddy , Naidu Challa Gangu , Bobde Yamini , Ghosh Balaram 
Published: April 2018

This paper describes a simple and practical protocol for the direct synthesis of a series of new hybrid molecules of carbamyl β‐lactam derivatives bearing quinone moiety via [2 + 2] cycloaddition of Staudinger reaction. The β‐lactam ring is tolerating carbamylation and further leads to a variety of quinone hybrid derivatives. The structures of the compounds were characterized by IR, MS, nuclear magnetic resonance, and high‐resolution mass spectra analysis. All the new synthesized compounds were screened for their in vitro antiproliferative activity using an MTT assay analysis. Out of 14 derivatives synthesized in the current study, compounds 9h, 9k, 9i, and 9b exhibited the very good anticancer activities in B16F10 cell line.
The effect of economic consequences on social judgment and choice: Reward interdependence and the preference for sociability versus competence
Authors: Belmi Peter , Pfeffer Jeffrey 
Published: April 2018

SummaryCompetence and sociability (warmth) are fundamental dimensions of social judgment in organizations. However, these qualities are frequently seen as negatively related, with mixed evidence on which is more important. In three studies (N = 993), we investigated the effects of reward interdependence on the preference for sociability versus competence. We predicted that reward interdependence would elicit a more instrumental, calculative mindset, which in turn, would lead individuals to value competence more. Study 1 surveyed working adults who were in actual work groups and found that those who worked in more (vs. less) reward interdependent environments were more likely to think instrumentally and calculatively when considering potential colleagues. This mindset, in turn, was associated with a greater tendency to value competence over sociability. Studies 2 and 3 used an experimental design and found that when people imagined or anticipated working in a situation in which their economic outcomes depended in part on others, they were more likely to adopt an instrumental focus and choose a “competent jerk” over a “lovable fool.” These results call into question a vast social judgment literature that has made claims about the importance of sociability and related constructs without considering the context, and particularly the reward interdependence, often inherent in organizational contexts.