bluuebunny/crossref_metadata_2025_split huggingface dataset:
Valuing health using EQ‐5D: The impact of chronic diseases on the stock of health
Authors: Sánchez‐Iriso Eduardo , Errea Rodríguez Maria , Cabasés Hita Juan Manuel 
Published: September 2019

AbstractChronic diseases strongly affect individuals' health status. In aggregate terms, this impact is reflected by the stock of health, which measures the amount of health of a population in a given period of time.The objectives of this study were to measure the relative burden of chronic illnesses by assessing health‐related quality of life using the EQ‐5D‐5L instrument, to rank diseases according to their associations with the stock of health, and to calculate the stock of health of the Spanish population and the amount of health loss attributable to each chronic disease from a social perspective.Data were gathered from the Spanish Health Survey (ENSE 2011–2012, N = 20,587). A population weighted least squares model was used.Chronic diseases represent 19.19% of the stock of health losses in Spain compared with a country free from those diseases. In Spain, the stock of health in 2011 was 31.86 million units on the visual analog scale.The diseases with the strongest impact in terms of loss of stock of health at the individual level were mental illness and embolism, stroke, or cerebral hemorrhage. Collectively, the diseases with the largest impact included osteoarthritis, arthritis, or rheumatism; chronic back pain; and high blood pressure.
Monoacylglycerol Lipase Inhibition Protects From Liver Injury in Mouse Models of Sclerosing Cholangitis
Authors: Tardelli Matteo , Bruschi Francesca V. , Fuchs Claudia D. , Claudel Thierry , Auer Nicole , Kunczer Victoria , Baumgartner Maximilian , A.H.O. Ronda Onne , Verkade Henk Jan , Stojakovic Tatjana , Scharnagl Hubert , Habib Aida , Zimmermann Robert , Lotersztajn Sophie , Trauner Michael 
Published: September 2019

Background and Aims
Monoacylglycerol lipase (MGL) is the last enzymatic step in triglyceride degradation, hydrolyzing monoglycerides into glycerol and fatty acids (FAs) and converting 2‐arachidonoylglycerol into arachidonic acid, thus providing ligands for nuclear receptors as key regulators of hepatic bile acid (BA)/lipid metabolism and inflammation. We aimed to explore the role of MGL in the development of cholestatic liver and bile duct injury in mouse models of sclerosing cholangitis, a disease so far lacking effective pharmacological therapy.

Approach and Results
To this aim we analyzed the effects of 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC) feeding to induce sclerosing cholangitis in wild‐type (WT) and knockout (MGL−/−) mice and tested pharmacological inhibition with JZL184 in the multidrug resistance protein 2 knockout (Mdr2−/−
) mouse model of sclerosing cholangitis. Cholestatic liver injury and fibrosis were assessed by serum biochemistry, liver histology, gene expression, and western blot characterization of BA and FA synthesis/transport. Moreover, intestinal FAs and fecal microbiome were analyzed. Transfection and silencing were performed in Caco2 cells. MGL−/− mice were protected from DDC‐induced biliary fibrosis and inflammation with reduced serum liver enzymes and increased FA/BA metabolism and β‐oxidation. Notably, pharmacological (JZL184) inhibition of MGL ameliorated cholestatic injury in DDC‐fed WT mice and protected Mdr2−/−
mice from spontaneous liver injury, with improved liver enzymes, inflammation, and biliary fibrosis. In vitro experiments confirmed that silencing of MGL decreases prostaglandin E2 accumulation in the intestine and up‐regulates peroxisome proliferator–activated receptors alpha and gamma activity, thus reducing inflammation.

Conclusions
Collectively, our study unravels MGL as a metabolic target, demonstrating that MGL inhibition may be considered as potential therapy for sclerosing cholangitis.
Comparative analysis of two different types of fills used in wet cooling tower for higher‐scale water with conventional film type fill
Authors: Raj Gaurav , Chandra Prakash , Pathak Piyush Kumar 
Published: September 2019

AbstractIn the present study, an induced draft wet cooling tower has been experimentally investigated using film, glass, and ball fills. Film fills are used only in industry where scaling is less or low‐scale process water is used because of clogging of fills. Whereas, glass fills and ball fills are used for higher‐scale water. The main objective of this study is to investigate the performance and compare the result of film fills with glass fills and ball fills and also predict the loss as compared to film fills when glass and ball fills were used for high‐scaling water under such environmental conditions and different ratio of water to air flow and water inlet temperatures. Various performance parameters are analyzed for each of the fills and it was found that tower characteristics of film fills are 18.56% and 15.59% more than that of glass and ball fills, respectively, at water inlet temperature of 43°C and water‐to‐air flow ratio of 0.62. Moreover, exergy destruction was also calculated for each of the fills and it was observed that film fills destruct less exergy as compared with glass and ball fills.
Life Cycle Air Emissions External Costs Assessment for Comparing Electric and Traditional Passenger Cars
Authors: Girardi Pierpaolo , Brambilla Cristina , Mela Giulio 
Published: September 2019

Abstract
This study compares the environmental air emissions external costs of electric, gasoline, and diesel private passenger cars during their entire life cycle. The results provide the decision makers with a complementary and unconventional interpretation of the results of an ISO 14040–compliant life cycle assessment (LCA). Indeed, LCA results are often difficult to communicate and to be understood by the general public; on the other hand, an environmental external costs evaluation, where a single monetary value synthesizes the environmental impacts, can be easily understood, communicated to the broad public, and compared with taxes, incentives, and other economic tools. In the present study, we demonstrate that it is possible to carry out the application of a damage factor to the physical inventory flow. The application of this methodology to an Italian context leads to the conclusion that if we compare the 3 types of vehicles—electric, diesel, and gasoline—of an average midsize car (e.g., Volkswagen Golf), the electric version produces less external cost than the traditional internal combustion engine vehicles, considering both air pollution and climate change. The total life cycle air emissions externalities are 12.07 €/1000 km for the electric version, 21.30 €/1000 km for the gasoline vehicle, and 24.25  €/1000 km for the diesel vehicle. At the same time, the electric vehicle produces less external cost related to the air emissions considering both the entire life cycle and only the processes that occur in Italy. Integr Environ Assess Manag 2019;00:1–11. © 2019 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)
Progranulin autoantibodies in systemic sclerosis and autoimmune connective tissue disorders: A preliminary study
Authors: Klemm Philipp , Assmann Gunter , Preuss Klaus‐Dieter , Fadle Natalie , Regitz Evi , Martin Thierry , Pfreundschuh Michael , Thurner Lorenz 
Published: September 2019

AbstractObjectiveThe present study aimed to investigate progranulin autoantibodies in systemic sclerosis and autoimmune connective tissue disorders. Progranulin is a physiologic tumor necrosis factor (TNF) antagonist. Progranulin antibodies decrease progranulin levels.MethodsSerum samples of 123 patients with systemic sclerosis and various autoimmune connective tissue disorders (Sjoegren's syndrome [SjS], mixed connective tissue disorder, polymyositis [PM] and dermatomyositis [DM], antiphospholipid syndrome [APLS], and undifferentiated connective tissue disease [UCTD]) were tested for progranulin antibodies using enzyme‐linked immunosorbent assay.ResultsProgranulin antibodies were found in 34 of 123 (27.6%) patients at least once during their disease. In detail, 2 of 8 (25%) patients with limited cutaneous systemic sclerosis, 10 of 31 (32.3%) patients with diffuse cutaneous systemic sclerosis, 9 of 22 (40.9%) patients with SjS, 1 of 3 (33.33%) patients with mixed connective tissue disease, 4 of 33 (12.1%) patients with DM or PM, 6 of 15 (40%) patients with APLS, and 2 of 11 (18.2%) patients with UCTD were positive for progranulin antibodies during the course of disease.ConclusionsProgranulin antibodies are frequently present in patients with systemic sclerosis and other autoimmune connective tissue disorders. Despite the lack of specificity for a given autoimmune disease, progranulin antibodies might not only indicate a potential subtype but also play a pathogenic role in patients with autoimmune connective disorders. Given the important role of TNF‐α in inflammatory processes in autoimmune connective tissue disorders, progranulin antibodies might support the proinflammatory environment by neutralizing the TNF blocker progranulin.
Effects of treatment with gold nanoparticles in a model of acute pulmonary inflammation induced by lipopolysaccharide
Authors: dos Santos Haupenthal Daniela Pacheco , Mendes Carolini , de Bem Silveira Gustavo , Zaccaron Rubya Pereira , Corrêa Maria Eduarda Anastácio Borges , Nesi Renata Tiscoski , Pinho Ricardo Aurino , da Silva Paula Marcos Marques , Silveira Paulo Cesar Lock 
Published: September 2019

AbstractThe bacterial lipopolysaccharide (LPS) is a highly toxic molecule derived from the outer membrane of gram‐negative bacteria. LPS endotoxin affects the lungs and is used as a model of acute pulmonary inflammation affecting the cellular morphology of the organ. Previously, gold nanoparticles (GNPs) have been shown to demonstrate anti‐inflammatory and antioxidative activity in muscle and epithelial injury models. The objective of this study was to investigate the effect of the intraperitoneal treatment using GNPs on the inflammatory response and pulmonary oxidative stress induced by LPS. Wistar rats were divided into four groups (N = 10): Sham; Sham + GNPs 2.5 mg/kg; LPS; and LPS + GNPs 2.5 mg/kg. Treatment with LPS upregulated the levels of markers of cellular and hepatic damage (CK, LDH, AST, and alanine aminotransferase); however, the group treated with only GNPs exhibited no toxicity. Treatment with GNPs reversed LPS‐induced changes with respect to total peritoneal leukocyte count and the pulmonary levels of pro‐inflammatory cytokines (IFN‐γ and IL‐6). Histological analysis revealed that treatment with GNPs reversed the increase in alveolar septum thickness due to LPS‐induced fibrosis. In addition, treatment with GNPs decreased production of oxidants (nitrite and DCFH), reduced oxidative damage (carbonyl and sulfhydryl), and downregulated activities of superoxide dismutase and catalase. Treatment with GNPs did not showed toxicity; however, it exhibited anti‐inflammatory and antioxidative activity that reversed morphological alterations induced by LPS.
A siRNA‐based method for efficient silencing of PYROXD1 gene expression in the colon cancer cell line HCT116
Authors: Shabani Samira , Mahjoubi Frouzandeh , Moosavi Mohammad A. 
Published: September 2019

AbstractPurposeThe aim of this study was to determine the biological function of pyridine nucleotide‐disulfide oxidoreductase domain 1 (PYROXD1), a recently discovered protein, in colon cancer cell line HCT116.MethodsThe small interfering RNA (siRNA) was designed rationally on the basis of the target sequence against PYROXD1. Relative PYROXD1 mRNA levels were measured by a quantitative real‐time polymerase chain reaction. Flow cytometry was performed to monitor tumor cells proliferation and apoptosis after siRNA transfection.ResultsKnockdown of PYROXD1 arrested the cell cycle, and induced late apoptosis in colon cancer cell line HCT116DiscussionTaken together, these results revealed the critical roles of PYROXD1 in regulating cell cycle and apoptosis and possibly will signify its therapeutic potential for targeting colorectal cancer models.
Dahuang Zhechong pill attenuates CCl4‐induced rat liver fibrosis via the PI3K‐Akt signaling pathway
Authors: Gong Zhenghua , Lin Jiayu , Zheng Jie , Wei Liya , Liu Li , Peng Yanzhong , Liang Weicheng , Hu Guoxin 
Published: September 2019

AbstractIt is well characterized that activated hepatic stellate cells (HSCs) exert critical functions in accelerating the progression of liver fibrosis. Previous studies have indicated that Dahuang Zhechong pill (DHZCP), a traditional Chinese herbal medicine, is capable of inactivating HSCs and thus attenuate the formation of liver fibrosis in rats. However, pharmacological mechanisms of DHZCP in alleviating liver fibrosis remain unclear. This study aims to investigate the antifibrotic role of DHZCP through inhibiting the phosphatidylinositol 3‐kinase (PI3K)‐protein kinase B (Akt) pathway. DHZCP was found to significantly suppresses extracellular matrix formation and immune cell infiltration, thus alleviating liver fibrosis symptoms in the in vivo model. Moreover, DHZCP reduced serum levels of transforming growth factor β1 and tumor necrosis factor‐α in rats with liver fibrosis. DHZCP treatment remarkably downregulated protein levels of PI3K and phosphorylated Akt, as well as fibrosis markers. In vitro experiments further demonstrated that DHZCP markedly suppressed HSCs proliferation by downregulating PI3K/Akt, which exerted a synergistic effect with the PI3K inhibitor LY294002. To sum up, our results confirmed that DHZCP exerted an antifibrotic effect in the animal model through inactivating the PI3K/Akt pathway, thus protecting rats from liver injury.
Analysis of clinical characteristics of 92 patients with paroxysmal nocturnal hemoglobinuria: A single institution experience in China
Authors: Fu Rong , Li Liyan , Li Lijuan , Liu Hui , Zhang Tian , Ding Shaoxue , Wang Guojin , Song Jia , Wang Huaquan , Xing Limin , Guan Jing , Shao Zonghong 
Published: September 2019

AbstractObjectivesWe performed a retrospective analysis to investigate the clinical characteristics and therapeutic strategies of Chinese paroxysmal nocturnal hemoglobinuria (PNH) patients, and assessed the efficacy and safety of glucocorticoid in PNH patients.MethodsThe clinical data of 92 PNH cases in our hospital were analyzed, including clinical manifestation, laboratory examination, treatment efficacy, and survival.ResultsThe main clinical manifestations of these patients included hemoglobinuria, anemia, fatigue, dyspnea, headache, abdominal pain, and erectile dysfunction. Glucocorticoid is still the first‐line treatment for PNH patients to control hemolytic attack, and the short‐term remission rate (12 months) is 79.01% (64/81). Meanwhile, the overall survival (OS) of 10 years after diagnosis was estimated as 70.77% (46/65). Moreover, Cox proportional risk model for multivariate analysis showed that the increase in LDH multiple, thrombosis complications, and complicated with bone marrow failure were the independent adverse prognostic factors affecting the survival of PNH patients.ConclusionParoxysmal nocturnal hemoglobinuria patients in mainland China have various clinical features, while lower incidences of thrombosis and renal damage. Thrombosis and bone marrow failure are two complications with worse prognosis.
Contribution of genetic polymorphism of methylene tetrahydrofolate reductase on the effect of methotrexate in ectopic pregnancy patients
Authors: Deng Jie , Chen Li , Xue Heng , Zeng Fan‐Xiang , Niu Pei‐Guang , Shi Dao‐Hua 
Published: September 2019

AbstractBackgroundMethotrexate (MTX) is the prior drug in ectopic pregnancy (EP). However, approximately 10% of patients suffer from failure by MTX therapy. Reduced folate carrier 1 (RFC1), methylene tetrahydrofolate reductase (MTHFR), and dihydrofolate reductase (DHFR) are involved in the transport and effects of MTX in vivo. In the present study, we aim to investigate the relationship between the genetic polymorphisms of RFC1, MTHFR, and DHFR and the clinical efficacy of MTX in tubal pregnancies.Methods100 patients of EP were enrolled in this study. Polymorphisms of RFC1 G80A, MTHFR C677T, and DHFR A‐317G were genotyped. β‐hCG level was detected in day 0, 4, and 7 after MTX injection. Association of MTX efficacy and genetic polymorphisms was analyzed.ResultsMethylene tetrahydrofolate reductase C677T was associated with MTX treatment (P = .017). The success rate of first MTX injection was superior in patients with harboring mutation allele of MTHFR gene than that in patients with wild‐type gene (P = .001). However, there was no significant association between the polymorphisms of RFC1 G80A, DHFR A‐317G, and surgical treatment (P = .709 and .476, respectively). In addition, β‐hCG level decrement was not significantly changed by MTX injection with different polymorphisms of RFC1, MTHFR, and DHFR on either day 4 (P = .214, 0.197 and 0.270, respectively) or day 7 (P = .172, .554, and .726, respectively).ConclusionOur results suggested that the reliable indicator was polymorphism of MTHFR C677T in failure by MTX injection.
Working with gender‐expansive clients in psychotherapy
Authors: Brewster Melanie E. , Motulsky Wei , Glaeser Elizabeth 
Published: September 2019

AbstractGender expansive individuals of all ages are at an elevated risk for mental and physical health problems compared not only to the general population, but also to lesbian, gay, and bisexual individuals. Yet mental healthcare providers tend to be underprepared to provide services to this population, which is due in part to the dearth of scholarship on how to provide competent care to gender‐expansive people. The present article introduces themes and terminology crucial to working with this population, as well as three case studies—two individuals and one family—highlighting the nuances inherent in workng with gender expansive clients. We conclude by offering ways to conceptualize each case, and by highlighting certain areas that we believe deserve specific considerations from care providers.
Incorporating Ontogeny in Physiologically Based Pharmacokinetic Modeling to Improve Pediatric Drug Development: What We Know About Developmental Changes in Membrane Transporters
Authors: Cheung Kit Wun Kathy , van Groen Bianca D. , Burckart Gilbert J. , Zhang Lei , de Wildt Saskia N. , Huang Shiew‐Mei 
Published: September 2019

AbstractDevelopmental changes in the biological processes involved in the disposition of drugs, such as membrane transporter expression and activity, may alter the drug exposure and clearance in pediatric patients. Physiologically based pharmacokinetic (PBPK) models take these age‐dependent changes into account and may be used to predict drug exposure in children. As a result, this mechanistic‐based tool has increasingly been applied to improve pediatric drug development. Under the Prescription Drug User Fee Act VI, the US Food and Drug Administration has committed to facilitate the advancement of PBPK modeling in the drug application review process. Yet, significant knowledge gaps on developmental biology still exist, which must be addressed to increase the confidence of prediction. Recently, more data on ontogeny of transporters have emerged and supplied a missing piece of the puzzle. This article highlights the recent findings on the ontogeny of transporters specifically in the intestine, liver, and kidney. It also provides a case study that illustrates the utility of incorporating this information in predicting drug exposure in children using a PBPK approach. Collaborative work has greatly improved the understanding of the interplay between developmental physiology and drug disposition. Such efforts will continue to be needed to address the remaining knowledge gaps to enhance the application of PBPK modeling in drug development for children.
Drug Transporters Expressed in the Human Placenta and Models for Studying Maternal‐Fetal Drug Transfer
Authors: Dallmann André , Liu Xiaomei I. , Burckart Gilbert J. , van den Anker John 
Published: September 2019

AbstractTremendous efforts have been directed to investigate the ontogeny of drug transporters in fetuses, neonates, infants, and children based on their importance for understanding drug pharmacokinetics. During development (ie, in the fetus and newborn infant), there is special interest in transporters expressed in the placenta that modulate placental drug transfer. Many of these transporters can decrease or increase drug concentrations in the fetus and at birth, stressing the relevance of elucidating expression in the placenta and potential gestational age‐dependent changes therein. Hence, the main objective of this review was to summarize the current knowledge about expression and ontogeny of transporters in the human placenta in healthy pregnant women. In addition, various in vitro, ex vivo, and in silico models that can be used to investigate placental drug transfer, namely, placental cancer cell lines, ex vivo cotyledon perfusion experiments, and physiologically based pharmacokinetic (PBPK) models, are discussed together with their advantages and shortcomings. A particular focus was placed on PBPK models because these models can integrate different types of information, such as expression data, ontogeny information, and observations obtained from the ex vivo cotyledon perfusion experiment. Such a mechanistic modeling framework may leverage the available information and ultimately help to improve knowledge about the adequacy and safety of pharmacotherapy in pregnant women and their fetuses.
Novel Pyrano[2,3‐d]thiazole and Thiazolo[4,5‐b]pyridine Derivatives: One‐pot Three‐component Synthesis and Biological Evaluation as Anticancer Agents, c‐Met, and Pim‐1 Kinase Inhibitors
Authors: Abdallah Amira E.M. , Mohareb Rafat M. , Ahmed Ebtsam A. 
Published: September 2019

AbstractPreparation of pyrano[2,3‐d]thiazole and thiazolo[4,5‐b]pyridine derivatives through multicomponent reactions (MCRs) was achieved by the reaction of 2‐(2‐amino‐4,5,6,7‐tetrahydrobenzo[b]thiophen‐3‐yl)thiazol‐4(5H)‐one with various active methylene reagents such as ethyl cyanoacetate or malononitrile in basic conditions containing diverse aromatic aldehyde. Furthermore, this study aims to evaluate the in vitro cytotoxic activity of the synthetic compounds against six cancer cell lines, and all the prepared compounds revealed valuable activity compared with the CHS‐828, which is the 2‐[6‐(4‐chlorophenoxy)hexyl]‐1‐cyano‐3‐pyridin‐4‐ylguanidine as the standard drug. Some of the pyrano[2,3‐d]thiazole and thiazolo[4,5‐b]pyridine derivatives showed the highest antitumor activity towards the six cancer cell lines. Moreover, (c‐Met) enzymatic activity of the most potent compounds showed that compounds 3b 2‐(2‐amino‐4,5,6,7 tetrahydrobenzo[b]thiophen‐3‐yl)‐5‐hydroxy‐7‐(2‐hydroxy‐phenyl)‐7H‐pyrano[2,3‐d]thiazole‐6 carbonitrile and 5e 2‐(2‐amino‐4,5,6,7‐tetrahydrobenzo[b]thiophen‐3‐yl)‐5‐hydroxy‐7‐phenyl‐4,7‐dihydrothiazolo[4,5‐b]pyridine‐6‐carbonitrile were with higher activities than foretinib. Three compounds were selected to examine their Pim‐1 kinase where compounds 3b and 7b showed the highest inhibitions.
Synthesis of some novel pyrazoline‐thiazole hybrids and their antimicrobial activities
Authors: Masoud Doaa M. , Azzam Rasha A. , Hamdy Fatma , Mekawey Amal A.I. , Abdel‐Aziz Hatem A. 
Published: September 2019

AbstractA series of novel thiazolyl pyrazolines7a‐h,9a‐f, and11a‐fhave been synthesized by the reaction of thioamide derivatives5a,bwith 1‐aryl‐2‐bromoethanones6a‐d, chloroacetones8a‐c, and hydrazonoyl chlorides10a‐c. Additionally, pyrazoles15a‐cand20were prepared starting from enaminone13. These newly synthesized compounds were screened for their in vitro antibacterial activity against four bacterial species. Compound11bshowed a moderate activity againstKlebsiella pneumoniae. Compounds7cand11crevealed a moderate activity againstPseudomonas aeruginosa. In addition, the antifungal activity of the newly synthesized compounds was determined against five fungal strains. Compounds7e,7g, and11eshowed a good activity againstAspergillus flavusandPenicillium expansum.