Pathobiology of aging & age related diseases最新文献

{"title":"Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammation.","authors":"Rita I Issa,&nbsp;Timothy M Griffin","doi":"10.3402/pba.v2i0.17470","DOIUrl":"https://doi.org/10.3402/pba.v2i0.17470","url":null,"abstract":"<p><p>Obesity is a significant risk factor for developing osteoarthritis in weight-bearing and non-weight-bearing joints. Although the pathogenesis of obesity-associated osteoarthritis is not completely understood, recent studies indicate that pro-inflammatory metabolic factors contribute to an increase in osteoarthritis risk. Adipose tissue, and in particular infrapatellar fat, is a local source of pro-inflammatory mediators that are increased with obesity and have been shown to increase cartilage degradation in cell and tissue culture models. One adipokine in particular, leptin, may be a critical mediator of obesity-associated osteoarthritis via synergistic actions with other inflammatory cytokines. Biomechanical factors may also increase the risk of osteoarthritis by activating cellular inflammation and promoting oxidative stress. However, some types of biomechanical stimulation, such as physiologic cyclic loading, inhibit inflammation and protect against cartilage degradation. A high percentage of obese individuals with knee osteoarthritis are sedentary, suggesting that a lack of physical activity may increase the susceptibility to inflammation. A more comprehensive approach to understanding how obesity alters daily biomechanical exposures within joint tissues may provide new insight into the protective and damaging effects of biomechanical factors on inflammation in osteoarthritis.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"2 2012","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v2i0.17470","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30663855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-dependent changes in innate immune phenotype and function in rhesus macaques (Macaca mulatta).","authors":"Mark Asquith,&nbsp;Kristen Haberthur,&nbsp;Monica Brown,&nbsp;Flora Engelmann,&nbsp;Ashleigh Murphy,&nbsp;Zainab Al-Mahdi,&nbsp;Ilhem Messaoudi","doi":"10.3402/pba.v2i0.18052","DOIUrl":"https://doi.org/10.3402/pba.v2i0.18052","url":null,"abstract":"<p><p>Aged individuals are more susceptible to infections due to a general decline in immune function broadly referred to as immune senescence. While age-related changes in the adaptive immune system are well documented, aging of the innate immune system remains less well understood, particularly in nonhuman primates. A more robust understanding of age-related changes in innate immune function would provide mechanistic insight into the increased susceptibility of the elderly to infection. Rhesus macaques have proved a critical translational model for aging research, and present a unique opportunity to dissect age-dependent modulation of the innate immune system. We examined age-related changes in: (i) innate immune cell frequencies; (ii) expression of pattern recognition receptors (PRRs) and innate signaling molecules; (iii) cytokine responses of monocytes and dendritic cells (DC) following stimulation with PRR agonists; and (iv) plasma cytokine levels in this model. We found marked changes in both the phenotype and function of innate immune cells. This included an age-associated increased frequency of myeloid DC (mDC). Moreover, we found toll-like receptor (TLR) agonists lipopolysaccharide (TLR4), fibroblast stimulating ligand-1 (TLR2/6), and ODN2006 (TLR7/9) induced reduced cytokine responses in aged mDC. Interestingly, with the exception of the monocyte-derived TNFα response to LPS, which increased with age, TNFα, IL-6, and IFNα responses declined with age. We also found that TLR4, TLR5, and innate negative regulator, sterile alpha and TIR motif containing protein (SARM), were all expressed at lower levels in young animals. By contrast, absent in melanoma 2 and retinoic acid-inducible gene I expression was lowest in aged animals. Together, these observations indicate that several parameters of innate immunity are significantly modulated by age and contribute to differential immune function in aged macaques.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v2i0.18052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30884828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast tumors in PyMT transgenic mice expressing mitochondrial catalase have decreased labeling for macrophages and endothelial cells.","authors":"Sy Fatemie,&nbsp;Jorming Goh,&nbsp;Christina Pettan-Brewer,&nbsp;Warren Ladiges","doi":"10.3402/pba.v2i0.17391","DOIUrl":"https://doi.org/10.3402/pba.v2i0.17391","url":null,"abstract":"<p><p>We show by immunohistochemical labeling that prominent cell types in the tumor microenvironment of PyMT transgenic mice are tumor-associated macrophages (TAMs) and endothelial cells, and that both populations are decreased in the presence of mitochondrial targeted catalase (mCAT). This observation suggests that mitochondrial ROS can drive tumor invasiveness in conjunction with the presence of TAMs and increased angiogenesis. Since primary PyMT tumor cells expressing mCAT undergo increased apoptosis, mitochondrial antioxidants might be attractive anti-tumor agents.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v2i0.17391","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30884823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth hormone, inflammation and aging.","authors":"Michal M Masternak,&nbsp;Andrzej Bartke","doi":"10.3402/pba.v2i0.17293","DOIUrl":"https://doi.org/10.3402/pba.v2i0.17293","url":null,"abstract":"<p><p>Mutant animals characterized by extended longevity provide valuable tools to study the mechanisms of aging. Growth hormone and insulin-like growth factor-1 (IGF-1) constitute one of the well-established pathways involved in the regulation of aging and lifespan. Ames and Snell dwarf mice characterized by GH deficiency as well as growth hormone receptor/growth hormone binding protein knockout (GHRKO) mice characterized by GH resistance live significantly longer than genetically normal animals. During normal aging of rodents and humans there is increased insulin resistance, disruption of metabolic activities and decline of the function of the immune system. All of these age related processes promote inflammatory activity, causing long term tissue damage and systemic chronic inflammation. However, studies of long living mutants and calorie restricted animals show decreased pro-inflammatory activity with increased levels of anti-inflammatory adipokines such as adiponectin. At the same time, these animals have improved insulin signaling and carbohydrate homeostasis that relate to alterations in the secretory profile of adipose tissue including increased production and release of anti-inflammatory adipokines. This suggests that reduced inflammation promoting healthy metabolism may represent one of the major mechanisms of extended longevity in long-lived mutant mice and likely also in the human.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v2i0.17293","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30885941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential of chromatin modifying compounds for the treatment of Alzheimer's disease.","authors":"Tom C Karagiannis,&nbsp;Katherine Ververis","doi":"10.3402/pba.v2i0.14980","DOIUrl":"https://doi.org/10.3402/pba.v2i0.14980","url":null,"abstract":"<p><p>Alzheimer's disease is a very common progressive neurodegenerative disorder affecting the learning and memory centers in the brain. The hallmarks of disease are the accumulation of β-amyloid neuritic plaques and neurofibrillary tangles formed by abnormally phosphorylated tau protein. Alzheimer's disease is currently incurable and there is an intense interest in the development of new potential therapies. Chromatin modifying compounds such as sirtuin modulators and histone deacetylase inhibitors have been evaluated in models of Alzheimer's disease with some promising results. For example, the natural antioxidant and sirtuin 1 activator resveratrol has been shown to have beneficial effects in animal models of disease. Similarly, numerous histone deacetylase inhibitors including Trichostatin A, suberoylanilide hydroxamic acid, valproic acid and phenylbutyrate reduction have shown promising results in models of Alzheimer's disease. These beneficial effects include a reduction of β-amyloid production and stabilization of tau protein. In this review we provide an overview of the histone deacetylase enzymes, with a focus on enzymes that have been identified to have an important role in the pathobiology of Alzheimer's disease. Further, we discuss the potential for pharmacological intervention with chromatin modifying compounds that modulate histone deacetylase enzymes.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v2i0.14980","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30884825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B16 melanoma tumor growth is delayed in mice in an age-dependent manner.","authors":"Christina Pettan-Brewer,&nbsp;John Morton,&nbsp;Rebecca Coil,&nbsp;Heather Hopkins,&nbsp;Sy Fatemie,&nbsp;Warren Ladiges","doi":"10.3402/pba.v2i0.19182","DOIUrl":"https://doi.org/10.3402/pba.v2i0.19182","url":null,"abstract":"<p><p>A major risk factor for cancer is increasing age, which suggests that syngeneic tumor implants in old mice would grow more rapidly. However, various reports have suggested that old mice are not as permissive to implanted tumor cells as young mice. In order to determine and characterize the age-related response to B16 melanoma, we implanted 5×10(5) tumor cells into 8, 16, 24, and 32-month-old male C57BL/6 (B6) and C57BL/6×BALB/c F1 (CB6 F1) mice subcutaneously in the inguinal and axillary spaces, or intradermally in the lateral flank. Results showed decreased tumor volume with increasing age, which varied according to mouse genetic background and the implanted site. The B6 strain showed robust tumor growth at 8 months of age at the inguinal implantation site, with an average tumor volume of 1341.25 mm(3). The 16, 24, and 32-month age groups showed a decrease in tumor growth with tumor volumes of 563.69, 481.02, and 264.55 mm(3), respectively (p≤0.001). The axillary implantation site was less permissive in 8-month-old B6 mice with an average tumor volume of 761.52 mm(3). The 24- and 32-month age groups showed a similar decrease in tumor growth with tumor volumes of 440 and 178.19 mm(3), respectively (p≤0.01). The CB6F1 strain was not as tumor permissive at 8 months of age as B6 mice with average tumor volumes of 446.96 and 426.91 mm(3) for the inguinal and axillary sites, respectively. There was a decrease in tumor growth at 24 months of age at both inguinal and axillary sites with an average tumor volume of 271.02 and 249.12 mm(3), respectively (p≤0.05). The strain dependence was not apparent in 8-month-old mice injected intradermally with B16 melanoma cells, with average tumor volumes of 736.82 and 842.85 mm(3) for B6 and CB6 F1, respectively. However, a strain difference was seen in 32-month-old B6 mice with an average decrease in tumor volume of 250.83 mm(3) (p≤0.01). In contrast, tumor growth significantly decreased earlier in CB6 F1 mice with average tumor volumes of 417.62 and 216.34 mm(3) in the 16- and 24-month age groups, respectively (p≤0.005). Histologically, implanted tumors in young mice exhibited characteristics of aggressive, rapidly growing tumor cells including high vascularity, mitosis, and invasiveness compared to tumors in old mice. We contend that the decrease in B16 melanoma tumor growth seen with increasing age in B6 and CB6 F1 mice represents a biological process, which we are calling age-dependent cancer resistance (ADCR). Our data provide a detailed description of conditions necessary to use the model to investigate the mechanisms of ADCR and determine its biological and clinical relevance.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v2i0.19182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30884829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of the biological properties of Cinnulin PF in the context of diabetes: mechanistic insights by genome-wide mRNA-Seq analysis.","authors":"Haloom Rafehi,&nbsp;Katherine Ververis,&nbsp;Aneta Balcerczyk,&nbsp;Mark Ziemann,&nbsp;Jenny Ooi,&nbsp;Sean Hu,&nbsp;Faith A A Kwa,&nbsp;Shanon J Loveridge,&nbsp;George T Georgiadis,&nbsp;Assam El-Osta,&nbsp;Tom C Karagiannis","doi":"10.3402/pba.v2i0.11905","DOIUrl":"https://doi.org/10.3402/pba.v2i0.11905","url":null,"abstract":"<p><p>The accumulating evidence of the beneficial effects of cinnamon (Cinnamomum burmanni) in type-2 diabetes, a chronic age-associated disease, has prompted the commercialisation of various supplemental forms of the spice. One such supplement, Cinnulin PF(®), represents the water soluble fraction containing relatively high levels of the double-linked procyanidin type-A polymers of flavanoids. The overall aim of this study was to utilize genome-wide mRNA-Seq analysis to characterise the changes in gene expression caused by Cinnulin PF in immortalised human keratinocytes and microvascular endothelial cells, which are relevant with respect to diabetic complications. In summary, our findings provide insights into the mechanisms of action of Cinnulin PF in diabetes and diabetic complications. More generally, we identify relevant candidate genes which could provide the basis for further investigation.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v2i0.11905","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30884827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapamycin selectively alters serum chemistry in diabetic mice.","authors":"Hooman Tabatabai-Mir,&nbsp;Kavithalakshmi Sataranatarajan,&nbsp;Hak Joo Lee,&nbsp;Alex F Bokov,&nbsp;Elizabeth Fernandez,&nbsp;Vivian Diaz,&nbsp;Goutam Ghosh Choudhury,&nbsp;Arlan Richardson,&nbsp;Balakuntalam S Kasinath","doi":"10.3402/pba.v2i0.15896","DOIUrl":"https://doi.org/10.3402/pba.v2i0.15896","url":null,"abstract":"<p><p>The study was undertaken to explore the effect of rapamycin, an anti-inflammatory agent, on the metabolic profile of type 2 diabetic mice. Seven-month-old diabetic db/db mice and their lean littermate non-diabetic controls (db/m) were randomized to receive control chow or chow mixed with rapamycin (2.24 mg/kg/day) (each group n =20, males and females) for 4 months and sacrificed. Serum samples were analyzed for the measurement of glucose, creatinine, blood urea nitrogen (BUN), alkaline phosphatase (ALP), alanine aminotransferase (ALT), total cholesterol, total triglyceride, and total protein, using the automated dry chemistry analysis. Rapamycin elevated serum glucose in female diabetic mice. Serum creatinine tended to be higher in diabetic mice but was not affected by rapamycin; there was no difference in BUN levels among the groups. Serum ALP was elevated in diabetic mice and rapamycin lowered it only in female diabetic mice; serum ALT levels were increased in female diabetic mice, unaffected by rapamycin. Serum total protein was elevated in diabetic mice of both genders but was not affected by rapamycin. Diabetic mice from both genders had elevated serum cholesterol and triglycerides; rapamycin did not affect serum cholesterol but decreased serum total triglycerides in male diabetic mice. We conclude that rapamycin elicits complex metabolic responses in aging diabetic mice, worsening hyperglycemia in females but improving ALP in female diabetic and total triglycerides in male diabetic mice, respectively. The metabolic effects of rapamycin should be considered while performing studies with rapamycin in mice.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v2i0.15896","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30884824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduction of glucose intolerance with high fat feeding is associated with anti-inflammatory effects of thioredoxin 1 overexpression in mice.","authors":"Adam B Salmon,&nbsp;Lisa C Flores,&nbsp;Yan Li,&nbsp;Holly Van Remmen,&nbsp;Arlan Richardson,&nbsp;Yuji Ikeno","doi":"10.3402/pba.v2i0.17101","DOIUrl":"https://doi.org/10.3402/pba.v2i0.17101","url":null,"abstract":"<p><p>Aging is associated with reduced ability to maintain normal glucose homeostasis. It has been suggested that an age-associated increase in chronic pro-inflammatory state could drive this reduction in glucoregulatory function. Thioredoxins (Trx) are oxido-reductase enzymes that play an important role in the regulation of oxidative stress and inflammation. In this study, we tested whether overexpression of Trx1 in mice [Tg(TRX1)(+/0)] could protect from glucose metabolism dysfunction caused by high fat diet feeding. Body weight and fat mass gains with high fat feeding were similar in Tg(TRX1)(+/0) and wild-type mice; however, high fat diet induced glucose intolerance was reduced in Tg(TRX1)(+/0) mice relative to wild-type mice. In addition, expression of the pro-inflammatory cytokine TNF-α was reduced in adipose tissue of Tg(TRX1)(+/0) mice compared to wild-type mice. These findings suggest that activation of thioredoxins may be a potential therapeutic target for maintenance of glucose metabolism with obesity or aging.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"2 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v2i0.17101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30884826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol has protective effects against airway remodeling and airway hyperreactivity in a murine model of allergic airways disease.","authors":"Simon G Royce,&nbsp;William Dang,&nbsp;Gao Yuan,&nbsp;Jenny Tran,&nbsp;Assam El Osta,&nbsp;Tom C Karagiannis,&nbsp;Mimi L K Tang","doi":"10.3402/pba.v1i0.7134","DOIUrl":"https://doi.org/10.3402/pba.v1i0.7134","url":null,"abstract":"<p><strong>Background: </strong>New therapies for asthma which can address three main interrelated features of the disease, airway inflammation, airway remodeling and airway hyperreactivity, are urgently required. Resveratrol, a well known red wine polyphenol has received much attention due to its potential anti-aging properties. This compound is an agonist of silent information regulator two histone deacetylases and has many effects that are relevant to key aspects of the pathophysiology of asthma including inflammation, cell proliferation and fibrosis. Therefore, resveratrol may offer a novel asthma therapy that simultaneously inhibits airway inflammation, and airway remodeling which are the main contributors to airway hyperreactivity and irreversible lung function loss.</p><p><strong>Methods: </strong>We evaluated the effects of systemic resveratrol treatment in a murine model of chronic allergic airways disease which displays most of the clinicopathological features of severe human asthma. Wild-type Balb/c mice with allergic airways disease were treated with 12.5 mg/kg resveratrol or vehicle control. Airway inflammation was assessed by bronchoalveolar lavage fluid cell counts and histological examination of lung tissue sections. Further, remodeling was assessed by morphometric analysis and lung function was assessed by invasive plethysmography measurement of airway resistance and dynamic compliance.</p><p><strong>Results: </strong>Mice treated with resveratrol exhibited reduced tissue inflammation as compared to vehicle treated mice (p<0.05). Additionally, resveratrol treatment resulted in reduced subepithelial collagen deposition as compared to vehicle treated mice (p<0.05) and attenuated airway hyperreactivity (p<0.05).</p><p><strong>Conclusions: </strong>These novel findings demonstrate that treatment with resveratrol can reduce structural airway remodeling changes and hyperreactivity. This has important implications for the development of new therapeutic approaches to asthma.</p>","PeriodicalId":89611,"journal":{"name":"Pathobiology of aging & age related diseases","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/pba.v1i0.7134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30885936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}