PharmaNutritionPub Date : 2024-12-01DOI: 10.1016/j.phanu.2024.100423
Vandana Garg , Deepapriya Velumani , Yu-Chieh Lin , Abdul Haye
{"title":"A comprehensive review of probiotic claims regulations: Updates from Asia-Pacific, United States, and Europe","authors":"Vandana Garg , Deepapriya Velumani , Yu-Chieh Lin , Abdul Haye","doi":"10.1016/j.phanu.2024.100423","DOIUrl":"10.1016/j.phanu.2024.100423","url":null,"abstract":"<div><h3>Background</h3><div>Probiotics are defined, classified, and regulated differently across countries, which affects consumer protection and market access for manufacturers. This review examined the regulatory similarities and differences for probiotics in the APAC region, the U.S., and Europe to address these challenges.</div></div><div><h3>Method</h3><div>A detailed literature search was conducted on databases such as Google Scholar, PubMed, and open sources of relevant regulatory authorities. Relevant articles, guidelines, and recommendations related to probiotics in APAC, U.S. and Europe were screened and reviewed.</div></div><div><h3>Results</h3><div>Probiotics are categorized as \"food\" in U.S., Europe, Japan, Thailand, Malaysia, Singapore, and Indonesia, with Malaysia, Singapore, and Indonesia also classifying them as \"health supplements.\" Other terms like “functional food,\" \"novel food,\" and \"health functional food\" are used in various countries. Claims for probiotics also vary internationally. Countries such as China, Philippines, and Singapore have pre-approved claims, while the U.S., South Korea, Australia & New Zealand, and India do not have any pre-approved claim. Europe enforces the strictest rules and generally does not approve any probiotic health claims, whereas U.S. and APAC regions are more flexible. For instance, in Thailand, claim of “reducing disease risk” is permitted.</div></div><div><h3>Conclusion</h3><div>Harmonizing the regulations could benefit consumers and manufacturers by ensuring consistent standards and facilitating market entry. This would help industry stakeholders navigate the complex regulatory landscape and aid consumers in understanding the benefits of probiotic products.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"30 ","pages":"Article 100423"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PharmaNutritionPub Date : 2024-12-01DOI: 10.1016/j.phanu.2024.100424
Salma Hosny Abd-allah Mohamed, Ghada Mahmoud Khafagy, Inas El Sayed, Hala Ahmed Hussein
{"title":"The gut brain axis, effect of dietary changes and probiotics supplement on depression symptoms","authors":"Salma Hosny Abd-allah Mohamed, Ghada Mahmoud Khafagy, Inas El Sayed, Hala Ahmed Hussein","doi":"10.1016/j.phanu.2024.100424","DOIUrl":"10.1016/j.phanu.2024.100424","url":null,"abstract":"<div><h3>Introduction</h3><div>Depression is a prevalent mental condition that adversely affects the lives of millions globally. Research has examined the correlation between alterations in gut microbiota composition and depression, leading to increasing interest in the possible use of probiotics to restore gut microbiota balance and enhance mental health outcomes.</div></div><div><h3>Aim</h3><div>Our aim is to examine the impact of probiotic supplementation on depression in healthy people. By assessing the impact of non-pharmacological therapies aimed at the gut-brain axis, we aspire to contribute to the advancement of accessible and efficacious treatments for depression.</div></div><div><h3>Methods</h3><div>We assessed socioeconomic status and depression score at baseline in a randomized controlled experiment of healthy people. We then randomly allocated individuals to the intervention group, which got probiotic supplements and health information regarding probiotic-rich diets, or the control group, which received their regular diet. At the end of 12 weeks, we repeated the same measurements.</div></div><div><h3>Results</h3><div>The study indicated a notable enhancement in depression levels within the intervention group. The median depression score declined from 8 (IQR: 6–9) prior to the intervention to 3 (IQR: 3–5) following the intervention, indicating a 62.5 % enhancement. The control group had a marginal deterioration in depression ratings within the same timeframe, with the median score rising from 8 (IQR: 6–9) to 8.5 (IQR: 7–10), indicating a 6.25 % drop.</div></div><div><h3>Conclusions</h3><div>Probiotics exert a beneficial influence on both the occurrence and intensity of depression symptoms in healthy people, greatly alleviating these symptoms.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"30 ","pages":"Article 100424"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143148846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PharmaNutritionPub Date : 2024-11-21DOI: 10.1016/j.phanu.2024.100421
Yugant Krishnakumar Talati, Anil Bhanudas Gaikwad
{"title":"A therapeutic approach to identify leading molecules from natural products and therapeutic targets in CKD by network pharmacology","authors":"Yugant Krishnakumar Talati, Anil Bhanudas Gaikwad","doi":"10.1016/j.phanu.2024.100421","DOIUrl":"10.1016/j.phanu.2024.100421","url":null,"abstract":"<div><div>Chronic kidney disease (CKD), a condition characterized by diminished kidney function, affects approximately 10 % of the population worldwide. With its high mortality rate of ∼1.2 million, CKD poses a high global burden. The complexity increases severalfold due to its vast variety of aetiologies and relatively limited treatment options that, too, are associated with adverse effects. The continuous deterioration of the kidneys makes them reliant on external purification systems <em>i.e.,</em> dialysis or whole kidney transplantation, both having certain limitations, making CKD one of the highly prevalent diseases across the globe. The multi-faceted disease requires multi-targeted therapies that can potentially improve CKD care. Natural products have long been considered the “holy grail” for many diseases, including CKD; their multi-targeting nature, fewer side effects, and ability to target multiple pathways have caught attention. The complexity increases when a single phytopharmaceutical cures a disease by acting on various targets and affecting diverse mechanisms. Identifying therapeutic targets and lead molecules thus becomes difficult and, at times, a big task! The network pharmacology (NP) tool has shifted this drug discovery paradigm towards a “multi-drug, multi-target” approach to underscore responsible molecular interconnections that unwind the therapeutic potential of natural products against CKD by predicting potential therapeutic targets and underlined molecular mechanisms. Applying NP for natural products in CKD can be a time-saving and cost-effective strategy. The present review emphasizes prominent classes of natural products and lead molecules obtained from herbal preparations, their explored multi-targeted effects against CKD, and novel targets predicted and validated using the NP approach.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"30 ","pages":"Article 100421"},"PeriodicalIF":2.4,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142723157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy and safety of crocin supplementation in patients with central serous chorioretinopathy, a pilot randomized double blinded clinical trial","authors":"Mohammadkarim Johari, Alireza Attar, Mojtaba Heydari","doi":"10.1016/j.phanu.2024.100422","DOIUrl":"10.1016/j.phanu.2024.100422","url":null,"abstract":"<div><h3>Background</h3><div>Central Serous Chorioretinopathy (CSCR) is a vision-threatening condition characterized by serous retinal detachment. Crocin, a carotenoid compound found in saffron, has demonstrated antioxidant and anti-inflammatory properties in various retinal diseases, but its efficacy in CSCR remains understudied.</div></div><div><h3>Methods</h3><div>In this randomized controlled trial, 40 patients with CSCR were assigned to receive either crocin (n=20) or placebo (n=20) over an eight-weeks period. Visual acuity, anatomical outcomes measured by optical coherence tomography (OCT), and adverse events were assessed at baseline and at the end of the intervention period.</div></div><div><h3>Results</h3><div>There were no significant differences observed in age, weight, body mass index, or gender distribution between the two groups (p > 0.05 for all comparisons). The changes in mean ETDRS letter score were significantly more in crocin group compared to the placebo group (4.27±3.63 vs 0.57±7.23, respectively, p=0.024). In the crocin group, 20 %, 40 % and 80 % of patients showed an improvement of 10,5 and 1 ETDRS letters, compared to only 7 %, 21 % and 29 % in the placebo group (p=0.316, p=0.280, p=0.005, respectively). While the crocin group exhibited greater mean reductions in sub-retinal fluid height, central macular thickness, and choroidal thickness compared to the placebo group, these differences did not reach statistical significance (p > 0.05 for all comparisons). No adverse events associated with the trial intervention were reported by any patient in either the crocin or placebo group.</div></div><div><h3>Conclusion</h3><div>The findings of this pilot study suggest that crocin supplementation may lead to improvements in visual acuity in patients with CSCR. Differences in anatomical outcomes between crocin and placebo groups did not reach statistical significance in this pilot study.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"30 ","pages":"Article 100422"},"PeriodicalIF":2.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PharmaNutritionPub Date : 2024-11-08DOI: 10.1016/j.phanu.2024.100420
Cato Wiegers, Sofia el Sarraf, Olaf F.A. Larsen
{"title":"Dietitians’ knowledge and practice regarding inflammaging and related interventions: A pilot survey","authors":"Cato Wiegers, Sofia el Sarraf, Olaf F.A. Larsen","doi":"10.1016/j.phanu.2024.100420","DOIUrl":"10.1016/j.phanu.2024.100420","url":null,"abstract":"<div><h3>Background</h3><div>The global population is aging rapidly, which is associated with an increase in chronic diseases. One of the possible underlying causes of these chronic diseases is inflammaging, characterised by the general low-grade inflammation that occurs in the body as we age. However, it is unclear to what extent this concept is already being considered as a base for prevention or therapy.</div></div><div><h3>Methods</h3><div>In this study, the willingness of practicing dietitians in the Netherlands to apply interventions targeting inflammaging was evaluated. Beforehand, a literature study was executed to identify possible parameters for intervention, covering most nutritional, biological, and medical aspects related to inflammaging. Based on the findings of the literature study, dietitians were asked about their awareness of the concept, the willingness to adopt more knowledge, and practical approaches regarding their clients.</div></div><div><h3>Results</h3><div>It was found that of the 56 surveyed dietitians, approximately two-third were already aware of the concept, and among this group, another two-third indicated that inflammaging plays a role in their provision of dietary advice. Generally, the information provided by the dietitians was in line with what was identified in literature.</div></div><div><h3>Conclusions</h3><div>As a first pilot, it appears that dietitians recognise the impact of nutrition and lifestyle factors on the progression of inflammaging. The willingness to adopt evidence-based practices signifies the importance of continued education and professional development in this area. Eventually, focusing on inflammaging in policy making could be a supporting factor for healthcare systems in the shift from curative to preventive care.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"30 ","pages":"Article 100420"},"PeriodicalIF":2.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142656416","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}
PharmaNutritionPub Date : 2024-11-03DOI: 10.1016/j.phanu.2024.100419
Satarupa Deb , Anupom Borah
{"title":"Exploring the molecular mechanisms and therapeutic benefits of L-theanine in counteracting inflammation","authors":"Satarupa Deb , Anupom Borah","doi":"10.1016/j.phanu.2024.100419","DOIUrl":"10.1016/j.phanu.2024.100419","url":null,"abstract":"<div><div>Chronic inflammation, a persistent condition that can significantly impact the body, is linked to the development and progression of numerous chronic degenerative diseases. Understanding its complex role is essential for discovering innovative therapeutic approaches, particularly those derived from natural sources. These strategies aim to reduce chronic inflammation and mitigate its associated diseases. Historically, natural products have been used for their therapeutic properties, including anti-inflammatory effects. They often offer advantages such as abundant availability, cost-effectiveness, and fewer side effects compared to synthetic drugs. L-theanine, an amino acid primarily found in tea leaves, has garnered significant attention for its potential health benefits, especially its anti-inflammatory properties. Research suggests that L-theanine may decrease levels of inflammatory markers in the body and modulate the immune system, preventing excessive inflammatory responses. While the growing evidence supports L-theanine's ability to attenuate harmful inflammation, the exact molecular mechanisms underlying its action remain largely unknown. This review seeks to elucidate these mechanisms, providing a comprehensive understanding of its role in modulating inflammation and its potential as a natural therapeutic agent.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"30 ","pages":"Article 100419"},"PeriodicalIF":2.4,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142656414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PharmaNutritionPub Date : 2024-11-02DOI: 10.1016/j.phanu.2024.100417
Christiane Schoen , Line Johnsen , Antje Micka , Manfred Wilhelm , Yunpeng Ding
{"title":"Enhanced absorption of omega-3 fatty acids from a novel krill oil-derived phospholipid formulation compared to fish oil ethyl esters: A randomized, two-way crossover pharmacokinetic study","authors":"Christiane Schoen , Line Johnsen , Antje Micka , Manfred Wilhelm , Yunpeng Ding","doi":"10.1016/j.phanu.2024.100417","DOIUrl":"10.1016/j.phanu.2024.100417","url":null,"abstract":"<div><h3>Background</h3><div>Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) offer many health benefits, yet the absorption from standard ethyl ester (EE) formulation requires concurrent intake of a fatty meal. This study aimed to evaluate the absorption of EPA and DHA from a novel omega-3 formulation, Phospholipids + EPA/DHA (PL+), which combines high phospholipdi krill oil (KO) and EE, in comparison to a standard EE product under a low-fat dietary condition in healthy adults.</div></div><div><h3>Methods</h3><div>In this randomized, cross-over, single-dose study, the pharmacokinetic profiles of EPA and DHA from PL+ and EE product was assessed. Each products contained approximately 1200 mg EPA+DHA. Participants consumed a single dose of the capsules under a low-fat diet regimen, with plasma samples collected at baseline and over a 72-hour period after dosing. Following a 14-day washout period, participants crossed over to the alternate treatment. Plasma concentrations of EPA, DHA, and combined EPA+DHA were analyzed.</div></div><div><h3>Results</h3><div>Twelve participants (six women and six men) were included, completed all study visits and were included in the analyses. The participants' mean age was 34.3 years (SD = 12.4), and the mean BMI was 22.6 kg/m² (SD = 3.2). The baseline-corrected incremental area under the curve (iAUC<sub>0–12h</sub>) for combined EPA+DHA was significantly higher for PL+ (255.5 [SD = 81.4] μg/mL*h) compared to EE (34.2 [SD = 33.4] μg/mL*h; P < 0.001). The treatment ratio of iAUC<sub>0–12h</sub> for PL+ relative to EE was 10.5 (95 % CI: 6.1 – 18.1; P < 0.001). Similar patterns were observed for iAUC<sub>0–24h</sub> and iAUC<sub>0–72h</sub> for combined EPA+DHA, as well as for EPA and DHA individually. Sensitivity analyses by adjusting the minimal difference on dose between products yielded consistent findings.</div></div><div><h3>Conclusions</h3><div>The results indicate that PL+ technology significantly enhances the absorption of EPA and DHA compared to standard EE alone in a low-fat dietary condition. These outcomes suggest that the absorption of EE formulations can be significantly improved through combination with high phospholipid krill oil, as evidenced by the performance of the PL+ formulation.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"30 ","pages":"Article 100417"},"PeriodicalIF":2.4,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142656415","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}
PharmaNutritionPub Date : 2024-10-31DOI: 10.1016/j.phanu.2024.100418
Victoria Martínez-Sánchez , Javier Fontecha , Antonio Pérez-Gálvez
{"title":"Milk fat globule membrane: Production, digestion, and health benefits evaluated through in vitro models","authors":"Victoria Martínez-Sánchez , Javier Fontecha , Antonio Pérez-Gálvez","doi":"10.1016/j.phanu.2024.100418","DOIUrl":"10.1016/j.phanu.2024.100418","url":null,"abstract":"<div><h3>Background</h3><div>Milk is a biologically complex fluid with a primary function as a bioactive compound and energy source for the offspring in the early stages of life. This role is largely due to its high lipid content, encapsulated in globules known as milk fat globules (MFG). Extensive research has led to the conclusion that MFGs are not only energy carriers, as they are surrounded by a milk fat globule membrane (MFGM) which is characterized by its complex architecture and bioactive components such as polar lipids and glycoproteins.</div></div><div><h3>Methods</h3><div>This literature review was performed by an extensive search of Pubmed, Scopus or Google Scholar database for studies using keywords such as “lactation”, “milk production”, “MFG”, “MFGM”, “polar lipids”, “in vitro”, “milk lipids”, “health benefits”, “human health”, “digestion”, “bioaccessibility”, “bioavailability”.</div></div><div><h3>Results</h3><div>Brain and intestinal development, modulation of the microbiota or the correct immunological response to infections are some of the benefits that MFGM has in infants. In addition, its therapeutic potential is extended to the adult population through the attenuation of lipid metabolism disorders or the prevention of neurodegenerative diseases. Consequently, the trend in the food industry is to incorporate this MFGM concentrate as a bioactive ingredient in functional foods.</div></div><div><h3>Conclusion</h3><div>This review provides an overview of the natural and industrial production of MFGM and their relationship to the health benefits identified in in vitro studies. Furthermore, this review highlights the importance of further research to understand the assimilation of MFGM lipids to optimize its incorporation into the human diet.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"30 ","pages":"Article 100418"},"PeriodicalIF":2.4,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142586171","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}
PharmaNutritionPub Date : 2024-10-24DOI: 10.1016/j.phanu.2024.100416
Smriti Mishra , Shikha Saxena , Rajendra Awasthi
{"title":"Advancements in psoriasis management: Integrating nutrient supplement with gut-brain-skin connection","authors":"Smriti Mishra , Shikha Saxena , Rajendra Awasthi","doi":"10.1016/j.phanu.2024.100416","DOIUrl":"10.1016/j.phanu.2024.100416","url":null,"abstract":"<div><h3>Background</h3><div>Psoriasis is a chronic inflammatory skin disease that affects a large population globally and poses a significant challenge in clinical care due to its multifaceted characteristics. Recent studies show the relationship between the gut, brain, and skin, unveiling the potential for novel therapeutic approaches.</div></div><div><h3>Methods</h3><div>This review includes papers published from 1991 to 2024 exploring various advancements in psoriasis management. We also explored various techniques to encapsulate natural bioactive molecules with anti-psoriatic activity. The published articles were searched using various databases, including Scopus, Web of Science, Clinical Trials, and Google Scholar.</div></div><div><h3>Results</h3><div>The gut microbiome contains numerous microorganisms that influence immune regulation and inflammation. The pathogenesis of psoriasis has implicated an imbalance in gut microbes, known as gut dysbiosis. Probiotics, prebiotics, and other dietary interventions can help restore microbial balance and improve psoriasis symptoms. Furthermore, the gut microbiota can modulate neurotransmitters and neuropeptides, impacting communication between the gut, brain, and skin. Stress, a well-established trigger for psoriasis exacerbations, disrupts the gut-brain-skin axis. Nutrient supplements like omega-3 fatty acids, polyphenols, probiotic supplements, herbal supplements, <em>etc</em>. can reduce inflammation and enhance skin health. Deficiency in nutrients like vitamin D may contribute to psoriasis development. Targeting inflammatory pathways, balancing gut microbiomes, and addressing nutritional deficiencies can improve psoriasis treatment outcomes.</div></div><div><h3>Conclusion</h3><div>Natural bioactives have demonstrated antipsoriatic efficacy in several preclinical and clinical studies done in more recent years. Large-scale clinical trials using encapsulated natural bioactives are still needed to demonstrate their antipsoriatic activity and ability to regulate the gut-brain-skin axis.</div></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"30 ","pages":"Article 100416"},"PeriodicalIF":2.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}