Pub Date : 2025-08-01Epub Date: 2025-06-20DOI: 10.52225/narra.v5i2.1989
Yudith V Paramitadevi, Cindy R Priadi, Iftita Rahmatika, Andriansjah Rukmana
Farm workers who handle livestock stools face an increased risk of infection by pathogenic bacteria, such as Escherichia coli O157 and Salmonella spp., leading to millions of severe health issues and thousands of fatalities annually. The aim of this study was to assess the impact of these pathogens by measuring their concentrations, determining rates of unintentional fecal consumption, and conducting a quantitative assessment of microbial risk. An integrated farm in Sukabumi City, Indonesia, was examined for E. coli O157 and Salmonella spp. in livestock stools. Additionally, the study monitored the rate of incidental fecal ingestion among farm workers. Stool samples were collected (n= 40) from ruminants and analyzed following ISO 16649-1:2018, ISO 9308-1:2014, and ISO 6579-1:2017/Amd.1:2020. The study tracked worker's behavior daily to determine the contact time. The fecal ingestion rate was calculated by multiplying the estimated stool weight ingested by the contact time workers spent cleaning livestock stools in the barn each day. Microbial analysis revealed that the highest concentration of E. coli O157 in beef cattle stools was 2.49 log10 CFU/g. The study determined mean fecal ingestion rates during the dry season (8.64 mg/day) and rainy season (6.84 mg/day). Results from the quantitative microbial risk assessment showed that stool from beef cattle posed a higher risk of E. coli O157 infection compared to other ruminants, with an estimated disease burden of 9.8 × 10-3 pppy. This study represents the first comprehensive quantitative evaluation of fecal ingestion by farm workers during animal husbandry. The findings underscore the need for improved worker safety measures, such as enhanced sanitation practices and protective equipment, to mitigate the risks of handling livestock stools.
{"title":"Fecal ingestion rate based on worker activity patterns during stool handling in a ruminant farm.","authors":"Yudith V Paramitadevi, Cindy R Priadi, Iftita Rahmatika, Andriansjah Rukmana","doi":"10.52225/narra.v5i2.1989","DOIUrl":"10.52225/narra.v5i2.1989","url":null,"abstract":"<p><p>Farm workers who handle livestock stools face an increased risk of infection by pathogenic bacteria, such as <i>Escherichia coli</i> O157 and <i>Salmonella spp</i>., leading to millions of severe health issues and thousands of fatalities annually. The aim of this study was to assess the impact of these pathogens by measuring their concentrations, determining rates of unintentional fecal consumption, and conducting a quantitative assessment of microbial risk. An integrated farm in Sukabumi City, Indonesia, was examined for <i>E. coli</i> O157 and <i>Salmonella spp</i>. in livestock stools. Additionally, the study monitored the rate of incidental fecal ingestion among farm workers. Stool samples were collected (n= 40) from ruminants and analyzed following ISO 16649-1:2018, ISO 9308-1:2014, and ISO 6579-1:2017/Amd.1:2020. The study tracked worker's behavior daily to determine the contact time. The fecal ingestion rate was calculated by multiplying the estimated stool weight ingested by the contact time workers spent cleaning livestock stools in the barn each day. Microbial analysis revealed that the highest concentration of <i>E. coli</i> O157 in beef cattle stools was 2.49 log<sub>10</sub> CFU/g. The study determined mean fecal ingestion rates during the dry season (8.64 mg/day) and rainy season (6.84 mg/day). Results from the quantitative microbial risk assessment showed that stool from beef cattle posed a higher risk of <i>E. coli</i> O157 infection compared to other ruminants, with an estimated disease burden of 9.8 × 10<sup>-3</sup> pppy. This study represents the first comprehensive quantitative evaluation of fecal ingestion by farm workers during animal husbandry. The findings underscore the need for improved worker safety measures, such as enhanced sanitation practices and protective equipment, to mitigate the risks of handling livestock stools.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e1989"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067210","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}
Pub Date : 2025-08-01Epub Date: 2025-06-04DOI: 10.52225/narra.v5i2.1649
Dani Rosdiana, Fajri M Siregar, Nabila C Ediwi, Rahmi T Putri, Zuyyina Er Nurrahma, Adinda Elisabet, Rosantia Sarassari, Dodi Safari, Cimi Ilmiawati, Aisyah Elliyanti
Community-acquired pneumonia (CAP) poses a significant impact on the healthcare system due to rehospitalization and mortality. About one-third of hospitalized CAP patients died within one year. In addition to advanced age, vulnerable groups with comorbidities such as cancer, diabetes, and cerebrovascular disease (CVD) are more likely to suffer from severe CAP. The aim of this study was to investigate the factors linked to mortality in adult hospitalized CAP patients. The study extracted the medical records of patients aged ≥18 years, admitted to a referral hospital in Riau Province, who were diagnosed with CAP between January and December 2023. Multiple logistic regression step-wise analysis was employed to determine the factors associated with mortality in CAP patients. The study involved 334 patients with a median age of 58 years. Based on the confusion, urea, respiratory rate, blood pressure, and age ≥65 years (CURB-65) score, 11.9% of patients had severe CAP (CURB-65 scores 3 and 4). Age was a significant predictor of severe CAP (p≤0.001). The most prevalent comorbidities were malignancy (33.2%), CVD (30.2%), and diabetes (28.4%). Mortality incidence during hospitalization reached 35.9%. Significant factors associated with mortality in hospitalized CAP patients included renal dysfunction/elevated serum urea levels (p=0.031), CURB-65 score (p=0.023), vasopressor use (p≤0.001), mechanical ventilator use (p≤0.01) and steroid use (p=0.029). However, CVD was associated with a decreased risk of mortality (p=0.019). Gram-negative bacteria predominated, accounting for 50.6% of all positive isolates. Several significant factors were associated with mortality in adult patients hospitalized with CAP at referral Hospital in Riau, including renal dysfunction, CURB-65 score, vasopressor use, mechanical ventilator use, and steroid use. This finding underscored the importance of early identification factors in CAP patients.
{"title":"Mortality and associated factors among community-acquired pneumonia patients: A cross-sectional study in a provincial referral hospital in Indonesia.","authors":"Dani Rosdiana, Fajri M Siregar, Nabila C Ediwi, Rahmi T Putri, Zuyyina Er Nurrahma, Adinda Elisabet, Rosantia Sarassari, Dodi Safari, Cimi Ilmiawati, Aisyah Elliyanti","doi":"10.52225/narra.v5i2.1649","DOIUrl":"10.52225/narra.v5i2.1649","url":null,"abstract":"<p><p>Community-acquired pneumonia (CAP) poses a significant impact on the healthcare system due to rehospitalization and mortality. About one-third of hospitalized CAP patients died within one year. In addition to advanced age, vulnerable groups with comorbidities such as cancer, diabetes, and cerebrovascular disease (CVD) are more likely to suffer from severe CAP. The aim of this study was to investigate the factors linked to mortality in adult hospitalized CAP patients. The study extracted the medical records of patients aged ≥18 years, admitted to a referral hospital in Riau Province, who were diagnosed with CAP between January and December 2023. Multiple logistic regression step-wise analysis was employed to determine the factors associated with mortality in CAP patients. The study involved 334 patients with a median age of 58 years. Based on the confusion, urea, respiratory rate, blood pressure, and age ≥65 years (CURB-65) score, 11.9% of patients had severe CAP (CURB-65 scores 3 and 4). Age was a significant predictor of severe CAP (<i>p≤</i>0.001). The most prevalent comorbidities were malignancy (33.2%), CVD (30.2%), and diabetes (28.4%). Mortality incidence during hospitalization reached 35.9%. Significant factors associated with mortality in hospitalized CAP patients included renal dysfunction/elevated serum urea levels (<i>p</i>=0.031), CURB-65 score (<i>p</i>=0.023), vasopressor use (<i>p≤</i>0.001), mechanical ventilator use (<i>p≤</i>0.01) and steroid use (p=0.029). However, CVD was associated with a decreased risk of mortality (<i>p</i>=0.019). Gram-negative bacteria predominated, accounting for 50.6% of all positive isolates. Several significant factors were associated with mortality in adult patients hospitalized with CAP at referral Hospital in Riau, including renal dysfunction, CURB-65 score, vasopressor use, mechanical ventilator use, and steroid use. This finding underscored the importance of early identification factors in CAP patients.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e1314"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067169","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}
Pub Date : 2025-08-01Epub Date: 2025-04-21DOI: 10.52225/narra.v5i2.1721
Didik S Heriyanto, Ika Trisnawati, Lisnawati Rachmadi, Jeffry B Tenggara, Vincent Lau, Andrew N Gunawan, Brigitta N Halim, Fara S Yuliani, Vincent Laiman, Soehartati Gondhowiardjo, Hsiao-Chi Chuang
Lung cancer patients in Indonesia exhibit a high prevalence of epidermal growth factor receptor (EGFR) mutations, with a substantial proportion attributed to rare or uncommon variants. The clinical significance of rare EGFR mutations lies in their differential sensitivity to tyrosine kinase inhibitors (TKIs). While they are frequently resistant to first- and second-generation TKIs, they often respond to third-generation TKIs, necessitating tailored treatment options. The need for improving access to advanced targeted therapies in Indonesia also highlights the importance of conducting research on rare EGFR mutations. The aim of this study was to identify the spectrum and frequency of EGFR mutations in patients with lung adenocarcinoma in Indonesia. A cross-sectional observational study with total sampling was conducted from January 2016 to April 2024 to investigate EGFR mutation profiles in lung adenocarcinoma patients. Samples were acquired from patients with a confirmed anatomical pathology diagnosis from various healthcare centers across Indonesia. A total of 4,778 samples were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) on various specimen types to determine EGFR mutation prevalence and patterns. Associations between demographic data and EGFR mutation status were assessed. EGFR mutations were detected in 54.6% of samples, with common mutations (exon 19 deletions/insertions and point mutation L858R) comprising 76.2% of positive cases and rare mutations (exon 20 insertions, point mutation G719X, S768I, T790M, and L861Q) accounted for 20.3%. Significant associations were found between geographic origin, age, and sex with EGFR mutation status. This study confirms substantial genetic variability and geographical differences in EGFR mutations among Indonesian lung adenocarcinoma patients, emphasizing the urgent need for further research to prompt enhanced molecular diagnostics and targeted therapies in the region.
{"title":"Spectrum of rare <i>EGFR</i> mutations in Indonesian lung adenocarcinoma: Findings from an 8-year analysis of 4,778 cases highlighting the need for advanced targeted therapies.","authors":"Didik S Heriyanto, Ika Trisnawati, Lisnawati Rachmadi, Jeffry B Tenggara, Vincent Lau, Andrew N Gunawan, Brigitta N Halim, Fara S Yuliani, Vincent Laiman, Soehartati Gondhowiardjo, Hsiao-Chi Chuang","doi":"10.52225/narra.v5i2.1721","DOIUrl":"10.52225/narra.v5i2.1721","url":null,"abstract":"<p><p>Lung cancer patients in Indonesia exhibit a high prevalence of epidermal growth factor receptor (<i>EGFR</i>) mutations, with a substantial proportion attributed to rare or uncommon variants. The clinical significance of rare <i>EGFR</i> mutations lies in their differential sensitivity to tyrosine kinase inhibitors (TKIs). While they are frequently resistant to first- and second-generation TKIs, they often respond to third-generation TKIs, necessitating tailored treatment options. The need for improving access to advanced targeted therapies in Indonesia also highlights the importance of conducting research on rare <i>EGFR</i> mutations. The aim of this study was to identify the spectrum and frequency of <i>EGFR</i> mutations in patients with lung adenocarcinoma in Indonesia. A cross-sectional observational study with total sampling was conducted from January 2016 to April 2024 to investigate <i>EGFR</i> mutation profiles in lung adenocarcinoma patients. Samples were acquired from patients with a confirmed anatomical pathology diagnosis from various healthcare centers across Indonesia. A total of 4,778 samples were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) on various specimen types to determine <i>EGFR</i> mutation prevalence and patterns. Associations between demographic data and <i>EGFR</i> mutation status were assessed. <i>EGFR</i> mutations were detected in 54.6% of samples, with common mutations (exon 19 deletions/insertions and point mutation L858R) comprising 76.2% of positive cases and rare mutations (exon 20 insertions, point mutation G719X, S768I, T790M, and L861Q) accounted for 20.3%. Significant associations were found between geographic origin, age, and sex with <i>EGFR</i> mutation status. This study confirms substantial genetic variability and geographical differences in <i>EGFR</i> mutations among Indonesian lung adenocarcinoma patients, emphasizing the urgent need for further research to prompt enhanced molecular diagnostics and targeted therapies in the region.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e1721"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067191","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}
Pub Date : 2025-08-01Epub Date: 2025-04-28DOI: 10.52225/narra.v5i2.1596
Muhammad I Rivai, Ronald E Lusikooy, Andani E Putra, Aisyah Elliyanti, Ade Sukma
Lactococcus lactis D4 is a probiotic produced through the fermentation of buffalo milk in bamboo, namely "dadih", a traditional food from West Sumatera, Indonesia. To the best of our knowledge, no specific research has investigated the effects of L. lactis D4, derived from dadih extraction, on colorectal cancer or its potential clinical applications. Therefore, the aim of this study was to evaluate the potential of L. lactis D4 from dadih to inhibit colorectal cancer growth in rat models, with a focus on its effects on cell proliferation, apoptosis, and inflammatory responses. An in vivo study was conducted using 37 male Sprague-Dawley rats, allocated into five groups: (1) control (no treatment), (2) dysplasia (induced with 1,2-dimethylhydrazine until dysplasia developed), (3) dysplasia + L. lactis D4 (induced with 1,2-dimethylhydrazine, then treated with L. lactis D4 after dysplasia confirmation), (4) cancer (induced with 1,2-dimethylhydrazine until cancer was confirmed), and (5) cancer + L. lactis D4 (induced with 1,2-dimethylhydrazine until cancer was confirmed, then treated with L. lactis D4 for 15 days). The effects of L. lactis D4 on cancer progression were assessed through immunohistochemical analysis of cell proliferation (cyclin D1, Bcl-2), apoptosis (p53, caspase-3), and inflammation (nuclear factor-κB (NF-κB) and cyclooxygenase-2 (COX-2)). This study found that L. lactis D4 treatment reduced adenocarcinoma and dysplasia severity in colorectal cancer models through significant reduction in cyclin D1, Bcl-2, NF-κB, and COX-2 expression observed across all groups (p<0.01), although changes in dysplasia and cancer subgroups were not statistically significant (p>0.05). No statistically significant change was noted in p53 expression (p=0.518), whereas caspase-3 expression varied significantly across groups (p=0.010). In conclusion, L. lactis D4 reduces the expression of cyclin D1, Bcl-2, NF-κB, and COX-2 proteins, offering insights into its potential to modulating proliferation and inflammation in colorectal cancer growth.
{"title":"Exploring the potential effects of <i>Lactococcus lactis</i> D4 on the proliferation, apoptosis, and inflammatory responses in colorectal cancer cells.","authors":"Muhammad I Rivai, Ronald E Lusikooy, Andani E Putra, Aisyah Elliyanti, Ade Sukma","doi":"10.52225/narra.v5i2.1596","DOIUrl":"10.52225/narra.v5i2.1596","url":null,"abstract":"<p><p><i>Lactococcus lactis</i> D4 is a probiotic produced through the fermentation of buffalo milk in bamboo, namely \"<i>dadih</i>\", a traditional food from West Sumatera, Indonesia. To the best of our knowledge, no specific research has investigated the effects of <i>L. lactis</i> D4, derived from <i>dadih</i> extraction, on colorectal cancer or its potential clinical applications. Therefore, the aim of this study was to evaluate the potential of <i>L. lactis</i> D4 from <i>dadih</i> to inhibit colorectal cancer growth in rat models, with a focus on its effects on cell proliferation, apoptosis, and inflammatory responses. An in vivo study was conducted using 37 male Sprague-Dawley rats, allocated into five groups: (1) control (no treatment), (2) dysplasia (induced with 1,2-dimethylhydrazine until dysplasia developed), (3) dysplasia + <i>L. lactis</i> D4 (induced with 1,2-dimethylhydrazine, then treated with <i>L. lactis</i> D4 after dysplasia confirmation), (4) cancer (induced with 1,2-dimethylhydrazine until cancer was confirmed), and (5) cancer + <i>L. lactis</i> D4 (induced with 1,2-dimethylhydrazine until cancer was confirmed, then treated with <i>L. lactis</i> D4 for 15 days). The effects of <i>L. lactis</i> D4 on cancer progression were assessed through immunohistochemical analysis of cell proliferation (cyclin D1, Bcl-2), apoptosis (p53, caspase-3), and inflammation (nuclear factor-κB (NF-κB) and cyclooxygenase-2 (COX-2)). This study found that <i>L. lactis</i> D4 treatment reduced adenocarcinoma and dysplasia severity in colorectal cancer models through significant reduction in cyclin D1, Bcl-2, NF-κB, and COX-2 expression observed across all groups (<i>p</i><0.01), although changes in dysplasia and cancer subgroups were not statistically significant (<i>p</i>>0.05). No statistically significant change was noted in p53 expression (<i>p</i>=0.518), whereas caspase-3 expression varied significantly across groups (<i>p</i>=0.010). In conclusion, <i>L. lactis</i> D4 reduces the expression of cyclin D1, Bcl-2, NF-κB, and COX-2 proteins, offering insights into its potential to modulating proliferation and inflammation in colorectal cancer growth.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e1596"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067205","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}
Smoking remains a prevalent habit in many households, particularly in regions where cultural norms strongly accept tobacco use. The aim of this study was to examine the influential role of wives in Gayo Lues, Aceh, Indonesia, in promoting smoking cessation within their families. Amidst cultural norms that widely accept smoking, these wives employed both persuasive and, occasionally, coercive methods to encourage healthier behaviors among family members. Utilizing a qualitative approach with Participatory Action Research (PAR), data were collected through in-depth interviews with seven wives who have firsthand experience with smoking behaviors in their families. The findings revealed that wives in Gayo Lues act as both health monitors and guardians, balancing emotional support with firm boundaries to foster a smoke-free home environment. Their roles extended beyond traditional caregiving, as they actively shape family health outcomes. In conclusion, this study underscored the importance of empowering wives as health advocates in public health efforts, particularly in culturally conservative settings. Future research could further explore the broader socio-cultural dynamics influencing wives' health advocacy roles and assess the sustainability of these behaviors over time.
{"title":"Striving for smoke-free families: Wives' role in Gayo Lues, Aceh-Indonesia.","authors":"Hasrizal Saffutra, Mustanir Yahya, Rizanna Rosemary, Rosaria Indah, Dedy Syahrizal","doi":"10.52225/narra.v5i2.1960","DOIUrl":"10.52225/narra.v5i2.1960","url":null,"abstract":"<p><p>Smoking remains a prevalent habit in many households, particularly in regions where cultural norms strongly accept tobacco use. The aim of this study was to examine the influential role of wives in Gayo Lues, Aceh, Indonesia, in promoting smoking cessation within their families. Amidst cultural norms that widely accept smoking, these wives employed both persuasive and, occasionally, coercive methods to encourage healthier behaviors among family members. Utilizing a qualitative approach with Participatory Action Research (PAR), data were collected through in-depth interviews with seven wives who have firsthand experience with smoking behaviors in their families. The findings revealed that wives in Gayo Lues act as both health monitors and guardians, balancing emotional support with firm boundaries to foster a smoke-free home environment. Their roles extended beyond traditional caregiving, as they actively shape family health outcomes. In conclusion, this study underscored the importance of empowering wives as health advocates in public health efforts, particularly in culturally conservative settings. Future research could further explore the broader socio-cultural dynamics influencing wives' health advocacy roles and assess the sustainability of these behaviors over time.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e1960"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067170","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}
Pub Date : 2025-08-01Epub Date: 2025-05-09DOI: 10.52225/narra.v5i2.2439
Shinta Kusumawati, Agustina T Endharti, Farhad Balafif, Shahdevi N Kurniawan, Aris Rosidah, Rabjhany Anaqah, Izzunazel A Barqillah, Husnul Khotimah
Parkinson's disease is a progressive, incurable neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and pathological aggregation of α-synuclein in the midbrain, leading to motor dysfunction. Thymoquinone (TQ), an active compound from Nigella sativa, has demonstrated antioxidant properties that may reduce dopamine degradation, while madecassoside (MA), a triterpenoid component of Centella asiatica, exhibits neuroprotective effects. To date, no study has investigated the combined effects of TQ and MA in a Parkinson's disease model. The aim of this study was to evaluate the synergistic neuroprotective potential of TQ and MA on motor function, dopamine levels, α-synuclein accumulation, and mature brain-derived neurotrophic factor (mBDNF) expression in a rotenone (ROT)-induced mouse model of early Parkinson's disease. Rotenone (2.5 mg/kg BW) was administered subcutaneously for two weeks to induce Parkinson's disease, while TQ alone, MA alone and combination of TQ and MA at various doses, as well as a reference drug (pramipexole) were given every 48 hours concurrently with rotenone. Motor symptoms were assessed through behavioral tests, including the open field test (OFT), beam walking test, and hanging wire test; midbrain dopamine levels were quantified via enzyme-linked immunosorbent assay (ELISA), α-synuclein expression was assessed using Western blotting, and immunohistochemistry was used to detect mBDNF-positive cells in the cerebral cortex. The combination of TQ and MA significantly increased midbrain dopamine levels and improved locomotor activity, as shown by increased total distance traveled and mean velocity in ROT-induced mice. Biochemically, this combined treatment reduced α-synuclein expression, suggesting attenuation of early pathological aggregation typically observed in Parkinson's disease. Although the increase in mBDNF expression in the cerebral cortex was not statistically significant, it was higher in the TQ-MA treatment group compared to controls and other groups. Collectively, these results highlight the therapeutic potential of TQ and MA in combination to counteract both motor deficits and early neurochemical disruptions in a ROT-induced model of Parkinson's disease.
{"title":"Thymoquinone and madecassoside improve motor function in a rotenone-induced mouse model of early Parkinson's disease: Role of dopamine, alpha-synuclein and mBDNF.","authors":"Shinta Kusumawati, Agustina T Endharti, Farhad Balafif, Shahdevi N Kurniawan, Aris Rosidah, Rabjhany Anaqah, Izzunazel A Barqillah, Husnul Khotimah","doi":"10.52225/narra.v5i2.2439","DOIUrl":"10.52225/narra.v5i2.2439","url":null,"abstract":"<p><p>Parkinson's disease is a progressive, incurable neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and pathological aggregation of α-synuclein in the midbrain, leading to motor dysfunction. Thymoquinone (TQ), an active compound from <i>Nigella sativa</i>, has demonstrated antioxidant properties that may reduce dopamine degradation, while madecassoside (MA), a triterpenoid component of <i>Centella asiatica</i>, exhibits neuroprotective effects. To date, no study has investigated the combined effects of TQ and MA in a Parkinson's disease model. The aim of this study was to evaluate the synergistic neuroprotective potential of TQ and MA on motor function, dopamine levels, α-synuclein accumulation, and mature brain-derived neurotrophic factor (mBDNF) expression in a rotenone (ROT)-induced mouse model of early Parkinson's disease. Rotenone (2.5 mg/kg BW) was administered subcutaneously for two weeks to induce Parkinson's disease, while TQ alone, MA alone and combination of TQ and MA at various doses, as well as a reference drug (pramipexole) were given every 48 hours concurrently with rotenone. Motor symptoms were assessed through behavioral tests, including the open field test (OFT), beam walking test, and hanging wire test; midbrain dopamine levels were quantified via enzyme-linked immunosorbent assay (ELISA), α-synuclein expression was assessed using Western blotting, and immunohistochemistry was used to detect mBDNF-positive cells in the cerebral cortex. The combination of TQ and MA significantly increased midbrain dopamine levels and improved locomotor activity, as shown by increased total distance traveled and mean velocity in ROT-induced mice. Biochemically, this combined treatment reduced α-synuclein expression, suggesting attenuation of early pathological aggregation typically observed in Parkinson's disease. Although the increase in mBDNF expression in the cerebral cortex was not statistically significant, it was higher in the TQ-MA treatment group compared to controls and other groups. Collectively, these results highlight the therapeutic potential of TQ and MA in combination to counteract both motor deficits and early neurochemical disruptions in a ROT-induced model of Parkinson's disease.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e2439"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067207","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}
Pub Date : 2025-08-01Epub Date: 2025-05-19DOI: 10.52225/narra.v5i2.1828
Bayu T Dirja, Agung Putra, Nur D Amalina
Mesenchymal stem cell-derived secretome (MSC-derived secretome) has shown promise in regenerative medicine; however, research specifically evaluating its efficacy in third-degree burn wounds remains scarce. The aim of this study was to investigate the effects of MSC-derived secretome on cellular proliferation, angiogenesis, myofibroblast activity, and collagen synthesis in a third-degree burn wound model. A total of 20 Wistar rats were randomly assigned to four groups: a healthy control group, a negative control group with untreated third-degree burn wounds, and two treatment groups receiving MSC-derived secretome at doses of 100 µL and 200 µL for 14 days. The wound healing was assessed 14 days post-treatment. Proliferating cell nuclear antigen (PCNA) protein expression was quantified via Western blot to assess cell proliferation; vascular endothelial growth factor (VEGF) gene expression was analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) to examine angiogenesis; alpha-smooth muscle actin (α-SMA) expression was assessed through immunohistochemistry to evaluate myofibroblast activity; and collagen density was measured using Masson's trichrome staining to determine tissue remodeling. Our data indicated that MSC-derived secretome treatment significantly enhanced multiple aspects of the healing process in a dose-dependent manner. PCNA expression increased by 2.8-fold in the 200 µL MSC-derived secretome group compared to the negative control (p<0.05). VEGF gene expression was upregulated by 2.14-fold in the 200 µL secretome group compared to the negative control (p<0.05). α-SMA protein expression increased by 12.67% in the 200 µL secretome group, while collagen density demonstrated the most pronounced improvement at the 200 µL dose, reaching an increase of 81.26% (p<0.05). In conclusion, MSC-derived secretome significantly accelerates burn wound healing by promoting cell proliferation, enhancing angiogenesis, and increasing collagen synthesis while modulating myofibroblast activity. This highlights the potential of MSC-derived secretome as a therapeutic option for optimizing burn wound repair and reducing fibrotic complications.
{"title":"Mesenchymal stem cell-derived secretome accelerates third-degree burn wound healing: Effects on proliferation, angiogenesis, and fibrosis regulation.","authors":"Bayu T Dirja, Agung Putra, Nur D Amalina","doi":"10.52225/narra.v5i2.1828","DOIUrl":"10.52225/narra.v5i2.1828","url":null,"abstract":"<p><p>Mesenchymal stem cell-derived secretome (MSC-derived secretome) has shown promise in regenerative medicine; however, research specifically evaluating its efficacy in third-degree burn wounds remains scarce. The aim of this study was to investigate the effects of MSC-derived secretome on cellular proliferation, angiogenesis, myofibroblast activity, and collagen synthesis in a third-degree burn wound model. A total of 20 Wistar rats were randomly assigned to four groups: a healthy control group, a negative control group with untreated third-degree burn wounds, and two treatment groups receiving MSC-derived secretome at doses of 100 µL and 200 µL for 14 days. The wound healing was assessed 14 days post-treatment. Proliferating cell nuclear antigen (PCNA) protein expression was quantified via Western blot to assess cell proliferation; <i>vascular endothelial growth factor</i> (<i>VEGF</i>) gene expression was analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) to examine angiogenesis; alpha-smooth muscle actin (α-SMA) expression was assessed through immunohistochemistry to evaluate myofibroblast activity; and collagen density was measured using Masson's trichrome staining to determine tissue remodeling. Our data indicated that MSC-derived secretome treatment significantly enhanced multiple aspects of the healing process in a dose-dependent manner. PCNA expression increased by 2.8-fold in the 200 µL MSC-derived secretome group compared to the negative control (<i>p</i><0.05). <i>VEGF</i> gene expression was upregulated by 2.14-fold in the 200 µL secretome group compared to the negative control (<i>p</i><0.05). α-SMA protein expression increased by 12.67% in the 200 µL secretome group, while collagen density demonstrated the most pronounced improvement at the 200 µL dose, reaching an increase of 81.26% (<i>p</i><0.05). In conclusion, MSC-derived secretome significantly accelerates burn wound healing by promoting cell proliferation, enhancing angiogenesis, and increasing collagen synthesis while modulating myofibroblast activity. This highlights the potential of MSC-derived secretome as a therapeutic option for optimizing burn wound repair and reducing fibrotic complications.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e1828"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067219","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}
Pub Date : 2025-08-01Epub Date: 2025-05-24DOI: 10.52225/narra.v5i2.2281
Edhijanto Widaja, Jeanne A Pawitan, Yetty Ramli
Alzheimer's disease is a progressive neurodegenerative disease that is characterized by toxic Amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). Treatment options include the use of human umbilical cord mesenchymal stem cell (hUC-MSC)-based therapy. Its secretome contains healing substances such as neprilysin (CD10), which breaks down Aβ42; anti-inflammatory cytokines, which lower inflammation; and growth factors, which promote neuronal regeneration. The aim of this study was to produce hUC-MSC secretomes preconditioned with tumor necrosis factor-alpha (TNF-α) and/or interferon-gamma (IFN-γ) to enhance the secretion of these healing substances. hUC-MSCs were sub-cultured in T-25 flasks at a seeding density of 5×103 cells/cm2 in 10 mL xeno-free medium. hUC-MSCs were preconditioned with TNF-α only, IFN-γ only, and a combination of TNF-α and IFN-γ. This study used 10 ng/mL TNF-α and 20 ng/mL IFN- γ. The secretome was harvested after 48 hours of preconditioning and then filtered through a 0.22 µm filter. In vitro tests were conducted to assess the effects of the secretome on neuronal survival using the neuroblastoma SH-SY5Y cell line. These cells were differentiated with retinoic acid (RA) and then exposed to Aβ42 to mimic Alzheimer's disease neurons. Secretome therapy was applied at concentrations of 5%, 10%, and 20% to evaluate neuroprotective effects. Four types of secretome were tested: unpreconditioned, TNF-α preconditioned, IFN-γ preconditioned, and a combination of TNF-α and IFN-γ. High levels of CD10 (neprilysin) expression were observed in hUC-MSCs treated with IFN-γ and TNF-α, although they did not release sufficient soluble neprilysin (sNEP). Viability results indicated that secretomes preconditioned with IFN-γ at 10% and 20% concentrations provided the highest increase in cell viability after 72 hours post-therapy. The combination of TNF-α and IFN-γ preconditioned secretome exhibited synergistic effects, particularly at 5% and 10% doses at 24- and 72-hours post- therapy. In conclusion, preconditioned hUC-MSC secretome represents a promising therapeutic approach for Alzheimer's disease, as it enhances neuronal cell viability and promotes neuronal regeneration. However, further studies are required to optimize sNEP release and maximize therapeutic efficacy in in vivo models.
{"title":"Therapeutic potential of hUC-MSC secretome preconditioned with IFN-γ and/or TNF-α: An in vitro study on Alzheimer's neuronal cell models.","authors":"Edhijanto Widaja, Jeanne A Pawitan, Yetty Ramli","doi":"10.52225/narra.v5i2.2281","DOIUrl":"10.52225/narra.v5i2.2281","url":null,"abstract":"<p><p>Alzheimer's disease is a progressive neurodegenerative disease that is characterized by toxic Amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs). Treatment options include the use of human umbilical cord mesenchymal stem cell (hUC-MSC)-based therapy. Its secretome contains healing substances such as neprilysin (CD10), which breaks down Aβ42; anti-inflammatory cytokines, which lower inflammation; and growth factors, which promote neuronal regeneration. The aim of this study was to produce hUC-MSC secretomes preconditioned with tumor necrosis factor-alpha (TNF-α) and/or interferon-gamma (IFN-γ) to enhance the secretion of these healing substances. hUC-MSCs were sub-cultured in T-25 flasks at a seeding density of 5×103 cells/cm<sup>2</sup> in 10 mL xeno-free medium. hUC-MSCs were preconditioned with TNF-α only, IFN-γ only, and a combination of TNF-α and IFN-γ. This study used 10 ng/mL TNF-α and 20 ng/mL IFN- γ. The secretome was harvested after 48 hours of preconditioning and then filtered through a 0.22 µm filter. In vitro tests were conducted to assess the effects of the secretome on neuronal survival using the neuroblastoma SH-SY5Y cell line. These cells were differentiated with retinoic acid (RA) and then exposed to Aβ42 to mimic Alzheimer's disease neurons. Secretome therapy was applied at concentrations of 5%, 10%, and 20% to evaluate neuroprotective effects. Four types of secretome were tested: unpreconditioned, TNF-α preconditioned, IFN-γ preconditioned, and a combination of TNF-α and IFN-γ. High levels of CD10 (neprilysin) expression were observed in hUC-MSCs treated with IFN-γ and TNF-α, although they did not release sufficient soluble neprilysin (sNEP). Viability results indicated that secretomes preconditioned with IFN-γ at 10% and 20% concentrations provided the highest increase in cell viability after 72 hours post-therapy. The combination of TNF-α and IFN-γ preconditioned secretome exhibited synergistic effects, particularly at 5% and 10% doses at 24- and 72-hours post- therapy. In conclusion, preconditioned hUC-MSC secretome represents a promising therapeutic approach for Alzheimer's disease, as it enhances neuronal cell viability and promotes neuronal regeneration. However, further studies are required to optimize sNEP release and maximize therapeutic efficacy in in vivo models.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e2281"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067228","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}
Pub Date : 2025-08-01Epub Date: 2025-04-21DOI: 10.52225/narra.v5i2.1152
Dessy Arisanty, Salsabila P Khairani, Kevin N Cuandra, Dhyani P Wahyudi, Isna C Kamila, Malya Cs Maharani, Eillen Theodora, Raymond E Budianto, Alifya R Shofiy, Ikwandi C Nugraha, Zaki S Aaliyya, Awalil Rk Rahman, Al H Ariouso
Atherosclerosis is a leading cardiovascular disease characterized by the buildup of plaques within arterial walls. The aim of this study was to investigate the potential of peptides derived from Lytechinus variegatus spines as novel therapeutic agents for atherosclerosis using an in silico approach. Key proteins involved in atherosclerosis were selected as target proteins: vascular endothelial growth factor receptor (VEGFR), protein kinase B (AKT1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 8 (MAPK8), and endothelin-1 (ET-1). Comprehensive analysis involving ligand and protein preparation, toxicity, and allergenicity assessments, absorption, distribution, metabolism and excretion (ADME) predictions, and molecular docking were conducted to evaluate the safety, pharmacokinetic properties, binding affinity (kcal/mol), root mean square deviation (RMSD) (Å), as well as a 2D and 3D visualization. Toxicity predictions revealed that peptide 9 was non-toxic and non-allergenic, with a lethal dose 50 (LD50) of 3,000 mg/kg, indicating its safety. Peptide 9 demonstrated the most promising results, effectively inhibiting VEGFR2 (-10,90 kcal/mol), AKT1 (-10,56 kcal/mol), EGFR (-9,82 kcal/mol), MAPK8 (-9,64 kcal/mol), and ET-1 (-11,41 kcal/mol) with strong binding affinities and specificity. These interactions suggested that peptide 9 from Lytechinus variegatus spines may serve as a competitive multitarget inhibitor, offering potential multitarget therapeutic activity against atherosclerosis. Peptide 9 also had high water solubility and did not affect the concentration or excretion of other drugs or compounds, minimizing the risk of drug-drug interactions.
{"title":"Peptide-based drug as atherosclerosis multitarget therapy from <i>Lytechinus variegatus</i> spine: An in silico study.","authors":"Dessy Arisanty, Salsabila P Khairani, Kevin N Cuandra, Dhyani P Wahyudi, Isna C Kamila, Malya Cs Maharani, Eillen Theodora, Raymond E Budianto, Alifya R Shofiy, Ikwandi C Nugraha, Zaki S Aaliyya, Awalil Rk Rahman, Al H Ariouso","doi":"10.52225/narra.v5i2.1152","DOIUrl":"10.52225/narra.v5i2.1152","url":null,"abstract":"<p><p>Atherosclerosis is a leading cardiovascular disease characterized by the buildup of plaques within arterial walls. The aim of this study was to investigate the potential of peptides derived from <i>Lytechinus variegatus</i> spines as novel therapeutic agents for atherosclerosis using an in silico approach. Key proteins involved in atherosclerosis were selected as target proteins: vascular endothelial growth factor receptor (VEGFR), protein kinase B (AKT1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 8 (MAPK8), and endothelin-1 (ET-1). Comprehensive analysis involving ligand and protein preparation, toxicity, and allergenicity assessments, absorption, distribution, metabolism and excretion (ADME) predictions, and molecular docking were conducted to evaluate the safety, pharmacokinetic properties, binding affinity (kcal/mol), root mean square deviation (RMSD) (Å), as well as a 2D and 3D visualization. Toxicity predictions revealed that peptide 9 was non-toxic and non-allergenic, with a lethal dose 50 (LD<sub>50</sub>) of 3,000 mg/kg, indicating its safety. Peptide 9 demonstrated the most promising results, effectively inhibiting VEGFR2 (-10,90 kcal/mol), AKT1 (-10,56 kcal/mol), EGFR (-9,82 kcal/mol), MAPK8 (-9,64 kcal/mol), and ET-1 (-11,41 kcal/mol) with strong binding affinities and specificity. These interactions suggested that peptide 9 from <i>Lytechinus variegatus</i> spines may serve as a competitive multitarget inhibitor, offering potential multitarget therapeutic activity against atherosclerosis. Peptide 9 also had high water solubility and did not affect the concentration or excretion of other drugs or compounds, minimizing the risk of drug-drug interactions.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e1152"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067234","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}
Pub Date : 2025-08-01Epub Date: 2025-05-12DOI: 10.52225/narra.v5i2.1654
Septyani Prihatiningsih, Tri Martiana, Noeroel Widajati, Jonny K Fajar
Safety performance among healthcare workers is an important issue, and currently, the factors related to it remain unclear. The aim of this study was to identify the factors related to safety performance among the healthcare worker population. This meta-analysis study was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) standards. Data on the factors affecting safety performance in the healthcare population were collected from each article to determine pooled point estimates. Data heterogeneity was evaluated using the Q statistic. Numerical data were analyzed using the inverse variance test, and the Mantel-Haenszel test was used for categorical data analysis. Pooled point estimates were presented as mean difference (MD) or odds ratio (OR) along with a 95% confidence interval (95%CI). Fifty articles were included in this study. Our results showed that nurses had lower safety performance compared to other professions (OR: 0.66; 95%CI: 0.56-0.79; p-Egger: 0.3739; p-Heterogeneity <0.0001; p<0.0001). On the other hand, it was also identified that housekeepers were associated with better safety performance compared to other professions (OR: 1.90; 95%CI: 1.08-3.35; p-Egger: 0.1577; p-Heterogeneity: 0.0950; p=0.0220). Furthermore, our findings revealed that healthcare workers who had undergone work safety training had better safety performance compared to those who had not (OR: 1.40; 95%CI: 1.01-1.95; p-Egger: 0.6124; p-Heterogeneity <0.0001; p=0.0430). In conclusion, this study has identified the factors contributing to safety performance in the healthcare population. These findings can inform policymakers in developing regulatory improvements regarding safety performance in healthcare workers.
{"title":"Determinants of safety performance in healthcare settings: A meta-analysis.","authors":"Septyani Prihatiningsih, Tri Martiana, Noeroel Widajati, Jonny K Fajar","doi":"10.52225/narra.v5i2.1654","DOIUrl":"10.52225/narra.v5i2.1654","url":null,"abstract":"<p><p>Safety performance among healthcare workers is an important issue, and currently, the factors related to it remain unclear. The aim of this study was to identify the factors related to safety performance among the healthcare worker population. This meta-analysis study was conducted in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) standards. Data on the factors affecting safety performance in the healthcare population were collected from each article to determine pooled point estimates. Data heterogeneity was evaluated using the Q statistic. Numerical data were analyzed using the inverse variance test, and the Mantel-Haenszel test was used for categorical data analysis. Pooled point estimates were presented as mean difference (MD) or odds ratio (OR) along with a 95% confidence interval (95%CI). Fifty articles were included in this study. Our results showed that nurses had lower safety performance compared to other professions (OR: 0.66; 95%CI: 0.56-0.79; <i>p</i>-Egger: 0.3739; <i>p</i>-Heterogeneity <0.0001; <i>p</i><0.0001). On the other hand, it was also identified that housekeepers were associated with better safety performance compared to other professions (OR: 1.90; 95%CI: 1.08-3.35; <i>p</i>-Egger: 0.1577; <i>p</i>-Heterogeneity: 0.0950; <i>p</i>=0.0220). Furthermore, our findings revealed that healthcare workers who had undergone work safety training had better safety performance compared to those who had not (OR: 1.40; 95%CI: 1.01-1.95; <i>p</i>-Egger: 0.6124; <i>p</i>-Heterogeneity <0.0001; <i>p</i>=0.0430). In conclusion, this study has identified the factors contributing to safety performance in the healthcare population. These findings can inform policymakers in developing regulatory improvements regarding safety performance in healthcare workers.</p>","PeriodicalId":517416,"journal":{"name":"Narra J","volume":"5 2","pages":"e1654"},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067243","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}