Biomedical Journal最新文献

{"title":"Longitudinal surveillance of carbapenem-resistant Serratia marcescens in neonatal intensive care units: transmission routes and effective control strategies","authors":"Chien-Chung Lee,&nbsp;Shih-Hau Chiu,&nbsp;Chien-Chi Chen,&nbsp;Ming-Chou Chiang,&nbsp;Shih-Ming Chu,&nbsp;Wei-Hung Wu,&nbsp;Chyi-Liang Chen,&nbsp;Cheng-Hsun Chiu","doi":"10.1016/j.bj.2025.100935","DOIUrl":"10.1016/j.bj.2025.100935","url":null,"abstract":"<div><h3>Background</h3><div><em>Serratia marcescens</em> is a known cause of nosocomial outbreaks in neonatal intensive care units (NICUs). In early 2021, an outbreak occurred in our NICUs, prompting the implementation of rigorous infection control measures. This study aimed to assess whether the outbreak strain was eliminated or persisted with sporadic transmission.</div></div><div><h3>Methods</h3><div>Ongoing surveillance for <em>S. marcescens</em> infections was conducted in the NICUs and pediatric intensive care unit (PICU) through June 2023. Nosocomial cases were defined as infections diagnosed more than three days after hospitalization. Whole-genome sequencing, average nucleotide identity and minimum spanning tree analyses were employed to assess genetic relatedness.</div></div><div><h3>Results</h3><div>A total of 44 infections were identified: 2 pre-outbreak, 14 during the outbreak, and 28 post-outbreak. Phylogenetic analysis of 35 isolates revealed six distinct clusters. Cluster 1 included pre-outbreak cases; Cluster 2 encompassed outbreak isolates, with one sporadic isolate detected in the PICU 18 months later. Clusters 3–6 emerged post-outbreak period and were genetically unrelated to the outbreak strain. The outbreak strain harbored multiple resistance genes, including <em>kpnH</em>, which potentially contributed to carbapenem resistance. Only one infection over the subsequent two years was genetically linked to the original outbreak strain, supporting the effectiveness of infection control interventions.</div></div><div><h3>Conclusions</h3><div>Prompt and stringent infection control measures effectively contained the <em>S. marcescens</em> outbreak. Continued genomic surveillance is essential to trace transmission and prevent recurrence.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 4","pages":"Article 100935"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145699713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends of disability-adjusted life years for non-communicable diseases in the northern states of peninsular Malaysia (2005–2021): Sex- and age-based analysis","authors":"Norhafizah Karim,&nbsp;Rozita Hod,&nbsp;Muhammad Ikram A. Wahab,&nbsp;Norfazilah Ahmad,&nbsp;Jamal Hisham Hashim,&nbsp;Mohd Firdaus Mohd Radi,&nbsp;Mohamad Fuad Mohamad Anuar,&nbsp;Mazrura Sahani,&nbsp;Mohd Talib Latif,&nbsp;Mohd Faiz Ibrahim,&nbsp;Yelmizaitun Osman,&nbsp;Rohaida Ismail","doi":"10.1016/j.bj.2025.100918","DOIUrl":"10.1016/j.bj.2025.100918","url":null,"abstract":"<div><h3>Background</h3><div>Non-communicable diseases (NCD) are the major silent contributors to mortality and morbidity globally. In Malaysia, 2.5 % of adults live with up to four NCD. However, long-term trend analyses and state-specific data on the NCD burden remain limited. This study assessed the burden of disease (BoD) trend of selected NCD in two northern states in Peninsular Malaysia.</div></div><div><h3>Method</h3><div>This was a descriptive observational study. Mortality data for cardiovascular disease (CVD), respiratory disease (RD), and diabetes mellitus (DM) were obtained from the Department of Statistics Malaysia. Hospital admission data were obtained from the Ministry of Health Malaysia, covering 2005–2021 for the states of Kedah and Kelantan. The BoD was estimated using Global Burden of Disease study methodology, which included the estimation of years of life lost (YLL), years lived with disability (YLD), and disability-adjusted life years (DALY). The descriptive findings were presented as the total DALY, DALY %, and DALY per 100,000 population, and stratified by sex and age.</div></div><div><h3>Results</h3><div>CVD and RD were notably increased in both states in Q4 (2017–2021). The CVD DALY % was highest in 2021 in Kelantan (14.4 %) and in 2020 in Kedah (14.5 %). The RD DALY % was highest in Kelantan in 2019 (6.2 %) and in Kedah in 2020 (8.2 %). The DM burden fluctuated over the years. The YLL component consistently exceeded the YLD for CVD and RD, while DM was YLD-driven. Males experienced a higher CVD and RD burden, while DM affected both sexes. The CVD and RD burden was highest in the elderly (&gt;60 years), while DM affected the elderly and young adults.</div></div><div><h3>Conclusion</h3><div>The CVD and RD DALY increased in Q4 in both states, whereas the DM burden fluctuated across the years. These results emphasize the pressing need for sex- and age-specific interventions to mitigate the long-term effects of NCD.</div></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 4","pages":"Article 100918"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to “Molecular diagnostic platforms for mitochondrial diseases by conventional and long-read sequencing: Missing pieces”","authors":"Ni-Chin Tsai,&nbsp;Yi-Chih Liang,&nbsp;Kuo-Chung Lan","doi":"10.1016/j.bj.2026.100991","DOIUrl":"10.1016/j.bj.2026.100991","url":null,"abstract":"","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"49 4","pages":"Article 100991"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imipramine Reverses Sorafenib Resistance in Hepatocellular Carcinoma by Targeting the BLOC1S5/FOXO1 Signaling Axis.","authors":"Yang-Hsiang Lin, Yu-Chin Liu, Chia-Jung Liao, Ya-Hui Huang, Chau-Ting Yeh, Kwang-Huei Lin","doi":"10.1016/j.bj.2026.101019","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101019","url":null,"abstract":"<p><p>Liver cancer, particularly hepatocellular carcinoma (HCC), is among the leading causes of cancer-related mortality worldwide, with drug resistance posing a significant therapeutic challenge. Therefore, overcoming this barrier is a critical step toward improving survival outcomes in patients with drug-resistant disease. Here, we demonstrate that the antidepressant imipramine effectively inhibits tumor growth in vitro and in vivo. Notably, imipramine enhances the anticancer efficacy of sorafenib, resulting in an additive suppression of tumor growth and cell migration. Moreover, imipramine treatment restores sensitivity in sorafenib-resistant hepatoma cells. RNA-sequencing analysis identified increased expression of BLOC1S5 in sorafenib-resistant cells compared to their parental counterparts. Functional assays indicated that overexpression of BLOC1S5 promotes tumor sphere formation, cell migration, sorafenib resistance, and metastasis through suppression of FOXO1. Imipramine treatment significantly reduced BLOC1S5 expression while inducing FOXO1 expression. Crucially, the inhibitory effect of imipramine on cell migration was reversed by BLOC1S5 overexpression, indicating that imipramine acts, at least in part, by suppressing this protein. Clinically, elevated BLOC1S5 expression correlated with poor prognosis, whereas higher FOXO1 levels were associated with favorable outcomes in HCC patients. Collectively, these results highlight the repurposing of imipramine as a promising therapeutic strategy to sensitize HCC cells to sorafenib via modulation of the BLOC1S5/FOXO1 signaling axis.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101019"},"PeriodicalIF":6.3,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148598550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corticosteroid Stewardship - From Awareness to Action.","authors":"Peter Anto Johnson, John Christy Johnson","doi":"10.1016/j.bj.2026.101018","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101018","url":null,"abstract":"","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101018"},"PeriodicalIF":6.3,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting long non-coding RNA H19 attenuates PKM2 deficiency-driven stemness property in tongue cancer.","authors":"Wan-Hsuan Sun, Ta-Jung Peng, Ru-Min Hsieh, Jyun-Wei Yang, Yu-Wen Tang, Kuang-Hui Sun","doi":"10.1016/j.bj.2026.101016","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101016","url":null,"abstract":"<p><strong>Background: </strong>Cancer stem cells (CSCs) drive tumor recurrence and metastasis via metabolic reprogramming. Although pyruvate kinase M2 (PKM2) is associated with poor prognosis in head and neck cancer (HNC), the loss of PKM2 promotes tumor formation in mice. Long non-coding RNAs (lncRNAs) have been widely implicated in cancer stemness regulation. However, their roles in PKM2 deficiency-mediated tumor progression remain unclear.</p><p><strong>Methods: </strong>PKM2 was knocked out in SAS tongue cancer cells using the CRISPR/Cas9 system. Stemness markers, sphere formation, and drug resistance were examined in CSCs. Whole-transcriptome analysis profiled metabolic, signaling, and lncRNA networks in PKM2-deficient CSCs. Reporter assay and signaling inhibitors were used to validate the pathways for PKM2 knockout-induced H19 expression in CSCs. Lentivirus-mediated shRNA silencing was used to knock down lncRNA H19 for functional analyses.</p><p><strong>Results: </strong>PKM2 knockout inhibited parental SAS cell clonogenicity and motility, but promoted sphere formation, stemness-related gene expression, invasiveness, and chemoresistance in CSCs. Transcriptomic and RT-qPCR analyses revealed lncRNA H19 gene upregulation in PKM2-deficient CSCs. Mechanistically, reporter assays confirmed c-Myc signaling activation, and Hedgehog or c-Myc signaling blockade inhibited this PKM2 deficiency-induced H19 expression. Functionally, H19 silencing further impaired clonogenicity and motility in PKM2-deficient parental cells, and effectively suppressed the sphere formation, stemness-related gene expression, invasive capacity, and chemoresistance of CSCs promoted by PKM2 deficiency.</p><p><strong>Conclusions: </strong>PKM2 loss promotes tongue cancer stemness via the induction of lncRNA H19. Co-targeting the PKM2/H19 axis may be a promising therapeutic strategy for tongue cancer.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101016"},"PeriodicalIF":6.3,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogen-generating silicon-based agent is effective in a mouse model of ovalbumin-induced allergic bronchial asthma.","authors":"Honoka Takeuchi, Marumi Taya, Sana Takashima, Nobumasa Hino, Chihaya Kakinuma, Yuki Kobayashi, Hikaru Kobayashi, Shinsaku Nakagawa","doi":"10.1016/j.bj.2026.101017","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101017","url":null,"abstract":"<p><strong>Background: </strong>Hydrogen therapy, which involves the intake of hydrogen as an antioxidant, has been reported to be effective against various oxidative stress-related diseases. However, current methods of hydrogen administration present various problems. Therefore, new methods that allow for the safe and sustained delivery of high doses of hydrogen are needed. Si-based agents offer a promising solution because they can easily and continuously generate large amounts of hydrogen in the digestive tract. Asthma is characterized by chronic airway inflammation, and allergic bronchial asthma-its most readily recognized phenotype-is suspected to be related to oxidative stress. We investigated the effects of Si-based agents on allergic bronchial asthma.</p><p><strong>Material and methods: </strong>Allergic bronchial asthma was induced in female C57BL/6N mice by epicutaneous sensitization and inhalation challenge with ovalbumin. Bronchial asthma was assessed by cell counts in bronchoalveolar lavage fluid (BALF) and lung histopathological analysis. mRNA expression levels of cytokines and chemokine in lung tissue and total IgE concentration in serum were measured.</p><p><strong>Results: </strong>The administration in the diet of this Si-based agent to a model mouse of allergic bronchial asthma significantly suppressed eosinophil counts in the BALF and reduced inflammatory cell infiltration in the lungs. In addition, the expressions of interleukins 5, and 13 and C-C motif chemokine 11 in lung tissue tended to decreased in the Si group compared with those in the control group. We examined the timing of administration of Si-based agents and found that Si-based agents worked during the sensitization and elicitation phases and tended to decrease the total IgE concentration in serum.</p><p><strong>Conclusions: </strong>Si-based agents are effective against allergic bronchial asthma and may serve as superior materials for hydrogen therapy. We anticipate that our study will provide valuable insights into the mechanisms of Si-based agents against type I allergy and facilitate their clinical application in the future.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101017"},"PeriodicalIF":6.3,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of HBsAg levels and HBV relapse patterns with HBsAg seroclearance following entecavir or tenofovir cessation.","authors":"Yuan-Hung Kuo, Yi-Hao Yen, Tsung-Hui Hu, Jing-Houng Wang, Chao-Hung Hung, Sheng-Nan Lu, Chien-Hung Chen","doi":"10.1016/j.bj.2026.101014","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101014","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the association between HBsAg levels at end of treatment (EOT) and different HBV relapse patterns or HBsAg seroclearance after discontinuing entecavir or tenofovir disoproxil fumarate (TDF).</p><p><strong>Methods: </strong>A total of 900 non-cirrhotic patients (616 HBeAg-negative and 284 HBeAg-positive at initiation) who had discontinued entecavir or TDF for at least 12 months were retrospectively analyzed.</p><p><strong>Results: </strong>HBeAg-negative patients achieved significantly higher rates of HBsAg seroclearance than HBeAg-positive patients (10 years: 29.8% vs. 19.7%, p=0.007), despite comparable rates of clinical relapse and retreatment. Among the 118 HBeAg-negative and 35 HBeAg-positive patients who experienced HBsAg seroclearance, 39 (33.1%) and 8 (22.8%) did experience clinical relapse prior to HBsAg seroclearance, respectively. In HBeAg-negative patients who achieved seroclearance, different HBV relapse patterns were associated with distinct HBsAg kinetic profiles. An HBsAg threshold of ≤20 and 20-100 IU/mL identifies patients with a high likelihood of HBsAg loss (10-year cumulative incidence of 82.7% and 50.4%, respectively) with 0% and 31.0% clinical relapse, respectively. In HBeAg-positive patients, those with an EOT HBsAg ≤100 IU/mL achieved the highest rate of HBsAg loss (10-year cumulative incidence of 64.8%) with only 6.7% (1/15) clinical relapse. There was no significant difference in HBsAg seroclearance rates between the initial and subsequent finite therapies. Eight patients developed hepatic decompensation upon clinical relapse (annual incidence rate of 0.13 per 100 person-years).</p><p><strong>Conclusion: </strong>HBV relapse patterns strongly affect HBsAg kinetics and HBsAg seroclearance. EOT HBsAg levels predict both HBsAg seroclearance and clinical relapse rates prior to HBsAg seroclearance.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101014"},"PeriodicalIF":6.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Letter Regarding \"Co-radiotherapy with Tyrosine Kinase Inhibitors Might Benefit Survival in Hepatoma Patients with Portal Vein Tumor Thrombosis\".","authors":"Hui-Ling Huang, Sheng-Nan Lu","doi":"10.1016/j.bj.2026.101015","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101015","url":null,"abstract":"","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101015"},"PeriodicalIF":6.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the mechanism of acupuncture for Chronic Atrophic Gastritis based on bioinformatics and network topology strategies.","authors":"Hongxiao Xu, Huangan Wu, Mengdie Wu, Qi Li, Handan Zheng, Lingjie Li, Feifei Li, Yawen Ding, Yan Huang, Jing Li, Luyi Wu","doi":"10.1016/j.bj.2026.101013","DOIUrl":"https://doi.org/10.1016/j.bj.2026.101013","url":null,"abstract":"<p><strong>Background: </strong>Chronic atrophic gastritis (CAG) is a progressive gastric disorder with the potential for malignant transformation. Conventional treatments primarily focus on Helicobacter pylori eradication and symptom management; however, long-term use may be associated with hepatic or renal adverse effects. Although acupuncture has demonstrated therapeutic benefits in CAG, its underlying mechanisms remain insufficiently understood. This study aimed to investigate the multi-target mechanisms of acupuncture in CAG through an integrated strategy combining network pharmacology and experimental validation.</p><p><strong>Methods: </strong>An integrative approach involving bioinformatics, text mining, and network analysis was employed, followed by in vivo validation in a rat model of CAG. Bioactive compounds generated following acupuncture intervention were identified through literature retrieval, and their potential targets were predicted using Search Tool for Interacting Chemicals (STITCH) and SwissTargetPrediction. CAG-related targets were collected from the GeneCards, OMIM, and UniProt databases. The overlapping targets were used to construct a protein-protein interaction network in Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using DAVID. For experimental validation, CAG was induced in rats, followed by acupuncture treatment. Gastric antral tissues were evaluated by histological staining, including hematoxylin-eosin and Prussian blue staining, as well as molecular assays, including western blotting, immunohistochemistry, immunofluorescence, and ELISA, to assess the expression of IL-6, TNF-α, IL-1β, GSH, mTOR, GPX4, FTH1, TP53, and Fe³⁺.</p><p><strong>Results: </strong>A total of 98 potential therapeutic targets and 159 signaling pathways associated with acupuncture treatment for CAG were identified, with TP53- and mTOR-related signaling pathways emerging as key regulatory pathways. In the rat model, CAG induced marked gastric pathological injury, iron accumulation, and increased inflammatory cytokine levels, accompanied by reduced levels of GSH, TP53, mTOR, GPX4, and FTH1. Acupuncture treatment significantly alleviated gastric mucosal atrophy and inflammation, reduced Fe³⁺ deposition and pro-inflammatory cytokine levels, and upregulated ferroptosis-related proteins.</p><p><strong>Conclusion: </strong>Acupuncture may ameliorate CAG by modulating the TP53 and mTOR signaling pathways, regulating ferroptosis, attenuating mucosal injury, and improving gastric pathological alterations.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"101013"},"PeriodicalIF":6.3,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}