Medicine Advances最新文献

{"title":"Case Report: Abemaciclib-Induced Chronic Renal Failure","authors":"Lu Lin,&nbsp;Jinhui Chen,&nbsp;Jing Li,&nbsp;Shuangxin Liu,&nbsp;Weihua Lai","doi":"10.1002/med4.70017","DOIUrl":"https://doi.org/10.1002/med4.70017","url":null,"abstract":"<p>Abemaciclib, a cyclin-dependent kinase 4/6 inhibitor, may induce kidney damage during the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. We report a case of a 52-year-old woman with normal baseline kidney function (serum creatinine, 68.19 μmol/L; eGFR, 89 mL/(min·1.73 m²); blood urea nitrogen, 7.74 mmol/L; cystatin C, 0.74 mg/L) who developed stage 2 chronic kidney disease after 12 months of abemaciclib therapy (150 mg/day, twice daily). Three months after discontinuation, kidney function recovered (serum creatinine, 73.80 μmol/L; normalized cystatin C and uric acid), but creatinine rose again to 92.5 μmol/L within 1 month of reinitiation. This case suggests that long-term abemaciclib use may lead to kidney damage, potentially progressing to chronic kidney failure. Regular monitoring of renal function indicators is recommended before and during treatment.</p>","PeriodicalId":100913,"journal":{"name":"Medicine Advances","volume":"3 2","pages":"112-115"},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med4.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINC00922: A Critical Oncogenic Long Non-Coding RNA Involved in Cancer Progression, Chemotherapy Resistance, and microRNA Regulation","authors":"Jiahua Si,&nbsp;Chenhao Liang,&nbsp;Xueting Zhang,&nbsp;Hening Xu,&nbsp;Xinming Su,&nbsp;Luqing Liu,&nbsp;Ruyi Yuan,&nbsp;Yuemin Ding,&nbsp;Shiwei Duan","doi":"10.1002/med4.70018","DOIUrl":"https://doi.org/10.1002/med4.70018","url":null,"abstract":"<p>LINC00922, a long non-coding RNA (lncRNA) located at chromosome 16q21, has emerged as a crucial regulatory molecule in cancer progression, chemotherapy resistance, and immune modulation. This lncRNA is predominantly localized in the cytoplasm, with limited expression in the nucleus and exosomes. Elevated LINC00922 expression levels are associated with poor patient prognosis across various cancer types. LINC00922 can regulate cancer cell behavior through complex gene regulatory networks, including interactions with several key signaling pathways, such as the Wnt, telomerase, and immune response pathways. Importantly, LINC00922 participates in multiple competing endogenous RNA axes, influencing the expression patterns of target microRNAs like miR-424-5p and miR-874-3p, which in turn regulate important cancer-related genes, such as TFAP2C and GDPD5 contributing to chemotherapy resistance. LINC00922 can also promote immune cell infiltration in tumors, with its high expression levels correlating with extensive immune cell presence, suggesting potential for cancer immunotherapy. Despite these promising findings, the upstream regulatory factors of LINC00922 remain poorly understood and further research is needed to fully uncover its clinical potential. In this review, we highlight the multifaceted roles of LINC00922 in cancer, emphasizing the need for future studies to explore its potential as a therapeutic target and diagnostic biomarker.</p>","PeriodicalId":100913,"journal":{"name":"Medicine Advances","volume":"3 2","pages":"65-79"},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med4.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relationships Between Serum Vitamin D, Inflammatory Markers, and Outcomes in Non-Critically Ill Patients With COVID-19: A Cross-Sectional Study","authors":"Zahra Khorasanchi,&nbsp;Ali Jafazadeh Esfehani,&nbsp;Mohammad Reza Shadmand Foumani Moghadam,&nbsp;Sara Shojaei Saadatqoli,&nbsp;Payam Sharifan,&nbsp;Majid Ghayour Mobarhan,&nbsp;Sajjad Arefinia,&nbsp;Afshin Roghani,&nbsp;Naghme Mirhossini,&nbsp;Masoud Pezeshki Rad,&nbsp;Saeid Eslami,&nbsp;Hamidreza Naderi,&nbsp;Hassan Vatanparast,&nbsp;Reza Rezvani","doi":"10.1002/med4.70010","DOIUrl":"https://doi.org/10.1002/med4.70010","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Backround</h3>\u0000 \u0000 <p>Treatment options for COVID-19 remain limited and are primarily focused on specific patient populations; accordingly, preventive measures continue to be a crucial aspect of effective management. There is evidence that vitamin D effectively prevents viral upper respiratory tract infections during epidemics. The aim of this study was to assess the association between serum vitamin D and inflammatory markers, mortality, and clinical symptoms in patients with COVID-19.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study involved non-critically ill patients with COVID-19 in a provincial reference hospital in Mashhad, Iran. Demographic and clinical data were extracted from patient medical records. Serum vitamin D was measured for each patient within 12 h of admission. Data were analyzed using linear and logistic regression models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 452 patients (mean age 63.87 ± 17.97 years) were included in this study during 2 months of data collection. The most common serum vitamin D status was sufficient (30.0%), followed by deficient (29.4%), insufficient (23.2%), and severely deficient (17.3%). Partial symptom improvement was observed in 326 (72.1%) patients after 22 days of hospitalization, disregarding the vitamin D status. The mortality rate was 22.6%. COVID-19 mortality was significantly related to serum urea (<i>p</i> = 0.002, OR = 1.020, 95% CI: 1.008–1.033), pulse rate (<i>p</i> = 0.015, OR = 1.047, 95% CI: 1.009–1.086), and age (<i>p</i> = 0.002, OR = 1.076, 95% CI: 1.027–1.127).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Among patients with COVID-19, serum vitamin D levels were linked to mortality and some clinical parameters, including urea and pulse rate. Further longitudinal studies should evaluate the relationship between serum vitamin D levels and COVID-19 outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100913,"journal":{"name":"Medicine Advances","volume":"3 2","pages":"97-106"},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med4.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticipating On-Target and Off-Target Effects of CRISPR/Cas9 Genome Editing Via a Feedforward Neural Network Model","authors":"Pavithra Nagendran,&nbsp;Gowtham Murugesan,&nbsp;Jeyakumar Natarajan","doi":"10.1002/med4.70016","DOIUrl":"https://doi.org/10.1002/med4.70016","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Clustered regularly interspaced short palindromic repeats —CRISPR-associated protein 9 (CRISPR/Cas9) is a gene editing technology that can deliver highly precise genome editing. However, it is difficult to predict both on- and off-target effects of CRISPR/Cas9, which is essential for ensuring the safety and efficiency of genetic modifications made using this technology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we used the SITE-Seq dataset, which comprises CRISPR targets, to classify sequences for both on- and off-target effects. To evaluate sequence pairs, we built a feedforward neural network (FNN) with 10 fully connected layers and compared its performance with that of other state-of-the-art models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We showed that our FNN model attained an accuracy rate of 0.95, greatly improving prediction reliability for both on- and off-target effects compared with other methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This work contributes a valuable predictive modeling framework to the field of CRISPR research, addressing both on- and off-target effects in a unified manner, which is an essential requirement for the safe and effective application of genomic editing technologies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100913,"journal":{"name":"Medicine Advances","volume":"3 2","pages":"88-96"},"PeriodicalIF":0.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med4.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Heart Health: Expanding the Use of SGLT2 Inhibitors in Cardiovascular Disease","authors":"Manahil Mubeen,&nbsp;Aasiya Shahbaz Sakarwala,&nbsp;Arif Imdad Bijarani,&nbsp;Muhammad Taha Kamal","doi":"10.1002/med4.70014","DOIUrl":"https://doi.org/10.1002/med4.70014","url":null,"abstract":"<p>SGLT2 inhibitors offer multifaceted cardiovascular benefits, including improved cardiac metabolism, reduced preload and afterload, and decreased myocardial infarction risk. These effects are driven by renoprotection, anti-inflammatory properties, improved mitochondrial function, osmotic diuresis, and glycemic control. Together, these mechanisms support the role of SGLT2 inhibitors in reducing cardiovascular morbidity and mortality.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":100913,"journal":{"name":"Medicine Advances","volume":"3 2","pages":"122-126"},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med4.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xanomeline-Trospium Chloride (Cobenfy): A New Era in Managing Schizophrenia—Comparative Effectiveness and Economic Challenges","authors":"Jawairya Muhammad Hussain,&nbsp;Wajiha Arif,&nbsp;Sharjeel Humayun,&nbsp;Nida Shoaib,&nbsp;Saim Mahmood Khan","doi":"10.1002/med4.70013","DOIUrl":"https://doi.org/10.1002/med4.70013","url":null,"abstract":"<p>Xanomeline-trospium chloride (cobenfy) is a muscarinic agonist used to treat hallucinations and psychotic illnesses such as Alzheimer's and Schizophrenia. It has been constructed for patients who are unable to tolerate dopamine-targeting therapies and a comparison is drawn against other similar drugs with variables like cost, mechanism of action, efficacy and contraindications taken into account. Specifically effective for schizophrenia, it is safer with fewer side effects and efficient with stronger success rates, offering pharmacists and physicians an alternative to mainstream antipsychotic drugs.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":100913,"journal":{"name":"Medicine Advances","volume":"3 2","pages":"116-121"},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med4.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surgical Management of a High-Grade Gastrointestinal Stromal Tumor in a Morbidly Obese Patient: A Case Study","authors":"Felipe Quistian,&nbsp;Kristen M. Quinn,&nbsp;Michael A. Deal,&nbsp;Rana Pullatt","doi":"10.1002/med4.70011","DOIUrl":"https://doi.org/10.1002/med4.70011","url":null,"abstract":"<p>Gastrointestinal stromal tumors (GISTs) are the most commonly occurring mesenchymal tumors within the gastrointestinal (GI) tract yet, those located at the gastroesophageal junction (GEJ) are rare. We present a 31-year-old woman with morbid obesity and large (4.9 cm) polypoid mass adjacent to the GEJ. She was offered a laparoscopic transgastric GIST resection and adjuvant imatinib. Intraoperatively, a gastrotomy was created through which the polypoid tumor was successfully delivered for resection. The increasing prevalence of obesity can pose unique challenges to peri-operative management. Thoughtful innovations in surgical approach can save obese patients from increased morbidity or surgical delay.</p>","PeriodicalId":100913,"journal":{"name":"Medicine Advances","volume":"3 2","pages":"107-111"},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med4.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Between Lipids and Lipid-Lowering Drug Target Genes and Osteomyelitis: A Mendelian Randomization Analysis","authors":"Zhiyi Zhou,&nbsp;Zhehan Yang,&nbsp;Junpan Chen,&nbsp;Minghao Wen,&nbsp;Jiayuan Lei,&nbsp;Wanzhe Liao,&nbsp;Yahan Li,&nbsp;Linghui Liu,&nbsp;Ziyuan Lu","doi":"10.1002/med4.70009","DOIUrl":"https://doi.org/10.1002/med4.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lipid metabolism is a key regulator of inflammation in acute and chronic conditions. However, whether dyslipidemia is related to the process of osteomyelitis remains unclear. This study aimed to use a Mendelian randomization (MR) analysis to examine the associations between triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and osteomyelitis. Additionally, the associations between the genes corresponding to these traits and osteomyelitis were investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Genetic variants associated with TG and TC were selected from the Global Lipids Genetics Consortium, while LDL-C datasets were extracted from the UK Biobank. Specifically, the lipid-lowering drug target regions were selected as proxies for drug target perturbation. Osteomyelitis was identified according to the FinnGen consortium. We also conducted supplementary analyses using C-reactive protein genome-wide association study data to examine the effect of drug targets on this inflammatory marker. Furthermore, we conducted mediation analyses focusing on several risk factors for osteomyelitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>No association was found between LDL-C, TG, or TC concentrations and osteomyelitis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was significantly associated with a lower risk of osteomyelitis (odds ratio [95% confidence interval] = 0.49 [0.32–0.76], <i>p</i> = 1.60 × 10⁻³) and a lower concentration of C-reactive protein (0.94 [0.92–0.97], <i>p</i> = 3.16 × 10⁻⁴). We found that waist circumference was an intermediate variable between PCSK9 and osteomyelitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study does not support a relationship between dyslipidemia and osteomyelitis. PCSK9 is associated with a lower risk of osteomyelitis. Our findings suggest that waist circumference is a potential mediator between osteomyelitis and PCSK9. Additionally, PCSK9 is associated with reduced CRP concentrations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100913,"journal":{"name":"Medicine Advances","volume":"3 2","pages":"80-87"},"PeriodicalIF":0.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med4.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of Remote Glucose Monitoring Versus Conventional Care in Diabetes Management: A Systematic Review and Meta-Analysis","authors":"Peter Olujimi Odutola,&nbsp;Peter Oluwatobi Olorunyomi,&nbsp;Olanrewaju Olamide Olatawura,&nbsp;Ifeoluwapo Olorunyomi","doi":"10.1002/med4.70008","DOIUrl":"https://doi.org/10.1002/med4.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Diabetes mellitus, especially type 2 diabetes (T2DM), is a growing global health issue characterized by poor blood glucose control, leading to severe complications and increased healthcare costs. Effective management requires accessible, responsive support systems to enhance self-management, particularly for those with limited access to traditional care. The aim was to evaluate remote monitoring versus standard care in managing diabetes mellitus, focusing on outcomes like Hemoglobin A1C (HbA1C) levels, fasting blood glucose (FBG), lipid profiles, body weight, body mass index (BMI), and blood pressure. A comprehensive literature search was performed in September 2024 using the Cochrane, Google Scholar, and PubMed databases with no time restriction. Seven studies totaling 883 participants were included, comparing remote monitoring with usual care in diabetic management. Data were analyzed using Review Manager (Cochrane), calculating mean differences and 95% confidence intervals (CIs) for continuous data, with statistical significance at <i>p</i> &lt; 0.05. Remote monitoring significantly improved glycemic control, reducing HbA1c levels (mean difference: −0.35; 95% CI: −0.67 to −0.02; <i>p</i> = 0.04) and FBG (mean difference: −0.82; 95% CI: −1.10 to −0.54; <i>p</i> &lt; 0.00001). Total cholesterol levels decreased significantly (mean difference: −0.28; 95% CI: −0.49 to −0.07; <i>p</i> = 0.01). HDL showed a minor but significant decline, while LDL reduction was non-significant. No significant differences were observed in body weight, BMI, or blood pressure. Remote monitoring shows significant potential in improving glycemic control and lipid profiles in diabetes management. Further long-term studies are needed to validate these findings, while addressing associated technological challenges.</p>\u0000 </section>\u0000 </div>","PeriodicalId":100913,"journal":{"name":"Medicine Advances","volume":"3 1","pages":"28-36"},"PeriodicalIF":0.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med4.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming Computational Resource Limitations in Deep Learning for Healthcare: Strategies Targeting Data, Model, and Computing","authors":"Han Yuan","doi":"10.1002/med4.70001","DOIUrl":"https://doi.org/10.1002/med4.70001","url":null,"abstract":"<p>Deep learning has been identified as an indispensable backbone in health data science. However, the computational constraints faced by many healthcare providers, who may lack access to high-performance computing resources, must be considered. This commentary illustrates three representative strategies from the perspective of data, model, and computing to mitigate computational constraints in resource-limited settings.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":100913,"journal":{"name":"Medicine Advances","volume":"3 1","pages":"42-45"},"PeriodicalIF":0.0,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/med4.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741333","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}