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1.
EClinicalMedicine ; 39: 101080, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34611615

RESUMO

Background: Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are relatively time-consuming and expensive. Several new pharmacologic treatments designed for tinnitus patients without specific origin had been developed but their efficacy remains unclear. Methods: The current Network Meta-Analysis (NMA) of randomised controlled trials (RCTs) was conducted to evaluate the efficacy of different pharmacologic treatments for tinnitus management in tinnitus patients without specific or treatable origin (i.e. primary tinnitus). Databases were searched from inception to April 5th, 2021. All network meta-analytic procedures were conducted under the frequentist model. We calculated the effect size of outcomes with different rating scales with standardized mean difference. PROSPERO registration: CRD42020177742. Findings: Overall, 36 RCTs were included with 2,761 participants. The main results revealed that pharmacologic interventions with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) and those with anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) were associated with superior improvement in tinnitus severity and response rate compared to placebo/control. Oral amitriptyline were associated with the highest improvement in tinnitus severity and the fourth highest response rate. None of the investigated interventions was associated with different changes in quality of life compared to placebo/control. All the investigated treatments were associated with similar drop-out rate to placebo/control. Interpretation: The current NMA suggests a potential role for treatments with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) or anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) as the preferable effective treatments for tinnitus without specific or treatable origin. Funding: none.

2.
Public Health Genomics ; : 1-10, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34634790

RESUMO

INTRODUCTION: Invasive ductal carcinoma (IDC) of the breast is a heterogeneous disease characterized by multiple subtypes. IDC survival is highly impacted by tumor burden, molecular subtypes, and gene profiles. Gene mutation is a type of genomic instability regarded as having a considerable effect on IDC prognosis. Using integrated survival analysis, this study identified candidate genes and a high-risk group of patients with early-stage IDC to provide further understanding of the genetic characteristics associated with poor survival. METHODS: The gene mutation profiles, baseline demographics, clinicopathologic variables, and treatment characteristics of the early-stage IDC subpopulation were downloaded from an open access data platform. These data were analyzed for a total of 444 patients. In total, 40 genes commonly involved in IDC were listed, and the genes exhibiting significant differences (as estimated using the log-rank test) were selected as the candidate genes. RESULTS: The patients were divided into control, low-risk, and high-risk groups according to their gene mutation profiles. The 5-year overall survival rates of low-risk, control, and high-risk patients were 97.4%, 96.1%, and 73.0%, respectively. The high-risk group had a significantly higher risk of poor overall -survival (adjusted hazard ratio = 6.57, 95% confidence interval = 1.51-28.7, p = 0.012) than that of the control group, and the low-risk group did not have a significant survival difference compared with control group. CONCLUSIONS: This study proposed an integrative approach for the identification of candidate genes for risk assessment of overall survival in these patients through typical survival analysis methods. The 14 candidate genes selected are particularly involved in cell-cycle processes, deoxyribonucleic acid repair, and drug resistance; their mutations were found to be generally associated with disease progression or therapeutic resistance, which is commonly associated with poor overall survival outcomes in IDC.

3.
Acta Cardiol Sin ; 37(5): 457-463, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34584378

RESUMO

Advances in cancer treatments have led to an increasing number of cancer survivors, but also high rates of short- and long-term cardiovascular (CV) toxicities. The number of new cancer drugs is constantly increasing, and the uncertain CV toxicities of these drugs make long-term care and monitoring difficult. Moreover, traditional type I and type II cardiotoxicities may not be applicable to all of these agents. Multidisciplinary care with expertise in oncology, cardiology and other related specialties is required to mitigate cancer therapeutics-related cardiovascular dysfunction (CTRCD). The aim of this review is to provide an overview of the main CTRCD, risk assessment, early diagnosis, and strategies for the prevention and management of patients receiving cancer therapies. There are still unmet needs for cardio- oncology researchers with regards to early detection measures, better treatment strategies, better follow-up protocols, and better management of CTRCD. Experts in cardiology, oncology, hematology, and radio-oncology should thus work closely in an attempt to foster patient awareness and research in this field, as well as call for support from public and industrial sources to initiate pivotal clinical trials to solve these unmet needs.

4.
Int J Mol Sci ; 22(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361085

RESUMO

A novel aptamer-based competitive drug screening platform for osteoporosis was devised in which fluorescence-labeled, sclerostin-specific aptamers compete with compounds from selected chemical libraries for the binding of immobilized recombinant human sclerostin to achieve high-throughput screening for potential small-molecule sclerostin inhibitors and to facilitate drug repurposing and drug discovery. Of the 96 selected inhibitors and FDA-approved drugs, six were shown to result in a significant decrease in the fluorescence intensity of the aptamer, suggesting a higher affinity toward sclerostin compared with that of the aptamer. The targets of these potential sclerostin inhibitors were correlated to lipid or bone metabolism, and several of the compounds have already been shown to be potential osteogenic activators, indicating that the aptamer-based competitive drug screening assay offered a potentially reliable strategy for the discovery of target-specific new drugs. The six potential sclerostin inhibitors suppressed the level of both intracellular and/or extracellular sclerostin in mouse osteocyte IDG-SW3 and increased alkaline phosphatase activity in IDG-SW3 cells, human bone marrow-derived mesenchymal stem cells and human fetal osteoblasts hFOB1.19. Potential small-molecule drug candidates obtained in this study are expected to provide new therapeutics for osteoporosis as well as insights into the structure-activity relationship of sclerostin inhibitors for rational drug design.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Aptâmeros de Nucleotídeos/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteócitos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Aptâmeros de Nucleotídeos/isolamento & purificação , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteócitos/citologia , Osteócitos/metabolismo , Osteoporose/metabolismo , Osteoporose/patologia
5.
Cancers (Basel) ; 13(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34359732

RESUMO

BACKGROUND: Biliary tract cancer (BTC) is a heterogenous collection of biliary tract cancer at different primary sites, and the prognosis of advanced BTC is dismal. Systemic chemotherapy with gemcitabine and cisplatin (GC) has been the reference regimen since 2010. How to improve therapeutic effects of GC regimen is an urgent mission at present. METHODS: Bevacizumab with a reduced dosage and modified schedule (10 mg/Kg/triweekly, 1 day before GS at the first 2 cycles) was combined with standard GC for patients with advanced BTC. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 every 2 months. Kaplan-Meier curves were estimated for time-to-treatment failure (TTF), progression-free survival (PFS) and overall survival (OS). RESULT: A total of thirty cases of advanced BTC accepted this treatment, and the overall response rate (ORR) was 50.0%, and the disease control rate was 80.0% for all patients. The median TTF was 5.8 months, the median PFS was 8.4 months, and the median OS was 13.6 months. Most responses were noted at the first evaluation. Adverse effects (AEs) were mostly tolerable. CONCLUSIONS: After modifying the schedule, adding bevacizumab to a traditional GC regimen could increase the ORR with a shorter time-to-response, a better PFS and OS than GC alone but without the addition of AE. This regimen can be applied to patients with advanced BTC, especially those who are with a big tumor burden and who need a rapid response.

6.
Curr Oncol ; 28(4): 3214-3226, 2021 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-34436045

RESUMO

BACKGROUND: The high proportion of blood transfusions before and during surgery carries unnecessary risk and results in poor prognosis in colorectal cancer patients. Different pharmacological interventions (i.e., iron supplement or recombinant erythropoietin) to reduce blood transfusion rates have shown inconclusive results. METHODS: This network meta-analysis (NMA) consisted of randomized controlled trials (RCTs) comparing the efficacy of different pharmacologic interventions (i.e., iron supplementation or recombinant erythropoietin) to reduce the blood transfusion rate. NMA statistics were conducted using the frequentist model. Results: Seven RCTs (688 participants) were included in this study. The NMA demonstrated that the combination of high-dose recombinant human erythropoietin and oral iron supplements was associated with the least probability of receiving a blood transfusion [odds ratio = 0.24, 95% confidence intervals (95% CIs): 0.08 to 0.73] and best reduced the amount of blood transfused if blood transfusion was necessary (mean difference = -2.62 U, 95% CI: -3.55 to -1.70 U) when compared to the placebo/control group. None of the investigated interventions were associated with any significantly different dropout rate compared to the placebo/control group. CONCLUSIONS: The combination of high-dose recombinant human erythropoietin and oral iron supplements might be considered as a choice for reducing the rate of blood transfusion in patients with colorectal cancer. However, future large-scale RCT with long-term follow-up should be warranted to approve the long-term safety.

7.
Immunotherapy ; 13(14): 1165-1177, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34261336

RESUMO

This meta-analysis investigated the clinical benefits of chemo-immunotherapy in extensive-stage small-cell lung cancer (ES-SCLC). Seven randomized controlled trials with a total of 2862 patients were analyzed. Compared with chemotherapy alone, chemo-immunotherapy provided a better progression-free survival (PFS) with a hazard ratio (HR) of 0.81, p < 0.00001, and overall survival (OS) with a HR of 0.82, p < 0.0001; however, the incidence of treatment-related adverse effects (TRAEs) was significantly increased. Subgroup analyses showed that good performance status, cisplatin-based chemotherapy, without brain metastases at baseline and non-Asian populations were associated with greater benefits in OS from chemo-immunotherapy. Chemo-immunotherapy demonstrated better PFS and OS compared with chemotherapy alone as first line treatment in ES-SCLC, but additional TRAEs should be closely monitored.

8.
BMC Cancer ; 21(1): 828, 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34273969

RESUMO

BACKGROUND: Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). METHODS: We prospectively investigated how these proteins affect clinical prognosis in 40 patients who underwent hepatectomy for cHCC-CC from 2011 to 2019 at a Taiwanese hospital. Levels of autophagy-related proteins, namely LC3, Beclin-1, and p62, were immunohistochemically assessed in patient tumor and non-tumor tissues. RESULTS: We noted that LC3 expression was significantly correlated with mild clinicopathological characteristics, including macrovascular invasion, lymph node metastasis, American Joint Committee on Cancer and Barcelona Clinic Liver Cancer stages, recurrence, and mortality. Ten patient showed tumor recurrence, and 15 patients died. Postresection 5-year OS and DFS rates were 43.7 and 57.4%, respectively. Cox regression analysis showed that high intratumoral LC3 expression was significantly associated with improved OS [hazard ratio (HR; 95% confidence interval (CI)): (1.68-26.9), p = 0.007], but multiple tumors and microvascular invasion was significantly correlated with poor OS [HR (95% CI): 0.03 (0.01-0.34), p = 0.004, and 0.07 (0.01-0.46), p = 0.006, respectively]. Furthermore, high LC3 expression and cirrhosis had improved DFS [HR (95% CI): 51.3 (2.85-922), p = 0.008, and 17.9 (1.05-306), p = 0.046, respectively]. The 5-year OS and DFS rates were respectively 61.2 and 74.6% in high LC3 expression patients and 0 and 0% in those with low LC3 expression. CONCLUSION: High LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.


Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Carcinoma Hepatocelular/cirurgia , Colangiocarcinoma/etiologia , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/patologia , Colangiocarcinoma/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
9.
Cancers (Basel) ; 13(14)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34298805

RESUMO

It has been acknowledged that excess body weight increases the risk of colorectal cancer (CRC); however, there is little evidence on the impact of body mass index (BMI) on CRC patients' long-term oncologic results in Asian populations. We studied the influence of BMI on overall survival (OS), disease-free survival (DFS), and CRC-specific survival rates in CRC patients from the administrative claims datasets of Taiwan using the Kaplan-Meier survival curves and the log-rank test to estimate the statistical differences among BMI groups. Underweight patients (<18.50 kg/m2) presented higher mortality (56.40%) and recurrence (5.34%) rates. Besides this, they had worse OS (aHR:1.61; 95% CI: 1.53-1.70; p-value: < 0.0001) and CRC-specific survival (aHR:1.52; 95% CI: 1.43-1.62; p-value: < 0.0001) rates compared with those of normal weight patients (18.50-24.99 kg/m2). On the contrary, CRC patients belonging to the overweight (25.00-29.99 kg/m2), class I obesity (30.00-34.99 kg/m2), and class II obesity (≥35.00 kg/m2) categories had better OS, DFS, and CRC-specific survival rates in the analysis than the patients in the normal weight category. Overweight patients consistently had the lowest mortality rate after a CRC diagnosis. The associations with being underweight may reflect a reverse causation. CRC patients should maintain a long-term healthy body weight.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34266911

RESUMO

BACKGROUND: Moderate-to-severe cancer-related fatigue occurs in 45% of patients with cancer and interferes with many aspects of quality of life. Although physical exercise has level 1 evidence for improvement of cancer-related fatigue, it has a relatively high behavioural demand compared with other non-pharmacological interventions. The aim of this updated meta-analysis was to address the efficacy of light therapy in improving cancer-related fatigue in patients with cancer. METHODS: We included randomised controlled trials investigating the efficacy of bright white light (BWL) therapy in ameliorating cancer-related fatigue in patients with cancer. This meta-analysis was conducted using a random-effects model. The target outcomes were changes in cancer-related fatigue associated with BWL or dim red light (DRL). RESULTS: There were 9 articles with 231 participants included. The main results revealed that daily morning BWL for 30 min was associated with significantly better improvement in fatigue severity compared with DRL (k=5, Hedges' g=-0.414, 95% CI -0.740 to -0.087, p=0.013). The subgroup without psychiatric comorbidities (k=4, Hedges' g=-0.479, 95% CI -0.801 to -0.156, p=0.004) was associated with significantly better improvement in fatigue severity with BWL than with DRL. In contrary, BWL was not associated with significantly different changes in depression severity or quality of life compared with DRL. Finally, BWL was associated with similar acceptability (ie, dropout rate) and safety profile (ie, any discomfort) as those of DRL. CONCLUSIONS: This meta-analysis provides an updated evidence on the rationale for application of BWL in ameliorating cancer-related fatigue in patients with different types of cancer. TRIAL REGISTRATION NUMBER: INPLASY202140090.

11.
12.
Brain Sci ; 11(6)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071756

RESUMO

The application of transcranial direct current stimulation (tDCS) to targeted cortices has been found to improve in skill acquisition; however, these beneficial effects remained unclear in fine and complicated skill. The aim of the current meta-analysis was to investigate the association between tDCS application and the efficacy of surgical performance during surgical skill training. We included randomized controlled trials (RCTs) investigating the efficacy of tDCS in enhancing surgical skill acquisition. This meta-analysis was conducted under a random-effect model. Six RCTs with 198 participants were included. The main result revealed that tDCS was associated with significantly better improvement in surgical performance than the sham control (Hedges' g = 0.659, 95% confidence intervals (95%CIs) = 0.383 to 0.935, p < 0.001). The subgroups of tDCS over the bilateral prefrontal cortex (Hedges' g = 0.900, 95%CIs = 0.419 to 1.382, p < 0.001) and the primary motor cortex (Hedges' g = 0.599, 95%CIs = 0.245 to 0.953, p = 0.001) were both associated with significantly better improvements in surgical performance. The tDCS application was not associated with significant differences in error scores or rates of local discomfort compared with a sham control. This meta-analysis supported the rationale for the tDCS application in surgical training programs to improve surgical skill acquisition.

13.
Int J Obes (Lond) ; 45(8): 1705-1716, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33972697

RESUMO

BACKGROUND/OBJECTIVES: Obesity has recently been recognized as a neurocognitive disorder involving circuits associated with the reward system and the dorsolateral prefrontal cortex (DLPFC). Noninvasive brain stimulation (NIBS) has been proposed as a strategy for the management of obesity. However, the results have been inconclusive. The aim of the current network meta-analysis (NMA) was to evaluate the efficacy and acceptability of different NIBS modalities for weight reduction in participants with obesity. METHODS: Randomized controlled trials (RCTs) examining NIBS interventions in patients with obesity were analyzed using the frequentist model of NMA. The coprimary outcome was change in body mass index (BMI) and acceptability, which was calculated using the dropout rate. RESULTS: Overall, the current NMA, consisting of eight RCTs, revealed that the high-frequency repetitive transcranial magnetic stimulation (TMS) over the left DLPFC was ranked to be associated with the second-largest decrease in BMI and the largest decrease in total energy intake and craving severity, whereas the high-frequency deep TMS over bilateral DLPFC and the insula was ranked to be associated with the largest decrease in BMI. CONCLUSION: This pilot study provided a "signal" for the design of more methodologically robust and larger RCTs based on the findings of the potentially beneficial effect on weight reduction in participants with obesity by different NIBS interventions.

14.
BMC Gastroenterol ; 21(1): 220, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33990184

RESUMO

BACKGROUND: The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages. METHODS: Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. RESULTS: In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0-96) months for the total cohort and was subdivided into 52 (8-96), 32 (1-96), 19 (0-84), and 12 (0-79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were (1) SR and cirrhosis; (2) SR, cirrhosis, and Child-Pugh (C-P) class; (3) SR, hepatitis B virus (HBV) infection, and C-P class; and (4) SR, HBV infection, and C-P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs. non-SR were 44.0% versus 28.7%, 72.2% versus 42.6%, 42.6% versus 36.2, 44.6% versus 23.5%, and 41.4% versus 15.3% (all P values < 0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages. CONCLUSIONS: SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Estadiamento de Neoplasias , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
16.
Expert Rev Anti Infect Ther ; : 1-11, 2021 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-33899657

RESUMO

Background: Oropharyngeal/esophageal candidiasis are the most common opportunistic infections observed in patients with human immunodeficiency virus (HIV). While the commonly recommended treatment is fluconazole, relapse of oropharyngeal or esophageal candidiasis has been gradually increasing in recent decades.Methods: The current network meta-analysis (NMA) included randomized controlled trials (RCTs) investigating the efficacy and acceptability (i.e. drop-out rate) of different anti-fungal interventions against oropharyngeal or esophageal candidiasis in adults with HIV. All NMA procedures were conducted using the frequentist model.Results: Twenty-seven RCTs and 6277 participants were included. For oropharyngeal candidiasis, photosensitizer-based antimicrobial photodynamic therapy (aPDT) with laser irradiation plus methylene blue was associated with the highest cure rate and the lowest relapse rate among the investigated interventions [odds ratio (OR) = 6.82, 95% confidence intervals (95%CIs) = 0.19 to 244.42, p = 0.293, and OR = 0.03, 95%CIs = 0.00 to 0.77, p = 0.034, compared to fluconazole]. None of the investigated anti-fungal interventions were superior to fluconazole for esophageal candidiasis in respect of cure rates/relapse rates. All investigated anti-fungal interventions were well-accepted.Conclusions: aPDT could be the preferred strategy to manage oropharyngeal candidiasis; however the evidence for esophageal candidiasis still remained inconclusive.

19.
Brain Sci ; 11(2)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530541

RESUMO

Few papers discuss how the economic burden of patients with stroke receiving rehabilitation courses is related to post-acute care (PAC) programs. This is the first study to explore the economic burden of stroke patients receiving PAC rehabilitation and to evaluate the impact of multidisciplinary PAC programs on cost and functional status simultaneously. A total of 910 patients with stroke between March 2014 and October 2018 were separated into a PAC group (at two medical centers) and a non-PAC group (at three regional hospitals and one district hospital) by using propensity score matching (1:1). A cost-illness approach was employed to identify the cost categories for analysis in this study according to various perspectives. Total direct medical cost in the per-diem-based PAC cohort was statistically lower than that in the fee-for-service-based non-PAC cohort (p < 0.001) and annual per-patient economic burden of stroke patients receiving PAC rehabilitation is approximately US $354.3 million (in 2019, NT $30.5 = US $1). Additionally, the PAC cohort had statistical improvement in functional status vis-à-vis the non-PAC cohort and total score of each functional status before rehabilitation and was also statistically significant with its total score after one-year rehabilitation training (p < 0.001). Early stroke rehabilitation is important for restoring health, confidence, and safe-care abilities in these patients. Compared to the current stroke rehabilitation system, PAC rehabilitation shortened the waiting time for transfer to the rehabilitation ward and it was indicated as an efficient policy for treatment of stroke in saving medical cost and improving functional status.

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