Melanoma Research最新文献

{"title":"Nectin-4 as predictive biomarker of immune-related adverse event subtypes in adjuvant anti-programmed-death-1 treatment of melanoma.","authors":"Sabrina Bruno, Andrew D Knight, Caroline J Layding, Hong Wang, Walter J Storkus, Lilit Karapetyan, John M Kirkwood","doi":"10.1097/CMR.0000000000001122","DOIUrl":"10.1097/CMR.0000000000001122","url":null,"abstract":"<p><p>Immune checkpoint inhibitors have transformed melanoma management; however, immune-related adverse events (irAEs) remain a major source of morbidity. Soluble immunomodulatory proteins are established biomarkers of autoimmune reactivity but have not been validated as predictors of irAEs. Evaluating their associations with irAEs may help identify patients at elevated risk and inform optimization of adjuvant checkpoint inhibitor therapy. Baseline serum samples from patients with resectable melanoma receiving adjuvant anti-programmed-death-1 therapy were obtained from the University of Pittsburgh Melanoma Center biospecimen repository ( n  = 43). Soluble immunomodulatory proteins were quantified using Milliplex technology. Mean pretreatment protein levels were compared between patients with and without irAEs using two-sample t -tests. Siglec-7 and Siglec-9 were elevated in patients who developed any irAE. Dermatitis was associated with elevated B7-H3 and major histocompatibility complex class I polypeptides. Thyroiditis was associated with elevated Nectin-4 and CXCL13 and reduced LAG3. Colitis was associated with elevated arginase. Hepatitis was associated with increased Galectin-3 and decreased Galectin-1, CD40L, CD226, and Nectin-4. Nectin-4 remained significant after false discovery rate adjustment in both thyroiditis and hepatitis, and CD226 remained significant in hepatitis. Potential biomarkers of recurrence-free survival (perforin, CD25, and ICOSL) and overall survival (FGL1) were also identified. Baseline soluble immunomodulatory proteins may predict the development of specific irAEs and survival outcomes from adjuvant anti-programmed-death-1 treatment. Notably, Nectin-4 may serve as a biomarker for both thyroiditis and hepatitis. Prospective studies are warranted to validate these findings.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"436-443"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An online cutaneous melanoma risk screen tool.","authors":"Wenhui Liu, Ya Xu, Yixin Yang, Maryam Taadolkhah, Bingjie Cai, Jiangan Zhang, Guangshuai Li","doi":"10.1097/CMR.0000000000001121","DOIUrl":"10.1097/CMR.0000000000001121","url":null,"abstract":"<p><p>To develop and deploy a publicly accessible online risk estimation tool for cutaneous melanoma that prioritizes high recall to minimize missed diagnoses, using real-world clinical photographs rather than dermoscopic images, and to bridge the gap between artificial intelligence research and clinical implementation. A 'segmentation-first, then-classification' strategy was adopted. Lesions were segmented using MFSNet pretrained on dermoscopic images. The classification model was customized from EfficientFormerV2-L by integrating dual attention, multi-scale pooling, and feature fusion modules. A balanced dataset of 934 clinical images (467 melanoma, 467 nevus) from PAD-UFES-20, Seven-Point Check, Med-node, and other sources was used. Weighted BCEWithLogitsLoss (positive weight up to 6) was applied to increase the penalty for false negatives. External validation was performed on 32 smartphone-captured images (16 melanoma, 16 nevus). The model was deployed online with an automated image quality check. The customized model (trained from scratch, positive weight 6) achieved a recall of 0.95, precision of 0.75, and F1 score of 0.84 on cross-validation, outperforming the base EfficientFormerV2-L (recall 0.88). Dermoscopic pretraining unexpectedly degraded classification performance on clinical images. External validation showed significantly higher malignant potential scores for melanoma versus nevus cases ( P  < 0.0001). The online tool is freely available at http://www.make-a-difference.top/mmscreen . This study provides a practical, high-recall online melanoma screening tool for real-world clinical images. Its free public access and emphasis on minimizing false negatives address critical gaps in early melanoma detection, particularly in primary care settings.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"416-423"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scalp melanoma presents with greater Breslow thickness and higher metastatic burden: analysis of 105 Korean cutaneous head and neck melanoma patients.","authors":"Hong Euy Kim, Jinkyeong Kim, Dong Hoon Lee, Hyun Jeong Shim, Sook Jung Yun","doi":"10.1097/CMR.0000000000001126","DOIUrl":"10.1097/CMR.0000000000001126","url":null,"abstract":"<p><p>Cutaneous head and neck melanoma (CHNM) accounts for a disproportionate share of melanoma-related mortality, yet the prognostic value of its precise anatomical site remains uncertain. We retrospectively reviewed 105 patients with CHNM diagnosed at Chonnam National University Hwasun Hospital between 2002 and 2023. Variables were compared across four sites (scalp, face, neck, ear), and overall survival (OS), melanoma-specific survival (MSS), and recurrence-free interval (RFI) were analyzed using Kaplan-Meier methods and multivariable Cox proportional hazards models. Scalp melanomas arose in younger patients yet displayed the greatest Breslow thickness. Distant metastasis occurred during follow-up in 67% of scalp and 64% of all nonfacial melanomas, compared with 19% of facial melanomas. By Kaplan-Meier analysis, OS and MSS did not differ significantly by anatomic site (log-rank P  = 0.18 and P  = 0.11), whereas RFI differed across subsites (log-rank P  < 0.001), with lower RFI for scalp than face in multiplicity-adjusted pairwise comparisons (adjusted P  = 0.002). In multivariable Cox models, Breslow thickness remained independently associated with poorer OS [hazard ratio: 1.457, 95% confidence interval (CI): 1.235-1.719, P  < 0.001), MSS (hazard ratio: 1.700, 95% CI: 1.414-2.045, P  < 0.001), and RFI (hazard ratio: 1.195, 95% CI: 1.087-1.329, P  < 0.001). Overall, scalp melanomas presented with the greatest Breslow thickness and higher metastatic burden, whereas Breslow thickness remained the primary independent prognostic factor for MSS and RFI in Korean patients with CHNM.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"453-460"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High dose interleukin-2 in combination with anti-programmed cell death protein 1 to overcome immune checkpoint inhibitor resistance in metastatic melanoma and renal cell carcinoma.","authors":"Tali Azenkot, Mina Nikanjam, Soham Mhatre, Jaren T Mullen, Donald A Barkauskas, Rana R McKay, Joel M Baumgartner, Gregory A Daniels","doi":"10.1097/CMR.0000000000001102","DOIUrl":"10.1097/CMR.0000000000001102","url":null,"abstract":"<p><p>To assess the combination of high dose interleukin 2 (HD IL2) and nivolumab in patients with checkpoint inhibitor-refractory melanoma or renal cell carcinoma (RCC), we performed a single-arm, Simon two-stage phase II trial for patients with unresectable stage III or IV melanoma or any histology RCC. The primary endpoint was overall response rate (ORR); secondary endpoints were adverse events and progression-free survival (PFS), defined as time to radiographic or clinical progression, whichever occurred first. Five patients enrolled, three with melanoma and two with RCC. Median age at registration was 47 (35-77) years. Two patients (40%) had treated or asymptomatic brain metastases, and one (20%) had liver metastases. Median prior lines of systemic therapy per patient were 3 (2-5). Patients completed a median of 1 (0.5-3) treatment cycle, involving two admissions for HD IL2 administration and two doses of nivolumab. ORR was 20%. Median PFS was 1.4 (0.8-45.0) months. Time to next therapy for each living patient was 2.5 and 45.6 months for local modalities, and 2.0, 2.3, and 45.9 months for systemic therapies. Adverse events reflected the known toxicity of HD IL2. One treatment-related death occurred, leading to trial termination. The combination of HD IL2 and nivolumab resulted in a durable response in one of five patients with PD-1-refractory advanced melanoma or RCC. Use of HD IL2 remains limited by its toxicity; augmented IL2 formulations and administration strategies are needed. ClinicalTrials.gov ID: NCT03889782 (Registered 6/16/2019; https://clinicaltrials.gov/study/NCT03889782 ).</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"444-452"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NF1 alterations as potential biomarker in acral melanoma: looking beyond low tumor mutational burden.","authors":"Elilea Boudzoumou, Manuel Croix, Jean-Matthieu L'Orphelin","doi":"10.1097/CMR.0000000000001130","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001130","url":null,"abstract":"","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"36 5","pages":"476-478"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissociation between systemic inflammatory markers and the tumor microenvironment in predicting sentinel lymph node metastasis in cutaneous melanoma.","authors":"Nilay Duman, Aslihan Özel, Damla Değirmenci, Banu Yaman, Ahmet Biçer, Yiğit Özer Tiftikcioglu, Işil Karaarslan, Ayşe Caner, Taner Akalin, Şaziye Burçak Karaca","doi":"10.1097/CMR.0000000000001139","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001139","url":null,"abstract":"<p><p>Systemic inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), are established prognostic biomarkers in melanoma, particularly in advanced disease. However, their utility in predicting early metastatic spread, such as sentinel lymph node (SLN) involvement, remains unclear. To evaluate the relative contributions of systemic inflammatory indices and tumor microenvironment (TME) features in predicting SLN metastasis in cutaneous melanoma. In this retrospective, single-center study, clinicopathological parameters, peripheral blood-derived inflammatory indices (NLR, PLR, lymphocyte-to-leukocyte ratio, lymphocyte-to-monocyte ratio, and neutrophil-to-eosinophil ratio), and TME features, including tumor-infiltrating lymphocytes (TILs) and tumor regression, were analyzed. Multivariable analyses and nested predictive models were constructed to identify independent predictors and to assess the incremental predictive value of each parameter group. SLN positivity was strongly associated with established histopathological markers, including Breslow thickness, ulceration, mitotic rate, and lymphovascular invasion (all P < 0.001). In contrast, systemic inflammatory indices showed no significant association with SLN involvement (all P > 0.05). TME-related features demonstrated significant associations; higher TIL density showed a dose-dependent inverse relationship with SLN positivity (P = 0.001), while tumor regression was linked to reduced nodal metastasis (P = 0.031). In addition, lower platelet counts were also associated with SLN positivity (P = 0.03). Incorporation of TME features improved model performance, whereas systemic inflammatory markers did not provide additional predictive value. Early nodal metastasis in melanoma appears to be driven by local tumor-immune interactions rather than systemic inflammation. These findings support the limited predictive value of circulating inflammatory markers and highlight the importance of TME features in risk stratification and clinical decision-making.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149081463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between perioperative antidepressant use and postoperative outcomes after cutaneous melanoma resection.","authors":"Brendon Wang, Steven Tran, Melanie Clark","doi":"10.1097/CMR.0000000000001144","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001144","url":null,"abstract":"<p><p>Cutaneous melanoma is the fifth most common cancer in the USA and the most fatal form of skin cancer. Antidepressants (ADPs) are among the most commonly prescribed medications in this population and may influence postoperative recovery through effects on platelet aggregation, immune signaling, and pain modulation. This study aimed to determine whether perioperative ADP use is associated with increased postoperative complications and healthcare utilization following melanoma resection. Using the TriNetX federated database, we conducted a propensity-matched retrospective cohort study comparing 90-day postoperative outcomes between adult melanoma patients with and without perioperative ADP use following surgical resection. Among 19 470 propensity-matched patients (9735 per group), ADP use was associated with significantly higher rates of opioid prescriptions (32.8% vs 21.2%), surgical site infection (2.1% vs 1.1%), sepsis (1.2% vs 0.4%), inpatient hospitalization (10.7% vs 5.2%), emergency department visits (6.9% vs 4.5%), and hemorrhage (0.3% vs 0.1%; all P < 0.01). Patients in the control cohort were more likely to undergo lymph node biopsy than ADP users (1.3% vs 0.9%; P = 0.006). Wound disruption did not differ significantly between groups. Perioperative ADP use was associated with increased postoperative morbidity and healthcare utilization. Because tumor characteristics and procedural complexity could not be assessed in this dataset, these findings are best interpreted as identifying ADP use as a marker of a higher-risk perioperative phenotype rather than evidence of a direct causal effect. These results support proactive monitoring, infection surveillance, and judicious opioid prescribing in this population.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic immune subtyping and connectivity mapping nominate DNA methyltransferase inhibitors for immunedepleted melanoma.","authors":"Sanja Brnić, Robert Likić","doi":"10.1097/CMR.0000000000001141","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001141","url":null,"abstract":"<p><p>Immune-cold melanomas respond poorly to immune checkpoint blockade (ICB). We assessed whether RNA-seq-based immune subtyping and connectivity mapping could nominate repurposable compounds to shift immune-depleted melanoma toward an immune-enriched phenotype. Using RNA-seq from 432 The Cancer Genome Atlas Skin Cutaneous Melanoma cases, we assigned published molecular functional portrait subtypes and compared depleted (D, n = 169) with combined immune-enriched (IE + IE/F, n = 184) subtypes using limma-voom. The resulting 300-up/300-down signature underwent Library of Integrated Network-based Cellular Signatures L1000 connectivity mapping, with compound-level aggregation and mechanism-of-action annotation. The pipeline was rerun on two stratified split-half folds. Canonical cytotoxic and antigen-presentation genes (CD8A, PDCD1, CXCL9, CXCL10, CD3D, GZMB, PRF1) were depleted in D, validating the contrast. Raw connectivity-mapping hits were dominated by generic cytotoxic-stress compounds. After aggregation and filtering, DNA methyltransferase (DNMT) inhibitors showed the most consistent positive pattern; fdcyd, azacitidine, and RG-108, but not decitabine, were robust to sample-type sensitivity analysis. Class enrichment was not significant after correction [false discovery rate (FDR) q = 0.126]. Indoleamine 2,3-dioxygenase inhibitors trended negative (FDR q = 0.095), and mitogen-activated protein kinase kinase inhibitors showed no class-level pattern (FDR q = 0.698). Across both folds, all seven canonical genes replicated and all four DNMT inhibitors retained above-median ranks, but the cold-elevated signature module was markedly less stable than the hot-elevated module (25.7 vs. 88.7% overlap). This suggestive pattern converges with a phase II trial of azacitidine/carboplatin priming before anti-programmed death-ligand 1 rechallenge in ICB-resistant melanoma, supporting prospective evaluation.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DPM2 promotes melanoma progression and serves as a prognostic factor.","authors":"Wei Ding, Chao Ci, Tao Yuan, Huijun Wei, Zhengxiang Zhang","doi":"10.1097/CMR.0000000000001132","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001132","url":null,"abstract":"<p><p>Recently, dolichol phosphate mannose synthase (DPMS) has emerged as a promising new target for treatment in various cancers. Nonetheless, DPM2, a crucial element of the DPMS family, remains unexplored in melanoma research. This study aims to explore the predictive significance and biological role of DPM2, utilizing extensive databases and functional tests conducted in vitro. We conducted an in-depth examination of the DPM2 expression feature within The Cancer Genome Atlas database. Group differences were evaluated using Student's t-test, one-way analysis of variance, and long-rank test, while survival distributions were estimated using the Kaplan-Meier method. Functional experiments were conducted in multiple melanoma cell lines to evaluate the effects of altered DPM2 expression. Our research indicated a direct correlation between the expression levels of DPM2 and the severity of melanoma. In addition, an elevated level of DPM2 expression was significantly linked to unfavorable prognoses. Suppression of DPM2 inhibits the proliferation, migration, and invasion of melanoma cells and induces their apoptosis. These findings suggest that DPM2 plays a pivotal role in melanoma progression and may serve as an independent prognostic biomarker for the disease.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted BRAF /MEK inhibition as a salvage therapy for patients with metastatic melanoma harboring a BRAF L597R mutation: two case reports and review of the literature.","authors":"Andrew Moufarrej, Sarah Biermann, Robin Springer, Norman-Philipp Hoff, Bernhard Homey, Harm-Henning Lindhof","doi":"10.1097/CMR.0000000000001135","DOIUrl":"https://doi.org/10.1097/CMR.0000000000001135","url":null,"abstract":"<p><p>Combined B-Raf proto-oncogene, serine/threonine kinase/MAPK kinase (BRAF/MEK) inhibition, along with immune checkpoint inhibition, has significantly improved the outcomes of patients with advanced melanoma harboring BRAF V600 mutations. However, the clinical efficacy of targeted therapy for melanomas with rare class II BRAF mutations, such as L597R, remains unclear. We report two patients with metastatic BRAF L597R-mutated melanoma who responded to BRAF/MEK inhibition. Both patients initially underwent dual immune checkpoint inhibition. Because of rapid clinical deterioration and disease progression, the treatment was switched to binimetinib in case 1 and binimetinib/encorafenib combination therapy in case 2. Both patients demonstrated a rapid clinical response to targeted therapy, including a notable reduction in the tumor burden and symptomatic improvement. In case 1, resistance developed after 3 months, resulting in disease progression. In case 2, targeted therapy was discontinued after 8 weeks because of the anticipated emergence of resistance, and immune checkpoint inhibition was reinitiated. Stable disease and symptom control were maintained for an additional 6 months, after which disease progression was observed. The overall survival rates were 10 and 11 months, respectively. These cases illustrate that targeted therapy can induce a rapid response in patients with metastatic melanoma harboring the BRAF L597R mutation while also highlighting the risk of early treatment resistance. This treatment option should be considered, particularly for patients with pronounced symptoms and high tumor burden.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}