Merriline M Satyamitra, Michael Abend, Christina Beinke, David R Cassatt, Andrea L DiCarlo, Patrick Ostheim, Mathias Port, Thomas A Winters, Stefan Eder
{"title":"National Institute of Allergy and Infectious Diseases (NIAID) - Bundeswehr Institute of Radiobiology (BIR) Joint Programmatic Workshop on a Global Approach to Medical Countermeasure Development in Radiological Public Health Preparedness.","authors":"Merriline M Satyamitra, Michael Abend, Christina Beinke, David R Cassatt, Andrea L DiCarlo, Patrick Ostheim, Mathias Port, Thomas A Winters, Stefan Eder","doi":"10.1667/RADE-25-00224","DOIUrl":"https://doi.org/10.1667/RADE-25-00224","url":null,"abstract":"<p><p>This invited commentary grew out of a presentation made at the 2025 ConRad Meeting in Munich, Germany, and summarizes talks made by researchers supported by the National Institute of Allergy and Infectious Diseases (NIAID) and the Bundeswehr Institute of Radiobiology (BIR) during a joint programmatic workshop held on September 11-12, 2024. The symposium focused on the global health readiness and responses to radiological or nuclear public health emergencies; the status of medical countermeasure development and models used to develop these countermeasures; identification of biomarkers of radiation injuries and biodosimetry tools, and recent advances in developing tools for triage, definitive dose assessment and predictive assays. Areas of common synergy between the two entities were also explored to inform potential future collaborative efforts. There are many tools at different stages of development, and emergence of substantive datasets that require cutting-edge machine learning approaches, multiparametric analyses, and integrated systems outcome to fully exploit the potential of this knowledge and accurately address radiological emergency preparedness. In these endeavors, now more than ever, it is critical to continue connecting with the world's scientific communities to accelerate scientific breakthroughs, close research gaps, and enhance radiation emergency readiness.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842086","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}
Hubert Peiffer, Olivier Grémy, Anne Van der Meeren
{"title":"Hypersaline Inhalation: an Alternative to Pulmonary Lavages for Removing Inhaled insoluble Radioactive Particles?","authors":"Hubert Peiffer, Olivier Grémy, Anne Van der Meeren","doi":"10.1667/RADE-25-00159","DOIUrl":"https://doi.org/10.1667/RADE-25-00159","url":null,"abstract":"<p><p>The medical management of victims after pulmonary intake of radioactive insoluble particles is a real challenge. The recommended treatment in case of plutonium or cobalt intake is the administration of the chelating agent DTPA, which remains poorly efficient in decreasing lung retention of oxide particles. Bronchoalveolar lavages may be recommended in case of intake expected to cause deleterious consequences, such as lung cancer or fibrosis. However, due to the risk associated to such procedure, bronchoalveolar lavages are not desirable. The inhalation of hypersaline solution is commonly carried out as an alternative to bronchoalveolar lavages in pulmonology for both therapeutic and diagnosis purposes. Based on extensive scientific publications reporting the effect of sputum induction by inhalation of hypertonic saline solution, we envision a new alternative for the treatment of pulmonary intake with poorly soluble radioactive particles by enhancing mucociliary clearance and thus accelerating the removal of deposited particles. In addition, the analysis of sputum samples obtained by hypersaline aerosol inhalation should bring valuable information regarding the properties of the inhaled radioactive compounds as well as the level of exposure intake. After a brief review of the literature, the present work will discuss which parameters influence the quality and the origin of the samples after sputum induction and will propose recommendations to apply this procedure as a first-line treatment and diagnosis after pulmonary of radioactive poorly soluble particles.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842075","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}
Prabal Subedi, Lukas Duchrow, Anne Dietz, Felix Kaestle, Saskia Pautz, Frank Bunk, Ingrid Baumgartner, Soley Rieger, Ute Roessler, Simone Moertl
{"title":"Application of Blood Smears for the Identification of Non-exposed Individuals after a Nuclear Incident.","authors":"Prabal Subedi, Lukas Duchrow, Anne Dietz, Felix Kaestle, Saskia Pautz, Frank Bunk, Ingrid Baumgartner, Soley Rieger, Ute Roessler, Simone Moertl","doi":"10.1667/RADE-25-00153","DOIUrl":"https://doi.org/10.1667/RADE-25-00153","url":null,"abstract":"<p><p>Healthcare systems will be overwhelmed in the case of a large-scale nuclear incident, not only by members of the exposed population, but also by non-exposed (\"worried-well\") individuals. Current methods of biodosimetry are time-consuming and resource-intensive for use in a large-scale triage operation. We present a rapid blood smear-based assay utilizing a modified γH2AX assay and a new calculation system (test score) to identify non- or low-exposed individuals within 1 h and 24 h after radiation exposure. Venous blood from seven healthy donors was irradiated, in vitro (0-4 Gy) and blood smears were prepared 1 and 24 h postirradiation. Smears were fixed and γH2AX immunostaining was performed. Fifty round nuclei were evaluated by a minimum of seven operators for the presence of γH2AX foci. The proportion of γH2AX foci-positive nuclei, called test score, was used to discriminate between irradiated and non-irradiated samples. Blood smears from non-exposed venous blood were correctly identified as non-exposed within 1 h against a minimum exposure of 0.1 Gy. After 24 h, the smears from non-exposed blood were identified as non-exposed against a minimum exposure of 1 Gy. This result was also validated with blinded samples irradiated at a partner institute. This established protocol was adapted for blood smears generated with capillary blood from three donors, which eliminates the need for a trained professional to draw venous blood and enables the use in field conditions. A discrimination of irradiated and non-irradiated blood was also possible, but thresholds established for venous blood have to be adjusted in future experiments. Together, this fast, operator-friendly assay will allow effective triage in radiological emergencies by reliable exclusion of non-exposed individuals within 6 h of sample arrival, using minimal resources and specialized equipment.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842134","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":"Dear Colleagues and Readers of Radiation Research.","authors":"Lt Colonel Mc Pd Dr Stefan Eder","doi":"10.1667/RADE-26-00CON.1","DOIUrl":"https://doi.org/10.1667/RADE-26-00CON.1","url":null,"abstract":"","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147842137","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":"Comparative Analysis of Proton and Carbon-Ion Therapy for Head and Neck Cancer: LET-Dependent α/β Ratios in EQD2 and NTCP.","authors":"Yushi Wakisaka, Yuya Miyasaka, Yuki Tominaga, Robabeh Rahimi, Takeo Iwai, Teiji Nishio","doi":"10.1667/RADE-25-00183.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00183.1","url":null,"abstract":"<p><p>Proton therapy (PT) and carbon-ion therapy (CIT) differ not only in their physical dose characteristics but also in their biological effects, attributable to variations in fractionation protocols and linear energy transfer (LET). These differences make direct comparisons challenging. This study aims to comprehensively compare the treatment planning of protons and carbon ions for head and neck cancer by incorporating LET-dependent variable α/β ratios into the calculations of equivalent dose in 2 Gy fractions (EQD2) and normal tissue complication probability (NTCP). We retrospectively created treatment plans for nine head and neck cancer patients using proton therapy and carbon-ion therapy. Variable α/β ratios, calculated via the microdosimetric kinetic model, were integrated into EQD2 calculations. NTCP assessments for both late and acute toxicities utilized the Lyman-Kutcher-Burman model. In addition to comparing EQD2 and NTCP outcomes between protons and carbon ions, we conducted robustness evaluations that considered a 2 mm positioning error and a 3.5% range uncertainty. The α/β ratio for protons remained consistent at approximately 3 Gy across all tissues. In contrast, the α/β ratio for carbon ions varied significantly, reaching up to 20 Gy along the beam path. This variability in α/β ratios showed that carbon ions achieved lower EQD2 values for organs at risk (OARs) such as the brain, skin, and oral mucosa compared to protons. Furthermore, NTCP analysis revealed a significant reduction in acute toxicities, particularly dermatitis, with carbon-ion therapy. Both treatment modalities effectively minimized the probability of late toxicities. No significant differences in robustness were observed between proton therapy and carbon-ion therapy. EQD2 calculations incorporating variable α/β ratios revealed that carbon ions offer a dosimetric advantage over protons for certain OARs. However, this difference was relatively minor and did not suggest a clinically significant impact beyond acute toxicities.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779564","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}
Jakub Vavra, Daniela Ekendahl, Lukas Kotik, Marie Davidkova, Christina Beinke, Ursula Oestreicher, David Endesfelder, Martin Bucher, Ondrej Huml, Johana Alaverdyan, Artur Sergunin, Miriam Slezakova
{"title":"Interlaboratory Comparison of the Dicentric Chromosome Assay for a Mixed Gamma-Neutron Radiation Field.","authors":"Jakub Vavra, Daniela Ekendahl, Lukas Kotik, Marie Davidkova, Christina Beinke, Ursula Oestreicher, David Endesfelder, Martin Bucher, Ondrej Huml, Johana Alaverdyan, Artur Sergunin, Miriam Slezakova","doi":"10.1667/RADE-25-00180.1","DOIUrl":"https://doi.org/10.1667/RADE-25-00180.1","url":null,"abstract":"<p><p>In the event of a criticality accident, there is a risk of high-dose exposure for affected individuals from a mixed gamma-neutron radiation field. Dosimetry in such cases is complex and requires multiple approaches. Biodosimetry methods, especially the dicentric chromosome assay (DCA), the most established method, can significantly support triage and medical care decisions after a criticality incident. However, large-scale events need collaboration between laboratories to enable timely dose assessments using DCA. We conducted a comparison among three biodosimetry laboratories, focusing on DCA-based estimates of the total dose, including the specific gamma-ray dose and neutron-heavy-particle dose for blood samples irradiated in a mixed gamma-neutron field. Although each laboratory used dose-effect curves derived from different radiation spectra and irradiation facilities, the dose estimates were acceptable, with relative deviations no greater than 21%. Overall, the study showed that collaborating between labs is feasible for individual dose estimation after a criticality accident.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779620","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}
Yu Feng Zhang, Yu Xu, Ke Zhou, Chen Wang, Ji Yu Xu, Ze Lin Xu, Yi Qi Yi, Po Bian, Ting Wang
{"title":"Lipophagy Mitigates Radiation-induced Liver Lipid Disorders and Damage in Adolescent Mice.","authors":"Yu Feng Zhang, Yu Xu, Ke Zhou, Chen Wang, Ji Yu Xu, Ze Lin Xu, Yi Qi Yi, Po Bian, Ting Wang","doi":"10.1667/RADE-26-00008","DOIUrl":"https://doi.org/10.1667/RADE-26-00008","url":null,"abstract":"<p><p>Ionizing radiation poses a significant health risk to adolescent livers by disrupting lipid metabolism, yet protective mechanisms remain poorly understood. We investigated this using a pubertal mouse model exposed to localized X-irradiation. Our approach combined transcriptomics, lipidomics, and pharmacological modulation of lipophagy with 3-methyladenine and rapamycin. We also introduced a high-fat diet (HFD) to explore its synergistic effects with radiation. Radiation exposure alone reduced liver mass, increased plasma transaminases [Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], caused intrahepatic lipid droplet retention, and impaired glucose tolerance. Lipidomics revealed significant accumulation of lysophosphatidylcholine, triglycerides, and diacylglycerols. Notably, combining high-fat diet with radiation synergistically worsened mild radiation-induced steatosis into severe hepatocellular damage, with sharply increased transaminases and insulin resistance. Mechanistically, radiation down-regulated key lipophagy-related genes like ATGL and LC3B-II. Pharmacological inhibition of lipophagy worsened steatosis and liver dysfunction, while its activation improved lipid clearance and considerably reduced liver injury. Our findings establish lipophagy as a vital adaptive response to radiation-induced metabolic stress in the adolescent liver. This study highlights the combined toxic effects of environment and diet and suggests that boosting lipophagy could be an effective strategy to lessen the adverse health effects of radiation exposure in vulnerable young populations.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779640","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}
Ling He, Purva Joshi, Angeliki Ioannidis, Anoushka Kathiravan, Mohammad Saki, Frank Pajonk
{"title":"Repurposing Quetiapine as an Adjuvant Therapeutic Agent for Triple-Negative Breast Cancer.","authors":"Ling He, Purva Joshi, Angeliki Ioannidis, Anoushka Kathiravan, Mohammad Saki, Frank Pajonk","doi":"10.1667/RADE-25-00222.1","DOIUrl":"10.1667/RADE-25-00222.1","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) lacks actionable molecular targets, so treatment primarily relies on cytotoxic chemotherapy and radiotherapy, yet relapse, resistance, and metastasis still drives poor long-term survival. Dopamine signaling has recently been linked to tumor aggressiveness, and dopamine-receptor antagonists have shown preclinical benefit in other cancers. We therefore evaluated quetiapine (QTP), an FDA-approved DRD2/DRD3 antagonist, as a therapeutic adjunct in TNBC. SUM159-PT, BT-549, and MDA-MB-231 cells were treated with QTP alone or combined with radiation or standard agents (doxorubicin, paclitaxel, 5-fluorouracil). Clonogenic and mammosphere assays measured proliferative and self-renewal potential. Annexin V/propidium-iodide flow cytometry quantified apoptosis, and γ-H2AX immunofluorescence tracked DNA double-strand breaks and repair kinetics. Transwell assays assessed migration of untreated bulk cells and radiation-surviving subclones. QTP significantly reduced clonogenicity and self-renewal in all TNBC models tested, both alone and in combination with radiation or chemotherapy. In apoptosis assays, QTP treatment induced a marked increase in early and late apoptotic cell populations. QTP also promoted DNA double-strand break formation and delayed repair, as indicated by persistent γ-H2AX foci at 24 h after treatment. Additionally, QTP impaired the migratory capacity of both untreated and radiation-surviving cells. Combination treatments with QTP and doxorubicin produced synergistic effects, resulting in complete loss of colony-forming ability and mammosphere formation. The data presented support the repurposing of quetiapine as an adjuvant therapeutic agent alongside radiotherapy and/or chemotherapy in TNBC. By targeting apoptosis, DNA repair, and cancer cell migration, QTP offers a novel, multi-faceted approach to improve outcomes in this high-risk breast cancer subtype.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779579","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}
Christina Beinke, Elizabeth A Ainsbury, Andreas Lamkowski, Matthias Port
{"title":"Case Report: The Limited Value of Dicentric Analysis in Cases of Suspected Overexposure to a Low X-ray Dose.","authors":"Christina Beinke, Elizabeth A Ainsbury, Andreas Lamkowski, Matthias Port","doi":"10.1667/RADE-25-00195","DOIUrl":"https://doi.org/10.1667/RADE-25-00195","url":null,"abstract":"<p><p>Dicentric analysis is used to confirm ionizing radiation exposure and to estimate individual absorbed doses. However, assessing doses below 100 mSv and clearly communicating the findings to the affected person is challenging, partly due to uncertainties in dose estimation. The case described here involves a materials tester who operated two different irradiation devices, one for gamma-ray irradiation and the other for X-ray irradiation, in parallel and was likely overexposed to X rays. A rapid evaluation of his personal dosimeter indicated a value of 5.6 mSv. Dicentric analysis was performed 2.5 months later through manual scoring of up to 3,006 metaphases and automatic evaluation of 8,677 metaphases. The dicentric yields were compared with the decision threshold, the detection limit, and the laboratory's zero-dose reference data. Individual absorbed radiation doses with 95% confidence intervals were estimated, and odds ratios along with probabilities of exposure were calculated using a Bayesian approach. While this scenario is less concerning for acute or long-term health effects, it can still cause psychological stress and legal issues related to occupational safety for the worker involved. This report discusses various options for presenting and interpreting results, as well as the diagnostic value and limitations of dicentric analysis regarding potential low-dose exposures. Although only one person is studied, this case offers valuable insights into the practical application of dicentric analysis.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779561","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}
Qiwei Wu, Cheng Zheng, Zihao Liu, Xiaogang Yuan, Yunwen Huang, Ning Zhao, Hui Liu, Yidong Yang
{"title":"Histological Evaluation of In Vivo Dose Delivery in Respiration-gated Small Animal Radiotherapy.","authors":"Qiwei Wu, Cheng Zheng, Zihao Liu, Xiaogang Yuan, Yunwen Huang, Ning Zhao, Hui Liu, Yidong Yang","doi":"10.1667/RADE-25-00189","DOIUrl":"https://doi.org/10.1667/RADE-25-00189","url":null,"abstract":"<p><p>Preclinical small-animal radiotherapy is essential for advancing radiobiological research. However, respiratory motion causes significant geometric uncertainty and dose blurring, reducing treatment accuracy. This study aims to develop and validate an integrated respiration-gated irradiation technique for mice and assess its effectiveness in decreasing motion-induced targeting errors. Respiratory motion was tracked in real time using an optical displacement sensor, and a mechanical shutter was employed to gate the X-ray beam. Both ungated and gated irradiation were delivered to the liver and lung (n = 8 per group). Ex vivo γH2AX immunofluorescence staining and an image analysis pipeline were used to evaluate the radiation field. The histological dimension in the irradiated tissue was adjusted using tissue-specific shrinkage factors to account for histology-related shrinkage, and the corrected measurements were compared between the ungated and gated groups. γH2AX analysis showed that respiratory gating significantly reduced the histological dimension along the superior-inferior axis in both the liver (ungated: 3.00 ± 0.85 mm vs. gated: 1.75 ± 0.24 mm; P < 0.01) and the lung (ungated: 2.55 ± 0.64 mm vs. gated: 1.33 ± 0.19 mm; P < 0.001). This resulted in a 1.25 mm reduction in the motion-related geometric margin for the liver and a 1.22 mm reduction for the lung. This study provides direct biological evidence that respiratory gating effectively reduces motion-induced dose blurring. The proposed gating method can significantly reduce treatment margins caused by motion, thereby enhancing targeting accuracy and sparingnormal tissue.</p>","PeriodicalId":20903,"journal":{"name":"Radiation research","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779592","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}