Einstein-Sao Paulo最新文献

{"title":"Oral mucous membrane pemphigoid as a window to systemic autoimmunity: two cases associated with rheumatoid arthritis and Sjögren's disease.","authors":"Isabella Castro de Oliveira, Laura Silva Dos Santos, Jessica Dos Santos Rodrigues, Renan Rodrigues Neves Ribeiro do Nascimento, Laura Caldas Dos Santos, Juliana Mota Siqueira","doi":"10.31744/einstein_journal/2026RC2514","DOIUrl":"10.31744/einstein_journal/2026RC2514","url":null,"abstract":"<p><p>Mucous membrane pemphigoid is a rare chronic autoimmune bullous disease that predominantly affects mucosal surfaces and may lead to significant morbidity when diagnosis is delayed. Increasing evidence suggests that oral manifestations may serve as reliable early indicators of systemic immune dysregulation and can precede the recognition of other autoimmune disorders. We report two cases of oral mucous membrane pemphigoid associated with systemic autoimmune diseases, emphasizing that the oral cavity is a sentinel site for systemic autoimmunity and highlighting the importance of integrated diagnostic and therapeutic strategies. In the first case, a 68-year-old woman with longstanding rheumatoid arthritis presented with recurrent oral ulcerations that were histopathologically confirmed as mucous membrane pemphigoid. During follow-up, ocular involvement was identified as peripheral ulcerative keratitis related to rheumatoid arthritis, requiring adjustment of systemic immunosuppressive therapy. Switching to B-cell depletion therapy with rituximab resulted in the control of both the extra-articular rheumatoid arthritis manifestation and mucous membrane pemphigoid activity. In the second case, a 44-year-old woman presented with desquamative gingivitis and oral bullous lesions. After a biopsy confirmed mucous membrane pemphigoid, progressive sicca symptoms prompted rheumatological investigation, leading to the diagnosis of Sjögren's disease based on serology, imaging, and minor salivary gland biopsy. Treatment with azathioprine resulted in the clinical stabilization of both diseases. These cases illustrate how oral lesions may reveal or precede systemic autoimmune disease and underscore the diagnostic challenges of overlapping immune-mediated rheumatic diseases. Recognizing shared immunopathogenic pathways may enable the selection of targeted therapies that simultaneously control multiple autoimmune conditions, thereby improving disease control and reducing the treatment burden.</p>","PeriodicalId":47359,"journal":{"name":"Einstein-Sao Paulo","volume":"24 spe3","pages":"eRC2514"},"PeriodicalIF":1.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13689956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246802","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":"Downregulation of TRMT9B and its association with clinicopathological features in thyroid cancer: an analysis of public datasets.","authors":"Isadora Biazon de Souza, Larissa Mikalauskas, Felipe Yuji Koyama Azeka, Alexander de Moraes Frankiw, Nathan Mignella Greco, Maria Alice Kawashita Dalla Vecchia, Helena Panteliou Lima-Valassi, Alessandra Valéria de Sousa Faria","doi":"10.31744/einstein_journal/2026AO2165","DOIUrl":"10.31744/einstein_journal/2026AO2165","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the association between TRMT9B expression and clinicopathological features in thyroid carcinoma.</p><p><strong>Methods: </strong>TRMT9B mRNA expression was analyzed using The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) and Genotype-Tissue Expression (GTEx) datasets as well as six independent Gene Expression Omnibus (GEO) datasets. Protein-level data were obtained from The Human Protein Atlas. Associations between TRMT9B expression and clinicopathological parameters were evaluated in the TCGA cohort.</p><p><strong>Results: </strong>TRMT9B mRNA was significantly downregulated in thyroid tumors compared with normal tissues across multiple cohorts. In the TCGA cohort, lower TRMT9B expression was significantly correlated with advanced T stage, lymph node involvement, and aggressive histological variants of papillary thyroid carcinoma. Immunohistochemistry data qualitatively supported these findings: protein staining was lower in tumor samples than in healthy tissue.</p><p><strong>Conclusion: </strong>TRMT9B is downregulated in thyroid carcinoma and is associated with markers of disease progression. These findings suggest that TRMT9B plays a role in thyroid tumor biology. Further functional studies are required to clarify its mechanisms and potential clinical utility as a biomarker.</p>","PeriodicalId":47359,"journal":{"name":"Einstein-Sao Paulo","volume":"24 ","pages":"eAO2165"},"PeriodicalIF":1.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246781","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":"Are Artificial Intelligence recommendations in medical practice reliable?","authors":"Thalya Fernanda Horsth Maltarollo, Lucas Domingues-Dos-Santos, Caleb Shitsuka, Mary Caroline Skelton-Macedo","doi":"10.31744/einstein_journal/2026CE2451","DOIUrl":"10.31744/einstein_journal/2026CE2451","url":null,"abstract":"","PeriodicalId":47359,"journal":{"name":"Einstein-Sao Paulo","volume":"24 ","pages":"eCE2451"},"PeriodicalIF":1.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246770","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":"Probabilistic clinical studies and deterministic physiology: building a Monte Carlo bridge with the \"Frank\" project.","authors":"Felipe Coelho Argolo, Arthur Vasconcelos de Luna Freire, Larrie Rabelo Laporte, Guilherme Moreira Magnavita, Luís Cláudio Lemos Correia","doi":"10.31744/einstein_journal/2026AE2239","DOIUrl":"10.31744/einstein_journal/2026AE2239","url":null,"abstract":"<p><strong>Objective: </strong>To resolve the apparent paradox between deterministic physiological laws and probabilistic clinical outcomes by framing clinical variability as epistemic uncertainty within a complex, non-linear system, demonstrating how deterministic mechanisms can account for empirical distributions and outcome heterogeneity.</p><p><strong>Methods: </strong>We developed the \"Frank\" project, a 0-dimensional computational agent-based model (ABM) of human cardiovascular hemodynamics implemented in Julia (Agents.jl). Using Monte Carlo simulations (n=100), myocardial infarction was modeled by varying initial conditions, specifically sampling the infarction area from a Gaussian distribution along with systemic compliance. Cardiogenic shock was defined by a systolic arterial pressure <90mmHg and a cardiac index <2.2L/min/m2, with parameters evaluated via grid search against literature incidence benchmarks (5-10%).</p><p><strong>Results: </strong>The simulation produced hemodynamically stable, physiologically sound boundary parameters and pressure-volume loops. When initialized with a mean infarction area of 35±5% and systemic compliance of 1.5±0.3mL/mmHg, the model yielded a 7% incidence of cardiogenic shock, closely matching empirical data. A strong linear inverse correlation was observed between infarction area and post-infarction systolic blood pressure (mean 93.96mmHg).</p><p><strong>Conclusion: </strong>Stochastic-appearing clinical trial outcomes can emerge from deterministic physiological systems characterized by sensitivity to initial parameters and hidden variables. The \"Frank\" framework establishes a Monte Carlo bridge between mechanistic physiology and epidemiological statistics, offering an approach to explore outcome heterogeneity and refine clinical trial interpretation and patient stratification.</p>","PeriodicalId":47359,"journal":{"name":"Einstein-Sao Paulo","volume":"24 spe1","pages":"eAE2239"},"PeriodicalIF":1.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13689971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246819","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":"Differences in the clinical profile between isolated lupus anticoagulant and triplepositive antiphospholipid antibody profiles in primary antiphospholipid syndrome.","authors":"Bruno Verza Azevedo, Flavio Signorelli, Gustavo Guimarães Moreira Balbi, Danieli Castro Oliveira Andrade","doi":"10.31744/einstein_journal/2026AO1654","DOIUrl":"10.31744/einstein_journal/2026AO1654","url":null,"abstract":"<p><strong>Objective: </strong>To compare the clinical phenotype of patients with primary antiphospholipid syndrome who have isolated lupus anticoagulant positivity versus those with triple positivity.</p><p><strong>Methods: </strong>This cross-sectional study included two cohorts from two tertiary centers in Brazil comprising patients diagnosed with primary antiphospholipid syndrome.</p><p><strong>Results: </strong>Of 313 patients, 135 were selected and divided into two groups. A total of 99 had isolated lupus anticoagulant positivity and 36 had triple positivity. Most participants were female (58.5%) and White (61.5%), with a mean age of 50.1±12.0 years and a median disease duration of 16 (12-22) years. Both groups showed similar rates of thrombosis (93.9% in the lupus anticoagulant group versus 100% in the triple positivity group, p=0.131) and obstetric events (55.8% versus 60.0%, p=0.754). Microthrombotic and non-thrombotic event rates were also comparable. Hydroxychloroquine use was higher in the triple-positive group (36.1%) than in the lupus anticoagulant group (15.2%, p=0.008).</p><p><strong>Conclusion: </strong>No more severe phenotype was observed in patients with triple positivity compared with those with isolated lupus anticoagulant positivity. The mixed ancestry and demographic composition of the Brazilian population may explain differences compared with more homogeneous populations.</p>","PeriodicalId":47359,"journal":{"name":"Einstein-Sao Paulo","volume":"24 ","pages":"eAO1654"},"PeriodicalIF":1.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246800","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":"Robotic resection of cardiac papillary fibroelastoma guided by three-dimensional transesophageal echocardiography: a case report.","authors":"Fernando Hideki Sakamoto, Ana Clara Tude Rodrigues, Claudio Henrique Fischer, Edgar Lira-Filho, Samira Saady Morhy, Adriana Venturini Reche, Robinson Poffo, Sergio Augusto Fudaba Curcio, João de Azevedo, Sofia Alves Figueiredo Faustino, José Henrique Dias de Sousa, Marcelo Luiz Campos Vieira","doi":"10.31744/einstein_journal/2026RC1564","DOIUrl":"10.31744/einstein_journal/2026RC1564","url":null,"abstract":"<p><p>Heart neoplasms are classified as primary or secondary, with primary tumors considered rare. Cardiac papillary fibroelastoma is the second most common benign cardiac tumor. It has distinct morphological features and carries a potential risk of embolization; therefore, surgical excision is generally recommended. The use of three-dimensional transesophageal echocardiography (3D TEE) enables improved characterization of the suspected lesion, provides a detailed anatomical assessment, and assists in intraoperative planning and management. We report the case of a patient diagnosed with a cardiac papillary fibroelastoma of the mitral valve who underwentrobotic-assisted surgery guided by 3D TEE.</p>","PeriodicalId":47359,"journal":{"name":"Einstein-Sao Paulo","volume":"24 ","pages":"eRC1564"},"PeriodicalIF":1.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246790","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":"Perceptions of residents and graduates regarding the theoretical-practical teaching model in orthopedics.","authors":"Marcus Vinicius Mota Garcia Moreno, Priscila Mina Falsarella, Pedro Henrique Machado Carani, Miguel José Francisco Neto, Guilherme Francchini Santos, Guilherme Ciconelli Del Guerra, Luiz Guilherme Carvalho Hartmann, Victor Arantes Jabour, Cesar Augusto Passos Braga, Marcelo Rocha Correia da Silva, Rodrigo Gobbo Garcia, Marcos Roberto Gomes de Queiroz","doi":"10.31744/einstein_journal/2026AO2040","DOIUrl":"10.31744/einstein_journal/2026AO2040","url":null,"abstract":"<p><strong>Objective: </strong>To assess residents' and graduates' perceptions of the theoretical-practical teaching and training model in Orthopedics and Traumatology residency programs in Bahia, Brazil; to determine whether the program meets educational expectations; and to suggest improvements.</p><p><strong>Methods: </strong>In this multicenter, cross-sectional observational study, a structured questionnaire was administered to 106 current and former orthopedic residents. It addressed the teaching model, workload, scientific training, and interpersonal relationships.</p><p><strong>Results: </strong>Of 106 respondents, 22 were excluded for incomplete responses, leaving 84. Overall, 77 (91.7%) recognized a need to improve residency training, yet 66 (78.6%) felt adequately prepared for professional practice on completion. Proposed improvements included expanding theoretical activities and lectures (36; 42.9%), strengthening practical training (40; 47.6%), and improving journal club article discussion sessions (48; 57.1%).</p><p><strong>Conclusion: </strong>Orthopedics and Traumatology residency programs in Bahia are generally perceived to meet residents' theoretical and practical learning needs. Enhancing scientific output and interpersonal development may further improve training outcomes.</p>","PeriodicalId":47359,"journal":{"name":"Einstein-Sao Paulo","volume":"24 ","pages":"eAO2040"},"PeriodicalIF":1.1,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246826","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":"Pan-hypoileism: an endocrine disease.","authors":"Sérgio Santoro","doi":"10.31744/einstein_journal/2026RW2548","DOIUrl":"10.31744/einstein_journal/2026RW2548","url":null,"abstract":"<p><p>Over the past four decades, the gastrointestinal tract has been increasingly recognized as a major endocrine organ. Each of its segments plays a distinct role in digestion, absorption, inter-organ signaling, and metabolic regulation, and each category of food requires a specific physiological response. Consequently, carnivores, herbivores, and omnivores have adapted their digestive systems to meet the demands of their typical diets. Signals arising from the digestive tract influence nearly all other organs and their metabolic activities. Gluconeogenesis, insulin resistance, energy expenditure, the hunger-satiety cycle, glucose effectiveness, lipid clearance, and gastric emptying are examples of metabolic processes profoundly regulated by the gut. Emerging evidence now suggests that the distal part of the human small intestine, the ileum, is progressively failing to perform its full range of functions, including its endocrine roles, in a substantial proportion of the population. This phenomenon may constitute a growing pandemic. The term pan-hypoileism has not previously been used. In this review, we explore why this term deserves recognition as an endocrine disease. Clarifying this condition may be important for both patients and physicians.</p>","PeriodicalId":47359,"journal":{"name":"Einstein-Sao Paulo","volume":"24 ","pages":"eRW2548"},"PeriodicalIF":1.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138733","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":"The utility of animal models in hiPSC-based studies of autism spectrum disorder: a systematic review.","authors":"Bruno Yukio Yokota-Moreno, André Luiz Teles E Silva, Isabella de Sousa Nóbrega, Lucas Barbosa Rossetti, Paulo César Maiorka, Andréa Laurato Sertié, Claudia Madalena Cabrera Mori","doi":"10.31744/einstein_journal/2026RW1868","DOIUrl":"10.31744/einstein_journal/2026RW1868","url":null,"abstract":"<p><strong>Introduction: </strong>Autism spectrum disorder is a highly prevalent and heritable neurodevelopmental condition. To investigate its pathogenesis, genetic and non-genetic animal models have been developed. However, no animal model can fully capture the human-specific characteristics and genetic complexity of autism spectrum disorder. In this context, human induced pluripotent stem cell (hiPSC) derived models have emerged as powerful tools in autism spectrum disorder research, offering the potential to reduce or replace animal experiments. Despite this potential, many hiPSC-based studies still incorporate animal use.</p><p><strong>Objective: </strong>To analyze the use of animals in hiPSC-based studies of autism spectrum disorder, with the aim of assessing the necessity of their inclusion and their contribution to our understanding of disease mechanisms.</p><p><strong>Methods: </strong>Following the PRISMA guidelines, we searched PubMed, Scopus, and Web of Science for articles published between 2009 and 2024 using the search terms \"autism\", \"ASD\", and \"autism spectrum disorder\" combined with \"iPSC\", \"induced pluripotent stem cells and \"organoid*\".</p><p><strong>Results: </strong>A total of 207 studies using hiPSCs to investigate Autism spectrum disorder were identified. Of these, 79 studies (38.16%) also involved animals or animal-derived cells. While nearly half of these studies used autism spectrum disorder animal models to explore neurobiological mechanisms of the disorder, the remaining studies employed animals for purposes not directly related to understanding autism spectrum disorder pathophysiology. These included teratoma formation assays to validate hiPSC pluripotency and the extraction of primary astrocytes for co-culture with hiPSC-derived neurons, an approach that may introduce confounding variables.</p><p><strong>Conclusion: </strong>Our review highlights the frequent and, in some cases, unnecessary use of animals in hiPSC-based studies of autism spectrum disorder.</p>","PeriodicalId":47359,"journal":{"name":"Einstein-Sao Paulo","volume":"24 ","pages":"eRW1868"},"PeriodicalIF":1.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138670","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":"Impact of social isolation on older outpatients during the COVID-19 pandemic.","authors":"Leonardo Trovo Zilotti, Alexandre Elias Romanos, Marcelo Kenzo Naya Takahashi, Alexandre Leopold Busse, Wilson Jacob Filho","doi":"10.31744/einstein_journal/2026AO1970","DOIUrl":"10.31744/einstein_journal/2026AO1970","url":null,"abstract":"<p><strong>Objective: </strong>We aimed to evaluate the impact of social isolation during the coronavirus disease 2019 (COVID-19) pandemic on the health of older outpatients in São Paulo, Brazil.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using the Multidimensional Assessment of the Elderly in Primary Care (AMPI-AB) tool to assess the functionality of individuals aged 60 years and older at three time-points: pre-pandemic (January 2019 - March 2020), during the pandemic (October 2021 - August 2022), and post-pandemic (September 2022 - July 2023). Data were extracted from medical records.</p><p><strong>Results: </strong>Among the 206 patients evaluated pre-pandemic, 94 were assessed during the pandemic, with 80 included in the final analysis. The mean age was 76.7 years; participants were predominantly female (66%). The number of healthy patients decreased from 52 pre-pandemic to 37 during the pandemic (18.8% reduction, p=0.001), while post-pandemic, the number of healthy patients increased to 45 (21.6% improvement from the pandemic period, p <0.001). The average AMPI-AB score rose from 4.8 points pre-pandemic to 6.2 points during the pandemic, then slightly decreased to 6.0 points post-pandemic, indicating a modest recovery in functionality.</p><p><strong>Conclusion: </strong>Our findings highlight significant consequences of social isolation on the health of the older population, which are characterized by a decline in well-being and functionality during the COVID-19 pandemic. However, a notable recovery was observed post-pandemic, emphasizing the need for targeted interventions to support vulnerable older individuals in future public health crises.</p>","PeriodicalId":47359,"journal":{"name":"Einstein-Sao Paulo","volume":"24 ","pages":"eAO1970"},"PeriodicalIF":1.1,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138726","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}