Neuroendocrinology最新文献

{"title":"Systemic Inflammation Mediates the Association between Thyroid Hormone Sensitivity and Depressive Symptoms in Euthyroid Population: Findings from NHANES.","authors":"Bindong Dai, Dandan Ma, Chunfeng Xiao, Yufei Wang, Tao Li, Jing Wei","doi":"10.1159/nen/advag004","DOIUrl":"https://doi.org/10.1159/nen/advag004","url":null,"abstract":"<p><strong>Aim: </strong>The relationship between thyroid function and depression remains unclear in euthyroid individuals. This study investigated the association between central thyroid hormone sensitivity (CTHS) and depression, and explored whether systemic inflammation mediated this relationship.</p><p><strong>Methods: </strong>This cross-sectional analysis included 6,728 adults from National Health and Nutrition Examination Survey 2007-2012. Depression was defined as Patient Health Questionnaire score ≥10. CTHS was assessed using four indices: thyroid-stimulating hormone index (TSHI), thyrotropin thyroxine resistance index (TT4RI), thyroid feedback quantile-based index (TFQI), and parametric TFQI (PTFQI). Multivariable logistic regression, generalized additive models, and mediation analysis were performed.</p><p><strong>Results: </strong>Participants with depression exhibited significantly lower CTHS across all four indices (all P < 0.05). Generalized additive models revealed non-linear associations between CTHS and depression. In quartile-based analyses, the strongest inverse associations were observed at the 3rd quartile for TSHI (adjusted OR 0.648, 95%CI 0.497-0.845), TFQI (adjusted OR 0.646, 95%CI 0.494-0.844), and PTFQI (adjusted OR 0.707, 95%CI 0.543-0.920), while the 2nd quartile of TT4RI showed the strongest association (adjusted OR 0.623, 95%CI 0.480-0.809). CTHS was most consistently associated with anhedonia among depressive symptoms. Mediation analysis revealed that C-reactive protein (CRP) partially mediated the relationship between PTFQI and depression (proportion mediated: 6.3%, P = 0.004).</p><p><strong>Conclusions: </strong>CTHS is non-linearly associated with depression in euthyroid adults, with CRP partially mediating this relationship. These findings highlight the potential role of neuroendocrine-immune interactions in depression and suggest that the indices of CTHS may capture clinically relevant variations missed by conventional thyroid function tests.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1"},"PeriodicalIF":2.4,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropeptides in Immunometabolism and Neuroinflammation: Insights from Traditional Chinese Medicine.","authors":"Chung-Hsin Wu, Chi-Feng Cheng, Thi Kim Ngan Nguyen, Li-Yu Su, Ming-Chung Lee, Wu-Chang Chuang","doi":"10.1159/nen/advag008","DOIUrl":"https://doi.org/10.1159/nen/advag008","url":null,"abstract":"<p><p>Neuropeptides are small bioactive peptides secreted by neurons and immune cells that serve as critical messengers in both central and peripheral systems. Recent studies have identified key neuropeptides-such as Substance P (SP), Vasoactive Intestinal Peptide (VIP), Neuropeptide Y (NPY), and Calcitonin Gene-Related Peptide (CGRP)-as pivotal regulators of immunometabolism and neuroinflammation. These peptides influence macrophage polarization, T cell differentiation, cytokine production, and neuroimmune crosstalk, linking chronic inflammation to conditions such as obesity, diabetes, autoimmunity, and neurodegeneration. This review synthesizes emerging evidence on Traditional Chinese Medicine (TCM) interventions-including herbal formulas, single herbs, bioactive compounds, and acupuncture-that modulate neuropeptide signaling via NF-κB, MAPK, and Nrf2 pathways. These mechanisms contribute to analgesia, emotional stabilization, metabolic regulation, and neuroprotection. The article further presents a modular framework connecting representative Chinese medicinal substances to specific neuropeptides and physiological functions, offering a translational foundation for neuropeptide-targeted therapies and integrative precision health strategies.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1"},"PeriodicalIF":2.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.1159/nen/advag006","DOIUrl":"10.1159/nen/advag006","url":null,"abstract":"<p><p>This is a correction to: Zhenwei Li, Yinzi Wu, Yike Gao, Ming Feng, Kan Deng, Bing Xing, Wei Lian, Yong Yao, Renzhi Wang, Jian Sun, Xinjie Bao; Pathological Classification and Clinical Characteristics of Growth Hormone-Secreting PitNETs. [Neuroendocrinology. 2026; https://doi.org/10.1159/000552989].In the originally published version of this article, Yike Gao was inadvertently omitted from the equal contribution footnote indicating co-first authorship.The author list note has been updated to include Yike Gao, and the equal contribution footnote has been amended to read:\"Zhenwei Li, Yinzi Wu, and Yike Gao contributed equally to this work and share joint first authorship.\"This error has been corrected online in the original article.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1"},"PeriodicalIF":2.4,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress on Mechanisms of Therapeutic Potential of Oxygen Delivery in Brain Disorders.","authors":"Junzhe Lv, Dazhi Guo","doi":"10.1159/nen/advag002","DOIUrl":"10.1159/nen/advag002","url":null,"abstract":"<p><strong>Background: </strong>Oxygen is both essential and potentially toxic to the brain, which consumes 20-25% of the body's resting metabolic rate despite comprising only 2% of the total body weight. The exquisite sensitivity of neural tissue to oxygen imbalance positions oxygen delivery as a critical determinant of both pathophysiology and therapeutic opportunity in brain disorders. This review synthesizes recent advances in our understanding of how oxygen sensing and delivery can be harnessed for therapeutic benefit across the spectrum of neurological conditions.</p><p><strong>Summary: </strong>We examine the molecular machinery of oxygen sensing, including the canonical prolyl hydroxylase domain/hypoxia-inducible factor/von Hippel-Lindau (PHD-HIF-pVHL) pathway as well as newly identified oxygen sensors such as Jumonji C domain histone demethylases and 2-aminoethanethiol (cysteamine) dioxygenase. We then explore how perturbations in oxygen delivery contribute to neurodegenerative diseases, stroke, traumatic brain injury, and neurodevelopmental disorders. Emerging therapeutic strategies are critically evaluated, including normobaric and hyperbaric oxygen therapy, therapeutic acute intermittent hypoxia, hypoxia preconditioning, and pharmacological targeting of oxygen-sensing pathways.</p><p><strong>Key messages: </strong>Moreover, the emerging concept of tissue-specific oxygen \"set points\" suggests that both hypoxia and hyperoxia can be pathological and that restoring optimal oxygenation, rather than simply maximizing oxygen delivery, may represent a more nuanced therapeutic approach. Notably, recent preclinical evidence demonstrating that hypoxia itself can reverse pathology in mitochondrial disease models challenges conventional assumptions and opens new avenues for treating brain disorders characterized by relative hyperoxia. Understanding the mechanisms by which oxygen delivery influences neuroinflammation, mitochondrial function, and neural plasticity will be essential for translating these insights into effective clinical interventions.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1"},"PeriodicalIF":2.4,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Should PTCH1 be Considered as a Kallman Syndrome Gene?","authors":"Agathe Hercent, Dimitri Tchernitchko","doi":"10.1159/nen/advag003","DOIUrl":"10.1159/nen/advag003","url":null,"abstract":"","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1"},"PeriodicalIF":2.4,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Thyroid-Brain Network: Exploring Inflammation, Immune Mechanisms, and Common Triggers in Thyroid-Related Neurological Dysfunction.","authors":"Mohammad Fahad Ullah","doi":"10.1159/nen/advag005","DOIUrl":"10.1159/nen/advag005","url":null,"abstract":"<p><strong>Background: </strong>Autoimmune thyroid diseases (AITD), encompassing Hashimoto's thyroiditis and Graves' disease, constitute the most prevalent endocrine disorders globally, affecting hundreds of millions of individuals. Despite their high prevalence, the neurological consequences of AITD remain substantially under-recognized in clinical practice. Historically, thyroid dysfunction has been viewed primarily within an endocrine premise, with neurological manifestations attributed solely to altered thyroid hormone levels. However, emerging evidence establishes inflammation and immunity as critical mediating links connecting peripheral thyroid dysfunction to central nervous system manifestations. This review engages current understanding of the mechanistic pathways through which AITD impacts brain function, emphasizing shared pathogenic origins and potential therapeutic implications.</p><p><strong>Summary: </strong>Thyroid hormones function as essential neuromodulators governing neurodevelopment, synaptic plasticity, and cognitive processing through both genomic and non-genomic mechanisms. The immunological perspective reveals that AITD propagates neuroinflammation via convergent pathways: molecular mimicry between thyroid and neural antigens, cytokine-mediated disruption of neurotransmitter metabolism, HMGB1-driven glial activation, and blood-brain barrier compromise facilitating immune cell infiltration. The thyroid-gut-microbiota axis emerges as a critical mediator wherein dysbiosis perpetuates both thyroid autoimmunity and neuroinflammation through impaired serotonin precursor availability and increased intestinal permeability. Mitochondrial dysfunction represents an energetic common denominator as thyroid hormone dysregulation impairs oxidative phosphorylation, producing region-specific cerebral metabolic disturbances. Simultaneous compromise of monoamine systems, cholinergic signaling abnormalities, and glutamate excitotoxicity creates a particularly toxic neurochemical state. Common triggers such as psychological stress, gut dysbiosis, and mitochondrial impairment may activate interconnected pathways that simultaneously compromise thyroid and brain function, revealing shared mechanistic origins.</p><p><strong>Key messages: </strong>Neurological consequences of AITD are prevalent but under-recognized. Inflammation and immunity serve as the mechanistic bridge. The thyroid-gut-microbiota axis is a critical therapeutic target. Mitochondrial dysfunction is the energetic common denominator. Untreated thyroid dysfunction creates a uniquely toxic neurochemical state. Shared triggers reveal fundamental mechanistic unity.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1"},"PeriodicalIF":2.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropsychological Outcomes and Behavioral Profiles in Children with Congenital Hypothyroidism: Impact of Timing of Thyroxine Initiation - A Cross-Sectional Study from Southern India.","authors":"Bhanu Teja Nalluri, Akhila Aitha, Neelaveni Kudugunti, Rakesh Kumar Sahay","doi":"10.1159/000553603","DOIUrl":"10.1159/000553603","url":null,"abstract":"<p><strong>Introduction: </strong>Congenital hypothyroidism (CH) is among the most common preventable causes of intellectual disability worldwide. In India, the absence of universal neonatal screening leads to delayed diagnosis and consequent neurocognitive morbidity. This study aimed to assess intelligence quotient (IQ) and behavioral profiles in children with CH in relation to the timing of levothyroxine (LT4) initiation and serum T4 levels at diagnosis.</p><p><strong>Methods: </strong>A cross-sectional study of 30 children with CH aged ≥3 years attending the endocrinology outpatient clinic at Osmania General Hospital, Hyderabad, was conducted between January 2017 and December 2018. IQ was assessed using the Binet Kamat Scale of Intelligence. Behavioral profiling was performed using the Achenbach Child Behavior Checklist (CBCL). Patients were stratified by age of LT4 initiation (<1 month, 1-6 months, >6 months). Analysis included ANOVA, box plot analysis, and one-sample t tests using SPSS version 20. Statistical significance was set at p < 0.05.</p><p><strong>Results: </strong>Of 30 patients (17 girls, 13 boys), 46.6% were initiated on LT4 after 6 months of age. Mean IQ was 79, 59.5, and 61.12 in those initiated on treatment within 1 month, 1-6 months, and after 6 months, respectively. Males had significantly lower serum T4 at diagnosis (0.45 ± 0.25 vs. 2.25 ± 1.48 μg/dL; p = 0.0002) and lower IQ (46.08 ± 22.59 vs. 76.6 ± 26.89; p = 0.003). Behavioral scores were within normal limits; however, withdrawn/anxiety/social/thought (WAST) composite score showed a trend toward elevation. Height SDS did not differ significantly between treatment initiation groups (p = 0.172).</p><p><strong>Conclusion: </strong>Children with CH in this Indian cohort demonstrated substantially lower IQ compared to internationally reported values, attributable to delayed diagnosis and suboptimal therapy adherence. Males exhibited more severe biochemical disease at diagnosis and greater neurocognitive impairment. Routine behavioral assessment and cognitive behavioral therapy should be incorporated into standard CH follow-up in resource-limited settings.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-9"},"PeriodicalIF":2.4,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contrast-Enhanced CT Features for Identifying Primary Origin and Differentiation Grade of Neuroendocrine Liver Metastases.","authors":"Yali Qu, Liuji Sheng, Haopeng Yu, Yanshu Wang, Hanyu Jiang, Jie Chen, Weixia Chen, Yun Qin","doi":"10.1159/000553586","DOIUrl":"10.1159/000553586","url":null,"abstract":"<p><strong>Introduction: </strong>Accurate identification of the primary tumor origin and differentiation grade of neuroendocrine liver metastases (NELMs) is critical for guiding treatment. This study aimed to evaluate contrast-enhanced CT (CECT) features of NELMs to differentiate pancreatic from non-pancreatic origins and neuroendocrine carcinoma (NEC) from neuroendocrine tumor (NET).</p><p><strong>Methods: </strong>This single-center retrospective study (July 2019 - December 2022) included consecutive patients with pathologically proven NELM who underwent CECT prior to surgery or biopsy. CT features, including tumor burden, basic characteristics, enhancement patterns, and malignancy-related features, were analyzed. The enhancement pattern was categorized as follows: (A) hypoenhancement (hypodensity in both the arterial phase and portal venous phase); (B) arterial phase hyperenhancement (APHE) and washout; (C) APHE and fade. Univariate and multivariate analyses were performed to identify CT features that differentiated pancreatic from non-pancreatic origins and NEC from NET.</p><p><strong>Results: </strong>Among 83 patients (median age, 52 years; 34 females), 49 patients had pancreatic NELM and 25 patients had NEC. In univariate analyses, hypoenhancement was significantly more frequent in non-pancreatic NELM compared to pancreatic NELM (32.4% vs. 8.2%; p = 0.01). This association was independent of age, sex, tumor size, and differentiation grade (p = 0.03). In addition, NEC was associated with ill-defined margins and targetoid appearances compared to NET, independent of age, sex, tumor size, and tumor origin (p = 0.045 and 0.003, respectively).</p><p><strong>Conclusion: </strong>The hypoenhancement of NELM facilitates identification of non-pancreatic primaries, and the presence of an ill-defined margin and a targetoid appearance are indicative of NEC. These features can aid in optimizing management strategies in patients with NELM.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-12"},"PeriodicalIF":2.4,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complex Interactions between Abnormal Thyroid Function and Neurodevelopmental Disorders: A Mendelian Randomization Study.","authors":"Xin Apos Ai Li, Zhe Li, Xiaoheng Chen, Han Bai, Ping Pan, Jingwei Zhou, Junhui Wang, Zhiguo Ding","doi":"10.1159/000553604","DOIUrl":"10.1159/000553604","url":null,"abstract":"<p><strong>Introduction: </strong>Neurodevelopmental disorders (NDDs), such as attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and tic disorders (TD), have been frequently investigated due to their profound impacts on social and emotional functions. In this regard, there is a new focus on the possible association between these disorders and thyroid dysfunction. The purpose of this study was to explore the relationship between NDDs and hyperthyroidism and hypothyroidism.</p><p><strong>Methods: </strong>In this study, we used MR analysis to explore the associations of ADHD, ASD, and TD with hyperthyroidism and hypothyroidism. MR analysis explores the associations between exposure and outcome using the Mendelian randomization framework and is based on extensive genomic datasets.</p><p><strong>Results: </strong>Our results suggested that hypothyroidism was associated with TD, while no individual genetic variant was associated with hypothyroidism, ADHD, or ASD. Additionally, we found no reliable evidence that ADHD, ASD, or TD were causally linked to hyperthyroidism. There was also no credible evidence that any individual genetic variant was associated with an increased risk of hyperthyroidism. Our findings remained robust in sensitivity analyses.</p><p><strong>Conclusion: </strong>Our study provides new insights into the relationship between NDDs and thyroid dysfunction. It suggests that there were potential risk factors and causal pathways and calls for early diagnosis, intervention, and integrated health care.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-13"},"PeriodicalIF":2.4,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reproduction under Siege: How Chronic Stress Hijacks the HPG Axis?","authors":"Duo Xu, Xu Zhao, Wanxin Chen, Yi Liu, Chaohu Wang","doi":"10.1159/000553429","DOIUrl":"10.1159/000553429","url":null,"abstract":"<p><strong>Background: </strong>Chronic stress profoundly disrupts homeostasis, with the hypothalamic-pituitary-gonadal (HPG) axis emerging as an active integrator rather than a passive target in stress pathophysiology.</p><p><strong>Summary: </strong>This review synthesizes evidence that chronic stress acts on the HPG axis at multiple levels: hypothalamic-pituitary-adrenal (HPA)-derived corticotropin-releasing hormone and glucocorticoids suppress the gonadotropin-releasing hormone (GnRH) pulse generator through kisspeptin/KNDy and gonadotropin-inhibitory hormone pathways; sympathetic overdrive impairs gonadal steroidogenesis while parasympathetic tone declines; and metabolic-inflammatory crosstalk amplifies suppression. The resulting decline in sex steroids - estradiol, progesterone, and testosterone - creates sex-specific vicious cycles that further dysregulate stress and immune circuits, contributing to affective, reproductive, and neurodegenerative disorders.</p><p><strong>Key messages: </strong>The HPG axis serves as a critical hub integrating stress signals, and its suppression is an active, regulated process with distinct sex differences. Hormone-based interventions, including estrogen, neurosteroid analogs, and testosterone, show therapeutic promise for stress-related conditions, and future research should focus on the neural circuits and molecular switches that govern HPA-HPG crosstalk to enable personalized, neuroendocrine-informed therapies.</p>","PeriodicalId":19117,"journal":{"name":"Neuroendocrinology","volume":" ","pages":"1-21"},"PeriodicalIF":2.4,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}