Evolution, Medicine, and Public Health最新文献

{"title":"Multicellular cooperation and the hallmarks of cancer: A new foundation.","authors":"Carlo C Maley, Amy M Boddy, Aurora M Nedelcu, Athena Aktipis","doi":"10.1093/emph/eoaf026","DOIUrl":"10.1093/emph/eoaf026","url":null,"abstract":"<p><p>Multicellularity evolved independently several times across the tree of life. In all cases, these events were dependent on various types of cellular cooperation. We previously identified five universal foundations of cellular cooperation that are required in all complex multicellular lineages to allow the collection of cells to function and reproduce as a whole (i.e. a multicellular individual). These include: proliferation inhibition, controlled cell death, resource allocation, division of labor, and maintenance of the extracellular environment. We propose that there is a sixth universal foundation of multicellularity that breaks down in cancer: proximity maintenance. By staying in close proximity, cells can more easily provide benefits for one another, communicate, coordinate their behavior, and evolve increased size and complexity. Here, we revisit and further develop the five original foundations of multicellular cooperation in the context of the evolution of multicellularity from unicellular ancestors and their implications for cancer progression. In our previous work, we suggested that the breakdown of all these cooperative behaviors is reflected in the universal hallmarks of cancer. Similarly, the breakdown of proximity maintenance maps to another hallmark of cancer-activating invasion and metastasis.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"13 1","pages":"374-380"},"PeriodicalIF":2.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proximate and ultimate causes of pregnancy sickness.","authors":"Daniel J Stadtmauer","doi":"10.1093/emph/eoaf025","DOIUrl":"10.1093/emph/eoaf025","url":null,"abstract":"<p><p>Evolutionary biologists have long been fascinated by pregnancy sickness, the heritable, stereotyped syndrome in early pregnancy that usually consists of benign nausea and vomiting and in around 1% of cases progresses to the pathological extreme hyperemesis gravidarum. Identification of the placental hormone GDF15 as a principal causal factor justifies reassessment of its proximate and ultimate causes. This Review synthesizes knowledge of pregnancy sickness at the four levels of analysis of classical ethology-mechanism, development, phylogeny, and adaptive function. Emerging insight into GDF15's role in innate sickness behaviors suggests pregnancy sickness is a heightened state of pre-existing behavioral defenses triggered by placental production of an emetogenic hormone which may hold a different primary function. Comparison of transcriptomes reveals that placental <i>GDF15</i> production rose 100- to 1000-fold to human-like levels in catarrhine primates, and is low or absent in New World monkeys, rodents, and other mammals, with the possible exception of elephants. This suggests that pregnancy sickness is phylogenetically restricted yet not human-specific, and associates with innovations in syncytiotrophoblast biology rather than diet. I re-evaluate leading adaptive hypotheses (prophylactic, metabolic rewiring, placental growth, and anti-rejection) and argue that the key to adjudicating among them hinges on whether GDF15 acts locally through non-canonical receptors and whether additional factors distinguish pregnancy sickness from sickness behavior. Finally, I evaluate explanations for the persistent risk of hyperemesis gravidarum in modern humans, including trade-offs, mismatch, and conflict. With recent advances, pregnancy sickness is not just a curiosity of human evolution, but a compelling opportunity to investigate the mechanistic bases of complex adaptive behaviors.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"13 1","pages":"307-330"},"PeriodicalIF":2.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12542990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal-fetal conflict and the timing of birth.","authors":"Andrew I Furness","doi":"10.1093/emph/eoaf023","DOIUrl":"10.1093/emph/eoaf023","url":null,"abstract":"<p><p>Evolutionary theory predicts mammalian offspring will favor greater investment than parents are willing to provide, leading to conflict over resource transfer. This theory of parent-offspring conflict has been applied to resource transfer across the placenta. Birthweight and gestation length are functionally linked, suggesting that the timing of birth might also represent a focal point of maternal-fetal conflict. This hypothesis relies on two assumptions: mother and offspring have different fitness optima and both parties exert partial control over the timing of birth. It is argued, and evidence is reviewed, that suggests offspring benefit from slightly longer gestation than the maternal optimum, and that fetal and maternal genes both influence gestation length. We might therefore expect an evolutionary history of maternal-fetal conflict over the control of parturition. Evidence consistent with this hypothesis includes the effect of imprinted genes, as revealed through imprinting disorders, on gestation length; the wide variability in parturition mechanism(s) among mammalian species; and the complex physiology of human parturition including initiation by multiple different pathways with inputs from both mother and offspring. One potential consequence of a history of maternal-fetal conflict over control of the mechanisms of parturition is that the timing of birth may be subject to a greater degree of dysregulation than simpler physiological systems subject to single-party control.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"13 1","pages":"292-306"},"PeriodicalIF":2.1,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12542988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145354179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging selection for function in tumor evolution: System-level cancer therapies.","authors":"Frédéric Thomas, Jean-Pascal Capp, Antoine M Dujon, Andriy Marusyk, Klara Asselin, Mario Campone, Pascal Pujol, Catherine Alix-Panabières, Benjamin Roche, Beata Ujvari, Robert Gatenby, Aurora M Nedelcu","doi":"10.1093/emph/eoaf022","DOIUrl":"10.1093/emph/eoaf022","url":null,"abstract":"<p><p>Current cancer therapies often fail due to tumor heterogeneity and rapid resistance evolution. A new evolutionary framework, 'selection for function,' proposes that tumor progression is driven by group phenotypic composition (GPC) and its interaction with the microenvironment, not by individual cell traits. This perspective opens new therapeutic avenues: targeting the tumor's functional networks rather than individual cells. Real-time tracking of GPC changes could inform adaptive treatments, delaying progression and resistance. By integrating evolutionary and ecological principles with conventional therapies, this strategy aims to transform cancer from a fatal to a manageable chronic disease. Crucially, it does not necessarily require new drugs but offers a way to repurpose existing therapies to impair a tumor's evolutionary potential. By steering tumor evolution toward less aggressive states, this approach could improve prognosis and long-term patient survival compared to current methods. We argue that leveraging GPC dynamics represents a critical, yet underexplored, opportunity in oncology.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"13 1","pages":"248-268"},"PeriodicalIF":2.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual targeting of conserved cell cycle and transcription programs in advanced colorectal cancer by fadraciclib.","authors":"Mohammad Zokaasadi, Wylie K Watlington, Divya L Dayanidhi, John B Mantyh, Gabrielle Rupprecht, Shannon McCall, David G Blake, Jason A Somarelli, David S Hsu","doi":"10.1093/emph/eoaf021","DOIUrl":"10.1093/emph/eoaf021","url":null,"abstract":"<p><strong>Background and objectives: </strong>Control of cell division is tightly regulated in eukaryotic cells, and dysfunction in cell cycle checkpoints is a key hallmark of malignant transformation that promotes a fitness advantage over non-cancer cells. One of the most critical mechanisms of cell cycle regulation is via the cyclin-dependent kinases (CDKs), which connect resource availability sensing and growth signaling with cell division and transcription elongation processes. Novel combination therapy approaches to co-target cell cycle and transcriptional CDKs may improve cancer-specific targeting of CDK dysfunction. In the current study, we assessed the effectiveness of fadraciclib, a new CDK2/9 inhibitor, for the treatment of advanced colorectal cancer (CRC).</p><p><strong>Methodology: </strong>A panel of eighteen CRC patient-derived organoids (PDOs) was used to assess the efficacy of fadraciclib. Efficacy was further validated in patient-derived xenografts (PDXs). CDK2/9 target inhibition, cell cycle arrest, and cell killing mechanisms were investigated using western blotting, flow cytometry, and immunofluorescence staining, respectively.</p><p><strong>Results: </strong>CRC PDOs exhibited greater sensitivity to fadraciclib compared to chemotherapy and palbociclib. This efficacy was validated <i>in vivo</i> using three matched PDXs, showing significant tumor growth inhibition with fadraciclib compared to vehicle (<i>P</i> < .05) and no serious adverse effects. Fadraciclib induced G2/M cell cycle arrest, leading to multipolar mitosis and anaphase catastrophe.</p><p><strong>Conclusions and implications: </strong>Our results using patient-derived models suggest that fadraciclib is a promising therapy for advanced CRC by inhibiting CDKs 2 and 9, which affects critical pathways in cell cycle regulation and transcription.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"13 1","pages":"281-290"},"PeriodicalIF":2.1,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolutionary medicine of emunctory functions of the kidney: an empirical review.","authors":"Noel T Boaz, Robert L Chevalier","doi":"10.1093/emph/eoaf019","DOIUrl":"10.1093/emph/eoaf019","url":null,"abstract":"<p><p>Primitive emunctory functions to expel harmful substances from cells and the interstitial space of multicellular organisms evolved over the past billion and a half years into the complex physiology of the metanephric kidney. Integrative biology allows empirical testing of hypotheses of the origins of renal structures from homologous single-celled precursors. Emunctory cell complexes called nephridia evolved in metazoan (cnidarian) ancestors 750 million years ago (mya). The pronephric kidney was a metameric structure that evolved some 700 mya in early bilaterians to excrete waste products through nephridial slits in the body wall from head to tail. The mesonephric kidney evolved 635 mya when pharyngeal slits differentiated into filter-feeding gills and a heart-kidney evolved in later bilaterians. The mesonephric filtering glomeruli lost their external exits through the body wall and now drained through an internal mesonephric duct into the coelom. When chordates moved into fresh water from the sea 588 mya the high-pressure glomerulus evolved in the mesonephros, increasing water excretion. Tetrapods moved onto land losing the buoyancy of water. Blood pressure and glomerular filtration rose and the metanephric kidney evolved in amniotes. The high pressure-flow glomerulus predisposes podocytes to injury and detachment leading to sclerosis, whereas the high mitochondrial activity of the tubule contributes to susceptibility to ischemia, hypoxia, and oxidative injury. The kidney evolved a counter-current mechanism and urea cycle to optimize water retention. Perturbations in the complex development of the metanephric kidney, which parallels its phylogeny, explain many renal pathologies, which are traceable to these adaptations.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"13 1","pages":"229-247"},"PeriodicalIF":2.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Higher blood lipid levels after the transition to menopause in two forager-horticulturalist populations.","authors":"M J Getz, J E Aronoff, C L Jenkins, S Ghafoor, J Vazquez, N T Appel, M Gatz, D K Cummings, P L Hooper, B Beheim, K H Buetow, C E Finch, G S Thomas, J Stieglitz, M Gurven, H Kaplan, B C Trumble","doi":"10.1093/emph/eoaf020","DOIUrl":"10.1093/emph/eoaf020","url":null,"abstract":"<p><strong>Background: </strong>Reproduction affects health and longevity among females across the life course. While significant focus has been devoted to the role of menarche, menopause remains understudied. Most menopause research is conducted in industrialized populations, where the risk of cardiovascular diseases increases progressively during the menopausal transition.</p><p><strong>Methodology: </strong>We worked with the Tsimane, Indigenous Bolivian forager-farmers with physically active lifestyles, and the Moseten, genetically and culturally related horticulturalists experiencing greater market integration. We assessed relationships between menopause status and lipid biomarkers (HDL, LDL, non-HDL, total cholesterol, triglycerides, and apolipoprotein-B). Using linear mixed-effects models, in an all-age sample of n = 1,121 women (15-92 years) we found positive associations between menopausal status and most lipid levels.</p><p><strong>Results: </strong>Menopause was associated with 5.0% higher total cholesterol (b = 7.038 mg/dL, <i>P</i> = .001), 9.4% higher LDL (b = 5.147 mg/dL, <i>P</i> = .017), 5.9% higher non-HDL cholesterol (b = 8.071 mg/dL, <i>P</i> < .001), 11.3% higher triglycerides (b = 19.119 mg/dL, <i>P</i> < .001), and 1.5% higher apolipoprotein-B (b = 0.248 mg/dL, <i>P</i> = .001), controlling for age, body mass index (BMI), year of data collection, and population. In contrast, HDL did not vary with menopause status.</p><p><strong>Conclusions: </strong>After controlling for age, BMI, and year of data collection, post-menopausal lipid profiles among the Tsimane across six biomarkers are 2-7 times lower than those documented in U.S./U.K. populations. These results support existing literature that documents distinct shifts in lipid profiles during and after the menopause transition in industrialized populations. Further, our results suggest lipids increase post-menopause similarly to those of industrialized populations, despite the differential diet, physical activity, fertility, and hormone exposure in industrialized environments.</p><p><strong>Lay summary: </strong>Menopause is a relatively rare life history trait primarily studied in industrial populations. We examined relationships between menopause and cardiovascular disease risk biomarkers in two forager-horticulturalist populations. We found positive associations between menopause and total cholesterol, HDL, LDL, non-HDL, triglycerides, and apolipoprotein-B, suggesting lipid increases post-menopause are a human universal.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"13 1","pages":"201-214"},"PeriodicalIF":2.1,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409787/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High water turnover, hydration status, and heat stress among Daasanach pastoralists in a hot, semi-arid climate.","authors":"Amanda McGrosky, Leslie Ford, Elena Hinz, Srishti Sadhir, Faith Wambua, David R Braun, Matthew Douglass, Emmanuel Ndiema, Rosemary Nzunza, Asher Y Rosinger, Herman Pontzer","doi":"10.1093/emph/eoaf017","DOIUrl":"10.1093/emph/eoaf017","url":null,"abstract":"<p><strong>Background and objectives: </strong>Water is essential for proper physiological function. As temperatures increase, populations may struggle to meet water needs despite adaptations or acclimation; chronic dehydration can cause kidney damage. We evaluate how daily water requirements are associated with ambient temperature (ambT), wet bulb globe temperature (WBGT), urine specific gravity (USG; marker of hydration status), and albumin:creatinine ratio (ACR; kidney function biomarker) among Daasanach pastoralists living in a hot, dry northern Kenyan climate.</p><p><strong>Methodology: </strong>Water turnover (WT), USG, and ACR were measured using deuterium depletion (WT), refractometry (USG), and urine dipstick (ACR) for 76 participants aged 5-68 years in June 2022-23. Relationships between WT, ambT, WBGT, USG, and ACR were evaluated using linear and generalized linear models.</p><p><strong>Results: </strong>Adult WT was higher than mean values worldwide, peaking around 7 l/day. Water demands increase from childhood through middle age before falling in later life. Adult WT was not correlated with ambT or WBGT. About 2/11 children's and 7/36 adults' USG indicated dehydration; USG was not correlated with child WT but was negatively correlated with adult WT when accounting for body size. WT was lower among adults with high (≥30 mg/g) ACR; high ACR was associated with higher USG.</p><p><strong>Conclusions and implications: </strong>High Daasanach WT is likely driven by hot, semi-arid conditions, and lifestyle, rather than by compromised kidney function. Most participants were well-hydrated. Despite nonsignificant correlations between temperature and adult WT, high WT highlights the physiological demands of hot, dry climates. As climate change increases the global population exposed to hotter temperatures, global water needs will likely increase.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"13 1","pages":"215-228"},"PeriodicalIF":2.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"'Everyone in my family has C-sections': increased likelihood of caesarean birth in family lineages in the United States.","authors":"Kathleen M Hanlon-Lundberg","doi":"10.1093/emph/eoaf018","DOIUrl":"10.1093/emph/eoaf018","url":null,"abstract":"<p><p>Caesarean birth has multiple, interrelated, and often mutually reinforcing bio-social etiologies. Evolutionary consequences of caesarean are uncertain. The goal of this study is to determine if caesarean births are more likely within family lineages by connecting and comparing lifetime birth experience (caesarean, vaginal) of individual women and generations of their families. A secondary goal is to identify potential parity differences between birth modes. Qualitative and quantitative methods were used to evaluate women's birth narratives of their own births and births to their maternal relatives: grandmothers, mothers, sisters, daughters. Participant data was analysed by birth year cohort and by familial generation (Grandmother, Mother, Index, and Daughter). 107 women participated in the study. Parous daughters of women who experienced any caesarean were more likely to experience caesarean than were daughters of women experiencing all vaginal birth (<i>P</i> = .0002; relative risk 2.1 [1.53-2.88]). Prevalence of any caesarean per mother is higher than the per-birth caesarean rate (44/107, 41.12% versus 71/229, 31.00%; <i>P</i> = .03). Parity was higher for women experiencing all vaginal births than all caesarean (2.14 versus 1.79; <i>P</i> = .03), yet highest for those experiencing any caesarean (2.75; <i>P</i> = .01). Caesarean for any indication is more common among daughters of mothers who themselves experienced any caesarean than those who experienced all vaginal births. Individual lifetime caesarean experience is more prevalent than commonly construed based on caesarean per live birth rate. Clustering of cesarean within families suggests that operative birth is altering our bio-social selves in potentially heritable ways.</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"13 1","pages":"188-200"},"PeriodicalIF":2.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction and replacement of: Regulating community well-being through traditional mourning rituals: Insights from the Luhya People of Kenya.","authors":"","doi":"10.1093/emph/eoaf013","DOIUrl":"https://doi.org/10.1093/emph/eoaf013","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.1093/emph/eoaf001.].</p>","PeriodicalId":12156,"journal":{"name":"Evolution, Medicine, and Public Health","volume":"13 1","pages":"151"},"PeriodicalIF":2.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}