Autoantibodies, Antigen-Autoantibody Complexes and Antigens Complement CA125 for Early Detection of Ovarian Cancer

BACKGROUND: Multiple antigens, autoantibodies (AAb), and antigen-autoantibody (Ag-AAb) complexes were compared for their ability to complement CA125 for early detection of ovarian cancer. METHODS: Twenty six biomarkers were measured in a single panel of sera from women with early stage (I-II) ovarian cancers (n = 64), late stage (III-IV) ovarian cancers (186), benign pelvic masses (200) and from healthy controls (502), and then split randomly (50:50) into a training set to identify the most promising classifier and a validation set to compare its performance to CA125 alone. RESULTS: Eight biomarkers detected ≥ 8% of early stage cases at 98% specificity. A four-biomarker panel including CA125, HE4, HE4 Ag-AAb and osteopontin detected 75% of early stage cancers in the validation set from among healthy controls compared to 62% with CA125 alone (p = 0.003) at 98% specificity. The same panel increased sensitivity for distinguishing early-stage ovarian cancers from benign pelvic masses by 25% (p = 0.0004) at 95% specificity. From 21 autoantibody candidates, 3 AAb (anti-p53, anti-CTAG1 and annt-Il-8) detected 22% of early stage ovarian cancers, potentially lengthening lead time prior to diagnosis. CONCLUSION: A four biomarker panel achieved greater sensitivity at the same specificity for early detection of ovarian cancer than CA125 alone

Exacerbated fires in Mediterranean Europe due to anthropogenic warming projected with non-stationary climate-fire models

The observed trend towards warmer and drier conditions in southern Europe is projected to continue in the next decades, possibly leading to increased risk of large fires. However, an assessment of climate change impacts on fires at and above the 1.5 °C Paris target is still missing. Here, we estimate future summer burned area in Mediterranean Europe under 1.5, 2, and 3 °C global warming scenarios, accounting for possible modifications of climate-fire relationships under changed climatic conditions owing to productivity alterations. We found that such modifications could be beneficial, roughly halving the fire-intensifying signals. In any case, the burned area is robustly projected to increase. The higher the warming level is, the larger is the increase of burned area, ranging from ~40% to ~100% across the scenarios. Our results indicate that significant benefits would be obtained if warming were limited to well below 2 °C

The R-based climate4R open framework for reproducible climate data access and post-processing

Climate-driven sectoral applications commonly require different types of climate data (e.g. observations, re-analysis, climate change projections) from different providers. Data access, harmonization and post-processing(e.g. bias correction) are time-consuming error-prone tasks requiring different specialized software tools at eachstage of the data workflow, thus hindering reproducibility. Here we introduce climate4R, an R-based climateservices oriented framework tailored to the needs of the vulnerability and impact assessment community thatintegrates in the same computing environment harmonized data access, post-processing, visualization and aprovenance metadata model for traceability and reproducibility of results. climate4R allows accessing localand remote (OPeNDAP) data sources, such as the Santander User Data Gateway (UDG), a THREDDS-basedservice including a wide catalogue of popular datasets (e.g. ERA-Interim, CORDEX, etc.). This provides a uniquecomprehensive open framework for end-to-end sectoral reproducible applications. All the packages, data anddocumentation for reproducing the experiments in this paper are available from http://www.meteo.unican.es/climate4R.This work has been funded by the Spanish R+D Program of theMinistry of Economy and Competitiveness, through grants MULTI-SDM(CGL2015-66583-R) and INSIGNIA (CGL2016-79210-R), co-funded byERDF/FEDER. We would like to thank the two anonymous reviewersfor their valuable suggestions and comments

Multiparameter single-cell proteomic technologies give new insights into the biology of ovarian tumors.

Acknowledgements: A.D-G. thanks the Fundacion Alfonso Martin Escudero for his postdoctoral fellowship. We thank Dr. Brooke Howitt for providing ovarian tissue. Figures 1, 3, and 4 were created using BioRender.Funder: BRCA FoundationFunder: V Foundation for Cancer Research; doi: http://dx.doi.org/10.13039/100001368Funder: Stanford Cancer Institute, Innovation Award 2019Funder: Stanford Cancer Institute, Innovation Award 2021Funder: CRUK CC (crukcambridgecentre.org.uk)Funder: Fundacion Alfonso Martin EscuderoHigh-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy. Its diagnosis at advanced stage compounded with its excessive genomic and cellular heterogeneity make curative treatment challenging. Two critical therapeutic challenges to overcome are carboplatin resistance and lack of response to immunotherapy. Carboplatin resistance results from diverse cell autonomous mechanisms which operate in different combinations within and across tumors. The lack of response to immunotherapy is highly likely to be related to an immunosuppressive HGSOC tumor microenvironment which overrides any clinical benefit. Results from a number of studies, mainly using transcriptomics, indicate that the immune tumor microenvironment (iTME) plays a role in carboplatin response. However, in patients receiving treatment, the exact mechanistic details are unclear. During the past decade, multiplex single-cell proteomic technologies have come to the forefront of biomedical research. Mass cytometry or cytometry by time-of-flight, measures up to 60 parameters in single cells that are in suspension. Multiplex cellular imaging technologies allow simultaneous measurement of up to 60 proteins in single cells with spatial resolution and interrogation of cell-cell interactions. This review suggests that functional interplay between cell autonomous responses to carboplatin and the HGSOC immune tumor microenvironment could be clarified through the application of multiplex single-cell proteomic technologies. We conclude that for better clinical care, multiplex single-cell proteomic technologies could be an integral component of multimodal biomarker development that also includes genomics and radiomics. Collection of matched samples from patients before and on treatment will be critical to the success of these efforts

Normal Risk Ovarian Screening Study: 21-Year Update

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. PURPOSE The Normal Risk Ovarian Screening Study (NROSS) tested a two-stage screening strategy in postmenopausal women at conventional hereditary risk where significantly rising cancer antigen (CA)-125 prompted transvaginal sonography (TVS) and abnormal TVS prompted surgery to detect ovarian cancer. METHODS A total of 7,856 healthy postmenopausal women were screened annually for a total of 50,596 woman-years in a single-arm study (ClinicalTrials.gov identifier: NCT00539162 ). Serum CA125 was analyzed with the Risk of Ovarian Cancer Algorithm (ROCA) each year. If risk was unchanged and <1:2,000, women returned in a year. If risk increased above 1:500, TVS was undertaken immediately, and if risk was intermediate, CA125 was repeated in 3 months with a further increase in risk above 1:500 prompting referral for TVS. An average of 2% of participants were referred to TVS annually. RESULTS Thirty-four patients were referred for operations detecting 15 ovarian cancers and two borderline tumors with 12 in early stage (I-II). In addition, seven endometrial cancers were detected with six in stage I. As four ovarian cancers and two borderline tumors were diagnosed with a normal ROCA, the sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23), and 70% of ROCA-detected cases (12 of 17) were in stage I-II. NROSS screening reduced late-stage (III-IV) disease by 34% compared with UKCTOCS controls and by 30% compared with US SEER values. The positive predictive value (PPV) was 50% (17 of 34) for detecting ovarian cancer and 74% (25 of 34) for any cancer, far exceeding the minimum acceptable study end point of 10% PPV. CONCLUSION While the NROSS trial was not powered to detect reduced mortality, the high specificity, PPV, and marked stage shift support further development of this strategy. 21-year ovarian cancer screening trial had 74% sensitivity with 70% of detected cases in early stag

Present and future climate conditions for winegrowing in Spain

This study deals with the question of how winegrowing in Spain may be altered by anthropogenic climate change. The present state and expected future development of three bioclimatic indices relevant for winegrowing were assessed by observation, and four regional climate models from the EU-ENSEMBLES project were investigated. When comparing the 2061–2090 scenario period to the 1961–1990 reference period, the models unanimously indicate a significant increase in the mean of the two considered thermal indices over the entire study region. However, for the index based on temperature and precipitation, the models are heavily biased when verified against observations and generally disagree on the size of the projected future change. For this index, unanimous model agreement was only found for northwestern Spain where all models indicated a significant decrease in the mean. From these results, regional climate change is expected to negatively affect the quality of wine in the growing regions of central and southern Spain, and the Ebro valley, whereas positive effects should be expected in the northwest. No significant changes in the risk of mildew infestation are to be expected except for the northwest, where this risk is projected to decrease.This work was supported by the Xunta de Galicia under Research Grant No. 10PXIB383169PR and co-financing by European Regional Development Fund (FEDER). Alexandre M. Ramos was supported by the Portuguese Foundation for Science and Technology (FCT) through Grant FCT/DFRH/SFRH/BPD/84328/2012. S. Brands would like to thank the Consejo Superior de Investigaciones Científicas JAE-PREDOC programme for financial support.Peer Reviewe