tbuckley/cabot-search huggingface dataset:
The buscopan study; A randomized controlled non-inferiority trial of a continuous butylscopolamine infusion versus placebo in patients with a renal colic insufficiently responding to oral non-steroidal anti-inflammatory drugs
Authors: S. Weltings, K.T. Buddingh, D. Van Diepen, R.C.M. Pelger, H. Putter, M. Rad, B.M.A. Schout, H. Roshani
Journal: European Urology (2021)
Abstract 169: Ephesus - A curated content knowledgebase for the clinical interpretation of genomic variants
Authors: Jian Li, Lili Niu, Fnu Kinshuk, Bernie Chu, John Mu, Nicole Greene, Vivian Douglas, Caitlin Schartner, Kalpana Kannan, Priyanka Rao, Shuba Krishna
Journal: Cancer Research (2021)

Abstract Accurate and comprehensive interpretation of genomic variants has become a bottleneck in clinical sequencing applications due to the implementation of precision oncology and the growth of biomedical findings. We therefore were motivated to build Ephesus, a framework enabling curation of predictive, prognostic and diagnostic evidence for clinical biomarkers in somatic cancers. Currently Ephesus is the primary content source for Roche NAVIFY Mutation Profiler (RUO). The Ephesus' data model ensures adherence to best practices in the field of clinical genomic content curation. Somatic variant classification followed the AMP guidelines. Approvals and recommendations from regulatory agencies and clinical practice guidelines were applied on a regional basis. The data model is mapped to a set of relational tables. Strategies such as data normalization according to standard ontologies, a submit-review-approval workflow with change logs, and biologically relevant data constraints are adopted to enforce data integrity. Ephesus is deployed as a web application whose UI allows users to conduct edits, sorting, filtering, and bulk operations on entities attributes. In order to minimize the manual effort and maximize content coverage, a number of inference rules are applied before the content is ingested into NMP. Currently Ephesus is developed to guide data collection, browsing and summarizing related to primary entities such as Biomarkers, Evidence items, Genes, Variants, Variant groups, and Drugs. The content from 10/28/20 snapshot contains 233k biomarker profiles (including biomarker combinations), in the context of 17 major cancer types. To evaluate the clinical reporting value of the curated knowledge, ~60k clinical cancer patient samples from the AACR GENIE project were queried against Ephesus. Compared our results against those from 3 other major knowledgebases (snapshotted at the same time as Ephesus), we see the performance of Ephesus/NMP exceeds all these knowledgebases. Patients% with at least one interpretation (numbers in parenthesis include matching by inferences)KnowledgebaseVariantVariant &amp; diseaseTier I variant &amp; diseaseEphesus53 (91)40 (89)19 (25)CGI3573CIViC402215ClinVar452313 Citation Format: Jian Li, Lili Niu, Fnu Kinshuk, Bernie Chu, John Mu, Nicole Greene, Vivian Douglas, Caitlin Schartner, Kalpana Kannan, Priyanka Rao, Shuba Krishna. Ephesus - A curated content knowledgebase for the clinical interpretation of genomic variants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 169.
Abstract 1071: Studying the ability of retinoids to inhibit growth of CRC cells based on their retinoid pathway genotype
Authors: Victoria O. Hunsu, Caroline O. Facey, Lynn M. Opdenaker, Bruce M. Boman
Journal: Cancer Research (2021)

Abstract Colorectal cancer (CRC) tumorigenesis arises through acquisition of mutations in a colonic stem cell (SC) that transforms it into a cancer stem cell (CSC). There are no curative treatments for advanced CRC because CSCs appear to be resistant to chemotherapy and/or radiation. Because all-trans retinoic acid (ATRA) is a highly effective and often curative treatment for acute promyelocytic leukemia patients, we conjecture that retinoids may be an efficacious treatment for CRC. Retinoic acid (RA) is a metabolite of vitamin A which is known to induce differentiation of SCs and inhibit cell proliferation. Our goal is to discover how to therapeutically target human CRC CSCs using the differentiation-inducing effects of retinoid agents. Our previous study on the RA metabolizing enzyme aldehyde dehydrogenase (ALDH) shows that ALDH marks normal and malignant colonic SCs and that RA signaling mainly occurs through colonic ALDH+ SCs. Hypothesis: The ability of retinoid agents, ATRA, 9-cis retinoic acid, 13-cis retinoic acid and Liarozole, to induce differentiation of CSCs depends on the RA pathway genotype according to mutations in RA signaling components in CRC cells. Indeed, our bioinformatics analysis shows that many RA pathway genes are overexpressed and often mutated in CRC. We have also evaluated the ability of the different RA ligands to inhibit cell growth and induce differentiation using a panel of CRC cell lines that have specific RA signaling mutations. Further investigation of RA signaling mechanisms that regulate colon SCs and how dysregulation contributes to the SC overpopulation that drives CRC growth should provide insight into strategies for designing new SC-targeted therapies for CRC. Citation Format: Victoria O. Hunsu, Caroline O. Facey, Lynn M. Opdenaker, Bruce M. Boman. Studying the ability of retinoids to inhibit growth of CRC cells based on their retinoid pathway genotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1071.
Laparoscopic partial nephrectomy with Thulium Laser enucleation of the tumour: Perioperative and functional outcomes
Authors: M. Maltagliati, L. Berti, C. Buizza, U. Besana, A. Calori, L. Rivolta, C. Gastaldi, G. Autieri, M.C. Sighinolfi, S. Micali, B. Rocco, G. Bozzini
Journal: European Urology (2021)
Abstract 458: Characterization of ATRX polyclonal, application of immunohistochemical analysis on astrocytoma and glioblastoma
Authors: Jose Jonathan Diaz, Tatiana Scoggin, Jason Ramos
Journal: Cancer Research (2021)

Abstract Introduction: Alpha thalassemia/mental retardation syndrome X-linked (ATRX) plays a role in chromatin regulation and maintenance of telomeres. It regulates incorporation of histone H3.3 into telomeric chromatin. ATRX is also a major component of various essential cellular pathways such as DNA replication and repair, chromatin higher-order structure regulation, and gene transcriptional regulation. ATRX loss was observed in grades II/III astrocytomas, oligoastrocytomas, oligodendrogliomas, and glioblastomas. In grades II/III gliomas, most ATRX-loss cases had IDH1/2 mutations. Assessment of ATRX loss by IHC staining captures the majority of mutations, giving a reasonable sensitivity in neuropathology diagnostics. In this study, the specificity and sensitivity of ATRX were analyzed on multiple tissues focusing on Astrocytoma and Glioblastoma tissues. Materials and Methods: IHC staining has been performed by using formalin-fixed paraffin-embedded tissue with standard deparaffinization steps and a heat-induced retrieval method using a citrate buffer solution in a pressure cooker (Decloaking chamber). Antibody was incubated for 30 minutes, followed by HRP detection and DAB solution for visualization. Slides were stained using semi-automated staining system (intelliPATH). ATRX polyclonal antibody [Biocare Medical, California, USA] diluted in a carrier at an optimal concentration with standard protocol. Results: ATRX stained 44% of diffuse and anaplastic astrocytoma and 57% of glioblastoma. Also, cross-reactivity testing determined ATRX polyclonal may stain normal brain in some cases. A more comprehensive data evaluation shown below: Conclusions: ATRX polyclonal shows a potential advantage when diagnosing brain tumors (especially astrocytoma and glioblastomas) even if some cross reactivity can be observed. ATRX in conjunction with other brain marker antibodies can offer a better tool in diagnosing brain tumors. Diseased Tissue Specificity and SensitivityTissuePositive CasesTotal Cases% +Astrocytoma163644Glioblastoma4757Breast Cancer132748Colon Cancer84020Lung Cancer245246Prostate Cancer164238Normal Tissue Cross-ReactivityCerebrum51145Cerebellum2367 Citation Format: Jose Jonathan Diaz, Tatiana Scoggin, Jason Ramos. Characterization of ATRX polyclonal, application of immunohistochemical analysis on astrocytoma and glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 458.
Adoption of guidelines on and use of oral pre-exposure prophylaxis: a global summary and forecasting study
Authors: Robin Schaefer, Heather-Marie A Schmidt, Giovanni Ravasi, Antons Mozalevskis, Bharat B Rewari, Frank Lule, Kouadio Yeboue, Anne Brink, Nabeel Mangadan Konath, Mukta Sharma, Nicole Seguy, Joumana Hermez, Ahmed S Alaama, Naoko Ishikawa, Boniface Dongmo Nguimfack, Daniel Low-Beer, Rachel Baggaley, Shona Dalal
Journal: The Lancet HIV (2021)

In 2016, the UN General Assembly set a global target of 3 million oral pre-exposure prophylaxis (PrEP) users by 2020. With this target at an end, we aimed to assess global trends in the adoption of WHO PrEP recommendations into national guidelines and numbers of PrEP users, defined as people who received oral PrEP at least once in a given year, and to estimate future trajectories of PrEP use.In this global summary and forecasting study, data on adoption of WHO PrEP recommendations and numbers of PrEP users were obtained through the Global AIDS Monitoring system and WHO regional offices. Trends in these indicators for 2016-19 by region and for 2019 by country were described, including by gender and priority populations where data were available. PrEP user numbers were forecasted until 2023 by selecting countries with at least 3 years of PrEP user data as example countries in each region to represent possible future PrEP user trajectories. PrEP user growth rates observed in example countries were applied to countries in corresponding regions under different scenarios, including a COVID-19 disruption scenario with static global PrEP use in 2020.By the end of 2019, 120 (67%) of 180 countries with data had adopted the WHO PrEP recommendations into national guidelines (23 in 2019 and 30 in 2018). In 2019, there were about 626 000 PrEP users across 77 countries, including 260 000 (41·6%) in the region of the Americas and 213 000 (34·0%) in the African region; this is a 69% increase from about 370 000 PrEP users across 66 countries in 2018. Without COVID-19 disruptions, 0·9-1·1 million global PrEP users were projected by the end of 2020 and 2·4-5·3 million are projected by the end of 2023. If COVID-19 disruptions resulted in no PrEP user growth in 2020, the projected number of PrEP users in 2023 is 2·1-3·0 million.Widespread adoption of WHO PrEP recommendations coincided with a global increase in PrEP use. Although the 2020 global PrEP target will be missed, strong future growth in PrEP use is possible. New PrEP products could expand the PrEP user base, and, with greater expansion of oral PrEP, further adoption of WHO PrEP recommendations, and simplified delivery, PrEP could contribute to ending AIDS by 2030.Unitaid, Bill & Melinda Gates Foundation, and WHO.
A nomogram to predict absence of clinically significant prostate cancer in men with negative MRI
Authors: M. Kaneko, G.E. Cacciamani, A. Fujihara, T. Iwata, M. Oishi, S.L. Palmer, M. Aron, V. Duddalwar, G. Horiguchi, S. Teramukai, O. Ukimura, I.S. Gill, A.L. Abreu
Journal: European Urology (2021)
Novel role for caspase recruitment domain family member 14 and its genetic variant rs11652075 in skin filaggrin homeostasis
Authors: Stanley B. DeVore, Mariana L. Stevens, Hua He, Jocelyn M. Biagini, John W. Kroner, Lisa J. Martin, Gurjit K. Khurana Hershey
Journal: Journal of Allergy and Clinical Immunology (2021)
Abstract 1488: Viral molecular mimicry influences the antitumor immune response in murine and human melanoma
Authors: Jacopo Chiaro, Henna Kasanen, Thomas Whalley, Cristian Capasso, Sara Feola, Mikaela Grönholm, Firas Hamdan, Karita Peltonen, Micaela Hernberg, Siru Mäkelä, Hanna Karhapää, Paul Brown, Beatriz Martins, Manlio Fusciello, Erkko Ylösmäki, Anna Kreutzman, Satu Mustjoki, Barbara Szomolay, Vincenzo Cerullo
Journal: Cancer Research (2021)

Abstract Molecular mimicry is known to be one of the leading mechanisms by which infectious agents may induce autoimmunity. However, whether a similar mechanism triggers anti-tumor immune response is unexplored, and the role of anti-viral T-cells infiltrating the tumor has remained anecdotal. To address this question, we first developed a bioinformatic tool to identify tumor peptides with high similarity to viral epitopes. Using peptides identified by this tool, we showed that, in mice, viral pre-existing immunity enhanced the efficacy of cancer immunotherapy via molecular mimicry. Specifically, when treated with a cancer vaccine consisting of peptides with a high degree of homology with specific viral peptides, the mice with induced pre-existing immunity to these viral peptides showed significantly better anti-tumor response.To understand whether this mechanism could partly explain immunotherapy-response in humans, we analyzed a cohort of melanoma patients undergoing PD1 treatment with high IgG titer for Cytomegalovirus (CMV). In this cohort of patients, we showed that high level of CMV-antibodies was associated with a prolonged progression free survival, and found that in some cases PBMCs could cross-react with both melanoma and CMV homologous peptides. Finally, T-cell TCR sequencing revealed expansion of the same CD8+ T-cell clones, when PBMCs were pulsed with tumor- or homologous viral peptides.In conclusion, we have demonstrated that pre-existing immunity and molecular mimicry could explain part of the response observed in immunotherapy. Most importantly, we have developed a tool able to identify tumor antigens and neoantigens based on their similarity to pathogen antigens, in order to exploit molecular mimicry and cross-reactive T-cells in cancer vaccine development. Citation Format: Jacopo Chiaro, Henna Kasanen, Thomas Whalley, Cristian Capasso, Sara Feola, Mikaela Grönholm, Firas Hamdan, Karita Peltonen, Micaela Hernberg, Siru Mäkelä, Hanna Karhapää, Paul Brown, Beatriz Martins, Manlio Fusciello, Erkko Ylösmäki, Anna Kreutzman, Satu Mustjoki, Barbara Szomolay, Vincenzo Cerullo. Viral molecular mimicry influences the antitumor immune response in murine and human melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1488.
Abstract 398: Tumor mutational burden estimated by whole-exome sequencing across multiple cancer types
Authors: Fei Xu, Jinwang Wei, Xiaochen Zhang, Jun Liu, Chun Dai, Guan Wang, Qiang Xu
Journal: Cancer Research (2021)

Abstract Purpose: Tumor mutational burden (TMB) is emerging as a promising biomarker in immune checkpoint inhibitor therapy. Although whole-exome sequencing (WES) is the gold standard to quantify TMB, most TMB measurements in routine diagnostic applications were done by gene panels due to their lower cost and technical accessibility. Therefore, data is lacking for WES derived TMB in several major tumors. However, panel derived TMB can be misleading because research found its correlation with WES derived TMB was compromised when a subset of samples with high TMB values were excluded from the dataset. In this study, we aim to establish the landscape of WES derived TMB in six tumor types in Chinese patients, test the association between WES-TMB and patient survival in immunotherapy, and compare the performance between WES-TMB and panel-TMB. Methods: We recruited 357 patients who had received immune checkpoint inhibition (ICI) therapy, representing six types of cancers (see Results for the list). We analyzed the tumors and patient-matched blood samples using WES and called somatic mutations of the patients. We defined our WES-TMB as the total number of somatic nonsynonymous mutations in the tumor exome. In each of the tumor types tested, we assigned the patients with the upper tertile TMB values as the high-TMB group and the remaining two thirds of patients as the low-TMB group. Results: The distribution of WES-TMB medians are highly variable among different tumors, ranging from 2.71 (cholangiocarcinoma), 2.97 (nervous system tumor), 3.69 (gastric cancer), 4.31 (hepatocellular carcinoma), 4.64 (colorectal cancer), to 5.67 (lung cancer) mutations/Mb. This trend is almost the same as other TMB studies done with panel sequencing, despite the values derived from WES tend to be lower. Additionally, TMB was significantly associated with overall survival in colorectal patients receiving ICI. The high-TMB group also showed better overall survival in hepatocellular carcinoma and gastric cancer. Conclusion: TMBs derived from panel are overestimated compared to that derived from WES although that doesn't affect the rank of TMBs in different cancer types. It is rational to define TMB subgroups by percentile within different cancer types. These results support TMB as a biomarker to predict clinical benefit to ICI therapy in colorectal cancer. Citation Format: Fei Xu, Jinwang Wei, Xiaochen Zhang, Jun Liu, Chun Dai, Guan Wang, Qiang Xu. Tumor mutational burden estimated by whole-exome sequencing across multiple cancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 398.
Match of Patient Reported Outcome Measures (PROMs) and the urologists’ assessment in non-metastatic prostate cancer: Results from a randomized controlled trial
Authors: J. Huber, P. Karschuck, R. Koch, A. Ihrig, T. Krones, A. Neisius, S. Von Ahn, C. Klopf, S. Weikert, M. Siebels, N. Haseke, C. Weißflog, M. Baunacke, P. Liske, G. Tosev, T. Benusch, M. Schostak, J. Stein, P. Spiegelhalder, C. Thomas, C. Groeben
Journal: European Urology (2021)
Abstract 2909: Tumor microbiota profiles are associated with molecular subtype and survival in colorectal cancer patients
Authors: Fangyu Li, Michael G. White, Jennifer Davis, Kristi L. Hoffman, David Menter, Nadim Ajami, Xiaotao Zhang, Jeffrey S. Morris, Robert R. Jenq, Joseph Petrosino, Jennifer A. Wargo, Scott Kopetz, Carrie R. Daniel
Journal: Cancer Research (2021)

Abstract Background: The intestinal microbiome is intimately involved in the pathogenesis of colorectal cancer and likely holds further insights to improve the treatment and management of this deadly disease. In a clinical cohort of patients with colon and rectal cancers, we characterized the tumor microbiota of surgical specimens and evaluated associations with prognostic factors, consensus molecular subtypes (CMS), and survival. Methods: In 167 patients diagnosed with stage II through IV colon and/or rectal cancer who underwent evaluation and surgical resection (no prior systemic therapy) at The University of Texas MD Anderson Cancer, we characterized the tumor microbiome via 16S rRNA gene sequencing. Each patient's tumor was classified via CMS, a gene expression-based colorectal cancer classification system; and all patients were prospectively followed for disease progression, recurrence, or death. Microbiota diversity and composition were assessed with regard to clinicopathologic and tumor features; and associations with survival were further evaluated in multivariable Cox proportional hazards models. Results: Left- vs. right-sided colon tumors were characterized by higher microbial diversity, distinct community features, and increased abundance of Bacteroides and Fusobacterium. CMS1 (microsatellite instability immune) vs. CMS2 (canonical) tumors were characterized by higher Bacteroides and Fusobacterium and lower Escherichia (all P&amp;lt;0.05). Fusobacterium-positive and Escherichia-positive tumors were associated with improved 5-year overall survival [presence vs. absence, multivariable-adjusted HR and 95% CI: 0.43 (0.20-0.93) and 0.32 (0.19-0.78), respectively]. Bacteroides was enriched among stage II/III patients who progressed within 2-years (log-rank p&amp;lt;0.001). Conclusions: Our findings are consistent with those of other groups suggesting the landscape of the tumor microbiome differs by sidedness and molecular subtype, holding important clues and exploitable targets to improve outcomes in colorectal cancer patients. Citation Format: Fangyu Li, Michael G. White, Jennifer Davis, Kristi L. Hoffman, David Menter, Nadim Ajami, Xiaotao Zhang, Jeffrey S. Morris, Robert R. Jenq, Joseph Petrosino, Jennifer A. Wargo, Scott Kopetz, Carrie R. Daniel. Tumor microbiota profiles are associated with molecular subtype and survival in colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2909.
Abstract 840: Gallstones and risk of cancers of the liver, biliary tract, and pancreas: A prospective study within two U.S. cohorts
Authors: Xiao Luo, wanshui yang, Amit Joshi, Kana Wu, Tracey Simon, Chen Yuan, Lina Jin, Lu Long, Mi Na Kim, Chun-Han Lo, Xing Liu, Thomas A. Abrams, Brian M. Wolpin, Andrew T. Chan, Edward L. Giovannucci, Xuehong Zhang
Journal: Cancer Research (2021)

Abstract Background: As one of the most common gastrointestinal diseases, gallstones may result in inflammation,altered bile flow, and changes in metabolic hormone levels, thereby increasing cancer risk. Previous studiesfor gallstones and cancers of the liver, biliary tract, and pancreas from the different data sources, inadequateconfounding adjustment, and whether the association varied by potential risk factors is unclear. Objective: We examined the association of gallstones and cholecystectomy with the risk of cancers of theliver, biliary tract, and pancreas in the United States. Methods: We followed 115 036 women from the Nurses' Health Study (1982-2012) and 49 729 men fromthe Health Professionals Follow-up Study (1986-2012). History of gallstones, including with or withoutperformed cholecystectomy, was reported at baseline and updated through biennial questionnaires. The Coxproportional hazard regression model was used to calculate multivariable hazard ratios (HRs) and 95%confidence intervals (95%CIs). Results: During up to 30-year follow-up, we identified 204 incident liver cancer, 225 biliary tract cancer, and1 147 pancreatic cancer cases. Compared to those without gallstones diagnosis, the multivariable HRs forindividuals with gallstones (untreated or with cholecystectomy) were 1.60 for liver cancer (95%CI: 1.14-2.26),4.79 for biliary tract cancer (95%CI: 3.02-7.58), and 1.13 for pancreatic cancer (95%CI: 0.96-1.32). Themultivariable HRs for individuals with cholecystectomy were 1.33 for liver cancer (95%CI: 0.90-1.95) and1.15 for pancreatic cancer (95%CI: 0.98-1.36). Conclusions: Gallstones were associated with a higher risk of cancers of the liver, biliary tract, and possiblypancreas. Cholecystectomy was associated with a suggestive increased risk of liver and pancreatic cancer.Our findings provide further evidence for a positive association of gallstones with the risk of cancers in thehepato-pancreato-biliary area. Citation Format: Xiao Luo, wanshui yang, Amit Joshi, Kana Wu, Tracey Simon, Chen Yuan, Lina Jin, Lu Long, Mi Na Kim, Chun-Han Lo, Xing Liu, Thomas A. Abrams, Brian M. Wolpin, Andrew T. Chan, Edward L. Giovannucci, Xuehong Zhang. Gallstones and risk of cancers of the liver, biliary tract, and pancreas: A prospective study within two U.S. cohorts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 840.