tbuckley/cabot-search huggingface dataset:
Abstract 2139: A seven lncRNA based risk score system for predicting the recurrence and prognosis of ovarian cancer patients
Authors: Haojie Yang, Changpeng Han
Journal: Cancer Research (2020)

Abstract Objective: Ovarian cancer (OC) has the third highest incidence and highest mortality among all gynecological tumors. This study was performed in order to establish a risk score system for OC patients. Methods: The RNA-seq data of OC (the training set) was extracted from TCGA database, and the GSE32062 (the validation set) data was selected from GEO database. Using the limma package, differentially expressed RNAs between the recurrence and non-recurrence groups were identified. For constructing a risk score system, the independent prognosis-correlated lncRNAs were selected using the survival package. Then, the independent clinical prognostic factors were identified using survival package, and the nomogram survival model was built using the rms package. Furthermore, enrichment analysis was conducted using the DAVID tool, and a lncRNA-mRNA co-expression network was constructed using Cytoscape software. Results: There were 550 DERs (497 mRNAs and 53 lncRNAs) between the recurrence and non-recurrence samples. After identification of 321 DERs significantly related to survival prognosis, seven independent prognosis-correlated lncRNAs (MORC2-AS1, LINC00189, MYCNOS, SNHG7, DSCR9, TCL6, and RBM26-AS1) were further selected for constructing the risk score system. Subsequently, the nomogram survival model based on independent clinical prognostic factors (including age, tumor recurrence, and RS model status) was established. There were five overlapping pathways (including Jak-STAT and Wnt signaling pathways and other pathways in cancer) between the searched and the enriched pathways. Additionally, the seven independent prognosis-correlated lncRNAs were involved in the co-expression network, which was directly correlated with OC. Conclusion: The risk score system and nomogram survival model based on lncRNAs (MORC2-AS1, LINC00189, MYCNOS, SNHG7, DSCR9, TCL6, and RBM26-AS1) may be valuable for predicting the prognosis of OC. Citation Format: Haojie Yang, Changpeng Han. A seven lncRNA based risk score system for predicting the recurrence and prognosis of ovarian cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2139.
Abstract 4702: DNA methylation enhances apoptosis resistance of renal cancer cells through the control of mitochondria related gene expression
Authors: Kosuke Miyakuni, Jun Nishida, Shogo Ehata, Kohei Miyazono
Journal: Cancer Research (2020)

Abstract Many gene alterations have been identified in the onset of renal carcinogenesis. However, molecular alterations might be added to renal cancer cells during the progression. In order to uncover additional molecular alterations, we established highly malignant cancer cells which possess identical background to original cancer cells, and analyzed them in the present study. Since our previous works demonstrated that interaction with cancer microenvironment aids cancer cells with malignant trait through “education” and “selection”, serial orthotopic transplantation was utilized. First, parental human clear cell renal cell carcinoma cells, OS-RC-2, were subjected to serial orthotopic transplantation. Then, novel derivatives were obtained from resulting primary renal tumors. These derivatives formed primary renal tumor faster than parental cells and exhibited increased lung metastasis, suggesting that these derivatives were defined as “highly malignant cancer cells”. Next, we tried to identify the underlying molecular mechanism(s) for renal cancer progression through the characterization of highly malignant cancer cells. Gene expressions in each cell were profiled using RNA-sequencing, and these analyses revealed that expression of several genes associated with mitochondrial functions were dramatically down-regulated in highly malignant cancer cells. Since mitochondrial electron transport chain triggers apoptotic cell death, decrease of these genes may contribute to suppression of apoptosis of highly malignant cancer cells. Cell culture and in vivo experiments demonstrated that mitochondrial dysfunction is responsible for increased survival of renal cancer cells and cancer metastasis. Finally, regulatory mechanism of downregulation of these mitochondria-related genes was analyzed. Bisulfite sequencing analysis revealed that the downregulation may occur by DNA hypermethylation of CpG islands in the promoter regions in renal cancer cells.Taken together, these findings suggested that renal cancer cells acquire additional anti-apoptotic ability through the DNA methylation during the interactions with renal microenvironment, which may in turn lead to the cancer progression and metastasis. We are currently investigating whether the effect of anti-cancer reagent is enhanced in the presence of DNA methylation inhibitors. Citation Format: Kosuke Miyakuni, Jun Nishida, Shogo Ehata, Kohei Miyazono. DNA methylation enhances apoptosis resistance of renal cancer cells through the control of mitochondria related gene expression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4702.
Abstract 1903: PTEN loss mediates clinical cross-resistance to CDK4/6 and PI3Ká inhibitors in breast cancer
Authors: Carlotta Costa, Ye Wang, Amy Ly, Yasuyuki Hosono, Ellen Murchie, Charlotte S. Walmsley, Tiffany Huynh, Christopher Healy, Rachel Peterson, Shogo Yanase, Charles T. Jakubik, Laura E. Henderson, Leah J. Damon, Daria Timonina, Ioannis Sanidas, Christopher J. Pinto, Mari Mino-Kenudson, James Stone, Nicholas J. Dyson, Leif W. Ellisen, Aditya Bardia, Hiromichi Ebi, Cyril H. Benes, Jeffrey A. Engelman, Dejan Juric
Journal: Cancer Research (2020)

Abstract The combination of CDK4/6 inhibitors with anti-estrogen therapies significantly improves clinical outcomes in ER-positive advanced breast cancer. To identify mechanisms of acquired resistance, we analyzed serial biopsies and rapid autopsies from patients treated with the combination of the CDK4/6 inhibitor ribociclib with letrozole. This study revealed that some resistant tumors acquired RB loss, whereas other tumors lost PTEN expression at the time of progression. In breast cancer cells ablation of PTEN, through increased AKT activation, was sufficient to promote resistance to CDK4/6 inhibition in vitro and in vivo. Mechanistically, PTEN loss resulted in exclusion of p27 from the nucleus, leading to increased activation of both CDK4 and CDK2. Since PTEN loss also causes resistance to PI3Kα-inhibitors, currently approved in the post-CDK4/6 setting, these findings provide critical insight into how this single genetic event may cause clinical cross-resistance to multiple targeted therapies in the same patient, with implications for optimal treatment sequencing strategies. Citation Format: Carlotta Costa, Ye Wang, Amy Ly, Yasuyuki Hosono, Ellen Murchie, Charlotte S. Walmsley, Tiffany Huynh, Christopher Healy, Rachel Peterson, Shogo Yanase, Charles T. Jakubik, Laura E. Henderson, Leah J. Damon, Daria Timonina, Ioannis Sanidas, Christopher J. Pinto, Mari Mino-Kenudson, James Stone, Nicholas J. Dyson, Leif W. Ellisen, Aditya Bardia, Hiromichi Ebi, Cyril H. Benes, Jeffrey A. Engelman, Dejan Juric. PTEN loss mediates clinical cross-resistance to CDK4/6 and PI3Ká inhibitors in breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1903.
Debates Around the Role of School Closures in the Coronavirus 2019 Pandemic
Authors: Sergio Verd, Marta López-García
Journal: JAMA Pediatrics (2020)

To the Editor: We read with great interest the article by Esposito and Principi, 1 who expressed skepticism as to whether school closure is an effective measure in mitigating the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).It was interesting to read that Taiwan successfully slowed the spread of SARS-CoV-2 without school closure.Additionally, they highlighted that school closure had no significant effect on the spread of SARS-CoV-2 in China.Other countries, such Japan, Israel, Denmark, and Norway, also closed their schools in an attempt to mitigate the spread of SARS-CoV-2.Interestingly, Denmark and Norway reopened their schools in April 2020 and have continued to see a decline in the number of new infections as of May 2020. 2 Denmark was one of the first countries to close schools and enforced school closure on March 11, 2020, with 262 confirmed coronavirus cases.After several weeks of closure, the Danish government reopened schools for young children on April 15, 2020. 2 In this period, the number of cases rose by 6249 to 6511 cases over a period of 35 days.As of May 25, 2020, the number of cases in Denmark stands at 11 360, a rise of 4849 cases in 40 days. 3 Thus, in a longer period with schools reopened, Denmark has seen fewer new cases of SARS-CoV-2 infection than when schools were closed.Norway was another country to close all educational institutions early, doing so on March 12, 2020, with 489 total confirmed cases. 3,4 Norway began reopening kindergartens on April 20, 2020, and junior schools on April 27. 5 Between March 12 and April 27, there was a rise of 7016 cases to a total of 7505.Since reopening primary schools, there have been just 804 new cases in Norway between April 27, 2020, and May 25, 2020, over 29 days. 3 As in Denmark, Norway has seen a huge decrease in the number of new cases while schools reopen.The reopening of schools is extremely important because children depend on schools for normal social and intellectual development.The decrease in new cases in Denmark and Norway as their schools reopen is a very encouraging sign.However, it would be nonetheless prudent to continuously monitor the number of new cases as schools reopen across the world.
Reimagining the Path to Reproducibility for <i>Cancer Research</i>
Authors: Chi Van Dang
Journal: Cancer Research (2020)

</br>![][1]</img> Our ability to discern truth from experimental dialogues with nature is imperfect and fraught with barriers. Irreproducibility in cancer research is one such barrier. It is our collective duty to create a path for reproducible research reports in Cancer Research . In this
SARS-CoV-2 Testing and Changes in Primary Care Services in a Multistate Network of Community Health Centers During the COVID-19 Pandemic
Authors: John Heintzman, Jean O’Malley, Miguel Marino, Jonathan V. Todd, Kurt C. Stange, Natalie Huguet, Rachel Gold
Journal: JAMA (2020)

This study uses electronic health record data to describe primary care services offered by US community health centers in March through May 2020, including SARS-CoV-2 testing, well-child visits, HbA1c testing, and cancer screening.
Trends in Internal Medicine Faculty by Sex and Race/Ethnicity, 1980-2018
Authors: S. Michelle Ogunwole, Michael Dill, Karen Jones, Sherita H. Golden
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Increasing diversity in the physician workforce is a fulcrum for reducing health disparities. Efforts to increase the diversity in the internal medicine (IM) workforce may improve health equity among an increasingly diverse population with increasing prevalence of chronic disease. <h3>Objectives</h3> To assess diversity trends in the academic IM workforce and evaluate how well these trends reflected medical student diversity and the changing demographic composition of the general population. <h3>Design, Setting, and Participants</h3> This secondary analysis of a cross-sectional study analyzed data from January 1, 1980, to December 31, 2018, from the Association of American Medical Colleges Faculty Roster and Applicant Matriculant File, which capture full-time US medical school faculty and matriculants, respectively, and population data through 2017 from the US Census Bureau. <h3>Main Outcomes and Measures</h3> The study calculated the proportions of women and individuals from racial/ethnic groups that are traditionally underrepresented in medicine (URM) among IM faculty and faculty in all other clinical departments. These data were compared with the proportions of female and URM matriculants in US medical schools and the proportions of women and individuals from underrepresented racial/ethnic groups in the population. The analysis was stratified by sex, race/ethnicity, and intersections of sex and race/ethnicity. <h3>Results</h3> From 1980 to 2018, the absolute number of full-time IM faculty increased from 10 964 to 42 547. Although IM was the department classification with the most women faculty, in 2018 it continued to have a lower proportion of women (n = 17 165 [40.3%]) compared with all other clinical departments (n = 48 936 [43.2%]). Among IM faculty, the percentage of URM faculty members more than doubled during the study period (from 4.1% to 9.7%) but still made up only a small portion of faculty members. The percentage of female matriculants among medical school matriculants increased steadily (from 28.7% in 1980 to 51.6% in 2018) and was nearly identical to their population representation in 2017 (50.7% compared with 50.8%). Although the percentage of URM matriculants had nearly doubled since 1980 (from 11.3% to 18.1%), it still lagged far behind the proportion of individuals in the US population who are members of underrepresented racial/ethnic groups (18.1% vs 31.5% in 2017). <h3>Conclusions and Relevance</h3> This cross-sectional study found that progress has been made in diversifying academic IM faculty; however, it does not yet reflect the diversity of medical students or the US population. Continued efforts to increase the diversity of the academic IM workforce are needed.
Abstract 3572: Merlin deficiency induces redox imbalance in breast cancer
Authors: Mateus Mota, Brandon Metge, Lalita Shevde-Samant
Journal: Cancer Research (2020)

Abstract Merlin is encoded by the NF2 gene and, as a tumor suppressor, stalls cell proliferation by contact-dependent growth inhibition. Prior work from our laboratory has established that Merlin levels are significantly decreased in breast tumor tissues representing advanced grade. Moreover, Merlin expression is completely lost in cases representing metastatic breast cancer. Therefore, we mimicked Merlin deficiency by stably knocking down NF2 in non-metastatic breast cancer cells. Recognizing the role of metabolic reprogramming in tumor progression, we undertook untargeted metabolomics analysis - this effort identified low levels of reduced glutathione (GSH) in Merlin-deficient cells. Given the role of GSH as the most abundant antioxidant cofactor, we explored if a major reactive oxygen species (ROS) clearance mechanism is compromised in Merlin-deficient breast cancer cells. Indeed, accumulated levels of ROS were detected in Merlin-deficient cells, suggesting that Merlin deficiency causes redox imbalance. Quenching of elevated ROS levels attenuated migration and invasion capabilities indicating a role of ROS in intensifying malignant behaviors upon Merlin deficiency. Furthermore, dysregulated STAT3 activity upregulated the expression of NADPH oxidase (NOX) enzymes in Merlin-deficient breast cancer cells compared to their control counterparts. These findings were also recapitulated in non-tumorigenic Nf2 −/- mouse embryonic fibroblasts further supporting the key role of Merlin in these phenotypes. In conclusion, ROS accumulation and increased malignancy in Merlin-deficient cells may be the result of a dysregulated cellular redox management system. Citation Format: Mateus Mota, Brandon Metge, Lalita Shevde-Samant. Merlin deficiency induces redox imbalance in breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3572.
Post-Marketing Safety Concerns with Esketamine: A Disproportionality Analysis of Spontaneous Reports Submitted to the FDA Adverse Event Reporting System
Authors: Chiara Gastaldon, Emanuel Raschi, John M. Kane, Corrado Barbui, Georgios Schoretsanitis
Journal: Psychotherapy and Psychosomatics (2020)

Esketamine nasal spray received approval for treatment-resistant depression in March 2019.Using the FDA Adverse Event Reporting System (FAERS) database (March 2019-March 2020), we analysed esketamine-related adverse events (AEs) to detect and characterize relevant safety signals.We used the consolidated case/non-case approach to estimate the reporting odds ratio (ROR) and information component (IC) with relevant confidence intervals (95% CI) for esketamine-related AEs with ≥4 counts. Comparisons between serious and non-serious AEs were performed using non-parametric tests.The FAERS database contained 962 cases of esketamine-related AEs, with signals detected for several AEs, such as dissociation (ROR = 1,612.64, 95% CI = 1,354.63, 1,919.79; IC = 8.19, 95% CI = 7.96, 8.35), sedation (ROR = 238.46, 95% CI = 202.98, 280.15; IC = 7, 95% CI = 6.75, 7.18), feeling drunk (ROR = 96.17, 95% CI = 61.42, 150.57; IC = 4.84, 95% CI = 4.09, 5.36), suicidal ideation (ROR = 24.03, 95% CI = 18.72, 30.84; IC = 4.31, 95% CI = 3.9, 4.61), and completed suicide (ROR = 5.75, 95% CI = 3.18, 10.41; IC = 2.25, 95% CI = 1.23, 2.94). Signals for suicidal and self-injurious ideation, but not suicide attempt and completed suicide, remained when comparing esketamine to venlafaxine. Females and patients receiving antidepressant polypharmacy, co-medication with mood stabilizers, antipsychotics, benzodiazepines, or somatic medications were more likely to suffer from serious versus non-serious AEs (χ2 = 125.29, p < 0.001, χ2 = 9.08, p = 0.003, χ2 = 8.14, p = 0.004, χ2 = 19.48, p < 0.001, χ2 = 25.62, p < 0.001, and χ2 = 16.79, p < 0.001, respectively).Esketamine may carry a clear potential for serious AEs, which deserves urgent clarification by means of further prospective studies.
Association of Family History With Incidence and Outcomes of Aortic Dissection
Authors: Shao-Wei Chen, Chang-Fu Kuo, Yu-Tung Huang, Wan-Ting Lin, Victor Chien-Chia Wu, An-Hsun Chou, Pyng-Jing Lin, Shang-Hung Chang, Pao-Hsien Chu
Journal: Journal of the American College of Cardiology (2020)

Aortic dissection (AD) is a life-threatening emergency. However, the heritability and association of family history with late outcomes are unclear. The purpose of this study was to evaluate the effect of family history of AD on the incidence and prognosis of AD and estimate the heritability and environmental contribution in AD in Taiwan. Both cross-sectional and cohort studies were conducted using Taiwan National Health Insurance database. A registry parent–offspring relationship algorithm was used to reconstruct the genealogy of this population for heritability estimation. The cross-sectional study included 23,868 patients with a diagnosis of AD in 2015. The prevalence and adjusted relative risks (RRs) were evaluated, and the liability threshold model was used to examine the effects of heritability and environmental factors. Furthermore, a 1:10 propensity score–matched cohort comprising AD patients with or without a family history of AD was included to compare late outcomes in the cohort study. A family history of AD in first-degree relatives was associated with an RR of 6.82 (95% confidence interval [CI]: 5.12 to 9.07). The heritability of AD was estimated to be 57.0% for genetic factors, and 3.1% and 40.0% for shared and nonshared environmental factors, respectively. After excluding individuals with Marfan syndrome or bicuspid aortic valve, a family history of AD was associated with an RR of 6.56 (95% CI: 4.92 to 8.77) for AD. Furthermore, patients with AD and a family history of AD had a higher risk of later aortic surgery than those with AD without a family history (subdistribution hazard ratio: 1.40; 95% CI: 1.12 to 1.76). A family history of AD was a strong risk factor for AD. Furthermore, patients with AD with a family history of AD had a higher risk of later aortic surgery than those with no family history of AD.
Fine-tuning sugar content in strawberry
Authors: Sinian Xing, Kunling Chen, Haocheng Zhu, Rui Zhang, Huawei Zhang, Bingbing Li, Caixia Gao
Journal: Genome biology (2020)

Abstract Fine-tuning quantitative traits for continuous subtle phenotypes is highly advantageous. We engineer the highly conserved upstream open reading frame (uORF) of FvebZIPs1.1 in strawberry ( Fragaria vesca ), using base editor A3A-PBE. Seven novel alleles are generated. Sugar content of the homozygous T1 mutant lines is 33.9–83.6% higher than that of the wild-type. We also recover a series of transgene-free mutants with 35 novel genotypes containing a continuum of sugar content. All the novel genotypes could be immediately fixed in subsequent generations by asexual reproduction. Genome editing coupled with asexual reproduction offers tremendous opportunities for quantitative trait improvement.
Abstract 4601: Toward the development of a $100 screening test for 6 major cancer types
Authors: Linhao Xu, Jun Wang, Ting Yang, Jinsheng Tao, Xin Liu, Zhujia Ye, Dezhi Zhao, Zeyu Jiang, Zhiwei Chen, Jian-Bing Fan
Journal: Cancer Research (2020)

Abstract Introduction: Early cancer detection remains a critical challenge to improve patients' survival rate and clinical outcomes. Alterations in DNA methylation play a key role in tumor initiation, development, progression and metastasis. Cell-free DNA (cfDNA) methylation analysis on liquid biopsies (e.g., blood and urine) holds a great promise for early detection of cancers even without symptoms. In this context, we are developing a non-invasive, cost-effective test that can detect several major cancer types, including lung (LnC), breast (BrC), colorectal (CRC), gastric (GC), esophageal (EC) and liver (LvC) cancers with high specificity (Sp) and sensitivity (Sn). These six cancer types represent two third of the newly diagnosed cancer patients and 72% of cancer deaths every year in China. Methods: In order to identify highly effective DNA methylation markers for early detection, we have conducted genome-wide methylation profiling on more than 2,000 benign and malignant tissue samples, including large number of early stage (Stage I/II) tumors and pre-cancerous lesions from lung, breast, colorectum, liver, stomach and esophagus. We then developed a high performance assay, Aurora, to capture cancer-specific DNA methylation signatures in plasma. Specifically, cfDNA was extracted from each of the plasma samples, bisulfite-converted, and analyzed by NGS on Illumina MiSeq system. Results and Discussion: To date, methylation profiles of plasma samples derived from, 1) 58 normal and 106 malignant pulmonary nodule patients, 2) 31 normal and 85 malignant CRC patients, and 3) 81 normal and 78 malignant breast nodule patients, were analyzed. Overall performances (Area Under Curve, AUC) of the Aurora test are 90%, 98% and 92% for LnC, BrC and CRC, respectively. Further clinical validation and evaluation are being conducted in larger independent cohorts of these three types of cancers as well as additional cohorts for the other cancers (GC, EC and LvC). The superior performance and low cost (~$100) make the Aurora test very promising for simultaneous screening of multiple major cancers in symptom-free, average risk populations. Citation Format: Linhao Xu, Jun Wang, Ting Yang, Jinsheng Tao, Xin Liu, Zhujia Ye, Dezhi Zhao, Zeyu Jiang, Zhiwei Chen, Jian-Bing Fan. Toward the development of a $100 screening test for 6 major cancer types [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4601.