tbuckley/cabot-search huggingface dataset:
Abstract 2341: Predictive analysis of gynecologic cancer risk factors using decision tree analysis
Authors: Zahra Bahrani-Mostafavi, Larissa B. Huber, Wei Sha, Christine Richardson
Journal: Cancer Research (2020)

Abstract Introduction: Gynecologic cancer (GYNC) accounts for 6.3% of all cancers and is the fourth leading cause of cancer death for women in the U.S. Autoimmune diseases (AD) are among the top ten leading causes of death among U.S. women age 65 and under. This high mortality rate among women with AD has been linked to cancer and other causes. Considering cancer and AD are the accumulative effect of genetics and lifestyle, and 90-95% of all cancers are linked to lifestyle and environmental factors, a study to investigate the association between patient-level predictors and GYNC among AD patients in the U.S. was imperative. Methods: 2007-2013 data from Florida State Inpatient samples of the Healthcare Cost and Utilization Project were used. The study population (n=836,717) was restricted to women who had any AD. The outcome variable was diagnosis of GYNC. 36 categorical transformed variables including race/ethnicity, age, insurance type, income level, GYN procedures, and comorbidities were analyzed as predictive variables (PV). Bootstrap Forest (JMP pro13) were was used to create a 10,000-decision tree (DT) model to identify independent predictors of GYNC. Multiple outputs such as confusion matrix, column contribution, and ROC was created for predictive analytics. Results: The analytical model used was confirmed by evaluating criteria such as AUC (0.82), sensitivity (0.68), specificity (0.82), false positive rate (0.18), wrongly predicted value (0.24), and overall accurate prediction (0.76) of the model. Using column contribution and single DT, the PV hysterectomy was the highest predictor of GYNC, followed by PV age;, and comorbidities such as diabetes, and obesity; along with race/ethnicity; and income level. Also, subpopulations of AD patients at risk for GYNC based on unique combinations of risk factors were established, including subpopulations such as women with AD, involved glandular disorders who had hysterectomy, and comorbidities such as diabetes and fluid and electrolyte disorders. Discussion: Both GYNC and AD are major chronic diseases among women. Because of high prevalence of AD among women, more elucidation on the association between GYNC and AD is essential for GYNC management. The unique combinations of characteristics that describe subgroups of patients at risk for GYNC among AD patients can be used as a potential risk assessment, as well as an early detection and/ or prevention tools for GYNC. Citation Format: Zahra Bahrani-Mostafavi, Larissa B. Huber, Wei Sha, Christine Richardson. Predictive analysis of gynecologic cancer risk factors using decision tree analysis [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 2341.
Clinical Characteristics of Lupus Erythematosus Panniculitis/Profundus
Authors: Lauren K. Rangel, Camila Villa-Ruiz, Kelly Lo, Gabriela Cobos, Kristen Lo Sicco, Ruth Ann Vleugels, Alisa N. Femia
Journal: JAMA Dermatology (2020)

This case series characterizes the initial presentation and treatment of lupus erythematosus panniculitis/profundus and its association with systemic lupus erythematosus and discoid lupus erythematosus.
Abstract 106: The inhibitory effects of baicalein on cell proliferation in breast cancer cells
Authors: Nicodemus C. Monear, Austin L. Kantola, Besa Xhabija
Journal: Cancer Research (2020)

Abstract Baicalein is a naturally occurring substance found in certain herbaceous species such as Scutellaria baicalensis and Oroxylum indicum, as well more well-known species such as Thymus vulgaris (thyme). Classified as a flavonoid derivative, baicalein has been shown to inhibit cell proliferation by signaling apoptotic pathways in cell lines typically resistant to induced cell death. In this analysis, we have assessed cell viability by methylene blue staining and have shown that T47D breast cancer cells exhibit stunted proliferation patterns within 24 hours of exposure to baicalein at concentrations as low as 100 µM. Additionally, we have performed an analysis of the cell cycle by flow cytometry for which we have observed an arrest in the S phase, further indicating inhibited cell proliferation. Citation Format: Nicodemus C. Monear, Austin L. Kantola, Besa Xhabija. The inhibitory effects of baicalein on cell proliferation in breast cancer cells [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 106.
Temporal Detection and Phylogenetic Assessment of SARS-CoV-2 in Municipal Wastewater
Authors: Artem Nemudryi, Anna Nemudraia, Tanner Wiegand, Kevin Surya, Murat Buyukyoruk, Calvin Cicha, Karl K. Vanderwood, Royce Wilkinson, Blake Wiedenheft
Journal: Cell Reports Medicine (2020)

SARS-CoV-2 has recently been detected in feces, which indicates that wastewater may be used to monitor viral prevalence in the community. Here, we use RT-qPCR to monitor wastewater for SARS-CoV-2 RNA over a 74-day time course. We show that changes in SARS-CoV-2 RNA concentrations follow symptom onset gathered by retrospective interview of patients but precedes clinical test results. In addition, we determine a nearly complete (98.5%) SARS-CoV-2 genome sequence from wastewater and use phylogenetic analysis to infer viral ancestry. Collectively, this work demonstrates how wastewater can be used as a proxy to monitor viral prevalence in the community and how genome sequencing can be used for genotyping viral strains circulating in a community.
HybridSucc: A Hybrid-Learning Architecture for General and Species-Specific Succinylation Site Prediction
Authors: Wanshan Ning, Haodong Xu, Peiran Jiang, Han Cheng, Wankun Deng, Yaping Guo, Yu Xue
Journal: Genomics Proteomics & Bioinformatics (2020)

As an important protein acylation modification, lysine succinylation (Ksucc) is involved in diverse biological processes, and participates in human tumorigenesis. Here, we collected 26,243 non-redundant known Ksucc sites from 13 species as the benchmark data set, combined 10 types of informative features, and implemented a hybrid-learning architecture by integrating deep-learning and conventional machine-learning algorithms into a single framework. We constructed a new tool named HybridSucc, which achieved area under curve (AUC) values of 0.885 and 0.952 for general and human-specific prediction of Ksucc sites, respectively. In comparison, the accuracy of HybridSucc was 17.84%-50.62% better than that of other existing tools. Using HybridSucc, we conducted a proteome-wide prediction and prioritized 370 cancer mutations that change Ksucc states of 218 important proteins, including PKM2, SHMT2, and IDH2. We not only developed a high-profile tool for predicting Ksucc sites, but also generated useful candidates for further experimental consideration. The online service of HybridSucc can be freely accessed for academic research at http://hybridsucc.biocuckoo.org/.
Abstract 659: Synergistic antitumor activity of futibatinib (TAS-120), a FGFR1-4 inhibitor, and PI3K pathway inhibitors
Authors: Akihiro Miura, Hiroshi Sootome, Toshiharu Komori, Hiroaki Ochiiwa, Hiroshi Hirai
Journal: Cancer Research (2020)

Abstract Background: Futibatinib, a selective irreversible small-molecule fibroblast growth factor receptor (FGFR) 1–4 inhibitor is currently being investigated in phase 2 studies in patients with various FGFR-deregulated cancers. FGFRs use the PI3K pathway to promote cell growth and survival, suggesting that a combination of futibatinib with PI3K pathway inhibitors may result in synergistic activity. Therefore, we investigated the antitumor effects of futibatinib plus PI3K pathway inhibitors, everolimus (mTOR inhibitor) or MK2206 (AKT inhibitor). Methods: Human endometrial FGFR2-N549K-mutated AN3CA cancer cells were treated with futibatinib plus either everolimus or MK2206 or with each agent alone. AKT, ERK, mTOR, and S6 phosphorylation, cell viability, and apoptosis (via caspase-3/7 activity) were assessed. Cell growth inhibition was measured and combination indices (CIs) determined using CalcuSyn software; a CI&amp;lt;0.9 indicates synergy. Antitumor activity of futibatinib plus everolimus in ANC3A xenografts was evaluated by assessing relative tumor volume (RTV). Results: In ANC3A cells, the combination of futibatinib with MK2206 inhibited AKT phosphorylation; futibatinib plus either MK2206 or everolimus inhibited mTOR phosphorylation to a greater degree than monotherapy. Apoptosis induction by caspase-3/7 was readily detected with futibatinib plus MK2206, but low to no activity was observed with either agent alone. A synergistic effect on cell growth inhibition was observed for futibatinib plus everolimus (CI=0.26) or MK2206 (CI=0.14). In AN3CA xenografts, there was a significant (P&amp;lt;0.05) decrease in RTV with futibatinib plus everolimus vs monotherapy (Table). Table.Relative tumor volume in AN3CA mouse xenografts treated with futibatinib or everolimus or combination therapyTreatment (mg/kg/d)Relative tumor volumeDay 0Day 3Day 6Day 10Day 15Control14.657.8116.4937.77Futibatinib (15)a13.084.516.8412.59Futibatinib (50)a12.292.703.154.76Everolimus (2)a12.664.046.3410.24Futibatinib + Everolimus (15 + 2)b11.841.921.681.91Futibatinib + Everolimus (50 + 2)b11.501.310.840.72aDays 1–14 (oral);bDays 1–14 + Days 1–14 (both oral). Conclusions: The combination of futibatinib plus a PI3K pathway inhibitor resulted in synergistic antitumor effects. These data are encouraging and can serve as a basis for investigating the combination of PI3K pathway inhibitors with futibatinib. Citation Format: Akihiro Miura, Hiroshi Sootome, Toshiharu Komori, Hiroaki Ochiiwa, Hiroshi Hirai. Synergistic antitumor activity of futibatinib (TAS-120), a FGFR1-4 inhibitor, and PI3K pathway inhibitors [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 659.
Loss of RNA-Binding Protein RBMS1 Promotes a Metastatic Transcriptional Program in Colorectal Cancer
Authors: Hannah Carter
Journal: Cancer Discovery (2020)

Abstract Summary: Yu and colleagues combined computational and experimental techniques to identify a new post-transcriptional regulator of metastatic potential in colon cancer. This study reveals that the RNA-binding protein RBMS1 is a positive regulator of mRNA stability for multiple genes, including the tumor suppressor AKAP12 and a WNT pathway interacting protein, SDCBP, and its loss is a common event associated with poor prognosis. See related article by Yu et al., p. 1410.
Abstract B21: Oncogenic BRAF and KRAS mutations in endosalpingiosis
Authors: M. Herman Chui, Ie-Ming Shih
Journal: Clinical Cancer Research (2020)

Abstract Endosalpingiosis, or ectopic fallopian tube epithelium, frequently involves the peritoneum and lymph nodes in patients with ovarian low-grade serous borderline tumor or carcinoma, but the pathogenic significance of these microscopic lesions remains unclear. Using laser-capture microdissection and digital droplet PCR, we investigated whether endosalpingiosis harbors the driver mutations in BRAF and KRAS, commonly seen in low-grade serous tumors. Of 21 women with endosalpingiosis associated with a synchronous or metachronous ovarian low-grade serous tumor, mutations were identified in 11 (52%) cases and the identical mutation was shared between the tumor and endosalpingiosis in 10/11 cases. In contrast, of 12 cases of endosalpingiosis not associated with an ovarian tumor, only 1 harbored a KRAS mutation. Across mutation-positive cases, the median mutant allelic frequency was 37% (range: 12 – 67%). Ki-67 immunohistochemical staining revealed significantly decreased proliferative index in endosalpingiosis relative to low-grade serous tumors, but no difference with eutopic tubal epithelium. BRAF or KRAS-mutated endosalpingiosis had significantly lower Ki-67 index compared to lesions lacking mutations in both genes. Functional studies using fallopian tube epithelial cell cultures demonstrate that enforced expression of KRAS-G12V causes phosphorylation of downstream ERK, with associated growth impairment and induction of p21, suggesting oncogene-induced senescence. We demonstrate that endosalpingiosis represents a striking example of cancer driver mutations in deceptively normal-appearing cells, signifying this innocuous-appearing lesion as a monoclonal proliferation with neoplastic potential. Citation Format: M. Herman Chui, Ie-Ming Shih. Oncogenic BRAF and KRAS mutations in endosalpingiosis [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B21.
Association and collaboration: the research antidote to physical distancing?
Authors: Philip Glasgow, Stephen Mutch
Journal: British Journal of Sports Medicine (2020)

Collaboration is an established and valued objective within the military, highly successful organisations, and applied sport. In the future, dissemination and realisation of high-quality research in sports medicine will be rooted in collaboration that bridges gaps between statisticians, researchers and clinical content experts. Distancing in this field is antisocial, smothering and silencing: ultimately keeping your distance undermines progress!

Similar to the sentiment expressed by Exeter’s Dr Robert Mann (UK) in his editorial about athletes as a community (see page 1071) , we, the wider sports medicine community, have demonstrated during these times of distancing a remarkable social interconnection that helps make us all better. This Association of Chartered Physiotherapists in Sport and Exercise Medicine (ACPSEM) issue of BJSM offers much to professionals with an interest in teamwork, and who value cooperation to help validate the evidence that can be implemented with appropriate sporting populations for future success. An antidote to antisocial distanced silos!

The extensive and fascinating analysis of 3600 muscle injuries over 23 years by …
Abstract 4138: Glycogen synthase kinase-3 inhibition impairs DNA damage response through ubiquitin ligase hHYD-mediated TopBP1 degradation
Authors: Li Ding, Kaely R. Roeck, Olga Alekhina, Daniel M. Schmitt, Daniel D. Billadeau
Journal: Cancer Research (2020)

Abstract Glycogen synthase kinase-3 (GSK-3) is overexpressed and accumulates in the nucleus in several human malignancies including pancreatic cancer. We recently demonstrated that GSK-3 inhibition sensitizes pancreatic cancer cells to chemotherapy by abrogating the TopBP1/ATR-mediated DNA damage response. Specifically, GSK-3 kinase activity is required to stabilize TopBP1 protein. Herein, we investigated the mechanism by which GSK-3 phosphorylation of TopBP1 prevents its degradation. Interestingly, GSK-3 inhibition not only decreased the total levels of TopBP1, but also reduced the ability of TopBP1 to bind chromatin following gemcitabine treatment. Mutation of a putative GSK-3 phosphorylation site in TopBP1 (S860A) resulted in decreased TopBP1 stability and chromatin recruitment, whereas a phosphomimetic mutant (S860E) had the opposite effect. Furthermore, we found enhanced TopBP1 ubiquitination after GSK-3 inhibition as well as an increased interaction between TopBP1 and hHYD, an ubiquitin ligase that has been shown to ubiquitylate TopBP1 resulting in its degradation. Significantly, the S860A mutation showed a stronger interaction with hHYD compared to WT or the S860E mutant of TopBP1. In conclusion, our study identifies GSK-3 phosphorylation of TopBP1 as a mechanism to prevent the interaction with and ultimate ubiquitylation-mediated degradation by hHYD. Citation Format: Li Ding, Kaely R. Roeck, Olga Alekhina, Daniel M. Schmitt, Daniel D. Billadeau. Glycogen synthase kinase-3 inhibition impairs DNA damage response through ubiquitin ligase hHYD-mediated TopBP1 degradation [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 4138.
Abstract 6007: Post-fasting refeeding enhances intestinal stem cell-mediated regeneration and tumorigenesis
Authors: Shinya Imada
Journal: Cancer Research (2020)

Abstract Although short-term fasting interventions improve intestinal stem cell (ISC) function, little is known about how much of this benefit comes from fasting versus the post-fasting refeeding response. Given the central role that ISCs play in driving injury-induced repair and in initiating early intestinal tumors, it is possible that fasting by boosting ISC function not only improves regeneration but also unexpectedly elevates intestinal tumorigenesis. To understand how fasting/refeeding interventions influence the role of ISCs in regeneration and early tumor formation, we assessed the function of ISCs to repair the intestinal lining after injury and to contribute to intestinal tumors. Notably, we find that 24 hours post-fasting refeeding boosts intestinal stem and progenitor cells proliferation and increases ISC function in organoid and in fate mapping assays compared to AL and fasted cohorts. Mechanistically, elevated mammalian target of rapamycin (mTOR) activity mediates the effects of refeeding in ISCs as treatment with mTOR inhibitor blocks these effects. Surprisingly, loss of the APC tumor suppressor gene in ISCs increased intestinal tumor numbers in the refed state compared to the AL and fasted states in an mTOR dependent manner. We propose that refeeding through mTOR signaling stimulates ISC function and in a context-dependent manner this can either improve repair after injury or promote intestinal tumorigenesis. Citation Format: Shinya Imada. Post-fasting refeeding enhances intestinal stem cell-mediated regeneration and tumorigenesis [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 6007.
Long-term Outcomes in Patients With Myelin Oligodendrocyte Glycoprotein Immunoglobulin G–Associated Disorder
Authors: A. Sebastian Lopez-Chiriboga, Elia Sechi, Marina Buciuc, John J. Chen, Sean J. Pittock, Claudia F. Lucchinetti, Eoin P. Flanagan
Journal: JAMA Neurology (2020)

This cohort study reports outcomes of long-term follow-up in patients with myelin oligodendrocyte glycoprotein antibody–associated disorder.
Abstract 2428: Emodin enhances efficacy of Oxaliplatin and 5 Fluorouracil in colon cancer by promoting cell cycle arrest
Authors: Ian T. Saunders, Dexter Ezeagwu, Naresh Kumar, Hina Mir, Shailesh Singh
Journal: Cancer Research (2020)

Abstract Dysregulation of cellular proliferation and evasion of apoptosis are key contributors to colon cancer (CoCa) development. Chemotherapeutic agents such as 5-Fluorouracil (5FU) and Oxaliplatin (OxT) which are frequently offered to treat CoCa are known to target cells in S and G2 phase of cell cycle. Cancer cells often overcome the effects of 5FU and OxT by deregulating cell cycle in response to these drugs. Therefore, to improve the cytotoxic effect of these chemotherapeutic agents it is important to keep CoCa cells in S and G2 phase. Hence, understanding the molecular mechanisms involved in CoCa cell-cycle progression and chemotherapeutic response could provide strategies for developing effective treatment options. Hence, in this study, we determined the effect of natural agent “Emodin” on CoCa cell-cycle regulation and its ability to increase the efficacy of 5FU and OxT by cell cycle regulation. The effects of Emodin, 5FU, and OxT as a single agent or in combination on CoCa (DLD-1, COLO-201, HCT116 p53WT, and HCT116 p53-/-) cell viability were determined by MTT assays. Combination index of Emodin, 5FU, and OxT were evaluated using Calcusyn. Emodin-induced changes in molecules involved in cell-cycle regulation and proliferation were analyzed via RT-PCR and confirmed by western blot (WB) analysis. Cell-cycle distribution with Emodin treatment alone and in combination with 5FU and OxT were assessed via flow cytometry and WB. Collectively, our data shows that Emodin alone was able to decrease cell survival and induced apoptosis in CoCa cells. Furthermore, cytotoxic ability of 5FU and OxT was increased when combined with Emodin as compared to when these chemotherapeutic drugs were given as single agents Emodin-induced cell-cycle regulation resulted in increased expression of tumor suppressor genes such as p21, p27 and p53, modulated cyclin/cyclin-dependent kinase expression, and induced cell-cycle arrest. Emodin also negatively impacted several signaling pathways associated with cell growth and differentiation. Overall, this study demonstrates that Emodin could be a promising adjuvant to either 5-Fluorouracil or Oxaliplatin in the treatment of CoCa. Citation Format: Ian T. Saunders, Dexter Ezeagwu, Naresh Kumar, Hina Mir, Shailesh Singh. Emodin enhances efficacy of Oxaliplatin and 5 Fluorouracil in colon cancer by promoting cell cycle arrest [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 2428.