tbuckley/cabot-search huggingface dataset:
Abstract 16838: Genetics of Insulin Response to Fenofibrate in the Goldn Study
Authors: Ryan Irvin, Alexis C Wood, Laura Kelly Vaughan, Edmond Kabagambe, Jin Sha, Hemant Tiwari, Ingrid Borecki, Jose Ordovas, Donna Arnett
Journal: Circulation (2011)

Background: Fenofibrate is an effective treatment for hypertriglyceridemia but also improves cholesterol levels, markers of inflammation, and insulin resistance. Fenofibrate binds to the transcription factor peroxisome proliferator-activated receptor-α (PPARα) which regulates expression of a number of genes. How fenofibrate improves measures of insulin resistance is not completely understood. We sought to determine whether there are genes that influence the effect of fenofibrate on measures of insulin resistance. Methods: We performed a genome wide association study (GWAS) of change in fasting insulin after fenofibrate treatment in the Genetics of Lipid Lowering and Diet Network (GOLDN) study. We calculated change in fasting insulin concentration among 750 GOLDN participants without diabetes that were treated with fenofibrate (160 mg/day) for 3 weeks. Genotyping was done with Affymetrix Human SNP Array 6.0. Of one million SNPs genotyped, 718, 542 met the genotype quality control criteria and were tested for association with change in fasting insulin. Genetic variants were modeled using multivariable linear regression models adjusting for age, sex, center, and family relationship. Results: The three most statistically significant loci were near inositol 1,4,5-triphosphate receptor, type 2 ( ITPR2 , rs16930147, P =2.6*10 -7 ), monooxygenase DBH-like 1 isoform 2 ( MOXD1 , rs7751860, P =1.3*10 -6 ) and chromatin modifying protein 4C ( CHMP4C , rs11996762, P =1.4*10 -6 ). ITPR2 has been associated with waist-to-hip ratio and is highly expressed in human adipocytes. MOXD1 has been shown to be upregulated in the livers of transgenic mice with reduced bioavailability of insulin. Finally, CHMP4C has been implicated in p53 regulation of the endosomal compartment in response to stress where the endosome plays a major role in intracellular cholesterol metabolism. Conclusions: The results show novel loci that may play a role in insulin response to fenofibrate treatment, and can shed light on the pathways underlying this treatment benefit which can help reduce cardiovascular disease risk in treated patients.
Neutrophil-to-lymphocyte ratio in unclassified renal cell carcinoma is associated with clinical outcome and varies between genomic subgroups
Authors: J. Marcon, R.G. Di Natale, S. Weng, M. Ghanaat, A.W. Silagy, R. Mano, K.A. Blum, K. Attalla, E. Reznik, M.I. Carlo, R.J. Motzer, J.A. Coleman, P. Russo, A.A. Hakimi, Y.B. Chen
Journal: European Urology (2021)
Behavioral Research in Cancer Prevention and Control: Emerging Challenges and Opportunities
Authors: William M P Klein, Mary E O’Connell, Michele H Bloch, Susan M Czajkowski, Paige A Green, Paul K J Han, Richard P Moser, Linda C Nebeling, Robin C Vanderpool
Journal: JNCI Journal of the National Cancer Institute (2021)

It is estimated that behaviors such as poor diet, alcohol consumption, tobacco use, sedentary behavior, and excessive ultraviolet exposure account for nearly one-half of all cancer morbidity and mortality. Accordingly, the behavioral, social, and communication sciences have been important contributors to cancer prevention and control research, with methodological advances and implementation science helping to produce optimally effective interventions. To sustain these contributions, it is vital to adapt to the contemporary context. Efforts must consider ancillary effects of the 2019 coronavirus disease pandemic, profound changes in the information environment and public understanding of and trust in science, renewed attention to structural racism and social determinants of health, and the rapidly increasing population of cancer survivors. Within this context, it is essential to accelerate reductions in tobacco use across all population subgroups; consider new models of energy balance (diet, physical activity, sedentary behavior); increase awareness of alcohol as a risk factor for cancer; and identify better communication practices in the context of cancer-related decisions such as screening and genetic testing. Successful integration of behavioral research and cancer prevention depends on working globally and seamlessly across disciplines, taking a multilevel approach where possible. Methodological and analytic approaches should be emphasized in research training programs and should use new and underused data sources and technologies. As the leadership core of the National Cancer Institute's Behavioral Research Program, we reflect on these challenges and opportunities and consider implications for the next phase of behavioral research in cancer prevention and control.
Comparing the ability of wearable devices and CPET to predict major complications following radical cystectomy
Authors: P. Khetrapal, J.W.F. Catto, N. Williams, G. Ambler, M.S. Khan, R. Thurairaja, M.E.L. Tan, A. Feber, I. Ahmed, S. Dixon, N. Vasdev, L. Goodwin, J. Mcgrath, P. Charlesworth, E. Rowe, A. Koupparis, C. Brew-Graves, J.D. Kelly
Journal: European Urology (2021)
Early melanoma invasivity correlates with gut fungal and bacterial profiles
Authors: F. Vitali, R. Colucci, M. Di Paola, M. Pindo, C. De Filippo, S. Moretti, D. Cavalieri
Journal: British Journal of Dermatology (2021)

Summary Background The microbiome is emerging as a crucial player of the immune checkpoint in cancer. Melanoma is a highly immunogenic tumour, and the composition of the gut microbiome has been correlated to prognosis and evolution of advanced melanoma and proposed as a biomarker for immune checkpoint therapy. Objectives We investigated the gut fungal and bacterial compositions in early-stage melanoma and correlated microbial profiles with histopathological features. Methods Sequencing of bacterial 16S rRNA and the fungal internal transcribed spacer region was performed on faecal samples of patients with stage I and II melanoma, and healthy controls. A meta-analysis with gut microbiota data from patients with metastatic melanoma was also carried out. Results We found a combination of gut fungal and bacterial profiles significantly discriminating patients with melanoma from controls. In patients with melanoma, we observed an abundance of Prevotella copri and yeasts belonging to the order Saccharomycetales. We found that the bacterial and fungal community correlated to melanoma invasiveness, whereas the specific fungal profile correlated to melanoma regression. Bacteroides was identified as general marker of immunogenicity, being shared by regressive and invasive melanoma. In addition, the bacterial communities in patients with stage I and II melanoma were different in structure and richer than those from patients with metastatic melanoma. Conclusions The composition of the gut microbiota in early-stage melanoma changes along the gradient from in situ to invasive (and metastatic) melanoma. Changes in the microbiota and mycobiota are correlated to the histological features of early-stage melanoma, and to the clinical course and response to immune therapies of advanced-stage melanoma, through direct or indirect immunomodulation.
Abstract 1789: Triggering anti-tumor immunity by overexpressing of MAVS in combination with PD-L1 ICB in immune insensitive colorectal cancers
Authors: Bin-Jin Hwang
Journal: Cancer Research (2021)

Abstract While the use of immune checkpoint blockade (ICB) has gained significant traction as a viable therapy for cancers, many more cancers remain refractory to these immunotherapies due to their highly immunosuppressive tumor microenvironment (TME). From both the earlier published report and our analysis of clinical cohorts of colorectal cancer, we found that the expression of MAVS (Mitochondrial Antiviral Signaling Protein) was significantly reduced. Because MAVS are known to play a key role in the initiation of anti-viral innate immunity, we hypothesized that MAVS may be critical in anti-tumor immune response and tumor cells are under evolutionary pressure to reduce MAVS expression. As such, the stimulation of the MAVS pathway in tumor cells may be a necessary precursor to trigger anti-tumor immune response and reverse local immunosuppressive TME. To circumvent issues associated with intracellular double stranded RNA ligand stimulation, we exploited the ability of MAVS to constitutively polymerize and elicit broad downstream interferon signaling through an overexpression strategy. This approach provided a novel genetic mean to elicit ligand free innate immune signaling in the TME, which we found to elicit robust stimulation of multiple interferon genes. Overexpression of MAVS in colorectal cell lines stimulated significant anti-tumors responses in vivo, which we found to be primarily mediated through the induction of tumor antigen-specific adaptive immunity. Utilizing viral vectors overexpressing MAVS, we demonstrate significant induction of interferon responses among different types of tumor cells and different types of cells in the tumor microenvironment. Intra-lesional injection of tumors using these vectors elicited profound anti-tumor responses against primary tumors, as well as, an abscopal effect against syngeneic implanted tumors. Overexpression of MAVS also stimulated the expression of PD-L1 as an immunosuppressive feedback mechanism due to stimulation of the MAVS pathway. As such, we tested the combination of MAVS overexpression and PD-L1 ICB in colorectal cancers and found that this combination allowed for significantly improved anti-tumor immunity. In conclusion, our findings suggest that a combination of MAVS cancer gene therapy and ICB may offer an alternative approach to activate immunity in "immunologically cold" tumors. Citation Format: Bin-Jin Hwang. Triggering anti-tumor immunity by overexpressing of MAVS in combination with PD-L1 ICB in immune insensitive colorectal cancers [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 1789.
Evaluation and comparison of scoring systems for predicting stone-free status after flexible ureteroscopy for renal and ureteral stones
Authors: M.H. Saadi, M. Bibi, Y. Ouanes, S. Ben Rhouma, W. Zakhama, Y. Bedoui, R. Boulma, H. Khouni, Y. Binous, Y. Nouira
Journal: European Urology (2021)
Outcomes after introducing intraoperative NeuroSAFE technique in robot-assisted radical prostatectomy
Authors: M.A. van der Slot, M.A. Den Bakker, C.F. Kweldam, S. Remmers, T. Tan, O.S. Klaver, M. Kliffen, M.B. Busstra, J.B.W. Rietbergen, M. Gan, K.E. Hamoen, L.M. Budel, N.T. Goemaere, C.H. Bangma, J. Helleman, M.J. Roobol, G.J.L.H. Van Leenders
Journal: European Urology (2021)
Abstract 2156: Genomics and molecular analysis of Aurora kinase B (AURKB) in response to antiretroviral (ARV) treatment in lung cancer
Authors: Rahaba Makgotso Marima, Rodney Hull, Zodwa Dlamini, Clement Penny
Journal: Cancer Research (2021)

Abstract Aurora kinase B (AURKB) is essential for normal physiological processes. However, aberrant AURKB expression has been reported in various cancers, including lung cancer. Lung cancer is a leading non-AIDS defining cancer (NADCs) and the relationship between the use of antiretrovirals (ARVs) and lung cancer is poorly understood. The anti-proliferative effects of Efavirenz (EFV) and Lopinavir/ritonavir (LPV/r) have also been documented. This study aimed at determining the genomic and molecular roles of AURKB in lung cancer in response to ARV treatment. For this purpose, cellular (xCELLigence RTCA), molecular (RT-qPCR) and bioinformatics tools were used in normal fibroblasts (MRC-5) and adenocarcinoma (A549) lung cells. Real-Time Cell Analysis (RTCA) data confirmed the anti-proliferative effects of ARVs in a time-dependent manner. AURKB gene expression was elevated in A549 compared to MRC-5 in non-ARV treated. Interestingly, p53 and CASP3 gene expression was downregulated. Contrarily, ARV treatment resulted in the formation of a negative signaling loop due to AURKB being downregulated, while CASP3 and p53 were upregulated. KEGG analysis demonstrated AURKB, CASP3 and p53 as cell cycle related genes. STRING database searches showed a strong protein-protein interaction (PPI) between AURKB and p53, and CAP3 and p53, but a weak PPI between AURKB and CASP3. Gene Ontology (GO) analysis revealed a decline in serine/threonine kinase (AURKB) activity in cancer cells in response to ARV treatment. Although not yet confirmed, AURKB displays oncogene features, while its overexpression has been shown to deregulate p53. The association between the use of ARVs and lung carcinogenesis remains to be fully comprehended and targeting AURKB signaling may help shed light on this relationship. Citation Format: Rahaba Makgotso Marima, Rodney Hull, Zodwa Dlamini, Clement Penny. Genomics and molecular analysis of Aurora kinase B (AURKB) in response to antiretroviral (ARV) treatment in lung cancer [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 2156.
Intravesical chemohyperthermia versus bacillus calmette-guerin instillation for intermediate- and high-risk non-muscle invasive bladder cancer: A systematic review and meta-analysis
Authors: H. Zhao, V.W. Chan, D. Castellani, E.O. Chan, W.L.K. Ong, Q. Peng, M. Moschini, W. Krajewski, B. Pradere, C. Ng, D. Enikeev, N. Vasdev, G. Ekin, A. Sousa, J. Leon, F. Guerrero-Ramos, W. Tan, J. Kelly, S.F. Shariat, J. Witjes, J.Y.. Teoh
Journal: European Urology (2021)
Bone Marrow Microenvironment Induces Genomic Instability and Enables Clonal Evolution in Multiple Myeloma
Authors: Tommaso Perini, Raphael Szalat, Mariateresa Fulciniti, Mehmet Kemal Samur, Michael A Lopez, Puru Nanjappa, Kenneth Wen, Na Li, Yan Xu, Yu-Tzu Tai, Masood A. Shammas, Kenneth C Anderson, Fabio Ciceri, Nikhil Munshi
Journal: Blood (2017)
Super-selective Ischemia in robotic partial nephrectomy does not provide better long-term renal function than renal artery clamping in a randomized controlled trial: Why bother and take risks?
Authors: J.A. Long, C. Lanchon, J. Giai, A. Moreau-Gaudry, Y. Teyssier, C. Overs, J. Rambeaud, G. Fiard, J.L. Descotes
Journal: European Urology (2021)
Postoperative Endophthalmitis in Immediate Sequential Bilateral Cataract Surgery
Authors: Emma Friling, Björn Johansson, Mats Lundström, Per Montan
Journal: Ophthalmology (2021)

PurposeTo report the incidence of postoperative endophthalmitis (PE) after immediate sequential bilateral cataract surgery (ISBCS) in Sweden.DesignRetrospective cohort registry study.ParticipantsPatient data from 1 457 172 cataract extractions, including 1 364 934 unilateral surgeries and 92 238 ISBCSs.MethodsEndophthalmitis cases reported to the Swedish National Cataract Register (NCR) during a 16-year period (2002–2017) were analyzed in comparison to all control cases with regard to patient characteristics, surgical technique, and capsule complication.Main Outcome MeasureIncidence and determinants for PE in ISBCS compared with unilateral surgeries.ResultsA total of 422 cases of PE were identified in 1 457 172 cataract extractions, yielding an overall incidence of 0.029% (95% confidence interval [CI], 0.0262–0.0317). For unilateral procedures, the rate was 0.0299% (95% CI, 0.0270–0.0328) or 408 cases in 1 364 934 operations, whereas that for ISBCS was 0.0152% (95% CI, 0.0072–0.0231) or 14 incidents in 92 238 operations (P = 0.01). In a logistic regression model including all cataract procedures, nonuse of intracameral (IC) antibiotics (ABs), capsule complication, age 85 years or more, male gender, and ocular comorbidity were found to be independent risk factors for PE. All these parameters were less frequent in ISBCS. Notwithstanding, in the same multivariate analysis, ISBCS in itself was associated with a significantly lower risk for PE. At follow-up, 5 of the 14 PE cases in the ISBCS cohort had a visual acuity (VA) of 20/200 or worse. Of these, one 93-year-old ISBCS patient developed bilateral infection.ConclusionsAfter ISBCS in Sweden, PE occurred once in 6600 surgeries. The risk of sustaining a final VA of 20/200 or less was 1 incident in 18 000 operated eyes. When counseling potential ISBCS patients about the risk of PE, it seems reasonable to state that the reported risk in the literature is lower than that with unilateral surgery but not negligible. Precautions remain necessary.
Deep transfer learning and data augmentation improve glucose levels prediction in type 2 diabetes patients
Authors: Yixiang Deng, Lu Lu, Laura Aponte, Angeliki M. Angelidi, Vera Novak, George Em Karniadakis, Christos S. Mantzoros
Journal: npj Digital Medicine (2021)

Accurate prediction of blood glucose variations in type 2 diabetes (T2D) will facilitate better glycemic control and decrease the occurrence of hypoglycemic episodes as well as the morbidity and mortality associated with T2D, hence increasing the quality of life of patients. Owing to the complexity of the blood glucose dynamics, it is difficult to design accurate predictive models in every circumstance, i.e., hypo/normo/hyperglycemic events. We developed deep-learning methods to predict patient-specific blood glucose during various time horizons in the immediate future using patient-specific every 30-min long glucose measurements by the continuous glucose monitoring (CGM) to predict future glucose levels in 5 min to 1 h. In general, the major challenges to address are (1) the dataset of each patient is often too small to train a patient-specific deep-learning model, and (2) the dataset is usually highly imbalanced given that hypo- and hyperglycemic episodes are usually much less common than normoglycemia. We tackle these two challenges using transfer learning and data augmentation, respectively. We systematically examined three neural network architectures, different loss functions, four transfer-learning strategies, and four data augmentation techniques, including mixup and generative models. Taken together, utilizing these methodologies we achieved over 95% prediction accuracy and 90% sensitivity for a time period within the clinically useful 1 h prediction horizon that would allow a patient to react and correct either hypoglycemia and/or hyperglycemia. We have also demonstrated that the same network architecture and transfer-learning methods perform well for the type 1 diabetes OhioT1DM public dataset.
Abstract 2466: Stochastic loss of GLUL expression correlates with STK11-loss-dependent glutamine addiction and may impact anti-PD1 therapy resistance in NSCLC
Authors: Sean M. Lenahan, Hailey M. Sarausky, David Joseph Seward
Journal: Cancer Research (2021)

Abstract Our work aims to delineate the molecular interactions linking somatic disruption of Serine-Threonine Kinase 11 (STK11) with anti-PD1 therapy resistance in KRAS-driven lung adenocarcinoma (LUAD). Data presented here suggests glutamine synthetase (GLUL) may modulate this phenotype. Immune checkpoint inhibitors (ICIs), including anti-PD1 monoclonal antibody therapy, represent a promising therapeutic option for non-small cell lung cancer (NSCLC) patients. Unfortunately, efficient use of these drugs is hampered by an inability to accurately predict which patients will respond. Clinical observations have correlated anti-PD1 therapy resistance in KRAS-driven LUAD with somatic STK11 disruption, but the mechanism(s) responsible remains unknown. To investigate this connection we knocked out STK11 in three different human KRAS-driven LUAD cell lines and performed RNA-seq analysis to identify STK11-loss-dependent differentially expressed genes. Intriguingly, GLUL expression was reproducibly lost in a subset of KRAS-driven/STK11 null clones across two different human lung adenocarcinoma cell lines. GLUL is an enzyme that converts glutamate to glutamine. Glutamine is a critical metabolite supplying carbon and nitrogen necessary for amino acid, nucleotide, and lipid synthesis. Additionally, glutamine plays an important role in redox homeostasis, chromatin organization, and intra-tumoral signaling. Glutamine dependency is a common phenotype across many solid tumor types, and has previously been linked with STK11-deficiency in the context of polycystic kidney disease. Our current work suggests loss of GLUL expression correlates with an altered tumor-intrinsic response to nutrient stress in KRAS-driven LUAD culminating in immune evasion and anti-PD1 therapy resistance. Ongoing experiments aimed to define the relationship between STK11 loss and GLUL expression suggest this phenomenon is stochastic in nature and may provide tumor cells with a selective advantage. In conclusion, understanding the biology underlying the molecular connection between STK11 and GLUL may reveal reliable biomarkers for anti-PD1 therapy response and suggest a method for restoring sensitivity to current therapies. Citation Format: Sean M. Lenahan, Hailey M. Sarausky, David Joseph Seward. Stochastic loss of GLUL expression correlates with STK11-loss-dependent glutamine addiction and may impact anti-PD1 therapy resistance in NSCLC [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 2466.
Presentation of endogenous antigen to MHC class II restricted T cells is independent of transporters associated with antigen processing (TAP)
Authors: Samudra K. Dissanayake, Natalia T. Tuera, Cordula Davis, Suzanne Ostrand-Rosenberg
Journal: Cancer Research (2004)

1258  Proteins involved in Class I MHC (MHC I) Ag processing such as Transporters Associated with Antigen Processing (TAP) are deficient in some tumor cells. Loss of TAP function leads to decreased cell surface expression of MHC I and the inability to activate CD8+ T lymphocytes. This may enable tumors and virus infected cells to escape immune surveillance. Since some endogenous protein-derived peptides are known to be class II MHC (MHC II) restricted, and are capable of activating CD4+ T lymphocytes, we examined the role of TAP in translocating endogenously synthesized peptides for loading onto MHC class II molecules. To address this issue, we have used matched panels of TAP-negative and TAP-positive tumor lines (the TAP2 negative B78H1 melanoma and its TAP2 transfected counterpart B78H1/TAP). We genetically modified B78H1, and B78H1/TAP cells to express MHC class II genes and a model antigen hen egg lysozyme (HEL). As measured by flow cytometry, transfected cells express high levels of cell surface MHC II I-Ak and internal HEL . Western blots show SDS stable MHC class II heterodimers in the absence of Ii. To examine if TAP was essential for processing and presenting HEL via MHC II, I-Ak+HEL+ B78H1 and B78H1/TAP cells were tested for their ability to activate four I-Ak restricted, HEL-specific CD4+ hybridomas in an in vitro antigen presentation assay. Our results show that I-Ak-restricted endogenous HEL peptide presentation occurred in TAP2 negative cells at levels equal to TAP positive cells for all hybridomas tested. Experiments using ammonium chloride to block the endosomal pathway indicate that antigen presentation depends on the endocytic pathway. We are currently using inhibitors of the proteosome to see if it plays a role in producing the peptides that bind to MHC class II molecules. The role of autophagy is also being tested. Collectively our data indicate that presentation of endogenous antigen via MHC II does not require a functional TAP complex and is dependent on the endosomal pathway.