tbuckley/cabot-search huggingface dataset:
Updated results of TRIBE2, a phase III, randomized strategy study by GONO in the 1st- and 2nd-line treatment of unresectable mCRC
Authors: C. Cremolini, C. Antoniotti, S. Lonardi, D. Rossini, F. Morano, S. Cordio, F. Bergamo, F. Marmorino, E. Maiello, A. Passardi, G. Masi, E. Tamburini, D. Santini, R. Grande, A. Zaniboni, C. Granetto, S. Murgioni, G. Aprile, L. Delliponti, L. Boni, A. Falcone
Journal: Annals of Oncology (2019)
Abstract 2929: Radiosensitization of head and neck cancer by FGFR inhibition
Authors: Gopika SenthilKumar, Margot Miller, Michael Fisher, Sean Brennan, Saakshi Kaushik, Lindsey Able, Paul M. Harari, Gopal Iyer, Randall J. Kimple, Andrew M. Baschnagel
Journal: Cancer Research (2019)

Abstract Objective: Fibroblast growth factor receptors are frequently amplified or overexpressed in head and neck squamous cell carcinomas (HNSCC). We assessed the potential of a selective FGFR-kinase inhibitor, AZD4547, to act as a radiosensitizer in head and neck cancer cell lines and xenografts. Methods: A panel of head and neck cancer (n=10) and normal oral mucosa (HTE) cell lines were screened for FGFR1, 2, and 3 gene copy number, RNA expression, and protein. Sensitivity to the FGFR inhibitor AZD4547, alone or in combination with radiation, was assessed using proliferation and clonogenic survival assays. Putative mechanisms of radiosensitization were investigated by immunoblot and by assessing for DNA repair capacity, cell cycle effects, apoptosis, senescence, and autophagy. Tumor response of cell line xenografts and patient derived xenografts was assessed in vivo. Results: Cells demonstrated varying responses to FGFR inhibition but this did not correlate with FGFR gene copy number, mRNA expression, or protein expression. Three cell lines which responded to AZD4547 alone (CCL30, Tu-138, and SCC6) were selected for further investigation. TU-138 and CCL30 featured high FGFR expression and were radiosensitized by AZD4547 in vitro. SCC6 was not. Cell lines which were insensitive to FGFR inhibition (including HTE) did not demonstrate radiosensitization by AZD4547. In the sensitive cell lines, enhanced p-MAPK inhibition was seen in a time-dependent manner following drug treatment. When added to radiation, AZD4547 resulted in increased apoptosis, autophagy, and senescence but did not alter the kinetics of DNA repair as assessed by resolution of gH2AX foci. No difference in the cell cycle distribution for irradiated cells treated with or without the addition of AZD4547 was seen. Treatment of two in vivo tumor xenografts with AZD4547 and radiation showed significant delay in tumor growth compared to treatment with radiation or drug alone. Conclusion: Our findings indicate that AZD4547 can augment the response of FGFR expressing HNSCC to radiation both in vitro and in vivo. Improved approaches to identify tumors most likely to benefit from FGFR inhibition could enable the selection of patients for combination therapy and has the potential to improve outcomes in these difficult to treat cancers. Citation Format: Gopika SenthilKumar, Margot Miller, Michael Fisher, Sean Brennan, Saakshi Kaushik, Lindsey Able, Paul M. Harari, Gopal Iyer, Randall J. Kimple, Andrew M. Baschnagel. Radiosensitization of head and neck cancer by FGFR inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2929.
Automated characterization of noise distributions in diffusion MRI data
Authors: Samuel St-Jean, Alberto De Luca, Chantal M.W. Tax, Max A. Viergever, Alexander Leemans
Journal: Medical Image Analysis (2020)

Knowledge of the noise distribution in magnitude diffusion MRI images is the centerpiece to quantify uncertainties arising from the acquisition process. The use of parallel imaging methods, the number of receiver coils and imaging filters applied by the scanner, amongst other factors, dictate the resulting signal distribution. Accurate estimation beyond textbook Rician or noncentral chi distributions often requires information about the acquisition process (e.g., coils sensitivity maps or reconstruction coefficients), which is usually not available. We introduce two new automated methods using the moments and maximum likelihood equations of the Gamma distribution to estimate noise distributions as they explicitly depend on the number of coils, making it possible to estimate all unknown parameters using only the magnitude data. A rejection step is used to make the framework automatic and robust to artifacts. Simulations using stationary and spatially varying noncentral chi noise distributions were created for two diffusion weightings with SENSE or GRAPPA reconstruction and 8, 12 or 32 receiver coils. Furthermore, MRI data of a water phantom with different combinations of parallel imaging were acquired on a 3T Philips scanner along with noise-only measurements. Finally, experiments on freely available datasets from a single subject acquired on a 3T GE scanner are used to assess reproducibility when limited information about the acquisition protocol is available. Additionally, we demonstrated the applicability of the proposed methods for a bias correction and denoising task on an in vivo dataset acquired on a 3T Siemens scanner. A generalized version of the bias correction framework for non integer degrees of freedom is also introduced. The proposed framework is compared with three other algorithms with datasets from three vendors, employing different reconstruction methods. Simulations showed that assuming a Rician distribution can lead to misestimation of the noise distribution in parallel imaging. Results on the acquired datasets showed that signal leakage in multiband can also lead to a misestimation of the noise distribution. Repeated acquisitions of in vivo datasets show that the estimated parameters are stable and have lower variability than compared methods. Results for the bias correction and denoising task show that the proposed methods reduce the appearance of noise at high b-value. The proposed algorithms herein can estimate both parameters of the noise distribution automatically, are robust to signal leakage artifacts and perform best when used on acquired noise maps.
Abstract 13422: Early Peritoneal Dialysis and Major Adverse Events After Paediatric Cardiac Surgery: A Propensity Score Analysis
Authors: Siva Namachivayam, Warwick Butt, Johnny Millar, Cattram Nguyen, Igor Konstantinov, Yves d’Udekem
Journal: Circulation (2018)

Introduction: Early peritoneal dialysis (PD) may have a role in modulating the inflammatory response after cardiopulmonary bypass (CPB). The aim of this study was to test the effect of early PD on ...
Locally advanced unresectable or metastatic pancreatic adenocarcinoma in patients under 65 years with good performance status (PS) at Ramón y Cajal University Hospital in Madrid
Authors: R. Martín Huertas, F. Longo Muñoz, J. Serrano Domingo, E. Corral de la Fuente, V. Pachón Olmos, M. Rodriguez Garrote, R. Fuentes, R. Ferreiro Monteagudo, M. Vaz, A. Carrato
Journal: Annals of Oncology (2019)
Caplacizumab Therapy without Plasma Exchange for Acquired Thrombotic Thrombocytopenic Purpura
Authors: Deepak P Chander, Michelle M Loch, Spero R Cataland, James N George
Journal: New England Journal of Medicine (2019)

Managing Acquired TTP without Plasma Exchange A case of acquired thrombotic thrombocytopenic purpura is reported in a Jehovah’s Witness who had neurologic manifestations but would not accept plasma...
Abstract 20298: Validation of the BASIL, FINNVASC and PREVENT Models for the Prediction of Post-Intervention Outcomes in Critical Limb Ischemia
Authors: Joep G Wijnand, Ian D van Koeverden, Martin Teraa, Marlon I Spreen, Gerard Pasterkamp, Gert J de Borst, Hendrik Gremmels, Marianne C Verhaar
Journal: Circulation (2017)

Background: Critical limb ischemia (CLI) represents the most severe form of peripheral artery disease (PAD) and has an immense impact on quality of life, morbidity and mortality. Interventions aim ...
Comparison of the Impact Factors of the Most-Cited Cardiovascular Journals
Authors: Tobias Opthof
Journal: Circulation Research (2019)

In this article, I show that the distribution of citations to papers published by the top 30 journals in the category Cardiac & Cardiovascular Systems of the Web of Science is extremely skewed. This skewness is to the right, which means that there is a long tail of papers that are cited much more frequently than the other papers of the same journal. The consequence is that there is a large difference between the mean and the median of the citation of the papers published by the journals. I further found that there are no differences between the citation distributions of the top 4 journals European Heart Journal, Circulation, Journal of the American College of Cardiology, and Circulation Research. Despite the fact that the journal impact factor (IF) varied between 23.425 for Eur Heart J and 15.211 for Circ Res with the other 2 journals in between, the median citation of their articles plus reviews (IF Median) was 10 for all 4 journals. Given the fact that their citation distributions were similar, it is obvious that an indicator (IF Median) that reflects this similarity must be superior to the classical journal impact factor, which may indicate a nonexisting difference. It is underscored that the IF Median is substantially lower than the journal impact factor for all 30 journals under consideration in this article. Finally, the IF Median has the additional advantage that there is no artificial ranking of 128 journals in the category but rather an attribution of journals to a limited number of classes with comparable impact.
Abstract 2769: A squalene epoxidase-cholesterolaxis drives colorectal cancer progression and metastatic dissemination
Authors: Soo Young Jun, Andrew J. Brown, Ji-Yong Yoon, Jeong-Ju Lee, Ngee Kiat Chua, Jin OK Yang, Ju-Sik Min, Insu Jang, Su-Jin Jeon, Min-Hyuk Choi, Tae-Ik Choi, Cheol-Hee Kim, Nam-Soon Kim
Journal: Cancer Research (2019)

Abstract Links between cholesterol and cancer are well-documented, but the mechanisms remain unclear. Squalene epoxidase (SQLE), a key enzyme in cholesterol biosynthesis degraded by excess cholesterol, is suggested as a proto-oncogene. Paradoxically, we found reduced SQLE in aggressive colorectal cancer (CRC); low SQLE being associated with a shortened survival of CRC patients. This was confirmed in a spontaneous CRC metastasis mouse model where SL-15 reduction, by either a high-cholesterol regimen or genetic knockdown, strikingly promotes CRC aggressiveness through the production of migratory cancer stem cells. Experiments in CRC cell-lines demonstrated that SQLE reduction helps overcome constraints for malignant transformation. Specifically, we uncovered a surprising interaction of SQLE with GSK3β and p53. Depletion of SQLE disrupted the GSK3β/p53 complex, resulting in a metastatic phenotype. Our findings provide mechanistic insights into the link between cholesterol and CRC, identifying SQLE as a key regulator in CRC progression and potentially a biomarker for risk assessment. Citation Format: Soo Young Jun, Andrew J. Brown, Ji-Yong Yoon, Jeong-Ju Lee, Ngee Kiat Chua, Jin OK Yang, Ju-Sik Min, Insu Jang, Su-Jin Jeon, Min-Hyuk Choi, Tae-Ik Choi, Cheol-Hee Kim, Nam-Soon Kim. A squalene epoxidase-cholesterolaxis drives colorectal cancer progression and metastatic dissemination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2769.
Abstract 17647: The Effect of Cumulative Burden of Blood Pressure on Cardiovascular Risk: Analysis of 23 Years of Ambulatory Blood Pressure Monitoring Data From GSH Cohort
Authors: Guang Hao, Xiaoling Wang, Frank Treiber, Gregory Harshfield, Gaston Kapuku, Shaoyong Su
Journal: Circulation (2017)

Background: Ambulatory blood pressure (BP) is considered more accurately reflect an individual's BP outside the physician's office and more representative of cumulative pressure exposure than is of...
Abstract 1424: Preclinical development of TAC01-CD19, a CD19 specific T-cell Antigen Coupler (TAC) therapy for the treatment of CD19-positive B cell malignancies
Authors: Christopher W. Helsen, Danielle Hayes, Joanne Hammill, Criag Aarts, Andreas Bader, Donna Rill, Jonathan Bramson
Journal: Cancer Research (2019)

Abstract Background: The T cell antigen coupler (TAC) is a chimeric receptor co-opting the natural TCR receptor signaling complex to target tumor antigens in an MHC-independent manner (Helsen et. al., Nat. Comm. 2018). TAC engineered T cells mediate biological effects that are distinct from conventional chimeric antigen receptors (CARs) and may offer safety advantages due to greater target selectivity and no detectable off-target toxicity. Here, we present preclinical data of TAC01-CD19, an autologous CD19-specific TAC-T cell product candidate for clinical testing in patients with CD19-positive B cell malignancies Materials and Methods: T cells from healthy donors and lymphoma patients were engineered with a CD19-specific TAC using lentivirus. Anti-tumor activity, T cell expansion and persistence were measured in the CD19-positive NALM-6 and Jeko-1 mouse tumor xenograft models. We used flow cytometry to determine surface expression of CD19-TAC, cytokine production and in vitro T cell proliferation. Cytotoxicity was evaluated in vitro using luciferase-based killing assay. Results: Cytotoxicity was measured against multiple CD19 positive tumors cells (NALM6/Jeko-1/Raji) showing strong cytotoxicity in all cases. Treatment of established NALM-6 (acute lymphoblastic leukemia) and Jeko-1 xenografts (mantle cell lymphoma) with CD19 TAC-T cells resulted in clearance of tumors within a few weeks of T cell infusion. In vivo efficacy was tested across multiple donors, establishing consistent and reproducible anti-tumor efficacy. Monitoring of TAC T cells post-infusion revealed robust expansion that peaked in the peripheral blood 1-2 weeks post-infusion. Mice that cleared tumors following TAC-T cell treatment were resistant to subsequent challenge with fresh tumor cells demonstrating persistence of TAC-T cells. In contrast, treatment with control TAC-T had no impact on tumor growth. A histological examination of normal mouse tissues failed to detect TAC-T cell induced toxicity. Conclusion: The pre-clinical evaluation of TAC01-CD19 has demonstrated specific anti-tumor responses without signs of toxicity. Results were reproducible across multiple donors demonstrating the robustness of the CD19 TAC system. TAC01-CD19 is expected to enter clinical testing in patients with CD19-positive hematological malignancies in Q2 2019. Citation Format: Christopher W. Helsen, Danielle Hayes, Joanne Hammill, Criag Aarts, Andreas Bader, Donna Rill, Jonathan Bramson. Preclinical development of TAC01-CD19, a CD19 specific T-cell Antigen Coupler (TAC) therapy for the treatment of CD19-positive B cell malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1424.
Abstract 2540: Mitotic Golgi vesiculation enables human papillomavirus to evade cGAS/STING
Authors: Brittany L. Forte, Shauna M. Bratton, Samuel K. Campos
Journal: Cancer Research (2019)

Abstract Oncogenic human papillomaviruses (HPVs) infect and replicate in differentiating mucosal epithelium, causing 5% of cancers worldwide and essentially all cervical cancers. During infection, HPV must traffic viral genome (vDNA) to the nuclei of basal keratinocytes. Minor capsid protein L2 facilitates intracellular transport of vDNA to the Golgi; upon mitosis, the L2-vDNA complex penetrates limiting membranes and localizes to mitotic chromosomes, ensuring infection of both daughter cells. Cytosolic DNA sensor cGAS recognizes cytosolic dsDNA and produces second messenger cGAMP; cGAMP causes activation and relocalization of ER-resident STING to the Golgi, where it recruits TBK1 to phosphorylate and activate IRF3, initiating a type-I IFN response. The cGAS/STING pathway is assumed, though never demonstrated, to be inactive during mitosis to avoid detecting self-DNA. Since the Golgi is a platform for STING/TBK1/IRF3 recruitment and activation, we hypothesize natural Golgi dispersal deactivates cGAS/STING during mitosis. Further, we hypothesize HPV has evolved to traffic to and translocate from the mitotic Golgi as an immunoevasive tactic to avoid detection by cGAS/STING during mitosis. HaCaTs, a human keratinocyte line, were transfected with DNA or infected with HPV pseudovirions and analyzed for cGAS/STING activation. DNA transfection resulted in IRF3 phosphorylation and nuclear translocation, and STING translocation to the Golgi, indicating cGAS/STING activity. Strikingly, chemical disruption of the Golgi ribbon potently blocked IRF3 activation in response to foreign DNA, suggesting Golgi morphology might modulate cGAS/STING activity during mitosis. In accordance, DNA-dependent IRF3 phosphorylation was transiently reduced in synchronized mitotic cells, but chemical impairment of mitotic Golgi vesiculation enabled cGAS/STING activation, even without foreign DNA transfection. Further, HPV infection resulted in minimal IRF3 phosphorylation, indicating HPV can efficiently evade detection during initial infection. To determine if HPV’s unique trafficking enables evasion, we used cationic liposomes to permit premature virion translocation across limiting membranes. Such treatment renders a non-infectious, translocation-defective mutant HPV infectious, yet susceptible to cGAS/STING sensing. Overall, the cGAS/STING pathway may be inactivated by mitotic Golgi dispersal, allowing HPV to evade detection during mitosis. Citation Format: Brittany L. Forte, Shauna M. Bratton, Samuel K. Campos. Mitotic Golgi vesiculation enables human papillomavirus to evade cGAS/STING [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2540.
Abstract 512: Adrenergic modulation of inflammatory cytokines in ovarian cancer
Authors: Claudia B. Colon-Echevarria, Tatiana Ortiz, Lizette Maldonado-Laboy, Melanie J. Hidalgo-Vargas, Alexandra N. Aquino, Guillermo N. Armaiz-Pena
Journal: Cancer Research (2019)

Abstract Work from our group and others suggest that chronic stress accelerates growth of existing tumors by activating the sympathetic nervous system. Specifically, our data suggest that sustained adrenergic signaling can induce tumor growth, secretion of pro-inflammatory cytokines and macrophage infiltration. Moreover, increased macrophage infiltration was associated with decreased survival in ovarian cancer patients. Hence, we investigated role of adrenergic-stimulated macrophages in ovarian cancer biology. To assess the effect of adrenergic stimulation in pro-tumoral functional outputs, we used cytokine arrays and invasion assays. A pre-clinical orthotopic model of ovarian cancer was used to assess the in vivo effect of daily restraint stress on tumor growth and adrenergic-induced macrophages. Cytokine array analyses showed that adrenergic stimulation modulated pro-inflammatory cytokine secretion in a SKOV3ip1 (ovarian cancer cells) /U937 (macrophages) co-culture system. Among these, 23 significantly upregulated cytokines were identified in both, epinephrine and norepinephrine, treated co-culture systems. PDGF-AA, ENA-78, Angiogenin, VEGF, GM-CSF, IL-5, Lipocalin-2, MIF, and TfR were among upregulated cytokines shared between treatment groups. In addition, daily restraint stress resulted in increased ovarian cancer growth and infiltration of CD68+ macrophages in two orthotopic models of ovarian cancer (SKOV3ip1 and HeyA8), while zoledronic acid (a bisphosphonate that has been shown to impair macrophage activity) abrogated this effect. Immunohistochemistry analyses showed restraint stress increased expression of PDGF-AA and ENA-78 inflammatory cytokines. Here, we show that adrenergic regulation of macrophages might play a key role in the progression of ovarian cancer. Citation Format: Claudia B. Colon-Echevarria, Tatiana Ortiz, Lizette Maldonado-Laboy, Melanie J. Hidalgo-Vargas, Alexandra N. Aquino, Guillermo N. Armaiz-Pena. Adrenergic modulation of inflammatory cytokines in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 512.
Anemia predicts lower white matter volume and cognitive performance in sickle and non‐sickle cell anemia syndrome
Authors: Soyoung Choi, Sharon H. O'Neil, Anand A. Joshi, Jian Li, Adam M. Bush, Thomas D. Coates, Richard M. Leahy, John C. Wood
Journal: American Journal of Hematology (2019)

Abstract Severe chronic anemia is an independent predictor of overt stroke, white matter damage, and cognitive dysfunction in the elderly. Severe anemia also predisposes to white matter strokes in young children, independent of the anemia subtype. We previously demonstrated symmetrically decreased white matter (WM) volumes in patients with sickle cell disease (SCD). In the current study, we investigated whether patients with non‐sickle anemia also have lower WM volumes and cognitive dysfunction. Magnetic Resonance Imaging was performed on 52 clinically asymptomatic SCD patients (age = 21.4 ± 7.7; F = 27, M = 25; hemoglobin = 9.6 ± 1.6 g/dL), 26 non‐sickle anemic patients (age = 23.9 ± 7.9; F = 14, M = 12; hemoglobin = 10.8 ± 2.5 g/dL) and 40 control subjects (age = 27.7 ± 11.3; F = 28, M = 12; hemoglobin = 13.4 ± 1.3 g/dL). Voxel‐wise changes in WM brain volumes were compared to hemoglobin levels to identify brain regions that are vulnerable to anemia. White matter volume was diffusely lower in deep, watershed areas proportionally to anemia severity. After controlling for age, sex, and hemoglobin level, brain volumes were independent of disease. WM volume loss was associated with lower Full Scale Intelligence Quotient (FSIQ; P = .0048; r 2 = .18) and an abnormal burden of silent cerebral infarctions ( P = .029) in males, but not in females. Hemoglobin count and cognitive measures were similar between subjects with and without white‐matter hyperintensities. The spatial distribution of volume loss suggests chronic hypoxic cerebrovascular injury, despite compensatory hyperemia. Neurocognitive consequences of WM volume changes and silent cerebral infarction were strongly sexually dimorphic. Understanding the possible neurological consequences of chronic anemia may help inform our current clinical practices.