tbuckley/cabot-search huggingface dataset:
Abstract A15: Noncanonical NF-kappaB signaling is associated with poor ovarian cancer prognosis
Authors: Demetra Hufnagel, Andrew J. Wilson, Jamie Saxon, Dineo Khabele, Timothy Blackwell, Marta A. Crispens, Fiona Yull, Alicia Beeghly-Fadiel
Journal: Clinical Cancer Research (2020)

Abstract Objective: Mediated by a family of transcription factors, the canonical and noncanonical nuclear factor-kappaB (NF-kB) signaling pathways have key roles in inflammation, innate immunity, and cancer development and progression. As prior ovarian cancer studies have evaluated only canonical NF-kB transcription factors in relation to survival, this study was undertaken to evaluate both canonical and noncanonical NF-kB pathway components in tumor samples from epithelial ovarian cancer cases from the Vanderbilt Tissue Repository for Ovarian Cancer (TROC). Methods: We abstracted clinical data from electronic medical records and assayed p65 (representing the canonical NF-kB pathway) and p52 (representing the noncanonical NF-kB pathway) by immunohistochemistry for 197 TROC samples. Nuclear and cytoplasmic staining in tumor cells was semiquantified by H-scores and dichotomized at median values. Associations with progression-free survival (PFS) and overall survival (OS) were quantified by hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional-hazards regression. Results: Median cytoplasmic and nuclear p65 and p52 H-scores were significantly higher among high-grade and serous cases; median p52 H-scores were also significantly higher among late-stage cases and patients treated with chemotherapy (all Wilcoxon rank sum p&amp;lt;0.05). In unadjusted regression models, higher nuclear p65 and higher nuclear p52 were associated with approximately 40% and 70% shorter PFS and OS, respectively, but these associations were attenuated by adjustment for age, stage, tumor type, race, chemotherapy, and residual disease. In multivariable adjusted models, higher cytoplasmic p52 was associated with more than 50% shorter PFS (HR 1.68, 95% CI 1.18-2.39) and OS (HR 1.53, 95% CI 1.06-2.21). Furthermore, when cytoplasmic and nuclear staining were combined, and mutually adjusted models included both p52 and p65, only p52 remained associated with worse PFS (HR 1.57, 95% CI 1.10-2.37) and OS (HR 1.51, 95% CI 1.05-2.15). Conclusions: This is the first study to demonstrate that p52, representing noncanonical NF-kB signaling, may be an independent prognostic factor for epithelial ovarian cancer. Approaches to inhibit noncanonical NF-kB signaling should be explored as novel therapies for ovarian cancer are needed. Citation Format: Demetra Hufnagel, Andrew J. Wilson, Jamie Saxon, Dineo Khabele, Timothy Blackwell, Marta A. Crispens, Fiona Yull, Alicia Beeghly-Fadiel. Noncanonical NF-kappaB signaling is associated with poor ovarian cancer prognosis [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 A15.
Abstract 4051: Anlotinib inhibits the progress of colorectal cancer cells by antagonizing glycolysis &amp; JAK2-STAT3 signaling
Authors: Zhenxian Jia, Zhi Zhang, Ze Li, Ang Li, Yuning Xie, Hongjiao Wu, Zhenbang Yang, Hongmei Zhang, Xuemei Zhang
Journal: Cancer Research (2020)

Abstract Background: Anlotinib is a novel multi-target tyrosine kinase receptor inhibitor (TKI) that has been proved to treat advanced NSCLC as a third-line regime in China. This study designed to investigate the effectiveness &amp; possible mechanism of anlotinib colorectal cancer (CRC) therapy. Methods: CCK-8 assay &amp; CyQUANT NF assay were used to detect the sensitivity of CRC cells to DDP &amp; anlotinib. Real time quantitative polymerase chain reaction was used to detect the mRNA level of hub genes. The protein expression of pVEGFR2, cleaved PARP, cleaved caspase 3, JAK2, pJAK2, STAT3 &amp; PSTAT3 were determined by western blot. The roles of DDP &amp; anlotinib in the progression, invasion &amp; metastasis of CRC cells were evaluated by colony formation, wound healing &amp; trans-well assay. Lactate release &amp; glucose consumption were measured to investigate glucose metabolism. Cell apoptosis was analyzed by Hoechst33342 fluorescence staining &amp; flow cytometer. Results: We found that anlotinib may improve the treatment of CRC by blocking the effects of VEGFA. Subsequently, in vitro assays demonstrated that anlotinib &amp;/or DDP inhibited cell proliferation, migration &amp; invasion &amp; also activated apoptosis in human colorectal cancer cells. Additionally, glucose metabolism in CRC HCT-116 &amp; LOVO cells was suppressed by anlotinib &amp;/or DDP. In other hand, anlotinib &amp;/or DDP may improve the treatment of CRC by inhibiting JAK2-STAT3 signaling pathway. Conclusions: Our preclinical studies showed that anlotinib inhibited cell proliferation, invasion, migration &amp; activated apoptosis by antagonizing glycolysis &amp; JAK2-STAT3 signaling. Combination chemotherapy of anlotinib with cisplatin is more sensitive to CRC. Citation Format: Zhenxian Jia, Zhi Zhang, Ze Li, Ang Li, Yuning Xie, Hongjiao Wu, Zhenbang Yang, Hongmei Zhang, Xuemei Zhang. Anlotinib inhibits the progress of colorectal cancer cells by antagonizing glycolysis &amp; JAK2-STAT3 signaling [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 4051.
Debates Around the Role of School Closures in the Coronavirus 2019 Pandemic—Reply
Authors: Susanna Esposito, Nicola Principi
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.
Special Care Is Needed in Applying Phylogenetic Comparative Methods to Gene Trees with Speciation and Duplication Nodes
Authors: Tina Begum, Marc Robinson-Rechavi
Journal: Molecular Biology and Evolution (2020)

How gene function evolves is a central question of evolutionary biology. It can be investigated by comparing functional genomics results between species and between genes. Most comparative studies of functional genomics have used pairwise comparisons. Yet it has been shown that this can provide biased results, as genes, like species, are phylogenetically related. Phylogenetic comparative methods should be used to correct for this, but they depend on strong assumptions, including unbiased tree estimates relative to the hypothesis being tested. Such methods have recently been used to test the "ortholog conjecture," the hypothesis that functional evolution is faster in paralogs than in orthologs. Although pairwise comparisons of tissue specificity (τ) provided support for the ortholog conjecture, phylogenetic independent contrasts did not. Our reanalysis on the same gene trees identified problems with the time calibration of duplication nodes. We find that the gene trees used suffer from important biases, due to the inclusion of trees with no duplication nodes, to the relative age of speciations and duplications, to systematic differences in branch lengths, and to non-Brownian motion of tissue specificity on many trees. We find that incorrect implementation of phylogenetic method in empirical gene trees with duplications can be problematic. Controlling for biases allows successful use of phylogenetic methods to study the evolution of gene function and provides some support for the ortholog conjecture using three different phylogenetic approaches.
In Situ Forming, Silanized Hyaluronic Acid Hydrogels with Fine Control Over Mechanical Properties and In Vivo Degradation for Tissue Engineering Applications
Authors: Killian Flegeau, Claire Toquet, Gildas Rethore, Cyril d'Arros, Léa Messager, Boris Halgand, Davy Dupont, Florent Autrusseau, Julie Lesoeur, Joëlle Veziers, Pascal Bordat, Anthony Bresin, Jérôme Guicheux, Vianney Delplace, Hélène Gautier, Pierre Weiss
Journal: Advanced Healthcare Materials (2020)

Abstract In situ forming hydrogels that can be injected into tissues in a minimally‐invasive fashion are appealing as delivery vehicles for tissue engineering applications. Ideally, these hydrogels should have mechanical properties matching those of the host tissue, and a rate of degradation adapted for neo‐tissue formation. Here, the development of in situ forming hyaluronic acid hydrogels based on the pH‐triggered condensation of silicon alkoxide precursors into siloxanes is reported. Upon solubilization and pH adjustment, the low‐viscosity precursor solutions are easily injectable through fine‐gauge needles prior to in situ gelation. Tunable mechanical properties (stiffness from 1 to 40 kPa) and associated tunable degradability (from 4 days to more than 3 weeks in vivo) are obtained by varying the degree of silanization (from 4.3% to 57.7%) and molecular weight (120 and 267 kDa) of the hyaluronic acid component. Following cell encapsulation, high cell viability (&gt; 80%) is obtained for at least 7 days. Finally, the in vivo biocompatibility of silanized hyaluronic acid gels is verified in a subcutaneous mouse model and a relationship between the inflammatory response and the crosslink density is observed. Silanized hyaluronic acid hydrogels constitute a tunable hydrogel platform for material‐assisted cell therapies and tissue engineering applications.
Overuse of Respiratory Viral Panels
Authors: Anya Greenberg, Peter Barish, Ari Hoffman
Journal: JAMA Internal Medicine (2020)

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Abstract LB-279: Multi-grain rice diet decreases risk of breast cancer in Korean women: Results from the Health Examinees study
Authors: Woo-Kyoung Shin, Hwi-Won Lee, Aesun Shin, Jong-koo Lee, Daehee Kang
Journal: Cancer Research (2020)

Abstract Background: Several studies have examined associations between breast cancer risk and individual foods and nutrients. Most studies have evaluated risks associated with individual foods and nutrients, rather than measures of whole-diet. The objective of this study was to investigate the association between dietary patterns and the risk for breast cancer. Methods: A total of 93,306 women aged 40-69 years were enrolled in the prospective cohort study in the Health Examinees-Gem (HEXA-G) study between 2004 and 2013. Information on cancer diagnosis in the eligible cohort was retrieved from the Korea Central Cancer Registry through 31 December 2014. Dietary patterns were identified using factor analysis of data from a 106-item validated food frequency questionnaire. We conducted a multivariable Cox regression model to obtain the hazard ratio (HR) and 95% confidence interval (CI) for the risk of breast cancer according to the dietary pattern scores. Results: A total of 359 incident cases of breast cancer occurred over an average follow-up period of 6.3 years. Using a factor analysis, we identified three major dietary patterns, which explained 23.9% of the total variance, based on the daily total food intake (g/day) from 37 food groups: the Vegetables and seaweed pattern (greater intake of yellow-green and other vegetables, seaweed, lean fish, and shellfish), the Flour and meat pattern (greater intake of bread, pizza and hamburger, red meat, and poultry), the White rice and salt fermented fish pattern (greater intake of white rice and salt fermented fish). We found that the women who had higher white rice and salt fermented fish pattern scores tend to have higher risk of breast cancer. Multivariate HR (95% CI) comparing the highest with the lowest quintiles of White rice and salt fermented fish pattern scores was 1.35 (1.00, 1.84) (p for trend = 0.0384). Other two dietary patterns, the Vegetables and seaweed pattern and the Flour and meat pattern, showed no significant association with the breast cancer risk for women. Conclusion: The White rice and salt fermented fish pattern was associated with a increased risk of breast cancer, but further investigation involving subgroup analysis is warranted. Citation Format: Woo-Kyoung Shin, Hwi-Won Lee, Aesun Shin, Jong-koo Lee, Daehee Kang. Multi-grain rice diet decreases risk of breast cancer in Korean women: Results from the Health Examinees study [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 LB-279.
THU0074 Vitamin e uncouples joint inflammation and articular destruction, in a transgenic mouse model of rheumatoid arthritis
Authors: MJ De Bandt, F Driss, M Grossin, J Pincemail, C Babin-Chevaye, C Gaertner, C Pasquier
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Reactive oxygen species (ROS) are suspected to play a role in human RA. Transient hypoxia and ischaemic-reperfusion phenomenon are involved in their chronic production, by monocytes and macrophages. Nevertheless the clinical interest of ROS scavengers is difficult to evaluate. <h3>Objectives</h3> <h3>Methods</h3> We studied the effects of Vitamin E (natural alpha tocopherol) on transgenic KRN/NOD mice, new model for rheumatoid arthritis. We determined clinical, histological and biochemical parameters so as to define the long-term benefit of Vitamin E in the disease. <h3>Results</h3> We found an increase in plasma Vit E, in treated mice. Vitamin E treatment did not modify the date of onset of the disease, neither the intensity of the disease (arthritic index and weight), but Vit-E prevented from articular destruction, suggesting uncoupling of the two phenomenon. Biochemical analysis, blood glutathion, urine isoprostane and the plasma hydroperoxide did not differ between Vit E-treated transgenic KRN/NOD mice and control mice. Blood chemiluminescence was increased in transgenic KRN/NOD mice as compared to non-transgenic mice, and was decreased in Vit E-treated transgenic KRN/NOD mice. TNF-a and IL1-b, low in control non-transgenic mice, were increased in transgenic KRN/NOD mice, however a significant decreased in IL-1b appeared in Vit E-treated mice. <h3>Conclusion</h3> These results suggest that ROS scavengers can modulate cytokines responses and provide new arguments for the interest of ROS scavengers in RA therapy.
Abstract 525: A novel anti-PD1-IL15 immunocytokine potentiates anti-tumor T cell activity of PD-1 checkpoint inhibition and IL-2R-beta-gamma agonism
Authors: Dan Lu, Zhanna Polonskaya, Tzi-Pei Chang, Stella Martomo, Xenia Luna, Zhikai Zhang, Faical Miyara, Jeedar Patel
Journal: Cancer Research (2020)

Abstract Therapeutic antibodies targeting immune checkpoint inhibitors (ICI) such as PD-1/PD-L1 effectively expand and reactivate T cells in patients, leading to long-lasting response in multiple tumor types. However, only a fraction of patients responded to approved ICIs, majority are either resistant or quickly become refractory. Other immunotherapy modalities including immunostimulatory cytokines IL-2, IL-12 and IL-15 demonstrated clinical benefits as monotherapy or in combination with ICIs. Cytokines exhibit in general a short half-life and systemic toxicities that limit their use as the optimal doses in treating cancer. An antibody-based immunocytokine fusion such as Kadmon lead candidate KD033 (anti-PDL1/IL15) and Roche anti-PD1/CEA/FAP-IL2v can extend the half-life of cytokine and reduce systemic toxicities. In this study, a fully human single-chain variable fragment (scFv) antibody against mouse PD1 (mPD1) have been isolated from the phage display library. The variable domains of these antibodies were fused to either human IgG1a or mouse IgG2a constant domain first, and then fused to either human IL15 receptor alpha sushi domain-hIL15 complex (hSD15) or mouse IL15 receptor alpha sushi domain-mIL15 complex (mSD15). These variations of fusion have been tested in in vitro binding and functional assays, and in vivo in PD1/PDL1 resistant mouse syngeneic model LL2 (Lewis Lung Carcinoma). We demonstrated that hSD15 fusion antibody can stimulate both IL2 dependent human and murine cells growth, surprisingly, mSD15 fusion antibody can only stimulate murine cell growth. Although mSD15 fusion antibody EC50 was 10 folds better than hSD15 fusion antibody in stimulating mouse spleen cell growth in vitro, it did not show a better efficacy than hSD15 fusion antibody in LL2 model. In vivo, mSD15 fusion antibody had higher maximum tolerate dose than hSD15 fusion antibody (up to 12mg/kg). In addition, anti-mPD1/mSD15 showed better efficacy than either the mIL15 and anti-mPD1 alone or the combination of anti-mPD1 plus mIL15 in vitro and in vivo. Together these preclinical data have confirmed that PD1-IL15 could be a promising next generation IL-15 fusion for cancer immunotherapy. Citation Format: Dan Lu, Zhanna Polonskaya, Tzi-Pei Chang, Stella Martomo, Xenia Luna, Zhikai Zhang, Faical Miyara, Jeedar Patel. A novel anti-PD1-IL15 immunocytokine potentiates anti-tumor T cell activity of PD-1 checkpoint inhibition and IL-2R-beta-gamma agonism [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 525.
Enhanced In Vivo Vascularization of 3D‐Printed Cell Encapsulation Device Using Platelet‐Rich Plasma and Mesenchymal Stem Cells
Authors: Jesus Paez‐Mayorga, Simone Capuani, Marco Farina, Maria Luisa Lotito, Jean A. Niles, Hector F. Salazar, Jessica Rhudy, Lucas Esnaola, Corrine Ying Xuan Chua, Francesca Taraballi, Bruna Corradetti, Kathryn A. Shelton, Pramod N. Nehete, Joan E. Nichols, Alessandro Grattoni
Journal: Advanced Healthcare Materials (2020)

Abstract The current standard for cell encapsulation platforms is enveloping cells in semipermeable membranes that physically isolate transplanted cells from the host while allowing for oxygen and nutrient diffusion. However, long‐term viability and function of encapsulated cells are compromised by insufficient oxygen and nutrient supply to the graft. To address this need, a strategy to achieve enhanced vascularization of a 3D‐printed, polymeric cell encapsulation platform using platelet‐rich plasma (PRP) and mesenchymal stem cells (MSCs) is investigated. The study is conducted in rats and, for clinical translation relevance, in nonhuman primates (NHP). Devices filled with PRP, MSCs, or vehicle hydrogel are subcutaneously implanted in rats and NHP and the amount and maturity of penetrating blood vessels assessed via histopathological analysis. In rats, MSCs drive the strongest angiogenic response at early time points, with the highest vessel density and endothelial nitric oxide synthase (eNOS) expression. In NHP, PRP and MSCs result in similar vessel densities but incorporation of PRP ensues higher levels of eNOS expression. Overall, enrichment with PRP and MSCs yields extensive, mature vascularization of subcutaneous cell encapsulation devices. It is postulated that the individual properties of PRP and MSCs can be leveraged in a synergistic approach for maximal vascularization of cell encapsulation platforms.