tbuckley/cabot-search huggingface dataset:
Response to: ‘Correspondence on ‘SARS-CoV-2 vaccination in rituximab-treated patients: evidence for impaired humoral but inducible cellular immune response’’ by Westhoff <i>et al</i>
Authors: Michael Bonelli, Daniel Aletaha
Journal: Annals of the Rheumatic Diseases (2021)

<h3>ABSTRACT</h3> Obesity and type 2 diabetes (T2D) remain major global healthcare challenges and developing therapeutics necessitate using nonhuman primate models. Here, we present transcriptomic and proteomic analyses of all the major organs of cynomolgus monkeys with spontaneous obesity or T2D in comparison to healthy controls. Molecular changes occur predominantly in the adipose tissues of individuals with obesity, while extensive expression perturbations among T2D individuals are observed in many tissues, such as the liver, kidney, brain, and heart. Immune response-related pathways are upregulated in obesity and T2D, whereas metabolism and mitochondrial pathways are downregulated. Incorporating human single-cell RNA sequencing findings corroborates the role of macrophages and monocytes in obesity. Moreover, we highlight some potential therapeutic targets including <i>SLC2A1</i> and <i>PCSK1</i> in obesity as well as <i>SLC30A8</i> and <i>SLC2A2</i> in T2D. Our findings provide insights into tissue-specific molecular foundations of obesity and T2D and reveal the mechanistic links between these two metabolic disorders.
Abstract 2022: Palmitate promotes breast cancer progression in vitro through induction of a senescent-like phenotype in fibroblasts
Authors: Brittany Susanne Harlow, Albert R. Davalos, Andrew J. Brenner, Christopher Jolly, Stefano Tiziani, Stephen D. Hursting, Linda A. deGraffenried
Journal: Cancer Research (2021)

Abstract Background: Obesity confers a worse breast cancer prognosis, including an increased risk of recurrence and mortality. While the causative mechanisms have yet to be fully uncovered, emerging evidence implicates palmitate, increased in the obese state, in development of cellular senescence, an inflammatory state associated with breast tumorigenesis in preclinical models. However, studies are warranted to corroborate the impact of palmitate on induction of a cohesive senescent-like phenotype as well as the extent to which palmitate-induced senescence impacts breast tumorigenesis either in vitro or in vivo. This said, we hypothesize that palmitate exposure induces a senescent-like phenotype in fibroblasts, contributing to measures of breast cancer progression. Methods: HCA2, IMR-90, and human mammary fibroblasts were exposed to bovine serum albumin or palmitate in media supplemented with 2% charcoal-stripped fetal bovine serum, after which the cells were measured through qPCR for expression of IL-1a, IL-6 and IL-8, some of the most prominent members of the senescence-associated secretory phenotype. Palmitate-exposed fibroblasts were also stained for senescence-associated beta-galactosidase and BrdU incorporation, well-established senescence markers. Experiments were then repeated with administration of eicosapentaenoic and docosahaexanoic acids to evaluate the potential of omega-3 fatty acids to limit the effects of palmitate on fibroblast senescence. Finally, we assessed the tumor-promoting potential of these palmitate-exposed fibroblasts by culturing MCF-7 and T47D breast cancer cells in their conditioned media and assessing changes in carcinogenic measures. Results and Conclusions: Palmitate induced pro-inflammatory gene expression and SA-beta-gal positivity and decreased proliferation in fibroblasts, while omega-3 fatty acid supplementation reversed these effects. These palmitate-exposed fibroblasts also appeared to be of pathological impact, as exposure to their CM increased proliferation in breast cancer cells. These findings are important in that they support emerging evidence implicating obesity-associated factors in the exacerbation of breast cancer progression as well as indicate the potential of omega-3 fatty acids to improve outcome. Citation Format: Brittany Susanne Harlow, Albert R. Davalos, Andrew J. Brenner, Christopher Jolly, Stefano Tiziani, Stephen D. Hursting, Linda A. deGraffenried. Palmitate promotes breast cancer progression in vitro through induction of a senescent-like phenotype in fibroblasts [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 2022.
Impact of clinical and pathological subtypes of Carcinoma In Situ (CIS) of the bladder: Lessons learned from long-term follow-up of a series of CIS patients treated with BCG
Authors: J.D. Subiela Henríquez, O. Rodríguez-Faba, J. Aumatell, W. Krajewski, J. Calderón, A. Mercadé, J. Balañà, R. Parada, J. Huguet, F. Algaba, A. Breda, J. Palou
Journal: European Urology (2021)
Progression of Early Subclinical Atherosclerosis (PESA) Study
Authors: Borja Ibanez, Antonio Fernández-Ortiz, Leticia Fernández-Friera, Inés García-Lunar, Vicente Andrés, Valentín Fuster
Journal: Journal of the American College of Cardiology (2021)

Atherosclerosis starts early in life and progresses silently for decades. Considering atherosclerosis as a "systemic disease" invites the use of noninvasive methodologies to detect disease in various regions before symptoms appear. The PESA-(Progression of Early Subclinical Atherosclerosis) CNIC-SANTANDER study is an ongoing prospective cohort study examining imaging, biological, and behavioral parameters associated with the presence and progression of early subclinical atherosclerosis. Between 2010 and 2014, PESA enrolled 4,184 asymptomatic middle-aged participants who undergo serial 3-yearly follow-up examinations including clinical interviews, lifestyle questionnaires, sampling, and noninvasive imaging assessment of multiterritorial subclinical atherosclerosis (carotids, iliofemorals, aorta, and coronaries). PESA tracks the trajectories of atherosclerosis and associated disorders from early stages to the transition to symptomatic phases. A joint venture between the CNIC and the Santander Bank, PESA is expected to run until at least 2029, and its significant contributions to date are presented in this review paper.
Unfavourable outcomes after Holmium Laser Enucleation of the Prostate (HoLEP) are common also in the hands of a very esperienced surgeon – Results from a prospective trial (ExpHo)
Authors: P. Capogrosso, E. Ventimiglia, A. Costa, F. Pellegrino, L. Candela, G. Fallara, W. Cazzaniga, D. Cignoli, N. Schifano, R. Matloob, F. Dehò, V. Scattoni, A. Salonia, F. Montorsi
Journal: European Urology (2021)
Predictors of complications after cytoreductive nephrectomy in the immunotherapy era: Results from a multicenter international study
Authors: M. Marchioni, G. Rebez, R. Campi, A. Minervini, M. Kriegmair, E. Linares, V. Hevia, A. Veccia, U. Carbonara, M. Musquera, M. D’Anna, I. Darweesh, M.F. Meagher, E. Rousel, M. Albersen, R. Autorino, N. Pavan, F. Claps, A. Antonelli, A. Tafuri, S. Erdem, N. Paksoy, M.C. Mir
Journal: European Urology (2021)
The development of a dynamic prediction model using MRI predicting Gleason upgrading on prostate biopsy in patients on active surveillance
Authors: D. Nieboer, H.B. Luiting, R. Valdagni, E.R. Boevé, A. Rannikko, A. Semjenow, F. Staerman, P.K. Chiu, V. Berge, M.J. Roobol
Journal: European Urology (2021)
Abstract 348: Development of an RNA based diagnostic panel to the tumor microenvironment to match cancer therapies for colorectal cancer
Authors: Kristen Strand-Tibbitts, Kerry Culm-Merdek, Valerie Chamberlain Santps, Laura Benjamin, Julia Carter, Larry Douglass, Roman Luštrik, Robert Cvitkovič, Luka Ausec, Rafael Rosengarten
Journal: Cancer Research (2021)

Abstract The most utilized targeted therapies in colorectal cancer (CRC) are focused on EGFR inhibition and anti-angiogenesis. In the ~5% of patients with microsatellite instability (MSI-H) or high tumor mutational burden (TMB), checkpoint inhibitors (CPIs) have been approved. Oncxerna has developed an RNA expression-based approach to characterize the ‘dominant' biology of a patient's tumor microenvironment with the diagnostic hypothesis to prospectively pair those patients with therapies and known mechanism of action that directly target these biologies. We developed an RNA-based gene expression panel (TME Panel-1) and machine learning (ML) algorithms to prospectively predict a patient's response to anti-angiogenesis or immune modulators, such as CPIs. In this study, we explore the potential of the TME Panel-1 to identify dominant biologies present in colorectal cancer specimens procured from the Wood-Hudson Cancer Research Lab. Total RNA expression counts from FFPE slides were analyzed with the ML algorithms and used to assign each sample into one of four subgroups. The respective prevalence of the subgroups are similar to those observed in gastric cancer and ovarian cancer samples, suggesting that the TME-Panel 1 has potential to be used to develop pan-tumor diagnostics. We will present these results, correlations with clinical outcomes and other relevant biomarkers for CRC. In summary, we conclude that RNA-based descriptors of biology may be a useful approach to enrich for better response to targeted therapies whose mechanism of action is to modify the TME biology. Citation Format: Kristen Strand-Tibbitts, Kerry Culm-Merdek, Valerie Chamberlain Santps, Laura Benjamin, Julia Carter, Larry Douglass, Roman Luštrik, Robert Cvitkovič, Luka Ausec, Rafael Rosengarten. Development of an RNA based diagnostic panel to the tumor microenvironment to match cancer therapies for colorectal 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 348.
Combinatorial immunotherapy of N-803 (IL-15 superagonist) and dinutuximab with ex vivo expanded natural killer cells significantly enhances in vitro cytotoxicity against GD2<sup>+</sup>pediatric solid tumors and in vivo survival of xenografted immunodeficient NSG mice
Authors: Yaya Chu, Gaurav Nayyar, Susiyan Jiang, Jeremy M. Rosenblum, Patrick Soon-Shiong, Jeffrey T Safrit, Dean A. Lee, Mitchell S. Cairo
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Children with recurrent and/or metastatic osteosarcoma (OS), neuroblastoma (NB) and glioblastoma multiforme (GBM) have a dismal event-free survival (&lt;25%). The majority of these solid tumors highly express GD2. Dinutuximab, an anti-GD2 monoclonal antibody, significantly improved event-free survival in children with GD2 + NB post autologous stem cell transplantation and enhanced natural killer (NK) cell-mediated antibody-dependent cell cytotoxicity. Thus, approaches to increase NK cell number and activity, improve persistence and trafficking, and enhance tumor targeting may further improve the clinical benefit of dinutuximab. N-803 is a superagonist of an interleukin-15 (IL-15) variant bound to an IL-15 receptor alpha Su-Fc fusion with enhanced biological activity. Methods The anti-tumor combinatorial effects of N-803, dinutuximab and ex vivo expanded peripheral blood NK cells (exPBNK) were performed in vitro using cytoxicity assays against GD2 + OS, NB and GBM cells. Perforin and interferon (IFN)-γ levels were measured by ELISA assays. Multiple cytokines/chemokines/growth factors released were measured by multiplex assays. Human OS, GBM or NB xenografted NOD/SCID/IL2rγnull (NSG) mice were used to investigate the anti-tumor combinatorial effects in vivo. Results N-803 increased the viability and proliferation of exPBNK. The increased viability and proliferation are associated with increased phosphorylation of Stat3, Stat5, AKT, p38MAPK and the expression of NK activating receptors. The combination of dinutuximab and N-803 significantly enhanced in vitro cytotoxicity of exPBNK with enhanced perforin and IFN-γ release against OS, GBM and NB. The combination of exPBNK+N-803+dinutuximab significantly reduced the secretion of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), platelet-derived growth factor-BB (PDGF-BB), and stem cell growth factor beta (SCGF-β) from OS or GBM tumor cells. Furthermore, OS or GBM significantly inhibited the secretion of regulated on activation, normal T cell expressed and presumably secreted (RANTES) and stromal cell-derived factor-1 alpha (SDF-1α) from exPBNK cells (p&lt;0.001) but significantly enhanced monokine induced by gamma interferon (MIG) secretion from exPBNK cells (p&lt;0.001). N-803 combined with dinutuximab and exPBNK cells significantly extended the survival of OS, GBM or NB xenografted NSG mice. Conclusions Our results provide the rationale for the development of a clinical trial of N-803 in combination with dinutuximab and ex vivo exPBNK cells in patients with recurrent or metastatic GD2 + solid tumors.
Abstract 2988: Characterization of 3D models of human breast, prostate and colorectal cancer
Authors: Katie Hudson, Neil Cross, Nicola Jordan-Mahy, Rebecca Leyland
Journal: Cancer Research (2021)

Abstract Tumorigenic expression of programmed death-ligand 1 (PD-L1) and its receptor PD-1 is found in many cancers, though the intrinsic roles of these proteins and how immunotherapy treatment may affect these pathways needs to be fully explored across human cancers. One platform to assess the expression and regulation of these proteins is 3D cell culture, which is thought to more closely mimic the architecture of solid tumors and more closely recapitulate in vivo human tumors in terms of cell heterogeneity, immunological and tumorigenic marker expression and treatment response, to investigate PD-L1/PD-1 signaling in cancer cells. Human breast (MDA-MB-231 and MCF-7), prostate (LNCaP and PC3) and colorectal (SW480 and SW620) cancer cell lines were cultured in both scaffold-free and scaffold-based 3D cell culture models to facilitate the formation of spheroids that display cell heterogeneity. 3D cancer models were analyzed by microscopy, qPCR and flow cytometry to assess the viability of spheroids, and measure any alterations in immunological and tumorigenic markers at mRNA and protein level, respectively, compared to their 2D monolayer counterparts. Breast, prostate and colorectal cancer cells cultured in 3D were highly viable over time and displayed significantly altered levels of immunological and tumorigenic marker expression at mRNA and/or protein level compared to their 2D monolayer counterparts. Importantly, PD-L1 expression changed in a 3D environment which may be linked to the increased cell-cell and cell-ECM interactions; increased expression of PD-L1 regulatory genes/proteins; or hypoxic regions that establish in 3D spheroids. The significantly altered expression levels of immunological and tumorigenic markers in a 3D cell culture environment is more likely to mimic that of an in vivo human tumor than standard 2D cell culture; allowing for optimized in vitro evaluation of the role of tumorigenic PD-L1/PD-1 and how immunotherapy treatment may affect these pathways. Citation Format: Katie Hudson, Neil Cross, Nicola Jordan-Mahy, Rebecca Leyland. Characterization of 3D models of human breast, prostate and colorectal 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 2988.
Does prostate volume affect early continence recovery after holmium laser enucleation of the prostate? Results from a prospective trial (ExpHo)
Authors: P. Capogrosso, E. Ventimiglia, A. Costa, F. Pellegrino, L. Candela, G. Fallara, W. Cazzaniga, D. Cignoli, N. Schifano, R. Matloob, F. Dehò, V. Scattoni, A. Salonia, F. Montorsi
Journal: European Urology (2021)
Transcriptional control of CBX5 by the RNA-binding proteins RBMX and RBMXL1 maintains chromatin state in myeloid leukemia
Authors: Camila Prieto, Diu T. T. Nguyen, Zhaoqi Liu, Justin Wheat, Alexendar Perez, Saroj Gourkanti, Timothy Chou, Ersilia Barin, Anthony Velleca, Thomas Rohwetter, Arthur Chow, James Taggart, Angela M. Savino, Katerina Hoskova, Meera Dhodapkar, Alexandra Schurer, Trevor S. Barlowe, Ly P. Vu, Christina Leslie, Ulrich Steidl, Raul Rabadan, Michael G. Kharas
Journal: Nature Cancer (2021)
Diabetes, Obesity, COVID-19, Insulin, and Other Antidiabetes Drugs
Authors: Paresh Dandona, Husam Ghanim
Journal: Diabetes Care (2021)

Coronavirus disease 2019 (COVID-19) viral infection, like other infections, triggers an inflammatory response that is usually confined to the respiratory system.However, there is evidence that in a full-blown case, almost all systems of the body may be involved.In addition, there is the syndrome of cytokine storm, characterized by severe systemic inflammation and a massive release of proinflammatory cytokines (1).It is well established that obesity and diabetes are major risk factors for COVID-19 infections and that the morbidity and mortality in association with these conditions is markedly increased.Since both obesity and diabetes are associated with chronic inflammation, it is likely that the inflammatory response to COVID-19 in such patients is affected by the background of chronic inflammation.This review aims to elucidate some of these processes and potential strategies to combat them. CHRONIC INFLAMMATORY STATES OF OBESITY AND DIABETESThe concept that obesity is associated with inflammation was initiated with the cardinal work of Hotamisligil et al. ( 2), which demonstrated that the proinflammatory cytokine tumor necrosis factor-a (TNF-a) was expressed in the adipose tissue and that its expression was markedly elevated in the ob/ob mouse.In addition, this increase was associated with insulin resistance.Neutralization of TNF-a with the infusion of soluble TNF-a receptor resulted in the reversal of insulin resistance in the ob/ob mouse.These remarkable observations resulted in the understanding that obesity is a state of chronic inflammation and that inflammatory mediators may contribute to the pathogenesis of insulin resistance.The same group then demonstrated that human adipose tissue also expresses TNF-a and that its expression is increased in obesity (3).Another research group simultaneously confirmed this observation (4).This observation was followed by the demonstration that plasma concentration of TNF-a was significantly elevated in obese humans and that TNF-a fell after weight loss (5).A more comprehensive description of inflammation in obesity and its relationship to insulin resistance was demonstrated by the work of Ghanim et al. (6,7).These features were then linked to the metabolic syndrome (8).These observations were further supported by the fact that human obesity was associated with chronic oxidative stress and that dietary restriction and weight loss led to a marked reduction in the indices of oxidative stress even over a short period of 4 weeks (9).These observations were confirmed by an article from Japan (10).Oxidative stress is known to trigger inflammatory processes and often occurs concomitantly with inflammation.The occurrence of inflammation in association with type 2 diabetes was first demonstrated by Pickup and Crook (11,12).These articles emphasize the increase in acute phase reactants to inflammation in patients with type 2 diabetes, including sialic acid and cytokines IL-6 and TNF-a in particular.
Efficacy and safety of the sublingual bacterial vaccine MV140 in women with recurrent urinary tract infections: An European phase III, multicentre, randomized, double-blind, placebo-controlled trial
Authors: M.F. Lorenzo Gomez, S. Foley, J.C. Nickel, B.Y. Padilla-Fernández, I. González-Casado, M. Martínez-Huélamo, B. Yang, P. Saz-Leal, M. Casanovas, M.B. García-Cenador
Journal: European Urology (2021)
The role of psa density in decision making to perform transperineal prostate biopsy in men with multi-parametric MRI Likert 2 or 3 scores: A retrospective analysis from a multi-centre cancer network study
Authors: J. Fanshawe, H. Warren, C. Clark, F. Kum, M. Smekal, E. Masiha, L. Saada, C. Tan, S. Deen, O. Farooq, M. Siddiqi, J. Apata-Omisore, L. Stroman, J. Rusere, A. Tasleem, N.M. Nkwam, C. Brown, O. Elhage, P. Cathcart, B. Challacombe, R. Popert, E. Di Benedetto, M. Hadjipavlou
Journal: European Urology (2021)
Free-hand MRI-TRUS transperineal prostate fusion biopsy under local anesthesia: A multicentre analysis of the learning curve
Authors: G. Calleris, G. Marra, J. Zhuang, X. Zhao, A. Marquis, Y. Kan, G. Montefusco, H. Huang, R. Faletti, Q. Zhang, L. Molinaro, W. Wang, M. Oderda, H. Guo, P. Gontero
Journal: European Urology (2021)
Motion-based camera localization system in colonoscopy videos
Authors: Heming Yao, Ryan W. Stidham, Zijun Gao, Jonathan Gryak, Kayvan Najarian
Journal: Medical Image Analysis (2021)

Optical colonoscopy is an essential diagnostic and prognostic tool for many gastrointestinal diseases, including cancer screening and staging, intestinal bleeding, diarrhea, abdominal symptom evaluation, and inflammatory bowel disease assessment. Automated assessment of colonoscopy is of interest considering the subjectivity present in qualitative human interpretations of colonoscopy findings. Localization of the camera is essential to interpreting the meaning and context of findings for diseases evaluated by colonoscopy. In this study, we propose a camera localization system to estimate the relative location of the camera and classify the colon into anatomical segments. The camera localization system begins with non-informative frame detection and removal. Then a self-training end-to-end convolutional neural network is built to estimate the camera motion, where several strategies are proposed to improve its robustness and generalization on endoscopic videos. Using the estimated camera motion a camera trajectory can be derived and a relative location index calculated. Based on the estimated location index, anatomical colon segment classification is performed by constructing a colon template. The proposed motion estimation algorithm was evaluated on an external dataset containing the ground truth for camera pose. The experimental results show that the performance of the proposed method is superior to other published methods. The relative location index estimation and anatomical region classification were further validated using colonoscopy videos collected from routine clinical practice. This validation yielded an average accuracy in classification of 0.754, which is substantially higher than the performances obtained using location indices built from other methods.