tbuckley/cabot-search huggingface dataset:
Abstract A47: In silico organoids: A model for deconvolution of microenvironmental and drug effects on tumor growth
Authors: Katarzyna A. Rejniak, Sharan Poonja, Jessica Kingsley, Shreya Mathur, Ibrahim Chamseddine, Aleksandra Karolak, Dmitry A. Markov, Lisa J. McCawley
Journal: Cancer Research (2020)

Abstract In vivo tumor microenvironments are heterogeneous in their architecture, cellular contents, metabolic landscape, and extracellular matrix (ECM) composition. Moreover, these microenvironments can undergo temporal and spatial changes. This may alter tumor responses to anticancer therapies. To examine the complex and dynamic changes within tumors and in tumor microenvironments, we developed a computational single cell-based model of the three-dimensional multicellular organotypic cultures: Organoid3D. This model was calibrated to experimental data and reproduced growth dynamics and morphologies of four human breast cell lines: a nontumorigenic epithelial MCF-10A, a mildly tumorigenic MCF-10AT1, and metastatic MCF-10CA-1a and MCF-10CA-1d lines grown in various microenvironmental conditions. By explicitly including the fibril structure of the ECM in the model, we examined how ECM properties promote or suppress the growth of in silico tumor organoids. The quantitative integration of experimental data for organoids exposed to different concentrations of doxorubicin allowed us to derive hypotheses on relative importance of microenvironmental factors and chemotherapeutic treatments on organoid growth. Thus, the in silico organoid model interrogated with experimental data provides a tool for fast and broad hypotheses testing and presents an opportunity to explore experimental conditions beyond what is physically feasible in laboratory experiments. Citation Format: Katarzyna A. Rejniak, Sharan Poonja, Jessica Kingsley, Shreya Mathur, Ibrahim Chamseddine, Aleksandra Karolak, Dmitry A. Markov, Lisa J. McCawley. In silico organoids: A model for deconvolution of microenvironmental and drug effects on tumor growth [abstract]. In: Proceedings of the AACR Special Conference on the Evolving Landscape of Cancer Modeling; 2020 Mar 2-5; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2020;80(11 Suppl):Abstract nr A47.
Association Between Mode of Delivery Among Pregnant Women With COVID-19 and Maternal and Neonatal Outcomes in Spain
Authors: Oscar Martínez-Perez, Manon Vouga, Sara Cruz Melguizo, Laura Forcen Acebal, Alice Panchaud, Mar Muñoz-Chápuli, David Baud
Journal: JAMA (2020)

Hui Zeng, MD; Chen Xu, BS; Junli Fan, MD; Yueting Tang, PhD; Qiaoling Deng, MD; Wei Zhang, MD, PhD; Xinghua Long, MD, PhD
Recent advances in screening active components from natural products based on bioaffinity techniques
Authors: Xiaofang Hou, Meng Sun, Tao Bao, Xiaoyu Xie, Fen Wei, Sicen Wang
Journal: Acta Pharmaceutica Sinica B (2020)

Natural products have provided numerous lead compounds for drug discovery. However, the traditional analytical methods cannot detect most of these active components, especially at their usual low concentrations, from complex natural products. Herein, we reviewed the recent technological advances (2015–2019) related to the separation and screening bioactive components from natural resources, especially the emerging screening methods based on the bioaffinity techniques, including biological chromatography, affinity electrophoresis, affinity mass spectroscopy, and the latest magnetic and optical methods. These screening methods are uniquely advanced compared to other traditional methods, and they can fish out the active components from complex natural products because of the affinity between target and components, without tedious separation works. Therefore, these new tools can reduce the time and cost of the drug discovery process and accelerate the development of more effective and better-targeted therapeutic agents.
Health Care Cost Growth Benchmarks in 5 States
Authors: Elsa Pearson, Austin Frakt
Journal: JAMA (2020)

In 2018, national health care spending increased by 4.6%, reaching $11 000 per person. Amid this growth, states are seeking novel ways to protect their budgets. One approach is to set a cost growth benchmark—a percentage growth rate under which states aim to maintain annual health care costs.
Crosstalk between maternal perinatal obesity and offspring dopaminergic circuitry
Authors: Yuki Yasumoto, Tamas L. Horvath
Journal: Journal of Clinical Investigation (2020)

The mechanism by which maternal obesity influences fetal brain development and behavior is not well understood. In this issue of the JCI, Lippert et al. showed that feeding maternal mice a high-fat diet (HFD) during lactation attenuated the activity of dopamine (DA) midbrain neurons and altered the DA-related behavioral phenotype seen in the offspring. The authors further suggested that the altered excitatory and inhibitory balance between D1 medium spiny neurons (MSN) and D2 MSN mediates this behavioral phenotype. These mechanisms may provide strategies for preventing the negative effects of maternal obesity on offspring development and adult health.
Treating Elderly Patients With Muscle-Invasive Bladder Cancer
Authors: Elizabeth R. Kessler, Janet B. Kukreja, Christopher L. Geiger, Stacy M. Fischer
Journal: Journal of the National Comprehensive Cancer Network (2020)

Bladder cancer is an extremely common cancer that primarily affects individuals aged &gt;65 years. In caring for patients with bladder cancer, clinicians must also consider care of older persons in general. Management of muscle-invasive bladder cancer (MIBC) involves multidisciplinary treatment planning, because curative-intent therapy includes either surgery or radiation, with consideration of the role of systemic therapy. As clinicians develop a treatment plan, considering a geriatric oncology perspective may enhance patient care and influence outcomes for this large and growing population. Similarly, treatment plan development must also consider aspects unique to an older patient population, such as altered organ function, increased comorbidity, decreased functional reserve, and perhaps altered goals of treatment. Thus a thorough evaluation inclusive of disease assessment and geriatric assessment is essential to care planning. Population-based data show that as patients with MIBC age, use of standard therapies declines. Given the complexities of coordinating a multidisciplinary care plan, as well the complexities of treating a heterogeneous and potentially vulnerable older patient population, clinicians may benefit from upfront assessments to inform and guide the process. This review highlights the unique treatment planning considerations for elderly patients diagnosed with MIBC.
Effects of Postoperative Radiotherapy on Survival of Patients With Stage IIIA Resected Non–Small Cell Lung Cancer: Analysis of the SEER Database
Authors: Fei Gao, Nan Li, YongMei Xu, GuoWang Yang
Journal: Journal of the National Comprehensive Cancer Network (2020)

Background: The role of postoperative radiotherapy (PORT) in patients with resected stage IIIA non–small cell lung cancer (NSCLC) remains controversial. The purpose of this study was to explore the effect of PORT on survival of these patients. Methods: Patients aged ≥18 years with stage IIIA NSCLC were identified in the SEER database from 2010 through 2015. Cox regression analysis was used to identify independant prognostic factors in patients with stage IIIA NSCLC. Subgroup analysis of patients stratified by N stage was also performed. Overall survival and lung cancer–related death were compared among the different groups by using Kaplan-Meier analysis and competitive risk analysis. Results: A total of 5,168 patients (1,711 of whom received PORT) were included in the study. In multivariable analysis, PORT was an independent prognostic risk factor for patients with N1 stage (hazard ratio [HR], 1.416, 95% CI, 1.144–1.753; P =.001). PORT was a favorable prognostic factor for patients with stage IIIA, N2 disease with ≥6 positive lymph nodes (HR, 0.742; 95% CI, 0.587–0.938; P =.012). Median survival time of patients with stage IIIA, N2 disease with ≥6 positive lymph nodes who received postoperative chemotherapy combined with PORT was significantly longer compared with those who received postoperative chemotherapy alone (32 vs 25 months, respectively; P =.009). The competitive risk model revealed that 3- and 5-year lung cancer–related mortality rates increased by 8.99% and 16.92%, respectively, in patients with N1 disease who were treated with PORT, whereas the 3-year mortality rate decreased by 4.67% and the 5-year mortality rate by 10.08% in patients with N2 disease and ≥6 positive lymph nodes who were treated using PORT. Conclusions: Our results revealed that PORT significantly improved overall survival and decreased lung cancer–related mortality in patients with stage IIIA, N2 disease with ≥6 positive lymph node metastases. PORT was not recommended for patients with N0 and N1 disease.
Germline TET2 loss of function causes childhood immunodeficiency and lymphoma
Authors: Jarmila Stremenova Spegarova, Dylan Lawless, Siti Mardhiana Binti Mohamad, Karin R. Engelhardt, Gina Doody, Jennifer Shrimpton, Anne Rensing-Ehl, Stephan Ehl, Frederic Rieux-Laucat, Catherine Cargo, Helen Griffin, Aneta Mikulasova, Meghan Acres, Neil V. Morgan, James A. Poulter, Eamonn G. Sheridan, Philip Chetcuti, Sean O'Riordan, Rashida Anwar, Clive R. Carter, Stefan Przyborski, Kevin Windebank, Andrew J. Cant, Majlinda Lako, Chris M. Bacon, Sinisa Savic, Sophie Hambleton
Journal: Blood (2020)
AB0133 INCREASED SOLUBLE SEMAPHORIN 4D/CD100 IN THE PLASMA OF SJÖGREN’S SYNDROME AND ITS EFFECTS ON HUMAN SALIVARY GLAND CELL AND CD4+ T CELL
Authors: S. E. Kang, S. U. Kim, R. H. Kim, H. J. Yoo, Y. J. Lee, I. A. Choi, J. K. Park, E. Y. Lee, Y. W. Song
Journal: Annals of the Rheumatic Diseases (2020)

Background: Semaphorin 4D (SEMA4D) / CD100, known as a subfamily of axonal guidance proteins, has also been reported to act as an immunoregulator in several infectious and inflammatory diseases [1]. Sjögren’s syndrome (SS) is a systemic autoimmune disease that primarily affects the exocrine glands by infiltrated lymphocytes resulting in dryness of mouth and eyes. IL-17 was reported to impair the integrity of tight junction barrier and attenuate the expression of aquaporin 5 (AQP5), causing salivary gland dysfunction in SS [2]. Objectives: This study was aimed to evaluate the role of SEMA4D in patients with SS and investigate the effect of SEMA4D on human salivary gland epithelial cell (SGEC) and T cell. Methods: Soluble SEMA4D levels in plasma were measured by enzyme-linked immunosorbent assay (ELISA) from patients with SS, non-SS sicca and healthy controls. Immortalized human SGECs, originated from acini (NS-SV-AC) and duct (NS-SV-DC), were used to evaluate the effects of SEMA4D. CD4 + T cells from human peripheral blood were isolated to determine the secretion of cytokines in response to SEMA4D. IFN-γ and IL-17 were used to determine the effects on AQP5 expression of SGEC. Results: The levels of soluble SEMA4D in plasma were increased in patients with SS (median [interquartile range]: 1221.3 [393.5] pg/mL) compared to non-SS sicca (940.2 [355.1] pg/mL, p = 0.006) or healthy controls (909.5 [108.0] pg/mL, p &lt; 0.0001). The levels of soluble SEMA4D in plasma were correlated with the levels of several autoantibodies including anti-SSA (Spearman’s rho = 0.358, p = 0.006), anti-SSB (rho = 0.350, p = 0.007), and anti-muscarinic receptor 3 (M3R) Ab (rho = 0.495, p &lt; 0.001), and also correlated with total IgG (rho = 0.431, p = 0.002). SEMA4D-stimulated SGECs showed decreased expression of tight junctions such as occludin and Zo-1. CD4 + T cells secreted IFN-γ ( p = 0.025), IL-17 ( p = 0.028), and IL-21 ( p = 0.007) with SEMA4D stimulation. IFN-γ and IL-17 decreased AQP5 expression in SGECs. Conclusion: SEMA4D contributed to decreased expression of tight junction in SGECs. SEMA4D induced production of IFN-γ and IL-17 in CD4 + T cells and these cytokine decreased AQP5 expression in SGECs. References: [1]Worzfeld T, Offermanns S. Nat Rev Drug Discov. 2014;13(8):603-21. [2]Bhattarai KR, Junjappa R, Handigund M, Kim HR, Chae HJ. Autoimmun Rev. 2018;17(4):376-90. Disclosure of Interests: None declared
Jasmonate Signaling Enhances RNA Silencing and Antiviral Defense in Rice
Authors: Zhirui Yang, Yu Huang, Jialin Yang, Shengze Yao, Kun Zhao, Donghui Wang, Qingqing Qin, Zhan Bian, Yan Li, Ying Lan, Tong Zhou, He Wang, Chang Liu, Wenming Wang, Yijun Qi, Zhihong Xu, Yi Li
Journal: Cell Host & Microbe (2020)
Regulation of pancreatic cancer microenvironment by an intelligent gemcitabine@nanogel system via in vitro 3D model for promoting therapeutic efficiency
Authors: Di Chen, Xiaofei Zhu, Wanru Tao, Yan Kong, Yong Huag, Yajun Zhang, Ri Liu, Lingong Jiang, Ying Tang, Haiyan Yu, Qiang Hao, Xiangqun Yang, Hao Zou, Jianming Chen, Ying Lu, Huojun Zhang, Wei Li
Journal: Journal of Controlled Release (2020)
AB0639 TREATMENT EFFICACY WITH SECUKINUMAB IN A COHORT OF SPONDYLOARTHRITIS PATIENTS
Authors: A. Castilla, Á. García Martos, L. Sala Icardo, A. Prada-Ojeda, L. Barrio Nogal, M. C. Ortega de la O, C. Arconada, L. González, A. Diaz Oca, P. Navarro
Journal: Annals of the Rheumatic Diseases (2020)

Background: Spondyloarthropathies are a heterogeneous group of similar diseases, with interrelated clinical manifestations, such as Psoriasis Arthritis (APs) and Ankylosing Spondylitis (EA). There are different treatments for this group of pathologies. Objectives: It is very important to differentiate between those that present predominantly axial (spine and/or sacroiliac) or peripheral involvement, since the response to treatment is very different. In some clinical trials, secukinumab significantly improved versus placebo, the symptoms and signs, physical function and quality of life, however, at present, we do not have enough data from secukinumab in real clinical practice. This is the real reason of this study: the use of secukinumab in clinical practice. Methods: Multicentric longitudinal observational study of 5 Hospitals in Madrid. Patients are over 18 years old and meet the following inclusion criteria: New York criteria for AS, ASAS for EA, CASPAR for APs, and all of them are with secukinumab or have received it. We will evaluate the effectiveness rate as well as its confidence interval at 95%. In addition, the effectiveness of secukinumab will be compared in the different pathologies by using χ 2 . Results: 72 patients were collected, 41 of them were women (57,75%). 12 patients (16,90%) had not received FAME before secukinumab and 22 patients (33,99%) were naive to biological treatment. In 4 patients, the reason for starting secukinumab was the patient’s comorbidities, in 2 the adverse effects of previous treatment and in the rest, was the lack of efficacy of the previous treatment. The patients were divided into 4 categories according to the level of DAS-28 or BASDAI, at the beginning of the treatment and the last recorded value, in: Absence of activity, mild, moderate and severe activity. Of the patients with data, they managed to improve the DAS-28 score (change category) by 30,95%, while only 4,76% worsened their score. With respect to BASDAI, of the total number of patients, only 3,03% worsened, while his score improved 27,27%. According to baseline diagnosis, a greater improvement of the disease activity in peripheral APs(66,67%) and mixed APs(61,54%) is achieved. Conclusion: In real clinical practice, treatment with secukinumab was effective in patients with spondyloarthritis, achieving improvement in previous activity rates. In this study, the most significant improvement was obtained in peripheral and mixed APs. Disclosure of Interests: None declared
Donor-derived acute promyelocytic leukemia presenting as myeloid sarcoma in a transplanted kidney
Authors: Risa L. Wong, Megan Ketcham, Trent Irwin, Shreeram Akilesh, Tian Yi Zhang, Jorge D. Reyes, Kerstin Edlefsen, Florencia Jalikis, Pamela S. Becker
Journal: Leukemia (2020)
Abstract 13459: Intima-media Thickness of Brachial Artery and Endothelial Function
Authors: Tatsuya Maruhashi, Yukihito Higashi, Yumiko Iwamoto, Yuichi Fujii, Naomi Idei, Noritaka Fujimura, Shinsuke Mikami, Masato Kajikawa, Takeshi Matsumoto, Ayumu Nakashima, Kensuke Noma, Yasuki Kihara
Journal: Circulation (2012)

Background: Cardiovascular diseases are associated with impaired flow-mediated vasodilation (FMD) and increase in carotid intima-media thickness (IMT). Both FMD and IMT are independent predictors f...
COVID-19 vaccines: neutralizing antibodies and the alum advantage
Authors: Peter J. Hotez, David B. Corry, Ulrich Strych, Maria Elena Bottazzi
Journal: Nature reviews. Immunology (2020)

Achieving high levels of neutralizing antibodies to the spike protein of SARS-CoV-2 in a safe manner is likely to be crucial for an effective vaccine. Here, we propose that aluminium-based adjuvants might hold the key to this. Here, Peter Hotez and colleagues discuss the advantages of using an aluminium-based adjuvant in candidate COVID-19 vaccines.
Telemedicine will not keep us apart in COVID-19 pandemic
Authors: Simone Perniola, Stefano Alivernini, Valentina Varriano, Annamaria Paglionico, Giacomo Tanti, Pietro Rubortone, Lucia Lanzo, Fabrizio Melpignano, Carlo Tur, Enrico De Lorenzis, Giusy Peluso, Annunziata Capacci, Elisa Gremese
Journal: Annals of the Rheumatic Diseases (2020)

We read with interest the letter by Bozzalla Cassione et al 1 about the role of telemedicine in their clinic during COVID-19 time. Telemedicine represents a useful tool not only in regions with limited access to healthcare2 but also in different settings like quarantine, when healthcare personnel became essential.

Since the Italian National lockdown decision3 and the WHO announcement of the COVID-19 pandemic,4 enormous demand to handle the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disease challenged the Italian healthcare system. Indeed, in the Fondazione Policlinico Universitario A. Gemelli (FPG) Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) in Rome, the delegated taskforce (Gemelli against COVID-19) gradually opened 14 COVID-19 dedicated wards, in accordance to the progressive increase of serious cases. Concomitantly, several clinics were remodulated to optimise the staff use and to avoid patient exposure to the hospital environment.

The Division of Rheumatology of the FPG-IRCCS is a high-flux rheumatological centre, with almost 16 000 visits performed in the last year for chronic inflammatory arthritis (38%), connective tissue diseases (CTDs) (34%) and other rheumatic diseases (27%) (ie, osteoarthritis and fibromyalgia) from all Italian regions. Before the spread of COVID-19, our rheumatology service was organised to …
The role of alcohol use and drinking patterns in socioeconomic inequalities in mortality: a systematic review
Authors: Charlotte Probst, Carolin Kilian, Sherald Sanchez, Shannon Lange, Jürgen Rehm
Journal: The Lancet Public Health (2020)

BackgroundIndividuals with low socioeconomic status (SES) experience disproportionately greater alcohol-attributable health harm than individuals with high SES from similar or lower amounts of alcohol consumption. Our aim was to provide an update of the current evidence for the role of alcohol use and drinking patterns in socioeconomic inequalities in mortality, as well as the effect modification or interaction effects between SES and alcohol use, as two potential explanations of this so-called alcohol-harm paradox.MethodsWe did a systematic review, searching Embase, Medline, PsycINFO, and Web of Science (published between Jan 1, 2013, and June 30, 2019) for studies reporting alcohol consumption, SES, and mortality. Observational, quantitative studies of the general adult population (aged ≥15 years) with a longitudinal study design were included. Two outcome measures were extracted: first, the proportion of socioeconomic inequalities in mortality explained by alcohol use; and second, the effect modification or interaction between SES and alcohol use regarding mortality risks. This study is registered with PROSPERO (CRD42019140279).FindingsOf 1941 records identified, ten met the inclusion criteria. The included studies contained more than 400 000 adults, more than 30 000 deaths from all causes, and more than 3000 100% alcohol-attributable events. Alcohol use explained up to 27% of the socioeconomic inequalities in mortality. The proportion of socioeconomic inequalities explained systematically differed by drinking pattern, with heavy episodic drinking having a potentially significant explanatory value. Although scarce, there was some evidence of effect modification or interaction between SES and alcohol use.InterpretationTo reduce socioeconomic inequalities in mortality, addressing heavy episodic drinking in particular, rather than alcohol use in general, is worth exploring as a public health strategy.FundingCanadian Institutes of Health Research.
Integrated Biophysical Modeling and Image Analysis: Application to Neuro-Oncology
Authors: Andreas Mang, Spyridon Bakas, Shashank Subramanian, Christos Davatzikos, George Biros
Journal: Annual Review of Biomedical Engineering (2020)

Central nervous system (CNS) tumors come with vastly heterogeneous histologic, molecular, and radiographic landscapes, rendering their precise characterization challenging. The rapidly growing fields of biophysical modeling and radiomics have shown promise in better characterizing the molecular, spatial, and temporal heterogeneity of tumors. Integrative analysis of CNS tumors, including clinically acquired multi-parametric magnetic resonance imaging (mpMRI) and the inverse problem of calibrating biophysical models to mpMRI data, assists in identifying macroscopic quantifiable tumor patterns of invasion and proliferation, potentially leading to improved ( a) detection/segmentation of tumor subregions and ( b) computer-aided diagnostic/prognostic/predictive modeling. This article presents a summary of ( a) biophysical growth modeling and simulation,( b) inverse problems for model calibration, ( c) these models' integration with imaging workflows, and ( d) their application to clinically relevant studies. We anticipate that such quantitative integrative analysis may even be beneficial in a future revision of the World Health Organization (WHO) classification for CNS tumors, ultimately improving patient survival prospects.
18F-FDG PET/CT Metabolic Behavior of COVID-19 Pneumonia
Authors: Domenico Albano, Luca Camoni, Roberto Rinaldi, Francesco Bertagna, Raffaele Giubbini
Journal: Clinical Nuclear Medicine (2020)

Abstract Between March 26 and April 6, among 80 patients who underwent 18 F-FDG PET/CT in our department (Brescia, Italy), 4 showed the presence of an interstitial pneumonia suspected for COVID-19 with reverse transcriptase polymerase chain reaction confirmation. All patients except one had bilateral ground-glass opacities and/or lung consolidations in at least 2 pulmonary lobes. Inferior lobes and basal segments were the most frequent site of disease. All lung lesions had an increased FDG uptake corresponding to the interstitial pneumonia, and in one case, mediastinal nodal involvement was registered.