tbuckley/cabot-search huggingface dataset:
Castration-mediated IL-8 promotes myeloid infiltration and prostate cancer progression
Authors: Zoila A. Lopez-Bujanda, Michael C. Haffner, Matthew G. Chaimowitz, Nivedita Chowdhury, Nicholas J. Venturini, Radhika A. Patel, Aleksandar Obradovic, Corey S. Hansen, Joanna Jacków, Janielle P. Maynard, Karen S. Sfanos, Cory Abate-Shen, Charles J. Bieberich, Paula J. Hurley, Mark J. Selby, Alan J. Korman, Angela M. Christiano, Angelo M. De Marzo, Charles G. Drake
Journal: Nature Cancer (2021)
核孔複合体コア内部のナノバイオフィラメントの時空追跡【JST・京大機械翻訳】
Authors: Mohamed Mahmoud Shaaban, Hazawa Masaharu, Kobayashi Akiko, Guillaud Laurent, Watanabe-Nakayama Takahiro, Nakayama Mizuho, Wang Hanbo, Kodera Noriyuki, Oshima Masanobu, Ando Toshio, W Wong Richard
Journal: Biomaterials (2020)
Lymphoma Microenvironment Signature Predicts Clinical Outcomes in Diffuse Large B-Cell Lymphoma Patients
Authors: Kohta Miyawaki, Takeshi Sugio, Koji Kato, Kensuke Sasaki, Hiroaki Miyoshi, Jon C. Aster, Frank C Kuo, Koichi Ohshima, Takahiro Maeda, Koichi Akashi
Journal: Blood (2017)
Application of an <i>in Vitro</i> Assay to Identify Chemicals That Increase Estradiol and Progesterone Synthesis and Are Potential Breast Cancer Risk Factors
Authors: Bethsaida Cardona, Ruthann A. Rudel
Journal: Environmental Health Perspectives (2021)

Established breast cancer risk factors, such as hormone replacement therapy and reproductive history, are thought to act by increasing estrogen and progesterone (P4) activity.We aimed to use in vitro screening data to identify chemicals that increase the synthesis of estradiol (E2) or P4 and evaluate potential risks.Using data from a high-throughput (HT) in vitro steroidogenesis assay developed for the U.S. Environmental Protection Agency (EPA) ToxCast program, we identified chemicals that increased estradiol (E2-up) or progesterone (P4-up) in human H295R adrenocortical carcinoma cells. We prioritized chemicals by their activity. We compiled in vivo studies and assessments about carcinogenicity and reproductive/developmental (repro/dev) toxicity. We identified exposure sources and predicted intakes from the U.S. EPA's ExpoCast.We found 296 chemicals increased E2 (182) or P4 (185), with 71 chemicals increasing both. In vivo data often showed effects consistent with this mechanism. Of the E2- and P4-up chemicals, about 30% were likely repro/dev toxicants or carcinogens, whereas only 5-13% were classified as unlikely. However, most of the chemicals had insufficient in vivo data to evaluate their effects. Of 45 chemicals associated with mammary gland effects, and also tested in the H294R assay, 29 increased E2 or P4, including the well-known mammary carcinogen 7,12-dimethylbenz(a)anthracene. E2- and P4-up chemicals include pesticides, consumer product ingredients, food additives, and drinking water contaminants.The U.S. EPA's in vitro screening data identified several hundred chemicals that should be considered as potential risk factors for breast cancer because they increased E2 or P4 synthesis. In vitro data is a helpful addition to current toxicity assessments, which are not sensitive to mammary gland effects. Relevant effects on the mammary gland are often not noticed or are dismissed, including for 2,4-dichlorophenol and cyfluthrin. Fifty-three active E2-up and 59 active P4-up chemicals that are in consumer products, food, pesticides, or drugs have not been evaluated for carcinogenic potential and are priorities for study and exposure reduction. https://doi.org/10.1289/EHP8608.
Abstract 17516: Screening for Heart Disease in Rural China with Fingerstick BNP and Echo: Results of the ALERT (Asia Pacific Link to Evaluation and Referral for Treatment) Trial
Authors: Alan S Maisel, Chris DeFilipi, Mark Richards, Mary Yin, Hu Dayi
Journal: Circulation (2011)

China is faced with a large percentage of the population with limited health care access, especially in rural areas. We proposed that a finger stick BNP test might identify children with compromised congenital heart disease as well as adults with cardiac dysfunction. Along with Peking's Peoples Hospital and the Chinese Red Cross, we traveled to three rural hospitals in Ruijin Jiangxi province, where significant congenital heart disease (CHD) exists. A notice was sent to all three communities that anyone with heart problems, symptoms of heart disease, or who would like to be screened for heart disease could attend. After consent was signed, a questionnaire (history and symptoms) was filled out, followed by blood pressure, ECG, echocardiography, and finger stick BNP (Alere, inc) test. Those with significant heart disease were referred on the spot to a cardiologist and/ or a cardiac surgeon. In this first session, we screened 38 children (at least 5 years old) and 142 adults (37% male, mean age 60). In children, while no absolute level of BNP was related to the presence or absence of CHD, finger stick BNP levels great than 35 pg/ml were associated with significant cardiac compromise. The area under the ROC curve was 0.75. In adults, BNP levels &gt; 150 pg/ml identified those with significant systolic or diastolic dysfunction or valvular disease with only 4% false positives (area under ROC= 0.90). Thus, it appears that a simple finger stick BNP test can identify those children with significant congenital heart disease and adults with advanced heart disease who should move to the “front-lines” of health care management.
MO31-6 Maintenance olaparib in Asian patients with germline BRCA-mutated metastatic pancreatic cancer
Authors: Do-Youn Oh, Joon Oh Park, Hedy L. Kindler, Pascal Hammel, Michele Reni, Eric Van Cutsem, Teresa Macarulla, Michael J. Hall, Dirk Arnold, Anke Reinacker-Schick, Giampaolo Tortora, Hana Algul, Eileen M. O'Reilly, David McGuiness, Yu-Zhen Liu, Karen Cui, Katia Schlienger, Gershon Y. Locker, Talia Golan
Journal: Annals of Oncology (2021)
MO32-7 High ALC, low NLR and PLR are associated with longer OS in patients with metastatic breast cancer treated with eribulin
Authors: Kazuo Matsuura, Akihiko Osaki, Ayako Nakame, Akihiro Fujimoto, Yuki Ichinose, Asami Nukui, Aya Asano, Hiroko Shimada, Hiroshi Sano, Yoshimasa Kosaka, Takahiro Hasebe, Ayaka Sakakibara, Toshiaki Saeki
Journal: Annals of Oncology (2021)
PS1133 GENOMIC ARRAYS IDENTIFY HIGH-RISK CHRONIC LYMPHOCYTIC LEUKEMIA WITH GENOMIC COMPLEXITY: A MULTI-CENTER STUDY
Authors: A. Leeksma, P. Baliakas, T. Moysiadis, C. Mellink, A. Puiggros, K. Plevova, A.-M. van der Kevie, A.N. Tran, R. Gunnarsson, H. Parker, E. van den Berg, P. Ghia, B. Espinet, S. Pospisilova, C. Tam, L. Ysebaert, M. Jarosova, F. Nguyen-Khac, D. Oscier, C. Haferlach, J. Schoumans, M. Stevens-Kroef, E. Eldering, K. Stamatopoulos, R. Rosenquist, J. Strefford, A. Kater
Journal: HemaSphere (2019)

Background: Chronic lymphocytic leukemia (CLL) is among the most heritable cancers, with 60% of disease risk genetically determined. However, most of the genetic heritability of CLL remains unexplained. Previously, we identified ATM as the first CLL risk gene. Aims: Here we leverage a deep-learning-based germline variant calling algorithm to explore germline mutational enrichment in DNA repair and cell cycle genes in CLL. Methods: A two-stage case-control analysis was conducted using gene-based mutational enrichment analysis of 50 established cancer predisposition DNA repair and cell cycle genes. In the discovery phase, a total of 285 Spanish patients and 5,608 ancestry-matched controls were evaluated. In the validation stage, an independent cohort of 514 European patients and 27,173 ancestry-matched controls were analyzed. An FDR correction was applied to both datasets and genes with a q-value <0.2 in both cohorts were considered significant. Results: Our joint analysis of 799 CLL patients from 2 genetically distinct cohorts and 32,781 ancestry-matched cancer-free controls identified ATM and CHEK2 as significantly enriched in both CLL datasets. First, our analysis recaptured the previously reported finding of ATM variant enrichment in CLL patients. Carriers of pathogenic ATM mutations in our cohorts (n = 9 patients, discovery: 1.05%, validation: 1.17%) were 2.8–3.7 times more likely to develop CLL compared to cancer-free individuals (discovery: OR = 2.8, 95%CI = 0.7–9.0, q-value = 0.181; validation: OR = 3.7, 95%CI = 1.6–8.3, q-value = 0.0454). In addition, our analysis identified 21 CLL patients carrying pathogenic CHEK2 alterations (discovery: 1.40%, validation: 3.31%), making CLL patients 4.4–8.0 times more likely to carry such alterations compared to controls (discovery: OR = 8.0, 95%CI = 2.3–27.0, q-value = 0.026; validation: OR = 4.4, 95%CI = 2.5–7.3, q-value <0.001). Summary/Conclusion: Our analysis of genetically distinct CLL cohorts, using a high-sensitivity variant calling algorithm, supports CHEK2 as a potentially novel CLL predisposition gene that may explain a portion of the missing monogenic heritability of CLL. In addition, this study highlights the DNA repair and cell cycle regulation pathways as potential drivers of CLL susceptibility.
Abstract 10879: Risk of Renal Failure With Multivessel vs. Culprit-Lesion Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock: An Updated Meta-Analysis
Authors: Amartya Kundu, Partha Sardar, Nikolaos Kakouros, Jinnette Dawn Abbott, Daniel Z Fisher
Journal: Circulation (2018)

Introduction: There is considerable debate regarding the optimal revascularization strategy in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS), particularly re...
Designer exosomes for targeted and efficient ferroptosis induction in cancer via chemo-photodynamic therapy
Authors: Jianbing Du, Zhuo Wan, Cong Wang, Fan Lu, Mengying Wei, Desheng Wang, Qiang Hao
Journal: Theranostics (2021)

Background: Efficient and specific induction of cell death in liver cancer is urgently needed. In this study, we aimed to design an exosome-based platform to deliver ferroptosis inducer (Erastin, Er) and photosensitizer (Rose Bengal, RB) into tumor tissues with high specificity. Methods: Exosome donor cells (HEK293T) were transfected with control or CD47-overexpressing plasmid. Exosomes were isolated and loaded with Er and RB via sonication method. Hepa1-6 cell xenograft C57BL/6 model was injected with control and engineered exosomes via tail vein. In vivo distribution of the injected exosomes was analyzed via tracking the fluorescence labeled exosomes. Photodynamic therapy was conducted by 532 nm laser irradiation. The therapeutic effects on hepatocellular carcinoma and toxic side-effects were systemically analyzed. Results: CD47 was efficiently loaded on the exosomes from the donor cells when CD47 was forced expressed by transfection. CD47 surface functionalization (ExosCD47) made the exosomes effectively escape the phagocytosis of mononuclear phagocyte system (MPS), and thus increased the distribution in tumor tissues. Erastin and RB could be effectively encapsulated into exosomes after sonication, and the drug-loaded exosomes (Er/RB@ExosCD47) strongly induced ferroptosis both in vitro and in vivo in tumor cells after irradiation of 532 nm laser. Moreover, compared with the control exosomes (Er/RB@ExosCtrl), Er/RB@ExosCD47 displayed much lower toxicity in liver. Conclusion: The engineered exosomes composed of CD47, Erastin, and Rose Bengal, induce obvious ferroptosis in hepatocellular carcinoma (HCC) with minimized toxicity in liver and kidney. The proposed exosomes would provide a promising strategy to treat types of malignant tumors.
P-1 Health-related quality of life of rectal cancer survivors treated with curative intent
Authors: A. Ferreira, M. Sardinha, M. Baleiras, M. Neves, A. Matos, M. Malheiro, E. Dutra, C. Rodrigues, M. Miguens, I. Guerreiro, R. da Luz, A. Martins
Journal: Annals of Oncology (2021)
A Data-Driven Transcriptional Taxonomy of Adipogenic Chemicals to Identify White and Brite Adipogens
Authors: Stephanie Kim, Eric Reed, Stefano Monti, Jennifer J. Schlezinger
Journal: Environmental Health Perspectives (2021)

BACKGROUND: Chemicals in disparate structural classes activate specific subsets of the transcriptional programs of peroxisome proliferator-activated receptor-c (PPARc) to generate adipocytes with distinct phenotypes.OBJECTIVES: Our objectives were to a) establish a novel classification method to predict PPARc ligands and modifying chemicals; and b) create a taxonomy to group chemicals on the basis of their effects on PPARc's transcriptome and downstream metabolic functions.We tested the hypothesis that environmental adipogens highly ranked by the taxonomy, but segregated from therapeutic PPARc ligands, would induce white but not brite adipogenesis.METHODS: 3T3-L1 cells were differentiated in the presence of 76 chemicals (negative controls, nuclear receptor ligands known to influence adipocyte biology, potential environmental PPARc ligands).Differentiation was assessed by measuring lipid accumulation.mRNA expression was determined by RNA-sequencing (RNA-Seq) and validated by reverse transcription-quantitative polymerase chain reaction.A novel classification model was developed using an amended random forest procedure.A subset of environmental contaminants identified as strong PPARc agonists were analyzed by their effects on lipid handling, mitochondrial biogenesis, and cellular respiration in 3T3-L1 cells and human preadipocytes.RESULTS: We used lipid accumulation and RNA-Seq data to develop a classification system that a) identified PPARc agonists; and b) sorted chemicals into likely white or brite adipogens.Expression of Cidec was the most efficacious indicator of strong PPARc activation.3T3-L1 cells treated with two known environmental PPARc ligands, tetrabromobisphenol A and triphenyl phosphate, which sorted distinctly from therapeutic ligands, had higher expression of white adipocyte genes but no difference in Pgc1a and Ucp1 expression, and higher fatty acid uptake but not mitochondrial biogenesis.Moreover, cells treated with two chemicals identified as highly ranked PPARc agonists, tonalide and quinoxyfen, induced white adipogenesis without the concomitant health-promoting characteristics of brite adipocytes in mouse and human preadipocytes.DISCUSSION: A novel classification procedure accurately identified environmental chemicals as PPARc ligands distinct from known PPARc-activating therapeutics.
association of mafld with mortality in patients with covid-19 in mexico
Authors: M. U. V. Medina, C. M. Velazquez, C. Vargas-de Leon, A. C. B. Campos, J. A. Almeyda-Farfan, A. G. Atemis, J. G. Gandara, C. P. Martinez, N. D. Fernandez-Martinez, M. D. H. Maceda, E. Reyes
Journal: Journal of Hepatology (2021)
Health4Sport: 13 safeguarding principles so that young athletes can thrive in multidisciplinary sporting environments
Authors: Boris Gojanovic, Katharina Albertin, Mario Bizzini, German Clenin, Joelle Leonie Flueck, Nicolas Mathieu, Simone Reber, Viviane Scherler
Journal: British Journal of Sports Medicine (2021)

The past year has brought on a new challenge for Swiss sport and the sports and exercise medicine (SEM) community. This is a global challenge that requires our unqualified attention. No, we are not talking about a virus, but rather about a much more insidious problem that plagues sports throughout the world: harassment and abuse.1 

In June 2020, Swiss gymnasts came forward and reported abusive experiences in their training environment.2 Soon athletes from other sports followed, feeling empowered. Most troubling was that many of the athletes were minors at the time of the reported incidents.

While situations of harassment and abuse in sport had previously been uncovered, never had they stirred the country like this. The magnitude of the testimonies, and the fact that national media outlets quickly investigated further, led to a parliamentary response: action is required and athletes must count on a system that effectively safeguards them. Currently, independent investigations are underway.

Elite sport requires high levels of commitment and pushes athletes to test their physical and mental limits. Equally, the training environment necessitates focus and discipline. Inevitably, athletes suffer from mental stress, illness …
Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts (vol 48, pg 1185, 2016)
Authors: Emma M. Jenkinson, Mathieu P. Rodero, Paul R. Kasher, Carolina Uggenti, Anthony Oojageer, Laurence C. Goosey, Yoann Rose, Christopher J. Kershaw, Jill E. Urquhart, Simon G. Williams, Sanjeev S. Bhaskar, James O'Sullivan, Gabriela M. Baerlocher, Monika Haubitz, Geraldine Aubert, Kristin W. Barañano, Angela J. Barnicoat, Roberta Battini, Andrea Berger, Edward M. Blair, Janice E. Brunstrom-Hernandez, Johannes A. Buckard, David M. Cassiman, Rosaline Caumes, Duccio M. Cordelli, Liesbeth M. de Waele, Alexander J. Fay, Patrick Ferreira, Nicholas A. Fletcher, Alan E. Fryer, Himanshu Goel, Cheryl A. Hemingway, Marco Henneke, Imelda Hughes, Rosalind J. Jefferson, Ram Kumar, Lieven Lagae, Pierre G. Landrieu, Charles M. Lourenço, Timothy J. Malpas, Sarju G. Mehta, Imke Metz, Sakkubai Naidu, Katrin Õunap, Axel Panzer, Prab Prabhakar, Gerardine Quaghebeur, Raphael Schiffmann, Elliott H. Sherr, Kanaga R. Sinnathuray, Calvin Soh, Helen S. Stewart, John Stone, Hilde van Esch, Christine E. G. van Mol, Adeline Vanderver, Emma L. Wakeling, Andrea Whitney, Graham D. Pavitt, Sam Griffiths-Jones, Gillian I. Rice, Patrick Revy, Marjo S. van der Knaap, John H. Livingston, Raymond T. O'Keefe, Yanick J. Crow
Journal: Nature Genetics (2017)
Acquired Decline in Ultrafiltration in Peritoneal Dialysis: The Role of Glucose
Authors: Raymond T. Krediet
Journal: Journal of the American Society of Nephrology (2021)

Ultrafiltration is essential in peritoneal dialysis (PD) for maintenance of euvolemia, making ultrafiltration insufficiency-preferably called ultrafiltration failure-an important complication. The mechanisms of ultrafiltration and ultrafiltration failure are more complex than generally assumed, especially after long-term treatment. Initially, ultrafiltration failure is mainly explained by a large number of perfused peritoneal microvessels, leading to a rapid decline of the crystalloid osmotic gradient, thereby decreasing aquaporin-mediated free water transport. The contribution of peritoneal interstitial tissue to ultrafiltration failure is limited during the first few years of PD, but becomes more important in long-term PD due to the development of interstitial fibrosis, which mainly consists of myofibroblasts. A dual hypothesis has been developed to explain why the continuous exposure of peritoneal tissues to the extremely high dialysate glucose concentrations causes progressive ultrafiltration decline. First, glucose absorption causes an increase of the intracellular NADH/NAD+ ratio, also called pseudohypoxia. Intracellular hypoxia stimulates myofibroblasts to produce profibrotic and angiogenetic factors, and the glucose transporter GLUT-1. Second, the increased GLUT-1 expression by myofibroblasts increases glucose uptake in these cells, leading to a reduction of the osmotic gradient for ultrafiltration. Reduction of peritoneal glucose exposure to prevent this vicious circle is essential for high-quality, long-term PD.
P-104 Risk of nausea and vomiting in a real-world data cohort of chemotherapy-treated patients with metastatic gastric or gastroesophageal junction adenocarcinoma by medical history of gastrectomy
Authors: S. de Vogel, J. van Schyndle, D. Nimke, M. Khalil, A. Arozullah, N. Robinson
Journal: Annals of Oncology (2021)
Abstract 8608: Oxidized Low Density Lipoprotein Synergizes with Toll-Like Receptor 4 Agonist to Induce the Inflammatory and Osteogenic Responses in Human Aortic Valve Interstitial Cells
Authors: Qingchun Zeng, Lihua Ao, Yufeng Zhai, David A Fullerton, Xianzhong Meng
Journal: Circulation (2011)

The inflammatory and osteogenic responses of aortic valve interstitial cells (AVICs) play an important role in the progression of calcific aortic valve stenosis. We found that stimulation of TLR4 induces the expression of inflammatory and osteogenic mediators in human HAVICs, indicating a role for TLR4 in the pathogenesis and progression of this cardiovascular disease. In patients with aortic valve stenosis, valvular tissue exhibits increased levels of oxidized LDL (oxLDL), and oxLDL induces the secretion of pro-inflammatory cytokines in monocytes and macrophages. However, it remains unclear whether oxLDL modulates the inflammatory and osteogenic responses in valvular cells. We tested the hypothesis that oxLDL augments the inflammatory and osteogenic responses to TLR4 stimulation in human AVICs. The purposes of this study were to determine: 1) whether oxLDL induces IL-6, ICAM-1 and BMP-2 in human AVICs, 2) whether oxLDL synergizes with TLR4 agonist endotoxin to augment the production of inflammatory and osteogenic mediators and 3) the mechanism by which oxLDL exerts an effect. Methods and results: Human AVICs isolated from normal aortic valve were treated with TLR4 agonist endotoxin (0.1 μg/ml), oxLDL (20 µg/ml) or endotoxin plus oxLDL for 48 h. Endotoxin alone induced the production of IL-6, ICAM-1 and BMP-2 in human AVICs. OxLDL alone had no effect on IL-6 secretion and cellular ICAM-1 protein levels, while it induced a slight increase in cellular BMP-2 protein levels. Surprisingly, cells exposed to oxLDL and endotoxin produced markedly higher levels of IL-6 (3.4 folds), ICAM-1 (4.0 folds) and BMP-2 (3.5 folds) than cells expose to endotoxin alone. Similarly, oxLDL enhanced endotoxin-induced activation of Notch1. Inhibition of Notch1 reduced IL-6, ICAM-1, BMP-2 levels in cells treated with oxLDL and endotoxin. Further, Notch1 ligand Jagged1 also augments the inflammatory and osteogenic responses to endotoxin. Conclusions: The Notch1 pathway augments TLR4-mediated inflammatory and osteogenic responses in human AVICs, and oxLDL synergizes with endotoxin to induce these responses through modulation of Notch1 activation. Thus, a synergy between oxLDL and TLR4 agonist may promote the progression of calcific aortic valve stenosis.
P25-4 Efficacy predictors of preoperative CRT and consolidation nivolumab in patients with locally advanced rectal cancer
Authors: Koji Inamori, Yosuke Togashi, Hideaki Bando, Yuichiro Tsukada, Shota Fukuoka, Ayako Suzuki, Yutaka Suzuki, Daisuke Kotani, Motohiro Kojima, Makoto Fukui, Satoshi Yuki, Yoshito Komatsu, Shigenori Homma, Akinobu Taketomi, Mamoru Uemura, Takeshi Kato, Masaaki Ito, Hiroyoshi Nishikawa, Takayuki Yoshino
Journal: Annals of Oncology (2021)
SO-29 Efficacy and safety of larotrectinib in patients with tropomyosin receptor kinase fusion-positive gastrointestinal cancer: An expanded dataset
Authors: V. Boni, A. Drilon, J. Deeken, E. Garralda, H. Chung, I. Kinoshita, D. Oh, J. Patel, R. Xu, R. Norenberg, N. Brega, L. Dima, D. Hong, J. Berlin
Journal: Annals of Oncology (2021)