tbuckley/cabot-search huggingface dataset:
Appendiceal orifice: more than it meets the eye
Authors: Cláudia Pinto, Rui Silva
Journal: Endoscopy (2021)

A healthy and asymptomatic 38-year-old man presented with accidental foreign body ingestion. The abdominal X-ray showed a radiopaque image in the right inferior quadrant ([Fig. 1]). An abdominopelvic computed tomography (CT) scan was performed and showed a metallic-density image apparently within the cecal appendix without evidence of an inflammatory process ([Fig. 2]).
Simultaneous disruption of PRC2 and enhancer function underlies histone H3.3-K27M oncogenic activity in human hindbrain neural stem cells
Authors: Gerard L. Brien, Raul Bardini Bressan, Craig Monger, Dáire Gannon, Eimear Lagan, Anthony M. Doherty, Evan Healy, Hannah Neikes, Darren J. Fitzpatrick, Orla Deevy, Vivien Grant, Maria-Angeles Marqués-Torrejón, Neza Alfazema, Steven M. Pollard, Adrian P. Bracken
Journal: Nature Genetics (2021)
Recombinant Erythroid Kruppel-Like Factor Fused to GATA1 up-Regulates δ-Globin Expression In Erythroid Cells.
Authors: Jianqiongz Zhu, Kyung Chin, Wulin Aerbajinai, Cecelia D Trainor, Gao Perter, Griffin P. Rodgers
Journal: Blood (2010)
The Intersection of Societal Inequalities and Health Care
Authors: Randy Vince
Journal: JAMA Oncology (2021)

Adrien N. Bernstein, MD; Ruchika Talwar, MD; Elizabeth Handorf, PhD; Kaynaat Syed, MHA; John Danella, MD; Serge Ginzburg, MD; Laurence Belkoff, DO; Adam C. Reese, MD; Jeffery Tomaszewski, MD; Edouard Trabulsi, MD; Eric A. Singer, MD, MA, MS; Bruce Jacobs, MD; Alexander Kutikov, MD; Robert Uzzo, MD, MBA; Jay D. Raman, MD; Thomas Guzzo, MD, MPH; Marc C. Smaldone, MD, MSHP; Andres Correa, MD
IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin
Authors: Nengzhi Pang, Jingxuan Shi, Le Qin, Aiming Chen, Yuou Tang, Hainan Yang, Yufeng Huang, Qingde Wu, Xufeng Li, Bingjia He, Tianheng Li, Baoxia Liang, Jinglin Zhang, Bihui Cao, Manting Liu, Yunfei Feng, Xiaodie Ye, Xiaopei Chen, Lu Wang, Yu Tian, Hao Li, Junping Li, Hong Hu, Jingping He, Yuling Hu, Cheng Zhi, Zhaoyang Tang, Yibo Gong, Fangting Xu, Linfeng Xu, Weijun Fan, Ming Zhao, Deji Chen, Hui Lian, Lili Yang, Peng Li, Zhenfeng Zhang
Journal: Journal of Hematology & Oncology (2021)

Abstract Although chimeric antigen receptor (CAR)-engineered T cells have shown great success in the treatment of B cell malignancies, this strategy has limited efficacy in patients with solid tumors. In mouse CAR-T cells, IL-7 and CCL19 expression have been demonstrated to improve T cell infiltration and CAR-T cell survival in mouse tumors. Therefore, in the current study, we engineered human CAR-T cells to secrete human IL-7 and CCL19 (7 × 19) and found that these 7 × 19 CAR-T cells showed enhanced capacities of expansion and migration in vitro. Furthermore, 7 × 19 CAR-T cells showed superior tumor suppression ability compared to conventional CAR-T cells in xenografts of hepatocellular carcinoma (HCC) cell lines, primary HCC tissue samples and pancreatic carcinoma (PC) cell lines. We then initiated a phase 1 clinical trial in advanced HCC/PC/ovarian carcinoma (OC) patients with glypican-3 (GPC3) or mesothelin (MSLN) expression. In a patient with advanced HCC, anti-GPC3-7 × 19 CAR-T treatment resulted in complete tumor disappearance 30 days post intratumor injection. In a patient with advanced PC, anti-MSLN-7 × 19 CAR-T treatment resulted in almost complete tumor disappearance 240 days post-intravenous infusion. Our results demonstrated that the incorporation of 7 × 19 into CAR-T cells significantly enhanced the antitumor activity against human solid tumor. Trial registration: NCT03198546. Registered 26 June 2017, https://clinicaltrials.gov/ct2/show/NCT03198546?term=NCT03198546&amp;draw=2&amp;rank=1
Quantitative disease risk scores from EHR with applications to clinical risk stratification and genetic studies
Authors: Danqing Xu, Chen Wang, Atlas Khan, Ning Shang, Zihuai He, Adam Gordon, Iftikhar J. Kullo, Shawn Murphy, Yizhao Ni, Wei-Qi Wei, Ali Gharavi, Krzysztof Kiryluk, Chunhua Weng, Iuliana Ionita-Laza
Journal: npj Digital Medicine (2021)

Labeling clinical data from electronic health records (EHR) in health systems requires extensive knowledge of human expert, and painstaking review by clinicians. Furthermore, existing phenotyping algorithms are not uniformly applied across large datasets and can suffer from inconsistencies in case definitions across different algorithms. We describe here quantitative disease risk scores based on almost unsupervised methods that require minimal input from clinicians, can be applied to large datasets, and alleviate some of the main weaknesses of existing phenotyping algorithms. We show applications to phenotypic data on approximately 100,000 individuals in eMERGE, and focus on several complex diseases, including Chronic Kidney Disease, Coronary Artery Disease, Type 2 Diabetes, Heart Failure, and a few others. We demonstrate that relative to existing approaches, the proposed methods have higher prediction accuracy, can better identify phenotypic features relevant to the disease under consideration, can perform better at clinical risk stratification, and can identify undiagnosed cases based on phenotypic features available in the EHR. Using genetic data from the eMERGE-seq panel that includes sequencing data for 109 genes on 21,363 individuals from multiple ethnicities, we also show how the new quantitative disease risk scores help improve the power of genetic association studies relative to the standard use of disease phenotypes. The results demonstrate the effectiveness of quantitative disease risk scores derived from rich phenotypic EHR databases to provide a more meaningful characterization of clinical risk for diseases of interest beyond the prevalent binary (case-control) classification.
Author response to Cunha <i>et al</i>
Authors: Rivka R Colen, Christian Rolfo, Murat Ak, Mira Ayoub, Sara Ahmed, Nabil Elshafeey, Priyadarshini Mamindla, Pascal O Zinn, Chaan Ng, Raghu Vikram, Spyridon Bakas, Christine B Peterson, Jordi Rodon Ahnert, Vivek Subbiah, Daniel D Karp, Bettzy Stephen, Joud Hajjar, Aung Naing
Journal: Journal for ImmunoTherapy of Cancer (2021)

The need to identify biomarkers to predict immunotherapy response for rare cancers has been long overdue. We aimed to study this in our paper, 'Radiomics analysis for predicting pembrolizumab response in patients with advanced rare cancers'. In this response to the Letter to the Editor by Cunha et al, we explain and discuss the reasons behind choosing LASSO (Least Absolute Shrinkage and Selection Operator) and XGBoost (eXtreme Gradient Boosting) with LOOCV (Leave-One-Out Cross-Validation) as the feature selection and classifier method, respectively for our radiomics models. Also, we highlight what care was taken to avoid any overfitting on the models. Further, we checked for the multicollinearity of the features. Additionally, we performed 10-fold cross-validation instead of LOOCV to see the predictive performance of our radiomics models.
MO18-5 Establishment of organoids derived from patients with advanced thoracic malignancies
Authors: Jun Oyanagi, Yasuhiro Koh, Koichi Sato, Masanori Tanaka, Katsuyuki Furuta, Takeya Sugimoto, Ryota Shibaki, Shunsuke Teraoka, Daichi Fujimoto, Nahomi Tokudome, Hiroaki Akamatsu, Atsushi Hayata, Yuichi Ozawa, Hiroki Ueda, Nobuyuki Yamamoto
Journal: Annals of Oncology (2021)
Government has failed to deliver on smoke-free pledge for England, say leading doctors
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The government has failed to take the “bold action” required to meet its pledge to make England smoke-free by 2030, and should introduce a levy on tobacco manufacturers to fund a more comprehensive strategy, a group of experts have urged.

Two years ago, ministers made a pledge to make England smoke-free by 2030, underpinned by making smoked tobacco obsolete and smokers quitting or moving to reduced risk products like e-cigarettes.

But in an open letter1 to …
MO24-1 Phase I/IIa trial evaluating safety and clinical activity of DuoBody®-PD-L1×4-1BB (GEN1046) in advanced solid tumors
Authors: Ignacio Melero, Ravit Geva, Eytan Ben-Ami, Corinne Maurice-Dror, Emiliano Calvo, Patricia LoRusso, Ozlem Tureci, Michelle Niewood, Ugur Sahin, Maria Jure-Kunkel, Ulf Forssmann, Tahamtan Ahmadi, Guzman Alonso
Journal: Annals of Oncology (2021)
Nanocellulose, a versatile platform: From the delivery of active molecules to tissue engineering applications
Authors: Tejal V. Patil, Dinesh K. Patel, Sayan Deb Dutta, Keya Ganguly, Tuhin Subhra Santra, Ki-Taek Lim
Journal: Bioactive Materials (2021)

Nanocellulose, a biopolymer, has received wide attention from researchers owing to its superior physicochemical properties, such as high mechanical strength, low density, biodegradability, and biocompatibility. Nanocellulose can be extracted from wide range of sources, including plants, bacteria, and algae. Depending on the extraction process and dimensions (diameter and length), they are categorized into three main types: cellulose nanocrystals (CNCs), cellulose nanofibrils (CNFs), and bacterial nanocellulose (BNC). CNCs are a highly crystalline and needle-like structure, whereas CNFs have both amorphous and crystalline regions in their network. BNC is the purest form of nanocellulose. The nanocellulose properties can be tuned by chemical functionalization, which increases its applicability in biomedical applications. This review highlights the fabrication of different surface-modified nanocellulose to deliver active molecules, such as drugs, proteins, and plasmids. Nanocellulose-mediated delivery of active molecules is profoundly affected by its topographical structure and the interaction between the loaded molecules and nanocellulose. The applications of nanocellulose and its composites in tissue engineering have been discussed. Finally, the review is concluded with further opportunities and challenges in nanocellulose-mediated delivery of active molecules.
An immunodominant NP105–113-B*07:02 cytotoxic T cell response controls viral replication and is associated with less severe COVID-19 disease
Authors: Yanchun Peng, Suet Ling Felce, Danning Dong, Frank Penkava, Alexander J. Mentzer, Xuan Yao, Guihai Liu, Zixi Yin, Ji-Li Chen, Yongxu Lu, Dannielle Wellington, Peter A. C. Wing, Delaney C. C. Dominey-Foy, Chen Jin, Wenbo Wang, Megat Abd Hamid, Ricardo A. Fernandes, Beibei Wang, Anastasia Fries, Xiaodong Zhuang, Neil Ashley, Timothy Rostron, Craig Waugh, Paul Sopp, Philip Hublitz, Ryan Beveridge, Tiong Kit Tan, Christina Dold, Andrew J. Kwok, Charlotte Rich-Griffin, Wanwisa Dejnirattisa, Chang Liu, Prathiba Kurupati, Isar Nassiri, Robert A. Watson, Orion Tong, Chelsea A. Taylor, Piyush Kumar Sharma, Bo Sun, Fabiola Curion, Santiago Revale, Lucy C. Garner, Kathrin Jansen, Ricardo C. Ferreira, Moustafa Attar, Jeremy W. Fry, Rebecca A. Russell, Hans J. Stauss, William James, Alain Townsend, Ling-Pei Ho, Paul Klenerman, Juthathip Mongkolsapaya, Gavin R. Screaton, Calliope Dendrou, Stephen N. Sansom, Rachael Bashford-Rogers, Benny Chain, Geoffrey L. Smith, Jane A. McKeating, Benjamin P. Fairfax, Paul Bowness, Andrew J. McMichael, Graham Ogg, Julian C. Knight, Tao Dong
Journal: Nature Immunology (2021)

Abstract NP 105–113 -B*07:02-specific CD8 + T cell responses are considered among the most dominant in SARS-CoV-2-infected individuals. We found strong association of this response with mild disease. Analysis of NP 105–113 -B*07:02-specific T cell clones and single-cell sequencing were performed concurrently, with functional avidity and antiviral efficacy assessed using an in vitro SARS-CoV-2 infection system, and were correlated with T cell receptor usage, transcriptome signature and disease severity (acute n = 77, convalescent n = 52). We demonstrated a beneficial association of NP 105–113 -B*07:02-specific T cells in COVID-19 disease progression, linked with expansion of T cell precursors, high functional avidity and antiviral effector function. Broad immune memory pools were narrowed postinfection but NP 105–113 -B*07:02-specific T cells were maintained 6 months after infection with preserved antiviral efficacy to the SARS-CoV-2 Victoria strain, as well as Alpha, Beta, Gamma and Delta variants. Our data show that NP 105–113 -B*07:02-specific T cell responses associate with mild disease and high antiviral efficacy, pointing to inclusion for future vaccine design.
Abstract 14264: Weight Loss-Induced Blood Pressure Reduction: Different Mechanisms Between a Calorie Restricted Diet and Exercise
Authors: Kazuko Masuo, Hiromi Rakugi, Toshio Ogihara, Gavin Lambert
Journal: Circulation (2011)

Objective: The present study compared the effectiveness of a mild calorie restricted diet (D) alone, exercise (EX) alone and a combination of D+EX on weight loss-induced blood pressure (BP) reducti...
A perspective on the radiopharmaceutical requirements for imaging and therapy of glioblastoma
Authors: Julie Bolcaen, Janke Kleynhans, Shankari Nair, Jeroen Verhoeven, Ingeborg Goethals, Mike Sathekge, Charlot Vandevoorde, Thomas Ebenhan
Journal: Theranostics (2021)

Despite numerous clinical trials and pre-clinical developments, the treatment of glioblastoma (GB) remains a challenge. The current survival rate of GB averages one year, even with an optimal standard of care. However, the future promises efficient patient-tailored treatments, including targeted radionuclide therapy (TRT). Advances in radiopharmaceutical development have unlocked the possibility to assess disease at the molecular level allowing individual diagnosis. This leads to the possibility of choosing a tailored, targeted approach for therapeutic modalities. Therapeutic modalities based on radiopharmaceuticals are an exciting development with great potential to promote a personalised approach to medicine. However, an effective targeted radionuclide therapy (TRT) for the treatment of GB entails caveats and requisites. This review provides an overview of existing nuclear imaging and TRT strategies for GB. A critical discussion of the optimal characteristics for new GB targeting therapeutic radiopharmaceuticals and clinical indications are provided. Considerations for target selection are discussed, i.e. specific presence of the target, expression level and pharmacological access to the target, with particular attention to blood-brain barrier crossing. An overview of the most promising radionuclides is given along with a validation of the relevant radiopharmaceuticals and theranostic agents (based on small molecules, peptides and monoclonal antibodies). Moreover, toxicity issues and safety pharmacology aspects will be presented, both in general and for the brain in particular.
Public reaction to the portrayal of the tobacco industry in the film The Insider
Authors: Hg Dixon, Dj Hill, R Borland, Sj Paxton
Journal: BMJ (2001)

OBJECTIVES: To assess public perceptions of the tobacco industry and behavioural intentions for tobacco use in response to watching the film The Insider. DESIGN: Self administered pre-film survey conducted immediately before viewing and post-film telephone survey conducted within 1-5 weeks of viewing. SETTING: Two commercial cinemas in Melbourne, Australia. SUBJECTS: 323 cinema patrons were recruited before screening of target films. 182 watched The Insider, 141 watched Erin Brockovich. INTERVENTIONS: Subjects watched one of two films: The Insider which featured information about unethical conduct by the tobacco industry and negative information about the health effects of smoking, or the control film Erin Brockovich which had an analogous plot without anti-tobacco content. MAIN OUTCOME MEASURES: Pre-film questionnaire: assessed movie viewing habits, demographic characteristics, smoking status, attitudes towards the tobacco industry, intentions for smoking. Post-film questionnaire: assessed same attitudes and intentions plus questions on the film viewed and perceptions of smoking prevalence. RESULTS: 266 (82%) subjects completed the post-film survey. Attitudes toward the tobacco industry were unfavourable at baseline. Those who saw The Insider held more negative views of business conduct by the tobacco industry than those who saw Erin Brockovich, once pre-existing attitudes to the industry were controlled for. The Insider also appears to have promoted a short term reduction in intentions to smoke. CONCLUSIONS: Results of this study suggest that if people were recurrently exposed to anti-tobacco content in movies there is potential for a more substantial and lasting impact on attitudes toward the tobacco industry and smoking.
O4-3 Utility of an artificial intelligence-curation system, QA Commons, for clinical sequencing: SCRUM-Japan MONSTAR-SCREEN
Authors: Satoshi Horasawa, Takao Fujisawa, Yasutoshi Sakamoto, Naomi Kuramoto, Yoshiaki Nakamura, Hiroya Taniguchi, Takayuki Yoshino
Journal: Annals of Oncology (2021)
A Honeycomb‐Like Bismuth/Manganese Oxide Nanoparticle with Mutual Reinforcement of Internal and External Response for Triple‐Negative Breast Cancer Targeted Therapy
Authors: Xingyi Xu, Rongyuan Zhang, Xianfeng Yang, Yao Lu, Zhongmin Yang, Mingying Peng, Zhijun Ma, Ju Jiao, Lihua Li
Journal: Advanced Healthcare Materials (2021)

Triple-negative breast cancer (TNBC) exhibits aggressive behavior and high levels of metastasis owing to its complex heterogeneous structure and lack of specific receptors. Here, tumor cell membrane (CM)-coated bismuth/manganese oxide nanoparticles (NPs) with high indocyanine green (ICG) payload up to 50.6 wt% (mBMNI NPs) for targeted TNBC therapy are constructed. The extra-high drug load Bi@Bi2 O3 @MnOx NPs (honey-comb like structure) are formed by Kirkendall effect and electrostatic attraction. After modified with CM, they can home into tumor sites precisely, where they respond to internal overexpressed glutathione (GSH), releasing Mn2+ for chemodynamic therapy (CDT) with GSH depletion, while H2 O2 degrades into O2 enabling relief of tumor hypoxia. In response to external near-infrared irradiation, mBMNI NPs intelligently generate vigorous heat and single oxygen (1 O2 ) for photothermal therapy (PTT) and photodynamic therapy (PDT) owing to high load. Importantly, O2 production and GSH consumption during the internal response reinforce external PDT, while the heat generated through PTT during the external response promotes internal CDT. The honeycomb-like structure with high ICG load and mutual reinforcement between internal and external response results in excellent therapeutic effects against TNBC.
Proteomic Profiling Identifies c-KIT and 53BP1 As Resistance Factors of AML Relapse Post Allogeneic Stem Cell Transplantation with G-CSF/Plerixafor/Busulfan-Fludarabine Conditioning
Authors: Zhihong Zeng, Hongbo Lu, Rui-Yu Wang, Wenbin Lu, Julianne Chen, Christopher B Benton, Keith Baggerly, Elizabeth J Shpall, Richard E Champlin, Marina Konopleva, Michael Andreeff
Journal: Blood (2017)
Epigenetic and transcriptional control of interferon-β
Authors: Andrew W. Daman, Steven Z. Josefowicz
Journal: The Journal of Experimental Medicine (2021)

The three classes of interferons (IFNs) share the ability to inhibit viral replication, activating cell transcriptional programs that regulate both innate and adaptive responses to viral and intracellular bacterial challenge. Due to their unique potency in regulating viral replication, and their association with numerous autoimmune diseases, the tightly orchestrated transcriptional regulation of IFNs has long been a subject of intense investigation. The protective role of early robust IFN responses in the context of infection with SARS-CoV-2 has further underscored the relevance of these pathways. In this viewpoint, rather than focusing on the downstream effects of IFN signaling (which have been extensively reviewed elsewhere), we will summarize the historical and current understanding of the stepwise assembly and function of factors that regulate IFNβ enhancer activity (the "enhanceosome") and highlight opportunities for deeper understanding of the transcriptional control of the ifnb gene.
Effects of N-Acetylcysteine Infusion in Patients with Sickle Cell Disease during Vaso-Occlusive Crises
Authors: Hasan Ozpolat, Junmei Chen, Xiaoyun Fu, Melissa Dominguez, Jennie Le, Minhua Ling, Sophie Schmitter, Sarah Ruuska, Dominic W. Chung, Jose A. Lopez, Barbara Konkle
Journal: Blood (2017)
Growth hormone receptor disrupts glucose homeostasis via promoting and stabilizing retinol binding protein 4
Authors: Jinxin Liu, Chenzhipeng Nie, Lamei Xue, Ying Yan, Shengnan Liu, Juan Sun, Mingcong Fan, Haifeng Qian, Hao Ying, Li Wang, Yan Li
Journal: Theranostics (2021)

Rationale: The molecular mechanisms underlying the pathogenesis of systemic insulin resistance in type 2 diabetes remain elusive. Growth hormone receptor (GHR) deficiency has long been known to improved insulin sensitivity. However, whether hepatic GHR overexpression or activation is a cause of insulin resistance is still unknown. The aim of this study was to identify the new role of GHR in systemic insulin resistance and explore the underlying mechanism. Method: Different samples obtained from obese humans, ob/ob mice, db/db mice, high-fat diet (HFD)-fed mice and primary mouse hepatocytes were used to evaluate the correlations between GHR and metabolic disorders. Recombinant adeno-associated viruses encoding GHR and STAT5 and GHR knockout mice were used to investigate the roles of hepatic GHR in glucose homeostasis. Tissue H&E, Oil Red O and PAS staining were performed for histomorphological analysis. Gel filtration chromatography was employed for the separation of serum RBP4-TTR complexes. Plasmids (related to GHR, STAT5 and HIF1α), siRNA oligos (siGHR and siSTAT5), luciferase activity and ChIP assays were used to explore the potential mechanism of hepatic GHR. Results: Here, we found that hepatic GHR expression was elevated during metabolic disorder. Accordingly, hepatic GHR overexpression disrupted systemic glucose homeostasis by promoting gluconeogenesis and disturbing insulin responsiveness in the liver. Meanwhile, hepatic GHR overexpression promoted lipolysis in white adipose tissue and repressed glucose utilization in skeletal muscle by promoting the circulating level of RBP4, which contributed to impaired systemic insulin action. A mechanistic study revealed that hepatic GHR disrupted systemic insulin sensitivity by increasing RBP4 transcription by activating STAT5. Additionally, overexpression of hepatic GHR promoted TTR transcriptional levels by enhancing the expression of HIF1α, which not only increased the protein stability of RBP4 but also inhibited renal clearance of RBP4 in serum. Conclusions: Hepatic GHR overexpression and activation accelerated systemic insulin resistance by increasing hepatic RBP4 production and maintaining circulating RBP4 homeostasis. Our current study provides novel insights into the pathogenesis of type 2 diabetes and its associated metabolic complications.
MO16-4 Development of a screening tool to determine support needs for Japanese adolescents and young adults with cancer
Authors: Takatoshi Hirayama, Yuko Yanai, Hiroto Ishiki, Akie Shindo, Moeko Tanaka, Tomomi Kobayashi, Rebekah Kojima, Ayako Mori, Tatsuya Suzuki, Eriko Satomi
Journal: Annals of Oncology (2021)