tbuckley/cabot-search huggingface dataset:
Metabolic Syndrome and Risk of Gastrointestinal Cancers: An Investigation Using Large-scale Molecular Data
Authors: Joseph A. Rothwell, Mazda Jenab, Mojgan Karimi, Thérèse Truong, Yahya Mahamat-Saleh, Pietro Ferrari, S. Ghazaleh Dashti, Tilman Kühn, Amanda J. Cross, Gianluca Severi, Marc J. Gunter, Neil Murphy
Journal: Clinical Gastroenterology and Hepatology (2021)

Gastrointestinal cancer risk is influenced by the presence of metabolic syndrome (MetS). However, previous epidemiologic studies lacked full serological biomarker data for the classification of MetS, and the interaction of MetS with germline cancer risk variants is unknown.
P70.14 PRKDC Mutations Recurrently Found in Non-Small Cell Lung Cancer in East Asian Patients
Authors: F. Lan, W. Wang, C. Xu, D. Wang, Y. Zhu, W. Zhuang, M. Fang, W. Li, G. Wang, Q. Wang, Y. Song, S. Lu
Journal: Journal of Thoracic Oncology (2021)
Impact of Joint Lung Cancer Screening and Cessation Interventions Under the New Recommendations of the U.S. Preventive Services Task Force
Authors: Rafael Meza, Pianpian Cao, Jihyoun Jeon, Kathryn L. Taylor, Jeanne S. Mandelblatt, Eric J. Feuer, Douglas R. Lowy
Journal: Journal of Thoracic Oncology (2021)

In 2021, the U.S. Preventive Services Task Force (USPSTF) revised its lung cancer screening recommendations expanding its eligibility. As more smokers become eligible, cessation interventions at the point of screening could enhance the benefits. Here, we evaluate the effects of joint screening and cessation interventions under the new recommendations. A validated lung cancer natural history model was used to estimate lifetime number of low-dose computed tomography screens, percentage ever screened, lung cancer deaths, lung cancer deaths averted, and life-years gained for the 1960 U.S. birth cohort aged 45 to 90 years (4.5 million individuals). Screening occurred according to the USPSTF 2013 and 2021 recommendations with varying uptake (0%, 30%, 100%), with or without a cessation intervention at the point of screening with varying effectiveness (15%, 100%). Screening 30% of the eligible population according to the 2021 criteria with no cessation intervention (USPSTF 2021, 30% uptake, without cessation intervention) was estimated to result in 6845 lung cancer deaths averted and 103,725 life-years gained. These represent 28% and 34% increases, respectively, relative to screening according to the 2013 guidelines (USPSTF 2013, 30% uptake, without cessation intervention). Adding a cessation intervention at the time of the first screen with 15% effectiveness (USPSTF 2021, 30% uptake, with cessation intervention with 15% effectiveness) was estimated to result in 2422 additional lung cancer deaths averted (9267 total, ∼73% increase versus USPSTF 2013, 30% uptake, without cessation intervention) and 322,785 life-years gained (∼318% increase). Screening 100% of the eligible according to the 2021 guidelines with no cessation intervention (USPSTF 2021, 100% uptake, without cessation intervention) was estimated to result in 23,444 lung cancer deaths averted (∼337% increase versus USPSTF 2013, 30% uptake, without cessation intervention) and 354,330 life-years gained (∼359% increase). Adding a cessation intervention with 15% effectiveness (USPSTF 2021, 100% uptake, with cessation intervention with 15% effectiveness) would result in 31,998 lung cancer deaths averted (∼497% increase versus USPSTF 2013, 30% uptake, without cessation intervention) and 1,086,840 life-years gained (∼1309% increase). Joint screening and cessation interventions would result in considerable lung cancer deaths averted and life-years gained. Adding a one-time cessation intervention of modest effectiveness (15%) results in comparable life-years gained as increasing screening uptake from 30% to 100% because while cessation decreases mortality from many causes, screening only reduces lung cancer mortality. This simulation indicates that incorporating cessation programs into screening practice should be a priority as it can maximize overall benefits.
Comparison of Different Investigation Strategies to Defer Cardiac Testing in Patients With Stable Chest Pain
Authors: Jia Zhou, Chunjie Li, Hongliang Cong, Lixiong Duan, Hao Wang, Chengjian Wang, Yahang Tan, Yujie Liu, Ying Zhang, Xiujun Zhou, Hong Zhang, Xing Wang, Yanhe Ma, Junjie Yang, Yundai Chen, Zhigang Guo
Journal: JACC. Cardiovascular imaging (2021)
P18.01 Treatment Efficacy of HER2-Mutant Lung Adenocarcinoma by Immune Checkpoint Inhibitors
Authors: X. Chu, H. Qiang, M. Xie, X. Li, J. Zhao, Y. Wu, J. Zhou, J. Ye, C. Zhao, C. Han, T. Chu, C. Su
Journal: Journal of Thoracic Oncology (2021)
Mechanism of boric acid cytotoxicity in breast cancer cell lines
Authors: Anu Elegbede, Shirly Shang, Casey Hall, Stephen Carper
Journal: Cancer Research (2007)

3384  Breast Cancer is the most common form of cancer in women. While there are several treatment regimens available, current efforts are being made toward early detection and chemo-prevention. Boric acid, an essential plant element, has recently been implicated as a chemo-preventive agent in prostate cancer. However, the mechanism of action is not yet fully known. Our interest is to determine if Boric acid displays this same preventative role in breast cancer and by what mechanism it acts. Integrins are heterodimeric, glycoprotein, transmembrane molecules responsible for cell adhesion, survival, motility, growth and interaction. We hypothesize that Boric acid molecules interact with integrins through cis-diol bonds and mediate a response in breast cancer cells. To test this hypothesis we use Phenylboronic acid (PBA), a bulkier analog of Boric acid, on both breast ductal carcinoma, ZR-75-1, and breast andenocarcinoma, MCF-7. We studied cell growth, cell adherance and cytotoxicity using PBA. Proliferation assays using 1mM PBA display a 68% inhibition of growth beginning on day 3 in ZR-75-1 cells and 70% inhibition of growth on day 5 in MCF-7. Adhesion assays with 1mM PBA resulted in a decrease in adherence of treated cells (ZR-75-1 and MCF-7) even in the presence of MnCl2 (ZR-75-1), which increases cell adherence. Cytotoxicity assays show a dose response in cell death with increasing concentrations of PBA (0.20 mM - 5.0 mM). In all these preliminary experiments, we also observed ZR-75-1 cells to be more sensitive to PBA treatment than MCF-7. We will investigate the role of integrins in Boric acid response through observing cell survival, identifying specific integrins involved with PBA through western blots and identifying up-regulated proteins following treatment with PBA using protein microarray analysis.
P10.02 Improved Survival of Elderly Patients with NSCLC Treated in the Immunotherapy Era: A Historical Cohort Study
Authors: G. Pelizzari, G. Targato, C. Corvaja, A. Fantin, G. De Maglio, C. Rossetto, S. Rizzato, G. Fasola, A. Follador
Journal: Journal of Thoracic Oncology (2021)
Molecular Pathology of Laminopathies
Authors: Ji-Yeon Shin, Howard J. Worman
Journal: Annual Review of Pathology Mechanisms of Disease (2021)

The nuclear envelope is composed of the nuclear membranes, nuclear lamina, and nuclear pore complexes. Laminopathies are diseases caused by mutations in genes encoding protein components of the lamina and these other nuclear envelope substructures. Mutations in the single gene encoding lamin A and C, which are expressed in most differentiated somatic cells, cause diseases affecting striated muscle, adipose tissue, peripheral nerve, and multiple systems with features of accelerated aging. Mutations in genes encoding other nuclear envelope proteins also cause an array of diseases that selectively affect different tissues or organs. In some instances, the molecular and cellular consequences of laminopathy-causing mutations are known. However, even when these are understood, mechanisms explaining specific tissue or organ pathology remain enigmatic. Current mechanistic hypotheses focus on how alterations in the nuclear envelope may affect gene expression, including via the regulation of signaling pathways, or cellular mechanics, including responses to mechanical stress.
Sequencing-based genome-wide association studies reporting standards
Authors: Aoife McMahon, Elizabeth Lewis, Annalisa Buniello, Maria Cerezo, Peggy Hall, Elliot Sollis, Helen Parkinson, Lucia A. Hindorff, Laura W. Harris, Jacqueline A.L. MacArthur
Journal: Cell Genomics (2021)

Genome sequencing has recently become a viable genotyping technology for use in genome-wide association studies (GWASs), offering the potential to analyze a broader range of genome-wide variation, including rare variants. To survey current standards, we assessed the content and quality of reporting of statistical methods, analyses, results, and datasets in 167 exome- or genome-wide-sequencing-based GWAS publications published from 2014 to 2020; 81% of publications included tests of aggregate association across multiple variants, with multiple test models frequently used. We observed a lack of standardized terms and incomplete reporting of datasets, particularly for variants analyzed in aggregate tests. We also find a lower frequency of sharing of summary statistics compared with array-based GWASs. Reporting standards and increased data sharing are required to ensure sequencing-based association study data are findable, interoperable, accessible, and reusable (FAIR). To support that, we recommend adopting the standard terminology of sequencing-based GWAS (seqGWAS). Further, we recommend that single-variant analyses be reported following the same standards and conventions as standard array-based GWASs and be shared in the GWAS Catalog. We also provide initial recommended standards for aggregate analyses metadata and summary statistics.
Ritonavir inhibits breast cancer cell proliferation, in part, by inhibiting Hsp90 function and Akt phosphorylation
Authors: Ranjana Mitra, Anjaiah Srirangam, Mu Wang, Janice Blum, Harikrishna Nakshatri, David A. Potter
Journal: Cancer Research (2005)

2288  The mechanisms by which the HIV protease inhibitor ritonavir inhibits cancer cell growth are poorly understood. We have previously demonstrated that ritonavir inhibits calpain and not the proteasome in the MDA-MB-231 line and that ritonavir inhibits the growth of the MDA-MB-231 line in vitro and in a mammary fat pad xenograft model. Ritonavir up-regulates the calpain target p27, and induces nuclear localization, associated with inhibition of cell cycle progression at the G1/S checkpoint. Apoptosis is induced 3-fold by ritonavir compared to the vehicle control at 24 h, from 5 to 18%, as measured by propidium iodide/Annexin-FITC staining. Akt levels are not affected at 24 of ritonavir exposure, while Akt phosphorylation is down-regulated by 80%. These results indicate that ritonavir inhibits two targets in the MDA-MB-231 line. Calpain inhibition by m-calpain siRNA or PD150606 does not inhibit Akt phosphorylation or induce apoptosis, but up-regulates p27, suggesting that ritonavir-induced apoptosis may involve a non-protease target. One candidate ritonavir target is Hsp90, which promotes Akt folding and phosphorylation. Surface plasmon resonance biosensor analysis revealed that ritonavir binds to human Hsp90, exhibiting a KD of 7.8 microM. Ritonavir inhibits Hsp90 /Akt and Hsp90/mutant p53 complex formation in the MDA-MB-231 line, suggesting that ritonavir blocks Hsp90 interaction with client proteins. These results indicate that ritonavir inhibits breast cancer growth, in part, by inhibiting Hsp90 function and associated Akt phosphorylation, resulting in apoptosis, and in part, by intracellular calpain inhibition and upregulation of p27, resulting in G1 cell cycle arrest.
56P Continuation treatment with immunotherapy beyond two years in patients with metastasic non-small cell lung cancer: Retrospective analysis of optimal duration treatment
Authors: A.V. Pellicer Boigues, J. Garde Noguera, J. Garcia Sanchez, N. Piera, T. Fenollosa Sanz, P. Llor Rodriguez, J. Iranzo Barreira, P. Riquelme Cabrera, M.L. Fernandez Murga Chavanne, A. Llombart Cussac
Journal: Annals of Oncology (2021)
Targeting human leukocyte antigen G with chimeric antigen receptors of natural killer cells convert immunosuppression to ablate solid tumors
Authors: Chia-Ing Jan, Shi-Wei Huang, Peter Canoll, Jeffrey N Bruce, Yu-Chuan Lin, Chih-Ming Pan, Hsin-Man Lu, Shao-Chih Chiu, Der-Yang Cho
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Immunotherapy against solid tumors has long been hampered by the development of immunosuppressive tumor microenvironment, and the lack of a specific tumor-associated antigen that could be targeted in different kinds of solid tumors. Human leukocyte antigen G (HLA-G) is an immune checkpoint protein (ICP) that is neoexpressed in most tumor cells as a way to evade immune attack and has been recently demonstrated as a useful target for chimeric antigen receptor (CAR)-T therapy of leukemia by in vitro studies. Here, we design and test for targeting HLA-G in solid tumors using a CAR strategy. Methods We developed a novel CAR strategy using natural killer (NK) cell as effector cells, featuring enhanced cytolytic effect via DAP12-based intracellular signal amplification. A single-chain variable fragment (scFv) against HLA-G is designed as the targeting moiety, and the construct is tested both in vitro and in vivo on four different solid tumor models. We also evaluated the synergy of this anti-HLA-G CAR-NK strategy with low-dose chemotherapy as combination therapy. Results HLA-G CAR-transduced NK cells present effective cytolysis of breast, brain, pancreatic, and ovarian cancer cells in vitro, as well as reduced xenograft tumor growth with extended median survival in orthotopic mouse models. In tumor coculture assays, the anti-HLA-G scFv moiety promotes Syk/Zap70 activation of NK cells, suggesting reversal of the HLA-G-mediated immunosuppression and hence restoration of native NK cytolytic functions. Tumor expression of HLA-G can be further induced using low-dose chemotherapy, which when combined with anti-HLA-G CAR-NK results in extensive tumor ablation both in vitro and in vivo. This upregulation of tumor HLA-G involves inhibition of DNMT1 and demethylation of transporter associated with antigen processing 1 promoter. Conclusions Our novel CAR-NK strategy exploits the dual nature of HLA-G as both a tumor-associated neoantigen and an ICP to counteract tumor spread. Further ablation of tumors can be boosted when combined with administration of chemotherapeutic agents in clinical use. The readiness of this novel strategy envisions a wide applicability in treating solid tumors.
Acetic acid-assisted underwater endoscopic mucosal resection for successful resection of sessile serrated lesions
Authors: Shunsuke Yamamoto, Hisashi Ishida, Eiji Mita
Journal: Endoscopy (2021)

Underwater endoscopic mucosal resection (UEMR) has become the new standard of endoscopic resection of ≥ 10-mm non-pedunculated colonic polyps [1] [2] [3] [4]. It is particularly difficult to delineate the margins of sessile serrated lesions (SSLs). Though submucosal injection of a blue-colored dye mixture (e. g., indigo carmine or methylene blue) is used to enhance these lesions, SSLs tend to expand owing to the injection of the dye. Hence, bigger snares are utilized or more pieces of resection are needed, resulting in bigger defects after removal or non-en bloc resection.
Clinical Management of End-Stage Renal Disease Patients on Dialysis Receiving Radioactive Iodine Treatment
Authors: Rahaf AlSadi, Landon C. Aziz, Michael Bohan, Shaheen Dewji, Othmane Bouhali, Mehdi Djekidel
Journal: Clinical Nuclear Medicine (2021)

Radioactive iodine (RAI) is used to treat thyroid cancer patients with a clear paradigm for most patients. End-stage renal disease (ESRD) patients pose several challenges when undergoing RAI treatment, primarily due to the lack of renal clearance. We retrospectively report our experience with RAI treatment in a cohort of patients with ESRD and provide a set of recommendations on aspects such as the need for adjusted dose activity, balancing scheduling between RAI therapy and dialysis, and radiation safety precautions.In this study, we report on 5 patients (6 cases), with ESRD on dialysis, treated with RAI for thyroid cancer. Retention measurements to determine individual biological clearance of RAI from the patient's body before and after dialysis sessions were assessed using external exposure dose rates measured at 1 m.Delayed biological clearance of RAI, after the first hemodialysis session, resulted in a longer RAI effective half-life as a consequence of longer retention periods, consistent with observations reported in scientific literature. To achieve a much closer radiation exposure compared with a nondialysis patient, one would recommend administering ~20%-30% of the dose activity normally administered to a thyroid cancer patient based on their medical history, histopathology, and uptake with the appropriate dialysis schedule.Special precautions should be taken with the administration of RAI in ESRD patients by adjusting the prescribed dose activity, dialysis sessions, and paying special attention to wastes. Pooling data from multiple centers may be useful to build a consensus and substantiated recommendations.
Accelerating precision anti-cancer therapy by time-lapse and label-free 3D tumor slice culture platform
Authors: Fuqiang Xing, Yu-Cheng Liu, Shigao Huang, Xueying Lyu, Sek Man Su, Un In Chan, Pei-Chun Wu, Yinghan Yan, Nana Ai, Jianjie Li, Ming Zhao, Barani Kumar Rajendran, Jianlin Liu, Fangyuan Shao, Heng Sun, Tak Kan Choi, Wenli Zhu, Guanghui Luo, Shuiming Liu, De Li Xu, Kin Long Chan, Qi Zhao, Kai Miao, Kathy Qian Luo, Wei Ge, Xiaoling Xu, Guanyu Wang, Tzu-Ming Liu, Chu-Xia Deng
Journal: Theranostics (2021)

The feasibility of personalized medicine for cancer treatment is largely hampered by costly, labor-intensive and time-consuming models for drug discovery. Herein, establishing new pre-clinical models to tackle these issues for personalized medicine is urgently demanded. Methods: We established a three-dimensional tumor slice culture (3D-TSC) platform incorporating label-free techniques for time-course experiments to predict anti-cancer drug efficacy and validated the 3D-TSC model by multiphoton fluorescence microscopy, RNA sequence analysis, histochemical and histological analysis. Results: Using time-lapse imaging of the apoptotic reporter sensor C3 (C3), we performed cell-based high-throughput drug screening and shortlisted high-efficacy drugs to screen murine and human 3D-TSCs, which validate effective candidates within 7 days of surgery. Histological and RNA sequence analyses demonstrated that 3D-TSCs accurately preserved immune components of the original tumor, which enables the successful achievement of immune checkpoint blockade assays with antibodies against PD-1 and/or PD-L1. Label-free multiphoton fluorescence imaging revealed that 3D-TSCs exhibit lipofuscin autofluorescence features in the time-course monitoring of drug response and efficacy. Conclusion: This technology accelerates precision anti-cancer therapy by providing a cheap, fast, and easy platform for anti-cancer drug discovery.
Computed Tomography and Ultrasonography To Detect Appendicitis
Authors: Junaid A. Razzak
Journal: Annals of Internal Medicine (2005)

Letters3 May 2005Computed Tomography and Ultrasonography To Detect AppendicitisJunaid A. Razzak, MBBSJunaid A. Razzak, MBBSFrom The Aga Khan University, Karachi, Pakistan.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-142-9-200505030-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In their meta-analysis, Terasawa and colleagues (1) suggested that overall, computed tomography (CT) is better than ultrasonography (1) for diagnosing appendicitis in patients with atypical presentations. Their findings will clarify clinical decision making for many but will complicate it for those practicing in low-resource settings. In many low-income countries, CT often costs many times a family's monthly salary. It is important to carefully answer the following questions before we recommend CT as a standard of care.First, what about cost and cost-effectiveness? In my practice setting, a focal appendiceal CT, which would probably tell the clinician whether ...Reference1. Terasawa T, Blackmore CC, Bent S, Kohlwes RJ. Systematic review: computed tomography and ultrasonography to detect acute appendicitis in adults and adolescents. Ann Intern Med. 2004;141:537-46. [PMID: 15466771] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Junaid A. Razzak, MBBSAffiliations: From The Aga Khan University, Karachi, Pakistan. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoSystematic Review: Computed Tomography and Ultrasonography To Detect Acute Appendicitis in Adults and Adolescents Teruhiko Terasawa , C. Craig Blackmore , Stephen Bent , and R. Jeffrey Kohlwes Computed Tomography and Ultrasonography To Detect Appendicitis Toshiya Shiga , Zen'ichiro Wajima , and Tetsuo Inoue Computed Tomography and Ultrasonography To Detect Appendicitis Masashi Goto Computed Tomography and Ultrasonography To Detect Appendicitis Teruhiko Terasawa and C. Craig Blackmore Metrics Cited bySex Hormone Effects on Physical Activity LevelsA Rhetorical Analysis of Apologies for Scientific Misconduct: Do They Really Mean It? 3 May 2005Volume 142, Issue 9Page: 798KeywordsAbdominal painAppendicitisComputed axial tomographyDecision makingPopulation statisticsSpecificitySurgeryUltrasound imaging ePublished: 3 May 2005 Issue Published: 3 May 2005 Copyright & PermissionsCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Macrophage migration inhibitory factor drives pathology in a mouse model of spondyloarthritis and is associated with human disease
Authors: Akihiro Nakamura, Fanxing Zeng, Sayaka Nakamura, Kyle T. Reid, Eric Gracey, Melissa Lim, Lin Leng, Sungsin Jo, Ye-Soo Park, Masaki Kusuda, Rohan Machhar, Shaghayegh F. Boroojeni, Brian Wu, Evgeny Rossomacha, Tae-Hwan Kim, Francesco Ciccia, Jason S. Rockel, Mohit Kapoor, Robert D. Inman, Igor Jurisica, Sarah Q. Crome, Richard Bucala, Nigil Haroon
Journal: Science Translational Medicine (2021)

Macrophage migration inhibitory factor produced by neutrophils worsens spondyloarthritis by inducing a pathogenic T H 17 phenotype in T regs .
Covid-19: Northern Syria faces severe wave of infections, MSF warns
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Northern Syria is experiencing its most severe wave of covid-19, with facilities running out of tests, oxygen, and ventilators, Médecins Sans Frontières (MSF) has warned. 1 1 Worst wave yet of covid-19 in northern Syria overwhelms health system.www.msf.org/health-system-overwhelmed-northern-syria-most-severe-covid-19outbreak-yet. 2