tbuckley/cabot-search huggingface dataset:
Naturally occurring homoisoflavonoids function as potent protein tyrosine kinases inhibitors by c-Src-based high-throughput screening
Authors: Hua Xie, Ligen Lin, Honglin Li, Linjiang Tong, Chunping Tang, Changqiang Ke, Liping Lin, Meiyu Geng, Hualiang Jiang, Weimin Zhao, Yang Ye, Jian Ding
Journal: Cancer Research (2008)

4861  Protein tyrosine kinases (PTK) have been recognized as promising therapeutic targets involved in a variety of human diseases and in particular several types of cancer. An effort towards the development of new and more effective PTK inhibitors represents an attractive therapeutic strategy for cancer therapy. Here we report the identification of some potent c-Src tyrosine kinase inhibitors by an automated high-throughput screening (HTS) strategy based on the orthogonal-compound-mixing ELISA method. Hematoxylin (26), the main component of the plant Heamatoxylon campechianum (Leguminosae), stood out as one of the most remarkable c-Src inhibitors of 32,200 compounds. Further studies revealed that hematoxylin is an ATP competitive broad-spectrum PTK inhibitor in vitro, with IC50 values ranging from nanomolar to micromolar level. In addition, hematoxylin is also noted to inhibit the phosphorylation of PTK and arrest the downstream signaling pathways in cellular level. Moreover, other ten new homoisoflavonoids (1-10), together with sixteen known homoisoflavonoids and chalcones (11-26), were isolated from the stems of H. campechianum upon bioassay-guided fractionation. The structure-activity relationship of these compounds was further performed by assessing the PTK inhibitory potency with concurrent molecular docking simulation. Interestingly, the catechol moiety in ring A and the hematoxylin-like three-dimensional structure are essential for c-Src-targeted activities. Together, with the availability of the established ELISA-based HTS screening approach, hematoxylin and its natural analogues were substantially validated to function as a new class of PTK inhibitors.
Abstract 15495: Atherosclerotic Cardiovascular Risk Score as a Predictor of Coronary Artery Disease Burden in Stable Chest Pain
Authors: Marissa K Edmiston, Jaclyn R Rivington, Sunil K Vasireddi, Meera Kondapaneni
Journal: Circulation (2019)

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality in the United States. Cost-effective screening of patients, particularly those with stable chest pain, t...
SAT0191 Quantitative ultrasound of the calcaneus in portuguese children and adolescents
Authors: MM Costa, P Nero, E Branco, J Branco
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> The aim of this study was to determine value range of the parameters SOS, BUA and stiffness for Portuguese children and adolescents in age, sex and race groups. <h3>Methods</h3> The study included 473 healthy children coming from two Lisbon schools. The population was 92,2% caucasian. There were 261 (55,2%) girls and 212 (44,8%) boys. Mean age was 10,7+2,4 year, range 6–17 yr. The Sahara Clinical Sonometer of Hologic was used to performed a quantitative ultrasound (QUS) measurement of the non-dominant calcaneus. Patient examination was performed by two rheumatologists. <h3>Results</h3> The mean of BUA, SOS and stiffness were: 70.07+19.82 db/MHz, 1563.64+26.65 m/s and 98.96+17.7. There were no statistical differences between sex or race in each groups. We observed an increased BUA, SOS and stiffness from 6 to 9 yr in caucasian boys and then stabilised. At this time the means were respectively 81.06 db/MHz, 1582 m/s and 110.86. In caucasian girls the increase of values occurred two years later and until 14 yr. The Spearman's rho correlation coefficient shown, in caucasian girls, a influence of age, height and weight on QUS parameters. In boys, this factors affect only SOS and stiffness. There were no correlation with this factors in black. <h3>Conclusion</h3> Measuring bone mass of children by QUS is good technique. However reference data ranges must be developed for each population.
Should All Patients With Pancreatic Cancer Receive Chemotherapy Before Surgery?
Authors: Linda Ye, O. Joe Hines
Journal: JAMA Surgery (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Dual Targeting of Mesothelin and CD19 with Chimeric Antigen Receptor-Modified T Cells in Patients with Metastatic Pancreatic Cancer
Authors: Andrew H. Ko, Alexander C. Jordan, Evan Tooker, Simon F. Lacey, Renee B. Chang, Yan Li, Alan P. Venook, Margaret Tempero, Lloyd Damon, Lawrence Fong, Mark H. O’Hara, Bruce L. Levine, J. Joseph Melenhorst, Gabriela Plesa, Carl H. June, Gregory L. Beatty
Journal: Molecular Therapy (2020)

B cells infiltrate pancreatic ductal adenocarcinoma (PDAC) and in preclinical cancer models, can suppress T cell immunosurveillance in cancer. Here, we conducted a pilot study to assess the safety and feasibility of administering lentiviral-transduced chimeric antigen receptor (CAR)-modified autologous T cells redirected against mesothelin to target tumor cells along with CART cells redirected against CD19 to deplete B cells. Both CARs contained 4-1BB and CD3ζ signaling domains. Three patients with chemotherapy-refractory PDAC received 1.5 g/m2 cyclophosphamide prior to separate infusions of lentiviral-transduced T cells engineered to express chimeric anti-mesothelin immunoreceptor SS1 (CART-Meso, 3 × 107/m2) and chimeric anti-CD19 immunoreceptor (CART-19, 3 × 107/m2). Treatment was well tolerated without dose-limiting toxicities. Best response was stable disease (1 of 3 patients). CART-19 (compared to CART-Meso) cells showed the greatest expansion in the blood, although persistence was transient. B cells were successfully depleted in all subjects, became undetectable by 7–10 days post-infusion, and remained undetectable for at least 28 days. Together, concomitant delivery of CART-Meso and CART-19 cells in patients with PDAC is safe. CART-19 cells deplete normal B cells but at the dose tested in these 3 subjects did not improve CART-Meso cell persistence. B cells infiltrate pancreatic ductal adenocarcinoma (PDAC) and in preclinical cancer models, can suppress T cell immunosurveillance in cancer. Here, we conducted a pilot study to assess the safety and feasibility of administering lentiviral-transduced chimeric antigen receptor (CAR)-modified autologous T cells redirected against mesothelin to target tumor cells along with CART cells redirected against CD19 to deplete B cells. Both CARs contained 4-1BB and CD3ζ signaling domains. Three patients with chemotherapy-refractory PDAC received 1.5 g/m2 cyclophosphamide prior to separate infusions of lentiviral-transduced T cells engineered to express chimeric anti-mesothelin immunoreceptor SS1 (CART-Meso, 3 × 107/m2) and chimeric anti-CD19 immunoreceptor (CART-19, 3 × 107/m2). Treatment was well tolerated without dose-limiting toxicities. Best response was stable disease (1 of 3 patients). CART-19 (compared to CART-Meso) cells showed the greatest expansion in the blood, although persistence was transient. B cells were successfully depleted in all subjects, became undetectable by 7–10 days post-infusion, and remained undetectable for at least 28 days. Together, concomitant delivery of CART-Meso and CART-19 cells in patients with PDAC is safe. CART-19 cells deplete normal B cells but at the dose tested in these 3 subjects did not improve CART-Meso cell persistence.
How Telemedicine and Centralized Care Changed the Natural History of Retinoblastoma in a Developing Country
Authors: Yacoub A. Yousef, Ibrahim Al-Nawaiseh, Mustafa Mehyar, Iyad Sultan, Maysa Al-Hussaini, Imad Jaradat, Mona Mohammad, Reem AlJabari, Nakhleh Abu-Yaghi, Carlos Rodriguez-Galindo, Ibrahim Qaddoumi, Matthew Wilson
Journal: Ophthalmology (2020)
Abstract 317: The Clinical Features and Outcomes of Vasospastic Angina in Patients Survived Out-of-Hospital Cardiac Arrest
Authors: Kyoung Min You, Hui Jai Lee, Jonghwan Shin
Journal: Circulation (2018)

Introduction: Acute myocardial infarction (AMI) is a major cause of cardiac arrest. Coronary vasospasm has been suggested to play a significant role in the acute phase of MI. Vasospastic angina (VSA) is characterized by spontaneous attacks of chest pain, caused by transient coronary vasospasm. Severe coronary vasospasm might cause AMI, fatal arrhythmia, and subsequent cardiac arrest, however, there have been limited studies about the clinical characteristics and prognosis of patients with VSA regarding cardiac arrest. This study investigated the clinical features and outcomes of VSA compared to other MI in patients survived out-of-hospital cardiac arrest (OHCA). Method and Results: We analyzed the data of adult OHCA patients from the prospectively collected post cardiac arrest syndrome (PCAS) registry of 3 urban academic hospitals from December 2013 to December 2017. During the study period, 721 OHCAs were collected, including 18 diagnosed with VSA and 133 with other MI as primary cause of cardiac arrest. Compared to other MI, more patients achieved pre-hospital return of spontaneous circulation (ROSC) in VSA group (72.2% vs. 47.4%, p =0.041). The advanced cardiovascular life support (ACLS) time (median, 4.0 min vs. 10.0 min; p =0.008) was shorter in VSA group. The SOFA (5.0 vs. 9.0, p =0.007) and APACHE II score (20.5 vs. 25.0, p =0.007) at admission were lower in VSA group. The proportion of the patients who underwent coronary angiography (CAG) did not differ between the two groups and there were no patients with a newly diagnosed coronary obstructive lesion in CAG performed after ROSC. More patients in VSA group had good neurologic outcome at hospital discharge (77.8% vs. 47.3%, p =0.022), 28 days (76.5% vs. 48.4%, p =0.038), and 6 months (76.5% vs. 47.7%, p =0.037). All-cause mortality rate at in-hospital (5.6% vs. 42.1%, p =0.002) and 28 days (11.2% vs. 44.5%, p =0.009) were lower in VSA group. In the subgroup analysis of patients who underwent CAG, more patients with VSA showed lower mortality rate at in-hospital (0.0% vs. 35.4%, p =0.003) and 28 days (6.7% vs. 38.0%, p =0.019). Conclusion: In patients survived OHCA, patients with VSA more achieved pre-hospital ROSC and showed better neurologic outcome and lower mortality rate compared to those with other MI.
SARS-CoV-2 IgG seroprevalence in blood donors located in three different federal states, Germany, March to June 2020
Authors: Bastian Fischer, Cornelius Knabbe, Tanja Vollmer
Journal: Eurosurveillance (2020)

Most cases of coronavirus disease 2019 are mild or asymptomatic. Therefore, many cases remain unrecorded. We determined seroprevalence of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 3,186 regular blood donors in three German federal states between 9 March and 3 June 2020. The IgG seroprevalence was 0.91% (95% confidence interval (CI): 0.58-1.24) overall, ranging from 0.66% (95% CI: 0.13-1.19) in Hesse to 1.22% (95% CI: 0.33-2.10) in Lower-Saxony.
Practice patterns of diagnostic upper gastrointestinal endoscopy during the initial COVID-19 outbreak in England
Authors: Sheraz R Markar, Jonathan Clarke, James Kinross
Journal: The Lancet. Gastroenterology & hepatology (2020)

During the initial outbreak of COVID-19, concerns have been raised regarding SARS-CoV-2 aerosolisation and transmission during invasive procedures such as upper gastrointestinal endoscopy.1,2 In the UK, this led to the strategic pause in endoscopic services for 6 weeks at the beginning of the COVID-19 crisis for all but emergency and essential procedures nationally, as advised by the British Society of Gastroenterology.3 The lack of adherence to National Institute for Health and Care Excellence criteria for urgent direct access upper gastrointestinal endoscopy4 and the continued reduction in diagnostic oesophagogastroduodenoscopy across England might lead to many undiagnosed oesophageal and gastric cancers, with delay in diagnosis and stage migration, substantially affecting long-term survival in these patients.
Mass masking as a way to contain COVID-19 and exit lockdown in low- and middle-income countries
Authors: Joseph Nelson Siewe Fodjo, Supa Pengpid, Edlaine Faria de Moura Villela, Vo Van Thang, Mohammed Ahmed, John Ditekemena, Bernardo Vega Crespo, Rhoda K Wanyenze, Janeth Dula, Takashi Watanabe, Christopher Delgado-Ratto, Koen Vanden Driessche, Rafael Van den Bergh, Robert Colebunders
Journal: Journal of Infection (2020)

In new guidelines published on June 5th 2020, the World Health Organization (WHO) recommends that in areas with ongoing COVID-19 community transmission, governments should encourage the general public to wear face masks in specific situations and settings as part of a comprehensive approach to suppress COVID-19 transmission. Recent online surveys in 206,729 persons residing in nine low- and middle-income countries showed that 32.7%-99.7% of respondents used face masks with significant differences across age groups and sexes. Targeted health promotion strategies and government support are required to increase mask use by the general population.
Thioredoxin activity confers resistance against oxidative stress in tumor-infiltrating NK cells
Authors: Ying Yang, Shi Yong Neo, Ziqing Chen, Weiyingqi Cui, Yi Chen, Min Guo, Yongfang Wang, Haiyan Xu, Annina Kurzay, Evren Alici, Lars Holmgren, Felix Haglund, Kai Wang, Andreas Lundqvist
Journal: Journal of Clinical Investigation (2020)

To improve the clinical outcome of adoptive NK cell therapy in patients with solid tumors, NK cells need to persist within the tumor microenvironment (TME) in which the abundance of ROS could dampen antitumor immune responses. In the present study, we demonstrated that IL-15-primed NK cells acquired resistance against oxidative stress through the thioredoxin system activated by mTOR. Mechanistically, the activation of thioredoxin showed dependence on localization of thioredoxin-interacting protein. We show that NK cells residing in the tumor core expressed higher thiol densities that could aid in protecting other lymphocytes against ROS within the TME. Furthermore, the prognostic value of IL15 and the NK cell gene signature in tumors may be influenced by tobacco smoking history in patients with non-small-cell lung cancer (NSCLC). Collectively, the levels of reducing antioxidants in NK cells may not only predict better tumor penetrance but potentially even the immune therapy response.
Development and Validation of a Risk Stratification Model Using Disease Severity Hierarchy for Mortality or Major Cardiovascular Event
Authors: Che Ngufor, Pedro J. Caraballo, Thomas J. O’Byrne, David Chen, Nilay D. Shah, Lisiane Pruinelli, Michael Steinbach, Gyorgy Simon
Journal: JAMA Network Open (2020)

Clinical domain knowledge about diseases and their comorbidities, severity, treatment pathways, and outcomes can facilitate diagnosis, enhance preventive strategies, and help create smart evidence-based practice guidelines.To introduce a new representation of patient data called disease severity hierarchy that leverages domain knowledge in a nested fashion to create subpopulations that share increasing amounts of clinical details suitable for risk prediction.This retrospective cohort study included 51 969 patients aged 45 to 85 years, with 10 674 patients who received primary care at the Mayo Clinic between January 2004 and December 2015 in the training cohort and 41 295 patients who received primary care at Fairview Health Services from January 2010 to December 2017 in the validation cohort. Data were analyzed from May 2018 to December 2019.Several binary classification measures, including the area under the receiver operating characteristic curve (AUC), Gini score, sensitivity, and positive predictive value, were used to evaluate models predicting all-cause mortality and major cardiovascular events at ages 60, 65, 75, and 80 years.The mean (SD) age and proportions of women and white individuals were 59.4 (10.8) years, 6324 (59.3%) and 9804 (91.9%), respectively, in the training cohort and 57.4 (7.9) years, 21 975 (53.1%), and 37 653 (91.2%), respectively, in the validation cohort. During follow-up, 945 patients (8.9%) in the training cohort died, while 787 (7.4%) had major cardiovascular events. Models using the new representation achieved AUCs for predicting death in the training cohort at ages 60, 65, 75, and 80 years of 0.96 (95% CI, 0.94-0.97), 0.96 (95% CI, 0.95-0.98), 0.97 (95% CI, 0.96-0.98), and 0.98 (95% CI, 0.98-0.99), respectively, while standard methods achieved modest AUCs of 0.67 (95% CI, 0.55-0.80), 0.66 (95% CI, 0.56-0.79), 0.64 (95% CI, 0.57-0.71), and 0.63 (95% CI, 0.54-0.70), respectively.In this study, the proposed patient data representation accurately predicted the age at which a patient was at risk of dying or developing major cardiovascular events substantially better than standard methods. The representation uses known relationships contained in electronic health records to capture disease severity in a natural and clinically meaningful way. Furthermore, it is expressive and interpretable. This novel patient representation can help to support critical decision-making, develop smart guidelines, and enhance health care and disease management by helping to identify patients with high risk.
18F-FDG PET/CT in Xanthoma Disseminatum
Authors: Esra Arslan, Tamer Aksoy, Cem Leblebici, Ayşe Esra Koku-Aksu, Tevfik Fikret Çermik
Journal: Clinical Nuclear Medicine (2020)

Abstract A 64-year-old woman who had yellowish orange–colored, sharp-edged, and flat skin plaques and back pain for about a year was referred for 18 F-FDG PET/CT imaging and her bone marrow biopsy revealed 10% to 20% atypical plasma cells suggestive of monoclonal gammopathy. PET/CT showed linear 18 F-FDG uptake on the surface of the skin on the neck, axillary, chest, inframammary, and inguinal regions. Punch biopsy revealed numerous histiocyte infiltrates with large vacuoles, xanthomized cytoplasm in the dermis, and midsection, and there are several Touton-type giant cells supporting the preliminary diagnosis of xanthoma disseminatum.
From Birth and Throughout Life: Fungal Microbiota in Nutrition and Metabolic Health
Authors: William D. Fiers, Irina Leonardi, Iliyan D. Iliev
Journal: Annual Review of Nutrition (2020)

The human gastrointestinal tract is home to a vibrant, diverse ecosystem of prokaryotic and eukaryotic microorganisms. The gut fungi (mycobiota) have recently risen to prominence due to their ability to modulate host immunity. Colonization of the gut occurs through a combination of vertical transmission from the maternal mycobiota and environmental and dietary exposure. Data from human and animal studies demonstrate that nutrition strongly affects the mycobiota composition and that changes in the fungal communities can aggravate metabolic diseases. The mechanisms pertaining to the mycobiota's influence on host health, pathology, and resident gastrointestinal communities through intrakingdom, transkingdom, and immune cross talk are beginning to come into focus, setting the stage for a new chapter in microbiota-host interactions. Herein, we examine the inception, maturation, and dietary modulation of gastrointestinal and nutritional fungal communities and inspect their impact on metabolic diseases in humans.
<i>RAD51AP1</i> Deficiency Reduces Tumor Growth by Targeting Stem Cell Self-Renewal
Authors: Allison E. Bridges, Sabarish Ramachandran, Rajneesh Pathania, Utkarsh Parwal, Adrienne Lester, Pragya Rajpurohit, Daley S. Morera, Nikhil Patel, Nagendra Singh, Hasan Korkaya, Santhakumar Manicassamy, Puttur D. Prasad, Vinata B. Lokeshwar, Bal L. Lokeshwar, Vadivel Ganapathy, Muthusamy Thangaraju
Journal: Cancer Research (2020)

RAD51-associated protein 1 (RAD51AP1) plays an integral role in homologous recombination by activating RAD51 recombinase. Homologous recombination is essential for preserving genome integrity and RAD51AP1 is critical for D-loop formation, a key step in homologous recombination. Although RAD51AP1 is involved in maintaining genomic stability, recent studies have shown that RAD51AP1 expression is significantly upregulated in human cancers. However, the functional role of RAD51AP1 in tumor growth and the underlying molecular mechanism(s) by which RAD51AP1 regulates tumorigenesis have not been fully understood. Here, we use Rad51ap1-knockout mice in genetically engineered mouse models of breast cancer to unravel the role of RAD51AP1 in tumor growth and metastasis. RAD51AP1 gene transcript was increased in both luminal estrogen receptor-positive breast cancer and basal triple-negative breast cancer, which is associated with poor prognosis. Conversely, knockdown of RAD51AP1 (RADP51AP1 KD) in breast cancer cell lines reduced tumor growth. Rad51ap1-deficient mice were protected from oncogene-driven spontaneous mouse mammary tumor growth and associated lung metastasis. In vivo, limiting dilution studies provided evidence that Rad51ap1 plays a critical role in breast cancer stem cell (BCSC) self-renewal. RAD51AP1 KD improved chemotherapy and radiotherapy response by inhibiting BCSC self-renewal and associated pluripotency. Overall, our study provides genetic and biochemical evidences that RAD51AP1 is critical for tumor growth and metastasis by increasing BCSC self-renewal and may serve as a novel target for chemotherapy- and radiotherapy-resistant breast cancer. SIGNIFICANCE: This study provides in vivo evidence that RAD51AP1 plays a critical role in breast cancer growth and metastasis by regulating breast cancer stem cell self-renewal.