tbuckley/cabot-search huggingface dataset:
The application of antibotoxsome, a novel cytotoxic conjugate, in cell death in in vitro models of pancreatic, liver, breast, cervical cancer, and myeloma.
Authors: Simon Tazzyman, Guillaume Hautbergue, Ali Khurram, Mathew Bryan, Andrew Chantry, Maria Fragiadaki
Journal: Journal of Clinical Oncology (2015)

e12018 Background: Antibotoxsome is a conjugate of two cytotoxic agents, Burkholderialethal factor one (BLF-1 a bacterial endotoxin that is only toxic if internalized) and TRAIL (which binds death receptors on tumour cells) and an antibody against a tumour specific internalising cell surface receptor. Once added to tumour cells the antibody binds to the tumour specific antigen expressed on the tumour cell surface leading to internalisation of the Antibotoxome complex. Upon internalisation BLF-1 and TRAIL induce tumour cell death. As a result of the tumour specific antibody and the fact that healthy cells express decoy death receptors Antibotoxsome is designed to be toxic to cancer cells but not to healthy tissue. Methods: Proof of concept complexes where made using CXCR4 as the tumour targeting antibody. Immunofluorescence staining was used to demonstrate cell surface expression of CXCR4 and internalisation of CXCR4/TRAIL coated beads. Response of tumour cells to Antibotoxome was measured using trypan blue exclusion, MTT and Western blot analysis for makers of apoptotic cell death. Effects of various Antibotoxsomeconstructs were assayed at 24 hrs, 48 hrs and 72 hours post treatment. Results: Expression of CXCR4 was observed on the cell surface and in the cytoplasm of human myeloma cells. Imaging of both renal carcinoma cells and myeloma cells demonstrated internalisation of the Antibotoxome complex. This resulted in the presence of apoptotic bodies in myeloma cells. MTT assays and trypan blue exclusion showed substantial cell death in Capan-1 pancreatic cancer cells, HepG2 liver cancer cells, MDA-MB-231 breast cancer cells, HeLa cervical cancer cells and JJN3 myeloma cells but not healthy cells treated with various different Antibotoxsome constructs. Conclusions: We have performed in vitro studies demonstrating that Antibotoxome is toxic to cancer cell lines including pancreatic, liver, breast, cervical cancer and myeloma. Furthermore, Antibotoxsome is not toxic to healthy cells. Antibotoxome may therefore form a novel, targeted, anti-cancer therapy.
Abstract 20345: Transplantation of Cardiac Progenitor Cells With the Self-Assembling Peptides Scaffold Into the Pericardial Space Improves Cardiac Function After Acute Myocardial Infarction in Mice
Authors: Naomichi Kondo, Nagai Toshio, Tokunaga Masakuni, Masato Kanda, Katsuhisa Matsuura, Issei Komuro, Yoshio Kobayashi
Journal: Circulation (2017)

Background: Cardiac progenitor cell (CPC) therapy for heart disease has been examined enthusiastically, however; optimal scaffolds to ensure the engraftment of transplanted cells are still elusive. Methods: We used clonally expanded stem cell antigen 1-positive CPCs from adult mice and produced a three-dimensional hydrogel scaffold (CPC-scaffold) in which CPCs were cultured up to 8 weeks with high viability. CPC-scaffold contained RGD peptide-conjugated self-assembling peptide with insulin-like growth factor-1. Immediately after creating myocardial infarction (MI), we transplanted CPC-scaffold into the pericardial space on the surface of MI area. Results: Four weeks after transplantation, both transplantation of red fluorescent protein expressing CPCs and in situ hybridization analysis in sex-mismatched transplantation revealed engraftment of CPCs in the transplanted scaffold that was celluralized with host cells. Averaged scar area of CPC-scaffold-treated group was significantly smaller than that of non-...
Prognosis of EGFR-mutant advanced lung adenocarcinoma patients with different intrathoracic metastatic patterns
Authors: F. Hu, B. Zhang, C. Li, J. Xu, H. Wang, P. Gu, X. Zheng, W. Nie, Y. Shen, H. Zhang, P. Hu, X. Zhang
Journal: Annals of Oncology (2019)

Background: Lung cancer diagnosed solely with intrathoracic metastases are classified as M1a, but intrathoracic metastases can be further divided into different patterns. The objective of our study was to analyze the survival difference between different metastatic patterns of intrathoracic metastases in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutations. Methods: EGFR-mutant patients diagnosed only with intrathoracic metastasis between March 2011 and October 2016 were collected. Prognosis was analyzed according to metastatic patterns based on univariate and multivariate analysis. Results: A total of 137 patients (60 patients who only had pleural metastasis [Group A], 44 patients who only had contralateral lung metastasis [Group B] and other 33 patients had both pleural and contralateral lung metastasis with or without pericardial effusion [Group C]) were included in the study. The median OS (overall survival) times were 38.1(95%confidence interval [CI]: 27.8-48.4), 35.7(95%CI: 23.4-48.0), and 29.7(95%CI: 22.8-36.6) months for Group A, Group B, and Group C, respectively (p = 0.037). Multivariate analysis demonstrated that Group A and Group B had longer OS than Group C (hazard ratio [HR]=0.524, 95%CI: 0.307-0.894, p = 0.018; HR = 0.473, 95%CI: 0.241-0.931, p = 0.030, respectively) among lung adenocarcinoma patients with EGFR mutation. With regard to patients with pleural or contralateral metastasis only, OS benefit (p = 0.579) was not significant between the two groups. Subgroup analysis demonstrated that the OS benefit of Group A was significant in patients with N0-1 disease and 21L858R mutant but not in EGFR exon 19 deletion, N2-3 stage and T3-4 stage disease patients. Conclusions: The prognosis of EGFR-mutant lung adenocarcinoma patients diagnosed only with intrathoracic metastasis is different, indicating that M1a may should be refined in the future. Legal entity responsible for the study: The authors. Funding: National Natural Science Foundation of China (No.81502450) and Science and Technology Commission of Shanghai Municipality, China (No.18441904700). Disclosure: All authors have declared no conflicts of interest.
SAT-394-Genetic Features Associated with 18F-FDG uptake in intrahepatic cholangiocarcinoma
Authors: Koo Jeong Kang, Keun Soo Ahn, Yong Hoon Kim, Tae-Seok Kim, Bong-Il Song, Hae Won Kim, Daniel O’Brien, Lewis R Roberts, Kwok Kei Mak, Kyoung Sook Won
Journal: Journal of Hepatology (2019)
PS-134-Oral treatment with PBI-4547 promotes beta-oxidation and energy expenditure, and reverses liver damage and white adipose tissue fibrosis in high-fat diet and ob/ob mouse models of NAFLD.
Authors: Brigitte Grouix, Alexandre Laverdure, François Sarra-Bournet, Mikaël Tremblay, Marie-Pier Cloutier, Liette Gervais, Jonathan Richard, Alexandra Felton, Pierre Laurin, Lyne Gagnon
Journal: Journal of Hepatology (2019)
Abstract 13386: Persistence of Transplanted Explant-derived Human Cardiac Stem Cells Contributes to Therapeutic Regeneration of Injured Mycardium
Authors: Elizabeth Richardson, Seth Mount, Audrey E Mayfield, Ghazaleh Rafatian, Nicholas Latham, Duncan J Stewart, Darryl R Davis
Journal: Circulation (2015)

Introduction: Cardiac stem cells (CSCs) mediated improvements in cardiac function have been attributed to the rescue of reversibly damaged tissue, proliferation of endogenous cells and differentiation of transplanted CSCs into new myocardium. Despite evidence that CSC therapy improves post-ischemic function, controversy surrounds the extent to which physical incorporation and persistence of transplanted cells contributes to the benefits of CSC therapy. In this study, we use “on demand” ablation of transplanted CSCs to dissect the contribution of engrafted cells to myocardial repair. Methods/Results: Diphtheria toxin (DT) was used to induce transplanted human cell death. Human CSCs were cultured from atrial appendage biopsies obtained during clinically-indicated surgery. Exposure of human CSCs to DT prompted expression of annexin V ± propidium iodide in 37±10% of treated cells within 12 hours (p≤0.05 vs. human CSCs not exposed to DT) and resulted in a progressive decline in viable human cell counts (Figure A); suggesting that DT may provide the ideal means of ablating transplanted human sourced cells within a DT resistant host. The influence of short term persistence of transplanted CSCs was investigated in a series of SCID mice by applying DT or vehicle 1 week after intra-myocardial injection of human CSCs (Figure B). A decline in the ejection fraction in CSC-treated mice underscores the importance of transplanted cell persistence on CSC-mediated cardiac repair. This decrease was paralleled by increases in scar size (1.4±1.0 fold greater % scar, p=0.05), reduced contractility (1.2±0.1 fold lower dP/dT max, p=0.04) and impaired relaxation (1.6±0.2 fold lower dP/dT min, p=0.05) as compared to mice that received CSCs alone. Conclusions: Elimination of CSCs 1 week after transplantation reduces CSC-mediated cardiac repair- suggesting that persistent paracrine secretion and/or cell replacement contribute to the maintenance of therapeutic regeneration.
Measles Vaccine Exemptions
Authors: Bridget Kuehn
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 19719: Ablation Strategies Targeting Left Atrial Anterior Wall Can be an Useful Alternative to Mitral Isthmus Ablation in Patients With Peri-Mitral Atrial Flutter
Authors: Kazuhiro Nagaoka, Yasushi Mukai, Shujiro Inoue, Daisuke Yakabe, Shunsuke Kawai, Susumu Takase, Akiko Chishaki, Hiroyuki Tsutsui
Journal: Circulation (2017)

Introduction: Peri-mitral atrial flutter (PMFL) remains challenging target of catheter ablation. Success rates of achieving conduction block of mitral isthmus is not satisfactory even in the recent...
Safety and efficacy of 24-h closed-loop insulin delivery in well-controlled pregnant women with type 1 diabetes: A randomized crossover case series (Diabetes Care (2011) 34, (2527-2529))
Authors: H. R. Murphy, K. Kumareswaran, D. Elleri, J. M. Allen, K. Caldwell, M. Biagioni, D. Simmons, D. B. Dunger, M. Nodale, M. E. Wilinska, S. A. Amiel, R. Hovorka
Journal: Diabetes Care (2012)
Challenges and facilitators in the diagnosis of lower‐limb cellulitis
Authors: M. Patel, S.I. Lee, K.S. Thomas, J. Kai
Journal: British Journal of Dermatology (2019)

Cellulitis is a common skin infection seen in the UK, with most cases affecting the lower limbs. It can be a challenging diagnosis to make, with one in three cases initially suspected as being cellulitis then being diagnosed as something different after further assessment. This can lead to unnecessary antibiotics being given and unnecessary hospital stays. Making a correct diagnosis at the outset is important both to patients and clinicians. This study aimed to identify the challenges of, and help available for, diagnosing cellulitis on the lower limb. The authors, based in Nottingham, UK, carried out a review of existing research and grouped the results into key topics. These topics were: 1) alternative diagnoses of suspected cellulitis 2) aids that have been developed to help diagnosis and 3) services that have been developed to help diagnosis. The authors identified multiple alternative final diagnoses for patients who were investigated for suspected cellulitis. The symptoms in these patients overlapped with typical features of cellulitis. Four studies looked at blood tests, scans or a set of rules to help detect cellulitis and two services had been developed to help reduce an inaccurate diagnosis. The present study showed the range of other diagnoses that clinicians need to consider when a patient presents with possible cellulitis. Future work is needed to further assess the efficacy of aids and services that have been developed. Interviews both with patients and clinicians on ways to make an initial diagnosis more accurate would be a beneficial part of further research.
The airway microbiota in children newly diagnosed with bronchiectasis largely retains its diversity
Authors: Naveen Pillarisetti, David Broderick, Alana Ainsworth, Anna Mulholland, Brett Wagner Mackenzie, Danielle Middleton, Catherine A. Byrnes, Michael W. Taylor
Journal: European Respiratory Journal (2019)

<b>Young children diagnosed with bronchiectasis have a lower airway microbiota that is highly diverse and very similar to healthy controls. <i>Haemophilus</i>, <i>Moraxella</i>, <i>Neisseria</i> and <i>Streptococcus</i> are the most abundant operational taxonomic units identified.</b>http://bit.ly/2SkqRrq
High-Sensitivity Troponin I and Incident Coronary Events, Stroke, Heart Failure Hospitalization, and Mortality in the ARIC Study
Authors: Xiaoming Jia, Wensheng Sun, Ron C. Hoogeveen, Vijay Nambi, Kunihiro Matsushita, Aaron R. Folsom, Gerardo Heiss, David J. Couper, Scott D. Solomon, Eric Boerwinkle, Amil Shah, Elizabeth Selvin, James A. de Lemos, Christie M. Ballantyne
Journal: Circulation (2019)

Background: We assessed whether plasma troponin I measured by a high-sensitivity assay (hs-TnI) is associated with incident cardiovascular disease (CVD) and mortality in a community-based sample without prior CVD. Methods: ARIC study (Atherosclerosis Risk in Communities) participants aged 54 to 74 years without baseline CVD were included in this study (n=8121). Cox proportional hazards models were constructed to determine associations between hs-TnI and incident coronary heart disease (CHD; myocardial infarction and fatal CHD), ischemic stroke, atherosclerotic CVD (CHD and stroke), heart failure hospitalization, global CVD (atherosclerotic CVD and heart failure), and all-cause mortality. The comparative association of hs-TnI and high-sensitivity troponin T with incident CVD events was also evaluated. Risk prediction models were constructed to assess prediction improvement when hs-TnI was added to traditional risk factors used in the Pooled Cohort Equation. Results: The median follow-up period was ≈15 years. Detectable hs-TnI levels were observed in 85% of the study population. In adjusted models, in comparison to low hs-TnI (lowest quintile, hs-TnI ≤1.3 ng/L), elevated hs-TnI (highest quintile, hs-TnI ≥3.8 ng/L) was associated with greater incident CHD (hazard ratio [HR], 2.20; 95% CI, 1.64–2.95), ischemic stroke (HR, 2.99; 95% CI, 2.01–4.46), atherosclerotic CVD (HR, 2.36; 95% CI, 1.86–3.00), heart failure hospitalization (HR, 4.20; 95% CI, 3.28–5.37), global CVD (HR, 3.01; 95% CI, 2.50–3.63), and all-cause mortality (HR, 1.83; 95% CI, 1.56–2.14). hs-TnI was observed to have a stronger association with incident global CVD events in white than in black individuals and a stronger association with incident CHD in women than in men. hs-TnI and high-sensitivity troponin T were only modestly correlated ( r =0.47) and were complementary in prediction of incident CVD events, with elevation of both troponins conferring the highest risk in comparison with elevation in either one alone. The addition of hs-TnI to the Pooled Cohort Equation model improved risk prediction for atherosclerotic CVD, heart failure, and global CVD. Conclusions: Elevated hs-TnI is strongly associated with increased global CVD incidence in the general population independent of traditional risk factors. hs-TnI and high-sensitivity troponin T provide complementary rather than redundant information.
Prospective validation of N‐terminal pro B‐type natriuretic peptide cut‐off concentrations for the diagnosis of acute heart failure
Authors: Nikola Kozhuharov, Zaid Sabti, Desiree Wussler, Albina Nowak, Patrick Badertscher, Raphael Twerenbold, Karin Wildi, Fabio Stallone, Fabian Vogt, Jonas Hilti, Christian Puelacher, Jeanne du Fay de Lavallaz, Samyut Shrestha, Dayana Flores, Thomas Nestelberger, Luca Koechlin, Jasper Boeddinghaus, Tobias Zimmermann, Joan Walter, Carmela Schumacher, Katharina Rentsch, Arnold von Eckardstein, Dagmar I. Keller, Assen Goudev, Otmar Pfister, Tobias Breidthardt, Christian Mueller
Journal: European Journal of Heart Failure (2019)
Good evidence on measurement properties of the Dermatology Life Quality Index, Itchy Quality of Life and 5‐dimensions itch scales in atopic eczema, but problems with structural validity remain
Authors: C.J. Apfelbacher, R. Ofenloch
Journal: British Journal of Dermatology (2019)

Linked Article: Patel et al. Br J Dermatol 2019; 180:1083–1089.
Brain ultrasonography: methodology, basic and advanced principles and clinical applications. A narrative review
Authors: Chiara Robba, Alberto Goffi, Thomas Geeraerts, Danilo Cardim, Gabriele Via, Marek Czosnyka, Soojin Park, Aarti Sarwal, Llewellyn Padayachy, Frank Rasulo, Giuseppe Citerio
Journal: Intensive Care Medicine (2019)
Circular RNAs as promising biomarkers in cancer: detection, function, and beyond
Authors: Shengli Li, Leng Han
Journal: Genome Medicine (2019)

Circular RNAs (circRNAs) are 3'-5' covalently closed RNA rings produced from back-splicing of precursor mRNA in eukaryotes. Recent studies, using both computational and experimental approaches, have allowed advanced characterization of circRNAs, leading the research field into a new era and shedding light on the contribution of circRNAs to disease.
HGG-08. ATRX LOSS IN PEDIATRIC GBM RESULTS IN EPIGENETIC DYSREGULATION OF G2/M CHECKPOINT MAINTENANCE AND SENSITIVITY TO ATM INHIBITION
Authors: Brendan Mullan, Tingting Qin, Ruby Siada, Carla Danussi, Jacqueline Brosnan-Cashman, Drew Pratt, Taylor Garcia, Viveka Nand Yadav, Xinyi Zhao, Meredith Morgan, Sriram Venneti, Alan Meeker, Jason Huse, Alnawaz Rehemtulla, Pedro Lowenstein, Maria Castro, Carl Koschmann
Journal: Neuro-Oncology (2019)

ATRX is a histone chaperone protein recurrently mutated in pediatric GBM. We previously confirmed its role in tumor progression and mutational burden in glioma. However, the mechanism which mediates the proliferative advantage of ATRX loss in pediatric GBM remains unexplained. Recent data revealed a distinct pattern of DNA binding sites of the ATRX protein using ChIP-seq in mouse neuronal precursor cells (mNPCs). Using the ATRX peaks identified in p53-/- mNPCs, we confirmed that ATRX binding sites were significantly enriched in gene promoters (p<0.0001) and CpG islands (p<0.0001) compared with random regions. Gene set enrichment (GSE) analysis identified that cell cycle and regulation of cell cycle were among the most significantly enriched gene sets (p=2.52e-16 and 1.61e-9, respectively). In line with this, the master cell cycle regulator CDKN1A was significantly down-regulated (p=0.0024) in human pediatric high-grade gliomas with ATRX mutation (PedsCbioPortal, n=247). We found that ATRX loss resulted in dysfunction of G2/M checkpoint maintenance: (1) ATRX-deficient pediatric GBM cells exhibited a seven-fold increase in mitotic index at 16 hours after sub-lethal radiation, and (2) murine GBM cells with ATRX knockdown demonstrated impaired pChk1 signaling on western blot at multiple time points after radiation compared to controls (p=0.0187). Notably the ATM signaling (pChk2) remained intact in those cells, suggesting a potential therapeutic target. ATRX-deficient mouse cells were uniquely sensitive to ATM inhibitors at 1 uM alongside 8 Gy radiation compared to controls with intact ATRX (AZD0156: p=0.0027 and AZD01390: p=0.0436). Using an ATM-luciferase reporter assay, AZD0156 demonstrated stronger ATM inhibition when compared to AZD1390. Mice intra-cranially implanted with ATRX-deficient GBM cells showed improved survival (n=10, p=0.0018) when treated with AZD0156 combined with radiation. Our findings suggest that ATRX loss in glioma results in unique sensitivity to ATM inhibition via epigenetic dysregulation of G2/M checkpoint maintenance.
US succeeds in diluting UN resolution on sexual violence against women
Authors: Janice Hopkins Tanne
Journal: BMJ (2019)

Pressure from the Trump administration has removed references to sexual health from a United Nations Security Council resolution against sexual violence during conflict.

The original resolution, proposed by Germany, said that women who had been raped needed access to safe abortions, as well as reproductive and sexual healthcare.

But the resolution approved by the Security Council by a vote of 13-0 on 23 April, with Russia and China abstaining, had any language relating to “sexual and reproductive health” removed.

The US news station CNN reported that the original draft had contained an appeal to the United Nations and donors to provide comprehensive health services, including sexual and reproductive healthcare, to victims of sexual violence.1

Speakers at the …