tbuckley/cabot-search huggingface dataset:
Synaptic Communication in Brain Cancer
Authors: Michelle Monje
Journal: Cancer Research (2020)

Increasing evidence indicates that the nervous system plays a critical role in cancer progression. This is particularly true in cancers that occur within the central nervous system. Communication between neurons and cancer cells is a fundamental component of brain cancer pathophysiology, both for primary gliomas and for brain metastases. Neuronal activity drives growth of glial malignancies through secreted growth factors and through direct electrochemical synaptic communication. Reciprocally, brain cancers influence neuronal function, increasing neuronal activity and modulating the function of the circuits into which the cancer cells structurally and electrically integrate. Advancing understanding of neuron-cancer interactions will elucidate new therapeutic strategies for these presently lethal brain cancers.
A Machine Learning Approach to Management of Heart Failure Populations
Authors: Linyuan Jing, Alvaro E. Ulloa Cerna, Christopher W. Good, Nathan M. Sauers, Gargi Schneider, Dustin N. Hartzel, Joseph B. Leader, H. Lester Kirchner, Yirui Hu, David M. Riviello, Joshua V. Stough, Seth Gazes, Allyson Haggerty, Sushravya Raghunath, Brendan J. Carry, Christopher M. Haggerty, Brandon K. Fornwalt
Journal: JACC Heart Failure (2020)
Public Health in the Selfie Generation
Authors: Sherry L. Pagoto, Alan C. Geller
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
High systemic and tumor-associated IL-8 correlates with reduced clinical benefit of PD-L1 blockade
Authors: Kobe C. Yuen, Li-Fen Liu, Vinita Gupta, Shravan Madireddi, Shilpa Keerthivasan, Congfen Li, Deepali Rishipathak, Patrick Williams, Edward E. Kadel, Hartmut Koeppen, Ying-Jiun Chen, Zora Modrusan, Jane L. Grogan, Romain Banchereau, Ning Leng, AnnChristine Thastrom, Xiadong Shen, Kenji Hashimoto, Darren Tayama, Michiel S. van der Heijden, Jonathan E. Rosenberg, David F. McDermott, Thomas Powles, Priti S. Hegde, Mahrukh A. Huseni, Sanjeev Mariathasan
Journal: Nature Medicine (2020)
Primary sclerosing cholangitis and ulcerative colitis: Evidence for increased neoplastic potential*1
Authors: U BROOME
Journal: Hepatology (1995)

Primary sclerosing cholangitis (PSC) is a biliary destructive disease mostly affecting patients with ulcerative colitis (UC). PSC has been suggested to be an independent risk factor for the development of colorectal malignancy in UC. Patients with PSC also have an increased risk of developing cholangiocarcinoma. This study aimed at assessing the cumulative risk of colorectal neoplasia in PSC and UC, and also to determine risk factors for the development of cholangiocarcinoma. Fifty-eight PSC patients were included. Forty PSC patients having extensive UC were each matched to two control patients of the same age, with extensive colitis and a comparable duration of the colitis, but without PSC. All UC patients had been under colonoscopic surveillance with multiple biopsies. Among the 40 PSC patients with UC, 16 developed colonic dysplasia or carcinoma, versus 10 in the control group (P < .001). The absolute cumulative risk of developing colorectal dysplasia/carcinoma in the PSC/UC groups was 9%, 31%, and 50% after 10, 20, and 25 years of disease duration. In the group with UC only, the corresponding risk was 2%, 5%, and 10%, respectively (P < .001). Ten patients with PSC developed cholangiocarcinoma, all but one having UC. In the control group, no cholangiocarcinoma occurred. Patients with PSC and UC with colorectal neoplasia developed cholangiocarcinoma significantly more often compared with patients with UC and PSC without colonic dysplasia/carcinoma (P < .02). This study demonstrates not only that patients with PSC and UC have a significantly higher risk of developing colorectal neoplasia compared with patients having UC only, but also that patients with PSC and UC having colorectal neoplasia are more prone to develop cholangiocarcinoma.
Engineered 3D hydrogels with full-length fibronectin that sequester and present growth factors
Authors: Sara Trujillo, Cristina Gonzalez-Garcia, Patricia Rico, Andrew Reid, James Windmill, Matthew J. Dalby, Manuel Salmeron-Sanchez
Journal: Biomaterials (2020)

Extracellular matrix (ECM)-derived matrices such as Matrigel are used to culture numerous cell types in vitro as they recapitulate ECM properties that support cell growth, organisation, migration and differentiation. These ECM-derived matrices contain various growth factors which make them highly bioactive. However, they suffer lot-to-lot variability, undefined composition and lack of controlled physical properties. There is a need to develop rationally designed biomaterials that can also recapitulate ECM roles. Here, we report the development of fibronectin (FN)-based 3D hydrogels of controlled stiffness and degradability that incorporate full-length FN to enable solid-phase presentation of growth factors in a physiological manner. We demonstrate, in vitro and in vivo, the effect of incorporating vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) in these hydrogels to enhance angiogenesis and bone regeneration, respectively. These hydrogels represent a step-change in the design of well-defined, reproducible, synthetic microenvironments for 3D cell culture that incorporate growth factors to achieve functional effects.
Three-Year Clinical Outcome of Paclitaxel- and Sirolimus-Eluting Stents Versus Bare Metal Stents in Patients with Diabetes Mellitus. From Western Denmark Herart Registry
Authors: L.O. Jensen, Anne Kaltoft, Per Thayssen, Michael Mæng, Hans-Henrik Tilsted Hansen, Jens Flensted Lassen, K.N. Hansen, Klaus Rasmussen, Morten Madsen, Søren Paaske Johnsen, Henrik Toft Sørensen, Leif Thuesen
Journal: Journal of the American College of Cardiology (2009)
Immunotherapeutic Response in Tumors Is Affected by Microenvironmental ROS
Authors: Simon W. Hayward
Journal: Cancer Research (2020)

Abstract Carcinoma-associated fibroblasts (CAF) are a potential therapeutic target for both direct and indirect regulation of cancer progression and therapy response. In this issue of Cancer Research, Ford and colleagues investigate the influence of CAF on the immune environment of tumors, specifically focusing on the regulation of CD8+ T cells, required for immune therapy response. Their work suggests a role for stromally expressed NADPH oxidase 4 (NOX4) as a modulator of reactive oxygen species that in turn can reduce the number of CD8+ T cells locally. Inhibition of NOX4 increased CD8+ T cells and restored responsiveness to immune therapy, suggesting an indirect stromally targeted avenue for therapy resensitization. See related article by Ford et al., p. 1846
Differentiating between different forms of moral obligations
Authors: Rajen A. Anderson, Benjamin C. Ruisch, David A. Pizarro
Journal: Behavioral and Brain Sciences (2020)

Abstract We argue that Tomasello's account overlooks important psychological distinctions between how humans judge different types of moral obligations, such as prescriptive obligations (i.e., what one should do) and proscriptive obligations (i.e., what one should not do). Specifically, evaluating these different types of obligations rests on different psychological inputs and has distinct downstream consequences for judgments of moral character.
Covid-19: NHS outlines services to be prioritised to restart in next six weeks
Authors: Gareth Iacobucci
Journal: BMJ (2020)

NHS England has set out details of which regular services should be prioritised for resumption over the next six weeks as part of the second phase of the health service’s response to the covid-19 pandemic.

On 17 March NHS hospitals in England were asked to suspend all non-urgent elective surgery to help free up general and acute care capacity in the wake of the pandemic.1 But on Monday 27 April the health and social care secretary, Matt Hancock, said that some services would resume this week as hospital admissions for covid-19 began to fall in most parts of the country.2

In a letter to all NHS …
EndoBronchial ultrasound: Morphological predictors of benign disease
Authors: Pratibha Gogia, Tabassum Insaaf, Tom Wilkinson Zoumot, Affroditi Baotau, William McNaulty, Pallav L. Shah
Journal: European Respiratory Journal (2014)

Rationale:  Endobronchial ultrasound (EBUS) has cemented its usefulness in the diagnosis and staging of mediastinal lymph nodes and it significantly obviates the requirement of mediastinoscopy. This study was performed to evaluate whether sonographic features could predict for benign diseases and hence avoid further invasive investigations.   Objective  To study the utility of EBUS morphology of mediastinal lymph nodes for predicting benign cytology in a prospective observational study.   Method  Morphological characteristics of mediastinal lymph nodes were recorded in all lymph nodes sampled during EBUS. Lymph nodes were evaluated for 5 parameters; size, shape, margins, echogenic appearance and the presence of a central blood vessel. These ultrasonographic characteristics were correlated with the final diagnosis.   Results  402 (237 males,165 females) patients underwent EBUS. The final diagnosis of malignant disease was in 244 (60.6%) of subjects and of benign or reactive lymph nodes in 153 (38.05% ) of patients and 5 patients (7 nodes sampled) were lost to follow up and final correlation could not be done. A total of 740 nodes were sampled. In 463 were ( 62.6%) malignant were identified whereas 270( 36.5%) nodes no malignant cells were identified. On Bivariate analysis small size, triangular shape and the presence of central vessel were predictive of a benign aetiology for the mediastinal lymph nodes. As per the final model, predictive probability of 0.811 (CI 0.72-0. 91s) was found if Ln size is    Conclusion:  Sonographic appearances of lymph nodes improves the negative predictive value of EBUS and reduce the need for investigations such as mediastinoscopy.
Efficacy of palonosetron (PAL) compared to other serotonin inhibitors (5-HT3R) in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately or highly emetogenic (MoHE) treatments: Systematic review and meta-analysis
Authors: O. Clark, T. Engel, L. Clark, L. Paladini, E. Faleiros, B. Pegoretti
Journal: Journal of Clinical Oncology (2009)

e20620 Background: Chemotherapy-induced nausea and vomiting (CINV) are frequent side effects of cancer treatment, with negative effects on quality of life. CINV may be acute (occurring within 24 hours after the chemotherapy) or delayed (up to 7 days after it). There are currently five serotonin inhibitors (5-HT3R) available on the market. PAL has the longer half-life, but there are controversies regarding if a better control of CINV (particularly delayed) is obtained with it. This controversy is reflected in recommendations of practice guidelines. Objective: To perform a systematic review and meta-analysis of all randomized controlled trials comparing a single intravenous dose of PAL 0,25mg with other 5-HT3R in patients receiving MoHE chemotherapy. Methods: We searched several databases, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were the incidence of acute and delayed nausea and vomiting. The side effects of each treatment were analyzed. A subgroup analysis on the impact of added corticosteroids was performed.The results of individual studies were pooled in a meta-analysis, using the RevMan 5.1 software. The results are expressed as Risk Ratio (RR) and the correspondent 95% Confidence Interval (CI). Results: We included 4 studies, with 1,298 patients. PAL was compared to ondansetron, granisetron and dolasetron. Patients in PAL group had less nausea, either acute (RR=0.75; CI= 0.64 to 0.88; P = 0.0004) or delayed (RR= 0.73; CI= 0.66 to 0.82; P &lt; 0.00001). They also had less acute vomiting (RR = 0.78; CI= 0.67 to 0.90; P = 0.0008) and delayed vomiting (RR= 0.75; CI= 0.67 to 0.84; P &lt; 0.00001). There were no statistical differences in side effects like headache (RR = 0.83; P = 0.29), dizziness (RR = 0.40; P = 0.12), constipation (RR = 1.35; P = 0.30) or diarrhea (RR = 0.67; P = 0.44). Patients receiving PAL presented less nausea and vomiting regardless of the use of corticoids. There was no statistical heterogeneity in the analises. Conclusions: PAL was more effective than the other 5-HT3R in preventing acute and delayed CINV in patients receiving MoHE treatments, regardless of the use of concomitant corticosteroids. [Table: see text]
Pay-it-forward gonorrhoea and chlamydia testing among men who have sex with men in China: a randomised controlled trial
Authors: Fan Yang, Tiange P Zhang, Weiming Tang, Jason J Ong, Marcus Alexander, Laura Forastiere, Navin Kumar, Katherine T Li, Fei Zou, Ligang Yang, Guodong Mi, Yehua Wang, Wenting Huang, Amy Lee, Weizan Zhu, Danyang Luo, Peter Vickerman, Dan Wu, Bin Yang, Nicholas A Christakis, Joseph D Tucker
Journal: The Lancet Infectious Diseases (2020)
Identification of the cystic fibrosis gene.
Authors: R A Knight, M E Hodson
Journal: BMJ (1990)

<b>Background:</b> Liver cirrhosis, which is caused by the accumulation of extracellular matrix materials, is a serious clinical problem that can progress to hepatic failure. Transforming growth factor-β (TGFβ) plays a pivotal role in extracellular matrix production, but bone morphogenetic protein (BMP)-7, a member of the TGFβ superfamily, can antagonise the fibrogenic activity of TGFβ. <b>Aim:</b> In this study, we examined whether adenovirus-mediated overexpression of BMP-7 (Ad-BMP-7) antagonised the effect of TGFβ in vitro and in vivo. <b>Methods and results:</b> In primary cultured rat stellate cells and the LX-2 human stellate cell line, induction of BMP-7 by Ad-BMP-7 infection decreased the expression of collagen 1A2 mRNA and smooth muscle α-actin in the presence or absence of TGFβ, via Smad 1/5/8 phosphorylation. BMP-7 triggered the mRNA expression of inhibitors of differentiation 2 (Id2) in LX-2. Although endogenous expression of BMP-7 was hardly detectable, Smad1 and Id2 overexpression increased BMP-7 expression in LX-2. A liver fibrosis model was induced by the repetitive intraperitoneal injection of thioacetamide (200 mg/kg body weight) twice per week for up to 7 weeks. In rats administered Ad-BMP-7 via the tail vein, hydroxyproline content and the areas stained by Sirius red dye in the liver were significantly reduced compared to controls. Ad-Id2 also reduced fibrosis. <b>Conclusion:</b> These data demonstrate that BMP-7, Smad 1/5/8 and Ids interact to antagonise hepatic fibrogenesis.
Leukocyte Adhesion Deficiency: An Inherited Defect In The Mac-1, LFA-1, And p150,95 Glycoproteins
Authors: D. Anderson
Journal: Annual Review of Medicine (1987)

Leukocyte adhesion deficiency (LAD) is a recently recognized autosomal-recessive trait characterized by recurrent bacterial infections, impaired pus formation and wound healing, and abnormalities in a wide spectrum of adherence-dependent functions of granulocytes, monocytes, and lymphoid cells. Features of this disease are attributable to deficiency (or absence) of cell surface expression of a family of functionally and structurally related glycoproteins. These include Mac-1 (complement receptor type 3), lymphocyte function-associated antigen-1 (LFA-1), and p150,95. Defective biosynthesis of the beta chain shared by each molecule (comprised of alpha 1 beta 1 complexes) represents the fundamental molecular basis of this disease. Recognition of the molecular pathogenesis of this disorder has allowed rich insights into the role of cellular adherence reactions in inflammation and host defense.
Circular RNA circ_0020710 drives tumor progression and immune evasion by regulating the miR-370-3p/CXCL12 axis in melanoma
Authors: Chuan-Yuan Wei, Meng-Xuan Zhu, Nan-Hang Lu, Jia-Qi Liu, Yan-Wen Yang, Yong Zhang, Yue-Dong Shi, Zi-Hao Feng, Jia-Xia Li, Fa-Zhi Qi, Jian-Ying Gu
Journal: Molecular Cancer (2020)

Circular RNAs (circRNAs) have been reported to have critical regulatory roles in tumor biology. However, their contribution to melanoma remains largely unknown.CircRNAs derived from oncogene CD151 were detected and verified by analyzing a large number of melanoma samples through quantitative real-time polymerase chain reaction (qRT-PCR). Melanoma cells were stably transfected with lentiviruses using circ_0020710 interference or overexpression plasmid, and then CCK-8, colony formation, wound healing, transwell invasion assays, and mouse xenograft models were employed to assess the potential role of circ_0020710. RNA immunoprecipitation, luciferase reporter assay and fluorescence in situ hybridization were used to evaluate the underlying mechanism of circ_0020710.Our findings indicated that circ_0020710 was generally overexpressed in melanoma tissues, and high level of circ_0020710 was positively correlated with malignant phenotype and poor prognosis of melanoma patients. Elevated circ_0020710 promoted melanoma cell proliferation, migration and invasion in vitro as well as tumor growth in vivo. Mechanistically, we found that high level of circ_0020710 could upregulate the CXCL12 expression via sponging miR-370-3p. CXCL12 downregulation could reverse the malignant behavior of melanoma cells conferred by circ_0020710 over expression. Moreover, we also found that elevated circ_0020710 was correlated with cytotoxic lymphocyte exhaustion, and a combination of AMD3100 (the CXCL12/CXCR4 axis inhibitor) and anti-PD-1 significantly attenuated tumor growth.Elevated circ_0020710 drives tumor progression via the miR-370-3p/CXCL12 axis, and circ_0020710 is a potential target for melanoma treatment.
B7-H3 Silencing By RNAi Inhibits Tumor Progression and Enhances Chemosensitivity in U937 Cells
Authors: Wei Zhang, Jing Wang, Yanfang Wang, Fei Dong, Mingxia Zhu, Wenli Wan, Haishen Li, Feifei Wu, Xinxing Yan, Xiao-Feng Yang, Xiaoyan Ke
Journal: Blood (2015)
The effect of pulmonary hypertension on aerobic exercise capacity in lung transplant candidates with advanced COPD
Authors: Yochai Adir, Jacob Ollech, Baruch Vainshelboim, Yael Shostak, Kramer Mordechai
Journal: European Respiratory Journal (2014)

Background:  Mild pulmonary hypertension (PH) in patients with advanced COPD is common but its effects on exercise capacity are controversial.   Objective : To investigated the effects of mild PH ( 35> mPAP ≥25 mmHG) on exercise capacity in lung transplant candidates with advanced COPD.   Methods : We retrospectively reviewed and compare the hemodynamic data and cardiopulmonary exercise test (CPET) variable in advanced COPD patients, candidate for lung transplantation with and without PH determined on right heart catheterization.   Results:  20 patients with COPD and no PH and 24 patients with COPD associated with mild PH included in the study. Both patients groups had severe airways obstruction with markedly reduced FEV1 (24.9%P±8.9 and 25.9%P±11.7, respectively), and severely reduced DLCO (35.2%P±17.3 and 39.2%P±15.9). No significant difference was found in any of the CPET variables except for VE/VCO 2  which was higher in patients with COPD and no PH and heart rate which was higher in the COPD and mild PH group. There was no correlation between mPAP and any of the exercise measurement.   Conclusions:  Our study suggests that exercise capacity in patients with advanced COPD is limited by the ventilatory impairment and the presence of mild PH has no farther impact on exercise capability.
Antiphospholipid Antibodies: Anticardiolipin and the Lupus Anticoagulant in Systemic Lupus Erythematosus (SLE) and in Non-SLE Disorders
Authors: Paul E. Love, Samuel A. Santoro
Journal: Annals of Internal Medicine (2020)

Abstract Purpose:To determine the prevalence of lupus anticoagulant and anticardiolipin in systemic lupus erythematosus (SLE) and in non-SLE disorders, and to evaluate the clinical significance of ...
A phase I study of AEE788, a novel multitargeted inhibitor of ErbB and VEGF receptor family tyrosine kinases, in recurrent GBM patients
Authors: D. Reardon, T. Cloughesy, C. Conrad, M. Prados, J. Xia, W. Mietlowski, M. Dugan, P. Mischel, H. Friedman, A. Yung
Journal: Journal of Clinical Oncology (2005)

3063 Background: AEE788 is an oral inhibitor with potent activity against multiple tyrosine kinases, including EGFR, HER2, and VEGFR2. This phase I study was to assess the safety and pharmacokinetics (PK) and to define the maximum tolerated dose (MTD)/dose limiting toxicity (DLT) of AEE788 in GBM patients (pts). Methods: Pts with GBM at 1st or 2nd recurrence were enrolled. Dose escalation followed accelerated titration design: 1 pt/cohort initially with expansion up to 3–6 pts. Two dose escalations occurred simultaneously: pts who received either non-enzyme inducing anticonvulsants (Gp A) or enzyme-inducing anticonvulsants (Gp B). Cardiac assessments were performed. A 24-hr PK was obtained on days 1, 15, and 28. A cycle (cyc) is 28 days. Results: To date, 26 pts (21 1st recurrent, 5 2nd recurrent; 20 male, 6 female), median age 50.5 (range 24–68), were treated with once daily AEE788 at doses of either 50 (2), 100 (6), 200 (1), 400 (3), 450 (1), or 550 (8) mg (Gp A); or 300 (2) or 600 (3) mg (Gp B). Two Gp A pts at 550 mg had DLTs (stomatitis, proteinuria, fatigue). No DLTs reported for Gp B pts to date. The most common (>15%) adverse events (AEs) included diarrhea (68%), skin rash (64%), fatigue (40%), nausea (36%), and anorexia, thrush, and emesis (each 16%). Most AEs were mild to moderate. Four pts had grade 3/4 reversible LFT increases; LFTs of 2 pts remained normal when rechallenged at a lower dose. One pt each had grade 4 thrombocytopenia and neutropenia. Three pts (550 mg) withdrew (<1 cyc) due to AEs. There were no effects on cardiac repolarization (measured by central tendency change from baseline in QTcF) and no change in cardiac conduction or heart rate in over 400 post-treatment ECGs. Exposure to AEE788 increased overproportionally with dose. Formation of the active metabolite (AQM674) was rapid, accounting for 30–40% of AEE788 exposure by day 15. Exposure to AEE788 and AQM674 was similar after 15 and 28 days of dosing. Gp B had lower exposure compared to Gp A at similar dose levels. Seven pts had SD (range 2–10 cycs), with 14% progression free survival at 6 months. Conclusions: AEE788 is well tolerated. DLT dose level for Gp A is 550 mg/day. Enrollment in both groups is continuing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis, Schering- Plough Novartis EMD, Novartis, Pfizer, Schering, Schering-Plough Genentech, Novartis