tbuckley/cabot-search huggingface dataset:
Targeting intracellular MMPs efficiently inhibits tumor metastasis and angiogenesis
Authors: Yaqi Lv, Xiangmei Zhao, Lidan Zhu, Sijia Li, Qingqing Xiao, Wei He, Lifang Yin
Journal: Theranostics (2018)

Treatment for metastatic cancer is a great challenge throughout the world.Commonly, directed inhibition of extracellular matrix metalloproteinases (MMPs) secreted by cancer cells can reduce metastasis.Here, a novel nanoplatform (HPMC NPs) assembled from hyaluronic acid (HA)-paclitaxel (PTX) prodrug and marimastat (MATT)/β-casein (CN) complexes was established to cure a 4T1 metastatic cancer model via targeting CD44 and intracellular, rather than extracellular, MMPs.Methods: HPMC NPs were prepared by assembling the complexes and prodrug under ultrasonic treatment, which the interaction between them was evaluated by förster resonance energy transfer, circular dichroism and fluorescence spectra.The developed nanoplatform was characterized via dynamic light scattering and transmission electron microscopy, and was evaluated in terms of MMP-sensitive release and stability.Subsequently, the cellular uptake, trafficking, and in vitro invasion were studied by flow cytometry, confocal laser microscopy and transwell assay.MMP expression and activity was determined by western blotting and gelatin zymography.Finally, the studies of biodistribution and antitumor efficacy in vivo were performed in a mouse 4T1 tumor breast model, followed by in vivo safety study in normal mouse. Results:The interaction between the prodrug and complexes is strong with a high affinity, resulting in the assembly of these two components into hybrid nanoparticles (250 nm).Compared with extracellular incubation with MATT, HPMC NP treatment markedly reduced the expression (100%) and activity (50%) of MMPs in 4T1 cells and in the tumor.HPMC NPs exhibited 1.4-fold tumor accumulation, inhibited tumor-growth by >8-fold in volume with efficient apoptosis and proliferation, and suppressed metastasis (>5-fold) and angiogenesis (>3-fold).Overall, HPMC NPs were efficient in metastatic cancer therapy.Conclusions: According to the assembly of polymer prodrug and protein-drug complexes, this study offers a new strategy for constructing nanoparticles for targeted drug delivery, biomedical imaging, and combinatorial treatment.Importantly, via inhibition of intracellular MMPs, metastasis and angiogenesis can be potently blocked, benefiting the rational design of nanomedicine for cancer treatment.
Reply to Pim J. van Leeuwen and Henk G. van der Poel's Letter to the Editor re: Karim A. Touijer, Robert J. Karnes, Niccolo Passoni, et al. Survival Outcomes of Men with Lymph Node-positive Prostate Cancer After Radical Prostatectomy: A Comparative Analysis of Different Postoperative Management Strategies. Eur Urol 2018;73:890–6.
Authors: Karim Touijer
Journal: European Urology (2018)
The death penalty.
Authors: M. O'Connor
Journal: BMJ (1992)

intervention can be recommended.In addition, use of a daytime average of 160/95mmHg must deny treatment to many patients who would receive it on the basis of the World Health Organisation criteria,8 and may deny some of them the benefits in terms of preventing stroke.Furthermore, as a separate issue, we are concerned that the common assumption that patients with "white coat" hypertension are not at risk may be flawed.9We believe that there is a need for prospectively collected data on the clinical outcome of patients managed on the basis of ambulatory rather than clinic pressures and suggest that this is an urgent concern.Such data might be collected by the joint action of academic centres working in this research area.Until such data have been collected, wholesale introduction of this technique in clinical practice may be premature.
Physician decision making in selection of second‐line treatments in immune thrombocytopenia in children
Authors: Rachael F. Grace, Jenny M. Despotovic, Carolyn M. Bennett, James B. Bussel, Michelle Neier, Cindy Neunert, Shelley E. Crary, Yves D. Pastore, Robert J. Klaassen, Jennifer A. Rothman, Kerry Hege, Vicky R. Breakey, Melissa J. Rose, Kristin A. Shimano, George R. Buchanan, Amy Geddis, Kristina M. Haley, Adonis Lorenzana, Alexis Thompson, Michael Jeng, Ellis J. Neufeld, Travis Brown, Peter W. Forbes, Michele P. Lambert
Journal: American Journal of Hematology (2018)

Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder which presents with isolated thrombocytopenia and risk of hemorrhage. While most children with ITP promptly recover with or without drug therapy, ITP is persistent or chronic in others. When needed, how to select second-line therapies is not clear. ICON1, conducted within the Pediatric ITP Consortium of North America (ICON), is a prospective, observational, longitudinal cohort study of 120 children from 21 centers starting second-line treatments for ITP which examined treatment decisions. Treating physicians reported reasons for selecting therapies, ranking the top three. In a propensity weighted model, the most important factors were patient/parental preference (53%) and treatment-related factors: side effect profile (58%), long-term toxicity (54%), ease of administration (46%), possibility of remission (45%), and perceived efficacy (30%). Physician, health system, and clinical factors rarely influenced decision-making. Patient/parent preferences were selected as reasons more often in chronic ITP (85.7%) than in newly diagnosed (0%) or persistent ITP (14.3%, P = .003). Splenectomy and rituximab were chosen for the possibility of inducing long-term remission (P < .001). Oral agents, such as eltrombopag and immunosuppressants, were chosen for ease of administration and expected adherence (P < .001). Physicians chose rituximab in patients with lower expected adherence (P = .017). Treatment choice showed some physician and treatment center bias. This study illustrates the complexity and many factors involved in decision-making in selecting second-line ITP treatments, given the absence of comparative trials. It highlights shared decision-making and the need for well-conducted, comparative effectiveness studies to allow for informed discussion between patients and clinicians.
Hospice Use and End-of-Life Care for Patients With End-stage Renal Disease
Authors: Margaret L. Schwarze, Kate Schueller, R. Allan Jhagroo
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
Improving Emergency Insulin Administration—Reply
Authors: D. Brock Hewitt, Cynthia Barnard, Karl Y. Bilimoria
Journal: JAMA (2018)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
ZEB Proteins in Leukemia: Friends, Foes, or Friendly Foes?
Authors: Bieke Soen, Niels Vandamme, Geert Berx, Jürg Schwaller, Pieter Van Vlierberghe, Steven Goossens
Journal: HemaSphere (2018)

Abstract ZEB1 and ZEB2 play pivotal roles in solid cancer metastasis by allowing cancer cells to invade and disseminate through the transcriptional regulation of epithelial‐to‐mesenchymal transition. ZEB expression is also associated with the acquisition of cancer stem cell properties and therapy resistance. Consequently, expression levels of ZEB1/2 and of their direct target genes are widely seen as reliable prognostic markers for solid tumor aggressiveness and cancer patient outcome. Recent loss‐of‐function mouse models demonstrated that both ZEBs are also essential hematopoietic transcription factors governing blood lineage commitment and fidelity. Interestingly, both gain‐ and loss‐of‐function mutations have been reported in multiple hematological malignancies. Combined with emerging functional studies, these data suggest that ZEB1 and ZEB2 can act as tumor suppressors and/or oncogenes in blood borne malignancies, depending on the cellular context. Here, we review these novel insights and discuss how balanced expression of ZEB proteins may be essential to safeguard the functionality of the immune system and prevent leukemia.
212Methylation, mis-splicing and expression of pathological isoforms in a disease causing Csrp3/Mlp mutation
Authors: Z Elbeck, V Azzimato, B Buyandelger, X Li, J W Wiseman, M Bohlooly, A Vegvari, R Knoell
Journal: Cardiovascular Research (2018)

Introduction:The changing landscape of chromatin activity is a crucial factor in transcriptional gene regulation.It is an important hallmark of diseases, however it has not yet been investigated systematically in human remodelled myocardium.Purpose: To address this gap of knowledge, we aim to reveal genome-wide chromatin activity based on myocardial samples from patients either with acquired myocardial remodelling due to severe aortic stenosis (AS) or inherited myocardial remodelling in patients with hypertrophic cardiomyopathy (HCM) due to mutated MYBPC3 gene; and donors without myocardial remodelling.Methods: Myocardial samples from 20 AS patients, 14 HCM patients and 5 healthy controls were included.We performed chromatin immunoprecipitation followed by sequencing using H3K27ac histon mark to identify differentially acetylated regions among three groups on a genome-wide scale.Comprehensive in silico analyses were performed, including (1) gene and pathway annotation of the whole dataset, (2) identification of transcription factor binding motifs and interacting genes, (3) identification of acquired-and inherited-specific H3K27ac signatures in remodelled myocardium.Results: In total, 5,634 regions with more activity (hyperacetylated) and 5,724 regions with less activity (hypoacetylated) were detected in acquired myocardial remodelling group compared to controls (FDR<0.05); while 7,216 hyperacetylated regions and 7,214 hypoacetylated regions were detected in inherited myocardial remodelling group compared to controls.Pathway annotation showed that genes in the vicinity of differentially acetylated regions were most enriched for fibrosis formation and decreased cell metabolism.Conclusions: This study presents for the first time a genome wide overview of H3K27ac profile using human cardiac tissue to study chromatin regulatory regions in both acquired and inherited myocardial remodelling.It demonstrates that chromatin regulatory signatures can provide valuable new information and aid in discovery of key pathways and transcription mechanisms in disease aetiology. 211High glucose exposure promotes epigenetic activation of pro-inflammatory RELA/p65 gene in cord blood-derived CD341 stem cells
Fecal microbiota profiles as a diagnostic biomarkers in cirrhosis and hepatocellular carcinoma and the impact of life style and nutrition
Authors: Y. Lapidot, R. Nosenko, B. Gayshis, M. Likhter, D. Ben-Ami, T. Engel, R. Margalit, I. Kalisky, P. Weiss, V. Ella, O. Cohen-Ezra, Y. Davidov, O. Koren, M. Safran, Z.B. Ari
Journal: Journal of Hepatology (2018)
Comparison of Early Intervention Services vs Treatment as Usual for Early-Phase Psychosis
Authors: Christoph U. Correll, Britta Galling, Aditya Pawar, Anastasia Krivko, Chiara Bonetto, Mirella Ruggeri, Thomas J. Craig, Merete Nordentoft, Vinod H. Srihari, Sinan Guloksuz, Christy L. M. Hui, Eric Y. H. Chen, Marcelo Valencia, Francisco Juarez, Delbert G. Robinson, Nina R. Schooler, Mary F. Brunette, Kim T. Mueser, Robert A. Rosenheck, Patricia Marcy, Jean Addington, Sue E. Estroff, James Robinson, David Penn, Joanne B. Severe, John M. Kane
Journal: JAMA Psychiatry (2018)

The value of early intervention in psychosis and allocation of public resources has long been debated because outcomes in people with schizophrenia spectrum disorders have remained suboptimal.To compare early intervention services (EIS) with treatment as usual (TAU) for early-phase psychosis.Systematic literature search of PubMed, PsycINFO, EMBASE, and ClinicalTrials.gov without language restrictions through June 6, 2017.Randomized trials comparing EIS vs TAU in first-episode psychosis or early-phase schizophrenia spectrum disorders.This systematic review was conducted according to PRISMA guidelines. Three independent investigators extracted data for a random-effects meta-analysis and prespecified subgroup and meta-regression analyses.The coprimary outcomes were all-cause treatment discontinuation and at least 1 psychiatric hospitalization during the treatment period.Across 10 randomized clinical trials (mean [SD] trial duration, 16.2 [7.4] months; range, 9-24 months) among 2176 patients (mean [SD] age, 27.5 [4.6] years; 1355 [62.3%] male), EIS was associated with better outcomes than TAU at the end of treatment for all 13 meta-analyzable outcomes. These outcomes included the following: all-cause treatment discontinuation (risk ratio [RR], 0.70; 95% CI, 0.61-0.80; P < .001), at least 1 psychiatric hospitalization (RR, 0.74; 95% CI, 0.61-0.90; P = .003), involvement in school or work (RR, 1.13; 95% CI, 1.03-1.24; P = .01), total symptom severity (standardized mean difference [SMD], -0.32; 95% CI, -0.47 to -0.17; P < .001), positive symptom severity (SMD, -0.22; 95% CI, -0.32 to -0.11; P < .001), and negative symptom severity (SMD, -0.28; 95% CI, -0.42 to -0.14; P < .001). Superiority of EIS regarding all outcomes was evident at 6, 9 to 12, and 18 to 24 months of treatment (except for general symptom severity and depressive symptom severity at 18-24 months).In early-phase psychosis, EIS are superior to TAU across all meta-analyzable outcomes. These results support the need for funding and use of EIS in patients with early-phase psychosis.
A Physician’s Suffering—Facing Depression as a Trainee
Authors: Colleen M. Farrell
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine 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 Internal Medicine journal
Tailored frequency-escalated primary prophylaxis for severe haemophilia A: results of the 16-year Canadian Hemophilia Prophylaxis Study longitudinal cohort
Authors: Brian M Feldman, Georges E Rivard, Paul Babyn, John K M Wu, MacGregor Steele, Man-Chiu Poon, Robert T Card, Sara J Israels, Nicole Laferriere, Kulwant Gill, Anthony K Chan, Manuel Carcao, Robert J Klaassen, Stephanie Cloutier, Victoria E Price, Saunya Dover, Victor S Blanchette
Journal: The Lancet Haematology (2018)
Association Between Proportion of Nuclei With High Chromatin Entropy and Prognosis in Gynecological Cancers
Authors: Birgitte Nielsen, Andreas Kleppe, Tarjei Sveinsgjerd Hveem, Manohar Pradhan, Rolf Anders Syvertsen, John Arne Nesheim, Gunnar Balle Kristensen, Jone Trovik, David James Kerr, Fritz Albregtsen, Håvard Emil Danielsen
Journal: JNCI Journal of the National Cancer Institute (2018)

Nuclear texture analysis measuring differences in chromatin structure has provided prognostic biomarkers in several cancers. There is a need for improved cell-by-cell chromatin analysis to detect nuclei with highly disorganized chromatin. The purpose of this study was to develop a method for detecting nuclei with high chromatin entropy and to evaluate the association between the presence of such deviating nuclei and prognosis.A new texture-based biomarker that characterizes each cancer based on the proportion of high-chromatin entropy nuclei (<25% vs ≥25%) was developed on a discovery set of 175 uterine sarcomas. The prognostic impact of this biomarker was evaluated on a validation set of 179 uterine sarcomas, as well as on independent validation sets of 246 early-stage ovarian carcinomas and 791 endometrial carcinomas. More than 1 million images of nuclei stained for DNA were included in the study. All statistical tests were two-sided.An increased proportion of high-chromatin entropy nuclei was associated with poor clinical outcome. The biomarker predicted five-year overall survival for uterine sarcoma patients with a hazard ratio (HR) of 2.02 (95% confidence interval [CI] = 1.43 to 2.84), time to recurrence for ovarian cancer patients (HR = 2.91, 95% CI = 1.74 to 4.88), and cancer-specific survival for endometrial cancer patients (HR = 3.74, 95% CI = 2.24 to 6.24). Chromatin entropy was an independent prognostic marker in multivariable analyses with clinicopathological parameters (HR = 1.81, 95% CI = 1.21 to 2.70, for sarcoma; HR = 1.71, 95% CI = 1.01 to 2.90, for ovarian cancer; and HR = 2.03, 95% CI = 1.19 to 3.45, for endometrial cancer).A novel method detected high-chromatin entropy nuclei, and an increased proportion of such nuclei was associated with poor prognosis. Chromatin entropy supplemented existing prognostic markers in multivariable analyses of three gynecological cancer cohorts.
Clinical and biological features according to fibrosis of HBV related HCC in a Western country
Authors: M. Allaire, E.H. Weam, S. Brichler, L. Blaise, N. Gisèle, B. Valerie, V. Grando, F. Arbadi, P. Nahon, M. Ziol, J. Charles Nault, N. Ganne-Carrié
Journal: Journal of Hepatology (2018)
P62Pathway analysis of RNA-sequencing of various stages of myodifferentiaion identifies conditions favoring type i and type II fibers, and highlights increased efficiency of combined differentiation
Authors: A Predeus, O A Ivanova, N V Khromova, A M Kiselev, D E Polev, N A Smolina, A A Kostareva, R I Dmitrieva
Journal: Cardiovascular Research (2018)

Neonatal mammalian heart has recently been shown to possess the capacity to regenerate completely after injury.This remarkable regenerative capacity is lost after postnatal day 7.This transition has been marked with cardiomyocyte cell cycle arrest and induction of fibrotic response similar to what occurs after myocardial infarction in adults.We have recently outlined the function of Meis1 as a new cardiogenic factor that plays a pivotal role in neonatal cardiac regeneration.However, underlying molecular mechanisms of neonatal cardiac regeneration and other cardiogenic factors remained elusive.Here, we investigated the involvement of novel putative cardiogenic factors in neonatal cardiac regeneration and cardiomyocyte cell cycle withdrawal.We have confirmed their expression in the heart and cardiomyocytes.We have shown that expressions of Inpp5d, Dnmt3a, c-Myc and Cbl are significantly downregulated during neonatal cardiac regeneration process.Intriguingly, these four factors are upregulated in non-regenerative period of 7-day old mice after injury.RNAi studies suggest a strong correlation of these cardiogenic factors in cardiomyocyte proliferation.Taken together, our findings suggest that Inpp5d, Dnmt3a, c-Myc and Cbl may be involved in the regulation of cardiomyocyte cell cycle progression and represent new targets for induction of cardiac regeneration.
Publisher Correction: Genome-wide association study of delay discounting in 23,217 adult research participants of European ancestry
Authors: Sandra Sanchez-Roige, Pierre Fontanillas, Sarah L. Elson, Anita Pandit, Ellen M. Schmidt, Johanna R. Foerster, Gonçalo R. Abecasis, Joshua C. Gray, Harriet de Wit, Lea K. Davis, James MacKillop, Abraham A. Palmer
Journal: Nature Neuroscience (2018)