tbuckley/cabot-search huggingface dataset:
In vitro studies on anti-cancer effect of Streptococcus pyogenes phage hyaluronidase (HylP) on breast cancer
Authors: Joo Hyoung Lee, Lakisha Moore, Sanjay Kumar, Lawrence DeLucas, David Pritchard, Selvarangan Ponnazhagan, Champion Deivanayagam
Journal: Cancer Research (2008)

1506   Hyaluronan (HA) is a non-sulfated glycosamioglycan that is vastly present in the extracellular matrix contributing to tissue homeostasis and structural integrity. The pathological relevance of HA to cancer has been extensively studied in many types of malignancies. Higher levels of HA in the tumor-stroma interface has been known to promote the tumor progression and metastasis through the constitutive HA-CD44 interactions and their related intracellular signalling pathways. We therefore hypothesize that reduction of extracellular HA by the catabolic process using hyaluronidase would attenuate the interaction of HA with CD44 receptor, and therefore decrease the rate of cancer cell proliferation and invasion. In this study,  Streptococcus pyogenes  bacteriophage H4489A hyaluronidase (HylP) and its mutant HylP H262A  have been expressed and purified to determine their effects on human breast cancer. Three different breast cancer cell lines (Hs578T, MDA-MB-231 and MCF-7) were chosen based on their HA production levels, and the colorimetric XTT assay and Matrigel invasion assay were performed to evaluate the effect of HylP on cell proliferation and invasion respectively. To further investigate the effect of the reduction in HA level on signalling pathways, the expression and activation of Erk1/2, Akt, RhoA, and metalloprotease were measured by immunoblotting and zymographic methods.  Upon treatment with HylP, decrement of both cell proliferation and invasion of aggressive breast cancer cell lines (Hs578T and MDA-MB-231) were observed, whereas the non-invasive cancer cells (MCF-7) showed no effect. The decrease in cell proliferation was proportional to the level of HA produced by the cell lines. The reduction of HA by HylP was shown to down-regulate the signaling pathways for cancer cell proliferation and invasion (Erk1/2, Akt, and RhoA). In the case of the mutant HylP H262A  that exhibits limited enzymatic activity, no such response was observed. These results suggest that the observed inhibitory effect of HylP is exerted by the reduction of HA. Furthermore, the external addition of longer HA polymers increased the invasiveness of both Hs578T and MDA-MB-231, however, when treated with HylP, a drastic reduction in cell invasion was observed. In accordance with cell invasion assays, the activation of MMP-2 was facilitated upon the addition of HA and its activation was decreased by 3-fold after treatment with HylP. Finally, the external addition of smaller HA oligosaccharides released by HylP enzyme exhibited negligible influence on cell proliferation and invasion. In conclusion, the diminution of extracellular HA by HylP enzyme effectively inhibits both cell proliferation and invasion of aggressive breast cancer cells and suggests the potential as a novel therapeutics.
Correlation between immuno-related adverse events (IRAEs) occurrence and clinical outcome in metastatic renal cell carcinoma (mRCC) patients treated with nivolumab: IRAENE trial, an Italian multi-institutional retrospective study
Authors: M.G. Vitale, S. Pipitone, S. Scagliarini, P.A. Zucali, L. Galli, S. Rossetti, C. Caserta, R. Iacovelli, C. Masini, C. Ficorella, S. Di Girolamo, S. Buti, B. Benedetti, M. Santoni, C. Porta, S. Bracarda, C. Baldessari, S. Giaquinta, S. Cascinu, R. Sabbatini
Journal: Annals of Oncology (2018)
Comparison of 2 Natural Language Processing Methods for Identification of Bleeding Among Critically Ill Patients
Authors: Maxwell Taggart, Wendy W. Chapman, Benjamin A. Steinberg, Shane Ruckel, Arianna Pregenzer-Wenzler, Yishuai Du, Jeffrey Ferraro, Brian T. Bucher, Donald M. Lloyd-Jones, Matthew T. Rondina, Rashmee U. Shah
Journal: JAMA Network Open (2018)

<h3>Importance</h3> To improve patient safety, health care systems need reliable methods to detect adverse events in large patient populations. Events are often described in clinical notes, rather than structured data, which make them difficult to identify on a large scale. <h3>Objective</h3> To develop and compare 2 natural language processing methods, a rules-based approach and a machine learning (ML) approach, for identifying bleeding events in clinical notes. <h3>Design, Setting, and Participants</h3> This diagnostic study used deidentified notes from the Medical Information Mart for Intensive Care, which spans 2001 to 2012. A training set of 990 notes and a test set of 660 notes were randomly selected. Physicians classified each note as<i>present</i>or<i>absent</i>for a clinically relevant bleeding event during the hospitalization. A bleeding dictionary was developed for the rules-based approach; bleeding mentions were then aggregated to arrive at a classification for each note. Three ML models (support vector machine, extra trees, and convolutional neural network) were developed and trained using the 990-note training set. Another instance of each ML model was also trained on a sample of 450 notes, with equal numbers of bleeding-present and bleeding-absent notes. The notes were represented using term frequency–inverse document frequency vectors and global vectors for word representation. <h3>Main Outcomes and Measures</h3> The main outcomes were accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for each model. Following training, the models were tested on the test set and sensitivities were compared using a McNemar test. <h3>Results</h3> The 990-note training set represented 769 patients (296 [38.5%] female; mean [SD] age, 67.42 [14.7] years). The 660-note test set represented 527 patients (211 [40.0%] female; mean [SD] age, 67.86 [14.7] years). Bleeding was present in 146 notes (22.1%). The extra trees down-sampled model and rules-based approaches were similarly sensitive (93.8% vs 91.1%; difference, 2.7%; 95% CI, −3.8% to 7.9%;<i>P</i> = .44). The positive predictive value for the extra trees model, however, was 48.6%. The rules-based model had the best performance overall, with 84.6% specificity, 62.7% positive predictive value, and 97.1% negative predictive value. <h3>Conclusions and Relevance</h3> Bleeding is a common complication in health care, and these results demonstrate an automated and scalable detection method. The rules-based natural language processing approach, compared with ML, had the best performance in identifying bleeding, with high sensitivity and negative predictive value.
Neoantigenic Potential of Complex Chromosomal Rearrangements in Mesothelioma
Authors: Aaron S. Mansfield, Tobias Peikert, James B. Smadbeck, Julia B.M. Udell, Enrique Garcia-Rivera, Laura Elsbernd, Courtney L. Erskine, Virginia P. Van Keulen, Farhad Kosari, Stephen J. Murphy, Hongzheng Ren, Vishnu V. Serla, Janet L. Schaefer Klein, Giannoula Karagouga, Faye R. Harris, Carlos Sosa, Sarah H. Johnson, Wendy Nevala, Svetomir N. Markovic, Aaron O. Bungum, Eric S. Edell, Haidong Dong, John C. Cheville, Marie Christine Aubry, Jin Jen, George Vasmatzis
Journal: Journal of Thoracic Oncology (2018)

IntroductionMalignant pleural mesothelioma is a disease primarily associated with exposure to the carcinogen asbestos. Whereas other carcinogen-related tumors are associated with a high tumor mutation burden, mesothelioma is not. We sought to resolve this discrepancy.MethodsWe used mate-pair (n = 22), RNA (n = 28), and T cell receptor sequencing along with in silico predictions and immunologic assays to understand how structural variants of chromosomes affect the transcriptome.ResultsWe observed that inter- or intrachromosomal rearrangements were present in every specimen and were frequently in a pattern of chromoanagenesis such as chromoplexy or chromothripsis. Transcription of rearrangement-related junctions was predicted to result in many potential neoantigens, some of which were proven to bind patient-specific major histocompatibility complex molecules and to expand intratumoral T cell clones. T cells responsive to these predicted neoantigens were also present in a patient's circulating T cell repertoire. Analysis of genomic array data from the mesothelioma cohort in The Cancer Genome Atlas suggested that multiple chromothriptic-like events negatively impact survival.ConclusionsOur findings represent the discovery of potential neoantigen expression driven by structural chromosomal rearrangements. These results may have implications for the development of novel immunotherapeutic strategies and the selection of patients to receive immunotherapies.
Impact of prenatal exercise on both prenatal and postnatal anxiety and depressive symptoms: a systematic review and meta-analysis
Authors: Margie H Davenport, Ashley P McCurdy, Michelle F Mottola, Rachel J Skow, Victoria L Meah, Veronica J Poitras, Alejandra Jaramillo Garcia, Casey E Gray, Nick Barrowman, Laurel Riske, Frances Sobierajski, Marina James, Taniya Nagpal, Andree-Anne Marchand, Megan Nuspl, Linda G Slater, Ruben Barakat, Kristi B Adamo, Gregory A Davies, Stephanie-May Ruchat
Journal: British Journal of Sports Medicine (2018)

To examine the influence of prenatal exercise on depression and anxiety during pregnancy and the postpartum period.Systematic review with random effects meta-analysis and meta-regression.Online databases were searched up to 6 January 2017.Studies of all designs were included (except case studies) if they were published in English, Spanish or French and contained information on the Population (pregnant women without contraindication to exercise), Intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise), Comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and Outcome (prenatal or postnatal depression or anxiety).A total of 52 studies (n=131 406) were included. 'Moderate' quality evidence from randomised controlled trials (RCTs) revealed that exercise-only interventions, but not exercise+cointerventions, reduced the severity of prenatal depressive symptoms (13 RCTs, n=1076; standardised mean difference: -0.38, 95% CI -0.51 to -0.25, I2=10%) and the odds of prenatal depression by 67% (5 RCTs, n=683; OR: 0.33, 95% CI 0.21 to 0.53, I2=0%) compared with no exercise. Prenatal exercise did not alter the odds of postpartum depression or the severity of depressive symptoms, nor anxiety or anxiety symptoms during or following pregnancy. To achieve at least a moderate effect size in the reduction of the severity of prenatal depressive symptoms, pregnant women needed to accumulate at least 644 MET-min/week of exercise (eg, 150 min of moderate intensity exercise, such as brisk walking, water aerobics, stationary cycling, resistance training).Prenatal exercise reduced the odds and severity of prenatal depression.
The Evolving Epidemiology and Management of Spontaneous Pneumothorax
Authors: Eric Savitsky, Scott S. Oh, Jay M. Lee
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 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
GW29-e1852 Coronary Artery Calcification Mediates the Association between 24-Hour Systolic Blood Pressure Variability and Major Adverse Cardiac Events
Authors: Weijing Feng, Kun Zhang, Suihua Huang, Feifei Huang, Zhibin Li, Jie Chen, Jingfeng Wang, Hui Huang
Journal: Journal of the American College of Cardiology (2018)
Antibodies targeting protein-arginine deiminase 4 (PAD4) demonstrate diagnostic value in rheumatoid arthritis
Authors: Laura Martinez-Prat, David Lucia, Claudia Ibarra, Michael Mahler, Thierry Dervieux
Journal: Annals of the Rheumatic Diseases (2018)

Although anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are widely used as part of the diagnosis of patients with rheumatoid arthritis (RA), they leave a serological gap.1 Recently, several novel autoantibodies have been described in RA including antibodies targeting protein-arginine deiminases (PAD).2 3 Similar to ACPA and RF, anti-PAD4 antibodies also precede the clinical onset of RA.4 A subset of autoantibodies cross-reactive to PAD3 and PAD4 decrease the enzyme’s calcium requirement into the physiologic range, thereby increasing the catalytic efficiency of PAD4.5 Here we aim to evaluate the diagnostic relevance of anti-PAD3/4 antibodies in a large cohort (n=1473) of patients with RA and relevant controls (details in figure 1, table 1).



Figure 1 
Distribution and diagnostic performance of anti-PAD3 and anti-PAD4 antibodies in patients with RA and controls. The prevalence and titres of both anti-PAD3 (A) and anti-PAD4 (B) antibodies were significantly higher in RA versus controls. Both anti-PAD3 and anti-PAD4 antibodies were found in ACPA+ and in ACPA− patients as well as in early RA. Cut-off values are indicated by the dotted red line (200 MFI for PAD3 and 1000 MFI for PAD4). Receiver operating characteristic (ROC) …
Reactive Oxygen and Nitrogen Species–Induced Protein Modifications: Implication in Carcinogenesis and Anticancer Therapy
Authors: Nurbubu T. Moldogazieva, Sergey V. Lutsenko, Alexander A. Terentiev
Journal: Cancer Research (2018)

Abstract Cancer is a complex disorder extremely dependent on its microenvironment and highly regulated by multiple intracellular and extracellular stimuli. Studies show that reactive oxygen and nitrogen species (RONS) play key roles in cancer initiation and progression. Accumulation of RONS caused by imbalance between RONS generation and activity of antioxidant system (AOS) has been observed in many cancer types. This leads to alterations in gene expression levels, signal transduction pathways, and protein quality control machinery, that is, processes that regulate cancer cell proliferation, migration, invasion, and apoptosis. This review focuses on the latest advancements evidencing that RONS-induced modifications of key redox-sensitive residues in regulatory proteins, that is, cysteine oxidation/S-sulfenylation/S-glutathionylation/S-nitrosylation and tyrosine nitration, represent important molecular mechanisms underlying carcinogenesis. The oxidative/nitrosative modifications cause alterations in activities of intracellular effectors of MAPK- and PI3K/Akt-mediated signaling pathways, transcription factors (Nrf2, AP-1, NFκB, STAT3, and p53), components of ubiquitin/proteasomal and autophagy/lysosomal protein degradation systems, molecular chaperones, and cytoskeletal proteins. Redox-sensitive proteins, RONS-generating enzymes, and AOS components can serve as targets for relevant anticancer drugs. Chemotherapeutic agents exert their action via RONS generation and induction of cancer cell apoptosis, while drug resistance associates with RONS-induced cancer cell survival; this is exploited in selective anticancer therapy strategies. Cancer Res; 78(21); 6040–7. ©2018 AACR.
Responsibility for Poor Health Status of Lower Income People Must Account for Morally Blameworthy Decisions Made by Employers Who Exploit Them
Authors: Michael Nair-Collins
Journal: The American Journal of Bioethics (2018)

In “Shrinking Poor White Life Spans: Class, Race, and Health Justice,” Erika Blacksher offers a thoughtful, rich, and courageous analysis of the impact of race, class, and their intersection on hea...
Pan-cancer analysis of ret fusions (FN) and rearrangements (RE) by genomic profiling of 158,360 tumors
Authors: L.M. Gay, D.C. Pavlick, S. Ramkissoon, S. Daniel, J.K. Killian, J.-A. Vergilio, E. Severson, G.M. Frampton, J.A. Elvin, J.S. Ross
Journal: Annals of Oncology (2018)
18F-NaF PET/CT in Prostatic Calculi
Authors: William Y. Raynor, Abdullah Al-Zaghal, Thomas J. Werner, Poul F. Høilund-Carlsen, Abass Alavi
Journal: Clinical Nuclear Medicine (2018)

Primary prostatic calculi commonly present asymptomatically in men over the age of 50 years. Individual calculi form when the secretory tube is blocked by inflammation, prostatic secretions, or corpora amylacea. Although small prostatic calculi have been described as a component of normal aging, increased prevalence of calculi has been associated with benign prostatic hyperplasia and prostatitis. We are presenting prostatic calcification in a 69-year-old man as incidentally detected on F-NaF PET/CT. Although previous publications have reported F-NaF uptake portraying calcification in soft tissue, these findings demonstrate a new domain in which to assess calcium metabolism using F-NaF PET/CT.
SMAC Mimetic Debio 1143 and Ablative Radiation Therapy Synergize to Enhance Antitumor Immunity against Lung Cancer
Authors: Zhen Tao, Neal S. McCall, Norbert Wiedemann, Grégoire Vuagniaux, Zhiyong Yuan, Bo Lu
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Adaptive antitumor immunity following ablative radiotherapy (ART) is attenuated by host myeloid-derived suppressor cell (MDSC), tumor-associated macrophage (TAM), and regulatory T-cell (Treg) infiltrates. We hypothesized treatment with ART and a secondary mitochondrial-derived activators of caspase (SMAC) mimetic could reverse the immunosuppressive lung cancer microenvironment to favor adaptive immunity. Experimental Design: To evaluate for synergy between ART and the SMAC mimetic Debio 1143 and the dependence upon CD8+ T cells and TNFα, we used LLC-OVA syngeneic mouse model of lung cancer and treated them with Debio 1143 and/or ART (30 Gy) with or without anti-CD8, anti-TNFα, or anti-IFNγ antibodies. Tumor-infiltrating OVA-specific CD8+ T cells, Tc1 effector cells, MDSCs, TAMs, and Tregs, were quantified by flow cytometry. Tc1-promoting cytokines TNFα, IFNγ, and IL1β and the immunosuppressive IL10 and Arg-1 within LLC-OVA tumor tissue or mouse serum were measured by RT-PCR and ELISA. Results: ART delayed tumor growth, and the addition of Debio 1143 greatly enhanced its efficacy, which included several complete responses. These complete responders rejected an LLC-OVA tumor rechallenge. ART and Debio 1143 synergistically induced a tumor-specific, Tc1 cellular and cytokine response while eliminating immunosuppressive cells and cytokines from the tumor microenvironment. Depletion of CD8+ cells, TNFα, and IFNγ with blocking antibody abrogated synergy between ART and Debio 1143 and partially restored tumor-infiltrating MDSCs. Conclusions: Debio 1143 augments the tumor-specific adaptive immunity induced by ART, while reversing host immunosuppressive cell infiltrates in the tumor microenvironment in a TNFα, IFNγ, and CD8+ T-cell–dependent manner. This provides a novel strategy to enhance the immunogenicity of ART.
Genotype effects contribute to variation in longitudinal methylome patterns in older people
Authors: Qian Zhang, Riccardo E Marioni, Matthew R Robinson, Jon Higham, Duncan Sproul, Naomi R Wray, Ian J Deary, Allan F McRae, Peter M Visscher
Journal: Genome Medicine (2018)

DNA methylation levels change along with age, but few studies have examined the variation in the rate of such changes between individuals. We performed a longitudinal analysis to quantify the variation in the rate of change of DNA methylation between individuals using whole blood DNA methylation array profiles collected at 2–4 time points (N = 2894) in 954 individuals (67–90 years). After stringent quality control, we identified 1507 DNA methylation CpG sites (rsCpGs) with statistically significant variation in the rate of change (random slope) of DNA methylation among individuals in a mixed linear model analysis. Genes in the vicinity of these rsCpGs were found to be enriched in Homeobox transcription factors and the Wnt signalling pathway, both of which are related to ageing processes. Furthermore, we investigated the SNP effect on the random slope. We found that 4 out of 1507 rsCpGs had one significant (P < 5 × 10−8/1507) SNP effect and 343 rsCpGs had at least one SNP effect (436 SNP-probe pairs) reaching genome-wide significance (P < 5 × 10−8). Ninety-five percent of the significant (P < 5 × 10−8) SNPs are on different chromosomes from their corresponding probes. We identified CpG sites that have variability in the rate of change of DNA methylation between individuals, and our results suggest a genetic basis of this variation. Genes around these CpG sites have been reported to be involved in the ageing process.
Conjugation of haematopoietic stem cells and platelets decorated with anti-PD-1 antibodies augments anti-leukaemia efficacy
Authors: Quanyin Hu, Wujin Sun, Jinqiang Wang, Huitong Ruan, Xudong Zhang, Yanqi Ye, Song Shen, Chao Wang, Weiyue Lu, Ke Cheng, Gianpietro Dotti, Joshua F. Zeidner, Jun Wang, Zhen Gu
Journal: Nature Biomedical Engineering (2018)
GW29-e0692 Branched Chain Amino Acids Attenuates Hepatic Akt Signaling and Results in Severe Liver Metabolic Disorder in High Fat Diets Induced Obese Mice
Authors: Huishou Zhao, Feng Yan, Shan Wang, Xiaomeng Zhang, Huaning Xie, Chong Huang, Yunlong Xia, Ling Tao
Journal: Journal of the American College of Cardiology (2018)
HLA class I and II alleles in susceptibility to ankylosing spondylitis
Authors: John D Reveille, Xiaodong Zhou, MinJae Lee, Michael H Weisman, Lin Yi, Lianne S Gensler, Hejian Zou, Michael M Ward, Mariko L Ishimori, Thomas J Learch, Dongyi He, Mohammad H Rahbar, Jiucun Wang, Matthew A Brown
Journal: Annals of the Rheumatic Diseases (2018)

Objective To examine associations of HLA class I and class II alleles with ankylosing spondylitis (AS) in three cohorts of patients of European, Asian and African ancestry. Methods HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1 alleles were genotyped in 1948 unrelated white and 67 African-American patients with AS from the Prospective Study of Outcomes in Ankylosing Spondylitis cohort, the North American Spondylitis Consortium and Australo-Anglo-American Spondyloarthritis Consortium, 990 white and 245 African-American Controls and HLA-B alleles in 442 Han Chinese patients with AS and 346 controls from Shanghai and Gansu, China. In addition to the case:control analyses, HLA-B*27 -negative patients with AS were analysed separately, and logistic regression and ‘relative predispositional effects’ (RPE) analyses were carried out to control for the major effect of HLA-B*27 on disease susceptibility. Results Although numerous associations were seen between HLA alleles and AS in whites, among HLA-B*27-negative patients with AS , positive associations were seen with HLA-A*29, B*38, B*49, B*52, DRB1*11 and DPB1*03:01 and negative associations with HLA-B*07, HLA-B*57, HLA-DRB1*15:01, HLA-DQB1*02:01 and HLA -DQB1*06:02 . Additional associations with HLA-B*14 and B*40 (B60) were observed via RPE analysis, which excludes the HLA-B*27 alleles. The increased frequency of HLA-B*40:01 and decreased frequency of HLA-B*07 was also seen in Han Chinese and African-Americans with AS. HLA-B*08 was decreased in whites with acute anterior uveitis. Conclusions These data, analysing the largest number of patients with AS examined to date in three ethnic groups, confirm that other HLA class I and II alleles other than HLA-B*27 to be operative in AS predisposition.