tbuckley/cabot-search huggingface dataset:
Prognostic value of gene expression of p63 by microarray analysis in estrogen receptor positive and negative breast cancer
Authors: L. C. Hanker, T. Karn, A. Rody, E. Ruckhäberle, C. Solbach, M. Kaufmann
Journal: Journal of Clinical Oncology (2009)

566 Background: The protein 63 (p63) represents a member of the p53 family (p53/p63/p73) located on chromosome 3q27. This gene family seems to play an important role in carcinogenesis and its members may act as oncogenes or tumor suppressor genes. P63 is overexpressed in many different tumors like head and neck cancer, lung cancers, uterine tumors and breast cancer, and has been associated with poor prognosis in some studies. P63 was found to be overexpressed in a subset of highly aggressive breast cancers that represent a basal and myoepithelial phenotype and have a poor clinical outcome. This protein seems to be a specific myoepithelial cell marker in normal breast tissue and might represent a prognostic factor in breast cancer. Methods: Large scale analysis was performed using Affymetrix microarray data from n=1581 breast cancer patients to evaluate p63 expression. Results: P63 expression showed a strong correlation with patient's age (χ 2 -test, p &lt; 0.001), tumor size (p &lt; 0.003), proliferation rate (p &lt; 0.001), Topo2α expression (p = 0.001) and estrogen receptor expression (p = 0.017). Survival analysis of all patients with available follow up data (n = 1263) showed a significant difference due to high and low p63 expression (log rank p &lt; 0.001). Patients with a low p63 expression had the worst prognosis. In univariate Cox regression analysis p63 showed a hazard ratio (HR) of 1.61 (95% CI 1.31–2.00, p &lt; 0.001) for disease free survival. This prognostic impact remained significant when samples were stratified by estrogen receptor status. High expression of p63 was significantly associated with longer OS in both ER negative (n = 334, log rank p = 0.022) and ER positive (n = 929, log rank p &lt; 0,001) breast cancer. The prognostic impact of p63 expression was independent of Ki67 expression (p = 0.011 and p = 0.001 for high and low Ki67, respectively). Moreover a worse prognosis of low p63 expressing tumors was found in both subgroups of ErbB2 positive tumors (p &lt; 0.001) and ErbB2 negative tumors (p &lt; 0.001). Conclusions: P63 expression is a prognostic factor in both ER positive and negative breast cancer and could be helpful for risk assessment in breast cancer patients. No significant financial relationships to disclose.
Age and ABO Blood Group Are Significant Predictors of Thrombosis in Children with Acute Lymphoblastic Leukemia (ALL): Results from Dana-Farber Cancer Institute (DFCI) ALL Consortium Trial 05-001
Authors: Uma H. Athale, Traci M. Blonquist, Kristen E. Stevenson, Menachem Spira, Peter D. Cole, Barbara L Asselin, Luis A. Clavell, Kara M. Kelly, Caroline Laverdière, Jean-Marie Leclerc, Bruno Michon, Marshall A. Schorin, Maria Luisa Sulis, Jennifer J.G. Welch, Marian H. Harris, Donna S. Neuberg, Stephen E. Sallan, Lewis B. Silverman
Journal: Blood (2017)
Intra-CSF trastuzumab in patients with neoplastic meningitis from breast cancer or primary brain tumors
Authors: D. L. Allison, M. Glantz, T. L. Werner, S. L. Kirkegaard, K. Murdock, R. Jensen
Journal: Journal of Clinical Oncology (2009)

2066 Background: Neoplastic meningitis is a devastating complication of extra-CNS malignancies and primary brain tumors with few available treatments and none of outstanding efficacy. Trastuzumab, a large molecule monoclonal antibody directed against the HER-2/neu receptor (overexpressed on some breast cancers, glioblastomas, and medulloblastomas), has negligible access to the CSF after intravenous administration. Intra-CSF administration could circumvent this barrier. Methods: Sixteen patients with neoplastic meningitis (11 GBM, 4 breast cancer, 1 medulloblastoma) and progressive neurologic deterioration were treated with intra-CSF trastuzumab (20–60 mg per dose, either weekly or every other week) for four treatments. Age ranged from 35 to 74 (median 51) years; KPS ranged from 60 to 90 (median 70). Patients who were neurologically and radiographically stable or improved after four treatments were continued on every other week therapy until neurologic progression. CSF cytology, neurologic status, and KPS were assessed at each treatment. MRI scanning of sites of previously demonstrated leptomeningeal tumor was performed after four treatments and then at 8 week intervals. HER-2/neu status of the primary tumors was also evaluated. Results: Two of the four patients with breast cancer (both HER-2/neu+) are responding clinically and cytologically 4 and 14 weeks after initiating treatment. The patient with medulloblastoma (also HER-2/neu+) continues to respond clinically and cytologically after 6 weeks. Seven of 11 patients with GBM have responded (two cytologically, two radiographically, all seven clinically), with response durations ranging from 4 to 12+ weeks. HER-2/neu status is being assessed. There were no adverse events related to the trastuzumab. Conclusions: Trastuzumab can be safely administered into the CSF in patients with solid tumor neoplastic meningitis. Sustained clinical and cytologic responses may occur in patients with breast cancer and primary brain tumors. HER-2/neu status may predict response. Further study to establish the biologically optimum dose and efficacy of this agent may be warranted. No significant financial relationships to disclose.
Risk of bevacizumab-associated gastrointestinal perforation in patients with colorectal cancer and noncolorectal cancer
Authors: D. T. Chu, S. Hapani, S. Wu
Journal: Journal of Clinical Oncology (2009)

9622 Background: Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor. It is a widely used angiogenesis inhibitor in the treatment of colorectal cancer (CRC) and other solid tumors. Gastrointestinal (GI) perforation is a potentially fatal adverse event associated with bevacizumab, but the risk unclear. This study was conducted to determine the risk of developing GI perforation among CRC and non-CRC patients receiving bevacizumab. Methods: Databases from PUBMED and the Web Science from January 1966 until July 2008 and abstracts presented at the American Society of Clinical Oncology conferences from January 2000 to through July 2008 were searched to identify relevant studies. Eligible studies included prospective phase III clinical trials in which standard anti-neoplastic therapy was administered with and without the use of bevacizumab with available data for GI perforation. Summary incidence rate, relative risk (RR), and 95% confidence interval (CI) were calculated using fixed or random effect models based upon the heterogeneity of the included studies. Results: A total of 12084 patients with various solid tumors from 14 phase III trials were included for analysis. Among patients receiving bevacizumab, the incidence of GI perforation was 0.8% (95% CI: 0.6–1.1%), and RR was 2.0 (95% CI: 1.1–3.8, p = 0.028) in compared with controls. The risk of GI perforation was significantly increased in patients receiving bevacizumab at 5 mg/kg/week (RR 2.6, 95% CI: 1.0–6.6, p=0.04), but not at 2.5 mg/kg/week (RR=1.5, 95%CI: 0.7–3.3, p=0.3). Among 2151 patients with CRC, the incidence of GI perforation was 0.8% (95% CI: 0.5–1.6%); while for 2.999 patients with non-CRC malignancies, the incidence of GI perforation was 0.7% (95% CI: 0.5–1.1%); The relative risk of GI perforation varied with tumor type, with significantly increased risk observed in patients with CRC (RR = 3.1, 95% CI: 1.2–8.2, p&lt;0.023), but not non-CRC (RR=1.5, 95% CI: 0.67–3.4, p=0.3). Conclusions: There is a significant difference in the risk of developing GI perforation in CRC and non-CRC patients receiving bevacizumab with a higher relative risk in patients with CRC. Further investigation into the etiology of this difference is recommended. No significant financial relationships to disclose.
Fructose stimulated de novo lipogenesis is promoted by inflammation
Authors: Jelena Todoric, Giuseppe Di Caro, Saskia Reibe, Darren C. Henstridge, Courtney R. Green, Alison Vrbanac, Fatih Ceteci, Claire Conche, Reginald McNulty, Shabnam Shalapour, Koji Taniguchi, Peter J. Meikle, Jeramie D. Watrous, Rafael Moranchel, Mahan Najhawan, Mohit Jain, Xiao Liu, Tatiana Kisseleva, Maria T. Diaz-Meco, Jorge Moscat, Rob Knight, Florian R. Greten, Lester F. Lau, Christian M. Metallo, Mark A. Febbraio, Michael Karin
Journal: Nature Metabolism (2020)
Immunogenicity of a single-dose compared with a two-dose primary series followed by a booster dose of ten-valent or 13-valent pneumococcal conjugate vaccine in South African children: an open-label, randomised, non-inferiority trial
Authors: Shabir A Madhi, Eleonora AML Mutsaerts, Alane Izu, Welekazi Boyce, Sutika Bhikha, Benit T Ikulinda, Lisa Jose, Anthonet Koen, Amit J Nana, Andrew Moultrie, Lucy Roalfe, Adam Hunt, David Goldblatt, Clare L Cutland, Jeffrey R Dorfman
Journal: The Lancet Infectious Diseases (2020)
AB0963 HOW OFTEN DO DOCTORS TREAT PATIENTS WITH LOCAL DAMAGE TO THE PERIARTICULAR SOFT TISSUES IN REAL CLINICAL PRACTICE?
Authors: A. Karateev, A. Lila, N. Zagorodniy, E. Pogozheva
Journal: Annals of the Rheumatic Diseases (2020)

Background: Damage of the periarticular soft tissues (DPST) - tendinitis, entesitis, bursitis, etc. are one of the most common reasons for patients to contact rheumatologists and orthopedic surgeons. Objectives: To evaluate the frequency and localization of DPST in real clinical practice, as well as the effectiveness of therapy for this pathology in the acute period. Methods: 68 outpatient orthopaedic surgeons evaluated the frequency of initial patient recourse due to DPST within one month. The study did not include patients with systemic rheumatic diseases such as spondyloarthritis. The localization of DPST and the dynamics of clinical manifestations were evaluated in 1227 patients (women 42.5%, cf. age 51.3±15.5 years). Non-steroidal anti-inflammatory drugs (NSAIDs), mainly meloxicam, were used as a first-line treatment for DPST. The results of treatment were evaluated after 10-14 days with repeated visits of patients. Results: 7766 cases of primary outpatient treatment by orthopedic surgeons were evaluated. DPST was the cause of treatment in 1227 (15.8%) patients. This was the third highest incidence after acute injuries (37.2%) and knee osteoarthritis (20.6%). In patients with DPST, the most common lesions were in the knee area (knee entesopathy, prepatellar bursitis, pes anserinus area tendinitis/bursitis) - 21.2%, the foot (plantar fasciitis) - 16.9%, the shoulder (tendinitis of the rotator cuff) – 16.4%, and the elbow (lateral and medial epicondylitis) - 15.3%. After treatment, there was a significant decrease in the severity of pain during movement – from 6.58±1.61 to 2.48±1.60 points on the numerical rating scale (p&lt;0.001), a decrease in the intensity of pain at rest, at night and during palpation, as well as the severity of functional disorders. The need for local injection of glucocorticoids occurred in 22.1% of patients. Significant improvement was observed in all DPST localities, with 68.1% of patients rating the treatment result as “good” and “excellent”. Adverse reactions were observed in 15.0% of patients, and no serious complications were reported. Conclusion: DPST is the third most frequent reason of recourse to a doctor after acute injuries and osteoarthritis of large joints in the practice of outpatient orthopedic surgeons. The use of NSAIDs in the maximum therapeutic dose for 10-14 days allows for significant improvement in DPST of different localization. Disclosure of Interests: None declared
Abstract 13008: Pluripotent Stem Cell-derived Cardiomyocytes From a Patient With Arg723gly β-myosin Heavy Chain Mutation Show Alterations in Twitch Contractions, Calcium Transients and Highly Variable Allele Specific Expression of Mutant/wildtype β-myosin Heavy Chain Mrna
Authors: Natalie Weber, Tim Holler, Joachim Meissner, Judith Montag, Neele Peschel, Anne Kathrin Mayer, Kristin Schwanke, Birgit Piep, Ulrich Martin, Robert Zweigerdt, Theresia Kraft
Journal: Circulation (2019)

Hypertrophic cardiomyopathy (HCM) is the most frequent inherited cardiac disease. In mutation-positive patients one third of the mutations are located in the β-cardiac myosin heavy chain protein (β...
Tau expression as a predictive marker in ovarian cancer patients (pts) treated with platinum/paclitaxel chemotherapy
Authors: M. Smoter, B. Grala, L. Bodnar, C. Szczylik
Journal: Journal of Clinical Oncology (2009)

5529 Background: Ovarian cancer is the most lethal gynecologic cancer and its standard treatment consists of cytoreductive surgery followed by paclitaxel/platinum-based chemotherapy. Additional prognostic biomarkers may allow for more tailored chemotherapy and an improved outcome. Recently, microtubule associated protein tau was identified as a marker of response to paclitaxel in breast cancer. Its predictive value in ovarian cancer has not been established. We evaluated the relevance of tau expression in ovarian cancer. Methods: Tissue specimens were obtained from 74 ovarian cancer patients (stage I-IV) who underwent cytoreductive surgery followed by standard paclitaxel/platinum (cisplatin or carboplatin) chemotherapy. Tau expression was determined by immunohistochemistry using semiquantitative DAKO test. Statistical analysis included long rank test and Mann Whitney test. Results: Median age of pts was 54 years (range 31–73). 25.7% and 74.3% of the pts were classified as tau-negative and tau-positive, respectively. In the univariate analysis 2-year progression free survival in tau-negative and tau-positive groups was 75.0% and 30.6%, respectively (p = 0.0153). This relationship was confirmed in the multivariate analysis including age, disease stage, histology type, and grade (HR 2.68; 95%CI [1.13–6.37]; p = 0.0255). Among the 46 pts with measurable disease, overall response rate in tau-negative and tau-positive groups was 90.9 and 54.5%, respectively (p = 0.0299, Z = 2.17). Conclusions: Tau protein expression seems to be a strong predictor of clinical outcome in ovarian cancer pts applied paclitaxel/platinum-based chemotherapy. No significant financial relationships to disclose.
Is remarriage of public health and occupational health advice on physical activity really necessary?
Authors: Wendy J Brown
Journal: British Journal of Sports Medicine (2020)

In recent years several governments and agencies have developed population-based physical activity (PA) guidelines to guide disease prevention and health promotion policies and strategies. Most guidelines for adults now recommend an overall volume of 150–300 min of at least moderate to vigorous activity per week (500–1000 MET.min/week), twice weekly muscle strengthening exercises and minimising time spent in prolonged sitting.1 2 As these guidelines do not distinguish between PA in different domains (eg, leisure, transport, occupational), it is assumed, for example, that walking for 60 min as part of paid work (as Morris’ postal workers did in the 1960s) is as beneficial for health as is walking for leisure or transport. The problem today is that few occupations involve continuous moderate intensity PA, even though many workers are ‘on their feet all day’ (eg, nurses, retailers, teachers, tradespersons and so on), although at a fairly low level of intensity.

In their editorial, Holtermann et al 3 appear to question the relevance of current guidelines for working adults, as most of the research underpinning their development was drawn from studies of leisure time PA and did not take account of occupational PA. This is true, and reflects the fact that, in the case …
dmPFC-vlPAG projection neurons contribute to pain threshold maintenance and antianxiety behaviors
Authors: Jun-Bin Yin, Shao-Hua Liang, Fei Li, Wen-Jun Zhao, Yang Bai, Yi Sun, Zhen-Yu Wu, Tan Ding, Yan Sun, Hai-Xia Liu, Ya-Cheng Lu, Ting Zhang, Jing Huang, Tao Chen, Hui Li, Zhou-Feng Chen, Jing Cao, Rui Ren, Ya-Nan Peng, Juan Yang, Wei-Dong Zang, Xiang Li, Yu-Lin Dong, Yun-Qing Li
Journal: Journal of Clinical Investigation (2020)

The dorsal medial prefrontal cortex (dmPFC) has been recognized as a key cortical area for nociceptive modulation. However, the underlying neural pathway and the function of specific cell types remain largely unclear. Here, we show that lesions in the dmPFC induced an algesic and anxious state. Using multiple tracing methods including a rabies-based transsynaptic tracing method, we outlined an excitatory descending neural pathway from the dmPFC to the ventrolateral periaqueductal gray (vlPAG). Specific activation of the dmPFC/vlPAG neural pathway by optogenetic manipulation produced analgesic and antianxiety effects in a mouse model of chronic pain. Inhibitory neurons in the dmPFC were specifically activated using a chemogenetic approach, which logically produced an algesic and anxious state under both normal and chronic pain conditions. Antagonists of the GABAA receptor (GABAAR) or mGluR1 were applied to the dmPFC, which produced analgesic and antianxiety effects. In summary, the results of our study suggest that the dmPFC/vlPAG neural pathway might participate in the maintenance of pain thresholds and antianxiety behaviors under normal conditions, while silencing or suppressing the dmPFC/vlPAG pathway might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors.
Assessment of Autonomy in Operative Procedures Among Female and Male New Zealand General Surgery Trainees
Authors: Daniel B. Joh, Bert van der Werf, Bridget J. Watson, Rowan French, Simon Bann, Elizabeth Dennet, Benjamin P. T. Loveday
Journal: JAMA Surgery (2020)

<h3>Importance</h3> The need for trainee sex equality within surgical training has resulted in an appraisal of the training experience in the New Zealand general surgery training program. <h3>Objective</h3> To investigate the association between trainee sex and surgical autonomy in the operating room in the New Zealand general surgery training program. <h3>Design, Setting, and Participants</h3> Retrospective cohort study conducted from December 10, 2012, to December 10, 2017, examining all endoscopic, major, and minor procedures performed by all New Zealand general surgery trainees in every training hospital in New Zealand. <h3>Main Outcomes and Measures</h3> The primary outcome was the level of meaningful autonomy by each New Zealand general surgery trainee (ie, trainee as primary operator without the surgeon mentor scrubbed for the case). Outcomes were compared using multivariable analysis. <h3>Results</h3> This study included 120 New Zealand general surgery trainees (42 women [35%] and 78 men [65%]) who were analyzed over 279.5 trainee-years (88.5 trainee-years for women and 191.0 trainee-years for men). Included were 119 380 general surgery procedures (17 465 endoscopic, 56 964 major, and 44 951 minor) in 18 hospitals. By the end of the 5-year training program, female trainees had a lower cumulative mean autonomous caseload than male trainees for endoscopic (284.0 [95% CI, 207.0-361.0] vs 352.2 [95% CI, 282.9-421.6],<i>P</i> = .03), major (139.9 [95% CI, 76.7-203.2] vs 198.1 [95% CI, 142.3-254.0],<i>P</i> = .02), and minor (456.3 [95% CI, 394.8-517.9] vs 519.9 [95% CI, 465.6-574.2],<i>P</i> = .007) procedures. <h3>Conclusions and Relevance</h3> After accounting for differences among trainees, hospital type, number of female and male surgeon mentors at each hospital, and trainee seniority, female trainees performed fewer cases with meaningful autonomy compared with male trainees. These findings support the need for pragmatic solutions to address this bias and further investigations on mechanisms contributing to discrepancies.
Inhibition of PI3K/Akt signaling suppresses epithelial-to-mesenchymal transition in hepatocellular carcinoma through the Snail/GSK-3/beta-catenin pathway
Authors: Seulki Lee, Eun Ji Choi, Eun Ju Cho, Yun Bin Lee, Jeong-Hoon Lee, Su Jong Yu, Jung-Hwan Yoon, Yoon Jun Kim
Journal: Clinical and Molecular Hepatology (2020)

Background/Aims: Patients with advanced hepatocellular carcinoma (HCC) have a poor prognosis due to the lack of effective systemic therapies. Epithelial-to-mesenchymal transition (EMT) is a pivotal event in tumor progression, during which cancer cells acquire invasive properties. In this study, we investigated the effects of phosphatidylinositol 3-kinase (PI3K) inhibitors, including LY294002 and idelalisib, on the EMT features of HCC cells in vitro.Methods: Human HCC cell lines, including Huh-BAT and HepG2, were used in this study. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, and cell cycle distributions were evaluated using a flow cytometer by propidium iodide staining. Immunofluorescence staining, quantitative real-time polymerase chain reaction, and immunoblotting were performed to detect EMT-associated changes.Results: PI3K inhibitors suppressed the proliferation and invasion of HCC cells and deregulated the expression of EMT markers, as indicated by increased expression of E-cadherin, an epithelial marker, and decreased expression of N-cadherin, a mesenchymal marker, and Snail, a transcription factor implicated in EMT regulation. Furthermore, LY294002 and idelalisib inhibited the phosphorylation of GSK-3β and induced the nuclear translocation of GSK-3β, which corresponded to the downregulation of Snail and β-catenin expressions in Huh-BAT and HepG2 cells.Conclusions: The inhibition of PI3K/Akt signaling decreases Snail expression by enhancing the nuclear translocation of GSK-3β, which suppresses EMT in HCC cells, suggesting the potential clinical application of PI3K inhibitors for HCC treatment.
Errors in Statistical Numbers and Data in Study of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From COVID-19
Authors: Eike Nagel, Valentina O. Puntmann
Journal: JAMA Cardiology (2020)

Valentina O. Puntmann, MD, PhD; M. Ludovica Carerj, MD; Imke Wieters, MD; Masia Fahim; Christophe Arendt, MD; Jedrzej Hoffmann, MD; Anastasia Shchendrygina, MD, PhD; Felicitas Escher, MD; Mariuca Vasa-Nicotera, MD; Andreas M. Zeiher, MD; Maria Vehreschild, MD; Eike Nagel, MD
CCL28 mucosal expression in SARS-CoV-2-infected patients with diarrhea in relation to disease severity
Authors: None Yan Yan, Xiufeng Jiang, Xu Wang, Bin Liu, Hui Ding, Mengjun Jiang, Zhenkun Yang, Yaping Dai, Difei Ding, Hui Yu, Shiliang Zhang, Jun Liu, Mingchao Sha, Chunyan Lui, Yuanwang Qiu, Hongzhou Lu, Qinxue Hu
Journal: Journal of Infection (2020)