tbuckley/cabot-search huggingface dataset:
Induction of DNMT3B by PGE2 and IL6 at Distant Metastatic Sites Promotes Epigenetic Modification and Breast Cancer Colonization
Authors: Jae Young So, Nicolas Skrypek, Howard H Yang, Anand S Merchant, George W Nelson, Wei-Dong Chen, Hiroki Ishii, Jennifer M Chen, Gangqing Hu, Bhagelu R Achyut, Esther C Yoon, Liying Han, Chuanshu Huang, Margaret C Cam, Keji Zhao, Maxwell P Lee, Li Yang
Journal: Cancer Research (2020)

Current cancer treatments are largely based on the genetic characterization of primary tumors and are ineffective for metastatic disease. Here we report that DNA methyltransferase 3B (DNMT3B) is induced at distant metastatic sites and mediates epigenetic reprogramming of metastatic tumor cells. Multiomics analysis and spontaneous metastatic mouse models revealed that DNMT3B alters multiple pathways including STAT3, NFκB, PI3K/Akt, β-catenin, and Notch signaling, which are critical for cancer cell survival, apoptosis, proliferation, invasion, and colonization. PGE2 and IL6 were identified as critical inflammatory mediators in DNMT3B induction. DNMT3B expression levels positively correlated with human metastatic progression. Targeting IL6 or COX-2 reduced DNMT3B induction and improved chemo or PD1 therapy. We propose a novel mechanism linking the metastatic microenvironment with epigenetic alterations that occur at distant sites. These results caution against the "Achilles heel" in cancer therapies based on primary tumor characterization and suggests targeting DNMT3B induction as new option for treating metastatic disease. SIGNIFICANCE: These findings reveal that DNMT3B epigenetically regulates multiple pro-oncogenic signaling pathways via the inflammatory microenvironment at distant sites, cautioning the clinical approach basing current therapies on genetic characterization of primary tumors.
Stimulation of interlukin-8 expression in prostate cancer cell lines by TGF-β1
Authors: Shan Lu, Zhongyun Dong
Journal: Cancer Research (2005)

4532  Human prostate cancer cells and the stroma in the tumor environment produce a number of pro-angiogenic factors. Among them are interleukin (IL)-8 and transforming growth factor (TGF)-β1, both are overexpressed in advanced prostate cancer. Our previous studies suggest that TGF-β1 may contribute to IL-8 regulation in advanced prostate cancer. The purpose of this study was to investigate the effects of TGF-β1 on IL-8 expression in human prostate cancer cells. Three lines of human prostate cancer cell (PC-3MM2, DU-145, and LNCaP-LN3) were used in the present study. IL-8 production was measured by ELISA and IL-8 mRNA levels were determined by real-time reverse transcriptase PCR. We observed that PC-3MM2 cells constitutively express low levels of IL-8, less than 10 ng/105 cells/24 h. Expression of IL-8 at both protein and mRNA levels in PC-3MM2 cells was augmented by TGF-β1 in both dose- and time-dependent manners. TGF-β1 had no direct effects on IL-8 production in LNCaP-LN3 cells. It, however, enhanced IL-1-induced IL-8 production in the cells. In contrast, TGF-β1 did not increase IL-8 expression in DU-145 cells. TGF-β1-induced IL-8 expression in PC-3MM2 cells could be inhibited by the general tyrosine protein kinase inhibitor genistein, the MEK1/2 inhibitor U0126, and the p42/44 mitogen activated protein kinase kinase (MAPKK) inhibitor PD98059, suggesting MAPK activities was required for TGF-β1-induced IL-8 expression. Western blot analysis confirmed that tyrosine-phosphorylatiion of p42/44 MAPK was significantly increased within 30 minutes upon exposure of PC-3MM2 cells to TGF-β1. The above data demonstrate that TGF-β1 upregulates IL-8 expression, through the activation of MAPK pathways in some prostate cancer cells and suggest that it could be one of the factors that regulates IL-8 expression and, hence, angiogenesis in the tumor environment of human prostate cancer.
Annals Graphic Medicine - Dr. Mom: Time to Decompress
Authors: Grace E. Farris
Journal: Annals of Internal Medicine (2020)

Web Exclusives7 April 2020Annals Graphic Medicine - Dr. Mom: Time to DecompressFREEGrace E. Farris, MDGrace E. Farris, MDMount Sinai School of Medicine, New York, New York (G.E.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G20-0005 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Mount Sinai School of Medicine, New York, New York (G.E.F.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G18-0042.Author/Illustrator Information: Grace E. Farris, MD, is an assistant professor of medicine at Icahn School of Medicine at Mount Sinai and chief of hospital medicine at Mount Sinai West hospital in New York, New York. You can view her work at her Web site: www.farrisgrace.com.About Dr. Mom: In Dr. Mom, physician and cartoonist Grace Farris examines work–life balance while mothering and doctoring. Dr. Mom appears monthly in Annals Graphic Medicine at Annals.org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 April 2020Volume 172, Issue 7Page: W87-W88KeywordsConflicts of interestDisclosureHospital medicineHospitalists ePublished: 7 April 2020 Issue Published: 7 April 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Making football safer for women: a systematic review and meta-analysis of injury prevention programmes in 11 773 female football (soccer) players
Authors: Kay M Crossley, Brooke E Patterson, Adam G Culvenor, Andrea M Bruder, Andrea B Mosler, Benjamin F Mentiplay
Journal: British Journal of Sports Medicine (2020)

Objective To evaluate the effects of injury prevention programmes on injury incidence in any women’s football code; explore relationships between training components and injury risk; and report injury incidence for women’s football. Design Systematic review and meta-analysis. Data sources Nine databases searched in August 2019. Eligibility criteria Randomised controlled trials evaluating any injury prevention programme (eg, exercise, education, braces) were included. Study inclusion criteria were: ≥20 female football players in each study arm (any age, football code or participation level) and injury incidence reporting. Results Twelve studies, all in soccer, met inclusion criteria, with nine involving adolescent teams (aged &lt;18 years). All studies (except one) had a high risk of bias. Eleven studies examined exercise-based programmes, with most (9/11) including multiple (≥2) training components (eg, strength, plyometric, balance exercises). Multicomponent exercise programmes reduced overall (any reported) injuries (incidence rate ratio (IRR) 0.73, 95% CI 0.59 to 0.91) and ACL injuries (IRR 0.55, 95% CI 0.32 to 0.92). For exercise-based strategies (single-component and multicomponent), hamstring injuries were also reduced (IRR 0.40, 95% CI 0.17 to 0.95). While exercise-based strategies resulted in less knee, ankle and hip/groin injuries, and the use of multiple training components was associated with greater reductions in overall and knee injuries, further studies would be required to increase the precision of these results. The incidence of overall injuries in women’s football was 3.4 per 1000 exposure hours; with ankle injuries most common. Conclusion In women’s football, there is low-level evidence that multicomponent, exercise-based programmes reduce overall and ACL injuries by 27% and 45%, respectively. PROSPERO registration number CRD42018093527.
Abstract 12347: C53: An Innovative GC-B Activating Drug Targeting Cardiorenal Fibrosis and the Progression to CKD-induced Heart Failure
Authors: Yang Chen, Seethalakshmi R Iyer, Gerald E Harders, Jacob J Schaefer, Tomoko Ichiki, John C Burnett, Jeson Sangaralingham
Journal: Circulation (2019)

Introduction: The development of fibrosis in both the kidney and heart is a major driver for the progression to heart failure (HF) in chronic kidney disease (CKD), which in part, is mediated by mod...
Long-term Outcomes in Patients With Severely Reduced Left Ventricular Ejection Fraction Undergoing Percutaneous Coronary Intervention vs Coronary Artery Bypass Grafting
Authors: Louise Y. Sun, Mario Gaudino, Robert J. Chen, Anan Bader Eddeen, Marc Ruel
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> Data are lacking on the outcomes of patients with severely reduced left ventricular ejection fraction (LVEF) who undergo revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <h3>Objective</h3> To compare the long-term outcomes in patients undergoing revascularization by PCI or CABG. <h3>Design, Setting, and Participants</h3> This retrospective cohort study performed in Ontario, Canada, from October 1, 2008, and December 31, 2016, included data from Ontario residents between 40 and 84 years of age with LVEFs less than 35% and left anterior descending (LAD), left main, or multivessel coronary artery disease (with or without LAD involvement) who underwent PCI or CABG. Exclusion criteria were concomitant procedures, previous CABG, metastatic cancer, dialysis, CABG and PCI on the same day, and emergency revascularization within 24 hours of a myocardial infarction (MI). Data analysis was performed from June 2, 2018, to December 28, 2018. <h3>Exposures</h3> Revascularization by PCI or CABG. <h3>Main Outcomes and Measures</h3> The primary outcome was all-cause mortality. Secondary outcomes were death from cardiovascular disease, major adverse cardiovascular events (MACE; defined as stroke, subsequent revascularization, and hospitalization for MI or heart failure), and each of the individual MACE. <h3>Results</h3> A total of 12 113 patients (mean [SD] age, 64.8 (11.0) years for the PCI group and 65.6 [9.7] years for the CABG group; 5084 (72.5%) male for the PCI group and 4229 (82.9%) male for the PCI group) were propensity score matched on 30 baseline characteristics: 2397 patients undergoing PCI and 2397 patients undergoing CABG. The median follow-up was 5.2 years (interquartile range, 5.0-5.3). Patients who received PCI had significantly higher rates of mortality (hazard ratio [HR], 1.6; 95% CI, 1.3-1.7), death from cardiovascular disease (HR 1.4, 95% CI, 1.1-1.6), MACE (HR, 2.0; 95% CI, 1.9-2.2), subsequent revascularization (HR, 3.7; 95% CI, 3.2-4.3), and hospitalization for MI (HR, 3.2; 95% CI, 2.6-3.8) and heart failure (HR, 1.5; 95% CI, 1.3-1.6) compared with matched patients who underwent CABG. <h3>Conclusions and Relevance</h3> In this study, higher rates of mortality and MACE were seen in patients who received PCI compared with those who underwent CABG. The findings may provide insight to physicians who are involved in decision-making for these patients.
Coronavirus Disease 2019 in Children — United States, February 12–April 2, 2020
Authors: Stephanie Bialek, Ryan Gierke, Michelle Hughes, Lucy A. McNamara, Tamara Pilishvili, Tami Skoff
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

As of April 2, 2020, the coronavirus disease 2019 (COVID-19) pandemic has resulted in >890,000 cases and >45,000 deaths worldwide, including 239,279 cases and 5,443 deaths in the United States (1,2). In the United States, 22% of the population is made up of infants, children, and adolescents aged <18 years (children) (3). Data from China suggest that pediatric COVID-19 cases might be less severe than cases in adults and that children might experience different symptoms than do adults (4,5); however, disease characteristics among pediatric patients in the United States have not been described. Data from 149,760 laboratory-confirmed COVID-19 cases in the United States occurring during February 12-April 2, 2020 were analyzed. Among 149,082 (99.6%) reported cases for which age was known, 2,572 (1.7%) were among children aged <18 years. Data were available for a small proportion of patients on many important variables, including symptoms (9.4%), underlying conditions (13%), and hospitalization status (33%). Among those with available information, 73% of pediatric patients had symptoms of fever, cough, or shortness of breath compared with 93% of adults aged 18-64 years during the same period; 5.7% of all pediatric patients, or 20% of those for whom hospitalization status was known, were hospitalized, lower than the percentages hospitalized among all adults aged 18-64 years (10%) or those with known hospitalization status (33%). Three deaths were reported among the pediatric cases included in this analysis. These data support previous findings that children with COVID-19 might not have reported fever or cough as often as do adults (4). Whereas most COVID-19 cases in children are not severe, serious COVID-19 illness resulting in hospitalization still occurs in this age group. Social distancing and everyday preventive behaviors remain important for all age groups as patients with less serious illness and those without symptoms likely play an important role in disease transmission (6,7).
Obesity and COVID-19 Severity in a Designated Hospital in Shenzhen, China
Authors: Qingxian Cai, Fengjuan Chen, Tao Wang, Fang Luo, Xiaohui Liu, Qikai Wu, Qing He, Zhaoqin Wang, Yingxia Liu, Lei Liu, Jun Chen, Lin Xu
Journal: Diabetes Care (2020)

OBJECTIVE Patients with obesity are at increased risk of exacerbations from viral respiratory infections. However, the association of obesity with the severity of coronavirus disease 2019 (COVID-19) is unclear. We examined this association using data from the only referral hospital in Shenzhen, China. RESEARCH DESIGN AND METHODS A total of 383 consecutively hospitalized patients with COVID-19 admitted from 11 January 2020 to 16 February 2020 and followed until 26 March 2020 at the Third People’s Hospital of Shenzhen were included. Underweight was defined as a BMI &amp;lt;18.5 kg/m2, normal weight as 18.5–23.9 kg/m2, overweight as 24.0–27.9 kg/m2, and obesity as ≥28 kg/m2. RESULTS Of the 383 patients, 53.1% were normal weight, 4.2% were underweight, 32.0% were overweight, and 10.7% were obese at admission. Obese patients tended to have symptoms of cough (P = 0.03) and fever (P = 0.06) compared with patients who were not obese. Compared with normal weight patients, those who were overweight had 1.84-fold odds of developing severe COVID-19 (odds ratio [OR] 1.84, 95% CI 0.99–3.43, P = 0.05), while those who were obese were at 3.40-fold odds of developing severe disease (OR 3.40, 95% CI 1.40–2.86, P = 0.007), after adjusting for age, sex, epidemiological characteristics, days from disease onset to hospitalization, presence of hypertension, diabetes, cardiovascular disease, chronic obstructive pulmonary disease, liver disease, and cancer, and drug used for treatment. Additionally, after similar adjustment, men who were obese versus those who were normal weight were at increased odds of developing severe COVID-19 (OR 5.66, 95% CI 1.80–17.75, P = 0.003). CONCLUSIONS In this study, obese patients had increased odds of progressing to severe COVID-19. As the severe acute respiratory syndrome coronavirus 2 may continue to spread worldwide, clinicians should pay close attention to obese patients, who should be carefully managed with prompt and aggressive treatment.
One more paper towel, longer protection
Authors: Nianzhou Yu, Lisha Wu, Juan Su, Kai Huang, Shuang Zhao, Xiang Chen
Journal: Journal of the American Academy of Dermatology (2020)

COVID-19 is currently wreaking havoc all over the world. Owing to the shortage of surgical mask resources, the life-saving use of surgical masks has become a prominent topic of the public. The life cycle of a surgical mask is usually approximately 4 hours. One of the factors that limits the effective useful life of the surgical mask is the high humidity of the wearer's expired air and the splutter that lead to moisture being trapped in the masks.1Li Y. Wong T. Chung J. et al.In vivo protective performance of N95 respirator and surgical facemask.Am J Ind Med. 2006; 49: 1056-1065Crossref PubMed Scopus (120) Google Scholar This not only leads to growth of bacteria but also irritates the delicate facial skin. Paper towels, which are daily necessities, are highly absorbent and low priced. The surgical mask with a paper towel significantly reduces the amount of water vapor and the splutter exhaled from the mouth. To ensure the ability of the paper towel to absorb water vapor, the paper towel may be properly folded in half (about 1-2 times, moderate thickness), forming a rectangle. The size of paper towel should be adjusted according to the mouth position and within the range of the mask. Then the folded paper towel is placed on the inside and middle of the mask (Fig 1). Finally, put on the mask. The paper towel can be changed when you feel uncomfortable or at 30-minute intervals. Through our practice, the mask with a paper towel is more moisture resistant than without it and skin friendly. We hope this idea will be conducive to the prevention and control of COVID-19.
Going Upstream to Advance Psychosis Prevention and Improve Public Health
Authors: Deidre M. Anglin, Sandro Galea, Peter Bachman
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Covid-19: doctors still do not have #properPPE
Authors: Abi Rimmer
Journal: BMJ (2020)

Doctors are still struggling to get the personal protective equipment (PPE) they need, despite government promises, a BMA survey has found.

A BMJ campaign, supported by the BMA, was launched this month calling for healthcare workers on the frontline to be given the appropriate level of PPE and using #properPPE on social media.1

On 20 March Keith Willett, strategic incident director at NHS England and NHS Improvement, wrote to trusts and clinical commissioning groups to say that the NHS would provide them with “substantial extra deliveries” of PPE.2

A snapshot survey conducted by the BMA between 3 and 6 April has found, however, that many of its members do not feel properly protected at work. The survey found that of the 504 hospital doctors whose work included carrying out high risk, aerosol generating procedures (AGP), 48.41% (244) faced a shortage of FFP3 respirators.

Updated Public Health England …
Predicting the extent of nodal disease in early breast cancer.
Authors: Abigail Suzanne Caudle, Henry Mark Kuerer, Huong T. Le-Petross, Wei Tse Yang, Isabelle Bedrosian, Savitri Krishnamurthy, Anthony Lucci, Kelly Hunt, Elizabeth Ann Mittendorf
Journal: Journal of Clinical Oncology (2013)

95 Background: In early-stage breast cancer patients, the number of positive lymph nodes (LN) is considered in decisions regarding surgery and radiation. The goal of this study was to characterize the extent of axillary nodal involvement based on clinicopathologic and imaging features. Methods: A prospective database was used to identify T1-2 patients who underwent regional nodal ultrasound (US) and axillary lymph node dissection (ALND) from 2002-2012. Patients who received neoadjuvant chemotherapy or had extra-axillary LN metastases were excluded. Subjects were grouped by whether axillary metastases (AxM) were identified by US confirmed by needle biopsy or by sentinel lymph node dissection (SLND) after a negative US, then compared using X 2 and Rank-Sum tests as appropriate. Results: AxM were identified by US in 190 patients and SLND in 518 patients. When compared to US-detected patients, SLND patients had fewer positive nodes (2.2 vs. 4.1, p &lt; 0.0001), smaller metastases (5.3 vs. 13.8 mm, p &lt; 0.0001), and a lower incidence of extranodal extension (ENE) (24% vs. 53%, p &lt; 0.0001). Limiting analyses to patients with ≤ 2 abnormal LN on US, US-detected patients still had more positive LN (3.6, p &lt; 0.001), larger metastases (13.4 mm, p &lt; 0.0001), and a higher incidence of ENE (50%, p &lt; 0.001) with more than 2 positive LN found in 45% of the US group versus 19% of the SLND group (p &lt; 0.001). In patients with lobular histology there were no differences in number of positive LN (4 in SLND vs. 3.6 in US, p = 0.36), or ENE (34% SLND vs. 36% US, p = 0.9). Positive non-SLN were found in 23% (96/415) of patients with ductal tumors and 36% (21/59) of those with lobular tumors. In multivariate analysis, having metastases found by US (OR 4.01, 95% CI 2.75-5.84) and lobular histology (OR 1.77, 95% CI 1.06-2.95) predicted having &gt; 2 positive LN adjusting for tumor size, receptor subtype, and histology. Conclusions: Patients with AxM found by US have more positive nodes, larger metastases, and higher risk of ENE, even if ≤ 2 suspicious LN are seen on US compared to patients with SLND-detected AxM. Tumor histology also predicts nodal burden. Clinicians can use imaging and clinicopathologic features to predict extent of nodal involvement and appropriately counsel patients regarding treatment decisions.
Structure of the Mucosal and Stool Microbiome in Lynch Syndrome
Authors: Yan Yan, David A. Drew, Arnold Markowitz, Jason Lloyd-Price, Galeb Abu-Ali, Long H. Nguyen, Christina Tran, Daniel C. Chung, Katherine K. Gilpin, Dana Meixell, Melanie Parziale, Madeline Schuck, Zalak Patel, James M. Richter, Peter B. Kelsey, Wendy S. Garrett, Andrew T. Chan, Zsofia K. Stadler, Curtis Huttenhower
Journal: Cell Host & Microbe (2020)
How Effective Is the Early Management Bundle for Severe Sepsis/Septic Shock?
Authors: Hannah Moreira, Richard Sinert
Journal: JAMA Internal Medicine (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 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