tbuckley/cabot-search huggingface dataset:
Abstract P211: Impact of Healthy Lifestyle Behaviors and Education Level on Cardiovascular Mortality: The Japan Collaborative Cohort Study
Authors: Eri Eguchi, Hiroyasu Iso, Kaori Honjo, Akiko Tamakoshi
Journal: Circulation (2016)

Introduction: Magnitude of impact of healthy lifestyle behaviors and education level on cardiovascular mortality is uncertain. Hypothesis: Impact of education on cardiovascular mortality is explained mostly by lifestyle behaviors Methods: The survey cohort was a total of 42,647 subjects (18,442 men and 24,205 women) aged 40-79 years with satisfactory information from 1988 to 1990, and followed up until the end of 2009. Education levels were sub-grouped into higher education (last school age of ≥16 years old) and lower education (&lt;16). We defined the healthy lifestyle score (fruits ≥1/day, fish ≥1/day, milk almost every day, exercise ≥5h/week and/or walking ≥0.5h/day, BMI 21-25kg/m2, ethanol intake &lt;46.0g/day, non-smoker, and sleep 5.5-7.5h/day, ranging 0 to 8), and calculated multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) to determine the magnitude of impacts of healthy lifestyle behaviors and education level on cardiovascular mortality with persons who have lower education and 0-3 lifestyle score category as reference. Population attributable fraction (PAF) of lifestyle behaviors on cardiovascular mortality stratified by education level were also calculated. Results: During the 19.3 median years of follow-up, there were 8,314 total deaths and 2,377 CVD deaths. Compared with persons with lower education and 0-3 healthy lifestyle score category, those with lower education and 7-8 healthy lifestyles score category and those with higher education and 7-8 healthy lifestyle score category showed lower risk of mortality from total CVD. The respective multivariable-adjusted HRs (95% CI) were 0.37 (0.28-0.48) for those with lower education and 7-8 lifestyle score category, and 0.37 (0.30-0.46) for those with higher education and 7-8 lifestyle score category in total men and women, 0.25 (0.14-0.44) and 0.43 (0.31-0.59), respectively, for men, and 0.43 (0.31-0.60) and 0.36 (0.27-0.49), respectively, for women. PAF of CVD mortality for those who were not in the category of 7-8 lifestyle behavior were 40.1% in higher education group and 68.5% in lower education. Conclusions: More than 50% of risk reduction of cardiovascular mortality for those who have 7-8 healthy lifestyle score category compared to those who have 0-3 healthy lifestyles were found irrespective of education level which suggests large part of impact of education on cardiovascular mortality is explained by lifestyle behaviors.
Gentle palpating liver sinusoidal endothelial cells reveals the dynamic behavior and formation of fenestrae: A new window for biomedical research
Authors: Filip Braet, Eddie Wisse
Journal: Hepatology (2017)

1Discipline of Anatomy and Histology, School of Medical Sciences, Cellular Imaging Facility, Charles Perkins CentreThe University of SydneySydneyNSWAustralia 2Division of Nanoscopy, Maastricht Multimodal Molecular Imaging InstituteDepartment of Internal Medicine, The University of MaastrichtMaastrichtThe Netherlands
Specialty Societies and Breast Cancer Screening Recommendations
Authors: Christoph I. Lee, John R. Scheel, Janie M. Lee
Journal: JAMA Internal Medicine (2017)

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
Contribution of cardiac and extra‐cardiac disease burden to risk of cardiovascular outcomes varies by ejection fraction in heart failure
Authors: Emil Wolsk, Brian Claggett, Lars Køber, Stuart Pocock, Salim Yusuf, Karl Swedberg, John J.V. McMurray, Christopher B. Granger, Marc A. Pfeffer, Scott D. Solomon
Journal: European Journal of Heart Failure (2017)
Vinculin is required to maintain glomerular barrier integrity
Authors: Franziska Lausecker, Xuefei Tian, Kazunori Inoue, Zhen Wang, Christopher E. Pedigo, Hossam Hassan, Chang Liu, Margaret Zimmer, Stephanie Jinno, Abby L. Huckle, Hellyeh Hamidi, Robert S. Ross, Roy Zent, Christoph Ballestrem, Rachel Lennon, Shuta Ishibe
Journal: Kidney International (2017)

Cell-matrix interactions and podocyte intercellular junctions are key for maintaining the glomerular filtration barrier. Vinculin, a cytoplasmic protein, couples actin filaments to integrin-mediated cell-matrix adhesions and to cadherin-based intercellular junctions. Here, we examined the role of vinculin in podocytes by the generation of a podocyte-specific knockout mouse. Mice lacking podocyte vinculin had increased albuminuria and foot process effacement following injury in vivo. Analysis of primary podocytes isolated from the mutant mice revealed defects in cell protrusions, altered focal adhesion size and signaling, as well as impaired cell migration. Furthermore, we found a marked mislocalization of the intercellular junction protein zonula occludens-1. In kidney sections from patients with focal segmental glomerulosclerosis, minimal change disease and membranous nephropathy, we observed dramatic differences in the expression levels and localization of vinculin. Thus, our results suggest that vinculin is necessary to maintain the integrity of the glomerular filtration barrier by modulating podocyte foot processes and stabilizing intercellular junctions.
The NLR and LMR ratio in newly diagnosed MM patients treated upfront with novel agents
Authors: Alessandra Romano, Nunziatina Laura Parrinello, Claudio Cerchione, Maria Letizia Consoli, Marina Parisi, Valeria Calafiore, Enrica Martino, Concetta Conticello, Francesco Di Raimondo, Giuseppe Alberto Palumbo
Journal: Blood Cancer Journal (2017)
Anticytokine autoantibodies in a patient with a heterozygous NFKB2 mutation
Authors: Kesava A. Ramakrishnan, William Rae, Gabriela Barcenas-Morales, Yifang Gao, Reuben J. Pengelly, Sanjay V. Patel, Dinakantha S. Kumararatne, Sarah Ennis, Rainer Döffinger, Saul N. Faust, Anthony P. Williams
Journal: Journal of Allergy and Clinical Immunology (2017)
Phase I study of X-82, an oral dual anti-VEGFR/PDGFR tyrosine kinase inhibitor, with everolimus in solid tumors.
Authors: Benjamin R. Tan, Joel Picus, Emily Chan, Albert C. Lockhart, Bruce J. Roth, Ashley Morton, Chris Liang, Andrea Wang-Gillam
Journal: Journal of Clinical Oncology (2016)

2588 Background: Anti-VEGFR tyrosine kinase inhibitors(TKI), combined with mTOR inhibitors, such as everolimus resulted in a significant response and progression-free survival benefit in pts with renal cell carcinoma. [Motzer]. In 2 Phase I studies of everolimus combined with sunitinib or lenvantinib, daily doses of everolimus above 2.5 mg and 5 mg, respectively, were not tolerated. [Molina]. X-82 is an oral multikinase inhibitor targeting VEGFR and PDGFR with a shorter half-life and limited tissue accumulation, thus, X-82 can potentially be combined with full therapeutic doses of everolimus. Methods: A 3+3 dose escalation design was utilized to determine the dose-limiting toxicities (DLT) and the recommended Phase II dose (RP2D) of daily oral X82 plus everolimus at 10 mg PO daily for patients with solid malignancies. Eligibility include PS 0-1, measurable disease, adequate organ function and normal LVEF. Results: 21 pts (10 M/ 11F) with various malignancies were enrolled. 3 pts were not evaluable for DLT: 1 non-compliance, 1 consent withdrawal and 1 never initiated study therapy. 1 of 6 evaluable pts treated at dose level 4 experienced DLTs (gr 3 fatigue and hypophosphatemia). 1 of 3 pts in cohort 5 experienced a gr 3 mucositis. Due to inability to maintain starting doses beyond 1 cycle in 2 of 3 pts on cohort 5, our RP2D is X82 300 mg with everolimus 10 mg. RESPONSE: At cohort 4, 2 partial responses (PR) were noted in pts with renal cell carcinoma (RCC) who progressed through prior TKI and another RCC pt had marked necrosis of his recurrent tumor (SD by RECIST). At cohort 5, 1 pt with RCC had a 16% tumor shrinkage (SD). 10 pts with neuroendocrine tumors (NET) had SD with response duration ranging from 3-23 months. Conclusions: The RP2D is X82 at 300 mg PO daily plus everolimus 10 mg PO daily. Favorable responses seen in RCC and prolonged SDs for NETs warrant further investigations in these tumor types. Clinical trial information: NCT01784861.Dose Level X82 Everolimus # pts pts with DLT Responses 1 100 mg 10 mg 3 0 2 SD panc NET and carcinoid 2 150 mg 10 mg 3 0 2 SD Carcinoid and glioblastoma 3 200 mg 10 mg 4 0 3 SD Panc NET (2), carcinoid 4 300 mg 10 mg 8 1-Gr 3 fatigue, Gr 3 hypophosphatemia 2 PR- RCC (2) 3 SD- panc NET (2), thymic NET 5 400 mg 10 mg 3 1-Gr 3 mucositis 2 SD- RCC and pancreatic NET
Abstract 17888: A Dynamically Updated Cardiac Transplant Waitlist Mortality Score
Authors: Vincent B Cruz, Robert Steffen, Randall Starling, David O Taylor, Kathy Hoercher, Jeevanantham Rajeswaran, Nicholas Smedira, Edward Soltesz, Eugene H Blackstone, Nader Moazami
Journal: Circulation (2015)

Introduction: U.S. heart allocation policies are currently under review. However, investigations into prioritization schemes for patients waiting for transplantation are hampered by the paucity of post-listing event data and complicated by widespread Mechanical Circulatory Support (MCS) usage. Hypothesis: A dynamic score can predict mortality and inform prioritization of patients awaiting heart transplant or considered for listing at time of MCS implant using clinical data, time-varying exposures, and laboratory values during listing. Methods: From 1/2008 to 6/2013, patients listed for transplant (n=314, 76%) or implanted with a MCS device with intention to list (n=101, 24%) were identified. Factors for a predictive, time-varying hazard model were selected from 74 pre-listing variables, 8 events and complications, and routine laboratory results after listing. Results: Seventy-eight deaths and 381 adverse events occurred during listing. A score based on 17 variables was developed, including black race, actual listing (vs. MCS), pulmonary artery pressure, history of coronary artery disease, diabetes, and ventricular tachycardia at listing, MCS implant and complications, dialysis, respiratory events, and neurologic events on the waitlist, and time-varying serum total bilirubin and creatinine. The figure shows a sample of predicted mortality scores varying over time as events and changes in biomarkers occur. Conclusions: We demonstrated a dynamic, updatable mortality risk score that predicts urgency among patients waiting for hearts independent of most demographics, heart failure etiology, symptoms, and cardiac function. This score tracks dynamic changes with time as biomarkers change and adverse events occur. MCS-related complications, neurologic events, and kidney failure significantly affect mortality. Future changes to U.S. heart transplant policies could use this newly developed tool as part of a larger allocation system.
<i>CXCR4</i> Is a Potential Target for Diagnostic PET/CT Imaging in Barrett's Dysplasia and Esophageal Adenocarcinoma
Authors: Hsin-Yu Fang, Natasha Stephens Münch, Margret Schottelius, Jonas Ingermann, Haibo Liu, Michael Schauer, Stefan Stangl, Gabriele Multhoff, Katja Steiger, Carlos Gerngroß, Moritz Jesinghaus, Wilko Weichert, Anja A. Kühl, Antonia R. Sepulveda, Hans-Jürgen Wester, Timothy C. Wang, Michael Quante
Journal: Clinical Cancer Research (2017)

Abstract Purpose: Barrett's esophagus represents an early stage in carcinogenesis leading to esophageal adenocarcinoma. Considerable evidence supports a major role for chronic inflammation and diverse chemokine pathways in the development of Barrett's esophagus and esophageal adenocarcinoma. Experimental Design: Here we utilized an IL1β transgenic mouse model of Barrett's esophagus and esophageal adenocarcinoma and human patient imaging to analyze the importance of CXCR4-expressing cells during esophageal carcinogenesis. Results: IL1β overexpression induces chronic esophageal inflammation and recapitulates the progression to Barrett's esophagus and esophageal adenocarcinoma. CXCR4 expression is increased in both epithelial and immune cells during disease progression in pL2-IL1β mice and also elevated in esophageal adenocarcinoma patient biopsy samples. Specific recruitment of CXCR4-positive (CXCR4+) immune cells correlated with dysplasia progression, suggesting that this immune population may be a key contributor to esophageal carcinogenesis. Similarly, with progression to dysplasia, there were increased numbers of CXCR4+ columnar epithelial cells at the squamocolumnar junction (SCJ). These findings were supported by stronger CXCR4-related signal intensity in ex vivo fluorescence imaging and autoradiography with advanced dysplasia. Pilot CXCR4-directed PET/CT imaging studies in patients with esophageal cancer demonstrate the potential utility of CXCR4 imaging for the diagnosis and staging of esophageal cancer. Conclusion: In conclusion, the recruitment of CXCR4+ immune cells and expansion of CXCR4+ epithelial cells in esophageal dysplasia and cancer highlight the potential of CXCR4 as a biomarker and molecular target for diagnostic imaging of the tumor microenvironment in esophageal adenocarcinoma. Clin Cancer Res; 24(5); 1048–61. ©2017 AACR.
The new classifications of ovarian, fallopian tube, and primary peritoneal cancer and their clinical implications
Authors: L.R. Duska, E.C. Kohn
Journal: Annals of Oncology (2017)

The roles of histologic characterization and staging are to provide reproducible metrics for cancer classification with which to direct the most appropriate clinical care and to yield the most stable reliable system to allow both prospective and retrospective data analysis. Both the histologic and staging classifications of malignant ovarian/tubal/peritoneal cancers have recently changed. The World Health Organization sponsored a review and reclassification of the pathology of cancers of the ovaries, fallopian tubes, and peritoneum, and published these updates in 2014. In so doing, they codified the two-tiered grading system that has been in use in serous ovarian cancers for nearly a decade. In parallel, FIGO reviewed and updated the surgical staging system, applied to all histotypes of ovarian, tubal, and peritoneal cancers, also published in 2014. In both cases, the changes made are meant to encompass a better understanding of disease, but both have important merits and drawbacks. Changes in staging complicate analysis of retrospective data against current data. Though in some aspects controversial, the changes overall are meant to represent a better biologic understanding of disease that we hope will lead to an improvement in patient care and directed therapy.
Further Actions Are Needed to Prevent Maternal Deaths From Epilepsy
Authors: Stephen J. McCall, Bryn Kemp, Marian Knight
Journal: JAMA Neurology (2017)

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 Neurology 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 Neurology journal
Gastrointestinal Stromal Tumors
Authors: Margaret von Mehren, Heikki Joensuu
Journal: Journal of Clinical Oncology (2017)

GI stromal tumors (GISTs) are neoplasms with a varying malignancy potential ranging from virtually indolent tumors to rapidly progressing cancers. GISTs occur throughout the intestinal tract, and most harbor an activating mutation in either KIT or platelet-derived growth factor A ( PDGFRA). Diagnosis is made using immunohistochemistry, but molecular testing with mutation analysis is paramount for selection of appropriate therapy. Most small GISTs are cured with surgery. Tyrosine kinase inhibitor (TKI) therapy has led to substantial improvements in survival, both for patients with localized GIST and those with advanced disease. Adjuvant therapy with imatinib benefits patients with a high risk of recurrence, with studies suggesting most benefit with at least 3 years of therapy. Neoadjuvant imatinib therapy should be considered for patients requiring extensive surgery, aiming at shrinking the tumor to allow organ preservation and less extensive surgery. The following three TKIs have been approved for the management of advanced disease: imatinib, sunitinib, and regorafenib; imatinib is usually the best tolerated of the three and the standard first-line treatment. TKIs benefit the majority of patients with advanced GIST but have no or limited efficacy in patients with the PDGFRA D842V mutation or patients with GIST lacking KIT and PDGFRA mutations. Surgery, the mainstay of primary tumor management, also plays a role in the advanced disease setting for selected patients, as do some other approaches such as palliative radiation therapy. Research continues to identify novel therapies, in particular effective agents to treat TKI-refractory disease.
Erythrocyte efferocytosis modulates macrophages towards recovery after intracerebral hemorrhage
Authors: Che-Feng Chang, Brittany A. Goods, Michael H. Askenase, Matthew D. Hammond, Stephen C. Renfroe, Arthur F. Steinschneider, Margaret J. Landreneau, Youxi Ai, Hannah E. Beatty, Luís Henrique Angenendt da Costa, Matthias Mack, Kevin N. Sheth, David M. Greer, Anita Huttner, Daniel Coman, Fahmeed Hyder, Sourav Ghosh, Carla V. Rothlin, J. Christopher Love, Lauren H. Sansing
Journal: Journal of Clinical Investigation (2017)

Macrophages are a source of both proinflammatory and restorative functions in damaged tissue through complex dynamic phenotypic changes. Here, we sought to determine whether monocyte-derived macrophages (MDMs) contribute to recovery after acute sterile brain injury. By profiling the transcriptional dynamics of MDMs in the murine brain after experimental intracerebral hemorrhage (ICH), we found robust phenotypic changes in the infiltrating MDMs over time and demonstrated that MDMs are essential for optimal hematoma clearance and neurological recovery. Next, we identified the mechanism by which the engulfment of erythrocytes with exposed phosphatidylserine directly modulated the phenotype of both murine and human MDMs. In mice, loss of receptor tyrosine kinases AXL and MERTK reduced efferocytosis of eryptotic erythrocytes and hematoma clearance, worsened neurological recovery, exacerbated iron deposition, and decreased alternative activation of macrophages after ICH. Patients with higher circulating soluble AXL had poor 1-year outcomes after ICH onset, suggesting that therapeutically augmenting efferocytosis may improve functional outcomes by both reducing tissue injury and promoting the development of reparative macrophage responses. Thus, our results identify the efferocytosis of eryptotic erythrocytes through AXL/MERTK as a critical mechanism modulating macrophage phenotype and contributing to recovery from ICH.
Dying at Home—Our Grandfather’s Great Escape
Authors: Benjamin Chin-Yee, Nicolas Chin-Yee
Journal: JAMA Internal Medicine (2017)

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
Long-Term Effects of G-CSF Therapy in Cyclic Neutropenia
Authors: David C Dale, AudreyAnna Bolyard, Tracy Marrero, Vahagn Makaryan, MaryAnn Bonilla, Daniel C Link, Peter Newburger, Akiko Shimamura, Laurence A Boxer, Charles Spiekerman
Journal: New England Journal of Medicine (2017)

Term Effects of G-CSF Therapy in Cyclic NeutropeniaTo the Editor: Cyclic neutropenia is a rare hematologic disease that is characterized by regular oscillations in blood neutrophil counts from normal levels (absolute neutrophil count [ANC], >1.5×10 9 per liter) to severe neutropenia (ANC, <0.2×10 9 per liter), usually with a cycle length of about 21 days. 1 When patients with this disorder have neutropenia, they often have fever and mouth ulcers and are at risk for severe infections.Cyclic neutropenia is usually an autosomal dominant disorder caused by mutations in the gene encoding neutrophil elastase (ELANE). 2 We first reported the use of granulocyte colonystimulating factor (G-CSF) in patients with cyclic neutropenia 28 years ago. 3Shortly thereafter, a randomized clinical trial showed that G-CSF prevented infections in such patients. 4Subsequently, we followed these patients and 350 others, including 191 affected patients in 37 families, through the Severe Chronic Neutropenia International Registry (SCNIR), which records treatments, serious infections, hospitalizations, cancers, and deaths. 5We defined severe infection as hospitalization for infection requiring antibiotics (e.g., febrile neutropenia, pneumonia, bacteremia, and peritonitis).The six patients in our original study are now between the ages of 38 and 94 years.Five of the