tbuckley/cabot-search huggingface dataset:
Paradoxical Increase in Microvascular Resistance During Tachycardia Downstream From a Severe Stenosis in Patients With Coronary Artery Disease
Authors: GianmarioSambuceti, MarioMarzilli, SilvioFedele, CeciliaMarini, AntonioL’Abbate
Journal: Circulation (2001)

Background—The pathophysiology of microvascular response to a severe coronary stenosis has not been conclusively identified. The aim of this study was to characterize the human vasomotor response to pacing-induced ischemia of both the stenotic arterial segment and the distal microcirculation. Methods and Results—Sixteen patients with stable angina and single-vessel disease were studied. Blood flow velocity and transstenotic pressure gradient were monitored at baseline, after intracoronary adenosine (2 mg), and during ischemia induced by atrial pacing with and without adenosine. At the end of this protocol, the study was repeated after intracoronary phentolamine in 7 patients and after angioplasty in 9. Stenosis resistance was calculated as the ratio between mean pressure gradient and mean flow, and microvascular resistance as the ratio between mean distal pressure and mean flow; values were expressed as percent of baseline. Adenosine decreased (P<0.05) baseline microvascular resistance to 52±17%, but not ...
A collagen-binding protein enables molecular imaging of kidney fibrosis in vivo
Authors: Maike Baues, Barbara M. Klinkhammer, Josef Ehling, Felix Gremse, Marc A.M.J. van Zandvoort, Chris P.M. Reutelingsperger, Christoph Daniel, Kerstin Amann, Janka Bábíčková, Fabian Kiessling, Jürgen Floege, Twan Lammers, Peter Boor
Journal: Kidney International (2019)
Male Hormonal Contraception
Authors: Arthi Thirumalai, Stephanie T. Page
Journal: Annual Review of Medicine (2019)

The economic and public health burdens of unplanned pregnancies are evident globally. Since the introduction of the condom >300 years ago, assumptions about male willingness to participate in contraception, as well as concerns about failure rates and side effects, have stagnated the development of additional reversible male contraceptives. However, changing attitudes and recent research advances have generated renewed interest in developing reversible male contraceptives. To achieve effective and reversible suppression of spermatogenesis, male hormonal contraception relies on suppression of testicular testosterone and sperm production using an androgen-progestin combination. While these may be associated with side effects-changes in libido, weight, hematocrit, and cholesterol-recently, novel androgens and progestins have shown promise for a "male pill" with reduced side effects. Here we summarize landmark studies in male contraceptive development, showcase the most recent advances, and look into the future of this field, which has the potential to greatly impact global public health.
Fundamentals for a Systematic Approach to Mild and Moderate Inherited Bleeding Disorders: An EHA Consensus Report
Authors: Francesco Rodeghiero, Ingrid Pabinger, Margaret Ragni, Rezan Abdul‐Kadir, Erik Berntorp, Victor Blanchette, Imre Bodó, Alessandro Casini, Paolo Gresele, Riitta Lassila, Frank Leebeek, David Lillicrap, Diego Mezzano, Patrizia Noris, Alok Srivastava, Alberto Tosetto, Jerzy Windyga, Barbara Zieger, Mike Makris, Nigel Key
Journal: HemaSphere (2019)

Healthy subjects frequently report minor bleedings that are frequently 'background noise' of normality rather than a true disorder. Nevertheless, unexpected or unusual bleeding may be alarming. Thus, the distinction between normal and pathologic bleeding is critical. Understanding the underlying pathologic mechanism in patients with an excessive bleeding is essential for their counseling and treatment. Most of these patients with significant bleeding will result affected by non-severe inherited bleeding disorders (BD), collectively denominated mild or moderate BD for their relatively benign course. Unfortunately, practical recommendations for the management of these disorders are still lacking due to the current state of fragmented knowledge of pathophysiology and lack of a systematic diagnostic approach. To address this gap, an International Working Group (IWG) was established by the European Hematology Association (EHA) to develop consensus-based guidelines on these disorders. The IWG agreed that grouping these disorders by their clinical phenotype under the single category of mild-to-moderate bleeding disorders (MBD) reflects current clinical practice and will facilitate a systematic diagnostic approach. Based on standardized and harmonized definitions a conceptual unified framework is proposed to distinguish normal subjects from affected patients. The IWG proposes a provisional comprehensive patient-centered initial diagnostic approach that will result in classification of MBD into distinct clinical-pathological entities under the overarching principle of clinical utility for the individual patient. While we will present here a general overview of the global management of patients with MBD, this conceptual framework will be adopted and validated in the evidence-based, disease-specific guidelines under development by the IWG.
N6-Methyladenosine Modulates Nonsense-Mediated mRNA Decay in Human Glioblastoma
Authors: Fuxi Li, Yang Yi, Yanyan Miao, Wenyong Long, Teng Long, Siyun Chen, Weisheng Cheng, Changye Zou, Yueyuan Zheng, Xingui Wu, Junjun Ding, Kaiyu Zhu, Delin Chen, Qiongcong Xu, Jinkai Wang, Qing Liu, Feng Zhi, Jian Ren, Qi Cao, Wei Zhao
Journal: Cancer Research (2019)

The N6-methyladenosine (m6A) modification influences various mRNA metabolic events and tumorigenesis, however, its functions in nonsense-mediated mRNA decay (NMD) and whether NMD detects induced carcinogenesis pathways remain undefined. Here, we showed that the m6A methyltransferase METTL3 sustained its oncogenic role by modulating NMD of splicing factors and alternative splicing isoform switches in glioblastoma (GBM). Methylated RNA immunoprecipitation-seq (MeRIP-seq) analyses showed that m6A modification peaks were enriched at metabolic pathway-related transcripts in glioma stem cells (GSC) compared with neural progenitor cells. In addition, the clinical aggressiveness of malignant gliomas was associated with elevated expression of METTL3. Furthermore, silencing METTL3 or overexpressing dominant-negative mutant METTL3 suppressed the growth and self-renewal of GSCs. Integrated transcriptome and MeRIP-seq analyses revealed that downregulating the expression of METTL3 decreased m6A modification levels of serine- and arginine-rich splicing factors (SRSF), which led to YTHDC1-dependent NMD of SRSF transcripts and decreased SRSF protein expression. Reduced expression of SRSFs led to larger changes in alternative splicing isoform switches. Importantly, the phenotypes mediated by METTL3 deficiency could be rescued by downregulating BCL-X or NCOR2 isoforms. Overall, these results establish a novel function of m6A in modulating NMD and uncover the mechanism by which METTL3 promotes GBM tumor growth and progression. SIGNIFICANCE: These findings establish the oncogenic role of m6A writer METTL3 in glioblastoma stem cells.
Screening for Breast Cancer in Average-Risk Women
Authors: Amanda Lenderink-Carpenter
Journal: Annals of Internal Medicine (2019)

Letters17 September 2019Screening for Breast Cancer in Average-Risk WomenAmanda Lenderink-Carpenter, MDAmanda Lenderink-Carpenter, MDKaiser Permanente Washington, Tacoma, Washington (A.L.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0473 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I wholeheartedly agree with ACP's statement (1) that “physicians play a key role in helping women accurately sort through the clinical evidence about benefits and harms” in relation to breast cancer screening. Unfortunately, their guidance statement on screening for breast cancer in average-risk women has left us poorly equipped to perform that role. It emphasizes that overdiagnosis rates are higher in women aged 39 to 49 years, which certainly causes one to take pause.We know that women in their 40s are more likely to have biologically aggressive cancer. We also know that women in their 40s ...References1. Qaseem A, Lin JS, Mustafa RA, et al; Clinical Guidelines Committee of the American College of Physicians. Screening for breast cancer in average-risk women: a guidance statement from the American College of Physicians. Ann Intern Med. 2019. [PMID: 30959525] doi:10.7326/M18-2147 LinkGoogle Scholar2. Hendrick RE. Obligate overdiagnosis due to mammographic screening: a direct estimate for U.S. women. Radiology. 2018;287:391-7. [PMID: 29267146] doi:10.1148/radiol.2017171622 CrossrefMedlineGoogle Scholar3. Monticciolo DL, Helvie MA, Hendrick RE. Current issues in the overdiagnosis and overtreatment of breast cancer. AJR Am J Roentgenol. 2018;210:285-91. [PMID: 29091010] doi:10.2214/AJR.17.18629 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Kaiser Permanente Washington, Tacoma, Washington (A.L.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0473. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoScreening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians Amir Qaseem , Jennifer S. Lin , Reem A. Mustafa , Carrie A. Horwitch , Timothy J. Wilt , and Screening for Breast Cancer in Average-Risk Women Jennifer S. Lin , Reem A. Mustafa , Timothy J. Wilt , Carrie A. Horwitch , and Amir Qaseem Screening for Breast Cancer in Average-Risk Women Lars J. Grimm Screening for Breast Cancer in Average-Risk Women Michelle V. Lee , Debbie L. Bennett , and Catherine M. Appleton Screening for Breast Cancer in Average-Risk Women Kelly W. Biggs Metrics 17 September 2019Volume 171, Issue 6Page: 450-451KeywordsBreast cancerBreast cancer screeningCancer screeningChildrenClimbingDisclosureForecastingMammographyObservational studies ePublished: 17 September 2019 Issue Published: 17 September 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Microfluidic Synthesis of Gd‐Based Nanoparticles for Fast and Ultralong MRI Signals in the Solid Tumor
Authors: Xuanyu Li, Qiang Feng, Xingyu Jiang
Journal: Advanced Healthcare Materials (2019)

Abstract Clinically used magnetic resonance imaging contrast agents (MRI CAs) for solid tumors suffer from short life spans and low accumulation at the tumor for their low molecular weights. A good solution is to incorporate these MRI CAs into nanoparticles. Food and Drug Administration‐approved compounds, poly(lactic‐ co ‐glycolic acid) (PLGA) and lipids, are chosen to assemble these nanoparticles. PLGA/lipid hybrid nanoparticles are assembled in microfluidic channels with a suitable size distribution for imaging tumors. These nanoparticles achieve clearly enhanced MRI contrast at the tumor at 0.5 h postinjection. The enhanced MRI contrast is sustained for 16 h. They can margin the tumor with as good an enhanced MRI contrast as clinical MRI CAs (which visualize the whole tumor) of the solid tumor with much less Gd. They are particularly useful for monitoring the solid tumor after therapy within a day and without repeated administration as clinical MRI CAs.
Time to change weight gain recommendations for pregnant women with obesity
Authors: Sarah S. Comstock
Journal: Journal of Clinical Investigation (2019)

Obesity during pregnancy is a major health problem in the United States. In this issue of the JCI, Most et al. fill an important gap in our understanding of energy homeostasis in pregnancy. The researchers measured energy intake, energy expenditure, and body composition in obese pregnant women. They demonstrated that energy intake need not increase in order for obese women to gain the recommended amounts of weight during pregnancy. Additionally, all of the gestational weight gain scenarios (inadequate, recommended, or excess) resulted in similar maternal and fetal perinatal outcomes. This evidence should guide new recommendations on this important topic.
Impairment of Thermoregulatory Control of Skin Sympathetic Nerve Traffic in the Elderly
Authors: GuidoGrassi, GinoSeravalle, CarloTurri, GiovanniBertinieri, RaffaellaDell’Oro, GiuseppeMancia
Journal: Circulation (2003)

Background— Human aging is characterized by a marked increase in muscle sympathetic nerve traffic (MSNA). No information exists, however, on the effects of aging on skin sympathetic nerve traffic (SSNA) and on its reflex modulation by thermoregulatory mechanisms. Methods and Results— In 13 young, 11 middle-aged, and 12 elderly healthy subjects, we measured arterial blood pressure (Finapres), skin temperature (thermocouples), and resting MSNA and SSNA (microneurography). Measurements also included the SSNA responses to (1) an acute increase and reduction (±8°C) in room temperature, each lasting 45 minutes and (2) an acoustic stimulus capable to trigger an emotional arousal. Although resting MSNA was progressively and significantly (P<0.05) increased from young to middle-aged and elderly groups, SSNA was significantly (P<0.05) reduced in the latter compared with the former 2 groups. Cold exposure induced a SSNA increase that was significantly (P<0.01) smaller in the elderly than in young and middle-aged sub...
Coronary Flow Reserve by Cardiac Magnetic Resonance Imaging in Patients With Diabetes Mellitus
Authors: Shingo Kato, Kazuki Fukui, Yusuke Saigusa, Kazumi Kubota, Sho Kodama, Naoki Asahina, Keigo Hayakawa, Kohei Iguchi, Masahiro Fukuoka, Tae Iwasawa, Daisuke Utsunomiya, Masami Kosuge, Kazuo Kimura, Kouichi Tamura
Journal: JACC. Cardiovascular imaging (2019)
Celebrating the 100th Anniversary of the <i>Archives of Neurology and Psychiatry</i>
Authors: Dost Öngür
Journal: JAMA Psychiatry (2019)

Medical Association launched the Archives of Neurology and Psychiatry along with several specialty journals in the first decades of the 20th century.The goal was to provide a scientific publication of high ideals that would serve researchers and experts but would also be of immediate practical value to the clinician.
Implementation of Vessel-Sealing Devices in Thyroid Surgery
Authors: Sophie Dream, Tracy S. Wang
Journal: JAMA Surgery (2019)

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 Surgery 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 Surgery journal
Lipid and Cholesterol Homeostasis after Arsenic Exposure and Antibiotic Treatment in Mice: Potential Role of the Microbiota
Authors: Liang Chi, Yunjia Lai, Pengcheng Tu, Chih-Wei Liu, Jingchuan Xue, Hongyu Ru, Kun Lu
Journal: Environmental Health Perspectives (2019)

Arsenic-induced liver X receptor/retinoid X receptor (LXR/RXR) signaling inhibition is a potential mechanism underlying the cardiovascular effects caused by arsenic. The gut microbiota can influence arsenic toxic effects.
Safingol- a potential therapeutic agent for human breast and ovarian cancer cells
Authors: Leong Uung Ling, Gigi Ngar Chee Chiu
Journal: Cancer Research (2007)

4781  Cancer cell survival is governed by the regulation of a wide variety of signaling pathways. Noteworthy among all the signaling pathways, protein kinase C (PKC) plays an important role in regulating cancer cell survival, proliferation, apoptosis and invasion. In addition, PKC is known to modulate multi-drug resistance, suggesting that it is rational to combine PKC inhibitors with conventional chemotherapeutics. The goal for our study is to investigate if safingol (L-threo-dihydrosphingosine), a specific PKC inhibitor, decreases human breast and ovarian cancer cell viability, and if it enhances the cytotoxic effect of doxorubicin and gemcitabine on the cell lines investigated. Furthermore, the effect of safingol on breast and ovarian cancer cell invasion was explored. Since elevated urokinase plasminogen activator-1 (uPA) level is associated with higher risk of cancer relapse and poor prognosis, we sought to determine whether safingol inhibits uPA secretion in breast cancer cells. The cell lines used in our studies include MCF-7, MDA-MB-231, JIMT-1 and SKOV-3. In aconcentration-dependent manner,safingol was effective in reducing viability of MDA-MB-231 (IC50 3.4 μM), JIMT-1 (IC50 1.8 μM) and SKOV-3 (IC50 0.73 μM) cells, but less effective in MCF-7 (IC50 9.5 μM). Interestingly, safingol showed synergism with doxorubicin in 4:1 molar ratio in all the cell lines tested (CI
Death to Mortality as a Reported Percutaneous Coronary Intervention Quality Metric
Authors: Gregory J. Dehmer
Journal: JAMA Cardiology (2019)

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 Cardiology 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 Cardiology journal
Abstract 19711: Thrombotic Complications and Thromboprophylaxis Effectiveness Across all 3 Stages of Univentricular Heart Palliation
Authors: Cedric Manlhiot, Leonardo R Brandao, Judith Kwok, Stefan Kegel, Ines Menjak, Caitlin Carew, Christopher A Caldarone, Glen S Van Arsdell, Brian W McCrindle
Journal: Circulation (2010)

Background: Thrombotic complications (TC) in pediatric cardiac patients are known to be associated with suboptimal outcomes and increased mortality. Risk of TCs for patients with univentricular def...
Hip fractures following denosumab discontinuation: three clinical cases reports
Authors: Manuel Sosa Henríquez, María Jesús Gómez de Tejada Romero, María Escudero-Socorro, Oscar Torregrosa Suau
Journal: Journal of the Royal Society of Medicine (2019)

Summary A significant loss of bone mineral density and the appearance of multiple vertebral fractures after discontinuation of denosumab treatment have been described. To date, no hip fractures have been reported. We present three cases of patients who suffered femoral fractures after denosumab suppression.
Activated Protein C Induces Stabilization of the Outer Retinal Barrier and Inhibits Laser Induced Choroidal Neovascularization in a Murine Model
Authors: Tami Livnat, Yael Nisgav, Ivan Budnik, Yehonatan Weinberger, Rima Dardik, Gili Kenet, Dov Weinberger
Journal: Blood (2018)
Germline Genetic Variations in Methotrexate Candidate Genes Are Associated with Pharmacokinetics and Outcome in Pediatric Acute Lymphoblastic Leukemia in China
Authors: Shuguang Liu, Chao Gao, Ruidong Zhang, Xiaoxi Zhao, Lei Cui, Weijing Li, Huyong Zheng, Zhigang Li
Journal: Blood (2016)
Comment on Gerbaud et al. Glycemic Variability Is a Powerful Independent Predictive Factor of Midterm Major Adverse Cardiac Events in Patients With Diabetes With Acute Coronary Syndrome. Diabetes Care 2019;42:674–681
Authors: You Yang, Yunzhao Hu
Journal: Diabetes Care (2019)

In their recently published article in Diabetes Care , Gerbaud et al. (1) reported that in a total of 327 patients with diabetes and acute coronary syndrome (ACS), glycemic variability (GV) defined as SD >2.70 mmol/L during initial hospitalization was the strongest independent predictive factor for midterm major cardiovascular events (MACE). This study was interesting and further supported the opinion that GV should be regarded as a risk factor for cardiovascular disease (2). However, there are several views that should be discussed.

First, the authors reported that the multivariate logistic regression analysis was performed to ascertain the contributions of GV for MACE and that the odds ratios were calculated. It should be noted that odds ratios are commonly used …
Study of Unilateral Retinoblastoma With and Without Histopathologic High-Risk Features and the Role of Adjuvant Chemotherapy: A Children’s Oncology Group Study
Authors: Patricia Chévez-Barrios, Ralph C. Eagle, Mark Krailo, Jin Piao, Daniel M. Albert, Yun Gao, Geeta Vemuganti, Mohammad Javed Ali, Vikas Khetan, Santosh G. Honavar, Joan O’Brien, Ann-Marie Leahey, Katherine Matthay, Anna Meadows, Murali Chintagumpala
Journal: Journal of Clinical Oncology (2019)

To prospectively determine the prevalence of high-risk histopathologic features (HRFs) in patients with unilateral retinoblastoma who undergo enucleation and to evaluate the role of chemotherapy in preventing recurrences.Children newly diagnosed with enucleated unilateral retinoblastoma were enrolled prospectively. After central histopathology review, patients with specific HRFs received chemotherapy; others were observed. Primary end points were event-free survivals (EFS).Of the 331 patients enrolled during 2005 to 2010, 321 eligible patients had central histopathologic review. Discordance between central review and contributing institutions occurred in 23% of patients with HRFs and in 17% of patients without HRFs. Postlaminar optic nerve involvement was present in 53 patients; 42 had massive posterior uveal invasion (≥ 3 mm); 15 had concomitant peripapillary 3 mm or greater choroid and postlaminar optic nerve involvement; and 15 had focal (< 3 mm) choroidal concomitant with lamina or prelamina optic nerve involvement. Two-year EFS for patients with HRFs requiring adjuvant chemotherapy was 0.96 (95% CI, 0.89 to 0.98), and 2-year EFS for patients without HRFs for which observation was indicated was 0.99 (95% CI, 0.96 to 1.0). The 2-year EFS for all patients was 0.98 (95% CI, 0.96 to 0.99).Adequate handling and interpretation of histopathology of eyes with retinoblastoma is necessary to assign metastatic risk. Concomitant less than 3 mm choroidal and any prelaminar/laminar optic nerve invasion show no recurrence and may warrant no adjuvant chemotherapy. In contrast, concomitant greater than 3 mm peripapillary choroidal invasion and 1.5 mm or greater of postlaminar optic nerve invasion have the poorest outcomes, supporting the need for a more intensive adjuvant chemotherapy regimen for this subgroup. Strict criteria for adjuvant therapy may improve outcomes of children who undergo enucleation at diagnosis and may avoid unnecessary adjuvant chemotherapy for those who are not at risk for recurrence.