tbuckley/cabot-search huggingface dataset:
Abstract 17557: Programmed Lower Rate Limit in Cardiac Resynchronization Therapy Defibrillators: Is There One Best Approach?
Authors: Brian Olshansky, Mark Richards, Arjun D Sharma, Paul W Jones, Nicholas Wold, David L Perschbacher, Bruce L Wilkoff
Journal: Circulation (2015)

Introduction: Recent remote follow-up data analysis suggests that Lower Rate Limit (LRL) programming at 40 beats per minute (bpm) is associated with lower mortality than higher LRL in patients receiving cardiac resynchronization defibrillators (CRT-d) devices. Purpose: We evaluated: 1. if LRL programming in CRT-d devices is based on implanting center or if it varies from patient-to-patient within centers and 2. if LRL programming is associated with survival. Method: The ALTITUDE remote follow-up database was analyzed for dual-chamber CRT-d devices implanted 2006-2011. LRL programming near implant was assessed. Patients were included if LRL remained constant during follow-up. Centers were included with &gt;25 implants. Mortality was determined from the Social Security Death Index. Results: Of 64,482 patients receiving CRT-d devices (not in chronic atrial fibrillation), 56,501 were from centers implanting &gt;25 devices. Of these, 4,683 were implanted in centers where most patients (&gt;75%) received the same LRL (homogeneous); 51,818 were implanted in centers with variable LRL programming (heterogeneous). No difference in overall survival existed between the two approaches to LRL programming. However, in centers that varied LRL programming, LRL&lt;60 bpm was associated with better 5-year survival (p&lt;0.001) (figure). Conclusion: Most patients in the ALTITUDE database received CRT-D devices from centers that vary LRL programming. At these centers, LRL &lt;60 bpm programming is associated with better survival but the mechanism of benefit is unknown. Alternatively, LRL &lt;60 bpm programming for all patients does not confer survival benefit.
Abstract 17767: Physical Activity, Vitamin D, and Incident Atherosclerotic Cardiovascular Disease in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Kathleen Chin, Di Zhao, Seth S Martin, Chiadi E Ndumele, Roberta Florido, B. G Windham, Eliseo Guallar, Pamela L Lutsey, Erin D Michos
Journal: Circulation (2016)

Background: Individuals with higher physical activity (PA) have higher 25-hydroxyvitamin D [25(OH)D] levels, but whether a dose threshold exists is unknown. Moreover, both low PA and 25(OH)D defici...
Online Professionalism—2018 Update of European Association of Urology (@Uroweb) Recommendations on the Appropriate Use of Social Media
Authors: Hendrik Borgmann, Matthew Cooperberg, Declan Murphy, Stacy Loeb, James N’Dow, Maria Jose Ribal, Henry Woo, Morgan Rouprêt, Andrew Winterbottom, Carl Wijburg, Manfred Wirth, James Catto, Alexander Kutikov
Journal: European Urology (2018)
Abstract 13325: Apoptogenic Protein is Involved in Endothelial Senescence Induced by High Glucose
Authors: Osamu Yasuda, Hirofumi Soejima, Keishi Miyata, Hisayo Yasuda, Yuichi Oike, Hisao Ogawa
Journal: Circulation (2015)

Background: The Apoptogenic protein (Apop) is a novel mitochondrial protein originally identified in the atherosclerotic smooth muscle cells cultured from thoracic aortas of ApoE-deficient mice. The production of Apop using an expression vector induces death of smooth muscle cells in culture, and the inhibition of the Apop gene using siRNA prevents the reduction of cell viability induced by death inducing molecules. However, the physiological functions of Apop and its implication in diseases remain to be elucidated. Herein, we show that Apop is involved in the mechanism of high glucose-induced ROS production and senescence in endothelial cells. Methods and Results: Apop gene siRNA was introduced into human umbilical vein endothelial cells (HUVECs) using cationic lipid reagent. High glucose induced ROS production in HUVECs. Apop gene inhibition by siRNA also induced ROS production from these cells; however, HUVECs cultured in the presence of high glucose did not produce higher levels of ROS after the introduction of Apop siRNA, suggesting that high glucose and Apop inhibition may induce ROS generation in a similar way. Cells cultured in the presence of high glucose produced higher levels of ATP than in normal glucose. As expected, Apop inhibition increased ATP production of HUVECs to a similar extent as did high glucose. Morphologically, mitochondrial fragmentation, which is considered to contribute to ROS overproduction because of high glucose, was observed in HUVECs by Apop inhibition, similar to as in high glucose treated cells. As in high glucose cells, Apop gene inhibition induced senescence of HUVEC as assessed by senescence-associated b-galactosidase expression. Moreover, the expression of endothelial nitric oxide synthase of HUVECs was reduced by the inhibition of Apop. Conclusion: These results suggest that the Apop gene is implicated in mitochondrial ROS generation enhanced by glucose, and in endothelial senescence, which play important roles in the development of atherosclerosis; therefore, Apop could be a novel therapeutic target for the prevention of atherosclerosis in diabetes mellitus patients.
HM1.24/CD317-directed immunotoxin to eliminate malignant plasma cells in vitro and in vivo.
Authors: Martin Gramatzki, Matthias Staudinger, Pia Glorius, Katja Klausz, Christian Kellner, Andreas Günther, Roland Repp, Renate Burger, Matthias Peipp
Journal: Journal of Clinical Oncology (2013)

8604 Background: Targeted immunotherapy, based on antibodies against tumor-associated antigens, is a promising approach for the treatment of multiple myeloma (MM). Recently, antibody-based strategies delivering a toxic payload have documented impressive clinical activity in hematological malignancies. In particular, surface molecules overexpressed on malignant plasma cells and efficiently internalized represent promising targets for developing myeloma-directed immunoconstructs. Here, the identification of CD317 (HM1.24) as a potent target structure and the characterization of a novel CD317-directed single-chain immunotoxin, HM1.24-ETA', is described. Methods: Using a novel screening tool, a panel of antibodies against MM-associated antigens was evaluated for their ability to mediate antigen-dependent delivery of a truncated version of Pseudomonas exotoxin A (ETA’) to MM cells. HM1.24-ETA' was generated by genetic fusion of a CD317-specific single-chain Fv antibody and ETA'. The anti-myeloma activity of the E. coli-expressed immunotoxin was evaluated in vitro and in a xenograft mouse model. Results: By screening a panel of antibodies including CD38, CS1, IL-6R, CD138 and CD317, CD317 was identified as a suitable receptor to deliver ETA’ to MM cells. The subsequently designed recombinant HM1.24-ETA' immunotoxin efficiently inhibited growth of MM cell lines with halfmaximal growth inhibition at concentrations of less than 1 nM. Antigen-specific MM cell killing occurred via induction of apoptosis. The proliferation of IL-6 dependent INA-6 cells was completely inhibited by HM1.24-ETA' even in the presence of bone marrow stromal cells that otherwise strongly support tumor cell growth. Importantly, HM1.24-ETA' strongly triggered apoptosis (up to 80%) in freshly isolated tumor cells from 7 out of 7 MM patients. In a xenograft SCID mouse model, establishment of INA-6 plasma cell tumors was efficiently abrogated by treatment with HM1.24-ETA' immunotoxin (p &lt; 0.04). Conclusions: The HM1.24-ETA' immunotoxin in vitro and in the preclinical xenograft model in vivo demonstrates that the CD317 antigen may represent a promising target structure for immunotherapy of MM using immunoconjugates with toxic payloads.
Pharmacogenetics in Psychiatry: A Companion, Rather Than Competitor, to Protocol-Based Care
Authors: Chad A. Bousman, Daniel J. Müller
Journal: JAMA Psychiatry (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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
Rare but Recurrent ROS1 Fusions Resulting From Chromosome 6q22 Microdeletions are Targetable Oncogenes in Glioma
Authors: Monika A. Davare, Jacob J. Henderson, Anupriya Agarwal, Jacob P. Wagner, Sudarshan R. Iyer, Nameeta Shah, Randy Woltjer, Romel Somwar, Stephen W. Gilheeney, Ana DeCarvalo, Tom Mikkelson, Erwin G. Van Meir, Marc Ladanyi, Brian J. Druker
Journal: Clinical Cancer Research (2018)

Gliomas, a genetically heterogeneous group of primary central nervous system tumors, continue to pose a significant clinical challenge. Discovery of chromosomal rearrangements involving kinase genes has enabled precision therapy, and improved outcomes in several malignancies.Positing that similar benefit could be accomplished for patients with brain cancer, we evaluated The Cancer Genome Atlas (TCGA) glioblastoma dataset. Functional validation of the oncogenic potential and inhibitory sensitivity of discovered ROS1 fusions was performed using three independent cell-based model systems, and an in vivo murine xenograft study.In silico analysis revealed previously unreported intrachromosomal 6q22 microdeletions that generate ROS1-fusions from TCGA glioblastoma dataset. ROS1 fusions in primary glioma and ependymoma were independently corroborated from MSK-IMPACT and Foundation Medicine clinical datasets. GOPC-ROS1 is a recurrent ROS1 fusion in primary central nervous system (CNS) tumors. CEP85L-ROS1 and GOPC-ROS1 are transforming oncogenes in cells of astrocytic lineage, and amenable to pharmacologic inhibition with several ROS1 inhibitors even when occurring concurrently with other cancer hotspot aberrations frequently associated with glioblastoma. Oral monotherapy with a brain-permeable ROS1 inhibitor, lorlatinib, significantly prolonged survival in an intracranially xenografted tumor model generated from a ROS1 fusion-positive glioblastoma cell line.Our findings highlight that CNS tumors should be specifically interrogated for these rare intrachromosomal 6q22 microdeletion events that generate actionable ROS1 fusions. ROS1 fusions in primary brain cancer may be amenable for clinical intervention with kinase inhibitors, and this holds the potential of novel treatment paradigms in these treatment-refractory cancer types, particularly in glioblastoma.
Systemic Complications of Acromegaly and the Impact of the Current Treatment Landscape: An Update
Authors: Mônica R Gadelha, Leandro Kasuki, Dawn S T Lim, Maria Fleseriu
Journal: Endocrine Reviews (2018)

Acromegaly is a chronic systemic disease with many complications and is associated with increased mortality when not adequately treated. Substantial advances in acromegaly treatment, as well as in the treatment of many of its complications, mainly diabetes mellitus, heart failure, and arterial hypertension, were achieved in the last decades. These developments allowed change in both prevalence and severity of some acromegaly complications and furthermore resulted in a reduction of mortality. Currently, mortality seems to be similar to the general population in adequately treated patients with acromegaly. In this review, we update the knowledge in complications of acromegaly and detail the effects of different acromegaly treatment options on these complications. Incidence of mortality, its correlation with GH (cumulative exposure vs last value), and IGF-I levels and the shift in the main cause of mortality in patients with acromegaly are also addressed.
Abstract 14969: The LDL Receptor Genotype Among Patients With Homozygous Familial Hypercholesterolemia is a Significant Determinant of the Rebound Increase in LDL-C Concentrations Following Lipoprotein Apheresis
Authors: Jean-Philippe Drouin-Chartier, André J Tremblay, Jean Bergeron, Benoît Lamarche, Patrick Couture
Journal: Circulation (2016)

Introduction: Lipoprotein apheresis (LA) is a reliable method to decrease LDL-C concentrations and remains the gold standard therapy in homozygous familial hypercholesterolemia (HoFH). Although it ...
A scalable, integrated intervention to engage people who inject drugs in HIV care and medication-assisted treatment (HPTN 074): a randomised, controlled phase 3 feasibility and efficacy study
Authors: William C Miller, Irving F Hoffman, Brett S Hanscom, Tran V Ha, Kostyantyn Dumchev, Zubairi Djoerban, Scott M Rose, Carl A Latkin, David S Metzger, Kathryn E Lancaster, Vivian F Go, Sergii Dvoriak, Katie R Mollan, Sarah A Reifeis, Estelle M Piwowar-Manning, Paul Richardson, Michael G Hudgens, Erica L Hamilton, Jeremy Sugarman, Susan H Eshleman, Hepa Susami, Viet Anh Chu, Samsuridjal Djauzi, Tetiana Kiriazova, Duong D Bui, Steffanie A Strathdee, David N Burns
Journal: The Lancet (2018)
Abstract 16874: Unraveling 3D-Myocardial Fiber Architecture by Novel Histological Technique and Correlation With Diffusion-tensor MRI in Normal and Diseased Mice
Authors: Sang-Eun Lee, Christopher Nguyen, Hyuk-Jae Chang, Jongjin Yoon, Sekeun Kim, Chul Hoon Kim, Namsik Chung, Debiao Li
Journal: Circulation (2016)

Introduction: The myocardium has a complex 3-dimensional (3D) microstructure which thought to be perturbed in a range of diseases. Hypothesis: We present a novel approach to characterize the micros...
Low Diastolic Blood Pressure Is Associated With Angina in Patients With Chronic Coronary Artery Disease
Authors: Poghni A. Peri-Okonny, Krishna K. Patel, Philip G. Jones, Tracie Breeding, Kensey L. Gosch, John A. Spertus, Suzanne V. Arnold
Journal: Journal of the American College of Cardiology (2018)
Abstract 14817: Left Atrial Booster Dysfunction Predicts the Poor Outcome After Catheter Ablation for Atrial Fibrillation
Authors: Hideyuki Kishima, Takanao Mine, Satoshi Takahashi, Masaharu Ishihara, Tohru Masuyama
Journal: Circulation (2017)

Introduction: Left atrium (LA) have reservoir, booster and conduit function. Hypothesis: We investigated which LA function play the most important role for atrial fibrillation (AF) recurrence after...
Lung γδ T Cells Mediate Protective Responses during Neonatal Influenza Infection that Are Associated with Type 2 Immunity
Authors: Xi-zhi J. Guo, Pradyot Dash, Jeremy Chase Crawford, E. Kaitlynn Allen, Anthony E. Zamora, David F. Boyd, Susu Duan, Resha Bajracharya, Walid A. Awad, Nopporn Apiwattanakul, Peter Vogel, Thirumala-Devi Kanneganti, Paul G. Thomas
Journal: Immunity (2018)
Stromal biology and therapy in pancreatic cancer: ready for clinical translation?
Authors: Albrecht Neesse, Christian Alexander Bauer, Daniel Öhlund, Matthias Lauth, Malte Buchholz, Patrick Michl, David A Tuveson, Thomas M Gress
Journal: Gut (2018)

Pancreatic ductal adenocarcinoma (PDA) is notoriously aggressive and hard to treat. The tumour microenvironment (TME) in PDA is highly dynamic and has been found to promote tumour progression, metastasis niche formation and therapeutic resistance. Intensive research of recent years has revealed an incredible heterogeneity and complexity of the different components of the TME, including cancer-associated fibroblasts, immune cells, extracellular matrix components, tumour vessels and nerves. It has been hypothesised that paracrine interactions between neoplastic epithelial cells and TME compartments may result in either tumour-promoting or tumour-restraining consequences. A better preclinical understanding of such complex and dynamic network systems is required to develop more powerful treatment strategies for patients. Scientific activity and the number of compelling findings has virtually exploded during recent years. Here, we provide an update of the most recent findings in this area and discuss their translational and clinical implications for basic scientists and clinicians alike.
Abstract 17146: Allopurinol Reduces Cardiac Keap1 and Activates Nrf2/p62 to Attenuate Diabetic Cardiomyopathy
Authors: Jierong Luo, Dan Yan, Sisi Li, Huansen Huang, Shiming Liu, Michael G. Irwin, Zhengyuan Xia
Journal: Circulation (2017)

Introduction: Allopurinol (ALP), a xanthine oxidase inhibitor, attenuates diabetes-induced oxidative stress and diabetic cardiomyopathy(DCM), but the mechanism is unclear. Activation of Nuclear fac...
Evidence for the Efficacy of Bright Light Therapy for Bipolar Depression
Authors: Francesco Benedetti, David H. Avery, Michael Bauer, William E. Bunney, Okan Çaliyurt, Giovanni Camardese, Cristina Colombo, Sara Dallaspezia, Tone Elise Henriksen, Siegfried Kasper, Kenichi Kuriyama, Raymond W. Lam, Klaus Martiny, Ybe Meesters, Kazuo Mishima, Raphael Schulte, Masahiro Suzuki, Łukasz Święcicki, Makoto Uchiyama, David Veale, Dietmar Winkler, Joseph Wu, Nese Yorguner Kupeli, Takuya Yoshiike, Xin Yu
Journal: American Journal of Psychiatry (2018)

EDITOR: The article by Sit and colleagues (1), published in the February 2018 issue of the Journal, reports the high efficacy of antidepressant midday light treatment for bipolar disorder.Bipolar depression is a difficult-to-treat condition, with low success rates of antidepressant drugs (2).We thus welcome midday light treatment as a new treatment option.However, the study infers that antidepressant morning light treatment of bipolar depression can trigger mixed states (3) or is equal to placebo (4), so that its use is contraindicated.We should not lose sight of a large body of evidence demonstrating that morning bright light treatment for bipolar depression is efficacious and safe.This has been highlighted in a meta-analysis ( 5) and in two recent randomized placebocontrolled trials (6, 7).Furthermore, a historical review (8) of 41 studies published between 1982 and 2017 administering light treatment to 799 patients with bipolar depression, mostly in the morning, showed that the rate of switch is lower than the 4% switch rate expected during placebo treatment of bipolar depression (9), thus not justifying specific concerns about manic switches after light treatment.Morning timing appears to have been forgotten, leading to an uncomfortable and unjustified either/or situation for midday or morning light treatment.We wish to emphasize, in the absence of trials directly comparing midday and morning light treatment, that because of its proven efficacy and safety, early morning bright light treatment for bipolar depression, as many of us have used it in everyday clinical practice as an antidepressant adjunct to mood stabilizers, should be recognized as a valid treatment option.
<i>In Situ</i> Vaccination with a TLR9 Agonist and Local Low-Dose Radiation Induces Systemic Responses in Untreated Indolent Lymphoma
Authors: Matthew J. Frank, Patrick M. Reagan, Nancy L. Bartlett, Leo I. Gordon, Jonathan W. Friedberg, Debra K. Czerwinski, Steven R. Long, Richard T. Hoppe, Robert Janssen, Albert F. Candia, Robert L. Coffman, Ronald Levy
Journal: Cancer Discovery (2018)

Abstract This multicenter phase I/II clinical trial evaluated intratumoral SD-101, a TLR9 agonist, and low-dose radiation in patients with untreated indolent lymphoma. Twenty-nine enrolled patients received 4 Gy of radiation followed by 5 weekly intratumoral injections of SD-101 at a single tumor site. No treatment-related grade 4 or serious adverse events occurred. Nearly all patients had tumor reduction at their treated site. More importantly, 24 patients had tumor reduction at their nontreated sites, with 5 patients achieving a partial response and one achieving a complete response. Treatment-related increases of CD8+ and CD4+ effector T cells and decreases of T follicular helper and T regulatory cells (Treg) were observed in the tumor microenvironment. Low pretreatment levels of CD4+ Tregs, proliferating CD8+ T cells, and Granzyme B+ CD8+ T cells were associated with favorable outcomes. Intratumoral SD-101 in combination with low-dose radiation is well tolerated and results in regression of both treated and untreated sites of disease. Significance: In situ vaccination with the TLR9 agonist SD-101, along with low-dose radiation, was safe and induced systemic responses in patients with indolent lymphoma. Low levels of CD4+ Tregs, proliferating CD8+ T cells, and Granzyme B+ CD8+ T cells in the tumor microenvironment predicted favorable response to treatment. Cancer Discov; 8(10); 1258–69. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 1195
Diagnosis and Treatment of <i>Clostridium difficile</i> Infection
Authors: Arjun Gupta, Adam S. Cifu, Sahil Khanna
Journal: JAMA (2018)

This JAMA Clinical Guidelines Synopsis summarizes the 2018 Infectious Diseases Society of America and Society for Healthcare Epidemiology of America recommendations on diagnosis and treatment of Clostridium difficile infection.
Suicide Prevention in the US Army
Authors: Mark A. Reger, Derek J. Smolenski, Sarah P. Carter
Journal: JAMA Psychiatry (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA 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
Reversing Mechanoinductive DSP Expression by CRISPR/dCas9–mediated Epigenome Editing
Authors: Jing Qu, Lanyan Zhu, Zijing Zhou, Ping Chen, Shuyan Liu, Morgan L. Locy, Victor J. Thannickal, Yong Zhou
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

DSP (desmoplakin), the most abundant component of desmosomes, which maintain the mechanical integrity of epithelium, is a genome-wide association study-identified genetic risk locus in human idiopathic pulmonary fibrosis (IPF). Subjects with IPF express a significantly higher level of DSP than control subjects.