tbuckley/cabot-search huggingface dataset:
Targeting Phospholipase D4 Attenuates Kidney Fibrosis
Authors: Priyanka Trivedi, Ramya K. Kumar, Ashwin Iyer, Sarah Boswell, Casimiro Gerarduzzi, Vivekkumar P. Dadhania, Zach Herbert, Nikita Joshi, James P. Luyendyk, Benjamin D. Humphreys, Vishal S. Vaidya
Journal: Journal of the American Society of Nephrology (2017)

Phospholipase D4 (PLD4), a single-pass transmembrane glycoprotein, is among the most highly upregulated genes in murine kidneys subjected to chronic progressive fibrosis, but the function of PLD4 in this process is unknown. Here, we found PLD4 to be overexpressed in the proximal and distal tubular epithelial cells of murine and human kidneys after fibrosis. Genetic silencing of PLD4, either globally or conditionally in proximal tubular epithelial cells, protected mice from the development of fibrosis. Mechanistically, global knockout of PLD4 modulated innate and adaptive immune responses and attenuated the upregulation of the TGF-β signaling pathway and α1-antitrypsin protein (a serine protease inhibitor) expression and downregulation of neutrophil elastase (NE) expression induced by obstructive injury. In vitro, treatment with NE attenuated TGF-β-induced accumulation of fibrotic markers. Furthermore, therapeutic targeting of PLD4 using specific siRNA protected mice from folic acid-induced kidney fibrosis and inhibited the increase in TGF-β signaling, decrease in NE expression, and upregulation of mitogen-activated protein kinase signaling. Immunoprecipitation/mass spectrometry and coimmunoprecipitation experiments confirmed that PLD4 binds three proteins that interact with neurotrophic receptor tyrosine kinase 1, a receptor also known as TrkA that upregulates mitogen-activated protein kinase. PLD4 inhibition also prevented the folic acid-induced upregulation of this receptor in mouse kidneys. These results suggest inhibition of PLD4 as a novel therapeutic strategy to activate protease-mediated degradation of extracellular matrix and reverse fibrosis.
変異:de novo変異の親起源特異的なシグネチャー
Authors: Goldmann Jakob M, Wong Wendy S W, Bodian Dale, Vockley Joseph G, Solomon Benjamin D, Niederhuber John E, Pinelli Michele, Farrah Terry, Stittrich Anna B, Glusman Gustavo, Roach Jared C, Vissers Lisenka E L M, Hoischen Alexander, Veltman Joris A, Gilissen Christian
Journal: Nature Genetics (2016)
Occurrence and enterotoxic characterisation of methicillin-resistant Staphylococcus aureus from raw milk in southern Italy
Authors: Angela Dambrosio, La . Salandra G, Marialaura Corrente, Nicoletta Cristiana Quaglia, Vanessa Lorusso, G. L. Germinarlo, G. Mula, Giovanni Giuseppe Normanno, Gaetano Vitale Celano
Journal: Clinical Microbiology and Infection (2007)
Caveolin-1-dependent nanoscale organization of the BCR regulates B cell tolerance
Authors: Susana Minguet, Kathrin Kläsener, Anna-Maria Schaffer, Gina J Fiala, Teresa Osteso-Ibánez, Katrin Raute, Inmaculada Navarro-Lérida, Frederike A Hartl, Maximilian Seidl, Michael Reth, Miguel A Del Pozo
Journal: Nature Immunology (2017)
Aspirin to Prevent Preeclampsia
Authors: Michael F. Greene, Caren G. Solomon
Journal: New England Journal of Medicine (2017)

Not long after the physiological effects of prostacyclin (epoprostenol) and thromboxane on platelets and vessel walls were elucidated,1 it was suggested that many of the pathophysiological features of preeclampsia might be explained by disordered eicosanoid metabolism. The effects of aspirin in low concentrations, including reductions in platelet aggregation and constriction of arterial smooth muscle, made it an attractive choice for potentially ameliorating the pathophysiological effects of preeclampsia. The largest trial to date of aspirin to prevent preeclampsia in pregnant women, the Collaborative Low-Dose Aspirin Study in Pregnancy (CLASP),2 which involved more than 9300 women at high risk for preeclampsia or . . .
Long Term Outcome of Splenectomy in Pediatric Patients with Non-Malignant Hematological Diseases: Four Decades of Follow up
Authors: Joanne Yacobovich, Shlomit Barzilai-Birenboim, Pinhas Stark, Idit Pazgal, Orna Steinberg-Shemer, Hannah Tamary
Journal: Blood (2016)
Understanding threats to polio vaccine commitment among caregivers in high-priority areas of Afghanistan: a polling study
Authors: Gillian K SteelFisher, Robert J Blendon, Sherine Guirguis, William Lodge, Hannah Caporello, Vincent Petit, Michael Coleman, Matthew R Williams, Sardar Mohammad Parwiz, Melissa Corkum, Scott Gardner, Eran N Ben-Porath
Journal: The Lancet Infectious Diseases (2017)
AAV-mediated direct in vivo CRISPR screen identifies functional suppressors in glioblastoma
Authors: Ryan D Chow, Christopher D Guzman, Guangchuan Wang, Florian Schmidt, Mark W Youngblood, Lupeng Ye, Youssef Errami, Matthew B Dong, Michael A Martinez, Sensen Zhang, Paul Renauer, Kaya Bilguvar, Murat Gunel, Phillip A Sharp, Feng Zhang, Randall J Platt, Sidi Chen
Journal: Nature Neuroscience (2017)
Notes from the Field: Fatal Pneumonic Tularemia Associated with Dog Exposure — Arizona, June 2016
Authors: Hayley Yaglom, Edwin Rodriguez, Marlene Gaither, Mare Schumacher, Natalie Kwit, Christina Nelson, Joel Terriquez, Jacob Vinocur, Dawn Birdsell, David M Wagner, Jeannine Petersen, Kiersten Kugeler
Journal: MMWR Morbidity and Mortality Weekly Report (2017)
Presenting to Primary Stroke Centers or Comprehensive Stroke Centers for Thrombolysis
Authors: Ken Uchino
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
Role of platinum-based chemotherapy for Merkel cell tumor in adjuvant and metastatic settings.
Authors: Shailesh R. Satpute, Natraj Reddy Ammakkanavar, Lawrence H. Einhorn
Journal: Journal of Clinical Oncology (2014)

9049 Background: Merkel Cell Carcinoma (MCC) is a rare, highly aggressive primary neuroendocrine carcinoma of skin. The tumor always stains positive for CK20. Chemotherapy for metastatic disease has been platinum plus etoposide, based upon small cell lung cancer studies. The role of adjuvant chemotherapy in resected high risk disease is controversial. The principles of adjuvant chemotherapy in solid tumors are demonstration of activity in the metastatic setting and a probability for postoperative relapse. Methods: We reviewed, retrospectively, 41 patients with MCC seen and followed at Indiana University Simon Cancer Center from 2000 – 2013. Most of these patients received cisplatin or carboplatin plus etoposide for 4-6 cycles. Demographics, disease variables, treatments and outcomes were analyzed. Results: Median age was 68 years with 64% males. Primary sites affected were extremities (21), head and neck (11) or others including lymph node only disease with unknown primary (9). 12 patients received chemotherapy for metastatic disease at presentation. 10 of 12 (83%) achieved a RECIST response to chemotherapy. Median duration of remission with chemotherapy was 4 months. 27 patients initially underwent wide local excision with sentinel lymph node biopsy followed by lymph node dissection, if clinically indicated. 2 did not receive any definitive therapy. 15 of these 27 patients received adjuvant chemotherapy based upon high risk features including lymph node involvement (8), positive surgical margins (2), bulky primary tumor (2) or rapid growth (3). 11 of these 15 patients remain continuously progression free with median of 3 years. 12 patients did not receive adjuvant chemotherapy. 5 of 12 remain disease free. 21 patients received adjuvant radiation either as their only therapy (9) or in addition to adjuvant chemotherapy (12). 21 of 41 patients remain alive and disease free, 3 are alive with disease, 13 died from metastatic MCC and 4 died of unrelated causes. Median follow up was 3 years. Conclusions: Platinum-based combination chemotherapy is active in metastatic MCC. We recommend adjuvant chemotherapy for MCC with high risk features.
ブレンド生物インクを用いた潅流血管構造物の直接3Dバイオプリンティング【Powered by NICT】
Authors: Jia Weitao, Gungor-Ozkerim P. Selcan, Zhang Yu Shrike, Yue Kan, Zhu Kai, Liu Wanjun, Pi Qingment, Byambaa Batzaya, Dokmeci Mehmet Remzi, Shin Su Ryon, Khademhosseini Ali
Journal: Biomaterials (2016)
Phase 1 clinical trial using mbIL21 ex vivo–expanded donor-derived NK cells after haploidentical transplantation
Authors: Stefan O. Ciurea, Jolie R. Schafer, Roland Bassett, Cecele J. Denman, Kai Cao, Dana Willis, Gabriela Rondon, Julianne Chen, Doris Soebbing, Indreshpal Kaur, Alison Gulbis, Sairah Ahmed, Katayoun Rezvani, Elizabeth J. Shpall, Dean A. Lee, Richard E. Champlin
Journal: Blood (2017)
BMJ family highlights
Authors: H. Marcovitch
Journal: BMJ (2003)

The trouble with families is that as they get larger and more diverse their members tend to lose touch with one another. Some are so busy they have no time for conversation. The BMJ Publishing Group is not exempt, with most readers probably unaware of what is afoot in its 27 constituent journals, let alone departments such as BMJ Books and BMJ Knowledge, which produces Clinical Evidence (http://www.clinicalevidence.com/).

Last year we began linking the editors of the specialist journals. Each accepted paper is assessed to …
Keratinocyte skin cancers in the spotlight
Authors: T. Nijsten, I.M. Leigh
Journal: British Journal of Dermatology (2017)

Tamar Nijsten is chair of the department of dermatology, Erasmus MC, Rotterdam. His research group has a strong focus on epidemiology and public health issues related to skin cancer. Irene Leigh is Professor of Cell and Molecular Medicine at the University of Dundee. She has a longstanding interest in keratinocyte biology, genetic skin disease and skin carcinogenesis. In this issue of the BJD, we present three excellent scholarly reviews on the epidemiology of keratinocyte skin cancers, namely basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and actinic keratosis (AK), by international experts from around the world.1,2,3 These reviews emphasize the enormous burden of disease of keratinocytic cancers (KCs) in the population due to extremely high incidence rates. In spite of this, for individual tumours the impact is less pronounced as local treatments are usually clinically effective. Although other tumours, including melanoma, are more significant in terms of mortality, the presence of field change, with a high burden of disease‐associated mutations, means that patients with KCs are at high risk of developing further subsequent tumours, often requiring multiple surgical interventions. Patients therefore need regular surveillance from professionals and repeated information regarding primary and secondary prevention to aid self‐management and promote photoprotection.
Growth and Pathology of Melanoma S91 in Mice of Strains Dba, a, and C&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: Glenn H. Algire
Journal: JNCI Journal of the National Cancer Institute (1944)

Growth and Pathology of Melanoma S91 in Mice of Strains Dba, a, and C Get access Glenn H. Algire Glenn H. Algire assistant surgeon (R) National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 5, Issue 3, December 1944, Pages 151–160, https://doi.org/10.1093/jnci/5.3.151 Published: 01 December 1944
Loss of host-derived osteopontin creates a glioblastoma-promoting microenvironment
Authors: Frank Szulzewsky, Nina Schwendinger, Dilansu Güneykaya, Patrick J Cimino, Dolores Hambardzumyan, Michael Synowitz, Eric C Holland, Helmut Kettenmann
Journal: Neuro-Oncology (2017)

BackgroundMicroglia and periphery-derived monocytes infiltrate human and mouse glioblastoma and their density is positively correlated with malignancy. Using microarray and RNA sequencing, we have previously shown that glioblastoma-associated microglia/monocytes (GAMs) express osteopontin/SPP1.
Use of Laboratory Markers in Addition to Symptoms for Diagnosis of Inflammatory Bowel Disease in Children
Authors: Gea A. Holtman, Yvonne Lisman-van Leeuwen, Andrew S. Day, Ulrika L. Fagerberg, Paul Henderson, Stevan T. Leach, Gøri Perminow, David Mack, Patrick F. van Rheenen, Els van de Vijver, David C. Wilson, Johannes B. Reitsma, Marjolein Y. Berger
Journal: JAMA Pediatrics (2017)

Blood markers and fecal calprotectin are used in the diagnostic workup for inflammatory bowel disease (IBD) in pediatric patients. Any added diagnostic value of these laboratory markers remains unclear.To determine whether adding laboratory markers to evaluation of signs and symptoms improves accuracy when diagnosing pediatric IBD.A literature search of MEDLINE and EMBASE from inception through September 26, 2016. Studies were identified using indexing terms and free-text words related to child, target condition IBD, and diagnostic accuracy.Two reviewers independently selected studies evaluating the diagnostic accuracy of more than 1 blood marker or fecal calprotectin for IBD, confirmed by endoscopy and histopathology or clinical follow-up, in pediatric patients with chronic gastrointestinal symptoms. Studies that included healthy controls and/or patients with known IBD were excluded.Individual patient data from each eligible study were requested from the authors. In addition, 2 reviewers independently assessed quality with Quality Assessment of Diagnostic Accuracy Studies-2.Laboratory markers were added as a single test to a basic prediction model based on symptoms. Outcome measures were improvement of discrimination by adding markers as a single test and improvement of risk classification of pediatric patients by adding the best marker.Of the 16 eligible studies, authors of 8 studies (n = 1120 patients) provided their data sets. All blood markers and fecal calprotectin individually significantly improved the discrimination between pediatric patients with and those without IBD, when added to evaluation of symptoms. The best marker-fecal calprotectin-improved the area under the curve of symptoms by 0.26 (95% CI, 0.21-0.31). The second best marker-erythrocyte sedimentation rate-improved the area under the curve of symptoms by 0.16 (95% CI, 0.11-0.21). When fecal calprotectin was added to the model, the proportion of patients without IBD correctly classified as low risk of IBD increased from 33% to 91%. The proportion of patients with IBD incorrectly classified as low risk of IBD decreased from 16% to 9%. The proportion of the total number of patients assigned to the intermediate-risk category decreased from 55% to 6%.In a hospital setting, fecal calprotectin added the most diagnostic value to symptoms compared with blood markers. Adding fecal calprotectin to the diagnostic workup of pediatric patients with symptoms suggestive of IBD considerably decreased the number of patients in the group in whom challenges in clinical decision making are most prevalent.
The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL
Authors: Paul J Emmerson, Feng Wang, Yong Du, Qian Liu, Richard T Pickard, Malgorzata D Gonciarz, Tamer Coskun, Matthew J Hamang, Dana K Sindelar, Kimberly K Ballman, Lisa A Foltz, Avinash Muppidi, Jorge Alsina-Fernandez, Gavin C Barnard, Jason X Tang, Xilin Liu, Xudong Mao, Robert Siegel, John H Sloan, Pamela J Mitchell, Bei B Zhang, Ruth E Gimeno, Bei Shan, Xinle Wu
Journal: Nature Medicine (2017)
The Expanding Spectrum of Zika Virus Infections of the Nervous System
Authors: Kenneth L. Tyler, Karen L. Roos
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
Nintedanib inhibits macrophage activation and ameliorates vascular and fibrotic manifestations in the Fra2 mouse model of systemic sclerosis
Authors: Jingang Huang, Christiane Maier, Yun Zhang, Alina Soare, Clara Dees, Christian Beyer, Ulrike Harre, Chih-Wei Chen, Oliver Distler, Georg Schett, Lutz Wollin, Jörg H W Distler
Journal: Annals of the Rheumatic Diseases (2017)

Nintedanib is an inhibitor targeting platelet-derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases that has recently been approved for the treatment of idiopathic pulmonary fibrosis. The aim of this study was to analyse the effects of nintedanib in the fos-related antigen-2 (Fra2) mouse model of systemic sclerosis (SSc).The effects of nintedanib on pulmonary arterial hypertension with proliferation of pulmonary vascular smooth muscle cells (PVSMCs) and luminal occlusion, on microvascular disease with apoptosis of microvascular endothelial cells (MVECs) and on fibroblast activation with myofibroblast differentiation and accumulation of extracellular matrix were analysed. We also studied the effects of nintedanib on the levels of key mediators involved in the pathogenesis of SSc and on macrophage polarisation.Nintedanib inhibited proliferation of PVSMCs and prevented thickening of the vessel walls and luminal occlusion of pulmonary arteries. Treatment with nintedanib also inhibited apoptosis of MVECs and blunted the capillary rarefaction in Fra2-transgenic mice. These effects were associated with a normalisation of the serum levels of vascular endothelial growth factor in Fra2 mice on treatment with nintedanib. Nintedanib also effectively blocked myofibroblast differentiation and reduced pulmonary, dermal and myocardial fibrosis in Fra2-transgenic mice. The antifibrotic effects of nintedanib were associated with impaired M2 polarisation of monocytes and reduced numbers of M2 macrophages.Nintedanib targets core features of SSc in Fra2-transgenic mice and ameliorates histological features of pulmonary arterial hypertension, destructive microangiopathy and pulmonary and dermal fibrosis. These data might have direct implications for the ongoing phase III clinical trial with nintedanib in SSc-associated interstitial lung disease.
Effectiveness of a Timing and Coordination Group Exercise Program to Improve Mobility in Community-Dwelling Older Adults
Authors: Jennifer S. Brach, Subashan Perera, Sandra Gilmore, Jessie M. VanSwearingen, Deborah Brodine, Neelesh K. Nadkarni, Edmund Ricci
Journal: JAMA Internal Medicine (2017)

<h3>Importance</h3> Timing and coordination exercises may be an important addition to community-based health promotion exercise programs to improve walking in older adults. <h3>Objective</h3> To compare the effectiveness of the On the Move group exercise program, which focuses on the timing and coordination of movement, with a seated strength, endurance, and flexibility program (usual care) at improving function, disability, and walking ability of older adults. <h3>Design, Setting, and Participants</h3> Cluster-randomized, single-blind intervention trial. Thirty-two independent living facilities, senior apartment buildings, and senior community centers were randomized to On the Move (16 sites; 152 participants) or usual care (16 sites; 146 participants). Participants were 65 years or older, able to ambulate independently with a gait speed of at least 0.60 m/s, able to follow 2-step commands, and were medically stable. <h3>Interventions</h3> Exercise classes were 50 minutes, twice a week for 12 weeks and had 10 or fewer participants per class. On the Move consisted of warm-up, timing and coordination (stepping and walking patterns), strengthening, and stretching exercises. The usual-care program consisted of warm-up, strength, endurance, and stretching exercises. <h3>Main Outcomes and Measures</h3> The primary outcomes were self-report of function and disability (Late Life Function and Disability Instrument) and mobility (6-minute walk distance and gait speed) assessed by blinded individuals. <h3>Results</h3> Participants (mean [SD] age, 80.0 [8.1] years) were mostly female (251 [84.2%]) and white (249 [83.6%]) and had a mean (SD) of 2.8 (1.4) chronic conditions. Intervention groups were similar on baseline characteristics. Postintervention, 142 (93.4%) participants in On the Move and 139 (95.2%) participants in usual care completed testing. On the Move had greater mean (SD) improvements than the usual-care group in gait speed (0.05 [0.13] vs −0.01 [0.11] m/s; adjusted difference = 0.05 [0.02] m/s;<i>P</i> = .002) and 6-minute walk distance (20.6 [57.1] vs 4.1 [55.6] m; adjusted difference = 16.7 [7.4] m;<i>P</i> = .03). Attendance was greater in the usual-care program compared with On the Move (95 [65.1%] vs 76 [50.0%] attended ≥20 classes;<i>P</i> = .03). There were no significant differences in any of the other primary or secondary outcomes. <h3>Conclusions and Relevance</h3> The On the Move group exercise program was more effective at improving mobility than a usual-care exercise program, despite lower attendance. Additional research examining the impact of the intervention on long-term disability outcomes is needed before recommending routine implementation into clinical practice. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01986647
Use of Oxyhemoglobin Saturation, Rather Than Oxygen Tension, as a Marker of Oxygenation in Cyanotic Patients
Authors: Humera Ahmed, Xiaoqi Tang, Brian Polizzotti, Kimberlee Gauvreau, Mark Kellogg, James DiNardo, John Kheir
Journal: JAMA Pediatrics (2017)

This study analyzes clinically indicated arterial blood gas values from patients with cyanotic congenital heart disease to determine whether oxyhemoglobin saturation or arterial oxygen tension provides a better measure of oxygenation.