tbuckley/cabot-search huggingface dataset:
Abstract 19409: β2-Adrenergic Receptor Regulation of Innate Immune Responses Following Acute Myocardial Injury
Authors: Laurel A Grisanti, Anna Gumpert, Joshua Gorsky, Ashley A Repas, Erhe Gao, Rhonda L Carter, Joseph E Rabinowitz, Walter J Koch, Douglas G Tilley
Journal: Circulation (2015)

Inflammatory responses are important for cardiac remodeling and tissue repair after myocardial infarction (MI). The sympathetic nervous system is known to regulate immune responses, in large part through the β2-adrenergic receptor (β2AR), however the influence of β2AR in regulating the inflammatory response following MI is unknown. Thus, to examine the contribution of β2AR on immune cells following MI, wild-type (WT) mice were irradiated and then received β2ARKO or WT control bone marrow (BM) transplants to create immune cell-specific knockout (KO) animals. Lack of β2AR expression in BM resulted in 100% mortality from cardiac rupture within two weeks of receiving MI, in contrast to their WT counterparts that had ∼20% death. Granulocyte populations were sequestered in the spleen of β2ARKO chimeric mice resulting in reductions in post-MI infiltration of monocyte/macrophage, neutrophil and mast cell populations into the heart. Additionally, alterations in chemokine receptor levels, particularly CCR2, on BM resulted in decreased cellular migration, and use of a CCR2 antagonist in vivo recapitulated the β2ARKO chimeric mouse phenotype following MI. Administration of β2AR agonists in vitro and in vivo increased CCR2 expression and BM migration while β2AR antagonists decreased CCR2 expression and increased splenic leukocyte retention in vivo . Use of pepducins as allosteric modulators of β2AR signaling demonstrated the importance of β-arrestin-mediated signaling in increasing CCR2 expression and responses. The impact of β2AR deletion on BM cell CCR2 expression and migration, splenic retention of leukocytes and reciprocal cardiac leukocyte infiltration following MI could be reversed via lentivirus-mediated β2AR rescue in the β2ARKO BM prior to transplantation. These results demonstrate the critical role of β2AR in the regulation of CCR2 expression on hematopoietic cells and its importance in mounting an immune response to promote healing following acute cardiac injury.
The copy number variation landscape of congenital anomalies of the kidney and urinary tract
Authors: Miguel Verbitsky, Rik Westland, Alejandra Perez, Krzysztof Kiryluk, Qingxue Liu, Priya Krithivasan, Adele Mitrotti, David A. Fasel, Ekaterina Batourina, Matthew G. Sampson, Monica Bodria, Max Werth, Charlly Kao, Jeremiah Martino, Valentina P. Capone, Asaf Vivante, Shirlee Shril, Byum Hee Kil, Maddalena Marasà, Jun Y. Zhang, Young-Ji Na, Tze Y. Lim, Dina Ahram, Patricia L. Weng, Erin L. Heinzen, Alba Carrea, Giorgio Piaggio, Loreto Gesualdo, Valeria Manca, Giuseppe Masnata, Maddalena Gigante, Daniele Cusi, Claudia Izzi, Francesco Scolari, Joanna A. E. van Wijk, Marijan Saraga, Domenico Santoro, Giovanni Conti, Pasquale Zamboli, Hope White, Dorota Drozdz, Katarzyna Zachwieja, Monika Miklaszewska, Marcin Tkaczyk, Daria Tomczyk, Anna Krakowska, Przemyslaw Sikora, Tomasz Jarmoliński, Maria K. Borszewska-Kornacka, Robert Pawluch, Maria Szczepanska, Piotr Adamczyk, Malgorzata Mizerska-Wasiak, Grazyna Krzemien, Agnieszka Szmigielska, Marcin Zaniew, Mark G. Dobson, John M. Darlow, Prem Puri, David E. Barton, Susan L. Furth, Bradley A. Warady, Zoran Gucev, Vladimir J. Lozanovski, Velibor Tasic, Isabella Pisani, Landino Allegri, Lida M. Rodas, Josep M. Campistol, Cécile Jeanpierre, Shumyle Alam, Pasquale Casale, Craig S. Wong, Fangming Lin, Débora M. Miranda, Eduardo A. Oliveira, Ana Cristina Simões-e-Silva, Jonathan M. Barasch, Brynn Levy, Nan Wu, Friedhelm Hildebrandt, Gian Marco Ghiggeri, Anna Latos-Bielenska, Anna Materna-Kiryluk, Feng Zhang, Hakon Hakonarson, Virginia E. Papaioannou, Cathy L. Mendelsohn, Ali G. Gharavi, Simone Sanna-Cherchi
Journal: Nature Genetics (2018)
Abstract 13600: Patients Identified as Low Risk May Be Safely Discharged From the Emergency Department After Presentation With Chest Pain
Authors: Oluwaseun Adeola, Nicholas Ruthmann, Barbara Boshard, Joshua Geltman, Sivakumar Ardhanari, Mary L Dohrmann
Journal: Circulation (2015)

Background: Chest pain accounts for over 8 million visits to the emergency department (ED) annually in the United States. However, only a minority of these patients are eventually diagnosed with acute myocardial infarction. Hypothesis: A protocol may be safely utilized to identify and evaluate low risk patients upon presentation to the ED with chest pain. Methods: A prospective study at a large academic medical center evaluated the safety of a protocol to schedule outpatient stress testing and follow-up for low risk patients discharged from the ED after presenting with chest pain. Patients were low risk if they were pain-free in the ED, had negative cardiac enzymes, non-ischemic electrocardiogram and TIMI risk score &lt; 1, or if a cardiologist deemed patient low risk for acute myocardial infarction. Selected patients were discharged from the ED and scheduled for stress testing within 1-3 business days. Patients with positive test results were evaluated by a cardiologist for medical management or coronary angiography as needed. Results: A total of 1,735 patients were enrolled in the protocol. Of the 1,036 patients completing a follow-up stress test, only 6.4% (66/1,036) had an abnormal result. Forty-two of these 66 patients (63.6%) were either determined to be false positive by the cardiologist or underwent medical management. The remaining 24 (36.4%) had coronary angiography, of which only 20.8% (5/24) had significant coronary artery disease requiring percutaneous coronary intervention. All patients were followed for 30 days after their ED visit. During this period, 1.9% (33/1735) of patients returned to the ED per protocol, and 1% (18/1735) were admitted to the hospital for chest pain or other cardiovascular presentation. Only 3 patients (0.2%) had myocardial infarction. No mortality was recorded during this period. With this protocol, patients and insurers avoided over $16 million in professional and facility charges and over $3 million in payments. Estimated cost savings from reducing hospitalization in our patient population was about $3.77 million. Conclusions: Our data support that an outpatient evaluation protocol for low risk patients presenting to the ED with chest pain is safe, avoids unnecessary hospitalization and reduces healthcare cost.
Psychiatry’s Opportunity to Prevent the Rising Burden of Age-Related Disease
Authors: Terrie E. Moffitt, Avshalom Caspi
Journal: JAMA Psychiatry (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 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
Later Sibling Recurrence of Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder
Authors: Tony Charman, Emily J. H. Jones
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Broad Spectrum Activity of the Checkpoint Kinase 1 Inhibitor Prexasertib as a Single Agent or Chemopotentiator Across a Range of Preclinical Pediatric Tumor Models
Authors: Caitlin D. Lowery, Michele Dowless, Matthew Renschler, Wayne Blosser, Alle B. VanWye, Jennifer R. Stephens, Philip W. Iversen, Aimee Bence Lin, Richard P. Beckmann, Kateryna Krytska, Kristina A. Cole, John M. Maris, Douglas S. Hawkins, Brian P. Rubin, Raushan T. Kurmasheva, Peter J. Houghton, Richard Gorlick, E. Anders Kolb, Min H. Kang, C. Patrick Reynolds, Stephen W. Erickson, Beverly A. Teicher, Malcolm A. Smith, Louis F. Stancato
Journal: Clinical Cancer Research (2018)

Checkpoint kinase 1 (CHK1) inhibitors potentiate the DNA-damaging effects of cytotoxic therapies and/or promote elevated levels of replication stress, leading to tumor cell death. Prexasertib (LY2606368) is a CHK1 small-molecule inhibitor under clinical evaluation in multiple adult and pediatric cancers. In this study, prexasertib was tested in a large panel of preclinical models of pediatric solid malignancies alone or in combination with chemotherapy.DNA damage and changes in cell signaling following in vitro prexasertib treatment in pediatric sarcoma cell lines were analyzed by Western blot and high content imaging. Antitumor activity of prexasertib as a single agent or in combination with different chemotherapies was explored in cell line-derived (CDX) and patient-derived xenograft (PDX) mouse models representing nine different pediatric cancer histologies.Pediatric sarcoma cell lines were highly sensitive to prexasertib treatment in vitro, resulting in activation of the DNA damage response. Two PDX models of desmoplastic small round cell tumor and one malignant rhabdoid tumor CDX model responded to prexasertib with complete regression. Prexasertib monotherapy also elicited robust responses in mouse models of rhabdomyosarcoma. Concurrent administration with chemotherapy was sufficient to overcome innate resistance or prevent acquired resistance to prexasertib in preclinical models of neuroblastoma, osteosarcoma, and Ewing sarcoma, or alveolar rhabdomyosarcoma, respectively.Prexasertib has significant antitumor effects as a monotherapy or in combination with chemotherapy in multiple preclinical models of pediatric cancer. These findings support further investigation of prexasertib in pediatric malignancies.
Electrical Stimulation by an Organic Transistor Architecture Induces Calcium Signaling in Nonexcitable Brain Cells
Authors: Ana Isabel Borrachero‐Conejo, Emanuela Saracino, Marco Natali, Federico Prescimone, Saskia Karges, Simone Bonetti, Grazia Paola Nicchia, Francesco Formaggio, Marco Caprini, Roberto Zamboni, Francesco Mercuri, Stefano Toffanin, Michele Muccini, Valentina Benfenati
Journal: Advanced Healthcare Materials (2018)

Abstract Organic bioelectronics have a huge potential to generate interfaces and devices for the study of brain functions and for the therapy of brain pathologies. In this context, increasing efforts are needed to develop technologies for monitoring and stimulation of nonexcitable brain cells, called astrocytes. Astroglial calcium signaling plays, indeed, a pivotal role in the physiology and pathophysiology of the brain. Here, the use of transparent organic cell stimulating and sensing transistor (O‐CST) architecture, fabricated with N , N′ ‐ditridecylperylene‐3,4,9,10‐tetracarboxylic diimide (P13), to elicit and monitor intracellular calcium concentration ([Ca 2+ ] i ) in primary rat neocortical astrocytes is demonstrated. The transparency of O‐CST allows performing calcium imaging experiments, showing that extracellular electrical stimulation of astrocytes induces a drastic increase in [Ca 2+ ] i . Pharmacological studies indicate that transient receptor potential (TRP) superfamily are critical mediators of the [Ca 2+ ] i increase. Experimental and computational analyses show that [Ca 2+ ] i response is enabled by the O‐CST device architecture. Noteworthy, the extracellular field application induces a slight but significant increase in the cell volume. Collectively, it is shown that the O‐CST is capable of selectively evoking astrocytes [Ca 2+ ] i , paving the way to the development of organic bioelectronic devices as glial interfaces to excite and control physiology of non‐neuronal brain cells.
Delays in Diagnosis and Treatment of Breast Cancer: A Safety-Net Population Profile
Authors: Kshama Jaiswal, Madelyne Hull, Anna L. Furniss, Reina Doyle, Natalia Gayou, Elizabeth Bayliss
Journal: Journal of the National Comprehensive Cancer Network (2018)

Background: Timely detection and treatment of breast cancer is important in optimizing survival and minimizing recurrence. Given disparities in breast cancer outcomes based on socioeconomic status, we examined time to diagnosis and treatment in a safety-net hospital. Methods: We conducted a retrospective review of all patients with breast cancer diagnosed between July 1, 2010, and June 30, 2012 (N=120). We limited our analytic sample to patients with nonrecurrent, primary stage 0-III breast cancer (N=105) and determined intervals from presentation to diagnosis, diagnosis to first treatment, last surgery to chemotherapy initiation, and last surgery to start of radiation therapy (RT). Using logistic regression, we calculated unadjusted odds of receiving timely treatment (< median time) versus more delayed treatment (≥ median time) as a function of age, language, ethnicity, insurance, Charlson comorbidity index, disease stage, method of first presentation (screening mammography vs care provider), symptoms at presentation, and type of surgical treatment. Results: Patients aged 55 to 64 years accounted for most of the sample (n=37; 35.2%). Median time from presentation to diagnosis (23 days), time from diagnosis to first treatment, and time from surgery to chemotherapy initiation fell within intervals published in the literature; median time from last surgery to start of RT was greater than recommended intervals. Factors significantly associated with longer intervals than median time included stage, method of presentation, language, surgical treatment, insurance, and ethnicity. Conclusions: Patients in this safety-net setting experienced acceptable diagnosis and treatment intervals, except for time to RT. Focused interventions that help care providers access imaging quickly for their symptomatic patients could improve time to diagnosis. Concentrating additional efforts on non-English-speaking, Hispanic patients and those who need to receive RT could improve time to treatment.
Erythematous Macular Eruption in an Older Woman
Authors: David McLaughlin, Neil M. Kernohan, Sudhir Tauro
Journal: JAMA Oncology (2018)

A white woman in her 70s with Alzheimer disease presented with a high hemoglobin level and red blood cell count as well as erythematous macular eruption over the trunk and limbs. What is your diagnosis?
TRIB2 functions as novel oncogene in colorectal cancer by blocking cellular senescence through AP4/p21 signaling
Authors: Zhenlin Hou, Kaixuan Guo, Xuling Sun, Fuqing Hu, Qianzhi Chen, Xuelai Luo, Guihua Wang, Junbo Hu, Li Sun
Journal: Molecular Cancer (2018)

Cellular senescence is a state of irreversible cell growth arrest and senescence cells permanently lose proliferation potential. Induction of cellular senescence might be a novel therapy for cancer cells. TRIB2 has been reported to participate in regulating proliferation and drug resistance of various cancer cells. However, the role of TRIB2 in cellular senescence of colorectal cancer (CRC) and its molecular mechanism remains unclear. The expression of TRIB2 in colorectal cancer tissues and adjacent tissues was detected by immunohistochemistry and RT-PCR. The growth, cell cycle distribution and cellular senescence of colorectal cancer cells were evaluated by Cell Counting Kit-8 (CCK8) assay, flow cytometry detection and senescence-associated β-galactosidase staining, respectively. Western blot, RT-PCR and luciferase assay were performed to determine how TRIB2 regulates p21. Immunoprecipitation (IP) and chromatin-immunoprecipitation (ChIP) were used to investigate the molecular mechanisms. We found that TRIB2 expression was elevated in CRC tissues compared to normal adjacent tissues and high TRIB2 expression indicated poor prognosis of CRC patients. Functionally, depletion of TRIB2 inhibited cancer cells proliferation, induced cell cycle arrest and promoted cellular senescence, whereas overexpression of TRIB2 accelerated cell growth, cell cycle progression and blocked cellular senescence. Further studies showed that TRIB2 physically interacted with AP4 and inhibited p21 expression through enhancing transcription activities of AP4. The rescue experiments indicated that silencing of AP4 abrogated the inhibition of cellular senescence induced by TRIB2 overexpression. These data demonstrate that TRIB2 suppresses cellular senescence through interaction with AP4 to down-regulate p21 expression. Therefore, TRIB2 could be a potential target for CRC treatment.
Abstract 20475: Investigating Molecular Mechanisms of Type 2 Long QT Syndrome With iPSC-Derived Cardiomyocytes
Authors: Fernanda C Mesquita, Gustavo Monnerat, Dayana S Araujo, Paulo C Arantes, Tais H Brunswick, Fernanda Gubert, Jorge Coutinho, Gabriel Neiman, Tamara Borgonovo, Isabela C Leitão, Danubia S dos Santos, Isadora M Vaz, Santiago Miriuka, Emiliano H Medei, Fernando E Cruz, Adriana B Carvalho, Antonio C Campos-de-Carvalho
Journal: Circulation (2017)

Patient-specific cardiomyocytes obtained from induced pluripotent stem cells (CM-iPSC) offer unprecedented mechanistic insights in the study of inherited cardiac diseases. The aim of this work was ...
Abstract 19506: Relevance of Fibroblast Growth Factor 21 in Cardio-metabolic Diseases
Authors: Scott M Damrauer, Wei Zhao, Ashif Rashid, Phillipe Frossard, John Danesh, Daniel J Rader, Danish Saleneeh
Journal: Circulation (2015)

Background: Fibroblast growth factor 21 (FGF-21) is an adipokine produced predominantly in the liver and is a metabolic regulator of glucose and lipid metabolism. Circulating FGF-21 levels have been shown to be independently associated with a host of cardio-metabolic traits, including: BMI and adiposity, metabolic syndrome, diabetes, cholesterol and triglycerides, and cardiovascular disease outcomes. Despite these epidemiological observations, causal relationships between FGF-21 and cardio-metabolic outcomes remain uncertain. Objectives: To identify the cross-sectional correlates of FGF-21 levels and to explore the causal relationship between FGF-21 and cardio-metabolic traits using a Mendelian randomization based approach. Methods &amp; Results: FGF-21 levels were measured by ELISA in 9,572 participants from the Pakistan Risk of Myocardial Infarction Study (PROMIS), a multi-ethnic case-control study aimed at identifying genetic and non-genetic determinants of cardio-metabolic diseases. Log serum FGF-21 levels were weekly but significantly correlated with measures of obesity (BMI r=0.1, p &lt; 0.0001) and serum lipids (total cholesterol r=0.08, p &lt; 0.0001; LDL-C r=0.06, p &lt; 0.0001; log triglycerides r=0.15, p &lt; 0.0001); there was, however, no significant association with biochemical indicators of glycemic control. A Genome Wide Association Study (GWAS) was conducted to identify genetic determinants of FGF-21 levels; genetic variants were further assessed for specific associations with FGF21 levels in order to to identify instruments suitable for Mendelian Randomization studies. Variants that specifically increased FGF21 levels were not found to be associated with either Type-2 diabetes (80,000 cases and 230,000 controls) or coronary heart disease (63,746 cases and 130,681 controls). Conclusions: Although FGF-21 is weekly correlated with a number of cardiovascular risk factors; however its relationship to cardio-metabolic outcomes is less likely to be causal.
Pakistani woman seeks court approval for sex change to earn a living
Authors: Ashfaq Yusufzai
Journal: BMJ (2018)

A 22 year old Pakistani woman has petitioned the Peshawar High Court for permission to have sex reassignment surgery so that she can work publicly and support her family.

Kainat Murad told The BMJ , “I want to work and earn a livelihood for my family. I have no brothers or sisters, and my parents, who cannot work, need my support.” She said …
Comparisons Between PET With 11C-Methyl-l-Methionine and Arterial Spin Labeling Perfusion Imaging in Recurrent Glioblastomas Treated With Bevacizumab
Authors: Takaaki Beppu, Yuichi Sato, Toshiaki Sasaki, Kazunori Terasaki, Fumio Yamashita, Makoto Sasaki, Kuniaki Ogasawara
Journal: Clinical Nuclear Medicine (2018)

Purpose The aim of this study was to clarify whether arterial spin labeling (ASL) perfusion imaging can assess biological effects from bevacizumab (BEV) therapy as reliably as PET with 11 C-methyl- l -methionine ( 11 C-met-PET). Materials and Methods Twenty-four patients with recurrent glioblastoma were examined using both ASL and 11 C-met-PET before and 4 and 8 weeks after starting BEV treatment. Tumor-to-normal brain (T/N) ratios, fluctuations in T/N ratio, and tumor volumes were compared between ASL and 11 C-met-PET. Accuracy of predicting patient with long progression-free survival (PFS) was assessed for T/N ratios and fluctuations for ASL and 11 C-met-PET in each phase and in each period using receiver operating characteristic curves. Between 2 groups of patients assigned by cutoff values from receiver operating characteristic curves, PFS was compared in each phase or in each period. Results T/N ratios, fluctuations in ratio, and tumor volumes correlated significantly between ASL and 11 C-met-PET at all time points and all periods. Arterial spin labeling was eligible as a predictor for long PFS only in assessment of fluctuations in T/N ratio. However, the most accurate predictors for long PFS were T/N ratio from 11 C-met-PET at 8 weeks and the fluctuation from baseline to 4 weeks in T/N ratio from 11 C-met-PET. Conclusions Blood flows on ASL correlated with accumulations of 11 C-met on PET in recurrent glioblastoma under BEV treatment. Although 11 C-met-PET offered superior accuracy for predicting patients with long PFS from time points, ASL offered reliable prediction of long PFS, provided that fluctuations in T/N ratio between consecutive scans are assessed.