tbuckley/cabot-search huggingface dataset:
Abstract 199: The Role of miR-987 in Homeostasis of the Aging Heart in <i>Drosophila</i>
Authors: Alyssa M Hohman, Elizabeth M McNeill
Journal: Circulation Research (2019)

Background: microRNAs (miRNAs) have emerged as ideal candidates to regulate the genes involved in tissue homeostasis of the aging heart. Our work suggests a novel role for miR-987 in heart tissue maintenance during aging. Drosophila miR-987 has a highly conserved seed sequence with human miR-95 and miR-545. Both miR-545 and mir-95 have been identified as possible biomarkers in cardiovascular disease and are known to be dysregulated following cardiac events. The physiological consequences of their dysregulation, their molecular mechanism of action and specific gene targets are unknown. Methods and Results: We have characterized the impact of miR-987 loss on homoeostasis of heart morphology and function during aging using a combination of null mutants and heart specific knock down of miR-987 expression. Using SOHA (semi-automated optical heartbeat analysis), we have identified an increase in heart area and diameter around middle age (20 days post eclosion), but no significant change in arrhythmicity index, diastolic interval, systolic interval, and fractional shortening in miR-987 null mutants. We have examined the effect of miR-987 loss on lifespan and found a significant impact on male survival starting at 20 days. Using in silico analysis we have identified multiple (130) human conserved putative miRNA-target gene interactions to further characterize the molecular mechanisms underlying the observed phenotypes. Conclusions: Our results suggest that miR-987 plays and important role in heart tissue homeostasis during aging and may impact the lifespan of mutant animals. The high conservation of Drosophila miR-987 with human miR-95 and miR-545 and their conserved predicted gene targets provides us with an excellent platform to facilitate the discovery of the molecular mechanisms underlying miRNA dysregulation in cardiovascular disease.
Revised Response Criteria for Malignant Lymphomas From the Members of the International Harmonization Project (IHP) of the Competence Network Malignant Lymphoma, Represented by:.
Authors: Bruce D. Cheson, Beate Pfistner, Malik E. Juweid, Lena Specht, Steven T. Rosen, Randy Gascoyne, Sigrid Stroobants, Volker Diehl
Journal: Blood (2005)
Abstract 583: Single Cell Analysis of Monocytes and Macrophages in the Infarcted Heart
Authors: Richard P Ng, Dave Calcagno, Avinash Toomu, Zhenxing Fu, Aaron Aguirre, Ralph Weissleder, Kevin King
Journal: Circulation Research (2019)

Introduction: Ischemic Heart Disease (IHD), the leading cause of death in the world, is often initiated by myocardial infarction (MI). In mice, death typically occurs on day 4 after acute MI is induced by coronary artery ligation. At this time the interferon regulatory factor 3 (IRF3)/type I interferon (IFN) pathway is activated almost exclusively in mononuclear cells in the infarct. We have shown that the genetic or pharmacologic disruption of critical components of this innate immune pathway reduces inflammation, limits ventricular dilation and contractile dysfunction, and improves survival. Hypothesis: Treatment with the IFNAR neutralizing antibody will bias the differentiation of cardiac macrophages and in doing so establish a cardioprotective environment in the infarct. Methods: We conducted single cell RNA-sequencing analysis of mononuclear cells isolated from infarct tissue collected on day 4 after MI from mice that had been treated with an IFNAR neutralizing antibody (Ab) as well as untreated mice. Results: Analyses demonstrate the presence of 3 core cell populations in the untreated sample: monocytes expressing Plac8 and Ms4a4c , phagocytic macrophages expressing Mrc1 and Ccl8 , and reparative macrophages expressing Arg1 and Fn1 . In addition, the dramatic co-expression of related genes in response to environmental stimuli, such as secreted type I IFNs or reactive oxygen species (ROS), resulted in the formation of two more clusters of cells. One cluster was marked by the expression of interferon stimulated genes. The other was marked by the expression of an established anti-oxidant transcriptional program. Anti-interferon therapy with IFNAR Ab inhibited both the interferon stimulated genes and the anti-oxidative transcriptional program. Conclusion: We have defined the differentiation patterns of monocytes and macrophages within the infarcted heart on day 4 after MI. Treatment with the IFNAR Ab after MI alters the composition of macrophage subsets.
Inducible Heme Oxygenase 1 (HMOX1) Promotes Osteoblastogenesis, and Inhibits Osteoclastogenesis and Myeloma-Induced Bone Disease
Authors: Xin Li, Sarah K. Johnson, Wen Ling, Sharmin Khan, Linda Saint John, Bart Barlogie, John D Shaughnessy, Shmuel Yaccoby
Journal: Blood (2011)
Abstract 919: Intercalated Disk Protein Xin-beta is Required for the Hippo/YAP Signaling in the Heart
Authors: Haipeng Guo, Yao Wei Lu, Zhiqiang Lin, Zhanpeng Huang, Jianming Liu, Xiaoyun Hu, Yi Wang, Tiago Fernandes, Yuxuan Guo, Jenny L.-C Lin, Jim J.-C Lin, Francisco Naya, William T Pu, Da-Zhi Wang
Journal: Circulation Research (2019)

Cardiovascular diseases continue to be a leading cause of death and disability. Despite this alarming fact, there is lack of effectual treatment and the molecular mechanisms underlying these devastating diseases remain elusive. Intercalated disk (ICD) is not only essential for the integrity of cardiomyocytes to withstand the strong mechanical forces imposed by constant heart beating; it is also critical for the dissemination of the electrical signal that initiates cardiac contraction. However, relatively less is known about how ICD transmits pathophysiological signals in cardiomyocytes to modulate gene expression and cardiac function. The Xin-α and Xin-β, belongs to a family of Xin-repeat containing proteins, are primarily located at the ICD of adult cardiomyocytes. They play an important role during heart development. Interestingly, the human homologue of the mouse Xin-β gene was mapped to a locus associated with cardiomyopathy; most importantly, mutations in Xin-α and Xin-β have been found in patients with cardiomyopathy, underscoring the importance of Xin genes to cardiac disease. Our previous studies have shown that Xin-β KO mice die postnatally with severe cardiomyopathy. Here, we report that loss of Xin-β results in defect in cardiomyocyte proliferation. Unbiased transcriptome analyses reveal that gene program related to the Hippo/Yap pathway is altered, leading to the hypothesis that Xin-β regulates cardiomyocyte proliferation and cardiac function by modulating the Hippo/Yap signaling. We identify physical and genetic interaction between Xin-β and components of the Hippo/Yap pathway. We further show that the expression of Xin-β is transcriptionally regulated by Mef2a, Yap and Tead1, suggesting the presence of a Xin-β/Yap feedback regulatory network in the heart. Strikingly, cardiac-specific overexpression of Yap markedly rescues cardiac defects in Xin-β KO mice; indicating a functional and genetic interaction between Xin-β and Yap. Together, our study reveals a novel molecular mechanism by which the ICD protein Xin-β modulates important pathophysiological Hippo/Yap signals to control heart development and cardiac function. Molecules uncovered here will become candidate targets for therapeutic treatment of cardiac disease.
Stem Cell Mobilization in Poor Mobilizers Using Plerixafor and G-CSF with or without Chemotherapy: A European Perspective
Authors: Maximilian M Fresen, Rafael F. Duarte, Jane F Apperley, Grzegorz Basak, Kenneth W Douglas, Ian H Gabriel, Catarina Geraldes, Ozren Jaksic, Zdenek Koristek, Nicolaus Kröger, Francesco Lanza, Roberto M. Lemoli, Gabor Mikala, Dominik Selleslag, Nina Worel, Florian Lange, Mohamad Mohty, Kai Hübel
Journal: Blood (2011)
Community oncologists' perceptions three years after the Oncology Care Model.
Authors: Jonathan Karl Kish, Ting-Chun Yeh, Ajeet Gajra, Yolaine Smith, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2019)

113 Background: The Oncology Care Model (OCM) is a Medicare-sponsored delivery and payment innovation pilot under the broader concept of value-based care (VBC). OCM aims to provide better quality and coordinated cancer care at reduced cost. The OCM participants, 176 practices and 10 payers who provide care to nearly half of Medicare beneficiaries, entered into payment arrangements based on financial and performance accountability for episodes of care surrounding chemotherapy administration. We sought to understand the impact of OCM adoption on community physicians 3 years into the pilot. Methods: A live meeting in April 2019 convened a sample of US-based community oncologists to discuss “The OCM Experience”. Audience response survey methodology addressed: participation in OCM and/or related commercial programs, implementation, operation and perceptions of outcomes to patient care and practice. Results: Regarding VBC initiatives at the practices (n = 48) of 57 providers: 61% identified their practice participated in OCM, 31% in other commercial payer pathway program, and 17% in other commercial payer VBC reimbursement (not mutually exclusive). Regarding impact of OCM on improving access to care: 60% indicated having same-day appointments, 45% 24/7 HCP access, 22% weekend hours and 18% evening clinic hours. Regarding changes to patient care: 58% stated OCM driven initiatives reduced ER visits, 48% reduced hospitalizations, 62% increased palliative care referrals, and 54% increased hospice referrals. Regarding impact on practice: 41% felt an increased administrative burden with 50% hiring administrative staff, advanced practice providers, and patient navigators, but only 11% hiring physicians. The 13-component oncology care plan was reported by 53% as “not easy” to devise. The “most challenging” components included estimating total out of pocket expenses (61%) and creating a plan to address psychosocial needs (16%). 49% respondents found their practices’ OCM transformation meaningful and 46% found it not very/not at all meaningful. Conclusions: The impact of OCM/VBC transformation upon community oncologists and their practices appear to be quite profound, while the precise impact on their patients remains to be determined.
Metabolic Subtyping for Novel Personalized Therapies Against Pancreatic Cancer
Authors: Kamiya Mehla, Pankaj K. Singh
Journal: Clinical Cancer Research (2019)

Abstract Through metabolic subtyping, metabolic vulnerabilities can be exploited for developing efficacious treatments. A glycolytic subtype indicates poor survival in patients with pancreatic cancer, whereas a cholesterogenic subtype correlates with better outcomes potentially due to more energy expenditure. Personalized medicine holds great promise for improving therapy outcomes by optimally targeting metabolic pathways. See related article by Karasinska et al., p. 135
Abstract 222: Single Cell Analysis of the Emergency Hematopoietic Response to Myocardial Infarction
Authors: Kevin R King, David M Calcagno, Richard P Ng, Avi Toomu, Kenneth Huang, Nika Taghdiri, Aaron D Aguirre, Zhenxing Fu
Journal: Circulation Research (2019)

Myocardial infarction (MI) is the initiating event in ischemic heart disease, the most common cause of death in the world. Although MI-induced injury is sterile, it nevertheless elicits a vigorous emergency hematopoietic response in the bone marrow that supplies abundant myeloid cells to the heart, which remove dying cell debris and orchestrate healing, repair, and fibrosis. Ensemble methods such as flow sorting of immunostained cells and qPCR have provided some insights into infarct leukocyte phenotypes using candidate markers/genes, but the full diversity remains unknown. Here, we used single cell RNA-Seq to perform genome-wide transcriptomic profiling of &gt;50,000 single cells from the hearts, blood, and bone marrow of infarcted and non-infarcted mice on days 1-4 after MI. We defined the diversification of myeloid cells, from their granulocytic and monocytic origins in the bone marrow, through the blood, and into the infarcted heart. This allowed construction of an atlas of MI-induced myeloid diversification and trafficking. Among the many observations enabled by this data were the origins of the type I interferon response. We recently discovered that MI induces a type I interferon response that can be targeted genetically or pharmacologically for therapeutic benefit. Our single cell data now reveal that interferon induced cells (IFNICs) derive from both neutrophilic and monocytic origins as early as 24 hours after MI. These cells are not only found within the heart, but can also be identified in the post-MI blood and bone marrow. Ongoing studies are investigating whether IFNICs can be detected in human blood after MI. Our results have clinical importance for understanding and modulating the immune response to myocardial injury. We show, using single cell transcriptomics, that post-MI treatment with anti-interferon alpha receptor antibody (IFNAR Ab) (the murine equivalent of a therapeutic antibody currently in Phase 3 clinical trials for lupus), completely abolishes MI-induced interferon signaling and shifts the intracardiac macrophage program towards a reparative posture. Our comprehensive atlas of the emergency hematopoietic response to MI can serve as a resource for others studying the inflammation in ischemic heart disease.
Development Assistance for Health in Low-Income Countries
Authors: Desmond T. Jumbam, Dominique Vervoort, Kee B. Park
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Generation of Multi-Antigen Specific T Cells for Adoptive Immunotherapy of Myeloid Leukemia and Identification of MHC Class I and II-Restricted Peptides for WT1, Proteinase 3 and Human Neutrophil Elastase
Authors: Gerrit Weber, Ulrike Gerdemann, Nancy F. Hensel, Ann M. Leen, Catherine M. Bollard, A. John Barrett
Journal: Blood (2011)
Reduced Intensity Conditioning with Combined Haploidentical and Cord Blood Transplantation Results in Rapid Engraftment and Durable Remissions in Hematological Malignancies
Authors: Hongtao Liu, Elizabeth Shima Rich, Lucy Godley, Olatoyosi Odenike, Loren Joseph, Susana Marino, Justin Kline, Vu H. Nguyen, John M Cunningham, Richard A. Larson, Paula Del Cerro, Linda Schroeder, Lisa Pape, Wendy Stock, Amittha Wickrema, Andrew Artz, Koen M. Van Besien
Journal: Blood (2011)
Disease Risk Index Is Independently Associated with Long-Term Outcomes of Allogeneic Transplantation Post Reduced-Intensity Conditioning in Lymphoid Malignancies
Authors: Ioanna Sakellari, Zoi Bousiou, Andriana Lazaridou, Eleni Gavriilaki, Ioannis Batsis, Despina Mallouri, Michalis Iskas, Niki Stavroyianni, Anastasia Marvaki, Magia Pilavaki, Styliani Papaemmanouil, Achilles Anagnostopoulos
Journal: Blood (2018)
Unplanned hospital admission in patients receiving concurrent chemotherapy and radiation.
Authors: Nicholas Damico, Ellen Tiemeier, Laura Krukowski, Lucy Colo, Christine Marie Sydenstricker, Barbara Kraska, Jennifer Anne Dorth
Journal: Journal of Clinical Oncology (2019)

258 Background: Concurrent chemotherapy and radiation therapy (CCRT) has become a curative treatment for many malignancies. Many patients are ultimately cured, but at the cost of significant acute toxicity. When severe, this can require unplanned hospitalization. More research is needed to better identify patients at risk for hospitalization and how to prevent it. Methods: As part of quality improvement at the Seidman Cancer Center, patients in the University Hospitals (UH) system who underwent CCRT were identified. A review was done to determine which patients experienced an unplanned admission in the UH system during their radiation course or within 30 days and the admission diagnosis. We recognized malnutrition and dehydration as causes for hospitalization that were preventable. Several interventions were then performed to reduce these admissions. The first was standardized nutrition screening that prompts earlier dietician referrals for patients at risk of malnutrition. We also instituted hydration assessments for patients beginning in the 3rd week of radiation. Patients found to be dehydrated were scheduled to receive intravenous (IV) fluids as an outpatient for the remainder of their treatment course. Admission rates for patients undergoing CCRT have been tracked as part of this initiative and are reported here. Results: From 7/2017 to 12/2018 we identified 303 patients who completed CCRT. 78 (26%) had an unplanned hospital admission during their treatment course or within 30 days of completing radiation. This included patients with primary head and neck, CNS, GI, lung, GYN, and GU malignancies for which admission rates were 36%, 32%, 23%, 29%, 19% and 8% respectively. 18 (23%) of these patients were admitted after completing the radiation course but within 30 days. The initial admission rate prior to intervention was 34%. This has since declined to 19% (table). Conclusions: Unplanned admission rates are high in patients who undergo CCRT across disease sites. Patients remain at risk following completion of radiation therapy for up to 30 days. Some admissions may be prevented by early dietician referrals and IV hydration. [Table: see text]
Abstract 302: Role of Acidic pH in Linking SIRT1 and Cardioprotective Metabolism
Authors: Chaitanya A Kulkarni, Alexander S Milliken, Paul S Brookes
Journal: Circulation Research (2019)

Metabolic acidosis is the hallmark of the ischemic period of ischemia-reperfusion injury and acidic pH is cardioprotective via unclear mechanisms. We previously reported induction of neomorphic activities in several dehydrogenase enzymes under acidic pH, leading to accumulation of non-canonical metabolite L-2-hydroxyglutarate (2-HG). Lysine deacetylase SIRT1 is required for cardioprotection via ischemic preconditioning (IPC) and 2-HG levels are elevated in IPC in a SIRT1 dependent manner. We hypothesized that acidic pH may be an independent variable that partly drives the metabolic character of not only ischemia, but also IPC. This hypothesis was tested using LC-MS/MS based metabolomics analysis of perfused hearts. Exposure of hearts to ischemia, hypoxia, IPC or intracellular acidosis resulted in partially overlapping metabolomes, with a number of metabolic adaptations previously attributed as either ischemic or IPC-driven, being induced by acidic pH alone. Furthermore, we observed that SIRT1 activator β-nicotinamide adenine mononucleotide induced cellular acidification in isolated cardiomyocytes. In the same cells it was observed that SIRT1 activation resulted in inhibition of sodium proton exchanger NHE1. These results suggest (i) a novel signaling mechanism in which SIRT1 is a cellular pH regulator via NHE1, and (ii) a role for acidic pH as a link between SIRT1 and cardioprotective metabolic adaptations.
UK must become more self reliant for sake of healthcare workforce, says top doctor
Authors: Adrian O’Dowd
Journal: BMJ (2019)

Predicted shortages of healthcare workers throughout Europe over the next few decades mean that the United Kingdom will have to find other ways to provide for a growing elderly population, peers have been told.

The message that the UK may need to become more self reliant in terms of finding doctors, nurses, and care workers was underlined by Chris Whitty, the new chief medical officer for England and chief scientific adviser at the Department of Health and Social Care.

Whitty appeared before the House of Lords science and technology committee on 15 October for an evidence session of its inquiry into ageing, science, and healthy living. He said that the current model used in recruiting …
Effects of moderately increased testosterone concentration on physical performance in young women: a double blind, randomised, placebo controlled study
Authors: Angelica Lindén Hirschberg, Jona Elings Knutsson, Torbjörn Helge, Manne Godhe, Maria Ekblom, Stephane Bermon, Björn Ekblom
Journal: British Journal of Sports Medicine (2019)

Objective To investigate the effects of a moderate increase in serum testosterone on physical performance in young, physically active, healthy women. Methods A double blind, randomised, placebo controlled trial was conducted between May 2017 and June 2018 (ClinicalTrials.gov ID: NCT03210558 ). 48 healthy, physically active women aged 18–35 years were randomised to 10 weeks of treatment with 10 mg of testosterone cream daily or placebo (1:1). All participants completed the study. The primary outcome measure was aerobic performance measured by running time to exhaustion (TTE). Secondary outcomes were anaerobic performance (Wingate test) and muscle strength (squat jump (SJ), counter movement jump (CMJ) and knee extension peak torque). Hormone levels were analysed and body composition assessed by dual energy X-ray absorptiometry. Results Serum levels of testosterone increased from 0.9 (0.4) nmol/L to 4.3 (2.8) nmol/L in the testosterone supplemented group. TTE increased significantly by 21.17 s (8.5%) in the testosterone group compared with the placebo group (mean difference 15.5 s; P=0.045). Wingate average power, which increased by 15.2 W in the testosterone group compared with 3.2 W in the placebo group, was not significantly different between the groups (P=0.084). There were no significant changes in CMJ, SJ and knee extension. Mean change from baseline in total lean mass was 923 g for the testosterone group and 135 g for the placebo group (P=0.040). Mean change in lean mass in the lower limbs was 398 g and 91 g, respectively (P=0.041). Conclusion The study supports a causal effect of testosterone in the increase in aerobic running time as well as lean mass in young, physically active women.
SMRT; Not So Smart in Multiple Myeloma.
Authors: Pushpankur Ghoshal, Christiane Houde, Angela Szafranek, Alain Nganga, Timothy Johnson, Ashley Bigelow, Joseph Moran-Guiati, Dominic Smiraglia, Asher Alban Chanan-Khan, Lionel J. Coignet
Journal: Blood (2007)