tbuckley/cabot-search huggingface dataset:
Abstract 496: Inhibition of the Rna Binding Protein Hur Protects Against Cardiac Ischemia/reperfusion Injury by Reducing Inflammatory Gene Expression
Authors: Samuel Slone, Salma Fleifil, Sarah Anthony, Lisa Green, Michelle L Nieman, John Lorenz, Michael Tranter
Journal: Circulation Research (2019)

Despite medical advances, cardiac ischemia/reperfusion (I/R) injury remains a leading cause of morbidity and a huge economic burden in the United States. RNA binding proteins are becoming recognized as potential mediators of cardiac physiology and pathology, but the role of HuR, an RNA binding protein highly expressed in myocytes, in acute cardiac I/R injury is unknown. HuR has been shown in other tissues to be a critical post-transcriptional mediator of pro-inflammatory chemokine and cytokine gene expression, and we have shown HuR to be activated (nuclear-to-cytoplasmic translocation) in cardiomyocytes 2 hours post-ischemia/reperfusion injury. To address the functional role of HuR in I/R, cardiomyocyte-specific HuR deletion mice (iCM-HuR -/- ) were subjected to 30 minutes of LAD (left anterior descending) coronary artery ligation followed by 24 hours of reperfusion. In parallel, a separate group of wild-type mice were subjected to 30 minutes ischemia with a pharmacological inhibitor of HuR given just prior to reperfusion. Analysis of infarct size showed a smaller infarct with both HuR genetic deletion (~10% decrease in infarct size compared to control, N=3, P&lt;0.05) and pharmacological inhibition (~11% decrease in infarct size compared to vehicle, N=4, P=0.069). Similarly, HuR inhibition significantly reduced cell death, caspase-3 activity, and inflammatory gene expression in an in vitro model of simulated I/R using neonatal rat ventricular myocytes. HuR inhibition results in a significant blunting of IL-6 and TNF-alpha gene expression two hours post-reperfusion in vivo , suggesting that HuR activity is necessary for the early induction of inflammatory gene expression networks. In addition, it appears that HuR inhibition attenuates macrophage infiltration following ischemia/reperfusion injury. In conclusion, our results suggest that inhibition of HuR is protective against cardiac I/R injury through a reduction in inflammatory gene expression.
FGM: surgeons who do cosmetic genital surgery may risk prosecution
Authors: Clare Dyer
Journal: BMJ (2019)

Surgeons who perform cosmetic genital operations such as labiaplasty should take steps to ensure that they are not risking prosecution for female genital mutilation, in the light of new guidance from the Crown Prosecution Service.1

Increasingly popular “designer vagina” operations are likely “in theory” to fall under the definition of female genital mutilation, which was first made a criminal offence in 1985, the CPS has said, because they involve excising labial tissue. In 2003 the Female Genital Mutilation Act increased the maximum penalty for female genital mutilation to 14 years in prison.

The guidance for crown prosecutors outlines factors to be weighed up in deciding …
Mogamulizumab Forecast: Clearer Patients, with a Slight Chance of Immune Mayhem
Authors: Cecilia Larocca, Thomas S. Kupper, Nicole R. LeBoeuf
Journal: Clinical Cancer Research (2019)

Mogamulizumab, approved by the FDA for relapsed or refractory mycosis fungoides and Sézary syndrome, improves progression-free survival compared with vorinostat in the largest trial to date in cutaneous T-cell lymphoma, with particular efficacy in leukemic disease, but carries a risk of immune-mediated toxicities with concomitant depletion of regulatory T cells.See related article by Kasamon et al., p. 7275.
Pyrvinium Pamoate Overcomes Cabozantinib-Resistance of FLT3-ITD AML Cells through Modulating the Mitochondria Functions and Signaling Pathways
Authors: Yu-Hsuan Fu, Wen-Hui Lu, Pei-Qi Lan, Chung-Yi Hu, Chien-Yuan Chen, Da-Liang Ou, Hwei-Fang Tien, Liang-In Lin
Journal: Blood (2018)
Abstract 336: The Effect Of Phosphodiesterase 9a Inhibition In 2 Mouse Models Of Diastolic Dysfunction
Authors: Mei Methawasin, Josh Strom, Zaynab Hourani, John E Smith, Henk L Granzier
Journal: Circulation Research (2019)

Low myocardial cGMP-PKG activity is associated with increased cardiomyocyte stiffness in HFpEF. cGMP is mainly hydrolyzed by PDE (phosphodiesterases)5a and PDE9a. Importantly, PDE9a protein expression was reported to be upregulated in human HFpEF myocardium and chronic administration of PDE9a inhibitor reversed pre-established cardiac hypertrophy and systolic dysfunction in mice subjected to TAC (Transverse Aortic Constriction). We evaluated whether PDE9a inhibition had a beneficial effect on diastolic dysfunction (DD). We investigated two mouse models of DD: 1) TAC-DOCA (TAC with deoxycorticosterone acetate (DOCA) supplementation) and 2) LepR db/db , a metabolically induced DD models. Mice were subjected to subcutaneous implantation with osmotic minipumps containing either PD9a inhibitor (PF-4449613) or vehicle for 4 wks. PDE9a transcript was not upregulated in myocardium of either TAC-DOCA or LepR db/db mice. PV analysis revealed that in TAC-DOCA mice, inhibition of PDE9a resulted in reduced LV diastolic stiffness, but impairment of systolic function observed as ventricular-vascular decoupling. In LepR db/db mice, cardiomyocyte stiffness was slightly but significantly reduced in PDE9a inhibitor treated animals. No differences in myocardial fibrosis or cardiac morphometry were observed. The effect of acute PDE9a inhibition was investigated in intact cardiomyocytes isolated from LVs of TAC-DOCA mice. Cellular work loop force measurement was conducted before and after administration of PDE9a inhibitor combined with ANP (Atrial Natriuretic Peptide) for 15 mins. Cardiomyocytes from TAC-DOCA had high diastolic stiffness compared to sham hearts, however, no stiffness reduction was observed after acute inhibitor treatment. Conclusion: Chronic inhibition of PDE9a ameliorates LV diastolic stiffness, but suppresses systolic function in TAC-DOCA induced DD mice. The LV stiffness reduction is in part due to cardiomyocyte stiffness reduction. The advantage of PDE9a inhibition on diastolic function might be more evident, with less systolic suppression, in hearts with PDE9a upregulation.
Abstract 301: Bone Marrow Niche-Mediates Cardiac Repair is Associated With Adiponectin in Retnla Deficiency
Authors: Yong Sook Kim, Hye-yun Jeong, Hye-jin Kang, Mi Ra Kim, Youngkeun Ahn
Journal: Circulation Research (2019)

Background: Resistin like α (Retnla) is known to be upregulated in anti-inflammatory macrophages and to modulate lipid profile in atherosclerosis. However, the role of Retnla is unknown in the cardiac pathology. Methods: Myocardial infarction (MI) was induced in wild type, Retnla knockout (KO), and Retnla transgenic (TG) mice. Cardiomyocytes, cardiac fibroblasts, macrophages and bone marrow cells were treated with Retnla protein for mechanistic studies. For an adoptive transfer, bone marrow cells were isolated from KO mice to transplant to the infarcted heart. Results: TUNEL staining showed the number of apoptotic cardiomyocytes was higher in the Retnla KO mice than in the TG mice 1 day after MI. Cardiac function and angiogenesis were significantly better in the Retnla KO group, while were worsen in the TG group. Retnla is an anti-inflammatory marker in macrophages, but the expressions of inflammation-related genes were not different between both groups. Interestingly, however, the numbers of macrophages isolated from bone marrow, peritoneum, and cardiac tissue of Retnla KO mice were higher than in the wild type mice. Moreover, phospho-histone H3-positive proliferating cells in the bone marrow were much more abundant in the Retnla KO mice than in the wild type mice. Adiponectin was highly expressed in bone marrow of KO mice, and we transplanted bone marrow cells from KO mice to recipient wild type mice. Two weeks after MI, recipient group transplanted with bone marrow cells from KO mice showed better angiogenesis, reserved cardiac function, and more anti-inflammatory macrophages. In Retnla-treated cardiomyocytes, bax, phopho-p38, and p21 were notably upregulated, while bcl2 and adiponectin were significantly reduced. To examine whether Retnla acted negatively on adiponectin, we administrated a synthetic adiponectin receptor agonist AdipoRon to Retnla-treated cardiomyocytes. AdipoRon blunted the effect of Retnla on cardiomyocytes. These data showed better cardiac recovery was associated with bone marrow-derived adiponectin in the Retnla KO group. Conclusion: Our study suggested that substantial cardiac recovery was strongly associated with adiponectin derived from highly proliferating bone marrow cells in Retnla KO mice.
Abstract P035: Feasibility of Stretching Exercise for Prevention of Late-Onset Preeclampsia: A Pilot Trial
Authors: Melissa C Caughey, Joyce S Cho, Ya-Ke Wu, W. B Nix, SeonAe Yeo
Journal: Circulation (2018)

Background: Preeclampsia is a leading cause of maternal morbidity and perinatal mortality. Manifestations include hypertension, proteinuria, and end-organ dysfunction in the latter half of pregnancy. The United States Preventive Services Task Force recommends low-dose aspirin as a modestly effective preventive treatment; however, no conclusive prevention is currently available. Moderate to vigorous physical activity is reported to reduce preeclampsia risk, but is increasingly difficult by the 3 rd trimester. Further, intense exercise may stimulate sympathetic overactivation, a precursor of late-onset (≥34 weeks gestation) preeclampsia associated with maternal obesity. Stretching exercise may be a feasible alternative to intense exercise, and more readily adopted by obese women at risk of late-onset preeclampsia. We hypothesized that stretching exercise would suppress sympathetic overactivity and enhance parasympathetic tone in pregnant women. Methods: Gravid women were recruited with informed consent for stretching exercise and cardiovascular testing during the 2 nd to 3 rd trimester of pregnancy. Exercises were standardized by video demonstration, and targeted 14 major muscle groups in the lower and upper extremities. Each muscle group was stretched for 20 seconds in 3 repetitions. Blood pressure, carotid-femoral pulse wave velocity (PWV), and heart rate variability (HRV) were acquired before and after stretching, with baseline values preceded by a 15 minute rest. Heart rate and HRV were averaged over 10 minute acquisitions. Total HRV variance was stratified into low frequency (LF; &lt; 0.15 Hz) and high frequency (HF; ≥ 0 .15 Hz) domains, with HF reflecting parasympathetic nerve activity and LF dominated by sympathetic activity. Sympathovagal balance was estimated by the LF/HF ratio. Pre- and post-exercise measurements were compared by paired t-tests. Results: A total of 20 women consented to enrollment; all completed stretching exercise and cardiovascular testing without complications. On average, study participants were 32 years old, 27 weeks pregnant, and had a BMI of 29 kg/m 2 . Over a third (35%) had a BMI &gt; 30 kg/m 2 . Significant reductions between pre- and post-exercise were observed for mean diastolic blood pressure (60 vs. 57 mmHg; p=0.02) and heart rate (78 vs. 75 bpm; p&lt;0.0001). However, mean systolic blood pressure was not significantly changed (104 vs. 105 mmHg; p=0.2), nor was mean PWV (5.3 vs. 5.2 m/s; p=0.4). Although non-significant, the mean LF/HF ratio decreased (2.4 vs. 1.7 Hz; p=0.3), suggesting parasympathetic dominance post-exercise. Conclusion: This pilot study demonstrates stretching exercise is well-tolerated by pregnant women in the 2 nd or 3 rd trimester, and may be a feasible prevention for obese women at risk of late-onset preeclampsia. A randomized controlled trial investigating outcomes of routine stretching exercise in pregnancy is warranted.
CD9 blockade suppresses disease progression of high-risk pediatric B-cell precursor acute lymphoblastic leukemia and enhances chemosensitivity
Authors: Kam Tong Leung, Chi Zhang, Kathy Yuen Yee Chan, Karen Li, John Tak Kit Cheung, Margaret Heung Ling Ng, Xiao-Bing Zhang, Tony Sit, Wayne Yuk Wai Lee, Wei Kang, Ka Fai To, Jasmine Wai Sum Yu, Toni Ki Fong Man, Han Wang, Kam Sze Tsang, Frankie Wai Tsoi Cheng, Grace Kee See Lam, Tin Wai Chow, Alex Wing Kwan Leung, Ting Fan Leung, Patrick Man Pan Yuen, Pak Cheung Ng, Chi Kong Li
Journal: Leukemia (2019)
The Challenge Of Quantifying CD34+ Myeloid Cells In Myelodysplastic Syndromes With Less Than 5% Bone Marrow Blasts. Reproducibility Among 6 Flow Cytometry Observers
Authors: Patricia Font, Dolores Subirá, Sergio Matarraz, Celina Benavente, Teresa Cedena, Marta Morado, Ana Pérez-Corral, Jose Maria Bellon, Christian Gil Borrelli, Jose Luis Diez-Martin
Journal: Blood (2013)
Improving Efficacy of Dendritic Cell Vaccination in AML: Optimization of the DC Generation Protocol and Maximization of T Cell Responses by Immune Checkpoint Blockade
Authors: Felix S Lichtenegger, Barbara Beck, Christiane Geiger, Dieter Munker, Miriam Schlueter, Rika Draenert, Frauke Schnorfeil, Gunnar Kvalheim, Wolfgang Hiddemann, Dolores J Schendel, Marion Subklewe
Journal: Blood (2013)
RNAi-Mediated Inhibition of Tmprss6 Elevates Hamp1 Expression and Reduces Serum Iron Levels in Mice
Authors: Ivanka Toudjarska, Zuhua Cai, Tim Racie, Stuart Milstein, Brian R Bettencourt, Julia Hettinger, Dinah WY Sah, Akshay Vaishnaw, David Bumcrot
Journal: Blood (2011)
Jacqueline Brenda Ketley
Authors: Jackie Applebee, Julia Davis
Journal: BMJ (2019)

Jacqueline Brenda Ketley (“Jackie”) was an exceptional GP who was passionate about the care of patients and supporting the profession. She was highly respected not just in her practice but throughout Tower Hamlets and beyond. She was loved by her patients, who included her in family occasions such as weddings.

She worked in Tower Hamlets, London, for her whole career. She did her clinical training at the London Hospital and joined the Tower Hamlets vocational training scheme in 1988. Jackie became a partner at Chrisp Street Health Centre in 1991 and then joined Tredegar Practice in 2006 …
Expression of (pro)Renin Receptor in Human Erythroid Cell Lines: The Effect of Interferon-γ,
Authors: Kiriko Kaneko, Akiko Shibasaki, Hiroshi Nishiyama, Takuo Hirose, Koji Ohba, Kazuhito Totsune, Kazumichi Furuyama, Kazuhiro Takahashi
Journal: Blood (2011)
Consultant who put risperidone in wife’s tea without her knowledge is suspended for three months
Authors: Clare Dyer
Journal: BMJ (2019)

A locum consultant who told his wife’s GP that he had been slipping the antipsychotic drug risperidone covertly into her tea—and who asked the GP for more risperidone so that he could continue doing so—has been suspended from the UK medical register for three months.

Chandranath Sarkar was originally suspended for four months in 2018 by a different panel of the medical practitioners tribunal service, but he appealed to the High Court. He argued that his right to stay in the UK would be threatened by suspension, since his tier 2 visa required him to be working in his current post with Cwm Taf Health Board.

The four month suspension was also appealed by the Professional Standards Authority for Health and Social Care (PSA), for being too lenient, although the General …
High and Low Tumor Infiltration Affect the Differences Among the Detection of Plasma Cells Evaluated in Bone Marrow By Flow Cytometry, Aspirate and Biopsy(Grupo Interdisciplinario de Mieloma Multiple, Hospital Universitario Fundacion Santa Fe, Colombia)
Authors: Diego Martinez, Maria Valencia, Juan Pablo Mayorga, Andres Melo, Carlos Saavedra, Hirlis Acevedo, Liliana Martin, Gina Cuellar, Sandra Quijano, Monica Duarte, Lina Abenoza, Oscar Rivero, Patricia Bernal, Andres Borda, Myriam Rodriguez, Guillermo Quintero, Jose De La Hoz, Martha Romero Prieto
Journal: Blood (2018)
Structuring clinical pathways: Creating common language where there is none.
Authors: Joanna M. Hamilton, Debra McNeil, Dana Milne, Victoria Hayne, Laura Holtz, David Michael Jackman, Joseph O. Jacobson, Houry Leblebjian, Emily Meserve, John Methot, Matthew Wolfson, Carole Kathleen Tremonti
Journal: Journal of Clinical Oncology (2019)

303 Background: Clinical pathways (PW) consist of Decision Criteria (DC) such as patient and disease characteristics, prior therapy, and genetic tests. Historical Dana-Farber Pathways (DFP) content was unstructured and maintained in static documents. This could lead to inconsistencies across and within PW, limits to the scope of DFP analytics, and potential discrepancies in clinical content. Methods: To transform DFP content into a digitally innovative structure the DFP team created a hierarchical Data Model (DM). The team compiled all unstructured DC in historical PW, organized them into parameters and attributes, and connected them to external ontologies (e.g., ICDO3) where appropriate. The team then applied the structured DC to historical PW to test comprehensiveness; and addressed any gaps identified in PW and the DM. Results: The DPF DM contains 32 parameters (e.g., Diagnosis) and 218 attributes (e.g., Group Stage) that can be combined to represent all 600+ pathway branch points. The comprehensiveness and nuance of the DM improves DFP’s specificity and clinical flexibility: The DM ensures that DFP gathers actionable data across all PW and creates common language that allows for disease-specific nuances; The DM rectifies gaps in historical PW, such as DC that were not mutually exclusive or conflated multiple clinical parameters; The DM creates complex DC to direct specific sub-groups of patients to the correct treatment path, even in cases where treatment recommendations differ within diagnostic groups. Conclusions: Structuring and standardizing PW content is a complex, time-intensive endeavor. However, this work addresses the challenges of managing clinical content and provides significant benefits for future PW development. A structured DM ensures PW are comprehensive, logical, and built on a framework of inter-operability standardization. A DM also allows DFP to connect with the EMR for auto-navigation, which streamlines provider workflow. The ongoing work required to build and maintain a structured PW DM is worth the result: rich actionable data that can illuminate and standardize practice patterns within and across diseases and institutions. It creates an insightful solution to broadly manage the cancer population.
Oregon doctor sues university, claiming that “irresponsible” use of his sperm created at least 17 children
Authors: Owen Dyer
Journal: BMJ (2019)

A US doctor who donated sperm to his university’s fertility clinic while a medical student is suing Oregon Health and Science University (OHSU) for $5.25m (£4.05m; €4.72m), alleging that it broke promises to limit the number of children produced with it to five.

Bryce Cleary said that the university also promised not to give the sperm to parents in the Pacific Northwest region. But a DNA search that he ran on Ancestry.com last year revealed that at least 17 children had been born from his donated sperm, most of them in Oregon, he said.

Cleary, 53, appeared at a press conference with one of the 17—his biological daughter, 25 year old Allysen Allee, whom …
Tumor board automation.
Authors: Stephanie Zechmann, Susan Schreiner
Journal: Journal of Clinical Oncology (2019)

297 Background: Coordinating tumor boards is a complex resource intensive process. Nebraska Medicine has 16 oncology-based Tumor Boards weekly. Preparation included multiple emails between disciplines for each conference regarding case request, case reminders, agenda modification, final agendas and printing. Other tasks include recording of attendance, completion of staging sheets, tracking tumor board summaries, totaling cases presented, and completion of CoC summaries. A full time employee completed these tasks. Developing an efficient streamlined approach to managing tumor boards became critical. Methods: Standardized agenda templates and tumor board communication processes were created. Multiple email groups were developed per tumor board to allow for specificity and clarity for individuals within a targeted tumor group to reduce email traffic. Leveraged available technology within Microsoft Office 365 Suite at our organization. Microsoft Flow and SharePoint applications were selected to manage data information sharing and ease communication flow as well as provide immediate notification of agenda changes. SharePoint subsites were set up for each tumor board including: current agenda Excel file, archive agendas and summaries. Microsoft Flow turns repetitive tasks into multistep workflows. It makes decisions in workflow, running specific actions when certain conditions are met. Flow is used for automated emails for case requests, submission reminders, and final agendas to selected group of individuals including Imaging, Pathology, Physicians, Researchers and nurse. A condition was built in Flow for agenda modification. This auto-checks the agenda for updates and auto email notifies targeted individuals of updates. Results: Oncology Tumor Boards/Multi-Disciplinary Conference processes are automated with streamlined flow of communication, reduction in emails, better accommodation of late additions and greater number of patient presentations. This has improved patient care and reduction in employee time. Conclusions: Through exploration, collaboration and innovation, it is possible to automate tumor boards/MDC to create a seamless process, expand number of conferences and patient presentation while reducing resource utilization and staffing expense.
Clinical and Patient-Reported Outcomes of Dasatinib Therapy in Patients with Imatinib-Resistant or -Intolerant Chronic Myeloid Leukemia
Authors: Tatyana I Ionova, Tatiana P Nikitina, Taras A Gritsenko, Valentina L Ivanova, Galina B Kuchma, Tatyana V Shnaider, Denis A Fedorenko, Kira A Kurbatova, Andrei A Novik
Journal: Blood (2012)
Germline Variants of RUNX-1 in Myeloid Malignancy
Authors: Alek d Nielsen, Sayer Alharbi, Cassandra M. Hirsch, Bartlomiej P Przychodzen, Mikkael A. Sekeres, Yogen Saunthararajah, Hetty E. Carraway, Jaroslaw P Maciejewski
Journal: Blood (2016)
Safety and Efficacy of Venetoclax in Relapsed Refractory Multiple Myeloma: A Systematic Review and Meta-Analysis
Authors: Ceren Durer, Seren Durer, Awais Ijaz, Ahmad Kamal, Muhammad Abu Zar, Abdul Rafae, Mustafa Nadeem Malik, Ali Younas Khan, Muhammad Usman, Insija Ilyas Selene, Muhammad Junaid Tariq, Muhammad Asad Fraz, Jemin Aby Jose, Faiz Anwer
Journal: Blood (2018)
NEPA (netupitant + palonosetron) Administration Is Safe and Effective in cHL Patients Receiving ABVD Regimen: A Single-Center Real Life Experience
Authors: Vittorio Ruggero Zilioli, Periana Minga, Lara Crucitti, Erika Meli, Monica Luigia Torretta, Anna Esposito, Chiara Rusconi, Roberto Cairoli
Journal: Blood (2018)
Impact of Post-Hematopoietic Cell Transplant (HCT) Survival on Cost-Effectiveness of CPX-351 Versus 7+3 in the Treatment of Therapy-Related AML or AML-MRC in the United States
Authors: Anuraag Kansal, Odette Reifsnider, Lora Todorova, Anna Coughlan, Kathleen F. Villa
Journal: Blood (2018)