tbuckley/cabot-search huggingface dataset:
Depression-Induced Neuropeptide Y Secretion Promotes Prostate Cancer Growth by Recruiting Myeloid Cells
Authors: Yan Cheng, Xin-Ying Tang, Yi-Xuan Li, Dan-Dan Zhao, Qiu-Hua Cao, Hong-Xi Wu, Hong-Bao Yang, Kun Hao, Yong Yang
Journal: Clinical Cancer Research (2018)

Psychologic depression has been shown to dysregulate the immune system and promote tumor progression. The aim of this study is to investigate how psychologic depression alters the immune profiles in prostate cancer.We used a murine model of depression in Myc-CaP tumor-bearing immunocompetent FVB mice and Hi-myc mice presenting with spontaneous prostate cancer. Transwell migration and coculture assays were used to evaluate myeloid cell trafficking and cytokine profile changes evoked by Myc-CaP cells that had been treated with norepinephrine (NE), a major elevated neurotransmitter in depression. Chemoattractant, which correlated with immune cell infiltration, was screened by RNA-seq. The chemoattractant and immune cell infiltration were further confirmed using clinical samples of patients with prostate cancer with a high score of psychologic depression.Psychologic depression predominantly promoted tumor-associated macrophage (TAM) intratumor infiltrations, which resulted from spleen and circulating monocytic myeloid-derived suppressor cell mobilization. Neuropeptide Y (NPY) released from NE-treated Myc-CaP cells promotes macrophage trafficking and IL6 releasing, which activates STAT3 signaling pathway in prostate cancer cells. Clinical specimens from patients with prostate cancer with higher score of depression revealed higher CD68+ TAM infiltration and stronger NPY and IL6 expression.Depression promotes myeloid cell infiltration and increases IL6 levels by a sympathetic-NPY signal. Sympathetic-NPY inhibition may be a promising strategy for patients with prostate cancer with high score of psychologic depression.See related commentary by Mohammadpour et al., p. 2363.
HIV in Europe and Central Asia: progress in 2018 towards meeting the UNAIDS 90-90-90 targets
Authors: Alison E Brown, Rosalie Hayes, Teymur Noori, Yusef Azad, Andrew J. Amato-Gauci, Anastasia Pharris, Valerie C. Delpech
Journal: Eurosurveillance (2018)

In 2018, 52 of 55 European and Central Asian countries reported data against the UNAIDS 90–90–90 targets. Overall, 80% of people living with HIV (PLHIV) were diagnosed, of whom 64% received treatment and 86% treated were virally suppressed. Subregional outcomes varied: West (87%–91%–93%), Centre (83%–73%–75%) and East (76%–46%–78%). Overall, 43% of all PLHIV were virally suppressed; intensive efforts are needed to meet the 2020 target of 73%.
Utility of Bladder-Sparing Therapy vs Radical Cystectomy for Muscle-Invasive Bladder Cancer
Authors: Jason K. Molitoris, Charles B. Simone
Journal: JAMA Surgery (2018)

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State-level differences in personality and geographic disparities in access to palliative care: Findings on openness.
Authors: Michael Hoerger, Laura M Perry, Brittany D. Korotkin, Leah E Walsh, Adina S Kazan, James Louis Rogers, Wasef Atiya, Sonia Malhotra, James I Gerhart
Journal: Journal of Clinical Oncology (2018)

57 Background: There are geographic disparities in access to palliative care that cause unnecessary suffering near the end of life in low-access U.S. states. The psychological mechanisms explaining state-by-state variation in access to palliative care are poorly understood. Our objective was to examine whether state-level differences in personality explain state-by-state variation in palliative care access. Methods: We combined four datasets with state-level data for the 50 U.S. states and the national capitol. Palliative care access was measured by the Center to Advance Palliative Care 2015 state-by-state report card. Statewide personality differences were identified from a report on 619,387 adults who completed the well-validated Big Five Inventory, which assesses the five core personality dimensions: openness, conscientiousness, agreeableness, neuroticism, and extraversion. The U.S. Census and Gallup provided data on covariates. Regression analyses examined whether state-level differences in personality predicted statewide access to palliative care, controlling for differences in population size, age, gender, race/ethnicity, socioeconomic status, and political views. Results: Access to palliative care was worse in states that were younger, more racially diverse, lower in socioeconomic status, more politically conservative, and lower in openness. In regression analyses that simultaneously accounted for all predictors and covariates, only lower openness continued to explain worse state-level access to palliative care (β = 0.428, p = 0.008). Conclusions: Palliative care access is worse in states where people are lower in openness, meaning residents who are more skeptical, traditional, and concrete. Personality theory offers specific recommendations for palliative care advocates communicating with hospital administrators, legislators, philanthropists, and patients to expand access in low-openness states.
Abstract 19520: Trends in Renal Complication Rates Among Medicare Beneficiaries Undergoing PCI: Fiscal Years 2009 Through 2013
Authors: Aaron Kugelmass, David J Cohen, Matthew R Reynolds, Phillip P Brown, April W Simon, Steven D Culler
Journal: Circulation (2015)

Background: Enhanced attention has focused on contrast induced nephropathy among patients undergoing PCI. This study reports five-year trends in the rate of renal complications among Medicare Beneficiaries (MB) undergoing PCI. Methods: A retrospective analysis was conducted using annual MedPar data files for fiscal years (FY) 2009 through 2013. The study sample consists of 1,552,960 Medicare Beneficiaries (MB) undergoing a PCI without CABG or valve surgery. Up to 25 ICD-9-CM procedure and diagnosis codes were use to identify the outcomes of interest. POA flags were used to identify patients who experienced complications from those patients admitted with the comorbidity. The analysis is descriptive. Results: This analysis identifies that both new acute renal failure (ARF) and new hemodialysis (HD) increased dramatically during this period. The incidence of new HD essentially doubled in MB’s undergoing PCI during an admission. MB undergoing elective PCIs were less likely than MBs undergoing non-elective PCI to experience ARF (both present on admission and as a complication). However, MB undergoing elective PCIs were more likely than MBs undergoing non-elective PCI to have had a prior HD and experience new HD than MBs undergoing non-elective PCI. Conclusion: These findings suggest, that despite a longstanding focus on preventing CIN, the complication is increasing steadily and that new efforts to reduce PCI related CIN are warranted.
Scotland’s consultant vacancies are double official tally, BMA finds
Authors: Bryan Christie
Journal: BMJ (2018)

The vacancy rate among hospital consultants in Scotland is twice as high as official figures show, an analysis by doctors’ leaders has found.

While official NHS workforce figures record an already high vacancy rate of 6.8%, data obtained by the BMA’s Scottish consultants committee under a freedom of information request to the country’s health boards showed an actual rate of 13.9%.

The anomaly is explained by the exclusion of certain types of vacancies from official figures, said the committee. Vacancies that …
Hypoxia-elicited mesenchymal stem cell-derived exosomes facilitates cardiac repair through miR-125b-mediated prevention of cell death in myocardial infarction
Authors: Ling-Ping Zhu, Tian Tian, Jun-Yao Wang, Jing-Ni He, Tong Chen, Miao Pan, Li Xu, Hui-xin Zhang, Xue-Ting Qiu, Chuan-Chang Li, Kang-Kai Wang, Hong Shen, Guo-Gang Zhang, Yong-Ping Bai
Journal: Theranostics (2018)

Exosomes (Exo) secreted from hypoxia-conditioned bone marrow mesenchymal stem cells (BM-MSCs) were found to be protective for ischemic disease.However, the role of exosomal miRNA in the protective effect of hypoxia-conditioned BM-MSCs-derived Exo (Hypo-Exo) remains largely uncharacterized and the poor specificity of tissue targeting of Exo limits their clinical applications.Therefore, the objective of this study was to examine the effect of miRNA in Hypo-Exo on the repair of ischemic myocardium and its underlying mechanisms.We further developed modified Hypo-Exo with high specificity to the myocardium and evaluate its therapeutic effects.Methods: Murine BM-MSCs were subjected to hypoxia or normoxia culture and Exo were subsequently collected.Hypo-Exo or normoxia-conditioned BM-MSC-derived Exo (Nor-Exo) were administered to mice with permanent condition of myocardial infarction (MI).After 28 days, to evaluate the therapeutic effects of Hypo-Exo, infarction area and cardio output in Hypo-Exo and Nor-Exo treated MI mice were compared through Masson's trichrome staining and echocardiography respectively.We utilized the miRNA array to identify the significantly differentially expressed miRNAs between Nor-Exo and Hypo-Exo.One of the most enriched miRNA in Hypo-Exo was knockdown by applying antimiR in Hypoxia-conditioned BM-MSCs.Then we performed intramyocardial injection of candidate miRNA-knockdown-Hypo-Exo in a murine MI model, changes in the candidate miRNA's targets expression of cardiomyocytes and the cardiac function were characterized.We conjugated Hypo-Exo with an ischemic myocardium-targeted (IMT) peptide by bio-orthogonal chemistry, and tested its targeting specificity and therapeutic efficiency via systemic administration in the MI mice.Results: The miRNA array revealed significant enrichment of miR-125b-5p in Hypo-Exo compared with Nor-Exo.Administration of miR-125b knockdown Hypo-Exo significantly increased the infarction area and suppressed cardiomyocyte survival post-MI.Mechanistically, miR-125b knockdown Hypo-Exo lost the capability to suppress the expression of the proapoptotic genes p53 and BAK1 in cardiomyocytes.Intravenous administration of IMT-conjugated Hypo-Exo (IMT-Exo) Ivyspring
Abstract MP044: Fatty Liver Disease, Visceral Fat and Pectoral Muscle Area Are Independently Associated with Subclinical Atherosclerosis in Heavy Smokers
Authors: Kendra A Young, Gregory L Kinney, Merry-Lynn McDonald, George R Washko, Sharon M Lutiz, Katherine A Pratte, Edwin K SIlverman, James D Crapo, Matthew J Budoff, John E Hokanson
Journal: Circulation (2017)

Introduction: Cardiovascular disease is a leading cause of death in those with chronic obstructive pulmonary disease. Coronary artery calcium (CAC) is a subclinical measure of cardiovascular disease. Fatty liver disease and visceral fat (VAT) are associated with CAC, and pectoral muscle area (PMA) has been shown to be associated with CAC in our population. However, it is unclear if fatty liver disease, VAT and PMA are all independently associated with CAC or if confounding exists. Hypothesis: We hypothesized that fatty liver disease will be associated with CAC independent of VAT and PMA. Methods: We utilized cross-sectional data from COPDGene, a cohort of former and current smokers with at least 10 pack-years of smoking history with CT measures of CAC, VAT, PMA, and liver and spleen attenuation. CAC positivity was defined as greater than 2.5 units of square root transformed total CAC volume to account for measurement variability. The liver/spleen ratio (LSR) was calculated, and fatty liver disease was defined as LSR &lt; 1. Multiple logistic regression was used to assess the association between the presence of CAC and fatty liver disease. Models were adjusted for age, sex, race, and current smoking, pack-years of smoking, high cholesterol, hypertension, diabetes, pectoral muscle area and visceral fat. Interactions between fatty liver disease and sex and fatty liver disease and race were tested. Results: Of the 5873 individuals with complete data, 3210 (54.7%) had CAC and 1153 (19.6%) had fatty liver disease. Both PMA (p&lt;0.0001) and VAT (p=0.0002) were associated with having CAC, and with having fatty liver disease (p&lt;0.0001 for both). There was a significant interaction between race and fatty liver disease (p=0.03). In non-Hispanic whites (NHW), fatty liver disease was associated with having CAC (OR=1.10, 95% CI 0.92-1.32), while in AA, fatty liver disease was not associated with CAC (OR=0.79, 95% CI 0.58-1.07). Removing VAT and PMA did not attenuate these results. There was no significant interaction between fatty liver disease and sex. Conclusion: In a large cohort of heavy smokers, fatty liver disease, VAT and PMA were associated with subclinical atherosclerosis independent of traditional cardiovascular risk factors in NHW but not AA. The racial differences in this association could indicate different biologic pathways in cardiovascular disease.
Abstract 19038: Neo-Sinus Washout is Faster in Supra-Annular Transcatheter Heart Valves
Authors: Prem A Midha, Ikechukwu Okafor, Vrishank Raghav, Vahid Sadri, Jose F Condado, Rahul Sharma, Raj R Makkar, Vasilis Babaliaros, Ajit P Yoganathan
Journal: Circulation (2017)

Introduction: Transcatheter aortic valve replacement (TAVR) leaflet thrombosis has been increasingly reported with raised clinical awareness. Based on published literature occurrence rates appear l...
Comics: Educating and introducing children to radiation therapy.
Authors: Mark Sueyoshi, Arthur Olch, Natalie Johns, Jordan Afaga, Kenneth Wong
Journal: Journal of Clinical Oncology (2018)

155 Background: Comics can address topics in medicine and other facets of life in a format that is widely accessible. Literature suggests that Human-Centered Design strategies can reduce child/caregiver anxiety prior to radiation therapy. Thus, appropriately designed comics can bridge the gap between the practical realities of radiotherapy, like understanding the importance of remaining still in immobilization molds and the pediatric patient's desire for imagination and play. Similar patient-care interventions have been implemented in the form of toys, games, and books. The aim of this project was to draw out best practices in the development of a comic to prepare patients for radiotherapy. Methods: Comic production underwent an iterative process whereby a multidisciplinary team of a radiation oncology department defined a set of principles and goals. An artist then developed several drafts with the input of staff, patients, and family. Readability for the intended audience was assessed by established readability tests. Results: A 25-panel comic draft was produced by the multidisciplinary team that explained in simple terms how radiotherapy is used in a relatable and entertaining way. The dialogue was developed to accommodate the education level of both pediatric patients and caregiver(s) with the intention to be read as a shared experience. The Automated Reliability Index, Flesch Kincaid Grade Level, and Gunning-Fox Index measured readability as fourth, less than sixth, and sixth grade, respectively. The messages included an explanation of radiation, its necessity and likely side effects, the important alliance with the radiation oncology staff, and the central role of the patient. Conclusions: The development of a clear, succinct, and entertaining comic that is relatable to children undergoing radiotherapy is a challenging process, especially in a world awash with competing media. However, a graphic medium can provide an opportunity to convey information and reassurance for both the patient and family. Comics have the potential for greater patient satisfaction over traditional methods of information dissemination. Next steps will involve clinic-wide validation using standardized anxiety and family impact assessment tools.
Exercise training in patients with ventricular assist devices: a review of the evidence and practical advice. A position paper from the Committee on Exercise Physiology and Training and the Committee of Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology
Authors: Stamatis Adamopoulos, Ugo Corrà, Ioannis D. Laoutaris, Massimo Pistono, Pier Giuseppe Agostoni, Andrew J.S. Coats, Maria G. Crespo Leiro, Justien Cornelis, Constantinos H. Davos, Gerasimos Filippatos, Lars H. Lund, Tiny Jaarsma, Frank Ruschitzka, Petar M. Seferovic, Jean‐Paul Schmid, Maurizio Volterrani, Massimo F. Piepoli
Journal: European Journal of Heart Failure (2018)
Hospice and hematologic malignancies: Utilization and caregiver perspective.
Authors: Jessica Trevino Jones, Anand B. Karnad, Sushanth Kakarla, David Gregorio, Annie Hung
Journal: Journal of Clinical Oncology (2018)

72 Background: Hematologic malignancies (HM) such as leukemias, lymphomas, and myeloma are potentially curable or may have long lasting remission with current therapy. While therapy may prolong life even in an incurable setting, treatments for relapsed or refractory disease for many hematological malignancies fail and a substantial number of patients with HM are terminally ill. Hospice care services are notably underutilized for HM. Methods: We performed a retrospective cohort analysis of 22 patients treated from 2013-2016 with terminal HM. Using an adapted version of the Burden Scale for Family Caregivers, surviving family members of deceased patients were surveyed for their perspective of hospice care services. Variables examined included date of diagnosis, data of hospice enrollment if applicable, if the patient experienced any resuscitation attempts, if the patient died in hospital, number of days for last hospitalization, and admissions/ER visits within 6 months of death. Results: 11/22 (50%) of patients had AML/ALL; 9/22 (41%) had refractory lymphoma; 1/22 (4.5%) had refractory myeloma; 1/22 (4.5%) could not be included as the patient was subsequently enrolled on clinical trials. Time from diagnosis to death for AML/ALL patients was 306 days; Refractory lymphoma and myeloma patients was 408 days. 8/21 (38%) of patients died in hospital, with 1 resuscitation attempt. For AML/ALL patients, 6/11 (55%) enrolled in hospice at average of 363 days. Once in hospice, average time to death was 25 days. For Refractory lymphoma and myeloma patients, 9/10 (90%) enrolled in hospice at average of 320 days. Once in hospice, average time to death was 70 days. 7/22 (31%) of surviving family were able to be reached to participate in our adapted survey. 4/7 caregivers would not have utilized hospice/palliative care sooner than they did; 2/7 caregivers would have enrolled sooner retrospectively; 1/7 caregivers did not have palliative care/hospice options offered to them. Conclusions: Terminally ill patients face significant barriers to hospice care despite evidence of worsening disease. Realistic expectations and discussions with patient and caregivers need to be addressed in patients with relapsed/refractory HM.
Abstract 5803: Interaction of Docking Protein Gab1 With Tyrosine Phosphatase SHP2 Regulates Hepatocyte Growth Factor-dependent ERK5 Activation and Upregulation of KLF2 in the Vascular Endothelium
Authors: Wataru Shioyama, Yoshikazu Nakaoka, Kaori Higuchi, Takashi Minami, Takao Hamakubo, Yoh Arita, Kaori Yamamoto, Hiroyasu Kidoya, Hisamichi Naito, Nobuyuki Takakura, Yasushi Fujio, Keiko Yamauchi-Takihara, Toshio Hirano, Tatsuhiko Kodama, Naoki Mochizuki, Issei Komuro
Journal: Circulation (2009)

Background : Docking protein Gab1 has been reported to have crucial roles for activation of both mitogen-acitvated protein kinase and AKT downstream of various receptor tyrosine kinases. In the last scientific session, we reported that endothelium-specific Gab1 knockout mice (Gab1ECKO) displayed severe limb necrosis after operatively-induced hindlimb ischemia (HLI) due to the defect of angiogenic response. We also reported that Gab1 was essential for activation of both extracellular signal-regulated kinase 1/2 (ERK1/2) via tyrosine phosphatase SHP2 and AKT via PI3-kinase p85 subunit in human umbilical vein endothelial cells (HUVECs) in response to hepatocyte growth factor (HGF), respectively. Here, we investigated the downstream target of the HGF/Met/Gab1-dependent signaling pathway responsible for the maintenance of endothelium. Methods and Results : We examined the effect of adenovirus-mediated overexpression of β -galactosidase ( β -gal), wild-type Gab1 (Gab1 WT ), or mutated Gab1 which can’t bind with SHP2 (Gab1 ΔSHP2 ) or p85 (Gab1 Δp85 ) on the activation of downstream signaling pathways in HUVECs. HGF-induced activation of both ERK1/2 and ERK5 was enhanced in the HUVECs expressing Gab1 WT or Gab1 Δp85 , but abrogated in those expressing Gab1 ΔSHP2 , compared with control cells expressing β -gal. HGF-induced AKT activation was specifically attenuated in cells expressing Gab1 Δp85 , compared with other three groups. Using DNA microarray analysis, we found that the stimulation with HGF upregulated the expression of Kruppel-like factor 2 (KLF2), a crucial transcriptional factor for endothelial maintenance, and thrombomodulin, a well-known target gene of KLF2, through interaction of Gab1 with SHP2 in HUVECs. Next, we examined the involvement of MEK5-ERK5 pathway for the KLF2 gene expression. HGF-dependent upregulation of KLF2 was almost abrogated by the adenoviral overexpression of either dominant-negative MEK5 or dominant-negative ERK5 in HUVECs. Furthermore, the expression of KLF2 and TM in the endothelium was significantly decreased in the Gab1ECKO, compared with control after HLI. Conclusion : Interaction of Gab1 with SHP2 is essential for both activation of ERK5 and upregulation of KLF2 in response to HGF in the endothelium.