tbuckley/cabot-search huggingface dataset:
The association between health insurance coverage disruptions and access to care and affordability among cancer survivors in the United States.
Authors: Jingxuan Zhao, Xuesong Han, Leticia Maciel Nogueira, Ahmedin Jemal, K Robin Yabroff
Journal: Journal of Clinical Oncology (2019)

121 Background: Having health insurance is a strong predictor of access to care and affordability. To date, most studies evaluating the effects of insurance coverage measured it only at a single time point. Little is known about the effects of coverage disruptions. This study aims to assess associations of a health insurance coverage disruption with access and affordability among cancer survivors in the United States. Methods: We identified 6476 cancer survivors aged 18-64 years with current health insurance coverage from the 2011-2017 National Health Interview Survey. Coverage disruption was measured by the question “In the past 12 months, was there any time when you did not have any health insurance or coverage?”. Access to care and affordability was measured by: 1) preventive services use (e.g. blood pressure check); and 2) forgoing care because of cost, respectively, in the past 12 months. We used separate multivariable logistic models to evaluate the associations between a coverage disruption and healthcare access and affordability, by current health insurance coverage. Results: Among survivors with current health insurance coverage, 3.7% of those with private and 8.1% with public insurance reported a coverage disruption in the past 12 months. Among survivors with current private coverage, those with a recent coverage disruption reported lower likelihood of any preventive services use (OR = 0.1, 95% CI: 0.1-0.3) and higher likelihood of forgoing any care because of cost (OR = 6.0, 95% CI: 3.9-9.5) compared to those with continuous private coverage. Among survivors with current public coverage, those with a recent coverage disruption reported lower likelihood of any preventive services use (OR = 0.4, 95% CI: 0.2-0.9) and higher likelihood of forgoing any care because of cost (OR = 4.3, 95% CI: 2.5-7.3) compared to those with continuous public coverage. Conclusions: Currently insured cancer survivors with a recent health insurance coverage disruption were more likely to report problems in access to care and affordability compared to the continuously insured. Improving private and public insurance coverage continuity may be effective in addressing these problems.
Pharmacokinetics, Efficacy and Safety of Lenalidomide (Len) in Myeloma Patients with Renal Impairment: Results From the Prospective Study “REVIR”
Authors: Frank Bridoux, Bertrand Arnulf, Stephane Moreau, Eric Moumas, Nianhang Chen, May Alakl, Estelle Desport, Valerie Neel, Arnaud Jaccard, Jean Paul Fermand
Journal: Blood (2011)
Management of Warfarin Associated Intracranial Hemorrhage with a 3-Factor Prothrombin Complex Concentrate and Low Dose Recombinant Factor VIIa.
Authors: Karén Matevosyan, Christopher Madden, Fleur M Aung, David P Chason, Garry Arbique, Jeffrey Guild, Shahid Shafi, Ravindra Sarode
Journal: Blood (2008)
Assessment of Anemia Prevalence Among Non-Pregnant Women in Urban Areas of Shanghai and Tokyo: A Retrospective Observational Study
Authors: Kana Yamamoto, Wang Na, Morihito Takita, Tomohiko Sato, Tomohiro Morita, Tsunehiko Komatsu, Suguru Tokiwa, Masahiro Kami, Shigeaki Kato, Tetsuya Tanimoto, Zhao Genming
Journal: Blood (2018)
Abstract 221: IKKe Deficiency Aggravates Cardiac Inflammation with Dysregulation of p52 and p38 in Myocardial Infarction
Authors: Hyang Hee Cho, Yong Sook Kim, Ju Hee Jun, Dong Im Cho, Meeyoung Cho, Youngkeun Ahn
Journal: Circulation Research (2019)

Inhibitor of NF-κB kinase (IKK), an upstream of nuclear factor-kappa B (NF-κB), is a critical modulator for pathophysiological inflammation. IKKε is a non-classical IKK and has been studied in infectious diseases and cancers. However, the role of IKKε in a myocardial infarction (MI) has not been addressed. In this study, we used IKKε knockout mice to induce MI by coronary artery ligation. Cardiac function was analyzed by echocardiograph after 2 weeks, and fractional shortening (FS) was 16.36±4.46% in the wild type group and 13.47±1.21% in the knockout group. Cardiac fibrosis and macrophage infiltration deteriorated in the knockout group. Next, we investigated the inflammatory responses and found that the expression of inducible nitric oxide synthase (iNOS), an inflammatory marker, was much higher in both infarcted heart tissues and bone marrow-derived macrophages (BMDM) isolated from knockout mice than from wild type mice. Besides, cardiac macrophages displayed more inflammatory phenotype in the IKKε knockout group than in the wild type group. To explore the responsible mediator, we performed phosphorylated protein array and found phosphorylated p38 was significantly downregulated in the IKKε knockout BMDM. Conversely, both knockdown of p38 by siRNA and inhibition of p38 by SB203580 treatment in RAW264.7 cells upregulated iNOS induction. In the infarcted heart tissue, non-canonical NF-κB2 (p52) protein was dramatically upregulated in the IKKε knockout group than in the wild type group, while mRNA level was not different in the both groups. Immunohistochemical analysis showed nuclear accumulation of p52 in cardiomyocytes and fibroblasts in the peri-infarct lesion. Our data showed excessive inflammation in IKKε knockout mice was associated with inactivation of p38 in macrophages and upregulated p52 in the infarcted myocardium. Collectively, IKKε is involved in the control of inflammation resolution through modulating p38 activity and p52 post-translational modification in the infarcted myocardium.
In vivo characterization of enTRinsic™ drug delivery technology capsule after intake in fed state: A cross-validation approach using salivary tracer technique in comparison to MRI
Authors: Maximilian Sager, Michael Grimm, Philipp Aude, Philipp Schick, Simon Merdivan, Mahmoud Hasan, Marie-Luise Kromrey, Aurélien Sivert, Hassan Benameur, Mirko Koziolek, Mladen V. Tzvetkov, Werner Weitschies
Journal: Journal of Controlled Release (2019)
Gene Mutations, Their Interactions and Associations with Immunophenotypes of Leukemia Cells in Patients with Primary Acute Myeloid Leukemia.
Authors: Chien-Yuan Chen, Hsin-An Hou, Woei Tsay, Jih-Luh Tang, Liang-Inn Lin, Wen-Cheng Chou, Chi-Fei Huang, Mei-Hsuan Tseng, Ming Yao, Bo-Sheng Ko, Hwei-Fang Tien
Journal: Blood (2007)
A Randomized, Double-Blind, Placebo-Controlled, Phase III Noninferiority Study of the Long-Term Safety and Efficacy of Darbepoetin Alfa for Chemotherapy-Induced Anemia in Patients With Advanced NSCLC
Authors: Pere Gascón, Rajnish Nagarkar, Martin Šmakal, Konstantinos N. Syrigos, Carlos H. Barrios, Jesús Cárdenas Sánchez, Li Zhang, David H. Henry, David Gordon, Vera Hirsh, Kaoru Kubota, Sergey Orlov, Gary Thomas, Tilman Steinmetz, Jin-Hyoung Kang, Dianne K. Tomita, Alexander N. Fleishman, Joseph K. Park, Cisio De Oliveira Brandao
Journal: Journal of Thoracic Oncology (2019)

This study evaluated noninferiority of darbepoetin alfa versus placebo for overall survival (OS) and progression-free survival (PFS) in anemic patients with NSCLC treated to a 12.0-g/dL hemoglobin (Hb) ceiling. Adults with stage IV NSCLC expected to receive two or more cycles of myelosuppressive chemotherapy and Hb less than or equal to 11.0 g/dL were randomized 2:1 to blinded 500 μg darbepoetin alfa or placebo every 3 weeks. The primary endpoint was OS; a stratified Cox proportional hazards model was used to evaluate noninferiority (upper confidence limit for hazard ratio [HR] < 1.15). Secondary endpoints were PFS and incidence of transfusions or Hb less than or equal to 8.0 g/dL from week 5 to end of the efficacy treatment period. The primary analysis set included 2516 patients: 1680 were randomized to darbepoetin alfa; 836 to placebo. The study was stopped early per independent Data Monitoring Committee recommendation after the primary endpoint was met with no new safety concerns. Darbepoetin alfa was noninferior to placebo for OS (stratified HR = 0.92; 95% confidence interval [CI]: 0.83‒1.01) and PFS (stratified HR = 0.95; 95% CI: 0.87‒1.04). Darbepoetin alfa was superior to placebo for transfusion or Hb less than or equal to 8.0 g/dL from week 5 to end of the efficacy treatment period (stratified odds ratio = 0.70; 95% CI: 0.57‒0.86; p < 0.001). Objective tumor response was similar between the groups (darbepoetin alfa, 36.4%; placebo, 32.6%). Incidence of serious adverse events was 31.1% in both groups. No unexpected adverse events were observed. Darbepoetin alfa dosed to a 12.0-g/dL Hb ceiling was noninferior to placebo for OS and PFS and significantly reduced odds of transfusion or Hb less than or equal to 8.0 g/dL in anemic patients with NSCLC receiving myelosuppressive chemotherapy.
Abstract 346: Tuberin S1365 Phosphorylation Regulates Mechanistic Target of Rapamycin Complex 1 (mTORC1) Pathological Signaling While Sustaining Metabolic Sensor Function
Authors: Brittany L Dunkerly-Eyring, Miguel P Vera, Christian U Oeing, Mark J Ranek, David A Kass
Journal: Circulation Research (2019)

Rationale: The Mechanistic Target of Rapamycin complex 1 (mTORC1) integrates signaling and sensory inputs to maintain cardiomyocyte homeostasis, and itself is negatively regulated by the signaling nexus tuberin (TSC2). We identified a novel TSC2 phosphorylation site S1365 (pS1365) targeted by protein kinase G (PKG), which suppressed hormonal growth factor (PE or ET1)-stimulated mTORC1 activity to attenuate pathological cardiomyocyte hypertrophy. This was recapitulated during growth factor stimulation with expression of a phospho-null (S1365A) or a phospho-mimetic (S1365E) TSC2 that exacerbated or blunted mTORC1 activation, respectively. The nature of TSC2 pS1365 as a potential metabolic sensor is unknown and will provide mechanistic insight into the TSC2 kinase input hierarchy that regulates the homeostatic function of mTORC1. Objective: To determine how pS1365 affects the ability of TSC2 to integrate metabolic dependent signals to regulate mTORC1. Methods/Results: TSC2 KO MEFs were infected with TSC2 WT or S1365A adenovirus, and then stimulated with ET1 (hormonal stress that also activates mTORC1), and 2-DG (AMPK stimulation). Both groups responded with similar decreases in mTORC1 activation regardless of pS1365. Phosphorylation of the AMPK site on TSC2 (S1387) was increased in all groups despite the presence of a phospho-null S1365. Both MEFs and neonatal rat cardiomyocytes (NRCMs) infected with TSC2 WT, S1365A, or S1365E adenovirus similarly increased mTORC1 activation with insulin (PI3K-Akt-TSC2 pathway) treatment. Serum withdrawal from NRCMs reduced mTORC1 activation in all groups regardless of whether a WT, S1365A, or S1365E TSC2 was expressed. In NRCMs subject to hypoxia (a combination of Erk, Akt, AMPK signaling), there was a similar observation with only nominal changes between WT, S1365A, and S1365E TSC2. Conclusions: The energy and nutrient sensing role of the TSC2-mTORC1 pathway remains intact regardless of the phospho-status of TSC2 S1365. These findings provide important mechanistic insight into the function of TSC2 pS1365 as a potent suppressor of pathological mTORC1 activation while not affecting the ability of TSC2 to respond to the metabolic dependent signals – AMPK (energy), PI3K-Akt (insulin), and serum starvation.
Abstract 468: Sirt1 Ameliorates High Fat Diet-induced Diastolic Heart Failure
Authors: Shinichi Oka, Peiyong Zhai, Junichi Sadoshima
Journal: Circulation Research (2019)

Approximately half of heart failure patients are diagnosed with diastolic heart failure, which is characterized by impaired relaxation. Cardiac fibrosis is observed in diastolic heart failure patients, which may promote diastolic dysfunction due to increased LV stiffness. Sirt1 is a protein deacetylase that regulates cardiac fibrosis. However, the role of Sirt1 in diastolic heart failure remains unknown. Since obesity is a significant risk factor for diastolic heart failure, we employed a high fat diet (HFD)-induced obese mouse model and cardiac-specific Sirt1 knockout (Sirt1cKO) and overexpression (Sirt1cTG) mice to define the role of Sirt1 in diastolic heart failure. Diastolic dysfunction induced by 1 and 3 months of HFD consumption was exacerbated in Sirt1cKO, evidenced by an increased end-diastolic pressure-volume relationship (EDPVR), an index of diastolic dysfunction obtained by pressure-volume loop analysis (EDPVR: wild-type mice (WT) Normal Diet (ND): 0.069; WT HFD (3 months): 0.11; Sirt1cKO ND: 0.063: Sirt1cKO HFD: 0.18*, p&lt;0.05 vs WT HFD). Consistently, HFD-induced diastolic dysfunction is ameliorated in Sirt1cTG mice (EDPVR: WT ND: 0.062; WT HFD: 0.11; Sirt1cTG ND: 0.061: Sirt1cTG HFD: 0.056*, p&lt;0.05 vs WT HFD). HFD-induced cardiac fibrosis was promoted in Sirt1cKO but ameliorated in Sirt1cTG mice. Moreover, exogenous expression of Sirt1 via adeno-associated virus vector ameliorated HFD-induced diastolic dysfunction and fibrosis (Figure). These results suggest that Sirt1 ameliorates diastolic heart failure, possibly through inhibition of cardiac fibrosis.
Cooperative Repression of IRF4 and Induction of IRF7 By CDK4/6 Inhibition Sensitizes Mantle Cell Lymphoma Cells to IMiD-Mediated Apoptosis Independent of p16 Deletion or c-Myc Overexpression
Authors: Basel A Humos, Maurizio Di Liberto, Xiangao Huang, Olivier Elemento, Selina Chen-Kiang
Journal: Blood (2018)
Abstract 605: Identification of Differential Roles of Microrna-33a and -33b During Atherosclerosis Progression with Genetically Modified Mice
Authors: Takahiro Horie, Satoshi Koyama, Yui Miyasaka, Takeshi Kimura, Koh Ono
Journal: Circulation Research (2019)

Backgrounds: MicroRNA (miR)-33a targets cholesterol transporter ATP-binding cassette protein A1 or other anti-atherogenic targets and contributes to atherogenesis. Its inhibition or deletion is known to result in the amelioration of atherosclerosis. However, mice lack the other member of miR-33 family, miR-33b, which exists in humans. Thus, precise evaluation and comparison of the responsibilities of these two miRs during the progression of atherosclerosis has not been investigated. Methods and Results: The difference between miR-33a and miR-33b were analyzed from multiple directions using genetically modified mice. We generated four strains with or without miR-33a and miR-33b. Comparison of these strains showed distinct distribution and regulation of miR-33 family. In particular, comparison between mice with only miR-33a (wild-type mice) and mice with only miR-33b (miR-33a -/- /miR-33b +/+ ) revealed the prevalence of miR-33b in the liver. Such differential expression resulted in a worsened serum cholesterol profile in mice with only miR-33b. On the contrary, in macrophages the expression level of miR-33 family genes was similar and their effects on cholesterol efflux capacity were almost comparable. To evaluate the whole body atherogenic potency, we developed ApoE -/- /miR-33a +/+ /miR-33b -/- mice and ApoE -/- /miR-33a -/- /miR-33b +/+ mice. ApoE -/- /miR-33a -/- /miR-33b +/+ mice developed increased atherosclerotic plaque compared with ApoE -/- /miR-33a +/+ /miR-33b -/- mice, in line with the predominant expression of miR-33b in the liver and worsened serum cholesterol profile. On the contrary, a bone marrow transplantation study showed no significant difference, and this was consistent with the relevant expression levels of miR-33a and miR-33b in bone marrow cells. Conclusions: miR-33 family exhibited differences in distribution and regulation, and particularly in the progression of atherosclerosis, miR-33b would be more potent than miR-33a.
Using Machine Learning to Classify the "Goodness" of Hmsc-Derived and AML-Derived EV's
Authors: Chibuikem Chukwudalu Nwizu, Lorin Crawford, Theo Borgovan, Sicheng Wen, Mark S Dooner, Pamela C Egan, John L. Reagan, Adam J Olszewski, Laura R Goldberg, Peter J. Quesenberry
Journal: Blood (2018)
Blocking Vasoactive Intestinal Peptide Signaling Enhances Anti-Viral Immunity without Increased Graft Versus Host Disease in Murine Allogeneic Bone Marrow Transplantation
Authors: Jian-Ming Li, Ying Wang, Katarzyna Darlak, Lauren T Southerland, Mohammad S Hossain, Cynthia R. Giver, James A. Waschek, Edmund K Waller
Journal: Blood (2011)
Abstract 212: Hypertrophic Cardiomyopathy Mutations With Opposite Effects on ß-myosin Biomechanics Show Similar Structural and Biomechanical Phenotypes in Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (hipsc-cms)
Authors: Alison Schroer, Guanghyun Jung, Kristina Kooiker, Arjun Adhikari, Linda Song, Chao Liu, Kathleen Ruppel, Sean Wu, Beth Pruitt, James Spudich, Daniel Bernstein
Journal: Circulation Research (2019)

Introduction: Hypertrophic cardiomyopathy (HCM) is the most prevalent heritable cardiovascular disease, commonly caused by mutations in beta cardiac myosin heavy chain (βMYH). We have measured the kinetics of isolated myosin proteins with different HCM mutations in βMYH and found an intriguing heterogeneity in kinetics and force production: some mutations increase whereas others decrease force and velocity; others result in no change. How these divergent molecular alterations converge to the final HCM phenotype: hypercontractility and cellular hypertrophy is still unknown. hiPSC-CMs provide a powerful tool for studying human cardiomyocyte biology including contractility, hypertrophic growth, and intracellular organization, but are limited by immature phenotypes and population heterogeneity in traditional culture environments. Methods and Results: We developed a micropatterned hydrogel platform that enhances force generation and promotes both structural and molecular hiPSC-CM maturation. Using CRISPR/Cas-9 gene editing in an isogenic hiPSC line, we created hiPSCs with two different βMYH mutations (P710R and D239N) that result in opposite effects on force at the molecular level, using in vitro motility and laser trap methods. Cell morphology was quantified by both fluorescence and transmission electron microscopy (EM) and force generation measured by traction force microscopy. Despite having opposite effects at the single molecule level, both HCM lines showed increased contractile force and cellular hypertrophy compared to isogenic controls. Immunostaining for βMYH and EM revealed organizational and microstructural changes including sarcomere and myofibrillar disarray, and thickened z-discs in cells containing these mutations. Both mutations had alterations in AMPK, MAPK, and calcineurin signaling shown to regulate hypertrophy. Discussion: Divergent biomechanical alterations due to HCM mutations at the single molecule level lead to common cellular-level structural and biomechanical phenotypes through activation of common signaling pathways.
Abstract 852: The Pathological Role of Coagulation Factors in Promoting Brown Adipose Tissue Dysfunction and Systemic Metabolic Disorder in Obesity
Authors: Yuka Hayashi, Ippei Shimizu, Yohko Yoshida, Ryutaro Ikegami, Goro Katsuumi, Masayoshi Suda, Shinya Fujiki, Tohru Minamino
Journal: Circulation Research (2019)

Obese individuals are predisposed to cardio-metabolic disorders. Brown adipose tissue (BAT) is an active metabolic organ abundant with mitochondria, and studies suggest a potential role of BAT in the maintenance of metabolic health in rodents and humans. Metabolic stress causes BAT dysfunction, but the underlying mechanisms are largely unknown. Coagulation factor Xa (FXa) is critically involved in a coagulation cascade, and it is also known to mediate biological effects by the activation of protease-activated receptor (PAR)-signaling. Accumulating evidence shows that PAR1 contributes to tissue remodeling in cardiovascular system. Here we show a previously unknown role of FXa-PAR signaling in promoting BAT dysfunction and systemic metabolic disorder in a murine dietary obese model. Imposing a high fat diet (HFD) on C57BL/6NCr mice led to a marked increase in tissue factor (TF), coagulation factor VII and FXa in BAT. TF-FVIIa (activated form of FVII)-FXa complex is known to activate PAR1, and we found a significant increase in PAR1 expression in BAT upon metabolic stress. Administration of a FXa inhibitor ameliorated BAT whitening, improved thermogenic response and systemic glucose intolerance upon dietary obesity. In contrast, administration of warfarin did not show any phenotype in BAT. BAT specific TF and PAR1 over-expression model showed significant whitening of this tissue, which was associated with systemic glucose intolerance. BAT specific PAR1 KO mice improved glucose intolerance and thermogenic response under a metabolically stressed condition. In differentiated brown adipocytes, FXa markedly increased mitochondrial reactive oxygen species (ROS) and reduced mitochondrial membrane potential. Inhibition of PAR1 ameliorated FXa-induced mitochondrial ROS production and reduction in membrane potential. We also found that plasma FXa level did not increase in obese mice as well as in obese individuals. These results suggest the previously unknown role of coagulation systems in promoting BAT dysfunction, leading to systemic metabolic disorders. Maintenance of BAT homeostasis through the suppression of FXa-PAR1 signaling would become a new therapeutic target for obesity and diabetes
Decreasing time to initiation of inpatient chemotherapy at LAC+USC medical center utilizing an admission checklist.
Authors: Ronak Patel, Victor Chiu, Darcy V. Spicer
Journal: Journal of Clinical Oncology (2019)

262 Background: Delays in the initiation of chemotherapy for scheduled inpatient admissions cause excess lengths of stay and shift infusion start times to the evenings when hospital staffing is decreased. We sought to characterize delays in our admission process and assess the feasibility of using an admission checklist to shorten start times in a large academic safety-net hospital. Baseline data for scheduled chemotherapy admissions in July and August of 2017 (n = 25) showed a mean time to chemotherapy initiation of 14.6 hours and mean excess LOS was 0.7 midnights. Significant delays were identified in the time between ordering and resulting of pre-chemotherapy labs (average 2.6 hours), and the time required to obtain imaging to confirm peripheral-inserted central catheter (PICC) position (1.6 hours). Methods: We created a checklist of a standardized admission workflow for physicians, which included moving all pre-chemotherapy labs, pharmacy verification of chemotherapy regimen, and PICC imaging to the outpatient setting. We organized multiple staff in-services to introduce the admission workflow prior to implementation on May 1, 2018. We then performed a retrospective chart review of all scheduled inpatient chemotherapy admissions from May to August of 2018. Results: In the first 2 months after intervention, the mean time to chemotherapy initiation was 8.5 hrs, representing a 42% reduction. In the subsequent 2 months, the mean time to chemotherapy initiation was 11.6 hours, representing a 21% reduction from baseline. Mean excess LOS was 0.4 midnights and 0.5 midnights for those time periods, respectively. For the entire post-intervention group, 7 out of 26 patients obtained pre-chemotherapy labs in the outpatient setting. Conclusions: We observed an initial mean reduction of 6.1 hours in the time to start chemotherapy, as well as a reduction in mean excess length of stay with the introduction of a new admission workflow and admission checklist. We observed incomplete adoption of the checklist, and an increase in time to chemotherapy initiation after the first two months of implementation, suggesting that physician non-adherence represents a significant barrier to maintaining these reductions.
The Expression Of CD200 As a Prognostic Factor In Newly Diagnosed Multiple Myeloma
Authors: Yi Li, Wenjun Wu, Jingsong He, Xiaoyan Han, Gaofeng Zheng, Fuming Zi, Li Yang, Cai Wu, Donghua He, Yi Zhao, Yang Yang, Lijuan Wang, Xiujin Ye, He Huang, Qing Yi, Zhen Cai
Journal: Blood (2013)