tbuckley/cabot-search huggingface dataset:
Utilization of imaging modalities in the staging of newly diagnosed rectal cancer: A survey of U.S. radiation oncologists.
Authors: Jehan Yahya, Matthew Farrell, Daniel Herzig, Catherine Degnin, Yiyi Chen, John M. Holland, Simon Brown, Jerry Jeff Jaboin, Charles R. Thomas, Timur Mitin
Journal: Journal of Clinical Oncology (2018)

564 Background: Accurate staging is crucial for management of patients (pts) with newly diagnosed rectal cancer. Endorectal ultrasound (EUS) has been a commonly used imaging modality for almost two decades, with magnetic resonance imaging (MRI) now preferred by national guidelines. Routine positron emission tomography (PET) is not recommended for initial staging. The current utilization of imaging modalities by radiation oncologists (ROs) in staging newly diagnosed rectal cancer pts in the United States is unknown. Methods: We conducted an anonymous IRB-approved online survey of practicing U.S. ROs. Respondent characteristics were tested for association with self-assessed utilization of imaging modalities using Chi-squared test. Staging 75% of more rectal cancer pts with a given modality was defined as high utilization. Results: We received 220 responses from practicing U.S. ROs. Among the responders, 85 are academically affiliated and the majority specialize in treating GI malignancies, with 98 seeing more than 10 rectal cancer pts annually. Most respondents utilize all three imaging modalities for rectal cancer staging - EUS, MRI and PET/CT. Fifty two percent and 38% of respondents are high utilizers of EUS and MRI, respectively. Nearly half (47%) of respondents are high PET utilizers. High utilization of PET was associated with practice in a private setting (p &lt; 0.05) and being within 10 years from residency training completion (p &lt; 0.05). Conclusions: Our analysis reveals a wide discordance between national guidelines and the practice patterns among U.S. ROs, with underutilization of MRI and overutilization of PET/CT. Substantial cost savings could be realized by following national guidelines recommendations to omit the routine use of PET/CT in the initial evaluation of pts with rectal cancer.
Endothelial Dysfunction and Cardiorenal Injury in Experimental Salt-Sensitive Hypertension
Authors: HiroshiHayakawa, KarenCoffee, LeopoldoRaij
Journal: Circulation (1997)

Background Pharmacological control of hypertension has contributed to a significant decrease in cardiovascular morbidity and mortality, although the beneficial effect on cardiac and renal diseases has been far more modest than the reduction in stroke. The endothelium plays a crucial homeostatic role in the regulation of vascular tone thrombogenesis and vascular remodeling. We studied the relationship between endothelial dysfunction and cardiorenal injury in hypertensive rats and evaluated the effects of two classes of antihypertensive agents commonly used in the clinical setting, a diuretic (DIU) and an ACE inhibitor (CEI). Methods and Results Dahl salt-sensitive rats (DS) given high dietary salt (4% NaCl) developed hypertension (systolic blood pressure [SBP], 218±9 versus 147±3 mm Hg in DS given 0.5% NaCl; P<.001), which was associated with impaired endothelium-dependent relaxations (EDRs) in aortic rings (ED50, 5.44±.18 versus 7.51±.10; P<.05) and mesenteric vessels (area under the curve, 299±11 versus ...
Abstract 9487: Implantation of Scaffold-Free Tubular Tissue Using a Bio-3D Printer Augments Vascular Remodeling and Endothelialization
Authors: ManabuItoh, KoichiNakayama, RyoNoguchi, KeijiKamohara, KojirouFurukawa, KazuyoshiUchihashi, ShujiToda, Jun-ichiOyama, KoichiNode, ShigekiMorita
Journal: Circulation (2014)

Introduction: Small caliber synthetic vascular grafts are not clinically available. We developed a novel method to create scaffold-free tubular tissue from multicellular spheroids (MCS) using a “Bio-3D printer”-based system, which enables the creation of various three-dimensional structures pre-designed using a computer system. With this system, we created a tubular structure (Fig. 1), and studied its biological features. Methods: We made 1.5 mm in diameter scaffold-free tubular tissues from MCS (1.25 x 10[[Unable to Display Character: ⁷]] cells) composed of human umbilical vein endothelial cells (40%), human aortic smooth muscle cells (10%) and normal human dermal fibroblasts (50%) using a Bio-3D printer. The vessels were cultured in a perfusion system. We implanted grafts into the abdominal aortas of F344 nude rats, and assessed the flow by ultrasonography and performed histological examinations on the second (N=5) and fifth (N=5) days after implantation. Results: All grafts were patent. Remodelin...
Abstract 2118: Single-cell analysis reveals dynamic interaction between myeloma and bone marrow microenvironment
Authors: Jaewoong Min, Daeun Ryu, Hae-Ock Lee, Areum Jo, Woong-Yang Park, Seok Jin Kim, Kihyun Kim
Journal: Cancer Research (2018)

Abstract Multiple myeloma (MM) is a monoclonal plasma cell (MPC) malignancy primarily propagating in the bone marrow. To understand molecular signatures of MM in association with tumor microenvironment, we performed single-cell RNA sequencing for bone marrow biopsies from seven newly diagnosed myeloma patients. Clinical parameters of 7 MM patients differed, which were recapitulated in the single-cell transcriptome analysis. In comparison to the normal bone marrow from healthy donors, patient-specific monoclonal immunoglobulin gene expression as well as high levels of plasma cell markers distinguished the MPC clusters in myeloma patients. For other cell type identification, reference transcriptome for bone marrow immune cells were utilized. Major cell populations were determined to be monocytes, T cells, B cells, and erythroid cells. T cells manifested a mature phenotype encompassing from naïve to cytotoxic effector gene expression characteristics. B cells and erythroid cell populations were in various developmental stages. Monocytes demonstrated relatively constant gene expression throughout healthy donors to myeloma patients. In more advanced tumor stages, the composition and gene expression characteristics of MPCs and bone marrow immune cells were altered. Taken together, single cell RNA sequencing reveals gene expression characteristics of both myeloma and bone marrow immune cells which provide potential therapeutic strategies targeting tumor or immune compartment. Citation Format: Jaewoong Min, Daeun Ryu, Hae-Ock Lee, Areum Jo, Woong-Yang Park, Seok Jin Kim, Kihyun Kim. Single-cell analysis reveals dynamic interaction between myeloma and bone marrow microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2118.
Abstract 12900: Pressure Overload Induces Hypertrophy and Impaired Cardiac Function in Long-chain Fatty Acid Transporter CD36 Knockout Mice
Authors: Kazuhiro Nakatani, Daisaku Masuda, Toru Oka, Takeshi Okada, Ryota Kawase, Hajime Nakaoka, Tohru Ohama, Makoto Nishida, Issei Komuro, Shizuya Yamashita
Journal: Circulation (2013)

Background:  CD36 is an important transporter of long-chain fatty acids (LCFA) in the myocardium. We previously reported that CD36-deficient patients demonstrate a marked reduction of myocardial uptake of LCFA, while myocardial glucose uptake is compensatorily increased, and are often accompanied by cardiomyopathy. However, its molecular mechanisms and functional role of CD36 in the myocardium remain unknown.   Aim:  To explore the pathophysiological role of CD36 in the heart, we analyzed CD36 knockout (KO) mice at the baseline and under the pressure overload.   Methods:  Using wild type (WT) and KO mice at 7-10 weeks(wks) old, we performed transverse aortic constriction (TAC) to generate pressure overload and analyzed cardiac functions by echocardiography. To assess cardiac hypertrophy and fibrosis, histological and molecular analyses were performed at 2 and 4 wks after TAC.   Results:  At the baseline, there were no significant differences in left ventricular wall thickness and left ventricular fractional shortening (LVFS) between KO and WT mice. By applying a TAC for 4 wks, the survival rate was significantly lower in KO than that in WT mice (30.0% vs 85.7%, P=0.0018). At 2wks after TAC, KO mice showed significantly higher heart weight (HW) to tibia length (TL) ratio than that of WT (HW/TL;10.4±1.0 mg/mm vs 8.4±0.8 mg/mm, P=0.003). We also observed significantly larger cross-sectional area of cardiomyocytes in KO than that of WT, suggesting that hypertrophic response of KO mice was more marked than WT mice. KO mice with TAC showed more enhanced phosphorylation of S6 ribosomal protein compared to WT mice with TAC, suggesting that protein synthesis in KO mice was more enhanced than that in WT mice. KO mice with TAC showed increased lung weight (LW) to TL ratio and singnificantly reduced LVFS rather than WT with TAC (LW/TL; 13.9±5.7mg/mm vs 9.2±2.0mg/mm, P=0.069, FS; 24.1±1.1% vs 34.9±3.0%, P=0.00007), suggesting that pressure overload induced early systolic dysfunction in KO mice even at 2 wks after TAC, when WT mice showed compensatory cardiac hypertrophy.   Conclusion:  The LFCA transporter CD36 plays important roles regulating cardiac hypertrophy and function, and deficiency of CD36 causes cardiac dysfunction in the pressure overload condition.
Abstract 10383: Comparative Assessment of Medical Therapy, PCI, or CABG on Clinical Outcomes in Diabetic Patients With Stable CAD According to Coronary Angiography and Left Ventricular Function: Patient-level Meta-analysis of the BARI-2D, COURAGE, and FREEDOM Trials
Authors: G. B. John Mancini, Michael E Farkouh, Bernard R Chaitman, William E Boden, Robert L Frye, Pamela M Hartigan, Helen Vlachos, Flora S Siami, Mandeep S Sidhu, Vera A Bittner, Valentin Fuster, Maria M Brooks
Journal: Circulation (2015)

Introduction: The benefits of optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery have been evaluated in patients with Type 2 Diabetes Mellitus (T2DM) and stable coronary artery disease (CAD) but analyses have not been stratified by detailed angiographic CAD burden or left ventricular ejection fraction (LVEF). Methods: A patient-level meta-analysis was undertaken among T2DM patients enrolled in COURAGE, BARI 2D and FREEDOM to assess the impact of randomization to OMT, PCI + OMT, or CABG + OMT on a composite end-point of Death/MI/Stroke and stratified by LVEF (≥ 50%, &lt; 50%), 1, 2 or 3 vessel disease (VD) (% diameter stenosis ≥ 50%) and presence or absence of proximal left anterior descending (pLAD) disease. Hazard ratios (HR) for treatment groups were calculated from Cox regression models including all patients adjusting for trial and revascularization stratum in BARI 2D. Multivariable adjustment for risk factors was performed as a sensitivity analysis. Results: There were 5,034 patients included in the analysis (BARI 2D: n=2,368, COURAGE: n=766, FREEDOM: n=1,900) of whom 17% had LVEF &lt; 50%, 29% had pLAD, and 77% had 2 or 3 VD. A total of 1,591 patients were randomized to OMT alone, 2,118 to PCI + OMT, and 1,325 to CABG + OMT. There were 1,116 events during a median 4.5 year follow-up. There was no significant effect on outcomes with OMT vs PCI + OMT irrespective of LVEF, presence/absence of pLAD and number of VD. By contrast, CABG + OMT significantly reduced the risk of Death/MI/Stroke in patients with 2 or 3 VD, irrespective of LVEF and presence/absence of pLAD (see Table). Results were similar with multivariable adjustment. Conclusions: In patients with T2DM and stable CAD, OMT alone appears to be as effective as PCI + OMT while CABG + OMT significantly reduces cardiovascular events in those with multivessel CAD, irrespective of LVEF or presence of pLAD.
Abstract 2490: Characterization of the role of DPPA3 in stemness regulation in hepatocellular carcinoma by DNA methylation
Authors: Qian Yan, Yu Zhang, Dandan Yu, Ngar Woon Kam, Xin-Yuan Guan
Journal: Cancer Research (2018)

Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers in the world with a very poor prognosis, which is closely associated with cancer stem cell (CSC). Global RNA-sequencing was used in different developmental stages of hepatocytes, including embryonic stem cell, endoderm, liver progenitor, and premature hepatocyte, as well as two pairs of nontumor and tumor tissues from HCC patients. We found that Developmental Pluripotency Associated 3 (DPPA3) was highest expressed in the stage of liver progenitor cells, and was down-regulated along with development. In HCC patients, DPPA3 was expressed in less than 1% tumor cells, while no staining was detected in normal counterparts. Functional assays revealed that DPPA3 overexpression increased HCC cells proliferation rate, the ability of foci formation and colony formation in soft agar, as well as migration and invasion. Furthermore, DPPA3 significantly increased HCC cells sphere formation frequency and sensitivity to chemotherapeutic agent including cisplatin, 5-Fu, and Sorafenib. In order to investigate the role of DPPA3 in CSC maintenance and stemness regulation in HCC, whole genome methylation sequencing was applied to compare methylation status between DPPA3- and empty vector-transfected cells. Results showed that DPPA3 reduced CG methylation level within functional regions in the genome. Of the 541 differentially methylated regions, the majority of them were involved in developmental process and cell differentiation. Overall, our findings give a novel insight into how methylation regulation controls the fate of cancer stem cells. Citation Format: Qian Yan, Yu Zhang, Dandan Yu, Ngar Woon Kam, Xin-Yuan Guan. Characterization of the role of DPPA3 in stemness regulation in hepatocellular carcinoma by DNA methylation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2490.
Hypersensitivity pneumonitis: Antigen diversity and disease implications
Authors: R. Nogueira, N. Melo, H. Novais e Bastos, N. Martins, L. Delgado, A. Morais, P. C. Mota
Journal: Pulmonology (2018)

Hypersensitivity pneumonitis (HP) is an immune-mediated syndrome triggered by inhalation of a wide variety of allergens, to which an individual has previously been sensitized. More than 200 agents responsible for the disease have already been identified; however, HP occurs only in a small number of individuals exposed to causal antigens. The present report provides an overview of the role of antigen role in HP, highlighting its diversity, research methods, and prevention strategies, as well as the impact on disease prognosis following elimination of antigen. HP is an underdiagnosed disease and, therefore, it is difficult to accurately estimate its incidence. Triggering antigens can be divided into six broad categories: bacteria, fungi, mycobacteria, animal and plant proteins, chemicals, and metals, represented by disease prototypes. The identification of causal antigen is a major challenge; it is impossible to obtain in about 30-60% of cases. The acute form of HP, with early detection and immediate eviction of causal antigen, tends to have an excellent prognosis. In the chronic form, partial recovery of disease is still possible; however, some cases tend to progress to fibrosis, even after removal from exposure. In conclusion, HP diagnosis should be based on a proactive search for potential antigen sources, although their identification is hampered by the lack of standardized methods of demonstrating the specific antigen sensitization. Antigen avoidance is a critical determinant in disease prognosis.
Abstract 18742: Exercise Echocardiography with Speckle-Tracking Derived Strain and Strain-Rate Analysis Allows Detection of Heart Transplant Recipients with Focal Coronary Stenoses
Authors: ShwanHussein, MichaelDandel, RolandHetzer
Journal: Circulation (2014)

Background: Transplant vasculopathy (TVP) is a major cause of graft failure after heart transplantation (HTx). Coronary angiography (CA) is necessary for TVP diagnosis but TVP surveillance by frequent angiographies is risky, especially for patients with renal dysfunction. Timing of CA by non-invasive methods especially by stress echocardiography (stressecho) thus appears necessary. Unfortunately, visual echo assessment of cardiac wall motion is highly operator dependent and allows only limited evaluation of radial deformation and no assessment of longitudinal shortening. This study assessed the usefulness of strain imaging for detection of exercise-induced left ventricle (LV) myocardial contraction abnormalities. Methods: HTx patients with known and unknown TVP (n = 20) underwent exercise stress-echo before their routine follow-up CA. A cohort of 20 healthy persons underwent the same stress-echo investigation. In all patients, the two-dimensional (2D) echo-loops acquired at unloaded phase, low load, peak ...
Sex, Age, Cardiovascular Risk Factors, and Coronary Heart Disease
Authors: PekkaJousilahti, ErkkiVartiainen, JaakkoTuomilehto, PekkaPuska
Journal: Circulation (1999)

Background—Coronary heart disease (CHD) is markedly more common in men than in women. In both sexes, CHD risk increases with age, but the increase is sharper in women. We analyzed the extent to which major cardiovascular risk factors can explain the sex difference and the age-related increase in CHD risk. Methods and Results—The study cohort consists of 14 786 Finnish men and women 25 to 64 years old at baseline. The following cardiovascular risk factors were determined: smoking, serum total cholesterol, HDL cholesterol, blood pressure, body mass index, and diabetes. Risk factor measurements were done in 1982 or 1987, and the cohorts were followed up until the end of 1994. The Cox proportional hazards model was used to assess the relation between risk factors and CHD risk. CHD incidence in men compared with women was ≈3 times higher and mortality was ≈5 times higher. Most of the risk factors were more favorable in women, but the sex difference in risk factor levels diminished with increasing age. Differen...
Influence of sleep on developing brain functions and structures in children and adolescents: A systematic review
Authors: Caroline Dutil, Jeremy J. Walsh, Ryan B. Featherstone, Katie E. Gunnell, Mark S. Tremblay, Reut Gruber, Shelly K. Weiss, Kimberly A. Cote, Margaret Sampson, Jean-Philippe Chaput
Journal: Sleep Medicine Reviews (2018)
Abstract 19540: US Center Variability in the Incidence of Stroke for the Berlin Heart EXCOR Pediatric Ventricular Assist Device
Authors: Christopher S Almond, Angela Lorts, Joseph W Rossano, Lori C Jordan, Christina VanderPluym, Jack F Price, Kevin P Daly, Katsuhide Maeda, Andrew Y Shin, David N Rosenthal
Journal: Circulation (2015)

Background: Ventricular assist device (VAD)-related stroke is an important performance benchmark for adult VAD programs. No benchmarks are available for pediatric VAD programs where the stroke rate is higher. We sought to describe center variability in the stroke rate for the Berlin Heart EXCOR® Pediatric VAD, the most commonly used durable VAD in US children, to support pediatric VAD quality improvement efforts. Methods: All children age &lt;18 years supported with a Berlin Heart EXCOR Pediatric VAD at a site participating in the EXCOR IDE or FDA Post-Approval Study were identified using the Sponsor’s database. The incidence of neurological dysfunction, defined by INTERMACS criteria, was estimated for patients at centers with at least 300 support days. Results: Between 2007 and March 2014, a total of 320 children underwent implantation of a Berlin Heart EXCOR Pediatric VAD at 42 centers, of which 271 patients at 25 centers met the study inclusion criteria. The baseline characteristics of the cohort have been reported previously. Overall, there were a total of 64 neurological dysfunction episodes in 53 unique patients over 20,875 days of support, yielding an overall stroke incidence of 0.31 events per 100 days of support and a prevalence of 19%. Centers varied considerably (ten-fold) in their incidence rate of stroke ranging from 0 events to 1.7 events per 100 days of support (Figure). Among 13 centers with at least 10 total implants (totaling 205 patients over 14,405 support days), the overall stroke prevalence was 20% (range 6 to 46%) (Incidence rate 0.33 events per 100 days of support). Centers with ≥10 implants did not have fewer strokes than lower volume centers (P=0.30). Conclusion: The incidence of stroke among pediatric VAD centers using the Berlin Heart EXCOR Pediatric VAD was 0.31 events per day of support and varied considerably across pediatric centers. These data may be useful for developing performance benchmarks for neurological dysfunction in pediatric VAD support.
Distinct Patterns of Transforming Growth Factor-β Isoform and Receptor Expression in Human Atherosclerotic Lesions
Authors: AlexBobik, AlexAgrotis, PeterKanellakis, RodneyDilley, AnatolyKrushinsky, VladimirSmirnov, EduardTararak, MelanieCondron, GinaKostolias
Journal: Circulation (1999)

Background—Some animal studies suggest that transforming growth factor-β (TGF-β) protects vessels from atherosclerosis by preventing intima formation, but others indicate a role in vessel proteoglycan accumulation and lipoprotein retention. To distinguish between these possibilities in humans, immunohistochemical studies were performed examining the coexpression of TGF-β isoforms and the TGF-β receptors ALK-5 and TβR-II in aorta during the various stages of atherosclerotic lesion development. Methods and Results—The spatial relationships between TGF-β1, TGF-β3, ALK-5, and TβR-II expression were compared in aortic segments from 21 subjects. Nonatherosclerotic intima contained predominantly TGF-β1, low concentrations of TβR-II, and barely detectable amounts of ALK-5. In contrast, fatty streaks/fibrofatty lesions contained high concentrations of both TGF-β isoforms. Smooth muscle cells (SMCs), macrophages, and foam cells of macrophage and SMC origin contributed to these high levels. These lesions also contai...
Metformin Prevents Progression of Heart Failure in Dogs
Authors: HideyukiSasaki, HiroshiAsanuma, MasashiFujita, HiroyukiTakahama, MasakatsuWakeno, ShinIto, AkikoOgai, MasanoriAsakura, JiyoongKim, TetsuoMinamino, SeijiTakashima, ShojiSanada, MasaruSugimachi, KazuoKomamura, NaokiMochizuki, MasafumiKitakaze
Journal: Circulation (2009)

Background— Some studies have shown that metformin activates AMP-activated protein kinase (AMPK) and has a potent cardioprotective effect against ischemia/reperfusion injury. Because AMPK also is activated in animal models of heart failure, we investigated whether metformin decreases cardiomyocyte apoptosis and attenuates the progression of heart failure in dogs. Methods and Results— Treatment with metformin (10 μmol/L) protected cultured cardiomyocytes from cell death during exposure to H2O2 (50 μmol/L) via AMPK activation, as shown by the MTT assay, terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling staining, and flow cytometry. Continuous rapid ventricular pacing (230 bpm for 4 weeks) caused typical heart failure in dogs. Both left ventricular fractional shortening and left ventricular end-diastolic pressure were significantly improved in dogs treated with oral metformin at 100 mg · kg−1 · d−1 (n=8) (18.6±1.8% and 11.8±1.1 mm Hg, respectively) compared with dogs receiving vehicle (n=...
Transcriptomic signature associated with carcinogenesis and aggressiveness of papillary thyroid carcinoma
Authors: Huajing Teng, Fengbiao Mao, Jialong Liang, Meiying Xue, Wenqing Wei, Xianfeng Li, Kun Zhang, Dongdong Feng, Baoguo Liu, Zhongsheng Sun
Journal: Theranostics (2018)

Papillary thyroid carcinoma (PTC) is the fastest-growing disease caused by numerous molecular alterations in addition to previously reported DNA mutations. There is a compelling need to identify novel transcriptomic alterations that are associated with the pathogenesis of PTC with potential diagnostic and prognostic implications.