tbuckley/cabot-search huggingface dataset:
Treatment of Macular Edema Due to Central Retinal Vein Occlusion
Authors: Neil M. Bressler
Journal: JAMA (2017)

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Inhibition of IL6 trans-signaling leads to gut microbiota-dependant mature-onset obesity and metabolic syndrome
Authors: T. Lanton, O. Levkovitch, S. Perless, Y. Tam, J. Rachmilewitz, R. Abramovitch, S. Rose-John, E. Galun, J.H. Axelrod
Journal: Journal of Hepatology (2017)
Abstract 6147: A Tissue Stem Cell Niche Regulates Bicuspid Aortic Valve Disease
Authors: Nalini M Rajamannan
Journal: Circulation (2008)

Bicuspid aortic valve disease is the most common congenital cardiac malformation and indication for surgery for aortic valve patients. The age of onset for the development of stenosis is earlier in bicuspid aortic valves than tricuspid aortic valves. Understanding the cellular mechanisms of this valve lesion, will help to develop novel approaches towards slowing disease progression. This study hypothesizes that bicuspid aortic valve disease develops secondary to a tissue stem cell niche to activate a cross-talk mechanism which induces Notch1 cleavage and Lrp5 mediated bone formation specific to the bicuspid aortic valve. Human ex vivo bicuspid valves versus control aortic valves were tested for Notch1 expression by RTPCR, Western Blot and Immunohistochemistry. eNOS null bicuspid mice: control (n=20), cholesterol (n=20), cholesterol + Atorvastatin (n=20), were tested for the development of aortic stenosis by Visual Sonics Echo, Immunohistochemistry for Notch1, Wnt, Lrp5, Osteocalcin, PCNA and RTPCR for Notch1, Lrp5, Cbfa1, Osteocalcin. In vitro studies were performed to characterize Wnt secretion from aortic valve endothelial cells and gene expression for Notch1, Lp5 and osteocalcin from the valve myofibroblast cells. This study characterizes the secretion of Wnt3a (&gt;300-fold, p&lt;0.01) from aortic valve endothelium in the presence of abnormal nitric oxide regulation and lipids as measured by eNOS enzymatic activity and tissue nitrite levels. Osteoblastogenesis in the adjacent myofibroblast cell is activated via Notch1 cleavage(p&lt;0.001) and upregulation of the Wnt3a/Lrp5 receptor. Human ex vivo valves express Notch1 cleavage as compared to normal valves from heart transplant(p&lt;0.01). Cholesterol treated eNOS mice develop severe stenosis with cleavage of Notch1, increase in Lrp5, Wnt3a, cyclin, Cbfa1, and Osteopontin,(3-fold increase(p&lt;0.01) which was not present in the controls and normalized in the statin treated valves. Targeting the Notch1/Wnt3a/Lrp5 pathway in bicuspid valvular calcification presents a novel approach towards treating this disease. The importance of this cross talk mechanism is demonstrated in three models of aortic valve disease and will have important clinical implications. This research has received full or partial funding support from the American Heart Association, AHA National Center.
Acute changes in endothelial function with cisplatin among germ cell tumor (GCT) patients (Pts).
Authors: Darren Richard Feldman, Erin Patricia Jacobsen, Kaitlin Woo, Richard Steingart, Martin Fleisher, Sujata Patil, Maryann Carousso, Shelly Laguerre, Talma D. Morales, Joel Sheinfeld, Robert J. Motzer, George J. Bosl, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2014)

9587 Background: We hypothesized that the increased risk of cardiovascular disease (CVD) in GCT pts following cisplatin-based chemotherapy (CBCT) may be due to endothelial damage. Methods: In this pilot study, men age ≥18 with GCT, no prior chemotherapy (CT) or radiation, and no history of CVD were enrolled to the CT group (CG) if CBCT was planned and to the surgery group (SG) if only surgical management (orchiectomy +/- RPLND) was planned. Endo-PAT2000, a noninvasive method of quantifying endothelial function, was used to measure the peripheral arterial tonometry reactive hyperemia index (PAT-RHI). Lower values correlate with endothelial dysfunction. Circulating endothelial cells (CECs) were quantified by immunomagnetic capture as a secondary endpoint. Covariates included hypertension, smoking status, dyslipidemia, diabetes, and fasting lipids, glucose, HbA1C, and testosterone. Measurements were obtained at time points T1-T5 for CG pts and T1, T2 and T5 for SG pts (Table). Nonparametric tests were used to compare PAT-RHI values at T1 (baseline) vs later time points in each group and at T1, T2, and T5 across the two groups. Results: Among 22 CG pts (median age 29, range 21-49), PAT-RHI was non-significantly lower at T2 (after the 1st dose of CT) and T5 (14-34 weeks post T1) vs T1. For SG pts (n=20, median age 35, range 25-45), PAT-RHI was non-significantly higher at T2 and T5 vs T1. However, PAT-RHI was significantly lower in CG men vs SG men at T2 and T5 (Table). There was also a trend toward greater decreases in PAT-RHI values at T2 vs T1 (p=0.08), T5 vs T1 (p=0.07), and T5 vs T3 (p=0.07) for CG pts with ≥1 (n=12) vs. no CVD risk factors (n=8). For CG men, median number of CECs/7.5mL was lower at T2 (18) vs T1 (35; p<0.01) and borderline higher at T5 (33) vs T2 (p=0.05). There were no differences in CECs over time for SG men. Conclusions: CBCT may acutely cause endothelial dysfunction. Further study with a larger sample size and longer follow-up is warranted. Clinical trial information: 01453660.Median PAT-RHI. T1 (C1D1 pre-CT) T2* (C1D1 post-CT)# T3 (C1D2 pre-CT) T4 (C1D5 post-CT) T5* (End of CT)£ CG N=20¥ 2.00 1.67 2.13 1.99 1.83 SG N=20 1.87 2.22 -- -- 2.31 Abbreviations: C, cycle; D, day. *p=0.03 for comparison of CG vs SG at both T2 and T5. #2-5 hrs post T1 for SG pts. ¥22 enrolled, 20 evaluable. £14-34 wks post T1.
Prevalence of combined PNPLA3 and GCKR variant genotype is increased in patients with risk factors for alcoholic or non-alcoholic liver disease who have clinically significant serum procollagen III levels
Authors: J.I. Grove, P. Thiagarajan, S. Astbury, R. Harris, T. Delahooke, T.R. Card, I.N. Guha, G.P. Aithal
Journal: Journal of Hepatology (2017)
A Freeze‐Concentration and Polyampholyte‐Modified Liposome‐Based Antigen‐Delivery System for Effective Immunotherapy
Authors: Sana Ahmed, Satoshi Fujita, Kazuaki Matsumura
Journal: Advanced Healthcare Materials (2017)

Immunotherapy is an exciting new approach to cancer treatment. The development of a novel freeze‐concentration method is described that could be applicable in immunotherapy. The method involves freezing cells in the presence of pH‐sensitive, polyampholyte‐modified liposomes with encapsulated ovalbumin (OVA) as the antigen. In RAW 264.7 cells, compared to unfrozen, freeze‐concentration of polyampholyte‐modified liposomes encapsulating OVA resulted in efficient OVA uptake and also allowed its delivery to the cytosol. Efficient delivery of OVA to the cytosol was shown to be partly due to the pH‐dependence of the polyampholyte‐modified liposomes. Cytosolic OVA delivery also resulted in significant up‐regulation of the major histocompatibility complex class I pathway through cross‐stimulation, as well as an increase in the release of IL‐1β, IL‐6, and TNF‐α. The results demonstrate that the combination of a simple freeze‐concentration method and polyampholyte‐modified liposomes might be useful in future immunotherapy applications.
Abstract B45: Insights into the anti-prostate cancer activity of pterostilbene
Authors: Mai F. Tolba, Hany A. Omar
Journal: Cancer Research (2017)

Abstract Castration-resistant prostate cancer (PC) is one of the most challenging cancers with limited therapeutic options. Angiogenesis is a key mechanism required for the progression of advanced metastatic stage of PC. Interference with angiogenesis halts prostate tumor progression and metastases. Estrogen receptor alpha (ER-α) is upregulated in PC compared to normal tissues. ER-α is implicated in tumor angiogenesis through activating vascular endothelial growth factor (VEGF) transcription. Pterostilbene (PT) is an active component of blueberries that exhibits anti-proliferative and antimetastatic effects in PC. The impact of PT on pro-angiogenic signals is not known. The current study tested the hypothesis that PT exhibits sensitizes prostate cancer (PC) cells to chemotherapy. We also examined the underlying mechanisms by which PT exhibits cytotoxic effects in PC with special emphasis on ER-α, Akt activity and angiogenesis signals. PT is cytotoxic against LNCaP, DU-145 and PC-3 with IC50 of 33.76, 41.17 and 58.9 µM. PT synergized doxorubicin in both LNCaP and PC-3 cells. Molecular docking indicated that PT interacts with ER-α active site with a comparable affinity to estradiol. Since, ER-α is implicated in the progression of PC. The effect of PT on PC migration and invasion was investigated and results showed significant reduction in both functions. PT suppressed ER-α expression, ER-α(Ser-167) and Akt(Ser473) phosphorylations in PC-3 cells. PT opposed the release of the pro-angiogenic growth factors VEGF, IGF-1 and TGF-β by 41.5, 36.5 and 28.8% (P&amp;lt;0.05). Our findings suggest that PT could serve as a promising antiangiogenic therapy/ adjuvant for the management of advanced stage PC. Citation Format: Mai F. Tolba, Hany A. Omar. Insights into the anti-prostate cancer activity of pterostilbene. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B45.
Tobacco use among people living with HIV: analysis of data from Demographic and Health Surveys from 28 low-income and middle-income countries
Authors: Noreen D Mdege, Sarwat Shah, Olalekan A Ayo-Yusuf, James Hakim, Kamran Siddiqi
Journal: The Lancet Global Health (2017)

BackgroundTobacco use among people living with HIV results in excess morbidity and mortality. However, very little is known about the extent of tobacco use among people living with HIV in low-income and middle-income countries (LMICs). We assessed the prevalence of tobacco use among people living with HIV in LMICs.MethodsWe used Demographic and Health Survey data collected between 2003 and 2014 from 28 LMICs where both tobacco use and HIV test data were made publicly available. We estimated the country-specific, regional, and overall prevalence of current tobacco use (smoked, smokeless, and any tobacco use) among 6729 HIV-positive men from 27 LMICs (aged 15–59 years) and 11 495 HIV-positive women from 28 LMICs (aged 15–49 years), and compared them with those in 193 763 HIV-negative men and 222 808 HIV-negative women, respectively. We estimated prevalence separately for males and females as a proportion, and the analysis accounted for sampling weights, clustering, and stratification in the sampling design. We computed pooled regional and overall prevalence estimates through meta-analysis with the application of a random-effects model. We computed country, regional, and overall relative prevalence ratios for tobacco smoking, smokeless tobacco use, and any tobacco use separately for males and females to study differences in prevalence rates between HIV-positive and HIV-negative individuals.FindingsThe overall prevalence among HIV-positive men was 24·4% (95% CI 21·1–27·8) for tobacco smoking, 3·4% (1·8–5·6) for smokeless tobacco use, and 27·1% (22·8–31·7) for any tobacco use. We found a higher prevalence in HIV-positive men of any tobacco use (risk ratio [RR] 1·41 [95% CI 1·26–1·57]) and tobacco smoking (1·46 [1·30–1·65]) than in HIV-negative men (both p<0·0001). The difference in smokeless tobacco use prevalence between HIV-positive and HIV-negative men was not significant (1·26 [1·00–1·58]; p=0·050). The overall prevalence among HIV-positive women was 1·3% (95% CI 0·8–1·9) for tobacco smoking, 2·1% (1·1–3·4) for smokeless tobacco use, and 3·6% (95% CI 2·3–5·2) for any tobacco use. We found a higher prevalence in HIV-positive women of any tobacco use (RR 1·36 [95% CI 1·10–1·69]; p=0·0050), tobacco smoking (1·90 [1·38–2·62]; p<0·0001), and smokeless tobacco use (1·32 [1·03–1·69]; p=0·030) than in HIV-negative women.InterpretationThe high prevalence of tobacco use in people living with HIV in LMICs mandates targeted policy, practice, and research action to promote tobacco cessation and to improve the health outcomes in this population.FundingSouth African Medical Research Council and the UK Medical Research Council.
Efficacy and safety of Direct-Acting Antiviral Drugs in patients with thalassemia major and crhonic hepatitis C: a preliminary report of a single italian center
Authors: L. Ponti, R. Origa, D. Murgia, C. Dessì, R. Canu, M.L. Foschini, G.B. Leoni, M. Morittu, P. Moi, R. Ganga
Journal: Journal of Hepatology (2017)
Worsening of serum lipid profile after direct acting antiviral treatment
Authors: S. Gitto, A.F.G. Cicero, E. Loggi, M. Giovannini, F. Conti, E. Grandini, V. Guarneri, A. Scuteri, G. Vitale, C. Cursaro, C. Borghi, P. Andreone
Journal: Journal of Hepatology (2017)
Genetic ablation of pannexin1 protects against acetaminophen-induced hepatotoxicity in mice
Authors: M. Maes, J.L. Weemhoff, J. Willebrords, S.C. Yanguas, T.C. da Silva, I.V.A. Pereira, M. Lebofsky, H. Jaeschke, B. Cogliati, M. Vinken
Journal: Journal of Hepatology (2017)
Abstract 147: The AMP-Activated Protein Kinase (AMPK) -Dependent Regulation of Endothelial Cell Angiotensin-Converting Enzyme (ACE) Expression Involves p53 and MicroRNA-143/145
Authors: Ingrid Fleming, Karin Kohlstedt
Journal: Circulation Research (2012)

High ACE-levels are associated with cardiovascular disease development, but little is known about its expressional regulation. ACE is a target of the miR143/145-cluster in murine vascular smooth muscle cells and can also be affected by AMPK activation in monocytes. Since shear stress activates AMPK in endothelial cells, we determined whether flow alters ACE expression and the involvement of AMPK and miR143/145. Shear stress decreased ACE expression in human endothelial cells, an effect prevented by downregulating (siRNA) the AMPK α2 subunit, but not AMPKα1.Pharmacological AMPK activation also suppressed endothelial ACE expression and AMPKα2 -/- (not AMPK α 1 -/- ) mice expressed significantly higher ACE levels in different arteries than wild-type littermates. While basal blood pressure was comparable in AMPKα2 +/+ and AMPKα2 -/- mice, AMPKα2 -/- mice were more sensitive to the hypotensive effect of the ACE-inhibitor ramipril and demonstrated an impaired bradykinin-induced hindlimb-vasodilatation. The suppressive effect of the miR-143/145-cluster on human endothelial ACE was confirmed by overexpression of pre-miR143/145 and AMPKα2 downregulation decreased miR143/145-levels . Since f low increased mature and pre-miR-143/145 levels, but not pri-miR143/145 levels, we focused on the post-transcriptional regulation of miR143/145 by AMPK via p53 . Indeed, p53 expression and phosphorylation (Ser15) increased in response to shear stress, and were sensitive to treatment with AMPK α 2 (but not AMPK α 1) siRNA. The data indicate that, AMPKα2 suppresses endothelial ACE expression via p53 activation and upregulation of miR143/145. Since AMPK (and p53) dysregulation is associated with several diseases (e.g. diabetes, cancer), their effect on miRNA143/145 and ACE might mediate disease-associated cardiovascular disorders.
Grading oesophageal varices in clinical practice: an inter-rater reliability study using high resolution endoscopy recordings
Authors: W. Fateen, S.S. Sami, K. Ragunath, E.A. Wilkes, M. James, J. Ortiz-Fernández-Sordo, J.R. White, A. Khanna, M. Coletta, S. Samuel, G.P. Aithal, I.N. Guha
Journal: Journal of Hepatology (2017)
Abstract IA12: Low rates of protein synthesis in hematopoietic stem cells are determined partly by relatively high levels of hypophosphorylated eIF4E-BP
Authors: Robert A. J. Signer, Le Qi, Sean J. Morrison
Journal: Cancer Research (2017)

Abstract Hematopoietic stem cells (HSCs) synthesize less protein per hour, on average, than other hematopoietic progenitors. Limited protein synthesis appears to be a widely shared feature of adult stem cells. The low rate of protein synthesis is necessary for HSC maintenance as genetic changes that modestly increase or decrease protein synthesis each impair HSC function. However, the mechanisms that suppress protein synthesis in adult stem cells remain unexplored. We assessed a number of potential mechanisms and found that the reduced rate of protein synthesis in HSCs as compared to other hematopoietic progenitors is not explained by differences in proteasome activity, cell division rate, or mRNA content. However, adult bone marrow HSCs had increased amounts of hypophosphorylated eukaryotic initiation factor 4E binding protein1 (eIF4E-BP1) and eIF4E-BP2 as compared to other hematopoietic progenitors. Since unphosphorylated eIF4E-BP negatively regulates protein synthesis, this raised the possibility that eIF4E-BPs hypophosphorylation suppresses protein synthesis in HSCs. Consistent with this, genetic inactivation of eIF4E-BP1 and eIF4E-BP2 increased protein synthesis in HSCs and impaired their reconstituting activity. These findings provide insight into the mechanisms that promote adult tissue regenerative capacity by attenuating protein synthesis in stem cells. Citation Format: Robert A. J. Signer, Le Qi, Sean J. Morrison. Low rates of protein synthesis in hematopoietic stem cells are determined partly by relatively high levels of hypophosphorylated eIF4E-BP. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr IA12.
Human Immunodeficiency Virus
Authors: David M. Phillips
Journal: New England Journal of Medicine (1995)

Figure 1. Transmission electron microphotographs of the human immunodeficiency virus (HIV) are shown. In Panel A, four viruses are shown budding from the surface of a cultured human lymphoma cell (×63,000). Like other enveloped viruses, HIV is unable to make lipids. The virus uses the lipid component of the membrane of the host cell as part of its envelope. During assembly at the cell surface, the viral envelope incorporates viral glycoprotein into the cell membrane. The membrane proteins of the cell are left behind when the virus buds off. Mature viruses are shown in Panel B (×50,000). The central dark . . .
Autonomic function is impaired across the spectrum of NAFLD
Authors: D. Houghton, P. Zalewski, S. Cassidy, C. Thoma, K. Hallsworth, L. Avery, A.B. Lukowska, T. Hardy, A.D. Burt, S. Masson, C. Day, S. McPherson, Q.M. Anstee, J.L. Newton, M.I. Trenell
Journal: Journal of Hepatology (2017)
A review of clinicopathologic characteristics, therapy, and outcomes of 22 patients with aggressive B-cell lymphoma.
Authors: Michael Jaglal, Deniz Peker, Celeste M. Bello, Bijal D. Shah, Lubomir Sokol, Ling Zhang, Eduardo M. Sotomayor, Jianguo Tao, Jennifer L. Cultrera
Journal: Journal of Clinical Oncology (2012)

e21123 Background: B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL) or Burkitt like lymphoma is a high grade lymphoma that is associated with a high proliferation index and a complex karyotype mostly involving MYC and BCL-2 genes, so called “double hit” as well as BCL-6 or CYCLIND1 genes, so called “triple hit”. This high grade lymphoma shows an aggressive behavior for which the most appropriate therapeutic approach is yet to be established. Methods: This was a single center retrospective review of pts with a confirmed diagnosis of B cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL from 2006 to 2011. The definitive diagnosis in all cases was based on morphological and phenotypic features, and genetic abnormalities involving MYC, BCL-2, BCL-6, and or CYCLIND1. Clinicopathological data was extracted including age, gender, primary disease location, phenotypic subtype, genetic abnormalities by FISH, IPI scores, treatment regimens and survival data . Descriptive statistical analyses were utilized. Kaplan-Meier method was used to estimate OS and log rank test was used to compare the groups. All data were analyzed using SPSS version 20.0 statistical software. Results: 22 pts with &amp;quot;Double or Triple Hit&amp;quot; lymphomas were identified between 2006 and 2011. The age range at diagnosis was 33-87 years with median age of 66. 16 of 22 pts (73%) were ≥ 60 years old. Male to female ratio was 1.75 :1 (14:8). The median ECOG PS was 1. No pts had HIV. A majority of pts presented with extranodal disease 17 with only 5 pts presenting with nodal disease. The median survival of the entire cohort was 9 months with ranges 32 to 2 months. 16 of 22 pts (73%) are currently alive. In the cohort of pts that are currently alive, 10 was treated with RCHOP and 6 with RHyperCVAD. Pts who presented with CNS disease had a worse prognosis when compared to the entire cohort with a median overall survival of 6.5 months (p=0.016). Conclusions: RCHOP was the most utilized treatment regimen in the cohort of alive patients. CNS disease is associated with worse prognosis in patients with &amp;quot;Double or Triple Hit&amp;quot; lymphomas.
Muscle mass is a protector factor against low bone mineral density in hepatitis C
Authors: T. Bering, K.G.D. Diniz, M.P.P. Coelho, D.A. Vieira, M.M.S. Soares, A.M. Kakehasi, M.I.T. Correia, R. Teixeira, G.A. Rocha, L.D. Silva
Journal: Journal of Hepatology (2017)