tbuckley/cabot-search huggingface dataset:
Abstract P002: Gender Differences in Atrial Fibrillation Hospitalizations
Authors: SaharNaderi, YunWang, JoAnneFoody
Journal: Circulation (2014)

Background: While there are recognized gender differences in cardiovascular disease, little is known regarding the role of gender in atrial fibrillation (AF). We therefore sought to determine differences in characteristics of AF hospitalization between men and women. Methods: Data from the 2009-2010 Healthcare Cost and Utilization Project were used to model AF hospitalizations as a function of patient age and gender. Results: Of 192,846 AF hospitalizations, 50% of patients were female. Mean age was 74 years versus 66 years for men. Figure I shows AF hospitalizations stratified by age and gender. Women were less likely than men to have diabetes (24 vs 25%, p<0.001), chronic kidney disease (11.2 vs 12.2%, p<0.001), and obesity (12.2 vs 12.9%, p<0.001). They were more likely to have a history of stroke (2.0 vs 1.7%, p<0.001), hypertension (68.7 vs 62.5%, p<0.001), and depression (9.6 vs 5.4%, p<0.001). Females were more likely to be admitted from the emergency room (72.9 vs 66.6%, p<0.001), were hospitalized...
Use of Angiotensin Receptor Blockers and the Risk of Cancer
Authors: BjörnPasternak, HenrikSvanström, TorbjörnCallréus, MadsMelbye, AndersHviid
Journal: Circulation (2011)

Background—A recent meta-analysis of randomized trials suggested that use of angiotensin receptor blockers (ARBs) may be associated with a modestly increased risk of incident cancer, particularly lung cancer. Methods and Results—We linked individual-level data from Danish registries on filled drug prescriptions, diagnostic information, and covariates. In a nationwide cohort of new users of ARBs and angiotensin-converting enzyme inhibitors ≥35 years of age during 1998 to 2006, we compared incidence rates of all cancer, cancer subgroups by anatomic site, and cancer mortality. Among 107 466 ARB users, 3954 cases of cancer were detected during 312 753 person-years of follow-up compared with 6214 cases during 435 207 person-years of follow-up in 209 692 angiotensin-converting enzyme inhibitor users (adjusted rate ratio, 0.99; 95% confidence interval, 0.95 to 1.03). Cancer risk did not increase with increasing duration of ARB exposure (increase in rate ratio per year, 0.99; 95% confidence interval, 0.99 to 1.00...
Abstract 1285: Deep mutagenesis analysis on BRCA1 variants in high throughput DNA repair assays
Authors: Mariame Diabate, Alexandrea Adamovich, Tapahsama Banerjee, Michael Freitas, Jeffrey Parvin
Journal: Cancer Research (2018)

Abstract Genetic screening of Hereditary Breast and Ovarian Cancer (HBOC)-associated genes can aid in prevention of the onset of cancer by increased surveillance or preventative surgery if the genetic information is clear. Often, the genetic information is ambiguous since missense substitutions may be common in aggregate but individually these missense variants occur too infrequently for genetic segregation to be conclusive and are known as Variants of Unknown Significance (VUS). One commonly screened HBOC gene is BRCA1, with mutations found in 40-45% of hereditary breast cancer cases. The BRCA1 protein has the critical tumor suppressive function mediating homology-directed repair (HDR), which is used for the repair of double-stranded breaks (DSB) in DNA. Clinical mutant databases, such as ClinVar, contain the clinical classification of BRCA1, but, unfortunately, in many of these databases, most of the variants are classified as VUS or have conflicting data. We suggest that laboratory-based functional analysis can augment the genetic and clinical data, enabling the understanding of whether a specific variant is benign or pathogenic and predisposing to breast and ovarian cancer. We have developed a high-throughput method for analyzing the function of individual missense variants of BRCA1 in the DNA repair process. The goal is to have functional analysis for every possible amino acid substitution in BRCA1, and this will be publicly available for geneticists to consider when evaluating the likelihood of cancer predisposition an individual with a VUS in BRCA1. We have completed analysis of the amino-terminal RING domain, and we will present new results for the carboxy-terminal BRCT domain. We develop a computational pipeline that starts with sequence data from DNA repair assays to obtain a score for each variant. This pipeline will include statistical programs to evaluate the confidence level for these results, which will then be compared to the information provided in the ClinVar database. In summary, this work describes a computational framework for deconvoluting sequencing results of a high-throughput approach to measure the functional impact of each possible missense variant in the BRCT domain of BRCA1. Citation Format: Mariame Diabate, Alexandrea Adamovich, Tapahsama Banerjee, Michael Freitas, Jeffrey Parvin. Deep mutagenesis analysis on BRCA1 variants in high throughput DNA repair assays [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 1285.
Elective cholecystectomy after reversal of septic shock using multimodality endoscopic gallbladder drainage
Authors: Pietro Fusaroli, Marta Serrani, Sandro Sferrazza, Romano Linguerri, Elio Jovine, Andrea Lisotti
Journal: Endoscopy (2018)

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is considered an effective therapy for acute cholecystitis in patients who are unfit for surgery [1] [2] [3].
Diffusion-Weighted Magnetic Resonance Imaging Detects Vessel Wall Inflammation in Patients With Giant Cell Arteritis
Authors: Gabriele Ironi, Enrico Tombetti, Angela Napolitano, Marta Campolongo, Federico Fallanca, Elena Incerti, Maria Picchio, Lorenzo Dagna, Angelo A Manfredi, Luigi Gianolli, Alessandro Del Maschio, Francesco De Cobelli
Journal: JACC. Cardiovascular imaging (2018)
Abstract 5052: ID3 mediated vascular reprogramming of PCB exposed endothelial cells and its potential contribution to lung tumorigenicity
Authors: Mayur Doke, Jayanta Das, Quentin Felty
Journal: Cancer Research (2018)

Abstract ID3, a transcription regulator, has been shown to contribute to the aggressive spread of certain cancers by facilitating the generation of tumor blood vessels. Tumor vascular cells characterized as CD133+ endothelial stem/progenitor cells are associated with poor prognosis in lung cancer. Previously, we have shown that ID3 overexpression reprograms adult endothelial cells to acquire vascular stem markers including CD133. However, little is known regarding the molecular contribution of ID3 to tumor vascular reprogramming and how this may impact the aggressive growth of lung cancer. In the current project, we evaluated ID3 mediated vascular reprogramming upon polychlorinated biphenyl (PCB) exposure. This idea is consistent with the literature, which shows that PCBs accumulate in the human lung; PCBs produce pathological vascular remodeling; high levels of PCBs are found in human lung tissue; and epidemiological studies associating lung toxicity with PCBs. Recent studies identify PCB153 as one of the largest contributors for total PCB body burden in humans. Using human lung endothelial and smooth muscle cells, we exposed ID3 overexpressing and vector control cells to PCB153. We observed a significant increase in cell proliferation as determined by the BrdU incorporation assay and FACS analysis. Similarly, a 3D HuBiogel model, which mimics in vivo conditions, showed a significant increase in size and number of vascular spheres upon PCB153 treatment. Pluripotent vascular stem cells showed the loss of VE-cadherin and gain of MMP9, N-cadherin, and vimentin, which are markers of endothelial-mesenchymal transition. RNA-seq analysis showed that PCB153 exposed vascular stem cells had a significant increase in lncRNAs MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) and HIF1A-AS2. A combination of ChIP-seq and transcriptome analysis identified significantly up-regulated genes (HES1, WEE1, E2F2) and down-regulated genes (SMURF2, CDKN2C, SH2B3). Our findings suggest that ID3 mediates vascular reprogramming through transcriptional regulation of pluripotency factors and epigenetic regulating lncRNAs. ID3 may also serve as a novel diagnostic/prognostic indicator for evaluating chemical-induced vascular reprogramming. Its potential application may be useful in identifying individuals who are susceptible to aggressive lung cancer from exposure to vascular toxicants. Citation Format: Mayur Doke, Jayanta Das, Quentin Felty. ID3 mediated vascular reprogramming of PCB exposed endothelial cells and its potential contribution to lung tumorigenicity [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 5052.
Abstract 3269: Metformin to prevent metabolic syndrome associated with androgen deprivation therapy (ADT): Metabolic analysis from a placebo-controlled study of metformin in non-diabetic men initiating ADT for advanced prostate cancer (PCa)
Authors: Devalingam Mahalingam, Salih Hanni, Christos Fountzilas, Joel Michalek, John Sarantopoulos, Sureshkumar Mulampurath Achuthan Pillai, John Kuhn, Michael Pollak, Ian Thompson
Journal: Cancer Research (2018)

Abstract Background: ADT results in metabolic syndrome, characterized by hyperinsulinemia, insulin resistance and obesity. The hyperinsulinemia may result in ADT resistance; therefore preventing metabolic syndrome could have a therapeutic impact on PCa. Metformin decreases glucose &amp; insulin by inhibiting hepatic gluconeogenesis. There is preclinical evidence for additional antineoplastic activity due to mTOR inhibition secondary to AMPK activation. Methods: We analyzed serum and PBMC from a recently completed clinical study of men with advanced PCa on ADT that were randomized 1:1 to metformin at 500mg TID or color matched placebo. Subjects serum insulin/glucose, metformin levels, weight and waist circumference (WC) was assessed at baseline, week 12 and 28. The primary endpoint of study was the metabolic consequences of metformin vs placebo cohort. Secondary endpoints were PSA response and PBMC analysis of downstream target of mTOR, phospho-S6 kinase. Results: There were 36 evaluable men. The mean age on study was 68.4. Mean weight, WC and insulin at baseline in metformin cohort was 187 lbs, 41.14 cm and 10.03 mIU/L respectively, and 177.65 lbs, 40.52 cm and 8.02 mIU/L in placebo cohort. An increase in mean weight, WC and insulin levels was seen in both cohorts. At week 12 and 28, no statistical difference in weight, WC and insulin was observe in either cohort. Four men randomized to metformin had undetectable serum drug levels despite drug-diary suggesting compliance; excluding them did not result in significant metabolic change. Assessing efficacy, 50% in metformin and 53.3% in placebo cohort achieved undetectable PSA at week 28; difference not statistically significant. PBMC analysis demonstrated variable down-regulation of phospho-S6 kinase in the metformin cohort. Conclusion: This study detected no impact of MET addition to ADT on the risk of metabolic syndrome and no additional anti-tumor effects. Control of hyperinsulinemia related to diabetes by MET does not necessarily imply MET has a similar action on hyperinsulinemia due to ADT. Citation Format: Devalingam Mahalingam, Salih Hanni, Christos Fountzilas, Joel Michalek, John Sarantopoulos, Sureshkumar Mulampurath Achuthan Pillai, John Kuhn, Michael Pollak, Ian Thompson. Metformin to prevent metabolic syndrome associated with androgen deprivation therapy (ADT): Metabolic analysis from a placebo-controlled study of metformin in non-diabetic men initiating ADT for advanced prostate cancer (PCa) [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 3269.
Abstract 17462: Relevance of Regulatory T Cells to Gender Dimorphism in Pulmonary Hypertension
Authors: Rasa Tamosiuniene, Linh Nguyen, Ayala Luria, Joshua Sante, Toshie Saito, Marlene Rabinovitch, Norbert Voelkel, Aida Habtezion, Mark Nicolls
Journal: Circulation (2015)

Idiopathic Pulmonary Arterial Hypertension (IPAH) is a disease with female predominance. A growing body of evidence shows reciprocal relationship between sex steroids and the immune system. The aim of the present study was to determine whether the absence of Tregs with the presence of endogenous estrogen mediate the development of PH in a gender-specific manner and if protective signaling pathways of Tregs prevent gender dimorphism of PH susceptibility in T cell deficient animal model of PH. Methods and Results: in two utilized models of PH inbred Wag T cell deficient athymic (AT) nude male and female rats were given s/c SU5416 in normoxia or treated with chronic hypoxia (CH) for 21d. In IR experiments, AT rats received purified CD4+CD25+hi/Tregs. We also tested the effect of murine/human Tregs or CD4+CD25- on primary rat lung, cardiac and human lung microvascular ECs (RLMECs, HLMECs, RCMECs) with set-up of cocultures. In both PH models treatment resulted in development of PH with significantly higher RVSP and particular significantly pronounced RVH in female than in male in both SU5416 and CH groups (Fulton index: 0.41±0.01vs.0.33±0.02 and 0.52±0.03vs.0.37±0.01, p&lt; 0.05). However, circulating estrogen levels were found to be significantly elevated in female than in male in all animal groups. For both female and male AT animals IR of Tregs prevented PH with RV remodeling, as well as decreased perivascular fibrosis and increased estrogen receptor (ER)β expression in lung and RV vascular wall. In vitro studies on coculture of Tregs with RLMECs and RCMECs resulted in an upregulation of IL-10, HO-1, PDL1, ERα, ERβ, activation of pAKT pathway, and endothelial nitric oxide synthase (eNOS), which was abrogated with ER antagonist ICI182,780. In addition, compared with control male AT rats, control female animals had increased expression of HO1, HO2 enzymes in lung and RV vascular wall endothelial/Reca+ cells as well as increased capillary density in RV. Thus, differential HO expression between the genders might account for the PH susceptibility. Conclusions: Our data suggest that Tregs signaling is required as a major mechanism with possible mutual interaction of endogenous estrogen to prevent endothelial injury related gender dimorphism for the development of PH.
Abstract 4914: IFI16 is increased in response to chemotherapeutic agents in breast cancer cells
Authors: Gayoung Lim, Na-Lee Ka, Mi-Ock Lee
Journal: Cancer Research (2018)

Abstract Breast cancer is the most common cancer in women worldwide and chemotherapy is one of the standard treatment options for breast cancer. Chemotherapeutic agents induce severe DNA damage in cancer cells, which have mutations in genes related with DNA repair, resulting in cancer cell death. Thus, controlling DNA damage response is an important factor in determining outcome upon chemotherapy. In this study, we identified IFN-γ inducible protein 16 (IFI16) as a regulator of DNA damage response in breast cancer cells. First, we found that the expression of IFI16 was increased in response to chemotherapeutic agents such as 5-fluouracil, doxorubicin and cisplatin. However, changes in mRNA level of IFI16 was not observed, suggesting that IFI16 expression could be regulated by post-translation modification. Second, nuclear fractionation and confocal analysis revealed that expression of nuclear IFI16 was increased and cytoplasmic IFI16 was decreased in response to doxorubicin. Taken together, IFI16 could be a possible candidate for regulating factor of DNA damage response upon chemotherapy in breast cancer cells. Citation Format: Gayoung Lim, Na-Lee Ka, Mi-Ock Lee. IFI16 is increased in response to chemotherapeutic agents in breast cancer cells [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 4914.
The vitamin D binding protein axis modifies disease severity in lymphangioleiomyomatosis
Authors: Suzanne Miller, Clare Coveney, Janice Johnson, Aliki-Eleni Farmaki, Nishant Gupta, Martin D. Tobin, Louise V. Wain, Francis X. McCormack, David J. Boocock, Simon R. Johnson
Journal: European Respiratory Journal (2018)

Lymphangioleiomyomatosis (LAM) is a rare disease of women. Decline in lung function is variable, making appropriate targeting of therapy difficult. We used unbiased serum proteomics to identify markers associated with outcome in LAM.101 women with LAM and 22 healthy controls were recruited from the National Centre for LAM in the UK. 152 DNA and serum samples with linked lung function and outcome data were obtained from patients in the National Heart, Lung and Blood Institute LAM Registry in the USA. Proteomic analysis was performed on a discovery cohort of 50 LAM and 20 control serum samples using a SCIEX SWATH mass spectrometric workflow. Protein levels were quantitated by ELISA and single nucleotide polymorphisms in GC (group-specific component) encoding vitamin D binding protein (VTDB) were genotyped.Proteomic analysis showed VTDB was 2.6-fold lower in LAM than controls. Serum VTDB was lower in progressive compared with stable LAM (p=0.001) and correlated with diffusing capacity of the lung for carbon monoxide (p=0.01). Median time to death or lung transplant was reduced by 46 months in those with CC genotypes at rs4588 and 38 months in those with non-A-containing haplotypes at rs7041/4588 (p=0.014 and 0.008, respectively).The VTDB axis is associated with disease severity and outcome, and GC genotype could help predict transplant-free survival in LAM.
Abstract 4265: Computational models of the role of base excision repair in sensitization of cancer cells to 5-fluorodeoxyuridine
Authors: Mengdi Qian, Alexandru Almasan, Evren Gürkan-Çavusoglu
Journal: Cancer Research (2018)

Abstract The purpose of this study is to computationally analyze the effect of inhibition of base excision repair (BER) in the response of cancer cells to treatment with 5-fluorodeoxyuridine. 5-fluorouracil (5-FU) and its metabolite 5-fluorodeoxyuridine (5-FdU) are standard treatments for different solid tumors and especially for colon cancer. In the literature, it is shown that the depletion of uracil DNA glycosylase (UDG), one of the enzymes that initiate the BER pathway, enhanced the cytotoxicity of 5-FdU, making UDG a potential target to enhance efficacy of chemotherapeutic agents. It is also shown that the activity of UDG is significantly higher in colon cancer cells compared to normal tissue. We have developed a computational model of the BER pathway to capture the BER dynamics in colon cancer cell lines after treatment with 5-FdU. Our model is composed of a series of ordinary differential equations where the parameters are the kinetic rate constants and the enzyme concentrations. We have used the data from the literature to initially parameterize our models. We have then used least square estimation to find the parameters that will capture the BER time course for colon cancer cells after 5-FU treatment using the experimental data from the literature. We have performed sensitivity and identifiability analyses to determine the parameters that are reliably estimated. The experimental data from the literature showed that the depletion of UDG resulted in incorporation of uracil and 5-FU in the DNA. We have computationally replicated this effect by decreasing the protein concentration of UDG in the models and simulating the amount of remaining 5-FU in the DNA after BER with reduced activity has taken place. We have studied the depletion effect for different protein concentrations of UDG and the results have shown that the accumulation of 5-FU in these colon cancer cells correlate with the level of UDG. The suppression of UDG activity has the potential to enhance the outcome of treatment with 5FdU, and we will use the developed computational models to quantitatively optimize these effects in our future work. Citation Format: Mengdi Qian, Alexandru Almasan, Evren Gürkan-Çavusoglu. Computational models of the role of base excision repair in sensitization of cancer cells to 5-fluorodeoxyuridine [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 4265.
Critical Roles of Muscle-Secreted Angiogenic Factors in Therapeutic Neovascularization
Authors: KaoruTateno, TohruMinamino, HaruhiroToko, HiroshiAkazawa, NaomiShimizu, ShinichiTakeda, TakeshigeKunieda, HideyukiMiyauchi, TomomiOyama, KatsuhisaMatsuura, Jun-ichiroNishi, YoshioKobayashi, ToshioNagai, YoichiKuwabara, YoichiroIwakura, FumioNomura, YasushiSaito, IsseiKomuro
Journal: Circulation Research (2006)

The discovery of bone marrow–derived endothelial progenitors in the peripheral blood has promoted intensive studies on the potential of cell therapy for various human diseases. Accumulating evidence has suggested that implantation of bone marrow mononuclear cells effectively promotes neovascularization in ischemic tissues. It has also been reported that the implanted cells are incorporated not only into the newly formed vessels but also secrete angiogenic factors. However, the mechanism by which cell therapy improves tissue ischemia remains obscure. We enrolled 29 “no-option” patients with critical limb ischemia and treated ischemic limbs by implantation of peripheral mononuclear cells. Cell therapy using peripheral mononuclear cells was very effective for the treatment of limb ischemia, and its efficacy was associated with increases in the plasma levels of angiogenic factors, in particular interleukin-1β (IL-1β). We then examined an experimental model of limb ischemia using IL-1β–deficient mice. Implanta...
Prevalence of Substandard and Falsified Essential Medicines
Authors: Tim K. Mackey
Journal: JAMA Network Open (2018)

Sachiko Ozawa, PhD, MHS; Daniel R. Evans, MSc; Sophia Bessias, MPH; Deson G. Haynie, MHS; Tatenda T. Yemeke, MSc; Sarah K. Laing, MPH; James E. Herrington, PhD
Abstract 17595: Characterization of Cardiac Lipotoxic Stress
Authors: Maria Juarez, Anne-Sophie Grenon-Girard, Jean-Claude Tardif, Nicolas Bousette
Journal: Circulation (2013)

Introduction: Accumulation of lipids in the heart, or cardiac steatosis, has been demonstrated in both insulin resistant and diabetic patients and is associated with diastolic dysfunction. However, the pathological mechanisms causing this cardiac lipotoxicity have yet to be fully elucidated. High fat diets have been shown to induce endoplasmic reticulum (ER) stress in a variety of tissues including liver, skeletal muscle and brain. Here we were interested in characterizing the ER stress response in primary cardiomyocytes treated with lipids as well as hearts from high fat fed mice. Methods and Results: We evaluated ER stress in mouse neonatal cardiomyocytes (mNCMs) treated with either saturated (palmitate) or mono-unsaturated (oleate) fatty acids, as well as in cardiac tissue from C57bl/6 mice fed a high fat diet. We evaluated the expression of Atf-4 & -6, Grp78, spliced Xbp1, Dnajb9, and Herp mRNA levels as well as protein levels of Atf6, Grp78 and phosphorylated Perk. We demonstrated significant inducti...
A diagnostic evaluation of a molecular assay used for testing and treating anorectal chlamydia and gonorrhoea infections at the point-of-care in Papua New Guinea
Authors: S.G. Badman, B. Willie, R. Narokobi, J. Gabuzzi, S. Pekon, A. Amos-Kuma, A.J. Hakim, D. Weikum, J. Gare, S. Silim, R.J. Guy, B. Donovan, P. Cunningham, J.M. Kaldor, A.J. Vallely, D. Whiley, A. Kelly-Hanku
Journal: Clinical Microbiology and Infection (2018)