tbuckley/cabot-search huggingface dataset:
Roles of TET and TDG in DNA demethylation in proliferating and non-proliferating immune cells
Authors: Atsushi Onodera, Edahí González-Avalos, Chan-Wang Jerry Lio, Romain O. Georges, Alfonso Bellacosa, Toshinori Nakayama, Anjana Rao
Journal: Genome biology (2021)

Abstract Background TET enzymes mediate DNA demethylation by oxidizing 5-methylcytosine (5mC) in DNA to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Since these oxidized methylcytosines (oxi-mCs) are not recognized by the maintenance methyltransferase DNMT1, DNA demethylation can occur through “passive,” replication-dependent dilution when cells divide. A distinct, replication-independent (“active”) mechanism of DNA demethylation involves excision of 5fC and 5caC by the DNA repair enzyme thymine DNA glycosylase (TDG), followed by base excision repair. Results Here by analyzing inducible gene-disrupted mice, we show that DNA demethylation during primary T cell differentiation occurs mainly through passive replication-dependent dilution of all three oxi-mCs, with only a negligible contribution from TDG. In addition, by pyridine borane sequencing (PB-seq), a simple recently developed method that directly maps 5fC/5caC at single-base resolution, we detect the accumulation of 5fC/5caC in TDG-deleted T cells. We also quantify the occurrence of concordant demethylation within and near enhancer regions in the Il4 locus. In an independent system that does not involve cell division, macrophages treated with liposaccharide accumulate 5hmC at enhancers and show altered gene expression without DNA demethylation; loss of TET enzymes disrupts gene expression, but loss of TDG has no effect. We also observe that mice with long-term (1 year) deletion of Tdg are healthy and show normal survival and hematopoiesis. Conclusions We have quantified the relative contributions of TET and TDG to cell differentiation and DNA demethylation at representative loci in proliferating T cells. We find that TET enzymes regulate T cell differentiation and DNA demethylation primarily through passive dilution of oxi-mCs. In contrast, while we observe a low level of active, replication-independent DNA demethylation mediated by TDG, this process does not appear to be essential for immune cell activation or differentiation.
Glomangiopericytoma Uptake With 99mTc-MIBI, 18F-FDG, and 11C-Choline
Authors: Ba Duong Nguyen
Journal: Clinical Nuclear Medicine (2021)

Abstract The author presents 3 incidental cases of glomangiopericytoma exhibiting avidity of 99m Tc-MIBI, 18 F-FDG, and 11 C-choline, respectively, during SPECT/CT evaluation of hyperparathyroidism, and PET/CT monitoring of metastatic melanoma and biochemical recurrence of prostate cancer. All the 3 cases show similar functional and anatomic features of tracer-avid lesion in the right nasal cavity from histologically proven glomangiopericytoma.
Expression of MCP-1 and its receptors in glioblastoma multiforme
Authors: Yu Liang, Andrew W. Bollen, Nalin Gupta
Journal: Cancer Research (2004)

1770  Inflammation in glioblastoma multiforme (GBM) involves infiltration of hematopoietic cells, tissue edema, and secretion of pro-inflammatory cytokines. The mechanisms underlying tumor-associated inflammation remain poorly defined. Monocyte chemoattractant protein-1 (MCP-1) is a dominant chemoattractant cytokine for monocytes and macrophages in response to inflammation. Higher expression of MCP-1 was seen in GBM than in low-grade glioma, and expression of MCP-1 by tumor cells is thought to be responsible for recruitment of macrophages that could induce angiogenesis and white matter edema, two hallmark histopathological features of GBM. Using immunohistochemistry, we investigated the expression of MCP-1 and its receptors, CCR2A and CCR2B, in 31 human GBM specimens. We found that all three proteins were detected in almost every tumor specimen examined, and in most cases the neoplastic cells positive with MCP-1 are also immunoreactive with CCR2A and CCR2B. We hypothesized that MCP-1 can directly affect the biology of glioma cells, potentially through autocrine-activating loops. We tested this hypothesis further in vitro using U87 glioma cells as a model and demonstrated that overexpression of CCR2A gene increases cell migration, suggesting that CCR2A expression might regulate glioma cell motility in response to MCP-1.
Abstract 14130: Ductus Diameter and Left Pulmonary Artery End-Diastolic Velocity at 3 Days of Age May Predict Future Needs of Surgical Closure for Patent Ductus Arteriosus in Preterm Infants : A Post Hoc Analysis of Prospective Multicenter Cohort Study
Authors: Satoshi Masutani, Tetsuya Isayama, Tohru Kobayashi, Masashi Mikami, Kyongsun Pak, Katsuaki Toyoshima
Journal: Circulation (2019)

Background: Early detection of future needs of surgical closure for patent ductus arteriosus (PDA) is of significant clinical relevance in the management of preterm infants. However, the results of...
Abstract 101: Mitochondrial and Cardiac Protection Evoked by a Novel Mitochondria-targeting Peptide-idebenone Conjugate
Authors: Justin B Perry, Rick J Alleman, Alvin M Tsang, William B Winfrey, Mitchell E Allen, Tom D Green, Joseph M McClung, David A Brown
Journal: Circulation Research (2016)

Dysfunction along the electron transport system contributes to cardiomyopathy in a number of mitochondrial diseases. Several pharmacological approaches are currently being tested for their ability to improve mitochondrial function, yet almost none of the leading candidates specifically target to mitochondria. In this study we determined the biological efficacy of a novel conjugate of idebenone and mitochondria-targeting peptide, SBT-61. Using a vertically-integrated approach we tested the ability of SBT-61 to improve functional recovery and bioenergetics in: perfused rat hearts subjected to ischemia-reperfusion, cultured cells exposed to hypoxia-reoxygenation injury, and isolated heart mitochondria where complexes I and/or III were inhibited. SBT-61 treatment preserved post-ischemic cardiac function as assessed by left ventricular developed pressure (40 ± 5 vs 24 ± 3 mmHg, P&lt;0.0001), rate of contraction (1853 ± 236 vs. 1069 ± 109 mmHg/s, P&lt;0.0001), rate of relaxation (-1349 ± 231 vs. -792 ± 52 mmHg/s, P&lt;0.0001), and a 30% reduction in infarct size. In cells expressing an shRNA knockdown of glutathione reductase, treatment with SBT-61 normalized maximal mitochondrial respiration after hypoxia-reoxygenation. In isolated mitochondria with complexes I or III inhibited, SBT-61 stimulated respiration and was shown to directly reduce complex III and cytochrome c, indicating that SBT-61 can bypass defects in the electron transport system. These data highlight the cardioprotective potential of a mitochondria-targeted idebenone conjugate to stabilize mitochondrial bioenergetics.
Biphasic Emergence of Active Tuberculosis in RA Patients Receiving TNF-α Inhibitors: the Utility of IFN-γ Assay
Authors: 陳得源, 沈光漢, Chen Yi Ming, Chen Hsin Hua, Hsieh Chia Wei, 藍忠亮
Journal: Annals of the Rheumatic Diseases (2012)
Diabetes Technology Use for Management of Type 1 Diabetes Is Associated With Fewer Adverse COVID-19 Outcomes: Findings From the T1D Exchange COVID-19 Surveillance Registry
Authors: Nudrat Noor, Osagie Ebekozien, Laura Levin, Sheri Stone, David P. Sparling, Robert Rapaport, David M. Maahs
Journal: Diabetes Care (2021)

People with coronavirus disease 2019 (COVID-19) and preexisting type 1 diabetes (T1D) are at high risk of diabetes-related outcomes such as diabetic ketoacidosis (DKA) and hospitalization (1). For people with elevated glucose levels, infections could further exacerbate the risk of acute complications. As part of the management of T1D, the use of diabetes technology including continuous glucose monitors (CGM) and insulin pumps is recommended to improve glycemic control (2). However, despite increasing evidence of the benefits of diabetes technology, its uptake remains low, in part owing to systemic racism and social inequities, including in diabetes and device education, patient motivation, and peer support (3,4). The aim of this article is to examine the association of technology use and clinical outcomes during the COVID-19 pandemic.

We analyzed data from the T1DX COVID-19 Surveillance Registry, a U.S.-based multicenter study for people with T1D, to examine the frequency of adverse outcomes across categories of technology use. The registry details have previously been described; briefly, all participating sites completed a chart review and via an online questionnaire submitted information on all patients with T1D at their sites who tested positive for COVID-19 (1,2).

This analysis included 447 people with T1D and laboratory-confirmed COVID-19 infection during March 2020–December 2020. Patients were grouped into four categories of diabetes technology use: “no device use,” including patients who did not report using a CGM or insulin pump device; “CGM use,” including all patients currently using a CGM device, regardless of insulin pump use; “insulin pump use,” including all …
Defective Flow-Migration Coupling Causes Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia
Authors: Hyojin Park, Jessica Furtado, Mathilde Poulet, Minhwan Chung, Sanguk Yun, Sungwoon Lee, William C. Sessa, Claudio A. Franco, Martin A. Schwartz, Anne Eichmann
Journal: Circulation (2021)

Activin receptor-like kinase 1 (ALK1) is an endothelial transmembrane serine threonine kinase receptor for BMP family ligands that plays a critical role in cardiovascular development and pathology. Loss-of-function mutations in the
Fishing for an Association With Sudden Cardiac Death
Authors: Emily R. Siegel, Zian H. Tseng
Journal: JAMA Internal Medicine (2021)

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Characterization of Benign Breast Diseases and Association With Age, Hormonal Factors, and Family History of Breast Cancer Among Women in Sweden
Authors: Annelie Johansson, Athanasia E. Christakou, Adina Iftimi, Mikael Eriksson, Jose Tapia, Lambert Skoog, Christopher C. Benz, Kenny A. Rodriguez-Wallberg, Per Hall, Kamila Czene, Linda S. Lindström
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Benign breast diseases (BBDs) are common and associated with breast cancer risk, yet the etiology and risk of BBDs have not been extensively studied. <h3>Objective</h3> To investigate the risk of BBDs by age, hormonal factors, and family history of breast cancer. <h3>Design, Setting, and Participants</h3> This retrospective cohort study assessed 70 877 women from the population-based Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) who attended mammographic screening or underwent clinical mammography from January 1, 2011, to March 31, 2013, at 4 Swedish hospitals. Participants took part in a comprehensive questionnaire on recruitment. All participants had complete follow-up through high-quality Swedish national registers until December 31, 2015. Pathology medical records on breast biopsies were obtained for the participants, and BBD subtypes were classified according to the latest European guidelines. Analyses were conducted from January 1 to July 31, 2020. <h3>Exposures</h3> Hormonal risk factors and family history of breast cancer. <h3>Main Outcomes and Measures</h3> For each BBD subtype, incidence rates (events per 100 000 person-years) and multivariable Cox proportional hazards ratios (HRs) with time-varying covariates were estimated between the ages of 25 and 69 years. <h3>Results</h3> A total of 61 617 women within the mammographic screening age of 40 to 69 years (median age, 53 years) at recruitment with available questionnaire data were included in the study. Incidence rates and risk estimates varied by age and BBD subtype. At premenopausal ages, nulliparity (compared with parity ≥3) was associated with reduced risk of epithelial proliferation without atypia (EP; HR, 0.62; 95% CI, 0.46-0.85) but increased risk of cysts (HR, 1.38; 95% CI, 1.03-1.85). Current and long (≥8 years) oral contraceptive use was associated with reduced premenopausal risk of fibroadenoma (HR, 0.65; 95% CI, 0.47-0.90), whereas hormone replacement therapy was associated with increased postmenopausal risks of epithelial proliferation with atypia (EPA; HR, 1.81; 95% CI, 1.07-3.07), fibrocystic changes (HR, 1.60; 95% CI, 1.03-2.48), and cysts (HR, 1.98; 95% CI, 1.40-2.81). Furthermore, predominantly at premenopausal ages, obesity was associated with reduced risk of several BBDs (eg, EPA: HR, 0.31; 95% CI, 0.17-0.56), whereas family history of breast cancer was associated with increased risk (eg, EPA: HR, 2.11; 95% CI, 1.48-3.00). <h3>Conclusions and Relevance</h3> These results suggest that the risk of BBDs varies by subtype, hormonal factors, and family history of breast cancer and is influenced by age. Better understanding of BBDs is important to improve the understanding of benign and malignant breast diseases.
Abstract 432: Elamipretide (BendaviaTM) Restores Aldehyde Dehydrogenase-2 Protein Levels and 4-Hydroxy-2-Nonenal Protein Adducts in Left Ventricular Myocardium of Dogs with Heart Failure
Authors: Ramesh C Gupta, Vinita Singh-Gupta, Hani N Sabbah
Journal: Circulation Research (2016)

Background: Reactive aldehydes such as 4-hydroxy-2-nonenal (4-HNE) are generated in the failing heart and contribute to cardiomyocyte injury and death and progressive left ventricular (LV) dysfunction. Aldehyde dehydrogenase-2 (ALDH2) plays a pivotal role in detoxifying mitochondrial (MITO) reactive aldehydes. We previously showed that long-term therapy with Elamipretide (ELA, Bendavia TM ), a novel MITO targeting peptide, improves LV systolic function and normalizes MITO function and rate of ATP synthesis in dogs with heart failure (HF). In this study, we examined the effects of long-term treatment with ELA on protein levels of 4-HNE adducts and ALDH2 in LV myocardium of dogs with coronary microembolization-induced HF (LV ejection fraction ~30%). Methods: LV tissue from 14 HF dogs randomized to 3 months monotherapy with subcutaneous injections of ELA (0.5 mg/kg once daily, n=7) or saline (control, CTR, n=7) and tissue from 6 normal (NL) dogs was used in the study. Using LV tissue extracts, 4-HNE protein adducts levels were quantified using a commercially available Elisa kit and expressed as ng/mg. In isolated MITO fractions prepared from LV tissue, protein levels of ALDH2 and porin, the latter used as an internal loading control, were determined by Western blotting coupled with Chemiluminescence. Band intensity was expressed in densitometric units (DU). Results: No changes in protein level of porin was observed among the 3 study groups (NL: 0.26±0.02; CTR: 0.24±0.01; BEN: 0.26±0.01 DU). 4-HNE protein adducts levels were increased in CTR dogs compared to NL dogs and treatment with ELA partially restored 4-HNE to near normal levels (NL: 185±21; CTR: 399±35*; ELA: 252 ± 18† ng/mg, *=p&lt;0.05 vs. NL; †=p&lt;0.05 vs. CTR). Compared to NL, dogs, ALDH2 protein levels were significantly reduced in HF CTR dogs (0.49±0.02 vs. 1.16±0.10; p&lt;0.05). Treatment with ELA significantly increased ALDH2 protein compared to untreated CTR (0.74±0.02 DU, p&lt;0.05). Conclusions: Long-term therapy with ELA normalizes ALDH2 and 4-HNE levels in LV myocardium of dogs with HF. Improved protein levels of ALDH2 in HF after therapy with ELA can account, in part, for the observed improvement of global LV function elicited by long-term therapy with ELA.
Allogenic C57B/6->B6D2F1 Transplantation As a Model for Graft Versus Host Disease in the Brain
Authors: Sarah Bryant, Ian Moore, Bianca Nagata, Danielle Springer, Audrey Noguchi, Morteza Peiravi, Karlie Sharma, Sherry M. Koontz, Harry Malech, Elizabeth Kang
Journal: Blood (2017)
Early rise in brain damage markers and high ICOS expression in CD4+ and CD8+ T cells during checkpoint inhibitor-induced encephalomyelitis
Authors: Sara Bjursten, Ankur Pandita, Zhiyuan Zhao, Charlotta Fröjd, Lars Ny, Christer Jensen, Tobias Ullerstam, Henrik Jespersen, Jan Borén, Malin Levin, Henrik Zetterberg, Anna Rudin, Max Levin
Journal: Journal for ImmunoTherapy of Cancer (2021)

We report a case of rapid eradication of melanoma brain metastases and simultaneous near-fatal encephalomyelitis following double immune checkpoint blockade. Brain damage marker S-100B and C reactive protein increased before symptoms or signs of encephalomyelitis and peaked when the patient fell into a coma. At that point, additional brain damage markers and peripheral T cell phenotype was analyzed. The analyses were repeated four times during the patient’s recovery. Axonal damage marker neurofilament light polypeptide (NFL) and astrocytic damage marker glial fibrillar acidic protein (GFAP) were very high in blood and cerebrospinal fluid and gradually normalized after immunosuppression and intensive care. The costimulatory receptor inducible T cell costimulatory receptor (ICOS) was expressed on a high proportion of CD4+ and CD8+T cells as encephalomyelitis symptoms peaked and then gradually decreased in parallel with clinical improvement. Both single and double immune checkpoint inhibitor-treated melanoma patients with other serious immune-related adverse events (irAE) (n=9) also expressed ICOS on a significantly higher proportion of CD4+ and CD8+T cells compared with controls without irAE (n=12). In conclusion, our results suggest a potential role for ICOS on CD4+ and CD8+T cells in mediating encephalomyelitis and other serious irAE. In addition, brain damage markers in blood could facilitate early diagnosis of encephalitis.
Cheyne-Stokes呼吸を伴ううっ血性心不全患者に対してadaptive servo-ventilationが有効であった2症例
Authors: Iwasaki Atsushi, Kono Kunihisa, Tanakaya Machiko, Yoshida Masanobu, Osawa Kazuhiro, Takeuchi Kazufumi, Takahashi Natsuki, Katayama Yusuke, Yumoto Akihisa, Shiraki Teruo, Saito Daiji
Journal: Circulation (2008)
Disrupted Dorsal Mid-Insula Activation During Interoception Across Psychiatric Disorders
Authors: Camilla L. Nord, Rebecca P. Lawson, Tim Dalgleish
Journal: American Journal of Psychiatry (2021)

Maintenance of bodily homeostasis relies on interoceptive mechanisms in the brain to predict and regulate bodily state. While altered neural activation during interoception in specific psychiatric disorders has been reported in many studies, it is unclear whether a common neural locus underpins transdiagnostic interoceptive differences.
the Efficacy of Extra-Corporal Photopheresis for Bronchiolitis Obliterans Syndrome after Hematopoietic Cell Transplantation: A Retrospective, Matched, Case-Control Study
Authors: Mehrdad Hefazi, Kimberly J. Langer, Alli Louise McClanahan, Jeffrey L. Winters, Dennis A. Gastineau, Eapen K. Jacob, Justin D. Kreuter, Manish Gandhi, William J. Hogan, Mark R. Litzow, Shahrukh K. Hashmi, Vivek N Iyer, Rodrigo Cartin-Ceba, Mrinal M. Patnaik
Journal: Blood (2017)
Effect of Statin Therapy on Cognitive Decline and Incident Dementia in Older Adults
Authors: Zhen Zhou, Joanne Ryan, Michael E Ernst, Sophia Zoungas, Andrew M Tonkin, Robyn L Woods, John J McNeil, Christopher M Reid, Andrea J Curtis, Rory Wolfe, Jo Wrigglesworth, Raj C Shah, Elsdon Storey, Anne Murray, Suzanne G Orchard, Mark R Nelson
Journal: Journal of the American College of Cardiology (2021)
Paraoxonases 1 and 2 (PON1 and 2) Polymorphisms in Diffuse Large B-Cell Lymphoma (DLBCL): Correlation with Clinical Outcomes
Authors: Debora Levy, Diego Reis, Karolline Santana da Silva, Luis A P C Lage, Bruno Sini, Luciana M. F. Maseli, Vanderson Rocha, Juliana Pereira, Sergio P Bydlowski
Journal: Blood (2017)
Obesity-induced changes in human islet G protein-coupled receptor expression: Implications for metabolic regulation
Authors: Patricio Atanes, Tanyel Ashik, Shanta J Persaud
Journal: Pharmacology & Therapeutics (2021)

G protein-coupled receptors (GPCRs) are a large family of cell surface receptors that are the targets for many different classes of pharmacotherapy. The islets of Langerhans are central to appropriate glucose homeostasis through their secretion of insulin, and islet function can be modified by ligands acting at the large number of GPCRs that islets express. The human islet GPCRome is not a static entity, but one that is altered under pathophysiological conditions and, in this review, we have compared expression of GPCR mRNAs in human islets obtained from normal weight range donors, and those with a weight range classified as obese. We have also considered the likely outcomes on islet function that the altered GPCR expression status confers and the possible impact that adipokines, secreted from expanded fat depots, could have at those GPCRs showing altered expression in obesity.