tbuckley/cabot-search huggingface dataset:
The role of the AMPK energy sensing pathway in Pten-deletion induced liver carcinogenesis in vivo
Authors: Vivian Galicia, Ni Zeng, Derik Han, Bangyan Stiles
Journal: Cancer Research (2008)

4566  Hepatocellular carcinoma (HCC) is the 5th most common cause of cancer related mortality worldwide. The disease progression for HCC is biphasic. The first stage consists of lipid accumulation in the liver, which progresses to the final stage characterized by tumor development. A number of studies have demonstrated a high correlation between PTEN loss and HCC development. PTEN (phosphatase and tensin homologue deleted on chromosome ten) is a negative regulator of the insulin signaling pathway. Hepatic insulin signaling plays a central role in glucose and lipid metabolism. The actions of insulin are mediated via cell surface receptors which in the presence of growth factor activate the phosphatidylinositol-3 kinase (PI3K) pathway. PI3K generates phosphatidylinositol, second messengers which can activate a number of downstream targets including the serine/threonine kinase (AKT). AKT regulates a number of key metabolic proteins including the mammalian target of rapamycin (mTOR) and AMP-activated kinase (AMPK). The AMPK pathway is an evolutionarily conserved sensor of cellular energy status. Activation of this pathway (via phosphorylation by upstream kinase LKB1) promotes ATP production and attenuation of ATP consuming biosynthetic processes. To better understand the molecular interactions between the PTEN and AMPK energy signaling pathways we have crossed PtenloxP/loxP;Alb-Cre+ mice with Lkb1loxP/loxP mice to obtain PtenloxP/loxP ; Lkb1loxP/loxP ;Cre+ mice, which are deficient in both PTEN and LKB1. Liver specific Pten null animals exhibit bile duct hyperplasia and develop liver cancer of both cholangiocyte and hepatocyte origin by 12 months of age. Because Pten deletion is consequential to decreased activation of the AMPK pathway via the actions of AKT, we hypothesize that concomitant deletion of Pten and Lkb1 will lead to advanced tumorigenesis observed in Pten null mice alone. Mice which harbor liver specific deletions of both of Pten and Lkb1 demonstrate lethality at weaning age (21-30 days). Phenotypically, double mutant mice weigh roughly one third as much as wildtype cohorts. In addition systemic glucose levels exhibited by double mutant mice in the fed state are a third to half that observed in control littermates. Therefore, we hypothesize that concurrent deletion of Ptenand Lkb1 in the liver induces hypoglycemia. Due to the observed lethality of homozygous mice, Lkb1loxP/+;PtenloxP/loxP;Alb-Cre+ mice will be used to acertain that Pten deletion and a bypass of AMPK energy sensing pathway may act synergistically to regulate the progression of HCC.
Dual directions to address the problem of aseptic loosening via electrospun PLGA @ aspirin nanofiber coatings on titanium
Authors: Yaojie Wei, Zhongqun Liu, Xu Zhu, Le Jiang, Weidong Shi, Yingjin Wang, Nan Xu, Fangli Gang, Xiumei Wang, Lingyun Zhao, Jun Lin, Xiaodan Sun
Journal: Biomaterials (2020)
Thrombosis in Hospitalized Patients With COVID-19 in a New York City Health System
Authors: Seda Bilaloglu, Yin Aphinyanaphongs, Simon Jones, Eduardo Iturrate, Judith Hochman, Jeffrey S. Berger
Journal: JAMA (2020)

Clinical Characteristics, Comorbidities, and Outcomes Among Patients With COVID-19 Hospitalized in the NYC Area
High sodium intake, glomerular hyperfiltration, and protein catabolism in patients with essential hypertension
Authors: Giacomo Rossitto, Giuseppe Maiolino, Silvia Lerco, Giulio Ceolotto, Gavin Blackburn, Sheon Mary, Giorgia Antonelli, Chiara Berton, Valeria Bisogni, Maurizio Cesari, Teresa Maria Seccia, Livia Lenzini, Alessio Pinato, Augusto Montezano, Rhian M Touyz, Mark C Petrie, Ronan Daly, Paul Welsh, Mario Plebani, Gian Paolo Rossi, Christian Delles
Journal: Cardiovascular Research (2020)

Abstract Aims A blood pressure (BP)-independent metabolic shift towards a catabolic state upon high sodium (Na+) diet, ultimately favouring body fluid preservation, has recently been described in pre-clinical controlled settings. We sought to investigate the real-life impact of high Na+ intake on measures of renal Na+/water handling and metabolic signatures, as surrogates for cardiovascular risk, in hypertensive patients. Methods and results We analysed clinical and biochemical data from 766 consecutive patients with essential hypertension, collected at the time of screening for secondary causes. The systematic screening protocol included 24 h urine (24 h-u-) collection on usual diet and avoidance of renin–angiotensin–aldosterone system-confounding medications. Urinary 24 h-Na+ excretion, used to define classes of Na+ intake (low ≤2.3 g/day; medium 2.3–5 g/day; high &amp;gt;5 g/day), was an independent predictor of glomerular filtration rate after correction for age, sex, BP, BMI, aldosterone, and potassium excretion [P = 0.001; low: 94.1 (69.9–118.8) vs. high: 127.5 (108.3–147.8) mL/min/1.73 m2]. Renal Na+ and water handling diverged, with higher fractional excretion of Na+ and lower fractional excretion of water in those with evidence of high Na+ intake [FENa: low 0.39% (0.30–0.47) vs. high 0.81% (0.73–0.98), P &amp;lt; 0.001; FEwater: low 1.13% (0.73–1.72) vs. high 0.89% (0.69–1.12), P = 0.015]. Despite higher FENa, these patients showed higher absolute 24 h Na+ reabsorption and higher associated tubular energy expenditure, estimated by tubular Na+/ATP stoichiometry, accordingly [Δhigh–low = 18 (12–24) kcal/day, P &amp;lt; 0.001]. At non-targeted liquid chromatography/mass spectrometry plasma metabolomics in an unselected subcohort (n = 67), metabolites which were more abundant in high versus low Na+ intake (P &amp;lt; 0.05) mostly entailed intermediates or end products of protein catabolism/urea cycle. Conclusion When exposed to high Na+ intake, kidneys dissociate Na+ and water handling. In hypertensive patients, this comes at the cost of higher glomerular filtration rate, increased tubular energy expenditure, and protein catabolism from endogenous (muscle) or excess exogenous (dietary) sources. Glomerular hyperfiltration and the metabolic shift may have broad implications on global cardiovascular risk independent of BP.
<i>Vital Signs:</i> Prescription Opioid Pain Reliever Use During Pregnancy — 34 U.S. Jurisdictions, 2019
Authors: Jean Y. Ko, Denise V. D’Angelo, Sarah C. Haight, Brian Morrow, Shanna Cox, Beatriz Salvesen von Essen, Andrea E. Strahan, Leslie Harrison, Heather D. Tevendale, Lee Warner, Charlan D. Kroelinger, Wanda D. Barfield
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Prescription opioid use during pregnancy has been associated with poor outcomes for mothers and infants. Studies using administrative data have estimated that 14%-22% of women filled a prescription for opioids during pregnancy; however, data on self-reported prescription opioid use during pregnancy are limited.CDC analyzed 2019 data from the Pregnancy Risk Assessment Monitoring System (PRAMS) survey in 32 jurisdictions and maternal and infant health surveys in two additional jurisdictions not participating in PRAMS to estimate self-reported prescription opioid pain reliever (prescription opioid) use during pregnancy overall and by maternal characteristics among women with a recent live birth. This study describes source of prescription opioids, reasons for use, want or need to cut down or stop use, and receipt of health care provider counseling on how use during pregnancy can affect an infant.An estimated 6.6% of respondents reported prescription opioid use during pregnancy. Among these women, 21.2% reported misuse (a source other than a health care provider or a reason for use other than pain), 27.1% indicated wanting or needing to cut down or stop using, and 68.1% received counseling from a provider on how prescription opioid use during pregnancy could affect an infant.Among respondents reporting opioid use during pregnancy, most indicated receiving prescription opioids from a health care provider and using for pain reasons; however, answers from one in five women indicated misuse. Improved screening for opioid misuse and treatment of opioid use disorder in pregnant patients might prevent adverse outcomes. Implementation of public health strategies (e.g., improving state prescription drug monitoring program use and enhancing provider training) can support delivery of evidence-based care for pregnant women.
Can Long-term Treatment of Obstructive Sleep Apnea With CPAP Improve Glycemia and Prevent Type 2 Diabetes?
Authors: Sirimon Reutrakul, Babak Mokhlesi
Journal: Diabetes Care (2020)

Obstructive sleep apnea (OSA) is a prevalent sleep disorder caused by intermittent partial or complete collapse of the upper airway during sleep resulting in intermittent hypoxemia and hypercapnia, sleep fragmentation, increased oxidative stress, and systemic inflammation. The prevalence of moderate-to-severe OSA in the general population, estimated at 23.4% in women and 49.7% in men, has increased over the past few decades (1,2), due in part to the obesity epidemic (3). Multiple observational studies have reported an association between OSA, insulin resistance, and increased risk of incident type 2 diabetes (4,5). In a meta-analysis, the presence of OSA was independently associated with a 1.35-fold increase in the risk of developing type 2 diabetes (4). In addition to being a risk factor for developing type 2 diabetes, OSA is highly prevalent in adults with type 2 diabetes, with prevalence estimates between 58% and 86%, with moderate-to-severe OSA being present in 25–59% of individuals (4).

Although increasing severity of OSA has been associated with worsened glycemic control (6), continuous positive airway pressure (CPAP), the gold standard treatment of OSA, has not been consistently shown to improve glycemic control or reduce insulin resistance in clinical trials in which CPAP was used for 1–6 months (4,7–10). Multiple factors may contribute to the heterogeneity of the results, including different levels of CPAP adherence, various durations of CPAP therapy, background glycemic control, and the use of antihyperglycemic agents, the number of which has been ever increasing. In well-controlled laboratory experiments, however, there is evidence that short-term CPAP use with ensured compliance of 8 h nightly for 1–2 weeks results in improved …
CD4+CD126low/− Foxp3+ Cell Population Represents a Superior Subset of Regulatory T Cells in Treating Autoimmune Diseases
Authors: Ye Chen, Zhenjian Xu, Rongzhen Liang, Julie Wang, Anping Xu, Ning Na, Bin Li, Ruoning Wang, Miller Joseph, Nancy Olsen, Willa Hsueh, Song Guo Zheng
Journal: Molecular Therapy (2020)

CD4+Foxp3+ regulatory T (Treg) cells are crucial for maintaining homeostasis and preventing autoimmune diseases. Nonetheless, we and others have previously reported that natural Treg cells are unstable and dysfunctional in the inflamed environment with a high-salt diet, limiting the Treg function in disease control. In this study, we made an innovative observation showing a high degree of heterogeneity within the Treg pool. We identified that CD126, interleukin (IL)-6 receptor alpha chain, contributed to Treg cell instability. Using a series of in vitro and in vivo experimental approaches, we demonstrated that CD126Lo/- Treg cells presented greater function and were more stable than CD126Hi nTreg cells, even in the presence of IL-6 and inflammation. Blockade of programmed death-1 (PD-1) interrupted CD126Lo/- nTreg cell stability. Additionally, CD126Lo/- Treg cells can treat colitis and established collagen-induced arthritis, while the CD126Hi cell population failed to do this. Moreover, we noted that CD126 expression of Treg cells had a positive correlation to rheumatoid arthritis (RA) severity and the stability of Treg cells. Our results strongly suggest that the manipulation of CD126Lo/- nTreg cells could be a novel strategy for the treatment of autoimmune diseases and for other conditions associated with a deficit of Treg cells.
Is Phylotranscriptomics as Reliable as Phylogenomics?
Authors: Seongmin Cheon, Jianzhi Zhang, Chungoo Park
Journal: Molecular Biology and Evolution (2020)

Abstract Phylogenomics, the study of phylogenetic relationships among taxa based on their genome sequences, has emerged as the preferred phylogenetic method because of the wealth of phylogenetic information contained in genome sequences. Genome sequencing, however, can be prohibitively expensive, especially for taxa with huge genomes and when many taxa need sequencing. Consequently, the less costly phylotranscriptomics has seen an increased use in recent years. Phylotranscriptomics reconstructs phylogenies using DNA sequences derived from transcriptomes, which are often orders of magnitude smaller than genomes. However, in the absence of corresponding genome sequences, comparative analyses of transcriptomes can be challenging and it is unclear whether phylotranscriptomics is as reliable as phylogenomics. Here, we respectively compare the phylogenomic and phylotranscriptomic trees of 22 mammals and 15 plants that have both sequenced nuclear genomes and publicly available RNA sequencing data from multiple tissues. We found that phylotranscriptomic analysis can be sensitive to orthologous gene identification. When a rigorous method for identifying orthologs is employed, phylogenomic and phylotranscriptomic trees are virtually identical to each other, regardless of the tissue of origin of the transcriptomes and whether the same tissue is used across species. These findings validate phylotranscriptomics, brighten its prospect, and illustrate the criticality of reliable ortholog detection in such practices.
Abstract 15926: Severe Metabolic Acidosis After Out-of-hospital Cardiac Arrest
Authors: Matthieu Jamme, Omar Ben Hadj Salem, Lucie Guillemet, Pierre Dupland, Wulfran Bougouin, Julien Charpentier, Jean Paul Mira, Frédérique Pène, Florence Dumas, Alain Cariou, Guillaume Geri
Journal: Circulation (2017)

Introduction: Metabolic acidosis is frequently observed as a consequence of global ischemia-reperfusion after out-of-hospital cardiac arrest (OHCA). Hypothesis: We aimed to identify risk factors an...
FRI0080 Long-term use of enbrel® (etanercept) in patients with dmard-refractory rheumatoid arthritis
Authors: LW Moreland, SB Cohen, SW Baumgartner, MH Schift, EA Tindall, DJ Burge
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Results have been previously presented from a long-term safety trial of ENBREL as monotherapy in adult patients with RA who had failed at least one DMARD. In this ongoing study, 628 patients have been followed for up to 4.3 years (median = 2.4 years) for a total of 1336 patient-years. <h3>Objectives</h3> Continue to observe the long-term safety and clinical benefit of ENBREL. <h3>Methods</h3> Patients were evaluated for disease activity using ACR criteria. Adverse event rates were compared with data from controlled studies. <h3>Results</h3> 479 adult patients have received ENBREL as monotherapy for over 1 year, 420 for over 2 years, 164 for over 3 years, and 12 for over 4 years. Response has been sustained for the duration of therapy. At baseline, the median tender joint count was 31 and the median swollen joint count was 25. At 3.5 years, the median tender and swollen joint counts were 3 each, and 69% of patients had achieved the ACR 20, 50% the ACR 50, and 25% the ACR 70. Also at 3.5 years, 24% of patients had zero tender joints, 26% had zero swollen joints, and 15% had disability scores of zero. In addition, 59% of patients who were receiving corticosteroids at study start have decreased their steroid doses by a mean of 71%, 29% of patients have completely discontinued steroids, and only 5% have increased their steroid dose. Compared to events seen in controlled trials or in the normal adult population, no significant differences in rate or type of adverse events were seen in patients treated with ENBREL over time. Serious adverse events occurred at a rate of 0.13 per patient-year in the long-term database compared to 0.13 in ENBREL-treated patients and 0.20 in placebo patients in the controlled studies. Likewise, serious infections (associated with hospitalisation or IV antibiotics) occurred at a rate of 0.05 per patient-year in the long-term database compared to 0.04 in ENBREL patients and 0.05 in placebo patients in the controlled studies. The number of malignancies reported in ENBREL patients was similar to the expected number calculated from the National Cancer Institute SEER database (9 reported vs. 12.7 expected). No opportunistic infections have been observed. <h3>Conclusion</h3> ENBREL as monotherapy continues to be safe and effective in patients with DMARD-refractory RA for over 4 years. <h3>Reference</h3> Moreland LW, <i>et al</i>. Arthritis Rheum. 2000;43:S270
Angiopoietin-1 enhanced myocyte mitosis, engraftment, and the reparability of hiPSC-CMs for treatment of myocardial infarction
Authors: Zhonghao Tao, Szejie Loo, Liping Su, Shihua Tan, Guizhen Tee, Shu Uin Gan, Jianyi Zhang, Xin Chen, Lei Ye
Journal: Cardiovascular Research (2020)

To examine whether transient over-expression of angiopoietin-1 (Ang-1) increases the potency of hiPSC-CMs for treatment of heart failure.
Peptide vaccination directed against IDO1-expressing immune cells elicits CD8<sup>+</sup> and CD4<sup>+</sup> T-cell-mediated antitumor immunity and enhanced anti-PD1 responses
Authors: Souvik Dey, Erika Sutanto-Ward, Katharina L Kopp, James DuHadaway, Arpita Mondal, Dema Ghaban, Inés Lecoq, Mai-Britt Zocca, Lauren M F Merlo, Laura Mandik-Nayak, Mads Hald Andersen, Ayako Wakatsuki Pedersen, Alexander J Muller
Journal: Journal for ImmunoTherapy of Cancer (2020)

The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which subverts T-cell immunity at multiple levels, is itself subject to inherent T-cell reactivity. This intriguing deviation from central tolerance has been interpreted as counterbalancing IDO1-mediated immunosuppression. Based on this hypothesis, clinical studies employing an IDO1 peptide-based vaccine approach for cancer treatment have been initiated, but there remains a pressing need to further investigate the immunological ramifications of stimulating the anti-IDO1 T-cell response in this manner.CT26 colon carcinoma tumors were evaluated for expression of IDO1 protein by western blot analysis, immunofluorescence microscopy and flow cytometry. Mouse IDO1-derived peptides, predicted to bind either major histocompatibility complex (MHC) class I or II of the H2d BALB/c strain, were emulsified in 50% Montanide for prophylactic or therapeutic vaccine treatment of CT26 tumor-bearing mice initiated either 7 days prior to or following tumor cell injection, respectively. In some therapeutic treatment experiments, administration of programmed cell death protein 1-binding antibody (anti-PD1 antibody) or epacadostat was concurrently initiated. Tumor size was determined by caliper measurements and comparative tumor growth suppression was assessed by longitudinal analyses of tumor growth data. For adoptive transfer, T cells from complete responder animals were isolated using paramagnetic beads and fluorescence-activated cell sorting.This study identifies mouse MHC class I-directed and II-directed, IDO1-derived peptides capable of eliciting antitumor responses, despite finding IDO1 expressed exclusively in tumor-infiltrating immune cells. Treatment of established tumors with anti-PD1 antibody and class I-directed but not class II-directed IDO1 peptide vaccines produced an enhanced antitumor response. Likewise, class I-directed and II-directed IDO1 peptides elicited an enhanced combinatorial response, suggesting distinct mechanisms of action. Consistent with this interpretation, adoptive transfer of isolated CD8+ T cells from class I and CD4+ T cells from class II peptide-vaccinated responder mice delayed tumor growth. The class II-directed response was completely IDO1-dependent while the class I-directed response included an IDO1-independent component consistent with antigen spread.The in vivo antitumor effects demonstrated with IDO1-based vaccines via targeting of the tumor microenvironment highlight the utility of mouse models for further exploration and refinement of this novel vaccine-based approach to IDO1-directed cancer therapy and its potential to improve patient response rates to anti-PD1 therapy.
Covid-19: Local public health teams being denied access to data that could help them trace cases
Authors: Ingrid Torjesen
Journal: BMJ (2020)

Covid-19: Local public health teams being denied access to data that could help them trace cases Ingrid TorjesenLocal public health teams are not being provided with the patient identifiable information on covid-19 cases that they need to manage and prevent local outbreaks effectively, directors of public health have said.
Covid-19 and Disparities in Nutrition and Obesity
Authors: Matthew J. Belanger, Michael A. Hill, Angeliki M. Angelidi, Maria Dalamaga, James R. Sowers, Christos S. Mantzoros
Journal: New England Journal of Medicine (2020)

Covid-19 and Disparities in Nutrition and Obesity Though the factors underlying racial and ethnic disparities in Covid-19 in the United States are multifaceted and complex, long-standing disparitie...
Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients
Authors: Linnan Zhu, Penghui Yang, Yingze Zhao, Zhenkun Zhuang, Zhifeng Wang, Rui Song, Jie Zhang, Chuanyu Liu, Qianqian Gao, Qumiao Xu, Xiaoyu Wei, Hai-Xi Sun, Beiwei Ye, Yanan Wu, Ning Zhang, Guanglin Lei, Lingxiang Yu, Jin Yan, Guanghao Diao, Fanping Meng, Changqing Bai, Panyong Mao, Yeya Yu, Mingyue Wang, Yue Yuan, Qiuting Deng, Ziyi Li, Yunting Huang, Guohai Hu, Yang Liu, Xiaoqian Wang, Ziqian Xu, Peipei Liu, Yuhai Bi, Yi Shi, Shaogeng Zhang, Zhihai Chen, Jian Wang, Xun Xu, Guizhen Wu, Fu-Sheng Wang, George F. Gao, Longqi Liu, William J. Liu
Journal: Immunity (2020)
The NIH COBRE Center for Cancer Experimental Therapeutics at the University of Kansas.
Authors: Gunda I. Georg
Journal: Cancer Research (2004)

Three state institutions, The University of Kansas, Kansas State University, and Emporia State University, combined their resources and faculty to establish a Center to mentor junior faculty in cancer-related research and to create novel infrastructure needed for experimentation at the interface between chemistry and biology. The COBRE-supported faculty are partnered with established, active, senior faculty who serve as mentors. Unique Core facilities needed to identify novel bioactive compounds that are useful as basic biomedical research tools, and potential therapeutic agents have been established. One new core facility is a laboratory for high throughput screening (http://www.hts.ku.edu/index.shtml), the other one provides medicinal and combinatorial chemistry support. Two new Cores are operated by an experienced group of investigators with expertise in the areas of medicinal chemistry, combinatorial chemistry, cell and molecular biology, biochemistry, cancer cell biology, and the development of novel bioassays for compound and cellular target identification. The combination of expertise for the generation and analysis of novel compounds, together with that for the development of bioassays for screening, offers a unique opportunity for joining two research areas into one combined effort. This presentation will review the major programmatic and scientific outcomes from this Center.
The Mechanisms of PIM Kinase Inhibitor, SGI-1776 Free Base, in Treating Myeloma-Associated Bone Disease
Authors: Qingxiao Chen, Jingsong He, Huiyao Gu, Xi Huang, Jing Chen, Zhang En Fan, Xing Guo, Haimeng Yan, He Huang, Zhen Cai
Journal: Blood (2017)
Abstract 15738: Smartphone Application for Instant Detection of Recurrent Atrial Fibrillation
Authors: Thijs Vandenberk, Lien Desteghe, Valentino D’Onofrio, Kiki Kluts, Tine Proesmans, Valerie Storms, Inge M Thijs, Paul Dendale, Pieter M Vandervoort
Journal: Circulation (2018)

Introduction: Atrial Fibrillation (AF) is the most common hearth rhythm disorder with a prevalence of 1 to 2% of the world population. Current usual care (UC) focuses on reconverting the irregular ...