tbuckley/cabot-search huggingface dataset:
The RNA Modification <i>N</i> <b>6</b>-Methyladenosine and Its Implications in Human Disease
Authors: Pedro J. Batista
Journal: Genomics Proteomics & Bioinformatics (2017)

Abstract Impaired gene regulation lies at the heart of many disorders, including developmental diseases and cancer. Furthermore, the molecular pathways that control gene expression are often the target of cellular parasites, such as viruses. Gene expression is controlled through multiple mechanisms that are coordinated to ensure the proper and timely expression of each gene. Many of these mechanisms target the life cycle of the RNA molecule, from transcription to translation. Recently, another layer of regulation at the RNA level involving RNA modifications has gained renewed interest of the scientific community. The discovery that N6-methyladenosine (m6A), a modification present in mRNAs and long noncoding RNAs, can be removed by the activity of RNA demethylases, launched the field of epitranscriptomics; the study of how RNA function is regulated through the addition or removal of post-transcriptional modifications, similar to strategies used to regulate gene expression at the DNA and protein level. The abundance of RNA post-transcriptional modifications is determined by the activity of writer complexes (methylase) and eraser (RNA demethylase) proteins. Subsequently, the effects of RNA modifications materialize as changes in RNA structure and/or modulation of interactions between the modified RNA and RNA binding proteins or regulatory RNAs. Disruption of these pathways impairs gene expression and cellular function. This review focuses on the links between the RNA modification m6A and its implications in human diseases.
Evolutionary divergence of human p53 binding sites: use of high throughput DNA binding assays to characterize functional variation in cell cycle and apoptosis pathways
Authors: Douglas Bell, Monica Horvath, Maher Noureddine
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4432 

Characterizing gene-environment interaction requires both identification disease pathway genes and evaluation of how their inherent variation affects exposure-response phenotype. The p53 master regulatory gene is activated upon exposure to DNA damaging agents and binds to cis-acting response elements (REs) that control expression of cell cycle, DNA repair, and apoptosis-related genes. We have developed new bioinformatics and molecular approaches for characterizing variation in p53 binding sites. We employed comparative genomics to evaluate the sequence conservation of 83 experimentally-validated human p53 REs and compared p53 RE conservation rates with those from NFKB and NRF2, genes that exhibit high interspecific conservation across mammals. Surprisingly, the average p53 RE was not significantly more conserved than background genomic sequence. The common technique of filtering binding site predictions by 80% rodent sequence identity would not only give a false positive rate of ~19%, but miss up to 57% of true p53 RE’s. Examination of interspecific DNA base substitutions as a function of position in the p53 consensus sequence revealed an unexpected excess of diversity in apoptosis-regulating RE's versus cell cycle-controlling RE’s (rodent comparisons: p-values <1.0 E-12). This suggests these two pathways have been under different selection pressures throughout mammalian evolution. Thus comparative genomics must be used judiciously in the identification and evaluation of new, putative p53 gene regulatory elements and may be productive for p53 RE’s regulating cell cycle genes but not for apoptosis genes.

To characterize p53 binding at the molecular level, a high-throughput multiplex method has been developed for measurement of p53 binding to RE sequences attached to fluorescent microspheres. The method shows low variability among replicates (<10%) and promises to be a useful alternative to laborious gel-shift assays (i.e. EMSA). We have tested the binding of activated p53 (nuclear extracts from doxorubicin-treated cells) to 10-15 multiplexed 50-mer oligos containing variants of the p53 response element consensus (RRRCWWGYYY-N-RRRCWWGYYY) and a nonbinding negative control oligo. Strong binding to the consensus sequence was observed and altering one or more nucleotides produced variation in binding over a large dynamic range (3 logs). Changing the conserved C or G nucleotides produced the largest magnitude changes. In order to test a position weight matrix-based binding model we have tested a total of 85 variants of the consensus element. This sensitive method detects single nucleotide binding differences. We are testing how single nucleotide polymorphisms in putative p53 response elements affect binding by p53 and evaluating binding to response elements in p53 regulated cell cycle and apoptosis genes.
Task Force 7: Pediatric Cardiology Fellowship Training in Pulmonary Hypertension, Advanced Heart Failure, and Transplantation
Authors: Steven A. Webber, Daphne T. Hsu, D. Dunbar Ivy, Thomas J. Kulik, Elfriede Pahl, David N. Rosenthal, W. Robert Morrow, Jeffrey A. Feinstein
Journal: Circulation (2015)
Recent advances: International perspectives on health inequalities and policy
Authors: D. A Leon
Journal: BMJ (2001)

Inequalities and inequities in health have long been central to the concerns of public health.Governments in several countries, including the United Kingdom, have recently shown renewed interest in tackling these issues. 1Concerted attempts have also been made to push them up the global health policy agenda, 2-4 and at the same time international agencies and donors are giving priority to efforts to reduce poverty.In this article we provide an overview of the current debates around inequity, inequalities, poverty, and health, drawing together current international understandings of the problem.
Comorbidities in Medicare patients with and without breast cancer
Authors: M. Danese, C. O'Malley, D. Kim, K. Lindquist, M. Gleeson, R. Griffiths, D. Wyszynski
Journal: Journal of Clinical Oncology (2009)

6533 Background: Patients with comorbidities may be at increased risk for adverse effects from treatment. We used the SEER-Medicare linked dataset to see if patients with breast cancer had a higher prevalence and subsequent incidence (after diagnosis) of comorbid conditions compared to patients without breast cancer. Methods: We selected all women with breast cancer across all stages, diagnosed from 1998–2002 with follow up through 2005. Patients were at least 66 years old with at least 12 months of non-HMO Medicare coverage prior to diagnosis. One non-cancer patient was matched to each breast cancer patient on sex and county of residence, and was assigned the cancer diagnosis date of her matched subject. Comorbidities were identified through groups of comorbidity-specific International Classification of Diseases, 9th revision (ICD-9) codes used in Medicare claims. Claims only for diagnostic testing were excluded, and outpatient-based diagnosis codes were required to be present at least twice with at least 30 days in between to be included. Prevalence at baseline (%) and incidence rates (per 1,000 person-years) and their 95% confidence intervals were calculated for each comorbidity. Rates in the non-cancer group were standardized to the age and race distribution of the breast cancer group to control for potential confounding. Results: 52,977 cancer patients met the inclusion criteria. See table for prevalence and incidence estimates. Conclusions: Physicians should be aware that patients with breast cancer have higher prevalence and subsequent incidence of these comorbidities compared to non-cancer subjects. These differences may be related to the diagnostic process, as well as to therapies used in cancer treatment. [Table: see text] [Table: see text]
Vaccination with NY-ESO-1 in Combination with Decitabine for Patients with MDS
Authors: Pragya Srivastava, Junko Matsuzaki, Benjamin E. Paluch, Stephanie Kaufman, Adam R. Karpf, Kunle Odunsi, Austin Miller, Justin Kocent, Eunice S. Wang, Michael J. Nemeth, Elizabeth A. Griffiths
Journal: Blood (2016)
Mepolizumab or Placebo for Eosinophilic Granulomatosis with Polyangiitis
Authors: Michael E. Wechsler, Praveen Akuthota, David Jayne, Paneez Khoury, Amy Klion, Carol A. Langford, Peter A. Merkel, Frank Moosig, Ulrich Specks, Maria C. Cid, Raashid Luqmani, Judith Brown, Stephen Mallett, Richard Philipson, Steve W. Yancey, Jonathan Steinfeld, Peter F. Weller, Gerald J. Gleich
Journal: New England Journal of Medicine (2017)

Eosinophilic granulomatosis with polyangiitis is an eosinophilic vasculitis. Mepolizumab, an anti–interleukin-5 monoclonal antibody, reduces blood eosinophil counts and may have value in the treatment of eosinophilic granulomatosis with polyangiitis.
Long-Term Administration of Pemetrexed Raised Toxicity of Peripheral Edema Treated with Oral Anti-Diuretics
Authors: Kenichi Chikamori, Keisuke Aoe, Daizo Kishino, Hideki Katayama, Keiji Oishi, Chihiro Seki, Yoriyuki Murata, Kenji Sakamoto, Masami Okumura, Tadashi Maeda, Hiroshi Ueoka
Journal: Annals of Oncology (2012)
Transplantation of Kidneys from Donors Whose Hearts Have Stopped Beating
Authors: Yong W. Cho, Paul I. Terasaki, J. Michael Cecka, David W. Gjertson
Journal: New England Journal of Medicine (1998)

Attempts have recently been made to expand the number of cadaveric kidneys available for transplantation by using kidneys from donors without heartbeats in addition to those from brain-dead donors with beating hearts. We studied the efficacy of transplanting kidneys from donors without heartbeats on the basis of aggregate results from the Kidney Transplant Registry of the United Network for Organ Sharing.We compared the early function and survival rates of 229 kidney grafts from donors without heartbeats with those of 8718 grafts from cadaveric donors with heartbeats. All transplantations were performed at 64 U.S. transplantation centers. Cox proportional-hazards analysis was used to evaluate 10 major risk factors for graft failure.The survival rate at one year was 83 percent for kidney grafts from donors without heartbeats, as compared with 86 percent for grafts from donors with heartbeats (P=0.26). Among the kidneys from donors without heartbeats, the survival rate at one year was 89 percent for grafts from donors who had died of trauma, as compared with 78 percent for grafts from donors who had died of other causes (P=0.04). The survival rates were high for grafts from donors without heartbeats despite the poorer early function of these grafts; 48 percent of the recipients required dialysis within the first week after transplantation, as compared with 22 percent of the recipients of grafts from donors with heartbeats. The primary-failure rate for kidneys from donors without heartbeats was 4 percent, as compared with 1 percent for kidneys from donors with heartbeats.Transplantation of kidneys from donors whose hearts have stopped beating, especially those who have died of trauma, is often successful, and the use of kidneys from such donors could increase the overall supply of cadaveric kidney transplants.
Abstract 1344: Does Knowledge of Elevated High Sensitivity C-reactive Protein (hsCRP) Motivate Patients to Make Positive Lifestyle Changes to Reduce Cardiovascular Disease (CVD) Risk?
Authors: Lori Mosca, Ming Liao, Heidi Mochari
Journal: Circulation (2009)

The AHA and CDC suggest a benefit of measuring hsCRP beyond traditional risk factors is to motivate patients to make lifestyle changes to reduce CVD risk, however this hypothesis has not been forma...
Using global expression changes to determine the function of menin in endocrine tumorigenesis
Authors: Youngmi Ji, Vyomesh Patel, J. Silvio Gutkind, Settara Chandrasekharappa
Journal: Clinical Cancer Research (2007)

A42   Multiple Endocrine Neoplasia, type 1 (MEN1) is a familial cancer syndrome characterized primarily by tumors of the parathyroid, anterior pituitary and enteropancreatic endocrine tissues. Inactivating mutations in the tumor suppressor gene MEN1, encoding the protein menin, are responsible for the syndrome. Mice with heterozygous deletion of MEN1 develop endocrine tumors resembling the human MEN1 condition. However, the homozygous loss of Men1 results in early embryonic lethality, with the null embryos displaying defects in the neural tube, heart, liver, cranial and/or facial regions, indicating the importance of menin in embryonic development. To begin to address the biological role of menin in these contexts, we chose a microarray approach to identify menin-regulated genes using RNAs from mouse embryonic fibroblast (MEF) cell lines established from wild-type and menin null embryos (E9.5). In addition, we expressed menin stable and transiently in menin-null MEFs, at different post infection time points (3h, 6h, 12h, 24h), to investigate gene expression changes caused by menin.  Among the genes that were down regulated in the absence of menin (>2 fold; p
The Epigenetics of Intrauterine Smoke Exposure: Can Maternal Vitamin C Supplementation Prevent Neonatal Respiratory Disease?
Authors: Sunita Sharma
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

yet to translate into meaningful clinical effects.Amiloride, the prototypical ENaC inhibitor, increases the ASL height of cultured airway, but several clinical trials have failed to demonstrate appreciable benefit after nebulized administration (14, 15).A long-acting and potent amiloride analog, GS-9411, had initial promise as well, but unfortunately, systemic effects including hyperkalemia limited its potential in early clinical trials ( 16).An additional long-acting ENaC inhibitor, Parion-1037 (now VX-371), is currently in clinical trials, and the results remain pending.SPX-101 has several distinguishing features that may improve its efficacy compared with amiloride derivatives.First, SPX-101 has a prolonged duration of action that may provide durable ASL expansion, simplify dosing, and prolong the effects of hydration strategies such as nebulized hypertonic saline.Another compelling feature of SPX-101 is that systemic effects of ENaC inhibition, such as hyperkalemia or volume depletion, have not been observed in preclinical animal models.Although Tarran and colleagues have made impressive progress in identifying SPLUNC1 and developing SPX-101, it remains to be seen whether these efforts will translate into clinical benefit, particularly above that seen with hypertonic saline, for individuals with CF.Novel therapeutics such as SPX-101 and the next-generation cystic transmembrane conductance regulator correctors make the CF future bright, and we look forward to these upcoming studies.
Hepatitis C Virus Infection: Evidence for an Association With Type 2 Diabetes
Authors: Alessandro Antonelli, Clodoveo Ferri, Poupak Fallahi, Silvia Martina Ferrar, Fernando Goglia, Ele Ferrannini
Journal: Diabetes Care (2006)

We agree with Skowronski et al. (1) that the type of diabetes manifested by patients with HCV chronic infection (HCV+) may not be classical type 2 diabetes, and the phenotypic characterization of our patients shows just that. The labeling of HCV+ patients as type 2 diabetes is purely conventional and possibly inaccurate: the lines separating type 1 diabetes, from latent autoimmune diabetes in …
Patient data were shared with Google on an “inappropriate legal basis,” says NHS data guardian
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The Department of Health for England’s most senior adviser on data protection has criticised the NHS for a deal it signed to share patient records with Google’s DeepMind program.

In a letter, obtained by Sky News, Fiona Caldicott, national data guardian, expressed the view that DeepMind had received 1.6 million patient records on an “inappropriate legal basis.”1

The data were collected from patients at the Royal Free London NHS Foundation Trust to test a new app designed to detect and rapidly inform doctors and nurses of patients who may be at risk of acute kidney disease.

Google DeepMind …
Russian data refute the CLASH model
Authors: Pavel N Prudkov, Olga N Rodina
Journal: Behavioral and Brain Sciences (2017)

Abstract We examined the CLASH model using the data on climate and violence from the Russian Federation. The Russian Federation is a huge country with dramatic climatic differences between regions. Our results are absolutely inconsistent with the model. We consider there are a range of climates in which the human organism functions optimally. Deviations from the range cause impulsiveness and aggression.
Efficacy of different anti-HER2 drugs in first-line therapy for advanced breast cancer: Systematic review and meta-analysis.
Authors: Andre Deeke Sasse, Flavio Mavignier Carcano, Lucas Vieira dos Santos, Joao Paulo Da S.N. Lima
Journal: Journal of Clinical Oncology (2013)

e11500 Background: Anti-HER2 therapy has brought major gains to therapy of advanced breast cancer (ABC), however it is still not know if there are difference in efficacy between trastuzumab and lapatinib. We execute a systematic review and meta-analysis in order to measure the impact of anti-HER2 therapy on ABC outcome and to assess if any particular drug is more effective in this scenario. Methods: Randomized controlled trials comparing first-line antineoplastic drug plus minus antiHER2 therapy (either trastuzumab or lapatinib) in ABC patients were searched in major meeting proceedings and databases. The outcomes were overall survival (OS), progression-free survival (PFS), tumor response and safety. Meta-analyses were performed using random-effects model and outcomes measured by hazard ratio (HR) and pertinent 95% confidence intervals were calculated. Subgroup analyses and meta-regression were undertaken to compare and measure the impact of anti-HER2 drug used over the estimated effect size. Results: eight trials (1848 patients) were included, two trials used lapatinib whereas six used trastuzumab. In two trials, anti-HER2 therapy was combined to hormone therapy. All trials, except the one by Slamon, demanded tumors to be ISH+ or IHC 3+. The methodological quality of included trials was moderate to good. Either trastuzumab or lapatinib improved overall survival (HR 0.79; 95% CI 0.69-0.91; P=0.0008; I2=0%) with no difference bet drugs (test for difference P=0.75). PFS was also increased with antiHER2 addition with similar activity of trastuzumab and lapatinib (HR = 0.58; 95% CI 0.51-0.66; P&lt;0.0001; I2=0%, test for difference P= 0.42). Conclusions: The present meta-analysis confirmed the role of antiHER2 drugs as a valid first-line therapy for ABC. Furthermore, we failed to show any difference in efficacy between lapatinib and trastuzumab when combined to systemic therapy, both being acceptable options for antiHER2 therapy for ABC.
Trends in Hospital Cost, Length of Stay, Mortality, and Complication Rates in Patients with Acute Myeloid Leukemia in Teaching Versus Non-Teaching Hospitals: Data from the Nationwide Inpatient Sample from 1999-2013
Authors: Ankit Shah, Stuthi Perimbeti, Parshva Patel, Rachel Nathan, Daniel Kyung, Kristine Ward, Michael Styler, Maneesh Jain
Journal: Blood (2016)
Mapping multiple drivers of human obesity
Authors: R. Alexander Bentley, Michael J. O'Brien
Journal: Behavioral and Brain Sciences (2017)

Abstract The insurance hypothesis is a reasonable explanation for the current obesity epidemic. One alternative explanation is that the marketing of high-sugar foods, especially sugar-sweetened beverages, drives the rise in obesity. Another prominent hypothesis is that obesity spreads through social influence. We offer a framework for estimating the extent to which these different models explain the rise in obesity.
Upregulation of the Anti-Apoptotic Protein, Survivin, in Hematopoietic Cells in Sickle Cell Anemia and Effects of Hydroxyurea Therapy.
Authors: Carolina Lanaro, Carla Fernanda Franco-Penteado, Mariana R. B. Mello, Kleber Yotsumoto Fertrin, Marcos André C Bezerra, Dulcinéia M. Albuquerque, Nicola Conran, Sara T.O. Saad, Aderson S. Araujo, Fernando F. Costa
Journal: Blood (2009)
Abstract P225: Possible Involvement of Homer-1b/c in Gq-Mediated Hypertrophy in Cardiomyocytes
Authors: David R Grubb, Jieting Luo, Peter Iliades, Elizabeth A Woodcock
Journal: Circulation Research (2011)

Receptor activation of Gq causes hypertrophy in cardiomyocytes, via the activation of phospholipase Cβ 1b (PLCβ1b). PLCβ1b, localizes to the cardiac sarcolemma through an interaction with the multi-domain scaffolding molecule Shank-3 (SH3 and multiple ankyrin repeat domains protein 3; Grubb et al., 2011), which is required for PLC activation and for hypertrophic responses. In the CNS, Shank-3 forms higher order oligomeric complexes with three isoforms of Homer protein homolog 1 (Homer-1), Homer-1a, Homer-1b and Homer-1c. Homer-1b and Homer-1c link G-protein coupled receptors, ionotropic receptors, canonical transient receptor potential channel (TrpC) and intracellular calcium store regulators into a signaling complex. Homer-1a acts as a natural dominant negative, in dynamic competition with Homer-1b and Homer-1c. Neonatal rat ventricular myocytes (NRVM) infected with adenovirus expressing either Gαq(Q209L) (constitutively active Gαq), or its immediate down-stream effector, PLCβ1b, increased Homer-1b/c transcription. Incubation with phenylephrine/propranalol (α 1 -adrenergic agonist, PE/Pro) also increased Homer-1b/c, but not Homer-1a, mRNA. All treatments caused cardiomyocyte hypertrophy. There was no comparable increase in Homer-1b/c mRNA in NRVM expressing PLCβ1a (inactive splice variant) or incubated with fetal calf serum to induce hypertrophy by Gq-independent mechanisms. Homer-1b/c protein induced by PLCβ1b, Gαq or PE/Pro was primarily localized close to the sarcolemma along with Shank3, PLCβ1b and TrpC4. We conclude that Gαq/PLCβ1b-mediated signaling leads to the up-regulation of Homer-1b/c, that co-localizes with a signaling complex close to the sacrolemma. Induction of Homer-1b/c may be critical in facilitating localized Ca 2+ signaling and thereby promoting Gq dependent hypertrophy.
Particulate Array of Well-Ordered HIV Clade C Env Trimers Elicits Neutralizing Antibodies that Display a Unique V2 Cap Approach
Authors: Paola Martinez-Murillo, Karen Tran, Javier Guenaga, Gustaf Lindgren, Monika Àdori, Yu Feng, Ganesh E. Phad, Néstor Vázquez Bernat, Shridhar Bale, Jidnyasa Ingale, Viktoriya Dubrovskaya, Sijy O’Dell, Lotta Pramanik, Mats Spångberg, Martin Corcoran, Karin Loré, John R. Mascola, Richard T. Wyatt, Gunilla B. Karlsson Hedestam
Journal: Immunity (2017)
Detection of Avian Influenza Virus from Cloacal Swabs Using a Disposable Well Gate FET Sensor
Authors: Sungwook Park, Jaebin Choi, Minhong Jeun, Yongdeok Kim, Seong‐Su Yuk, Sang Kyung Kim, Chang‐Seon Song, Seok Lee, Kwan Hyi Lee
Journal: Advanced Healthcare Materials (2017)

Current methods to detect avian influenza viruses (AIV) are time consuming and lo inw sensitivity, necessitating a faster and more sensitive sensor for on‐site epidemic detection in poultry farms and urban population centers. This study reports a field effect transistor (FET) based AIV sensor that detects nucleoproteins (NP) within 30 minutes, down to an LOD of 10 3 EID 50 mL −1 from a live animal cloacal swab. Previously reported FET sensors for AIV detection have not targeted NPs, an internal protein shared across multiple strains, due to the difficulty of field‐effect sensing in a highly ionic lysis buffer. The AIV sensor overcomes the sensitivity limit with an FET‐based platform enhanced with a disposable well gate (DWG) that is readily replaceable after each measurement. In a single procedure, the virus‐containing sample is immersed in a lysis buffer mixture to expose NPs to the DWG surface. In comparison with commercial AIV rapid kits, the AIV sensor is proved to be highly sensitive, fast, and compact, proving its potential effectiveness as a portable biosensor.