tbuckley/cabot-search huggingface dataset:
Molecular Approaches to Hereditary Diseases of the Nervous System: Huntington's Disease as a Paradigm
Authors: N S Wexler, E A Rose, D E Housman
Journal: Annual Review of Neuroscience (1991)

It should come as no surprise to the neurobiologist that two fifths of the 50,000-100,000 genes in the human genome are expressed in the brain. Rather more daunting is the fact that of the more than 3000 hereditary disorders described in Mendelian Inheritance in Man (McKusick 1989), one third of them produce significant CNS pathology. Only recently have we had the tools to understand these disorders on a more fundamental basis. These naturally occurring lesions of the nervous system can be exceptionally fine scalpels revealing molecules, pathways, and connections hitherto unknown. Huntington's disease (HD) has for years served as a model for teaching
Computerized telephone assessment of the "concrete" needs of chemotherapy outpatients: a feasibility study.
Authors: K Siegel, F P Mesagno, J Y Chen, L Klein, M E Bowles, M McKenna, S Peyser, G Christ
Journal: Journal of Clinical Oncology (1988)

The feasibility of using a computer-automated telephone outreach system to routinely assess the needs of chemotherapy outpatients was evaluated. The automated intervention was designed as a cost-efficient strategy for assessing patients' needs on a periodic basis so that emerging needs could be identified in a timely way. Ninety-seven chemotherapy outpatients were surveyed at least once over the telephone by a computer in a high-quality, digitally stored voice asking 12 questions regarding the patients' "concrete" needs. Early results of this larger ongoing study, in which patients are scheduled to be called every 4 to 6 weeks for approximately four months, indicated that computer-automated surveys had broad-based acceptance among our outpatients and that patients were able to comply accurately with the survey's instructions. Furthermore, the speech recognition system was found to be reliable, and patients' response patterns to the automated surveys valid. Nonparticipation in this study (28.0%) was not substantially higher than in our previous research within this patient population and neither nonparticipation nor attrition appeared significantly attributable to the automation itself. This method offers the potential for cost-efficient, universal, and ongoing assessment of patient needs, facilitating timely intervention, and efficient use of professional staff.
Bortezomib Combined Chemotherapy for Multiple Myeloma Patients Who are Candidate for Autologous Stem Cell Transplant
Authors: Natsuko Tsushita, Kanae Imai, Toshiyasu Sakai, Kotaro Miyao, Tomonori Kato, Keiko Niimi, Masashi Sawa
Journal: Annals of Oncology (2014)
Functional Tests for Myocardial Ischemia
Authors: J R Levinson, T E Guiney, C A Boucher
Journal: Annual Review of Medicine (1991)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
A randomized trial of adjuvant chemotherapy in head and neck cancer.
Authors: S G Taylor, E Applebaum, J L Showel, M Norusis, L D Holinger, J C Hutchinson, A K Murthy, D D Caldarelli
Journal: Journal of Clinical Oncology (1985)

Ninety-five patients with squamous cell carcinoma of the head and neck were entered into a randomized study testing a two-week course of induction chemotherapy with methotrexate and leucovorin given prior to regional therapy. In addition, following regional therapy, patients randomized to chemotherapy were to receive similar methotrexate courses every three months for one year. Poor tolerance to this regimen after radiation and surgery led to a change in the chemotherapy following regional therapy to a combination of Adriamycin (Adria Laboratories, Columbus, Ohio) and cisplatin every three weeks for four cycles after the first 35 patients had been entered. Nine cases were ineligible and four lacked any follow-up data, leaving 82 analyzable cases. Using Cox regression analysis, no differences in the percentage of patients achieving disease control, the relapse-free survival, or the overall survival were identified between any treatment group. As has been described in many pilot studies of induction chemotherapy of head and neck cancer, chemotherapy responders had a more favorable disease-free survival than chemotherapy nonresponders in the total group of patients receiving adjuvant chemotherapy. However, correcting for imbalances in the expected three year disease-free survival of these patients, based on their disease site and stage, erased this difference, indicating tumor response to this regimen of chemotherapy is not an independent factor affecting disease outcome. The division of patients into arbitrary prognostic categories based on the expected outcome for each specific tumor site and stage proved to be a useful method for balancing treatment groups, given the multiple site-stage combinations within the upper aerodigestive tract. The defined prognostic categories were the single most sensitive predictors of relapse-free and overall survival.
Hemochromatosis: Course and Treatment
Authors: S Sherlock
Journal: Annual Review of Medicine (1976)

The iron storage diseases include all conditions with excess iron in the liver. Two types are sometimes distinguished: hemochromatosis with associated tissue damage and usually cirrhosis, and hemosiderosis where iron overload is seen without liver injury (1). The term hemochromatosis is usually associated with the inborn, idi­ opathic hereditary hemochromatosis, but other forms of hemochromatosis must also be considered, including that associated with alcoholic liver disease, with blood disorders and with some forms of porphyria.
Clinical Assessment of Individualized Glycemic Goals in Patients With Type 2 Diabetes: Formulation of an Algorithm Based on a Survey Among Leading Worldwide Diabetologists
Authors: Avivit Cahn, Itamar Raz, Yosef Kleinman, Ran Balicer, Moshe Hoshen, Nicky Lieberman, Naomi Brenig, Stefano Del Prato, William T. Cefalu
Journal: Diabetes Care (2015)

OBJECTIVE Observations over the past few years have demonstrated the need to adjust glycemic targets based on parameters pertaining to individual patient characteristics and comorbidities. However, the weight and value given to each parameter will clearly vary depending on the experience of the provider, the characteristics of the patient, and the specific clinical situation. RESEARCH DESIGN AND METHODS To determine if there is current consensus on a global level with regard to identifying these parameters and their relative importance, we conducted a survey among 244 key worldwide opinion-leading diabetologists. Initially, the physicians were to rank the factors they take into consideration when setting their patients' glycemic target according to their relative importance. Subsequently, six clinical vignettes were presented, and the experts were requested to suggest an appropriate glycemic target. The survey results were used to formulate an algorithm according to which an estimate of the patient's glycemic target based on individualized parameters can be computed. Three additional clinical cases were submitted to a new set of experts for validation of the algorithm. RESULTS A total of 151 (61.9%) experts responded to the survey. The parameters “life expectancy” and “risk of hypoglycemia from treatment” were considered to be the most important. “Resources” and “disease duration” ranked the lowest. An algorithm was constructed based on survey results. It was validated by presenting three new cases to 57 leading diabetologists who suggested glycemic targets that were similar to those calculated by the algorithm. CONCLUSIONS The resultant suggested algorithm is an additional decision-making tool offered to the clinician to supplement clinical decision making when considering a glycemic target for the individual patient with diabetes.
Parabens and Human Epidermal Growth Factor Receptor Ligand Cross-Talk in Breast Cancer Cells
Authors: Shawn Pan, Chaoshen Yuan, Abderrahmane Tagmount, Ruthann A. Rudel, Janet M. Ackerman, Paul Yaswen, Chris D. Vulpe, Dale C. Leitman
Journal: Environmental Health Perspectives (2015)

Background:Xenoestrogens are synthetic compounds that mimic endogenous estrogens by binding to and activating estrogen receptors. Exposure to estrogens and to some xenoestrogens has been associated with cell proliferation and an increased risk of breast cancer. Despite evidence of estrogenicity, parabens are among the most widely used xenoestrogens in cosmetics and personal-care products and are generally considered safe. However, previous cell-based studies with parabens do not take into account the signaling cross-talk between estrogen receptor α (ERα) and the human epidermal growth factor receptor (HER) family.Objectives:We investigated the hypothesis that the potency of parabens can be increased with HER ligands, such as heregulin (HRG).Methods:The effects of HER ligands on paraben activation of c-Myc expression and cell proliferation were determined by real-time polymerase chain reaction, Western blots, flow cytometry, and chromatin immunoprecipitation assays in ERα- and HER2-positive human BT-474 breast cancer cells.Results:Butylparaben (BP) and HRG produced a synergistic increase in c-Myc mRNA and protein levels in BT-474 cells. Estrogen receptor antagonists blocked the synergistic increase in c-Myc protein levels. The combination of BP and HRG also stimulated proliferation of BT-474 cells compared with the effects of BP alone. HRG decreased the dose required for BP-mediated stimulation of c-Myc mRNA expression and cell proliferation. HRG caused the phosphorylation of serine 167 in ERα. BP and HRG produced a synergistic increase in ERα recruitment to the c-Myc gene.Conclusion:Our results show that HER ligands enhanced the potency of BP to stimulate oncogene expression and breast cancer cell proliferation in vitro via ERα, suggesting that parabens might be active at exposure levels not previously considered toxicologically relevant from studies testing their effects in isolation.Citation:Pan S, Yuan C, Tagmount A, Rudel RA, Ackerman JM, Yaswen P, Vulpe CD, Leitman DC. 2016. Parabens and human epidermal growth factor receptor ligand cross-talk in breast cancer cells. Environ Health Perspect 124:563–569; http://dx.doi.org/10.1289/ehp.1409200
Development of siRNA-loaded chitosan nanoparticles targeting Galectin-1 for the treatment of glioblastoma multiforme via intranasal administration
Authors: Matthias Van Woensel, Nathalie Wauthoz, Rémi Rosière, Véronique Mathieu, Robert Kiss, Florence Lefranc, Brecht Steelant, Ellen Dilissen, Stefaan W. Van Gool, Thomas Mathivet, Holger Gerhardt, Karim Amighi, Steven De Vleeschouwer
Journal: Journal of Controlled Release (2016)
Is higher serum cholesterol associated with altered tendon structure or tendon pain? A systematic review
Authors: Benjamin J Tilley, Jill L Cook, Sean I Docking, James E Gaida
Journal: British Journal of Sports Medicine (2015)

Background Tendon pain occurs in individuals with extreme cholesterol levels (familial hypercholesterolaemia). It is unclear whether the association with tendon pain is strong with less extreme elevations of cholesterol. Objective To determine whether lipid levels are associated with abnormal tendon structure or the presence of tendon pain. Methods We conducted a systematic review and meta-analysis. Relevant articles were found through an electronic search of 6 medical databases—MEDLINE, Cochrane, AMED, EMBASE, Web of Science and Scopus. We included all case–control or cross-sectional studies with data describing (1) lipid levels or use of lipid-lowering drugs and (2) tendon structure or tendon pain. Results 17 studies (2612 participants) were eligible for inclusion in the review. People with altered tendon structure or tendon pain had significantly higher total cholesterol, low-density lipoprotein cholesterol and triglycerides, as well as lower high-density lipoprotein cholesterol; with mean difference values of 0.66, 1.00, 0.33, and −0.19 mmol/L, respectively. Conclusions The results of this review indicate that a relationship exists between an individual’s lipid profile and tendon health. However, further longitudinal studies are required to determine whether a cause and effect relationship exists between tendon structure and lipid levels. This could lead to advancement in the understanding of the pathoaetiology and thus treatment of tendinopathy.
Impending airway obstruction after dental extractions
Authors: Kemal Tekeli, Guven Kaya, Samuel Grant, Michael Williams, David Howlett
Journal: BMJ (2015)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Impending airway obstruction after dental extractions Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Cortical connections and parallel processing: Structure and function
Authors: Dana H. Ballard
Journal: Behavioral and Brain Sciences (1986)

Abstract The cerebral cortex is a rich and diverse structure that is the basis of intelligent behavior. One of the deepest mysteries of the function of cortex is that neural processing times are only about one hundred times as fast as the fastest response times for complex behavior. At the very least, this would seem to indicate that the cortex does massive amounts of parallel computation. This paper explores the hypothesis that an important part of the cortex can be modeled as a connectionist computer that is especially suited for parallel problem solving. The connectionist computer uses a special representation, termed value unit encoding, that represents small subsets of parameters in a way that allows parallel access to many different parameter values. This computer can be thought of as computing hierarchies of sensorimotor invariants. The neural substrate can be interpreted as a commitment to data structures and algorithms that compute invariants fast enough to explain the behavioral response times. A detailed consideration of this model has several implications for the underlying anatomy and physiology.
New cases of HIV in Europe reach highest level since 1980s
Authors: Jacqui Wise
Journal: BMJ (2015)

Europe has recorded the highest number of new HIV cases ever, and most of the growth came from eastern European countries, figures have shown.

Surveillance data released by the European Centre for Disease Prevention and Control and the World Health Organization’s Regional Office for Europe1 showed that 142 197 people had HIV newly diagnosed in 2014, the highest number recorded since reporting began in the 1980s. Some 77% of these new cases were diagnosed in the east of the region.

Since 2005 the rates of new diagnoses have …
PKM2 regulates neural invasion of and predicts poor prognosis for human hilar cholangiocarcinoma
Authors: Guanzhen Yu, Wenlong Yu, Guangzhi Jin, Dongyun Xu, Ying Chen, Tian Xia, Allan Yu, Wenzheng Fang, Xiaoli Zhang, Zhaosheng Li, Keping Xie
Journal: Molecular Cancer (2015)

The therapeutic and prognostic value of the glycolytic enzymes hexokinase, phosphofructokinase, and pyruvate kinase (PK) has been implicated in a variety of cancers, while their roles in treatment of and prognosis for hilar cholangiocarcinoma (HC) remain unclear. In this study, we determined the expression of PKM2 in and its impact on biology and clinical outcome of human HC.The regulation and function of PKM2 in HC pathogenesis was evaluated using human tissues, molecular and cell biology, and animal models, and its prognostic significance was determined according to its impact on patient survival.We found that expression of hexokinase 1 and the M2 splice isoform of PK (PKM2) was upregulated in HC tissues and that this expression correlated with tumor recurrence and outcome. PKM2 expression was increased in HC cases with chronic cholangitis as demonstrated by isobaric tags for relative and absolute quantification. High PKM2 expression was highly correlated with high syndecan 2 (SDC2) expression and neural invasion. PKM2 downregulation led to a decrease in SDC2 expression. Treatment with metformin markedly suppressed PKM2 and SDC2 expression at both the transcriptional and posttranscriptional levels and inhibited HC cell proliferation and tumor growth.PKM2 regulates neural invasion of HC cells at least in part via regulation of SDC2. Inhibition of PKM2 and SDC2 expression contributes to the therapeutic effect of metformin on HC. Therefore, PKM2 is an independent prognostic factor and potential therapeutic target for human HC.
Guidelines for the Early Management of Adults With Ischemic Stroke
Authors: Harold P. Adams, Gregory del Zoppo, Mark J. Alberts, Deepak L. Bhatt, Lawrence Brass, Anthony Furlan, Robert L. Grubb, Randall T. Higashida, Edward C. Jauch, Chelsea Kidwell, Patrick D. Lyden, Lewis B. Morgenstern, Adnan I. Qureshi, Robert H. Rosenwasser, Phillip A. Scott, Eelco F.M. Wijdicks
Journal: Circulation (2007)

Purpose— Our goal is to provide an overview of the current evidence about components of the evaluation and treatment of adults with acute ischemic stroke. The intended audience is physicians and other emergency healthcare providers who treat patients within the first 48 hours after stroke. In addition, information for healthcare policy makers is included. Methods— Members of the panel were appointed by the American Heart Association Stroke Council’s Scientific Statement Oversight Committee and represented different areas of expertise. The panel reviewed the relevant literature with an emphasis on reports published since 2003 and used the American Heart Association Stroke Council’s Levels of Evidence grading algorithm to rate the evidence and to make recommendations. After approval of the statement by the panel, it underwent peer review and approval by the American Heart Association Science Advisory and Coordinating Committee. It is intended that this guideline be fully updated in 3 years. Results— Management of patients with acute ischemic stroke remains multifaceted and includes several aspects of care that have not been tested in clinical trials. This statement includes recommendations for management from the first contact by emergency medical services personnel through initial admission to the hospital. Intravenous administration of recombinant tissue plasminogen activator remains the most beneficial proven intervention for emergency treatment of stroke. Several interventions, including intra-arterial administration of thrombolytic agents and mechanical interventions, show promise. Because many of the recommendations are based on limited data, additional research on treatment of acute ischemic stroke is needed.
Tailored-CuO-nanowire decorated with folic acid mediated coupling of the mitochondrial-ROS generation and miR425-PTEN axis in furnishing potent anti-cancer activity in human triple negative breast carcinoma cells
Authors: Manisha Ahir, Saurav Bhattacharya, Soumendu Karmakar, Ayan Mukhopadhyay, Sudeshna Mukherjee, Swatilekha Ghosh, Sreya Chattopadhyay, Prasun Patra, Arghya Adhikary
Journal: Biomaterials (2015)
A Metabolome-Wide Association Study of Kidney Function and Disease in the General Population
Authors: Peggy Sekula, Oemer-Necmi Goek, Lydia Quaye, Clara Barrios, Andrew S. Levey, Werner Römisch-Margl, Cristina Menni, Idil Yet, Christian Gieger, Lesley A. Inker, Jerzy Adamski, Wolfram Gronwald, Thomas Illig, Katja Dettmer, Jan Krumsiek, Peter J. Oefner, Ana M. Valdes, Christa Meisinger, Josef Coresh, Tim D. Spector, Robert P. Mohney, Karsten Suhre, Gabi Kastenmüller, Anna Köttgen
Journal: Journal of the American Society of Nephrology (2015)

Small molecules are extensively metabolized and cleared by the kidney. Changes in serum metabolite concentrations may result from impaired kidney function and can be used to estimate filtration (e.g., the established marker creatinine) or may precede and potentially contribute to CKD development. Here, we applied a nontargeted metabolomics approach using gas and liquid chromatography coupled to mass spectrometry to quantify 493 small molecules in human serum. The associations of these molecules with GFR estimated on the basis of creatinine (eGFRcr) and cystatin C levels were assessed in ≤1735 participants in the KORA F4 study, followed by replication in 1164 individuals in the TwinsUK registry. After correction for multiple testing, 54 replicated metabolites significantly associated with eGFRcr, and six of these showed pairwise correlation (r≥0.50) with established kidney function measures: C-mannosyltryptophan, pseudouridine, N-acetylalanine, erythronate, myo-inositol, and N-acetylcarnosine. Higher C-mannosyltryptophan, pseudouridine, and O-sulfo-L-tyrosine concentrations associated with incident CKD (eGFRcr <60 ml/min per 1.73 m(2)) in the KORA F4 study. In contrast with serum creatinine, C-mannosyltryptophan and pseudouridine concentrations showed little dependence on sex. Furthermore, correlation with measured GFR in 200 participants in the AASK study was 0.78 for both C-mannosyltryptophan and pseudouridine concentration, and highly significant associations of both metabolites with incident ESRD disappeared upon adjustment for measured GFR. Thus, these molecules may be alternative or complementary markers of kidney function. In conclusion, our study provides a comprehensive list of kidney function-associated metabolites and highlights potential novel filtration markers that may help to improve the estimation of GFR.
Identification of ANLN as ETV6 partner gene in recurrent t(7;12)(p15;p13): a possible role of deregulated ANLN expression in leukemogenesis
Authors: Paulo Vidal Campregher, Welbert de Oliveira Pereira, Bianca Lisboa, Renato Puga, Ricardo Helman, Mariana Miyagi, Evelyn Helena Ascendino da Mata, Tarcila Santos Datoguia, Elvira Deolinda Rodrigues Pereira Velloso, Nydia Strachman Bacal, Jeffrey S. Ross, Siraj Ali, Vincent Miller, Fernando Ferreira Costa, Nelson Hamerschlak, Fabio Pires de Souza Santos
Journal: Molecular Cancer (2015)

The ETV6 gene encodes an ETS family transcription factor that is involved in a myriad of chromosomal rearrangements found in hematological malignancies and other neoplasms. A recurrent ETV6 translocation, previously described in patients with acute myeloid leukemia (AML) (Genes Chromosomes Cancer 51:328-337,2012, Leuk Res 35:e212-214, 2011), whose partner has not been identified is t(7;12)(p15;p13). We herein report that the t(7;12)(p15;p13) fuses ETV6 to ANLN, a gene not previously implicated in the pathogenesis of hematological malignancies, and we demonstrate that this translocation leads to high expression of the fusion transcript in the myeloid and lymphoid lineages.