tbuckley/cabot-search huggingface dataset:
Quantifying the Landscape for Development and Cancer from a Core Cancer Stem Cell Circuit
Authors: Chunhe Li, Jin Wang
Journal: Cancer Research (2015)

Abstract Cancer presents a serious threat to human health. The understanding of the cell fate determination during development and tumor-genesis remains challenging in current cancer biology. It was suggested that cancer stem cell (CSC) may arise from normal stem cells or be transformed from normal differentiated cells. This gives hints on the connection between cancer and development. However, the molecular mechanisms of these cell-type transitions and the CSC formation remain elusive. We quantified landscape, dominant paths, and switching rates between cell types from a core gene regulatory network for cancer and development. Stem cell, CSC, cancer, and normal cell types emerge as basins of attraction on associated landscape. The dominant paths quantify the transition processes among CSC, stem cell, normal cell, and cancer cell attractors. Transition actions of the dominant paths are shown to be closely related to switching rates between cell types, but not always to the barriers in between, because of the presence of the curl flux. During the process of P53 gene activation, landscape topography changes gradually from a CSC attractor to a normal cell attractor. This confirms the roles of P53 of preventing the formation of CSC through suppressing self-renewal and inducing differentiation. By global sensitivity analysis according to landscape topography and action, we identified key regulations determining cell-type switchings and suggested testable predictions. From landscape view, the emergence of the CSCs and the associated switching to other cell types are the results of underlying interactions among cancer and developmental marker genes. This indicates that the cancer and development are intimately connected. This landscape and flux theoretical framework provides a quantitative way to understand the underlying mechanisms of CSC formation and interplay between cancer and development. Cancer Res; 75(13); 2607–18. ©2015 AACR.
Different Th1, Th2, Th17 and Treg associated chemokine local pattern expression in lung in a murine model of allergic inflammation
Authors: You Lu, Carina Malmhäll, Madeleine Rådinger, Margareta Sjöstrand, Serena O'Neil, Bo Lundbäck, Jan Lötval, Apostolos Bossios
Journal: European Respiratory Journal (2011)

We have reported that Th1, Th2, Th17 and Treg cells is differently distributed in the lung during airway allergic inflammation. T helper cells express different chemokine receptors.We hypothesize that Th1, Th2, Th17 and Treg cells distribution in the lung is a result by different local chemokine expression.  Ovalbumin (OVA)-sensitized C57BL/6 mice were exposed intranasally to OVA or PBS on five days and lung tissue was taken 24 h after final allergen exposure. Peribronchial (Pb), perivascular (Pv) and alveoli (A) tissue was selected from lung tissue sections using Laser Microdissection and Pressure Catapulting technology. Total RNA was extracted and each location was pooled from three OVA/OVA mice. Chemokine gene expression was performed using RT-PCR gene array. Tissue from whole lung tissue section of an OVA/PBS mouse was used as control and results were expressed as fold change from control.  Chemokines/ligands for Th1-associated receptors; CCR2 (CCL2, CCL5, CCL7) and CCR5 (CCL3, CCL4, CCL5) were increased mainly in A followed by Pv and Pb tissue, while CXCR3 (CXCL10) was increased in Pv followed by A and Pb tissue. In Th2-associated CCR8 (CCL8) was most highly induced Pv (21.3fold) followed by Pb and A tissue. In Th2/Treg-associated CCR4 (CCL17, CCL22) the pattern was A, Pv, Pb, while in Treg/Th17 CCR7 (CCL19) was increased mainly in Pv then in Pb but not in A tissue.  Allergen exposure increased gene expression of all Th1, Th2, Treg and Th17 associated chemokines in lung. However, the expression pattern shows differences in both tissue distribution and magnitude, arguing for a high complex local milieu that can regulate T-cell subsets distribution.
IL-3 contributes to development of lupus nephritis in MRL/Ipr mice
Authors: Kerstin Renner, Fabian Johannes Hermann, Kathrin Schmidbauer, Yvonne Talke, Manuel Rodriguez Gomez, Gabriela Schiechl, Jens Schlossmann, Hilke Brühl, Hans-Joachim Anders, Matthias Mack
Journal: Kidney International (2015)
X-linked retinitis pigmentosa in two families with a missense mutation in the RPGR gene and putative change of glycine to valine at codon 60
Authors: Gerald A Fishman, Sandeep Grover, Samuel G Jacobson, Kenneth R Alexander, Deborah J Derlacki, Weiping Wu, Monika Buraczynska, Anand Swaroop
Journal: Ophthalmology (1998)
Abstract P5-15-12: Clinico-biological characteristics of patients surviving more than two years with metastatic breast cancer (MBC): Results of a transversal national multicentric survey
Authors: Delphine Loirat, Camille Tlemsani, Jennifer Arrondeau, Audrey Bellesoeur, Christophe Le Tourneau, Benoit Rousseau
Journal: Cancer Research (2015)

Abstract Introduction: MBC cancer patients may have prolonged survival, and MBC cancers can be considered as a chronic disease. The main goal of the present study was to describe the clinico-biological features of patients surviving more than two years with MBC. Method: During 4 months, we conducted a national multicentric survey about patients aged ≥ 18 in metastatic setting (all solid tumors) for more than 24 months. Clinico-biological data from 200 patients were collected in 39 French centers. Preliminary results of MBC patients (N=88, 87 women/one man) are presented. Results: Most of them were ductal carcinoma (88%), expressing hormonal receptor HR (77%). 43% of tumors overexpressed HER2 (HER2+ tumors: 43%; Triple negative tumors: 6%). Median age at MBC diagnosis was 53 years [29-85]. 18% had metastatic disease at diagnosis and 82 % were localized with a disease-free survival of 65 months [4-312]. Median time of MBC disease was 4,5 years [2-20]. At the time of MBC diagnosis, 64% of patients were not single; 55% were working while 30% were retired. At data collection, 89% of non-single patients were not separated, and 43 % of working patients at diagnosis were still working. Mean number of treatment lines in advanced disease was 4.7 [1-13]. 89% of MBC patients received at least one chemotherapy, 68% hormonotherapy, 70% targeted therapy and 38% had been included in at least one clinical trial. 97% of patients had a local treatment of their primary tumor. Concerning metastasis, 23% had a surgical treatment and 40% radiotherapy treatment. 80% of patients remain with PS of 0 or 1. Only 9% of patients were followed by a palliative care team, 24% by a psychologist and 23% by a nutritionist. Conclusion: Our preliminary results of suggest that an important proportion of MBC cancer patients who live more than 2 years are young, have been treated with chemotherapy, hormonal and targeted therapy, have participated to clinical trials and still have good performance status. No change in marital status was observed. Half of working patients at MBC diagnosis continue to work. Few of them received palliative care. This study may help to better describe long-term survivors with MBC, and socio-medical burden as cancer became a chronic disease. Citation Format: Delphine Loirat, Camille Tlemsani, Jennifer Arrondeau, Audrey Bellesoeur, Christophe Le Tourneau, Benoit Rousseau. Clinico-biological characteristics of patients surviving more than two years with metastatic breast cancer (MBC): Results of a transversal national multicentric survey [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-15-12.
Energy Metabolism in Human Erythrocytes
Authors: Stephen A. Feig, Stephen B. Shohet, David G. Nathan
Journal: Journal of Clinical Investigation (1971)

Exposure of red cells to fluoride produces a variety of metabolic alterations, most of which are based upon the secondary effects of enolase inhibition, which reduces pyruvate synthesis and interferes with the regeneration of diphosphopyridine nucleotide (NAD). Adenosine triphosphate (ATP) is consumed in the hexokinase and phosphofructokinase reactions but is not regenerated since the deficiency of NAD limits glyceraldehyde phosphate dehydrogenase. ATP depletion in the presence of fluoride and calcium induces a massive loss of cations and water.
New insights on dandruff/seborrhoeic dermatitis: the role of the scalp follicular infundibulum in effective treatment strategies
Authors: J.R. Schwartz, R. Shah, H. Krigbaum, J. Sacha, A. Vogt, U. Blume-Peytavi
Journal: British Journal of Dermatology (2011)

Journal Article New insights on dandruff/seborrhoeic dermatitis: the role of the scalp follicular infundibulum in effective treatment strategies Get access J.R. Schwartz, J.R. Schwartz Procter & Gamble, Sharon Woods Innovation Center, 11511 Reed Hartman Hwy, Cincinnati, OH 45241, U.S.A. James R. Schwartz. E‐mail: schwartz.jr.2@pg.com Search for other works by this author on: Oxford Academic Google Scholar R. Shah, R. Shah Procter & Gamble, Sharon Woods Innovation Center, 11511 Reed Hartman Hwy, Cincinnati, OH 45241, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar H. Krigbaum, H. Krigbaum Procter & Gamble, Sharon Woods Innovation Center, 11511 Reed Hartman Hwy, Cincinnati, OH 45241, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar J. Sacha, J. Sacha Procter & Gamble, Sharon Woods Innovation Center, 11511 Reed Hartman Hwy, Cincinnati, OH 45241, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar A. Vogt, A. Vogt Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science, Charité– Universitätsmedizin Berlin, Charitéplatz 1, D‐10117 Berlin, Germany Search for other works by this author on: Oxford Academic Google Scholar U. Blume‐Peytavi U. Blume‐Peytavi Department of Dermatology and Allergy, Clinical Research Center for Hair and Skin Science, Charité– Universitätsmedizin Berlin, Charitéplatz 1, D‐10117 Berlin, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 165, Issue s2, 1 October 2011, Pages 18–23, https://doi.org/10.1111/j.1365-2133.2011.10573.x Published: 01 October 2011
Abstract 11698: Pulmonary Hypertension in S100A1 KO Mice is Associated With Endothelial Cell Dysfunction and Impaired eNOS Activation Dependent in Part on the Receptor for Advanced Glycation End-Products (RAGE)
Authors: Krystyna Teichert-Kuliszewska, Jean-Francois Desjardins, Wolfgang M Kuebler, Thomas G Parker
Journal: Circulation (2014)

Background:  S100A1, a 10-kDa, Ca  2+ - binding protein is expressed in endothelial cells and its absence is associated with impaired production of nitric oxide (NO) and mild systemic hypertension. As endothelial dysfunction contributes to clinical and experimental pulmonary hypertension (PH), we investigated the impact of deleting S100A1 in knockout mice (KO) on pulmonary hemodynamic and endothelial function.   Methods and Results:  Under basal conditions in vivo, S100A1 deficient mice exhibited a significant elevation in right ventricular systolic pressure (28.41±3.6 vs.14.9±2.41 mmHg in wild-type (WT), p -4  M increased fluorescence 1.43±0.31-fold vs. 3.91±0.43-fold in WT, p 1177 , by exogenous S100A1 treatment (100nM, 30 min) was 2.19- fold greater in WT vs. KO (p   Conclusion:  Absence of S100A1 results in PH by disrupting its normal capacity to enhance pulmonary endothelial cell function by induction of eNOS activity and NO levels. The ability of exogenously administered S100A1 to rescue this phenotype mediated by RAGE represents a possible therapeutic target in the treatment of PH.
Original article: Impact of allergic rhinitis on asthma: effects on spirometric parameters
Authors: G. Ciprandi, I. Cirillo, A. Pistorio
Journal: Allergy (2007)

Close association exists between allergic rhinitis and asthma. Moreover, allergic rhinitis is a strong risk factor for the onset of asthma in adults. This study was aimed at evaluating a large group of patients with moderate-to-severe and persistent allergic rhinitis alone for investigating the presence of spirometric abnormalities and possible risk factors related to it.A total of 392 patients with persistent allergic rhinitis were prospectively and consecutively evaluated. Clinical examination, skin prick test and spirometry were performed in all patients.There were 24 (6.1%) patients with forced vital capacity (FVC < 80%) of predicted, 50 (12.8%) with forced expiratory volume in the first second (FEV(1) < 80%) of predicted and 341 (87.0%) with forced expiratory flow at 25% and 75% of the pulmonary volume (FEF(25-75)) < 80% of predicted. The logistic regression analysis evidenced that rhinitis duration (OR(Adj): 1.9/year) and sensitization to house dust mites (OR(Adj): 8.2) were significantly associated with impaired values of 2 or 3 spirometric parameters.This study highlights the close link between upper and lower airways and the role of some risk factors, such as duration and mites sensitization, as early prognostic markers of bronchial involvement in patients with moderate-to-severe and persistent allergic rhinitis alone.
Juxtaposed regions of extensive and minimal linkage disequilibrium in human Xq25 and Xq28
Authors: Patricia Taillon-Miller, Irma Bauer-Sardiña, Nancy L. Saccone, Jenna Putzel, Tarja Laitinen, Antonio Cao, Juha Kere, Giuseppe Pilia, John P. Rice, Pui-Yan Kwok
Journal: Nature Genetics (2000)
“Epigenethics” in the Neonatal Intensive Care Unit
Authors: Livio Provenzi, Rosario Montirosso
Journal: JAMA Pediatrics (2015)

Human behavioral epigenetics (HBE) is a fascinating area of research that holds promise to change our view of nature-nurture interconnection. In particular, the study of changes in DNA methylation applied to human development is revealing pathways through which early adversities are embedded in the developing biology of children, contributing to long-lasting programming of health and disease. 1 Notwithstanding, HBE holds the risk of a new reductionism grounded in nurture instead of nature. Researchers and clinicians have been recently warned about the lure of epigenetics and the risk of translating animal results and interpreting human findings in a strict deterministic way. 2 Critically, misleading conclusions would convey the idea of a direct impact of maternal behavior and physiology on the long-term wellbeing of infants and children, without taking into account the importance of the broader socioeconomic and health care environment. Herein, we reflect on HBE, referring to prematurity as an example to highlight potential benefits for research and clinical practice as well as ethical issues conveying a complex view of neonatal health care.
Breast Cancer: Diagnosis and Treatment.
Authors: I.M. Ariel, J.B. Clearly
Journal: Annals of Internal Medicine (1987)

This is a publication about the diagnosis and treatment of breast cancer with an appeal for unified reporting of end results. Nine chapters cover historical reviews, risk factors, pathology-receptors-immunology, detection and diagnosis, treatment of the potentially curable patient, and treatment of the patient with advanced disease. The three concluding chapters discuss reconstruction, special clinical situations, and support for the patient. The role of radiation therapy is presented well. The current status of chemotherapy, hormonal therapy and combined therapies is also addressed by authoritative authors.
Abstract MP02: Quantifying The Impact Of Maintenance And Changes Of Lifestyles On Risk Of Cardiovascular Disease And All-cause Mortality - The Doetinchem Cohort Study
Authors: Gerben Hulsegge, Martha L Daviglus, Yvonne T van der Schouw, Henriëtte A Smit, W M Verschuren
Journal: Circulation (2014)

Background: It is not fully understood to what extent changes in lifestyle over time influence the risk of cardiovascular disease (CVD) and death among healthy adults, since most studies assessed lifestyle at a single point in time. Objective: To investigate the association of maintenance and changes in lifestyle profiles over 5 years with risk of CVD and all-cause mortality. Methods: Healthy lifestyle factors (HLF), i.e., healthy diet, physically active, not smoking, moderate alcohol consumption, sufficient sleep duration, and normal weight were assessed among 5,290 CVD- and cancer-free adults aged 25-65 years in 1993-1997 (baseline examination). Participants were categorized as having unhealthy (0-2 HLF), moderately healthy (3-4 HLF), or healthy (5-6 HLF) lifestyles. They were subdivided as maintained, improved, or deteriorated HLF 5 years later (1998-2002). Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (95%CI) for combined fatal and non-fatal CVD and all-cause mortality following the risk-change period were estimated using Cox proportional hazards models. Results: Individuals who maintained their HLF had 62% lower risk of CVD (HR: 0.38, 95%CI: 0.23-0.64) (Figure 1) and 54% for all-cause mortality (HR: 0.46, 95%CI: 0.27-0.77) than those who maintained unhealthy lifestyles. In general, compared to maintenance of HLF, improvement and deterioration of HLF were associated with better or worse HRs than their baseline risks for CVD and all-cause mortality, respectively. Conclusion: Maintenance of a healthy lifestyle is associated with significant and independent low risk of CVD and all-cause mortality. Effort is needed to improve the adoption and maintenance of a healthy lifestyle.
More Scrutiny for Ingredients in Over-the-Counter Antiseptics
Authors: Rita Rubin
Journal: JAMA (2015)

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Abstract 2769: Impaired Skeletal Muscle Oxygen Utilization Contributes to Exercise Intolerance in Barth Syndrome
Authors: Carolyn T Spencer, Randall M Bryant, Barry Byrne, Elisabeth Heal, Renee Margossian, W. Todd Cade
Journal: Circulation (2007)

Objective s: Barth Syndrome (BTHS) is an X-linked mutation in the TAZ gene characterized by cardiolipin deficiency, mitochondrial dysfunction and cardio-skeletal myopathy. We hypothe- sized that abnormal skeletal muscle oxygen (O 2 ) utilization contributes to exercise intolerance in BTHS. Methods : Boys with BTHS (n=13) and healthy male controls (n=7) performed a graded exercise test on a cycle ergometer with continuous metabolic and EKG monitoring. Near infrared spectroscopy (NIRS), an indirect measure of tissue O 2 saturation and index of skeletal muscle O 2 utilization, was applied to the vastus lateralis during exercise. Cardiac function in BTHS was assessed by echocardiography and serum BNP to examine the relationship between resting cardiac function and exercise capacity in BTHS. Results : Age (16±5 vs 13±3 years; p=0.22), BMI (17±3 vs. 20±5; p=0.14) and BSA (1.0±0.5 vs 1.2±0.6 m 2 ; p=0.3) were not different between BTHS and controls. BTHS had lower peak VO 2 (19±6 vs. 52±6 ml/kg/min, p &lt; 0.001), lower % of predicted peak VO 2 (40±10% vs. 115±12%, p=0.0004), lower peak work rate (58±18 vs. 205±69 watts, p=0.0004), and lower peak O 2 pulse (4.6±1.6 vs. 14±6 ml O 2 /kg/beat, p&lt; 0.00001) than controls. Peak HR in BTHS was lower but remained within normal peak predicted rate (172±14 vs. 197±11 bpm, p=0.001). Vastus lateralis tissue O 2 saturation at peak exercise decreased from baseline in controls as expected (-18±16%, p&lt;0.001) but paradoxically increased from baseline in BTHS (+17±14%, p&lt;0.03, p=0.0005 BTHS vs. controls) indicating impaired muscle O 2 utilization. Absolute (r= - 0.70, p&lt;0.0001) and percent (r= - 0.70, p&lt;0.001) change in NIRS from baseline was negatively associated with peak VO 2 . There was no correlation between peak VO 2 and resting EF (55±7%; r=0.12), SF (30±4%; r= -.26), myocardial performance index (0.4±0.1; r= -.3) or serum BNP (232±381; r=0.1). Conclusion : O 2 consumption during exercise in BTHS is severely reduced and caused, at least in part, by impaired skeletal muscle O 2 utilization. Resting cardiac function is not related to O 2 consumption in BTHS but cardiac dysfunction during exercise in BTHS is not excluded without further studies. Mitochondrial dysfunction likely mediates skeletal muscle O 2 utilization deficits during exercise in BTHS.
Abstract 13283: Testing the Menopausal Hormone Therapy Timing Hypothesis: The Early versus Late Intervention Trial with Estradiol
Authors: Howard N Hodis, Wendy J Mack, Donna Shoupe, Stanley P Azen, Frank Z Stanczyk, Juliana Hwang-Levine, Matthew J Budoff, Victor W Henderson
Journal: Circulation (2014)

The Early versus Late Intervention Trial with Estradiol (ELITE) is a 2x2, double-blinded, placebo-controlled trial specifically designed to determine whether menopausal hormone therapy (HT) has a differential effect on slowing the progression of subclinical atherosclerosis according to time-since-menopause when HT is initiated. The ELITE cohort is comprised of 643 healthy postmenopausal (>6 months) women without clinical evidence of cardiovascular disease (CVD) or diabetes mellitus who were randomized according to their time-since-menopause (<6 years, n=271 or &gt10 years, n=372). The primary trial end point is progression of carotid artery intima media thickness (CIMT) by high resolution B-mode ultrasound measured at baseline and every 6 months for up to 6 years. Women with a median (interquartile range) of 3.5 (1.9,5.0) and 14.3 (11.4,18.6) years-since-menopause were randomized to oral 17β-estradiol 1 mg daily with (uterine intact) or without (hysterectomy) vaginal micronized progesterone gel 4% (45 mg)...