tbuckley/cabot-search huggingface dataset:
IOC consensus statement: “training the elite child athlete”
Authors: M Mountjoy, N Armstrong, L Bizzini, C Blimkie, J Evans, D Gerrard, J Hangen, K Knoll, L Micheli, P Sangenis, W Van Mechelen
Journal: British Journal of Sports Medicine (2007)

<h3>Abstract</h3> The human adrenal gland is a complex endocrine tissue. Developmental studies on this tissue have been limited to animal models or human foetus. Here, we present a cell atlas analysis of the adult human normal adrenal gland, combining single-nuclei RNA sequencing and spatial transcriptome data to reconstruct adrenal gland development and tumourigenesis. We identified two populations of potential progenitor cells resident within the adrenal cortex: adrenocortical progenitors NR2F2<sup>+</sup>-ID1<sup>+</sup> cells, located within and underneath the capsule, and medullary progenitors SYT1<sup>+</sup>-CHGA<sup>−</sup> cells, located in islets in the subcapsular region. Using pseudotime analyses, we provided evidence of the centripetal nature of adrenocortical cell development and of the essential role played by the Wnt/β-catenin pathway in the adrenocortical self-renewal. By comparing transcriptional profiles of cells of normal adrenal glands and adrenocortical adenomas we revealed a high heterogeneity with six adenoma-specific clusters. Overall, our results give insights into adrenal plasticity and mechanisms underlying adrenocortical tumourigenesis.
Cytochrome P450 Profile of Colorectal Cancer: Identification of Markers of Prognosis
Authors: Meera Kumarakulasingham, Patrick H. Rooney, Sinclair R. Dundas, Colin Telfer, William T. Melvin, Stephanie Curran, Graeme I. Murray
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The cytochromes P450 (P450) are a multigene family of enzymes with a central role in the oxidative metabolism of a wide range of xenobiotics, including anticancer drugs, carcinogens, and endogenous compounds. The purpose of this study was to define the P450 profile of colorectal cancer and establish the prognostic significance of expression of individual P450s in colorectal cancer. Experimental Design: Immunohistochemistry for a panel of 23 P450s was done on a colorectal cancer tissue microarray consisting of 264 primary colorectal cancers, 91 lymph node metastasis, and 10 normal colorectal samples. The intensity of immunoreactivity in each sample was established by light microscopy. Results: The most frequently expressed form of P450 in normal colon was CYP3A4. In primary colorectal cancer, several P450s (CYP1B1, CYP2S1, CYP2U1, CYP3A5, and CYP51) were present at a significantly higher level of intensity compared with normal colon. P450 expression was also detected in lymph node metastasis and the presence of several P450s (CYP1B1, CYP2A/2B, CYP2F1, CYP4V2, and CYP39) in the lymph node metastasis strongly correlated with their presence in corresponding primary tumors. The presence of strong CYP51 (log-rank = 12.11, P = 0.0005) or strong CYP2S1 (log-rank = 6.72, P = 0.0095) immunoreactivity were associated with poor prognosis. CYP51 was also an independent marker of prognosis (P = 0.009). Conclusions: The expression of individual P450s has been established in colorectal cancer. Several P450s show increased expression in colorectal cancer. High expression of CYP51 or CYP2S1 were associated with poor prognosis and CYP51 is an independent marker of prognosis.
Aminopeptidases do not directly degrade tau protein
Authors: K Chow, Hanjun Guan, Louis B Hersh
Journal: Molecular Neurodegeneration (2010)

Tau hyperphosphorylation and aggregation to form intracellular neurofibrillar tangles is prevalent in a number of tauopathies. Thus there is current interest in the mechanisms involved in Tau clearance. It was recently reported that Tau can be degraded by an aminopeptidase known as the puromycin sensitive aminopeptidase (PSA). Until now PSA has been reported to only cleave peptides, with the largest reported substrates having 30-50 amino acids. We have studied this unique PSA cleavage reaction using a number of different PSA preparations.An N-terminally His tagged-PSA was expressed and purified from Sf9 insect cells. Although this PSA preparation cleaved Tau, product analysis with N and C terminal Tau antibodies coupled with mass spectrometry showed an endoproteolytic cleavage atypical for an aminopeptidase. Furthermore, the reaction was not blocked by the general aminopeptidase inhibitor bestatin or the specific PSA inhibitor puromycin. In order to test whether Tau hydrolysis might be caused by a protease contaminant the enzyme was expressed in E. coli as glutathione S-transferase and maltose binding protein fusion proteins or in Sf9 cells as a C-terminally His-tagged protein. After purification to near homogeneity none of these other recombinant forms of PSA cleaved Tau. Further, Tau-cleaving activity and aminopeptidase activities derived from the Sf9 cell expression system were separable by molecular sieve chromatography. When tested in a cellular context we again failed to see a PSA dependent cleavage of Tau. A commercial preparation of a related aminopeptidase, aminopeptidase N, also exhibited Tau cleaving activity, but this activity could also be separated from aminopeptidase activity.It is concluded that PSA does not directly cleave Tau.
Identification of a motif for HLA-DR1 binding peptides using M13 display libraries.
Authors: J Hammer, B Takacs, F Sinigaglia
Journal: The Journal of Experimental Medicine (1992)

Oligonucleotides encoding peptides known to bind to HLA-DR1 molecules have been inserted into the gene III of filamentous M13 phages. DR1 molecules purified from human lymphoblastoid cell lines could specifically bind to these peptide sequences expressed on the phage surface. A M13 phage peptide library was next constructed and screened with DR1 molecules. After four rounds of selection, more than 80% of the phages were able to bind to DR1. Competition experiments with both isolated phages and corresponding synthetic peptides showed that the binding was specific. Sequence analysis of the peptide encoding region of 60 phages binding to DR1 molecules and comparison with phages of the original library revealed two potential anchor positions. The first was an aromatic residue (Tyr, Phe, or Trp) at the NH2 terminus of the peptide sequences, and the second was located three residues downstream and consisted of Met or Leu. In addition, the negatively charged amino acids Asp and Glu were mostly excluded from the DR1 binding sequences, and the small amino acid residues Gly and Ala were enriched at position 6. As for DR1, this approach should enable one to easily determine the binding motifs of other MHC class II alleles and isotypes. Furthermore, it could have interesting applications in the design of major histocompatibility complex-specific antagonists.
Ku in the Cytoplasm Associates with CD40 in Human B Cells and Translocates into the Nucleus following Incubation with IL-4 and Anti-CD40 mAb
Authors: Tomohiro Morio, Silva H Hanissian, Leonard B Bacharier, Hirobumi Teraoka, Shigeaki Nonoyama, Makoto Seki, Jun Kondo, Hiroyasu Nakano, Sang-Kyou Lee, Raif S Geha, Jun-ichi Yata
Journal: Immunity (1999)
Randomized placebo-controlled study of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin.
Authors: C Isaacs, N J Robert, F A Bailey, M W Schuster, B Overmoyer, M Graham, B Cai, K J Beach, J W Loewy, J A Kaye
Journal: Journal of Clinical Oncology (1997)

PURPOSE Thrombocytopenia may compromise cancer treatment, causing chemotherapy dose reductions, schedule alterations, or the need for platelet transfusions. We evaluated the efficacy and safety of recombinant human interleukin-11 (rhIL-11; Neumega, Genetics Institute, Inc, Cambridge, MA), a novel thrombopoietic growth factor, in reducing the need for platelet transfusions in patients who undergo dose-intensive chemotherapy. PATIENTS AND METHODS Women with advanced breast cancer received cyclophosphamide (3,200 mg/m2) and doxorubicin (75 mg/m2) plus granulocyte colony-stimulating factor (G-CSF; 5 microg/kg/d). Patients were randomized to blinded treatment with placebo or 50 microg/kg/d rhIL-11 subcutaneously for 10 or 17 days after the first two chemotherapy cycles. RESULTS Seventy-seven patients were randomized and constitute the intent-to-treat (ITT) population. Sixty-seven patients (the assessable subgroup) either completed both cycles without a major protocol violation (n = 62) or received a platelet transfusion before treatment was discontinued after the first cycle. In the ITT population, rhIL-11 significantly decreased the requirement for platelet transfusions; 27 of 40 (68%) patients who received rhIL-11 did not require transfusions, compared with 15 of 37 (41%) in the placebo group (P = .04). Treatment with rhIL-11 significantly reduced the total number of platelet transfusions required in the assessable subgroup (P = .03) and the time to platelet recovery to more than 50,000/microL in the second cycle (P = .01). Most adverse events associated with rhIL-11 were reversible, mild to moderate in severity, and likely related to fluid retention. CONCLUSION rhIL-11 is safe and effective in reducing treatment-associated thrombocytopenia and the need for platelet transfusions in patients who undergo dose-intensive chemotherapy, and thus may permit chemotherapy to be administered as planned at intended doses and thereby maximize the potential for a successful outcome.
US Trends in Prevalence, Awareness, Treatment, and Control of Hypertension, 1988-2008
Authors: Brent M. Egan
Journal: JAMA (2010)

Hypertension is a major risk factor for cardiovascular disease and treatment and control of hypertension reduces risk. The Healthy People 2010 goal was to achieve blood pressure (BP) control in 50% of the US population.To assess progress in treating and controlling hypertension in the United States from 1988-2008.The National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999-2008 in five 2-year blocks included 42 856 adults aged older than 18 years, representing a probability sample of the US civilian population.Hypertension was defined as systolic BP of at least 140 mm Hg and diastolic BP of at least 90 mm Hg, self-reported use of antihypertensive medications, or both. Hypertension control was defined as systolic BP values of less than 140 mm Hg and diastolic BP values of less than 90 mm Hg. All survey periods were age-adjusted to the year 2000 US population.Rates of hypertension increased from 23.9% (95% confidence interval [CI], 22.7%-25.2%) in 1988-1994 to 28.5% (95% CI, 25.9%-31.3%; P < .001) in 1999-2000, but did not change between 1999-2000 and 2007-2008 (29.0%; 95% CI, 27.6%-30.5%; P = .24). Hypertension control increased from 27.3% (95% CI, 25.6%-29.1%) in 1988-1994 to 50.1% (95% CI, 46.8%-53.5%; P = .006) in 2007-2008, and BP among patients with hypertension decreased from 143.0/80.4 mm Hg (95% CI, 141.9-144.2/79.6-81.1 mm Hg) to 135.2/74.1 mm Hg (95% CI, 134.2-136.2/73.2-75.0 mm Hg; P = .02/P < .001). Blood pressure control improved significantly more in absolute percentages between 1999-2000 and 2007-2008 vs 1988-1994 and 1999-2000 (18.6%; 95% CI, 13.3%-23.9%; vs 4.1%; 95% CI, -0.5% to 8.8%; P < .001). Better BP control reflected improvements in awareness (69.1%; 95% CI, 67.1%-71.1%; vs 80.7%; 95% CI, 78.1%-83.0%; P for trend = .03), treatment (54.0%; 95% CI, 52.0%-56.1%; vs 72.5%; 95% CI, 70.1%-74.8%; P = .004), and proportion of patients who were treated and had controlled hypertension (50.6%; 95% CI, 48.0%-53.2%; vs 69.1%; 95% CI, 65.7%-72.3%; P = .006). Hypertension control improved significantly between 1988-1994 and 2007-2008, across age, race, and sex groups, but was lower among individuals aged 18 to 39 years vs 40 to 59 years (P < .001) and 60 years or older (P < .001), and in Hispanic vs white individuals (P = .004).Blood pressure was controlled in an estimated 50.1% of all patients with hypertension in NHANES 2007-2008, with most of the improvement since 1988 occurring after 1999-2000. Hypertension control was significantly lower among younger than middle-aged individuals and older adults, and Hispanic vs white individuals.
Vacuolar protein sorting 35 (Vps35) rescues locomotor deficits and shortened lifespan in Drosophila expressing a Parkinson’s disease mutant of Leucine-rich repeat kinase 2 (LRRK2)
Authors: Radek Linhart, Sarah Anne Wong, Jieyun Cao, Melody Tran, Anne Huynh, Casey Ardrey, Jong Min Park, Christine Hsu, Saher Taha, Rentia Peterson, Shannon Shea, Jason Kurian, Katerina Venderova
Journal: Molecular Neurodegeneration (2014)

Parkinson’s disease (PD) is the most common movement neurodegenerative movement disorder. An incomplete understanding of the molecular pathways involved in its pathogenesis impedes the development of effective disease-modifying treatments. To address this gap, we have previously generated a Drosophila model of PD that overexpresses PD pathogenic mutant form of the second most common causative gene of PD, Leucine-Rich Repeat Kinase 2 (LRRK2). We employed this model in a genetic modifier screen and identified a gene that encodes for a core subunit of retromer – a complex essential for the sorting and recycling of specific cargo proteins from endosomes to the trans-Golgi network and cell surface. We present evidence that overexpression of the Vps35 or Vps26 component of the cargo-recognition subunit of the retromer complex ameliorates the pathogenic mutant LRRK2 eye phenotype. Furthermore, overexpression of Vps35 or Vps26 significantly protects from the locomotor deficits observed in mutant LRRK2 flies, as assessed by the negative geotaxis assay, and rescues their shortened lifespan. Strikingly, overexpressing Vps35 alone protects from toxicity of rotenone, a neurotoxin commonly used to model parkinsonism, both in terms of lifespan and locomotor activity of the flies, and this protection is sustained and even augmented in the presence of mutant LRRK2. Finally, we demonstrate that knocking down expression of Vps35 in dopaminergic neurons causes a significant locomotor impairment. From these results we conclude that LRRK2 plays a role in the retromer pathway and that this pathway is involved in PD pathogenesis.
Study finds almost half of Spanish children are overweight or obese
Authors: A. Garcia Rada
Journal: BMJ (2011)

More than a quarter (26%) of Spanish children are overweight and a fifth (19%) are obese, show preliminary data of a new prevalence study presented on 30 June by the country’s health minister Leire Pajin. 

Ms Pajin, who will present final results of the study at the Interterritorial Council of the National Health Service, the body that meets regularly to coordinate state and regional health actions, said that “about 60% of children who are overweight before puberty will be overweight when becoming young adults, advancing mean age of onset of non-communicable diseases and also generating a huge increase …
Troglitazone and 15-deoxy-Δ-prostaglandin J inhibit shear-induced coupling factor 6 release in endothelial cells
Authors: H TOMITA, T OSANAI, T TOKI, S SASAKI, N MAEDA, R MURAKAMI, K MAGOTA, M YASUJIMA, K OKUMURA
Journal: Cardiovascular Research (2005)

Objective: We previously showed that mitochondrial coupling factor 6 (CF6), an endogenous inhibitor of prostacyclin synthesis and a vasoconstrictor, is present on the surface of human umbilical vein endothelial cells (HUVEC) and is released outside of the cells by shear stress. We investigated the intracellular signaling mechanism for shear-induced release of CF6 in HUVEC and the effects of troglitazone and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), both peroxisome proliferator-activated receptor (PPAR)-γ ligands, on it.
American Cancer Society lung cancer screening guidelines
Authors: Richard Wender, Elizabeth T. H. Fontham, Ermilo Barrera, Graham A. Colditz, Timothy R. Church, David S. Ettinger, Ruth Etzioni, Christopher R. Flowers, G. Scott Gazelle, Douglas K. Kelsey, Samuel J. LaMonte, James S. Michaelson, Kevin C. Oeffinger, Ya‐Chen Tina Shih, Daniel C. Sullivan, William Travis, Louise Walter, Andrew M. D. Wolf, Otis W. Brawley, Robert A. Smith
Journal: CA A Cancer Journal for Clinicians (2013)

Abstract Answer questions and earn CME/CNE Findings from the National Cancer Institute's National Lung Screening Trial established that lung cancer mortality in specific high‐risk groups can be reduced by annual screening with low‐dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to high‐volume, high‐quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30–pack‐year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision‐making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with low‐dose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation. CA Cancer J Clin 2013;. © 2013 American Cancer Society.
Prospective Study of Blood and Tibia Lead in Women Undergoing Surgical Menopause
Authors: Gertrud S. Berkowitz, Mary S. Wolff, Robert H. Lapinski, Andrew C. Todd
Journal: Environmental Health Perspectives (2004)

Despite the dramatic decline in environmental lead exposure in the United States during the past couple of decades, concern has been expressed regarding mobilization during menopause of existing lead stored in bone. To investigate whether bone lead concentrations decrease and blood lead levels increase, we conducted a prospective study of 91 women who were scheduled to undergo a bilateral oophorectomy for a benign condition at Mount Sinai Hospital in New York City during October 1994 through April 1999. We excluded women who were younger than 30 years of age or who were postmenopausal at the time of the surgery. We observed a small but significant increase in median blood lead levels between the baseline visit and the 6-month visit (0.4 microg/dL, p<0.0001), particularly for women who were not on estrogen replacement therapy (0.7 microg/dL, p=0.008). No significant change was observed in blood lead values between 6 and 18 months postsurgery, nor was there evidence of significant changes in tibia lead concentrations during the follow-up period. These findings do not point to substantial mobilization of lead from cortical bone during menopause.
The tubular maximum for calcium reabsorption in patients with chronic active thoracic sarcoidosis
Authors: PD Broulik, V Votava, V Pacovsky
Journal: European Respiratory Journal (1990)

The tubular maximum for calcium reabsorption (TmCa) was evaluated in 52 patients with chronic active thoracic sarcoidosis. Hypercalcaemia was found in five patients (9.6%). The mean serum calcium value of 2.54 +/- 0.18 mmol.l-1 in patients with sarcoidosis was significantly higher than that obtained in the control group (2.42 +/- 0.11 mmol.l-1). The mean TmCa in patients with sarcoidosis (2.11 +/- 0.26 mmol.l-1 glomerular filtrate (GF] was not statistically different from the mean TmCa for the group of healthy subjects (2.18 +/- 0.23 mmol.l-1 GF). Urinary sodium corrected TmCa in both groups of patients was affected in a similar way. Our study demonstrates for the first time that there is no increase in TmCa in patients with chronic active thoracic sarcoidosis. Hypercalcaemia is not a result of an increased TmCa.
Natural history of multiple system atrophy in the USA: a prospective cohort study
Authors: Phillip A Low, Stephen G Reich, Joseph Jankovic, Clifford W Shults, Matthew B Stern, Peter Novak, Caroline M Tanner, Sid Gilman, Frederick J Marshall, Frederick Wooten, Brad Racette, Thomas Chelimsky, Wolfgang Singer, David M Sletten, Paola Sandroni, Jay Mandrekar
Journal: The Lancet Neurology (2015)
Allogeneic Hematopoietic Cell Transplantation for Patients With Mycosis Fungoides and Sézary Syndrome: A Retrospective Analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation
Authors: Rafael F. Duarte, Carmen Canals, Francesco Onida, Ian H. Gabriel, Reyes Arranz, William Arcese, Augustin Ferrant, Guido Kobbe, Franco Narni, Giorgio Lambertenghi Deliliers, Eduardo Olavarría, Norbert Schmitz, Anna Sureda
Journal: Journal of Clinical Oncology (2010)

To analyze the outcome of allogeneic transplantation for mycosis fungoides and Sézary syndrome (MF/SS) in terms of nonrelapse mortality (NRM), relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) and to identify factors associated with the outcome.Sixty patients with MF (n = 36) and SS (n = 24) who received a first allogeneic hematopoietic cell transplantation (HCT) from a matched related (mRD; n = 45) or unrelated donor (mUD; n = 15) between 1997 and 2007 and who were registered in the European Group for Blood and Marrow Transplantation database were analyzed: 37 men and 23 women, median age 46.5 years (range, 22 to 66 years). Forty-four patients had TNM stage IV, and 40 patients were at advanced phase at transplantation. Forty-four patients received reduced-intensity conditioning (RIC) regimens, and 25 underwent T-cell depletion (TCD).Allogeneic transplantation in MF/SS offers an estimated OS of 66% at 1 year and 54% at 3 years, primarily driven by donor type, disease phase, and type of conditioning. RIC decreased NRM (relative risk [RR] = 4.7; P = .008) without increasing REL, leading to a higher OS (RR = 2.8; P = .03). Advanced-phase disease increases REL (RR = 3.0; P = .03) and reduces PFS (RR = 4.4; P = .002) and OS (RR = 3.5; P = .023). Recipients of mRD allogeneic HCT had better PFS (RR = 2.7; P = .006) and OS (RR = 4.0; P = .001) than their mUD counterparts. The risk of REL increases with TCD (RR = 3.2; P = .005). Some patients who experience relapse can successfully undergo rescue treatment with donor lymphocyte infusions.Allogeneic transplantation is a valid therapeutic alternative for high-risk patients with advanced-stage MF/SS. Our data also suggest the existence of a clinically relevant graft-versus-lymphoma effect in MF/SS.
Intestinal permeability in coeliac disease: insight into mechanisms and relevance to pathogenesis
Authors: Martine Heyman, Juliette Abed, Corinne Lebreton, Nadine Cerf-Bensussan
Journal: Gut (2011)

Coeliac disease is a gut disease driven by an abnormal immune response towards dietary gluten in genetically susceptible individuals. Whether and, if so, how abnormal transport of gluten across the gut epithelium may participate in the pathogenesis of coeliac disease remains debatable. This paper summarises the interactions of gluten-derived peptides with the intestinal epithelium and discusses the mechanisms that control their transport across the epithelium. It shows how recent data point to a key role for the transcellular pathway and highlights the ‘Trojan horse’ role of secretory IgA which can hijack the transferrin receptor and allow the rapid translocation of intact gluten peptides into the mucosa. These recent findings might be useful for the design of new treatments.