tbuckley/cabot-search huggingface dataset:
Factors Associated With Concussion-like Symptom Reporting in High School Athletes
Authors: Grant L. Iverson, Noah D. Silverberg, Rebekah Mannix, Bruce A. Maxwell, Joseph E. Atkins, Ross Zafonte, Paul D. Berkner
Journal: JAMA Pediatrics (2015)

Every state in the United States has passed legislation for sport-related concussion, making this health issue important for physicians and other health care professionals. Safely returning athletes to sport after concussion relies on accurately determining when their symptoms resolve.To evaluate baseline concussion-like symptom reporting in uninjured adolescent student athletes.In this cross-sectional, observational study, we studied 31 958 high school athletes from Maine with no concussion in the past 6 months who completed a preseason baseline testing program between 2009 and 2013.Symptom reporting was more common in girls than boys. Most students with preexisting conditions reported one or more symptoms (60%-82% of boys and 73%-97% of girls). Nineteen percent of boys and 28% of girls reported having a symptom burden resembling an International Classification of Diseases, 10th Revision (ICD-10) diagnosis of postconcussional syndrome (PCS). Students with preexisting conditions were even more likely to endorse a symptom burden that resembled PCS (21%-47% for boys and 33%-72% for girls). Prior treatment of a psychiatric condition was the strongest independent predictor for symptom reporting in boys, followed by a history of migraines. For girls, the strongest independent predictors were prior treatment of a psychiatric condition or substance abuse and attention-deficit/hyperactivity disorder. The weakest independent predictor of symptoms for both sexes was history of prior concussions.In the absence of a recent concussion, symptom reporting is related to sex and preexisting conditions. Consideration of sex and preexisting health conditions can help prevent misinterpretation of symptoms in student athletes who sustain a concussion.
NASH, from diagnosis to treatment: Where do we stand?
Authors: Stephen A. Harrison
Journal: Hepatology (2015)

1Division of GastroenterologySan Antonio Military Medical Center, Fort Sam HoustonTX *Address reprint requests to: Stephen A. Harrison, M.D., Division of Gastroenterology, San Antonio Military Medical Center, Fort Sam Houston, TX 78234. E‐mail: [email protected]; fax: +1‐210‐916‐2601.
Role of T Lymphocytes and Interferon-γ in Ischemic Stroke
Authors: Gokhan Yilmaz, Thiruma V. Arumugam, Karen Y. Stokes, D. Neil Granger
Journal: Circulation (2006)

Although lymphocyte recruitment and activation are associated with cerebral ischemia-reperfusion (I/R) injury, the contributions of specific lymphocyte subpopulations and lymphocyte-derived interferon-gamma (IFN-gamma) to stroke remain unknown. The objectives of this study were to define the contribution of specific populations of lymphocytes to the inflammatory and prothrombogenic responses elicited in the cerebral microvasculature by I/R and to investigate the role of T-cell-associated IFN-gamma in the pathogenesis of ischemic stroke.Middle cerebral artery occlusion was induced for 1 hour (followed by 4 or 24 hours of reperfusion) in wild-type mice and mice deficient in lymphocytes (Rag1(-/-)), CD4+ T cells, CD8+ T cells, B cells, or IFN-gamma. Platelet and leukocyte adhesion was assessed in cortical venules with intravital video microscopy. Neurological deficit and infarct volume were determined 24 hours after reperfusion. Rag1(-/-), CD4+ T-cell(-/-), CD8+ T-cell(-/-), and IFN-gamma(-/-) mice exhibited comparable significant reductions in I/R-induced leukocyte and platelet adhesion compared with wild-type mice exposed to I/R. Infarct volume was reduced and I/R-induced neurological deficit was improved in immunodeficient Rag1(-/-) mice. These protective responses were reversed in Rag1(-/-) mice reconstituted with either wild-type or, to a lesser extent, IFN-gamma(-/-) splenocytes. B-cell-deficient mice failed to show improvement against ischemic stroke injury.These findings indicate that CD4+ and CD8+ T lymphocytes, but not B lymphocytes, contribute to the inflammatory and thrombogenic responses, brain injury, and neurological deficit associated with experimental stroke. Although IFN-gamma plays a pivotal role in stroke-induced inflammatory responses, T lymphocytes appear to be a minor source of this cytokine.
Targeting Anaplastic Lymphoma Kinase in Lung Cancer
Authors: Alice T. Shaw, Benjamin Solomon
Journal: Clinical Cancer Research (2011)

Several decades of cancer research have revealed a pivotal role for tyrosine kinases as key regulators of signaling pathways, controlling cell growth and differentiation. Deregulation of tyrosine kinase-mediated signaling occurs frequently in cancer and is believed to drive the initiation and progression of disease. Chromosomal rearrangements involving the tyrosine kinase anaplastic lymphoma kinase (ALK) occur in a variety of human malignancies including non-small cell lung cancer (NSCLC), anaplastic large cell lymphomas, and inflammatory myofibroblastic tumors. The aberrant activation of ALK signaling leads to "oncogene addiction" and marked sensitivity to ALK inhibitors such as crizotinib (PF-02341066). This review focuses on ALK rearrangements in NSCLC, starting with the discovery of the EML4-ALK fusion oncogene, and culminating in the recent validation of ALK as a therapeutic target in patients with ALK-rearranged NSCLC. Current efforts seek to expand the role of ALK kinase inhibition in lung and other cancers and to address the molecular basis for the development of resistance.
The Cellular Fate of Glucose and Its Relevance in Type 2 Diabetes
Authors: Clara Bouché, Shanti Serdy, C. Ronald Kahn, Allison B. Goldfine
Journal: Endocrine Reviews (2004)

Type 2 diabetes is a complex disorder with diminished insulin secretion and insulin action contributing to the hyperglycemia and wide range of metabolic defects that underlie the disease. The contribution of glucose metabolic pathways per se in the pathogenesis of the disease remains unclear. The cellular fate of glucose begins with glucose transport and phosphorylation. Subsequent pathways of glucose utilization include aerobic and anaerobic glycolysis, glycogen formation, and conversion to other intermediates in the hexose phosphate or hexosamine biosynthesis pathways. Abnormalities in each pathway may occur in diabetic subjects; however, it is unclear whether perturbations in these may lead to diabetes or are a consequence of the multiple metabolic abnormalities found in the disease. This review is focused on the cellular fate of glucose and relevance to human type 2 diabetes.
Adenovirus serotype 5 E1A sensitizes tumor cells to NKG2D-dependent NK cell lysis and tumor rejection
Authors: John M. Routes, Sharon Ryan, Kristin Morris, Rayna Takaki, Adelheid Cerwenka, Lewis L. Lanier
Journal: The Journal of Experimental Medicine (2005)

The expression of the Adenovirus serotype 5 (Ad5) E1A oncogene sensitizes tumor cells to natural killer (NK) cell–mediated killing and tumor rejection in vivo. These effects are dependent on the ability of E1A to bind the transcriptional coadaptor protein p300. To test the hypothesis that E1A up-regulates ligands recognized by the NKG2D-activating receptor, we stably transfected the highly tumorigenic mouse fibrosarcoma cell line MCA-205 with Ad5-E1A or a mutant form of E1A that does not interact with p300 (E1A-Δp300). Ad5-E1A, but not E1A-Δp300, up-regulated the expression of the NKG2D ligand retinoic acid early inducible (RAE)-1, but not murine ULBP-like transcript 1, another NKG2D ligand, in four independently derived MCA-205 transfectants. The up-regulation of RAE-1 by E1A targeted MCA-205 tumor cells to lysis by NK cells, resulting in NKG2D-dependent tumor rejection in vivo. Moreover, the up-regulation of NKG2D ligands by E1A was not limited to mouse tumor cells, as E1A also increased the expression of NKG2D ligands on primary baby mouse kidney cells, human MB435S breast cancer cells, and human H4 fibrosarcoma cells.
A risk model for severe anemia to select cancer patients for primary prophylaxis with epoetin α: a prospective randomized controlled trial of the ELYPSE study group
Authors: I. Ray-Coquard, S. Dussart, C. Goillot, D. Mayeur, P. Debourdeau, H. Ghesquieres, T. Bachelot, A. Le Cesne, B. Anglaret, C. Agostini, J.-P. Guastalla, L. Lancry, P. Biron, F. Desseigne, J.-Y. Blay
Journal: Annals of Oncology (2009)
Immunoliposomal Delivery of 213Bi for α-Emitter Targeting of Metastatic Breast Cancer
Authors: Mohanambe Lingappa, Hong Song, Sarah Thompson, Frank Bruchertseifer, Alfred Morgenstern, George Sgouros
Journal: Cancer Research (2010)

Abstract Current treatment for late-stage metastatic breast cancer is largely palliative. α-Particles are highly potent, short-range radiation emissions capable of sterilizing individual cells with one to three traversals of the cell nucleus. The α-emitter, 213Bi (T1/2 = 45.6 min), was conjugated to a 100-nm diameter liposomal-CHX-A″-DTPA construct, upon which the rat HER2/neu reactive antibody, 7.16.4, was grafted. A conjugation time of 10 minutes was achieved giving a specific activity corresponding to 0.1 213Bi atom per liposome; stability in vitro and in vivo was confirmed. Efficacy in a rat/neu transgenic mouse model of metastatic mammary carcinoma was investigated. Three days after left cardiac ventricular injection of 105 rat HER-2/neu–expressing syngeneic tumor cells, macrophage-depleted Neu-N mice were treated by i.v. injection with (a) 19.2 MBq (520 μCi) of liposome-CHX-A″-DTPA-213Bi, (b) 19.2 MBq of liposome-CHX-A″-DTPA-213Bi-7.16.4, (c) 4.44 MBq (120 μCi) of 213Bi-7.16.4, and (d) cold (nonradioactive) liposome-CHX-A″-DTPA-7.16.4 as control. Treatment with (a) increased median survival time to 34 days compared with 29 days for the untreated controls (P = 0.013) and 27 days for treated cold controls. Treatment with the radiolabeled antibody–conjugated liposome (b) increased median survival time to 38 days (P = 0.0002 relative to untreated controls). The radiolabeled antibody–treated group (c) gave a median survival of 39 days, which was similar to that for the radiolabeled antibody–conjugated liposome-treated group (P = 0.5). We have shown that the 213Bi radiolabeled immunoliposomes are effective in treating early-stage micrometastases, giving median survival times similar to those obtained with antibody-mediated delivery of 213Bi in this animal model. Cancer Res; 70(17); 6815–23. ©2010 AACR.
A Polymorphism in the <i>Cytidine Deaminase</i> Promoter Predicts Severe Capecitabine-Induced Hand-Foot Syndrome
Authors: Daniela Caronia, Miguel Martin, Javier Sastre, Julio de la Torre, José Angel García-Sáenz, Maria R. Alonso, Leticia T. Moreno, Guillermo Pita, Eduardo Díaz-Rubio, Javier Benítez, Anna González-Neira
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Hand-foot syndrome (HFS) is one of the most relevant dose-limiting adverse effects of capecitabine, an oral prodrug of 5-fluorouracil used in the standard treatment of breast and colorectal cancer. We investigated the association between grade 3 HFS and genetic variations in genes involved in capecitabine metabolism. Experimental Design: We genotyped a total of 13 polymorphisms in the carboxylesterase 2 (CES2) gene, the cytidine deaminase (CDD) gene, the thymidine phosphorylase (TP) gene, the thymidylate synthase (TS) gene, and the dihydropyrimidine dehydrogenase (DPD) gene in 130 patients treated with capecitabine. We correlated these polymorphisms with susceptibility to HFS. Results: We found an association of HFS appearance with rs532545 located in the promoter region of CDD (OR = 2.02, 95% CI = 1.02–3.99, P = 0.039). Because we found no association between the rs532545 genotype and CDD mRNA expression in Epstein-Barr virus lymphoblastoid cells, we explored additional genetic variations across the CDD promoter. We found an insertion, rs3215400, in linkage disequilibrium with rs532545 (D′ = 0.92), which was more clearly associated with HFS (OR = 0.51, 95% CI = 0.27–0.95, P = 0.028) in patients and with total CDD gene expression (P = 0.004) in lymphoblastoid cells. In silico analysis suggested that this insertion might create a binding site for the transcriptional regulator E2F. Using a SNaPshot assay in lymphoblastoid cells, we observed a 5.7-fold increased allele-specific mRNA expression from the deleted allele. Conclusions: The deleted allele of rs3215400 shows an increased allele-specific expression and is significantly associated with an increased risk of capecitabine-induced HFS. Clin Cancer Res; 17(7); 2006–13. ©2011 AACR.
Growing wrist mass
Authors: W C G Peh
Journal: Annals of the Rheumatic Diseases (2001)

A 46 year old man presented with a growing mass over his wrist. Erosions of the triquetrum and hamate were present radiographically. Magnetic resonance imaging (MRI) showed a solid mass arising from the extensor carpi ulnaris tendon, which was T<sub>1</sub> hypointense and isointense, T<sub>2</sub> hypointense, and bloomed on gradient echo images. The preoperative diagnosis of giant cell tumour of the tendon sheath was confirmed on histopathological examination of the excised specimen. The clinical, pathological, and imaging features, with emphasis on MRI findings, of this condition are reviewed.
Full Facial Edema: A Novel Presentation of Subcutaneous Panniculitis-Like T-Cell Lymphoma
Authors: Nicole F. Velez, Rumey C. Ishizawar, Paul F. Dellaripa, Arturo P. Saavedra, Alvaro C. Laga, George F. Murphy, David C. Fisher, Thomas S. Kupper, Ruth Ann Vleugels
Journal: Journal of Clinical Oncology (2012)

Subcutaneous Panniculitis-Like T-Cell Lymphoma Case ReportA 26-year-old woman with a history of discoid lupus presented with recurrent episodes of periorbital edema and intermittent fevers.Although initially responsive to systemic corticosteroids, edema became increasingly prominent, such that her pupils were obscured and vision impaired (Figs 1A and 1B).Magnetic resonance imaging of the orbits disclosed diffuse periorbital and infraorbital soft tissue swelling and prominent bilateral jugular chain lymph nodes without postseptal extension or soft tissue abscess.She was evaluated in consultation by the Allergy and Immunology as well as Rheumatology divisions, with negative comprehensive evaluations.Swelling spread to involve the entire face and neck and grew refractory even to high doses of pulsed intravenous corticosteroids.There was no laryngeal swelling, stridor, dysphagia, wheeze, cough, or dyspnea.She reported increasing fatigue but was otherwise well.She denied photosensitivity, oral ulcers, arthralgias, or Raynaud's phenomenon.Given the unusual clinical presentation and resulting diagnostic dilemma, a thorough workup was performed to exclude acquired forms of angioedema, nephrotic syndrome, systemic lupus erythematosus, vascular or lymphatic ob-struction, infection, and granulomatous processes.Extensive evaluation, including three hospitalizations for recurrent fevers, two skin biopsies, and a lymph node biopsy, was largely not revealing.Two weeks after her third hospitalization, the patient developed a nontender nodule on the left shoulder (Fig 1C) associated with recurrent fevers to 102.7°F, chills, and night sweats.Positron emission tomography/computed tomography imaging revealed intensely fludeoxyglucose-avid diffuse swelling of the bilateral subcutaneous periorbital, infraorbital, and lateral facial soft tissues as well as subcutaneous lesions in the neck, upper chest, back, and breast parenchyma (Figs 2A and 2B).Wedge biopsy of the left shoulder nodule revealed a lobular panniculitis with an atypical lymphoid infiltrate, rimming individual adipocytes, and areas of focal necrosis (Fig 3A, ϫ40 magnification; Fig 3B, ϫ600 magnification, arrow).Lymphocytes were pleomorphic with irregular nuclei.Immunoperoxidase staining showed predominantly CD3-positive (Fig 3C), CD8-positive (Fig 3D), and CD4-negative T cells with strong expression of cytotoxic markers: granzyme B (Fig 3E), perforin, and T-cell intracytoplasmic antigen-1.Immunoperoxidase staining was positive for T-cell receptor (TCR) -␤F1 and negative for TCR-␥ (Fig 3F).TCR rearrangement studies did not identify a clonal population.A diagnosis of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) was made, which makes this the first reported case, to our knowledge, of SPTCL presenting as full facial edema.The patient initially B A C Fig 1.
Proposal and Validation of Prognostic Scoring Systems for IgG and IgA Monoclonal Gammopathies of Undetermined Significance
Authors: Francesca Rossi, Maria Teresa Petrucci, Andrea Guffanti, Luigi Marcheselli, Davide Rossi, Vincenzo Callea, Federico Vincenzo, Marianna De Muro, Alessandra Baraldi, Oreste Villani, Pellegrino Musto, Andrea Bacigalupo, Gianluca Gaidano, Giuseppe Avvisati, Maria Goldaniga, Lorenzo DePaoli, Luca Baldini
Journal: Clinical Cancer Research (2009)

The presenting clinico-hematologic features of 1,283 patients with IgG and IgA monoclonal gammopathies of undetermined significance (MGUS) were correlated with the frequency of evolution into multiple myeloma (MM).Two IgG MGUS populations were evaluated: a training sample (553 patients) and a test sample (378 patients); the IgA MGUS population consisted of 352 patients.Forty-seven of the 553 training group patients and 22 of 378 test group IgG patients developed MM after a median follow-up of 6.7 and 3.6 years, respectively. Multivariate analysis showed that serum monoclonal component (MC) levels of < or =1.5 g/dL, the absence of light-chain proteinuria and normal serum polyclonal immunoglobulin levels defined a prognostically favorable subset of patients, and could be used to stratify the patients into three groups at different 10-year risk of evolution (hazard ratio, 1.0, 5.04, 11.2; P < 0.001). This scoring system was validated in the test sample. Thirty of the 352 IgA patients developed MM after a median follow-up of 4.8 years, and multivariate analysis showed that hemoglobin levels of <12.5 g/dL and reduced serum polyclonal immunoglobulin correlated with progression. A pooled statistical analysis of all of the patients confirmed the validity of Mayo Clinic risk model showing that IgA class, serum MC levels, and light-chain proteinuria are the most important variables correlated with disease progression.Using simple variables, we validated a prognostic model for IgG MGUS. Among the IgA cases, the possible prognostic role of hemoglobin emerged in addition to a decrease in normal immunoglobulin levels.
Draft genome sequence of the Daphnia pathogen Octosporea bayeri: insights into the gene content of a large microsporidian genome and a model for host-parasite interactions
Authors: Nicolas Corradi, Karen L Haag, Jean-François Pombert, Dieter Ebert, Patrick J Keeling
Journal: Genome biology (2009)

Abstract Background The highly compacted 2.9-Mb genome of Encephalitozoon cuniculi placed the microsporidia in the spotlight, encoding a mere 2,000 proteins and a highly reduced suite of biochemical pathways. This extreme level of reduction is not universal across the microsporidia, with genomes known to vary up to sixfold in size, suggesting that some genomes may harbor a gene content that is not as reduced as that of Enc. cuniculi . In this study, we present an in-depth survey of the large genome of Octosporea bayeri , a pathogen of Daphnia magna , with an estimated genome size of 24 Mb, in order to shed light on the organization and content of a large microsporidian genome. Results Using Illumina sequencing, 898 Mb of O. bayeri genome sequence was generated, resulting in 13.3 Mb of unique sequence. We annotated a total of 2,174 genes, of which 893 encodes proteins with assigned function. The gene density of the O. bayeri genome is very low on average, but also highly uneven, so gene-dense regions also occur. The data presented here suggest that the O. bayeri proteome is well represented in this analysis and is more complex that that of Enc. cuniculi . Functional annotation of O. bayeri proteins suggests that this species might be less biochemically dependent on its host for its metabolism than its more reduced relatives. Conclusions The combination of the data presented here, together with the imminent annotated genome of Daphnia magna , will provide a wealth of genetic and genomic tools to study host-parasite interactions in an interesting model for pathogenesis.
Flt-1 expression influences apoptotic susceptibility of vascular smooth muscle cells through the NF-κB/IAP-1 pathway
Authors: Augusto Orlandi, Amedeo Ferlosio, Gaetano Arcuri, Maria Giovanna Scioli, Sandro De Falco, Luigi Giusto Spagnoli
Journal: Cardiovascular Research (2009)

AimsFlt-1 is an fms-like tyrosine kinase receptor which binds to vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). Ligand activation and blocking of flt-1 influence several vascular smooth muscle cell (SMC) functions, including apoptotic susceptibility. However, downstream signal transduction pathways by which flt-1 regulates SMC apoptosis have still to be investigated.
P4-02-10: The Relationship between Estrogen Receptor Gene Polymorphism and Mammographic Density in Postmenopausal Women.
Authors: FDG Baldisserotto, S Elias, IDCG Silva, ACP Nazario
Journal: Cancer Research (2011)

Abstract Background Assess the relation between the presence of PVUII and XBAI polymorphisms in the estrogen receptor alpha gene and mammographic density in postmenopausal women. Methods For the present analysis, 189 postmenopausal women who had never used hormonal therapy and who did not have clinical or mammographic features were selected. Based on the ACR-BIRADSâ 2003 classification, the mammographic density was determined by three independent readers (two subjective ratings and one computerized - Adobe Photoshop â 7.0 software). Blood samples were available to extract DNA according to KIT GFX â protocol. PCR-RFLP (Polymerase Chain Reaction - Restriction Fragment Length Polymorphism) was then used to identify the polymorphisms. Results There was a high degree of agreement among the three readers to determine the mammographic density (Kappa&amp;gt;0.75). Sixty women (32%) had dense breasts and 129 (68%) had non-dense breasts. The PVUII polymorphism was found in 132 (69.8%) of 189 women, while the XBAI was found in 135 (71.4%) of women. Parity (p=0.02) and body mass index (p&amp;lt;0.0001) were associated with mammographic density. It was observed that for the XBAI polymorphism, women with two mutated alleles were approximately 2.5 times more likely to be classified in dense breasts group (p=0.003) and the presence of both wild alleles was associated with fibroglandular tissue replacement by fat (p=0.02). Conclusions There was no significant association of the PVUII polymorphism in the estrogen receptor alpha gene with mammographic density (p=0.34). However, the XBAI polymorphism was observed at a higher mutated homozygous frequency in women with dense breasts and there was an increased frequency of wild-type homozygous and heterozygous women with fat-replaced breasts (p=0.01). Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-02-10.