tbuckley/cabot-search huggingface dataset:
Hemoglobin A1c and Mean Glucose in Patients With Type 1 Diabetes
Authors: Darrell M. Wilson, Dongyuan Xing, Roy W. Beck, Jennifer Block, Bruce Bode, Larry A. Fox, Irl Hirsch, Craig Kollman, Lori Laffel, Katrina J. Ruedy, Michael W Steffes, William V. Tamborlane
Journal: Diabetes Care (2011)

To determine the relationship between mean sensor glucose concentrations and hemoglobin A(1c) (HbA(1c)) values measured in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications laboratory at the University of Minnesota in a cohort of subjects with type 1 diabetes from the Juvenile Diabetes Research Foundation continuous glucose monitoring randomized trial.Near-continuous glucose sensor data (≥ 4 days/week) were collected for 3 months before a central laboratory-measured HbA(1c) was performed for 252 subjects aged 8-74 years, the majority of whom had stable HbA(1c) values (77% within ± 0.4% of the patient mean).The slope (95% CI) for mean sensor glucose concentration (area under the curve) versus a centrally measured HbA(1c) was 24.4 mg/dL (22.0-26.7) for each 1% change in HbA(1c), with an intercept of -16.2 mg/dL (-32.9 to 0.6). Although the slope did not vary with age or sex, there was substantial individual variability, with mean sensor glucose concentrations ranging from 128 to 187 mg/dL for an HbA(1c) of 6.9-7.1%. The root mean square of the errors between the actual mean sensor glucose concentration versus the value calculated using the regression equation was 14.3 mg/dL, whereas the median absolute difference was 10.1 mg/dL.There is substantial individual variability between the measured versus calculated mean glucose concentrations. Consequently, estimated average glucose concentrations calculated from measured HbA(1c) values should be used with caution.
Phenotypic changes of lymphocyte in a patient with IgG4-related disease after corticosteroid therapy
Authors: Shigeru Iwata, Kazuyoshi Saito, Shintaro Hirata, Yoshiya Tanaka
Journal: Annals of the Rheumatic Diseases (2012)

Immunoglobulin G4-related disease (IgG4RD) is a novel clinical disease entity characterised by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells.1 ,2 Interleukin 4 (IL-4) and IL-10, which were detected with B cells in the salivary gland in this disease,3 direct naive B cells to switch to IgG4 production.4 B cells are therefore considered to be important for the pathogenesis of IgG4RD. However, the phenotype of B cells in patients with IgG4RD remains elusive. In this report we show the phenotypic changes of peripheral blood B cells in a patient with IgG4RD analysed by flow cytometry during treatment with a corticosteroid.

In January 2011 a 53-year-old man presented with symmetrical swelling of the lachrymal glands and a tumour located in the left junction of the renal pelvis and ureter, serum IgG4 >135 mg/dl and IgG4+/IgG+ cells >40% with significant invasion of lymphocytes and plasma cells, typical tissue fibrosis and sclerosis in the salivary gland. He was diagnosed with …
Molecular Selection Trumps Clinical Selection
Authors: Frances A. Shepherd
Journal: Journal of Clinical Oncology (2011)

practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 19:1539-1569, 2001 18. Bhargava R, Striebel J, Beriwal S, et al: Prevalence, morphologic features and proliferation indices of breast carcinoma molecular classes using immunohistochemical surrogate markers. Int J Clin Exp Pathol 2:444-455, 2009 19. Belletti B, Vaidya JS, D’Andrea S, et al: Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding. Clin Cancer Res 14:1325-1332, 2008
Closure or Medical Therapy for Cryptogenic Stroke with Patent Foramen Ovale
Authors: Anthony J. Furlan, Mark Reisman, Joseph Massaro, Laura Mauri, Harold Adams, Gregory W. Albers, Robert Felberg, Howard Herrmann, Saibal Kar, Michael Landzberg, Albert Raizner, Lawrence Wechsler
Journal: New England Journal of Medicine (2012)

The prevalence of patent foramen ovale among patients with cryptogenic stroke is higher than that in the general population. Closure with a percutaneous device is often recommended in such patients, but it is not known whether this intervention reduces the risk of recurrent stroke.
Prognosis in patients with low left ventricular ejection fraction after myocardial infarction. Importance of exercise capacity.
Authors: L Pilote, J Silberberg, R Lisbona, A Sniderman
Journal: Circulation (1989)

The measurement of left ventricular ejection fraction (LVEF) plays a key role in many strategies for managing patients after acute myocardial infarction. We tested the hypothesis that exercise capacity 1 month after myocardial infarction provides additional information in patients with a low LVEF and therefore assists in risk stratification. One hundred fifteen patients, with documented myocardial infarction and LVEF less than 35% by gated radionuclide scan 1 month after acute myocardial infarction, were followed up for 2 months to 7 years. Exercise capacity was estimated from a treadmill test 1 month after infarction. Using the Cox proportional hazards model, exercise capacity was a significant predictor of death or reinfarction. The relative risk of death, based on a comparison between the lowermost quintile (less than 4 METS) and uppermost quintile (greater than 7 METS), was 3.5 (95% confidence interval, 1.1-9.7); the relative risk in the fourth, third, and second quintile was 2.7, 2.1, and 1.6, respectively. In a multivariate analysis, the observed effect of a good exercise capacity was independent of LVEF. These data indicate that in patients with a low LVEF after myocardial infarction, useful prognostic information can be obtained from exercise testing.
Therapeutic effects of a reducible poly (oligo-d-arginine) carrier with the heme oxygenase-1 gene in the treatment of hypoxic-ischemic brain injury
Authors: Hyesun Hyun, Young-Wook Won, Kyung-Min Kim, Jiyoung Lee, Minhyung Lee, Yong-Hee Kim
Journal: Biomaterials (2010)
Detection of Human Papillomavirus Infection of the Cervix in Very Elderly Women Using PCR
Authors: Kaiyo Takubo, Naotaka Shimomura-Izumiyama, Hidemi Koiwai, Naoko Honma, Yukiyoshi Esaki, Tomomi Yoshida, Takashi Nakajima, Motoji Sawabe, Tomio Arai
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To determine the incidence of human papillomavirus (HPV) infection and the morphologic lesions induced by HPV infection of the uterine cervix in elderly Japanese women (including very elderly women) and to clarify the natural history and outcome of HPV infection. Experimental Design: We detected squamous intraepithelial lesions (SIL) by cytology and the presence of HPV infection by PCR on cervical smears obtained at autopsy from 335 women ages 60 to 105 years (mean, 82.7 years). Two primers were used for PCR, one for low-risk HPV subtypes and one for high-risk HPV subtypes. Results: SILs were observed in 20 (6.0%) of the women autopsied; 18 (5.4%) had low-grade SIL and 2 (0.6%) had high-grade SIL. HPV-DNA was not detected in any of the women with normal cervical cytology but was found in 9 (45.0%) of the 20 with SIL (2.7% of all subjects). Of these 9 women, 2 (22%) were positive for low-risk types of HPV and 7 (78%) were positive for high-risk types. All 9 had spent their last days in hospitals or nursing homes, the duration of institutional care ranging from 17 days to 10 years 2 months. Conclusions: Our results suggest that HPV infection of the cervix may occasionally persist for long periods of time (the maximum duration noted in this study being 10 years 2 months). It is also possible that HPV infection in young women with normal cervical cytology will not persist into advanced age.
Understanding the Epigenetic Syntax for the Genetic Alphabet in the Kidney
Authors: Katalin Susztak
Journal: Journal of the American Society of Nephrology (2013)

The cells in a human body have identical DNA sequences, yet the body has >200 cell types with different phenotypes. The basis for this nongenetic cellular memory, which records developmental and environmental cues, is epigenetics. The epigenome includes covalent modifications of the DNA and its associated proteins and defines DNA accessibility to the transcriptional machinery. Notably, the epigenome has emerged as an important mediator of the long-term programming effect of environmental exposure, and multiple lines of evidence point to the epigenome as an important missing link in our understanding of CKD development. For example, recent studies identified epigenetic differences in the enhancer regions of fibrosis-related genes in diseased human kidney samples. Furthermore, chromatin profiling and epigenome analysis are powerful tools for annotating gene regulatory regions that can be harnessed to interpret disease-causing polymorphisms for complex traits such as CKD. This review highlights the results of studies investigating the renal epigenome and discusses the significance of these findings and future directions in the context of novel diagnostic and treatment strategies for CKD.
IER3 supports KRASG12D-dependent pancreatic cancer development by sustaining ERK1/2 phosphorylation
Authors: Maria Noé Garcia, Daniel Grasso, Maria Belen Lopez-Millan, Tewfik Hamidi, Celine Loncle, Richard Tomasini, Gwen Lomberk, Françoise Porteu, Raul Urrutia, Juan L. Iovanna
Journal: Journal of Clinical Investigation (2014)

Activating mutations in the KRAS oncogene are prevalent in pancreatic ductal adenocarcinoma (PDAC). We previously demonstrated that pancreatic intraepithelial neoplasia (PanIN) formation, which precedes malignant transformation, associates with the expression of immediate early response 3 (Ier3) as part of a prooncogenic transcriptional pathway. Here, we evaluated the role of IER3 in PanIN formation and PDAC development. In human pancreatic cancer cells, IER3 expression efficiently sustained ERK1/2 phosphorylation by inhibiting phosphatase PP2A activity. Moreover, IER3 enhanced KrasG12D-dependent oncogenesis in the pancreas, as both PanIN and PDAC development were delayed in IER3-deficient KrasG12D mice. IER3 expression was discrete in healthy acinar cells, becoming highly prominent in peritumoral acini, and particularly high in acinar ductal metaplasia (ADM) and PanIN lesions, where IER3 colocalized with phosphorylated ERK1/2. However, IER3 was absent in undifferentiated PDAC, which suggests that the IER3-dependent pathway is an early event in pancreatic tumorigenesis. IER3 expression was induced by both mild and severe pancreatitis, which promoted PanIN formation and progression to PDAC in KrasG12D mice. In IER3-deficient mice, pancreatitis abolished KrasG12D-induced proliferation, which suggests that pancreatitis enhances the oncogenic effect of KRAS through induction of IER3 expression. Together, our data indicate that IER3 supports KRASG12D-associated oncogenesis in the pancreas by sustaining ERK1/2 phosphorylation via phosphatase PP2A inhibition.
High prevalence of vertebral fractures in women with breast cancer starting aromatase inhibitor therapy
Authors: B. Bouvard, E. Hoppé, P. Soulié, M. Georgin-Mege, E. Jadaud, S. Abadie-Lacourtoisie, A. Petit Le Manac’h, A. Laffitte, R. Levasseur, M. Audran, D. Chappard, E. Legrand
Journal: Annals of Oncology (2011)
A Longitudinal Approach to Assessing Urban and Suburban Children’s Exposure to Pyrethroid Pesticides
Authors: Chensheng Lu, Dana B. Barr, Melanie Pearson, Scott Bartell, Roberto Bravo
Journal: Environmental Health Perspectives (2006)

We conducted a longitudinal study to assess the exposure of 23 elementary school-age children to pyrethroid pesticides, using urinary pyrethroid metabolites as exposure biomarkers. We substituted most of the children's conventional diets with organic food items for 5 consecutive days and collected two daily spot urine samples, first morning and before bedtime voids, throughout the 15-day study period. We analyzed urine samples for five common pyrethroid metabolites. We found an association between the parents' self-reported pyrethroid use in the residential environment and elevated pyrethroid metabolite levels found in their children's urine. Children were also exposed to pyrethroids through their conventional diets, although the magnitude was smaller than for the residential exposure. Children's ages appear to be significantly associated with pyrethroids exposure, which is likely attributed to the use of pyrethroids around the premises or in the facilities where older children engaged in the outdoor activities. We conclude that residential pesticide use represents the most important risk factor for children's exposure to pyrethroid insecticides. Because of the wide use of pyrethroids in the United States, the findings of this study are important for both children's pesticide exposure assessment and environmental public health.
Analysis of Chinese herbal creams prescribed for dermatological conditions
Authors: F M Keane, S E Munn, A W P du Vivier, N F Taylor, E M Higgins
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objective:</b> To determine whether Chinese herbal creams used for the treatment of dermatological conditions contain steroids. <b>Design:</b> 11 herbal creams obtained from patients attending general and paediatric dermatology outpatient clinics were analysed with high resolution gas chromatography and mass spectrometry. <b>Setting:</b> Departments of dermatology and clinical biochemistry. <b>Main outcome measure:</b> Presence of steroid. <b>Results:</b> Eight creams contained dexamethasone at a mean concentration of 456μg/g (range 64to 1500μg/g). All were applied to areas of sensitive skin such as face and flexures. <b>Conclusion:</b> Greater regulation needs to be imposed on Chinese herbalists to prevent illegal and inappropriate prescribing of potent steroids.
The Kidney and Ear: Emerging Parallel Functions
Authors: Elena Torban, Paul Goodyer
Journal: Annual Review of Medicine (2008)

The association between renal dysplasia and minor malformations of the external ear is weak. However, there is a remarkable list of syndromes that link the kidney to the inner ear. To organize these seemingly disparate syndromes, we cluster representative examples into three groups: (a) syndromes that share pathways regulating development; (b) syndromes involving dysfunction of the primary cilium, which normally provides critical information to epithelial cells about the fluid in which they are bathed; (c) syndromes arising from dysfunction of specialized proteins that transport ions and drugs in and out of the extracellular fluid or provide structural support.
Reproducibility of continuous 24 hour oesophageal pH monitoring in infants and children.
Authors: Y Vandenplas, R Helven, H Goyvaerts, L Sacre
Journal: Gut (1990)

The reproducibility of 24 hour oesophageal pH monitoring was studied in 30 infants and children including the proportions of the investigation time with a pH less than 4 (reflux index), the number of episodes with a pH less than 4 or lasting longer than five minutes, and the duration of the longest episodes with a pH less than 4. Twenty four hour pH monitoring was performed using identical equipment on two consecutive days under similar conditions. Pearson correlation coefficients range from 0.88 to 0.98. The results obtained on two consecutive days were similar. The reflux index and the number of reflux episodes greater than five minutes were the most reproducible parameters. Despite the many patient related factors influencing pH data, the reproducibility of 24 hour pH monitoring data are satisfactory for routine clinical application.
Phase II Evaluation of Temozolomide and 13-cis-Retinoic Acid for the Treatment of Recurrent and Progressive Malignant Glioma: A North American Brain Tumor Consortium Study
Authors: Kurt A. Jaeckle, Kenneth R. Hess, W.K. Alfred Yung, Harry Greenberg, Howard Fine, David Schiff, Ian F. Pollack, John Kuhn, Karen Fink, Minesh Mehta, Timothy Cloughesy, M. Kelly Nicholas, Susan Chang, Michael Prados
Journal: Journal of Clinical Oncology (2003)

Purpose: Temozolomide (TMZ) and 13-cis-retinoic acid (cRA) have shown activity in prior single-agent trials of recurrent malignant gliomas (MG). This phase II trial evaluated efficacy and toxicity of combination temozolomide and cRA treatment in recurrent MG. Patients and Methods: Adults with recurrent supratentorial MG for whom surgery, radiation, and/or chemotherapy failed were eligible. Treatment included oral TMZ 150 or 200 mg/m 2 /d, days 1 through 5, and cRA 100 mg/m 2 /d, days 1 to 21, every 28 days. Primary end point was progression-free survival at 6 months (PFS 6); secondary end points included response, survival, and PFS12. Results: Eighty-eight eligible patients (glioblastoma multiforme [n = 40]; anaplastic gliomas [n = 48; astrocytoma, 28; oligodendroglioma, 14; mixed glioma, six]) received treatment. PFS 6 was 43% (95% confidence interval [CI], 33% to 54%) and PFS12 was 16% (95% CI, 10% to 26%). Median overall PFS was 19 weeks (95% CI, 16 to 27 weeks), and median overall survival (OS) was 47 weeks (95% CI, 36 to 58 weeks). OS was 46% (95% CI, 36% to 57%) at 52 weeks and 21% (95% CI, 13% to 31%) at 104 weeks. Of 84 assessable patients, there were two (3%) complete responses and eight (12%) partial responses (complete plus partial response, 15%). Among 499 treatment cycles, the most common grade 3/4 events included granulocytopenia (1.8%), thrombocytopenia (1.4%), and hypertriglyceridemia (1.2%). Conclusion: TMZ and cRA were active, exceeding our 20% thresholds for PFS 6 success, assuming 20% improvement over our previously reported database (glioblastoma multiforme: expected, 30%; observed, 32%; anaplastic glioma: expected, 40%; observed, 50%).
Mice Lacking the Amplified in Breast Cancer 1/Steroid Receptor Coactivator-3 Are Resistant to Chemical Carcinogen–Induced Mammary Tumorigenesis
Authors: Shao-Qing Kuang, Lan Liao, Shu Wang, Daniel Medina, Bert W. O'Malley, Jianming Xu
Journal: Cancer Research (2005)

Abstract Amplified in breast cancer 1 (AIB1; steroid receptor coactivator-3, p/CIP, RAC3, ACTR, TRAM-1, or NCoA-3) is a transcriptional coactivator for nuclear receptors and certain other transcription factors and is a newly defined oncogene overexpressed in human breast cancer. Although the role and molecular mechanism of AIB1 in normal physiology and in breast cancer are currently under intensive investigation, the role of AIB1 in determination of the susceptibility of mammary gland to chemical carcinogens remains uncharacterized. In this study, we used back-crossed FVB wild-type (WT) and AIB1 mutant mice to assess the role of AIB1 in mammary gland development and in carcinogen-induced tumorigenesis. We show that mammary ductal growth was delayed in AIB1−/− mice with FVB strain background, and mammary ductal outgrowths emanating from the AIB1−/− mammary epithelial transplants in WT mice also were attenuated, indicating that the role of AIB1 in mammary ductal growth is a mammary epithelial autonomous function. In mice treated with the chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA), AIB1 deficiency protected the mammary gland, but not the skin, from tumorigenesis. AIB1 deficiency suppressed the up-regulation of the insulin receptor substrate (IRS)-1 and IRS-2 and thereby inhibited the activation of Akt, expression of cyclin D1, and cell proliferation. The suppression of these components for insulin-like growth factor-I signaling might be partially responsible for the decreased DMBA-induced mammary tumor initiation and progression in AIB1−/− mice. Our results suggest that AIB1 may serve as a potential target for prevention of carcinogen-induced breast cancer initiation and for treatment of breast cancer progression.
The ligase chain reaction as a primary screening tool for the detection of culture positive tuberculosis
Authors: T M O'Connor
Journal: Thorax (2000)

The ligase chain reaction Mycobacterium tuberculosis assay uses ligase chain reaction technology to detect tuberculous DNA sequences in clinical specimens. A study was undertaken to determine its sensitivity and specificity as a primary screening tool for the detection of culture positive tuberculosis.The study was conducted on 2420 clinical specimens (sputum, bronchoalveolar lavage fluid, pleural fluid, urine) submitted for primary screening for Mycobacterium tuberculosis to a regional medical microbiology laboratory. Specimens were tested in parallel with smear, ligase chain reaction, and culture.Thirty nine patients had specimens testing positive by the ligase chain reaction assay. Thirty two patients had newly diagnosed tuberculosis, one had a tuberculosis relapse, three had tuberculosis (on antituberculous therapy when tested), and three had healed tuberculosis. In the newly diagnosed group specimens were smear positive in 21 cases (66%), ligase chain reaction positive in 30 cases (94%), and culture positive in 32 cases (100%). Using a positive culture to diagnose active tuberculosis, the ligase chain reaction assay had a sensitivity of 93.9%, a specificity of 99.8%, a positive predictive value of 83.8%, and a negative predictive value of 99.9%.This study is the largest clinical trial to date to report the efficacy of the ligase chain reaction as a primary screening tool to detect Mycobacterium tuberculosis infection. The authors conclude that ligase chain reaction is a useful primary screening test for tuberculosis, offering speed and discrimination in the early stages of diagnosis and complementing traditional smear and culture techniques.
Inhibitory Interactions between BK and JC Virus among Kidney Transplant Recipients
Authors: Xingxing S. Cheng, Daniel L. Bohl, Gregory A. Storch, Caroline Ryschkewitsch, Monique Gaudreault-Keener, Eugene O. Major, Parmjeet Randhawa, Karen L. Hardinger, Daniel C. Brennan
Journal: Journal of the American Society of Nephrology (2011)

BK and JC polyomaviruses can reactivate after transplantation, causing renal dysfunction and graft loss. The incidence of JC reactivation after renal transplant is not well understood. Here, we characterized JC reactivation using samples collected during the first year after transplantation from 200 kidney recipients. We detected BK and JC viruses in the urine of 35 and 16% of transplant recipients, respectively. The median viral load in the urine was 400 times higher for BK virus than JC virus. The presence of BK viruria made concurrent JC viruria less likely: JC viruria was detected in 22% of non-BK viruric recipients compared with 4% of BK viruric recipients (<i>P</i> = 0.001). The co-detection rate was 1.5%, which is less than the expected 5.6% if reactivation of each virus was independent (<i>P</i> = 0.001). We did not observe JC viremia, JC nephropathy, or progressive multifocal leukoencephalopathy. The onset of JC viruria was associated with donor, but not recipient, JC-specific antibody in a titer-dependent fashion and inversely associated with donor and recipient BK-specific antibody. Donor and recipient JC seropositivity did not predict BK viruria or viremia. In conclusion, among renal transplant recipients, infection with one polyomavirus inversely associates with infection with the other.
Personalized copy number and segmental duplication maps using next-generation sequencing
Authors: Can Alkan, Jeffrey M Kidd, Tomas Marques-Bonet, Gozde Aksay, Francesca Antonacci, Fereydoun Hormozdiari, Jacob O Kitzman, Carl Baker, Maika Malig, Onur Mutlu, S Cenk Sahinalp, Richard A Gibbs, Evan E Eichler
Journal: Nature Genetics (2009)