tbuckley/cabot-search huggingface dataset:
Abstract 5175: Preclinical monitoring of prostate cancer lesions in bone by intravital multiphoton microscopy
Authors: Eleonora Dondossola, Stephanie Alexander, Steve Alexander, Boris Holzapfel, Christopher Logothetis, Dietmar Hutmacher, Peter Friedl
Journal: Cancer Research (2015)

Abstract Bone metastases are a major complication in patients with advanced prostate cancer (PCa) and frequent cause of therapy resistance. Besides cell intrinsic mechanisms, signals received from the bone microenvironment critically contribute to support PCa cell survival and growth. Recent advances in intravital microscopy enable to investigate this complex PCa cell-microenvironment interaction and allow preclinical examination of tumor responses to both conventional and targeted therapy. We developed a window model amenable to intravital multiphoton microscopy (MPM) to longitudinally monitor PCa lesions in humanized neobone established in the dermis of the mouse. Tissue engineered bone constructs, TEBCs, were generated by functionalizing polymeric polycaprolactone scaffolds with human mesenchymal stem cells differentiated to osteoblasts, and characterized in vitro for cell distribution and calcium deposition. After in vivo implantation, TEBC maturation was monitored by μCT, MPM and histological analysis over time to generate a miniaturized-neobone with defined cortical thickness (50-60 μm) suitable for intravital imaging through a body window. PCa (PC3) lesions, after implantation into the bone cavity, were longitudinally monitored for growth and niche development, using multi-parameter recording of: collagen/bone matrix (SHG), bone surface (THG), blood vessels/stromal phagocytes (fluorescent dextran), and PC3 cells (nuclear H2BeGFP, cytoplasmatic DsRed2). By combining innovative tissue engineering with optical windows, state-of-the-art fluorescence reporter technology and intravital MPM, this model will provide mechanistic and applied insight into the therapy response of bone metastasis. Citation Format: Eleonora Dondossola, Stephanie Alexander, Steve Alexander, Boris Holzapfel, Christopher Logothetis, Dietmar Hutmacher, Peter Friedl. Preclinical monitoring of prostate cancer lesions in bone by intravital multiphoton microscopy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5175. doi:10.1158/1538-7445.AM2015-5175
Orbital Varix
Authors: Lee Kiang, Alon Kahana
Journal: New England Journal of Medicine (2015)

A 63-year-old man presented with a history of intermittent vision loss, binocular diplopia, and left-eye blepharoptosis during bending or straining. A video shows a Valsalva maneuver inducing 6 mm of proptosis in the left eye, with anterosuperior globe displacement and blepharoptosis.
FRI0009 Decreased Frequencies of Circulating CD19+CD24<sup>high</sup>CD38<sup>high</sup>B Cells in ACPA+ Rheumatoid Arthritis (RA) Patients
Authors: I. Arroyo-Villa, M.-B. Bautista-Caro, A. Balsa, P. Aguado, M.-G. Bonilla-Hernán, C. Plasencia, A. Villalba, L. Nuño, A. Puig-Kröger, E. Martín-Mola, M.-E. Miranda-Carús
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> CD19+CD24<sup>high</sup>CD38<sup>high</sup> B cells have been described to have a regulatory capacity and their frequency is altered in the peripheral blood of patients with various autoimmune diseases. <h3>Objectives</h3> To determine the frequency of circulating CD19+CD24<sup>high</sup>CD38<sup>high</sup> B cells in patients with RA, and establish a correlation with clinical parameters. <h3>Methods</h3> Peripheral blood was drawn from RA patients treated with non-biological DMARDs (n=48), RA patients treated with anti-TNFalpha drugs (n=15) and healthy controls (n=63) that were matched with patients for age and gender. After isolation by Ficoll-Hypaque gradient, PBMCs were stained with antibodies to CD3, CD4, CD19, CD24, and CD38, and examined by flow cytometry. <h3>Results</h3> A decreased frequency of CD19+CD24<sup>high</sup>CD38<sup>high</sup> B cells was apparent in in ACPA+ but not ACPA- RA patients, and this was observed not only in patients treated with non-biological DMARDs but also in patients receiving anti-TNFalpha drugs. In addition, the frequency of CD19+CD24<sup>high</sup>CD38<sup>high</sup> B cells showed a significant negative correlation with ACPA titers (r = -0.43, p=0.023). In contrast, no correlation was found between the frequency of circulating CD19+CD24<sup>high</sup>CD38<sup>high</sup> B cells and either rheumatoid factor titres or disease activity as determined by the DAS28 score. <h3>Conclusions</h3> A decreased frequency of CD19+CD24<sup>high</sup>CD38<sup>high</sup> B cells is observed in ACPA+ but not ACPA- RA patients treated with either nonbiological DMARDs or anti-TNFalpha drugs, that is related with ACPA titres but not with rheumatoid factor titres or disease activity. <h3>Disclosure of Interest</h3> None declared
Comprehensive promoter level expression quantitative trait loci analysis of the human frontal lobe
Authors: Cornelis Blauwendraat, Margherita Francescatto, J. Raphael Gibbs, Iris E. Jansen, Javier Simón-Sánchez, Dena G. Hernandez, Allissa A. Dillman, Andrew B. Singleton, Mark R. Cookson, Patrizia Rizzu, Peter Heutink
Journal: Genome Medicine (2016)

Expression quantitative trait loci (eQTL) analysis is a powerful method to detect correlations between gene expression and genomic variants and is widely used to interpret the biological mechanism underlying identified genome wide association studies (GWAS) risk loci. Numerous eQTL studies have been performed on different cell types and tissues of which the majority has been based on microarray technology. We present here an eQTL analysis based on cap analysis gene expression sequencing (CAGEseq) data created from human postmortem frontal lobe tissue combined with genotypes obtained through genotyping arrays, exome sequencing, and CAGEseq. Using CAGEseq as an expression profiling technique combined with these different genotyping techniques allows measurement of the molecular effect of variants on individual transcription start sites and increases the resolution of eQTL analysis by also including the non-annotated parts of the genome. We identified 2410 eQTLs and show that non-coding transcripts are more likely to contain an eQTL than coding transcripts, in particular antisense transcripts. We provide evidence for how previously identified GWAS loci for schizophrenia (NRGN), Parkinson's disease, and Alzheimer's disease (PARK16 and MAPT loci) could increase the risk for disease at a molecular level. Furthermore, we demonstrate that CAGEseq improves eQTL analysis because variants obtained from CAGEseq are highly enriched for having a functional effect and thus are an efficient method towards the identification of causal variants. Our data contain both coding and non-coding transcripts and has the added value that we have identified eQTLs for variants directly adjacent to TSS. Future eQTL studies would benefit from combining CAGEseq with RNA sequencing for a more complete interpretation of the transcriptome and increased understanding of eQTL signals.
Processing cost and its consequences
Authors: William O'Grady
Journal: Behavioral and Brain Sciences (2016)

Abstract I focus on two challenges that processing-based theories of language must confront: the need to explain why language has the particular properties that it does, and the need to explain why processing pressures are manifested in the particular way that they are. I discuss these matters with reference to two illustrative phenomena: proximity effects in word order and a constraint on contraction.
Transplantation and Cancer
Authors: J G Fortner
Journal: CA A Cancer Journal for Clinicians (1972)

Thomas Starzl and their associates reported that five renal allograft recipients from the collective transplantation programs of Denver, Minneapolis and Edinburgh developed malignant lymphomas.This brought to the forefront the controver sial question: Is there an increased incidence of de novo cancer in patients following transplantation and immunosupression?
Whole-Body Pediatric Neuroblastoma Imaging
Authors: Atmaram S. Pai Panandiker, Jamie Coleman, Barry Shulkin
Journal: Clinical Nuclear Medicine (2015)

Pediatric cancer imaging stands to benefit from higher tumor detection sensitivity without ionizing radiation exposure. A prospective protocol compared diagnostic I-metaiodobenzylguanidine (I-mIBG) with whole-body diffusion-weighted MRI (DWI) to validate adjunctive methods of identifying small-volume oligometastatic neuroblastoma tumor deposits. Dual-modality imaging (I-mIBG and DWI) was obtained within a 3- and 25-day window at baseline and again at one year in the first enrolled patient. MRI was able to define the full extent of metastatic disease foci with improved resolution. These findings may provide critical information for definitive locoregional surgery and radiotherapy for high-risk neuroblastoma treatment.
The Vulnerable Esophagus: Riboflavin Deficiency and Squamous Cell Dysplasia of the Skin and the Esophagus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: H Foy, A Kondi
Journal: JNCI Journal of the National Cancer Institute (1984)

Eleven male baboons fed a synthetic diet completely lacking in riboflavin developed, after 15-36 weeks, profound macroscopic and microscopic architectural disorganization of the skin, mouth, and esophagus. The cutaneous lesions showed hyperkeratosis, gross derangement of keratinization with acanthosis, and impressive pseudocarcinomatous hyperplasia. In 5 baboons that died or were killed, there were large penetrating lesions having raised epithelial edges at the lower third of the esophagus or at the cardioesophageal junction, with gross epithelial hyperplasia and grossly deranged and thickened keratinization and numerous mitotic figures. None of the 8 control animals given riboflavin showed these abnormalities.
Heterogeneity of EGFR Aberrations and Correlation with Histological Structures: Analyses of Therapy-Naive Isogenic Lung Cancer Lesions with EGFR Mutation
Authors: Kenichi Suda, Isao Murakami, Hui Yu, Kim Ellison, Masaki Shimoji, Carlo Genova, Christopher J. Rivard, Tetsuya Mitsudomi, Fred R. Hirsch
Journal: Journal of Thoracic Oncology (2016)
Detection of cranial metastases by F-18 FDG positron emission tomography.
Authors: ALVIN YAMAMOTO, HONGMING ZHUANG, ABASS ALAVI
Journal: Clinical Nuclear Medicine (2001)

Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scanning has been useful in the management of various cancers. The normal glucose use of gray matter often limits the detection of metastatic lesions to the brain and skull with FDG PET. The authors report two cases of calvarial metastases: one with pheochromocytoma and the other with non–small-cell lung carcinoma. These cases illustrate the crucial role that FDG PET can play when patients are examined for metastases. The important concept of contrast resolution that is achieved with PET imaging is discussed as an advantage that significantly overcomes its limited spatial resolution in detecting small lesions that may not be detected by anatomic imaging techniques with high spatial resolution.
Model for Predicting Breast Cancer Risk in Women With Atypical Hyperplasia
Authors: Amy C. Degnim, Stacey J. Winham, Ryan D. Frank, V. Shane Pankratz, William D. Dupont, Robert A. Vierkant, Marlene H. Frost, Tanya L. Hoskin, Celine M. Vachon, Karthik Ghosh, Tina J. Hieken, Jodi M. Carter, Lori A. Denison, Brendan Broderick, Lynn C. Hartmann, Daniel W. Visscher, Derek C. Radisky
Journal: Journal of Clinical Oncology (2018)

Purpose Women with atypical hyperplasia (AH) on breast biopsy have an aggregate increased risk of breast cancer (BC), but existing risk prediction models do not provide accurate individualized estimates of risk in this subset of high-risk women. Here, we used the Mayo benign breast disease cohort to develop and validate a model of BC risk prediction that is specifically for women with AH, which we have designated as AH-BC. Patients and Methods Retrospective cohorts of women age 18 to 85 years with pathologically confirmed benign AH from Rochester, MN, and Nashville, TN, were used for model development and external validation, respectively. Clinical risk factors and histologic features of the tissue biopsy were selected using L1-penalized Cox proportional hazards regression. Identified features were included in a Fine and Gray regression model to estimate BC risk, with death as a competing risk. Model discrimination and calibration were assessed in the model-building set and an external validation set. Results The model-building set consisted of 699 women with AH, 142 of whom developed BC (median follow-up, 8.1 years), and the external validation set consisted of 461 women with 114 later BC events (median follow-up, 11.4 years). The final AH-BC model included three covariates: age at biopsy, age at biopsy squared, and number of foci of AH. At 10 years, the AH-BC model demonstrated good discrimination (0.63 [95% CI, 0.57 to 0.70]) and calibration (0.87 [95% CI, 0.66 to 1.24]). In the external validation set, the model showed acceptable discrimination (0.59 [95% CI, 0.51 to 0.67]) and calibration (0.91 [95% CI, 0.65 to 1.42]). Conclusion We have created a new model with which to refine BC risk prediction for women with AH. The AH-BC model demonstrates good discrimination and calibration, and it validates in an external data set.
Confirmed inguinal lymphogranuloma venereum genovar L2c in a man who had sex with men, Slovenia, 2015
Authors: Mojca Matičič, Irena Klavs, Jerneja Videčnik Zorman, Darja Vidmar Vovko, Rok Kogoj, Darja Keše
Journal: Eurosurveillance (2016)

A laboratory-confirmed lymphogranuloma venereum (LGV) case in Slovenia was reported in 2015, in a human immunodeficiency virus (HIV)-negative man presenting with inguinal lymphadenopathy. He reported unprotected insertive anal intercourse with two male partners in Croatia. Variant L2c of Chlamydia trachomatis was detected in clinical samples. Although the patient was eventually cured, the recommended treatment regimen with doxycycline had to be prolonged.
大動脈留置型特殊リザーバー(システム-1)を用いた頻回分割TACEによって加療を試みた巨大肝細胞癌の1例
Authors: 有松秀敏, 板野哲, 久富順次郎, 秋吉順史, 岩本英希, 佐田通夫
Journal: Liver Cancer (2010)
AB0255 The Impact of Patients Reported Flares on Functional Impairment in Rheumatoid Arthritis Patients With Low-Disease Activity: A Prospective Cohort Study Based on the Ambra Trial
Authors: D. Kuettel, R. Christensen, J. Primdahl, K. Hørslev-Petersen
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Flares - episodes of worsening in disease activity - are common features in patients with rheumatoid arthritis (RA), even in remission or in low disease activity state. There are different definitions of flare. It is unknown whether patient reported flares lead to suboptimal long-term outcomes. <h3>Objectives</h3> To investigate whether transient patient reported flares can influence functional disability in patients with established low active RA. <h3>Methods</h3> Out of 287 patients from the AMBRA trial (1), 268 RA patients with low disease activity (DAS28CRP &lt;3.2 and no swollen joints at baseline) and data about flares were included in analyses. The patients were followed for two years and were asked, at annual clinical controls, to recall the occurrence of flares during the past year, according to: no flares, transient flares or persistent joint complaints with tender and swollen joints. Functional capacity was assessed by the Danish version of the Health Assessment Questionnaire (HAQ). The proportion of patients who worsened in HAQ (ΔHAQ&gt; MCID of 0.22) was compared across three groups and the association between flare phenotype and functional outcome was analyzed by logistic regression. <h3>Results</h3> 70% were female, median age [IQR] was 63 years [55;70], 73% were rheumatoid factor positive, 71% anti-CCP positive and all had established RA (median [IQR] 7 years [4;13]). Based on the flare questionnaire three groups were distinguished: No-flares group (n=77), transient flares group (n=141) and patients with persistent joint complaints (n=50). Worsening in functional capacity (ΔHAQ&gt;0.22) was seen in 13%, 21% and 40% of patients with no flares, with transient flares and those with persistent joint complaints, respectively (p=0.0015). Compared to the reference group (no flares) worsening in functional capacity was potentially related to "flare phenotype": OR 1.81 (95%CI: 0.83-3.94, p=0.134) for the transient flare status, and statistically significantly associated with persistent joint complaints OR 2.01 (1.22-3.31, p=0.006). <h3>Conclusions</h3> RA patients with established low disease activity, who self-report persistent joint complaints have worse functional outcome compared to patients with transient flares and without flares. <h3>References</h3> Primdahl J, et al.: Ann Rheum Dis 2014; 73: 357-364. <h3>Disclosure of Interest</h3> None declared
Issues in developing psychotherapy groups for preschool children in outpatient clinics
Authors: T Haizlip, C McRee, B F Corder
Journal: American Journal of Psychiatry (1975)

A survey of 10 randomly selected clinics indicated that only 1 offered group psychotherapy for preschool children. Reasons given for the lack of such programs resembled the resistances encountered in the authors' clinic. The authors describe the solutions they found in creating and running therapy groups for preschool children and in integrating parent counseling with this treatment. It is suggested that professional groups provide in-service training opportunities in this area to counteract resistances resulting from clinic staffs' perceived lack of experience and expertise.
Genome-Wide Analysis of DNA Methylation and Fine Particulate Matter Air Pollution in Three Study Populations: KORA F3, KORA F4, and the Normative Aging Study
Authors: Tommaso Panni, Amar J. Mehta, Joel D. Schwartz, Andrea A. Baccarelli, Allan C. Just, Kathrin Wolf, Simone Wahl, Josef Cyrys, Sonja Kunze, Konstantin Strauch, Melanie Waldenberger, Annette Peters
Journal: Environmental Health Perspectives (2016)

Background:Epidemiological studies have reported associations between particulate matter (PM) concentrations and cancer and respiratory and cardiovascular diseases. DNA methylation has been identified as a possible link but so far it has only been analyzed in candidate sites.Objectives:We studied the association between DNA methylation and short- and mid-term air pollution exposure using genome-wide data and identified potential biological pathways for additional investigation.Methods:We collected whole blood samples from three independent studies—KORA F3 (2004–2005) and F4 (2006–2008) in Germany, and the Normative Aging Study (1999–2007) in the United States—and measured genome-wide DNA methylation proportions with the Illumina 450k BeadChip. PM concentration was measured daily at fixed monitoring stations and three different trailing averages were considered and regressed against DNA methylation: 2-day, 7-day and 28-day. Meta-analysis was performed to pool the study-specific results.Results:Random-effect meta-analysis revealed 12 CpG (cytosine-guanine dinucleotide) sites as associated with PM concentration (1 for 2-day average, 1 for 7-day, and 10 for 28-day) at a genome-wide Bonferroni significance level (p ≤ 7.5E-8); 9 out of these 12 sites expressed increased methylation. Through estimation of I2 for homogeneity assessment across the studies, 4 of these sites (annotated in NSMAF, C1orf212, MSGN1, NXN) showed p > 0.05 and I2 < 0.5: the site from the 7-day average results and 3 for the 28-day average. Applying false discovery rate, p-value < 0.05 was observed in 8 and 1,819 additional CpGs at 7- and 28-day average PM2.5 exposure respectively.Conclusion:The PM-related CpG sites found in our study suggest novel plausible systemic pathways linking ambient PM exposure to adverse health effect through variations in DNA methylation.Citation:Panni T, Mehta AJ, Schwartz JD, Baccarelli AA, Just AC, Wolf K, Wahl S, Cyrys J, Kunze S, Strauch K, Waldenberger M, Peters A. 2016. A genome-wide analysis of DNA methylation and fine particulate matter air pollution in three study populations: KORA F3, KORA F4, and the Normative Aging Study. Environ Health Perspect 124:983–990; http://dx.doi.org/10.1289/ehp.1509966
Progress in antisense therapeutics
Authors: S T Crooke
Journal: Medicinal Research Reviews (1996)

Antisense technology offers the potential to create compounds specific enough to support highly isotypically selective pharmacology (i.e., pharmacologic agents specific enough to affect only one isotype in a multigene family of related proteins). However, enthusiasm about the potential of the technology has been appropriately tempered by questions about its ability to deliver on its promise. The fundamental issue is: Can oligonucleotides that have acceptable drug properties be created? This review discusses recent progress that helps to define the pharmacokinetic, pharmacologic, and toxicologic properties of phosphorothioate oligonucleotides. Progress in the medicinal chemistry of oligonucleotides that has resulted in a wide range of new chemical classes is also described.
Umbilical Plugoma Mimics Melanoma Metastasis on FDG PET/CT
Authors: Yazan Z. Alabed, Christopher Sakellis
Journal: Clinical Nuclear Medicine (2015)

An 84-year-old man with history of left forehead melanoma was found on a restaging F-FDG PET/CT scan with hypermetabolic lung nodules and a mildly FDG-avid soft tissue nodule posterior to the umbilicus. Biopsy of a right lower lobe nodule revealed metastatic melanoma. Follow-up posttreatment PET/CT scan showed complete resolution of lung nodules and unchanged FDG uptake at the level of the umbilicus. Review of the patient's medical history revealed a remote history of umbilical hernia repair. We present a case of postsurgical plugoma mimicking the appearance of melanoma metastasis on FDG PET/CT.
DESOXYCORTICOSTERONE ACETATE AND WOUND HEALING
Authors: Conrad L. Pirani, Robert C. Stepto, Kenneth Sutherland
Journal: The Journal of Experimental Medicine (1951)

The effect of desoxycorticosterone acetate (DCA) on the granulation tissue of healing and healed linear laparotomy wounds was studied in young adult male guinea pigs maintained on a complete diet and on a known intake of ascorbic acid. DCA induces the production of an excessive amount of granulation tissue, as evidenced by a relatively great number of fibroblasts and by a larger amount of ground substance. This effect was accompanied by a slight to moderate lag in the maturation process of both cellular and intercellular elements. These changes were observed when DCA administration was begun 5 days prior to operation, but were less obvious or absent if DCA was injected, beginning on the 5th or 10th postoperative day. The results indicate that the action of DCA on immature, proliferating connective tissue is marked, and is considerably less or absent when connective tissue elements have reached partial or almost complete maturity. The effect of DCA on connective tissue does not appear to rest on the basis of an altered nutritional status. Chemical and histochemical studies of the adrenals suggest that the action of DCA on connective tissue is probably mediated through a disturbance of adrenocortical function, namely an imbalance between hormones of the zona glomerulosa (excess of DCA) and those of the zona fasciculata (deficiency of glucocorticoids). The presence of changes in granulation tissue and the lack of them in mature resting connective tissue of DCA-treated guinea pigs confirm the view that a profound difference in the response mechanism exists between resting and actively proliferating connective tissue.