tbuckley/cabot-search huggingface dataset:
CT screening for lung cancer: Figure 1
Authors: Robert P Young, Raewyn J Hopkins
Journal: Thorax (2011)

<h3>BACKGROUND AND PURPOSE:</h3> Wide-neck intracranial aneurysms in patients with acute SAH are often challenging lesions to treat by neurosurgical and endovascular approaches. The aim of this study was to investigate the feasibility, safety, and efficacy of the use of temporary Solitaire AB stent–assisted technique with coiling for the treatment of acutely ruptured wide-neck aneurysms without perioperative antiplatelet therapy. <h3>MATERIALS AND METHODS:</h3> A retrospective review of our endovascular data base identified all patients treated in the acute phase with a temporary stent–assisted technique by use of a fully resheathable Solitaire AB stent and coiling. One-year clinical and angiographic outcomes were evaluated. <h3>RESULTS:</h3> Eight patients (5 women and 3 men; mean age, 57.5 years) with 8 ruptured wide-neck aneurysms were treated. There were 3 complications without clinical impact. Postoperative complete occlusion was achieved in 5 aneurysms, and 3 had a neck remnant. Three patients had an mRS score of 0, and 1 an mRS score of 3. Among the 4 patients admitted with a World Federation of Neurological Societies grade of V, 1 died, 1 improved to an mRS score of 1, and the other 2 achieved mRS scores of 4 and 5. Five had a stable occlusion, and 2 of the 3 incompletely occluded aneurysms underwent recanalization. <h3>CONCLUSIONS:</h3> In this small series, temporary placement of the Solitaire AB stent during coiling was a feasible and effective treatment for acutely ruptured wide-neck aneurysms. This technique, avoiding the need for perioperative antiplatelet therapy, could be a valuable option for the treatment of such lesions when the balloon remodeling technique is either not an option or unsuccessful.
MicroRNA profiling in pediatric pilocytic astrocytoma reveals biologically relevant targets, including PBX3, NFIB, and METAP2
Authors: Cheng-Ying Ho, Eli Bar, Caterina Giannini, Luigi Marchionni, Matthias A. Karajannis, David Zagzag, David H. Gutmann, Charles G. Eberhart, Fausto J. Rodriguez
Journal: Neuro-Oncology (2012)

Pilocytic astrocytoma (PA) is a World Health Organization grade I glioma that occurs most commonly in children and young adults. Specific genetic alterations have been described in PA, but the pathogenesis remains poorly understood. We studied microRNA (miRNA) alterations in a large cohort of patients with PA. A total of 43 PA, including 35 sporadic grade I PA, 4 neurofibromatosis-1 (NF1)–associated PA, and 4 PA with pilomyxoid features, as well as 5 nonneoplastic brain controls were examined. BRAF fusion status was assessed in most cases. RNA was examined using the Agilent Human miRNA Microarray V3 platform. Expression of miRNA subsets was validated using quantitative real-time PCR (qRT-PCR) with Taqman probes. Validation of predicted protein targets was performed on tissue microarrays with the use of immunohistochemistry. We identified a subset of miRNAs that were differentially expressed in pediatric PAs versus normal brain tissue: 13 miRNAs were underexpressed, and 20 miRNAs were overexpressed in tumors. Differences were validated by qRT-PCR in a subset, with mean fold change in tumor versus brain of -17 (miR-124), -15 (miR-129), and 19.8 (miR-21). Searching for predicted protein targets in Targetscan, we identified a number of known and putative oncogenes that were predicted targets of miRNA sets relatively underexpressed in PA. Predicted targets with increased expression at the mRNA and/or protein level in PA included PBX3, METAP2, and NFIB. A unique miRNA profile exists in PA, compared with brain tissue. These miRNAs and their targets may play a role in the pathogenesis of PA.
Convergence of the epidemiology and pathology of COPD
Authors: J Vestbo
Journal: Thorax (2005)

The epidemiology of chronic obstructive pulmonary disease (COPD) has been dominated by one hypothesis stating that cigarette smoking and chronic bronchitis were the key to pathogenesis and another that asthma, chronic bronchitis, and even emphysema are related to different expressions of a primary airway abnormality. The first hypothesis was rejected in the late 1960s based on a longitudinal study of working men where only a fraction of smokers developed COPD and where development of COPD was independent of the absence or presence of chronic bronchitis. Chronic bronchitis in more advanced COPD was subsequently associated with a more rapid decline in lung function and more frequent exacerbations. The second hypothesis is more difficult to test but longitudinal studies have shown that the presence of bronchial hyperresponsiveness may predict the subjects who go on to develop COPD. This brief review attempts to reconcile these findings with the pathology found in the lung.
Performance-Based Measurement of Functional Disability in Schizophrenia: A Cross-National Study in the United States and Sweden
Authors: Philip D. Harvey, Lars Helldin, Christopher R. Bowie, Robert K. Heaton, Anna-Karin Olsson, Fredrik Hjärthag, Torsten Norlander, Thomas L. Patterson
Journal: American Journal of Psychiatry (2009)

Objective: Recent advances in the assessment of disability in schizophrenia have separated the measurement of functional capacity from real-world functional outcomes. The authors examined the similarity of performance-based assessments of everyday functioning, real-world disability, and achievement of milestones in people with schizophrenia in the United States and Sweden. Method: The UCSD Performance-Based Skills Assessment–Brief Version (UPSA-B) and a neuropsychological assessment were administered to schizophrenia patients living in rural areas in Sweden (N=146) and in the New York City area (N=244), and patients' functioning was rated by their case managers. Information from records and case managers was used to determine the frequency of living independently, working, and having ever experienced a stable romantic relationship. Results: Performance on the UPSA-B was essentially identical in the two samples (New York, mean score=13.84; Sweden, mean score=13.30), as were scores on the case manager ratings of everyday activities (New York, mean=49.0; Sweden, mean=48.8). The correlations between UPSA-B score, neuropsychological test performance, and case manager ratings did not differ across the two samples. The proportion of patients who had never had a close relationship and the rate of vocational disability were also nearly identical. However, while 80% of the Swedish patients were living independently, only 46% of the New York patients were. Conclusions: While scores on performance-based measures of everyday living skills were similar in people with schizophrenia across cultures, real-world residential outcomes were very different. These data suggest that cultural and social support systems can lead to divergent real-world outcomes among individuals who show evidence of the same levels of ability and potential.
Aromatase Inhibitors in the Treatment and Prevention of Breast Cancer
Authors: Paul E. Goss, Kathrin Strasser
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The purpose of this article is to provide an overview of the current clinical status and possible future applications of aromatase inhibitors in breast cancer. METHODS: A review of the literature on the third-generation aromatase inhibitors was conducted. Some data that have been presented but not published are included. In addition, the designs of ongoing trials with aromatase inhibitors are outlined and the implications of possible results discussed. RESULTS: All of the third-generation oral aromatase inhibitors—letrozole, anastrozole, and vorozole (nonsteroidal, type II) and exemestane (steroidal, type I)—have now been tested in phase III trials as second-line treatment of postmenopausal hormone-dependent breast cancer. They have shown clear superiority compared with the conventional therapies and are therefore considered established second-line hormonal agents. Currently, they are being tested as first-line therapy in the metastatic, adjuvant, and neoadjuvant settings. Preliminary results suggest that the inhibitors might displace tamoxifen as first-line treatment, but further studies are needed to determine this. CONCLUSION: The role of aromatase inhibitors in premenopausal breast cancer and in combination with chemotherapy and other anticancer treatments are areas of future exploration. The ongoing adjuvant trials will provide important data on the long-term safety of aromatase inhibitors, which will help to determine their suitability for use as chemopreventives in healthy women at risk of developing breast cancer.
Molecular Analysis of Plasma DNA for the Early Detection of Lung Cancer by Quantitative Methylation-Specific PCR
Authors: Kimberly Laskie Ostrow, Mohammad O. Hoque, Myriam Loyo, Marianna Brait, Alissa Greenberg, Jill M. Siegfried, Jennifer R. Grandis, Autumn Gaither Davis, William L. Bigbee, William Rom, David Sidransky
Journal: Clinical Cancer Research (2010)

Aberrant promoter hypermethylation of tumor suppressor genes is a promising marker for lung cancer detection. We investigated the likelihood of detecting aberrant DNA methylation of tumor suppressor genes in plasma samples of patients with abnormalities of the lung detected upon computed tomography (CT) scan.In a small evaluation cohort, four gene promoters (DCC, Kif1a, NISCH, and Rarb) were found to be methylated with increased frequency in samples from cancer patients specifically. We then examined DNA from 93 plasma samples from patients with abnormal findings in the lung detected upon CT scan for aberrant methylation of these four gene promoters by quantitative fluorogenic real-time PCR. The patients were divided into two groups, ground glass opacity (n = 23) and cancerous tumors (n = 70). Plasma DNA from age-matched nodule-free individuals were used as controls (n = 80).In plasma, 73% of patients with cancerous tumors showed methylation of at least one gene with a specificity of 71% (P = 0.0001). Only 22% patients with ground glass opacity exhibited methylation of at least one gene. When smoking history was taken into account, 72% of cancer patients with no smoking history or those who smoked <20 pack-years showed methylation of at least one gene with 100% specificity (P = 0.05) when compared with matched controls. Among heavy smokers with 20+ pack-years of smoking history, 30% of the control group and 73% of the patients with cancerous tumors showed methylation (P = 0.0001).These biomarkers can distinguish between cancerous and noncancerous abnormal CT findings.
Primary leiomyoma of the pulmonary vein.
Authors: P Peters, S E Trotter, M N Sheppard, P Goldstraw
Journal: Thorax (1992)

The first case of a primary leiomyoma in a pulmonary vein in an adult is presented. Although rare, leiomyoma and leiomyosarcoma of the lung and great vessels should be included in the differential diagnosis of intrathoracic space occupying lesions.
Contrasting Testosterone Concentrations in Type 1 and Type 2 Diabetes
Authors: R. Tomar
Journal: Diabetes Care (2006)

We have recently reported (1) that male patients with type 2 diabetes have frequent hypogonadotrophic hypogonadism. We have now asked whether a similar defect may be observed in type 1 diabetic males to determine whether diabetes per se is the cause of hypogonadotrophic hypogonadism.

Fifty patients with type 1 diabetes (age range 23–58 years) and 50 age-matched patients with type 2 diabetes (age range 28–51 years) were included in the study. Patients with known history of hypogonadism, panhypopituitarism, or chronic debilitating disease such as renal failure, cirrhosis, or HIV infection were excluded from the study. Fasting blood samples were obtained from the patients, and total testosterone (TT), free testosterone (FT), sex hormone–binding globulin (SHBG), leutinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured as previously described (1). FT and bioavailable testosterone (bioT) were calculated from SHBG and TT as previously described (1). Hypogonadism was defined as low FT or low calculated FT (2). Mann-Whitney rank-sum test or Student’s t test for unpaired data, χ2 test, and Spearman’s test were used as appropriate (Sigmastat software).

The mean TT, FT, calculated FT, and bioT concentrations in type 1 diabetic patients were in the middle of the normal range (Table 1). No patient had subnormal TT concentrations; three patients had supranormal TT, while two patients had subnormal FT and bioT concentrations.

The mean TT concentration in patients with type 2 diabetes was significantly lower than that in type 1 diabetic subjects …
Clinical assessment of the scapula: a review of the literature
Authors: Filip Struyf, Jo Nijs, Sarah Mottram, Nathalie A Roussel, Ann M J Cools, Romain Meeusen
Journal: British Journal of Sports Medicine (2012)

Scientific evidence supporting a role for faulty scapular positioning in patients with various shoulder disorders is cumulating. Clinicians who manage patients with shoulder pain and athletes at risk of developing shoulder pain need to have the skills to assess static and dynamic scapular positioning and dynamic control. Several methods for the assessment of scapular positioning are described in scientific literature. However, the majority uses expensive and specialised equipment (laboratory methods), making their use in clinical practice nearly impossible. On the basis of biometric and kinematic studies, guidelines for interpreting the observation of static and dynamic scapular positioning pattern in patients with shoulder pain are provided. At this point, clinicians can use reliable clinical tests for the assessment of both static and dynamic scapular positioning in patients with shoulder pain. However, this review also provides clinicians several possible pitfalls when performing clinical scapular evaluation. On the basis of its clinical relevance, its proven reliability, its relation to body length and its applicability in a clinical setting, this review recommends to assess the scapula both static (visual observation and acromial distance or Baylor/double square method for shoulder protraction) and semidynamic (visual observation and inclinometry for scapular upward rotation). In addition, when the patient demonstrates with shoulder impingement symptoms, the scapular repositioning test and scapular assistant test are recommended for relating the patients' symptoms to the position or movement of the scapula.
microRNA regulation of mammalian target of rapamycin expression and activity controls estrogen receptor function and RAD001 sensitivity
Authors: Elizabeth C Martin, Lyndsay V Rhodes, Steven Elliott, Adrienne E Krebs, Kenneth P Nephew, Erik K Flemington, Bridgette M Collins-Burow, Matthew E Burow
Journal: Molecular Cancer (2014)

The AKT/mammalian target of rapamycin (mTOR) signaling pathway is regulated by 17α-estradiol (E2) signaling and mediates E2-induced proliferation and progesterone receptor (PgR) expression in breast cancer. Here we use deep sequencing analysis of previously published data from The Cancer Genome Atlas to demonstrate that expression of a key component of mTOR signaling, rapamycin-insensitive companion of mTOR (Rictor), positively correlated with an estrogen receptor-α positive (ERα+) breast tumor signature. Through increased microRNA-155 (miR-155) expression in the ERα+ breast cancer cells we demonstrate repression of Rictor enhanced activation of mTOR complex 1 (mTORC1) signaling with both qPCR and western blot. miR-155-mediated mTOR signaling resulted in deregulated ERα signaling both in cultured cells in vitro and in xenografts in vivo in addition to repressed PgR expression and activity. Furthermore we observed that miR-155 enhanced mTORC1 signaling (observed through western blot for increased phosphorylation on mTOR S2448) and induced inhibition of mTORC2 signaling (evident through repressed Rictor and tuberous sclerosis 1 (TSC1) gene expression). mTORC1 induced deregulation of E2 signaling was confirmed using qPCR and the mTORC1-specific inhibitor RAD001. Co-treatment of MCF7 breast cancer cells stably overexpressing miR-155 with RAD001 and E2 restored E2-induced PgR gene expression. RAD001 treatment of SCID/CB17 mice inhibited E2-induced tumorigenesis of the MCF7 miR-155 overexpressing cell line. Finally we demonstrated a strong positive correlation between Rictor and PgR expression and a negative correlation with Raptor expression in Luminal B breast cancer samples, a breast cancer histological subtype known for having an altered ERα-signaling pathway. miRNA mediated alterations in mTOR and ERα signaling establishes a new mechanism for altered estrogen responses independent of growth factor stimulation.
Inhibition of Tumor-Derived Prostaglandin-E2 Blocks the Induction of Myeloid-Derived Suppressor Cells and Recovers Natural Killer Cell Activity
Authors: Yumeng Mao, Dhifaf Sarhan, André Steven, Barbara Seliger, Rolf Kiessling, Andreas Lundqvist
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Increased frequencies of myeloid-derived suppressor cells (MDSC) correlate with poor prognosis in patients with cancers. Tumor-derived prostaglandin-E2 (PGE2) plays an important role in inducing MDSCs. However, the detailed mechanisms of this induction remain unknown. To develop targeted therapies for MDSCs, we sought to investigate the molecular basis of PGE2-regulated accumulation of MDSCs and their functional consequence on natural killer (NK) cell activity. Experimental Design: The effects of PGE2 in inducing phenotypic, signaling, and functional alternations on monocytes were analyzed in vitro. Suppression of NK-cell activity by PGE2-treated monocytes was compared with that of freshly isolated CD14+HLA-DRlow/− monocytic MDSCs (moMDSC) from patients with melanoma. In addition, to explore the in vivo relevance of targeting PGE2 to reduce MDSC-mediated suppression of NK cells, we established a murine model, where tumor cells were disabled from cyclooxygenase-2 (COX-2) production. Results: Patient-derived moMDSCs inhibited NK-cell activity through the production of TGFβ. In vitro, binding of PGE2 to EP2 and EP4 receptors on monocytes activated the p38MAPK/ERK pathway and resulted in elevated secretion of TGFβ. Similar to moMDSCs, PGE2-treated monocytes potently suppressed NK-cell activity through production of TGFβ. Furthermore, silencing COX-2 in murine 4T1 tumor cells reduced the accumulation of CD11b+Gr1+ MDSCs in the spleen, resulting in concomitant improved in vivo clearance of NK-cell sensitive YAC-1 cells. Conclusions: Our results reveal an indispensable role of tumor-derived PGE2 in inducing MDSCs and suggest a favorable outcome of combining COX-2–targeted therapy and adoptive NK-cell transfer in patients with cancer. Clin Cancer Res; 20(15); 4096–106. ©2014 AACR.
Modafinil as Adjunct Therapy for Daytime Sleepiness in Obstructive Sleep Apnea
Authors: ALLAN I. PACK, JED E. BLACK, JONATHAN R. L. SCHWARTZ, JEAN K. MATHESON
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Patients with obstructive sleep apnea/hypopnea syndrome can experience residual daytime sleepiness despite regular use of nasal continuous positive airway pressure therapy. This randomized, double-blind, placebo-controlled, parallel group study assessed the efficacy and safety of modafinil for the treatment of residual daytime sleepiness in such patients. Patients received modafinil (n = 77) (200 mg/d, Week 1; 400 mg/d, Weeks 2 to 4) or matching placebo (n = 80) once daily for 4 wk. Modafinil significantly improved daytime sleepiness, with significantly greater mean changes from baseline in Epworth Sleepiness Scale scores at Weeks 1 and 4 (p < 0.001) and in multiple sleep latency times (MSLT) at Week 4 (p < 0.05). The percentage of patients with normalized daytime sleepiness (Epworth score < 10) was significantly higher with modafinil (51%) than with placebo (27%) (p < 0.01), but not for MSLT ( > 10 min; 29% versus 25%). Headache (modafinil, 23%; placebo, 11%; p = 0.044) and nervousness (modafinil, 12%; placebo, 3%; p = 0.024) were the most common adverse events. During modafinil or placebo treatment, the mean duration of nCPAP use was 6.2 h/night, with no significant change from baseline observed between groups. Modafinil may be a useful adjunct treatment for the management of residual daytime sleepiness in patients with obstructive sleep apnea/hypopnea syndrome who are regular users of nasal continuous positive airway pressure therapy.
HLA-DR2–restricted responses to proteolipid protein 95-116 peptide cause autoimmune encephalitis in transgenic mice
Authors: Kazuyuki Kawamura, Takashi Yamamura, Kazumasa Yokoyama, De-Hua Chui, Yoshinori Fukui, Takehiko Sasazuki, Hidetoshi Inoko, Chella S. David, Takeshi Tabira
Journal: Journal of Clinical Investigation (2000)

In multiple sclerosis (MS) patients who carry the Class II major histocompatibility (MHC) type HLA-DR2, T cells specific for amino acids 95-116 in the proteolipid protein (PLP) are activated and clonally expanded. However, it remains unclear whether these autoreactive T cells play a pathogenic role or, rather, protect against the central nervous system (CNS) damage. We have addressed this issue, using mice transgenic for the human MHC class II region carrying the HLA-DR2 (DRB1*1502) haplotype. After stimulating cultured lymph node cells repeatedly with PLP95-116, we generated 2 HLA-DR2–restricted, PLP95-116–specific T-cell lines (TCLs) from the transgenic mice immunized with this portion of PLP. The TCLs were CD4+ and produced T-helper 1 (Th1) cytokines in response to the peptide. These TCLs were adoptively transferred into RAG-2–/– mice expressing HLA-DR2 (DRB1*1502) molecules. Mice receiving 1 of the TCLs developed a neurological disorder manifested ataxic movement without apparent paresis on day 3, 4, or 5 after cell transfer. Histological examination revealed inflammatory foci primarily restricted to the cerebrum and cerebellum, in association with scattered demyelinating lesions in the deep cerebral cortex. These results support a pathogenic role for PLP95-116–specific T cells in HLA-DR2+ MS patients, and shed light on the possible correlation between autoimmune target epitope and disease phenotype in human CNS autoimmune diseases.
Treatment of Pulmonary Tuberculosis by Thoracoplasty in Patients Over 50 Years of Age
Authors: P. Beaconsfield, H. S. Coulthard, F. G. Kergin
Journal: Thorax (1954)

According to the standards established by the National Tuberculosis Association the extent of the disease in this group of patients was classified as follows: (1) far advanced in 24 patients, unilateral in eight, bilateral in 16 (bilateral cavitation five);(2) moderately advanced in 31 patients, unilateral in 24, bilateral in seven (bilateral cavitation none).
Primary cicatricial alopecias: a U.K. survey
Authors: L.L. Griffin, C. Michaelides, C.E.M. Griffiths, R. Paus, M.J. Harries
Journal: British Journal of Dermatology (2012)

Supporting information Additional Supporting Information may be found in the online version of the article: Figure S1. Questionnaire: U.K. survey of cicatricial alopecia. Figure S2. Comparative proportion of all types of primary cicatricial alopecia (PCA) seen by dermatologists with a special interest in hair disorders, general dermatologists and trichologists. Figure S3. Method of diagnosis of types of primary cicatricial alopecia (PCA) (dermatologists with a special interest in hair disorders). Please note: Wiley-Blackwell is not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.