tbuckley/cabot-search huggingface dataset:
Survival rates after a rehabilitation program in patients with interstitial lung disease
Authors: Veronica Barbier, Miek Hornikx, Iris Coosemans, Ilse Muylaert, Wim Wuyts, Wim Janssens, Thierry Troosters
Journal: European Respiratory Journal (2014)

Introduction   Previous studies have indicated that patients with Interstitial Lung Disease (ILD) have a poor prognosis and a rapid disease progression. Exercise training in pulmonary rehabilitation programs has shown positive effects in terms of exercise capacity, dyspnea and quality of life. The impact of a pulmonary rehabilitation program on survival in ILD has, however, not been explored.   Methods   60 patients were randomly assigned to receive a 6 month rehabilitation program or usual care. These data are a subanalysis of the randomized controlled trial NCT: B3220095560. The average follow-up in the training and control group were respectively 2.99±1.29 years vs 2.51±1.41 years. 3 patients in the control group were censored, when they started rehabilitation at 1.15 until 1.80 years of follow-up. Survival status was recorded over a period of 2 years for the whole group.   Results   At baseline, there were no significant differences between the 2 groups in terms of age, gender, lung function parameters and functional exercise capacity. 1 year after initial assessment, the survival rate in the training group was 86% and 83% in the control group. After 2 years, survival rates decreased in both groups and accounted 76%. Figure 1 shows the Kaplan-Meier survival curve for both groups.   Conclusion   No significant differences were found in survival rates between the training group and the control group, 2 years after initial assessment.
DNA Methylation Biomarkers Offer Improved Diagnostic Efficiency in Lung Cancer
Authors: Georgios Nikolaidis, Olaide Y. Raji, Soultana Markopoulou, John R. Gosney, Julie Bryan, Chris Warburton, Martin Walshaw, John Sheard, John K. Field, Triantafillos Liloglou
Journal: Cancer Research (2012)

Abstract The exceptional high mortality of lung cancer can be instigated to a high degree by late diagnosis. Despite the plethora of studies on potential molecular biomarkers for lung cancer diagnosis, very few have reached clinical implementation. In this study, we developed a panel of DNA methylation biomarkers and validated their diagnostic efficiency in bronchial washings from a large retrospective cohort. Candidate targets from previous high-throughput approaches were examined by pyrosequencing in an independent set of 48 lung tumor/normal paired. Ten promoters were selected and quantitative methylation-specific PCR (qMSP) assays were developed and used to screen 655 bronchial washings from the Liverpool Lung Project (LLP) subjects divided into training (194 cases and 214 controls) and validation (139 cases and 109 controls) sets. Three statistical models were used to select the optimal panel of markers and to evaluate the performance of the discriminatory algorithms. The final logit regression model incorporated hypermethylation at p16, TERT, WT1, and RASSF1. The performance of this 4-gene methylation signature in the validation set showed 82% sensitivity and 91% specificity. In comparison, cytology alone in this set provided 43% sensitivity at 100% specificity. The diagnostic efficiency of the panel did not show any biases with age, gender, smoking, and the presence of a nonlung neoplasm. However, sensitivity was predictably higher in central (squamous and small cell) than peripheral (adenocarcinomas) tumors, as well as in stage 2 or greater tumors. These findings clearly show the impact of DNA methylation-based assays in the diagnosis of cytologically occult lung neoplasms. A prospective trial is currently imminent in the LLP study to provide data on the enhancement of diagnostic accuracy in a clinical setting, including by additional markers. Cancer Res; 72(22); 5692–701. ©2012 AACR.
Acyl-Coenzyme A:Cholesterol Acyltransferase Inhibition Ameliorates Proteinuria, Hyperlipidemia, Lecithin-Cholesterol Acyltransferase, SRB-1, and Low-Denisty Lipoprotein Receptor Deficiencies in Nephrotic Syndrome
Authors: N.D. Vaziri, K.H. Liang
Journal: Circulation (2004)

Nephrotic syndrome (NS) is associated with hyperlipidemia, altered lipid regulatory enzymes and receptors, and increased risk of progressive renal and cardiovascular diseases. Acyl-coenzyme A:cholesterol acyltransferase (ACAT) catalyzes intracellular esterification of cholesterol and plays an important role in production of apolipoprotein B-containing lipoproteins, regulation of cholesterol-responsive proteins, and formation of foam cells. Because hepatic ACAT-2 is markedly upregulated in NS, we tested the hypothesis that inhibition of ACAT may improve cholesterol metabolism in NS.Rats with puromycin-induced NS were treated with either the ACAT inhibitor CI-976 or placebo for 2 weeks. Normal rats served as controls. Plasma lipids, renal function, and key lipid regulatory factors were measured. Untreated NS rats showed heavy proteinuria; hypoalbuminemia; elevated plasma cholesterol, triglyceride, LDL, VLDL, and total cholesterol-to-HDL cholesterol ratio; increased hepatic ACAT activity, ACAT-2 mRNA, and ACAT-2 protein; and reduced LDL receptor, HDL receptor, otherwise known as scavenger receptor B-1 (SRB-1) and plasma lecithin-cholesterol acyltransferase (LCAT). ACAT inhibitor reduced plasma cholesterol and triglycerides, normalized total cholesterol-to-HDL cholesterol ratio, and lowered hepatic ACAT activity without changing ACAT-2 mRNA or protein. This was accompanied by near normalizations of plasma LCAT, hepatic SRB-1, and LDL receptor and a significant amelioration of proteinuria and hypoalbuminemia.Pharmacological inhibition of ACAT reverses NS-induced LDL receptor, HDL receptor, and LCAT deficiencies; improves plasma lipid profile; and ameliorates proteinuria in nephrotic animals. Further studies are needed to explore the effect of ACAT inhibition in nephrotic humans.
A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans
Authors: Hui Li, Hui Xie, Wei Liu, Rong Hu, Bi Huang, Yan-Fei Tan, Er-Yuan Liao, Kang Xu, Zhi-Feng Sheng, Hou-De Zhou, Xian-Ping Wu, Xiang-Hang Luo
Journal: Journal of Clinical Investigation (2009)

MicroRNAs (miRNAs) interfere with translation of specific target mRNAs and are thought to thereby regulate many cellular processes. Recent studies have suggested that miRNAs might play a role in osteoblast differentiation and bone formation. Here, we identify a new miRNA (miR-2861) in primary mouse osteoblasts that promotes osteoblast differentiation by repressing histone deacetylase 5 (HDAC5) expression at the post-transcriptional level. miR-2861 was found to be transcribed in ST2 stromal cells during bone morphogenetic protein 2-induced (BMP2-induced) osteogenesis, and overexpression of miR-2861 enhanced BMP2-induced osteoblastogenesis, whereas inhibition of miR-2861 expression attenuated it. HDAC5, an enhancer of runt-related transcription factor 2 (Runx2) degradation, was confirmed to be a target of miR-2861. In vivo silencing of miR-2861 in mice reduced Runx2 protein expression, inhibited bone formation, and decreased bone mass. Importantly, miR-2861 was found to be conserved in humans, and a homozygous mutation in pre-miR-2861 that blocked expression of miR-2861 was shown to cause primary osteoporosis in 2 related adolescents. Consistent with the mouse data, HDAC5 levels were increased and Runx2 levels decreased in bone samples from the 2 affected individuals. Thus, our studies show that miR-2861 plays an important physiological role in osteoblast differentiation and contributes to osteoporosis via its effect on osteoblasts.
Conformational Change in Coronary Artery Structure Assessed by Optical Coherence Tomography in Patients With Vasospastic Angina
Authors: Atsushi Tanaka, Kenei Shimada, Guillermo J. Tearney, Hironori Kitabata, Haruyuki Taguchi, Shota Fukuda, Manabu Kashiwagi, Takashi Kubo, Shigeho Takarada, Kumiko Hirata, Masato Mizukoshi, Junichi Yoshikawa, Brett E. Bouma, Takashi Akasaka
Journal: Journal of the American College of Cardiology (2011)
Medical aspects of male circumcision
Authors: Padraig Malone, Henrik Steinbrecher
Journal: BMJ (2007)

#### Summary points

Circumcision is the commonest surgical procedure in males, because routine infant circumcision is practised in many countries for religious and cultural reasons. It originated over 15 000 years ago, being performed for religious, ritualistic, and cultural reasons, and it was not until the 19th century that the procedure was “medicalised.” It is one of the most controversial surgical interventions: proponents claim benefits such as improved hygiene and reduced risks of infection (urinary and sexually transmitted) and of penile and cervical cancer, whereas opponents deny or minimise these benefits and cite substantial complication rates and reduced penile sensation. Many parents and patients have firmly held beliefs, placing medical workers under extreme pressure at times when dealing with requests for circumcision. It is vital for all medical staff to be aware of the various indications for circumcision and the operative techniques and their complications to cope with these consultations with an evidence base.

This review concentrates solely on the medical indications for circumcision and does not address the issues of routine, religious, or ritual infant circumcision. It highlights clinical conditions frequently referred for circumcision but which are normal physiological variants and do not require surgery. It also lists the absolute medical indications for circumcision and the complications of the procedure. The various surgical …
US AND DOPPLER-GUIDED SURGICAL TREATMENT BASED ON IMMUNOHISTOCHEMICAL FINDINGS IN MIDPORTION ACHILLES TENDINOPATHY SHOWS GOOD CLINICAL RESULTS AND FAST RETURN TO ACTIVITY
Authors: H Alfredson, G Andersson, L Backman, J Bagge, P Danielson, S Forsgren
Journal: British Journal of Sports Medicine (2013)

Introduction Treatment of midportion Achilles tendinopathy has been known to be difficult. Recent ultrasound(US) and Doppler(CD) findings (high blood flow outside ventral tendon), together with results of immunohistochemical analyses (marked presence of blood vessels accompanied by nerve fascicles in the ventral peritendinous tissue) have led to new treatment approaches like sclerosing polidocanol injections, where US and CD-guided injections in the region with high blood flow and nerves outside the tendon have shown good results. However, for satisfying pain relief multiple injection treatments were often needed. Therefore, based on the same principles as for the sclerosing injections, a more radical and one stage mini-surgical procedure has been invented. Methods 107 patients (66 men, 41 women), mean age 43 years (range 24–77), with tendinosis in 125 Achilles tendons were, in local anaesthesia, treated with a US+CD-guided new surgical approach outside the ventral tendon. Pain during tendon loading activity (VAS) and satisfaction with treatment, were evaluated. Results Before surgery , the mean VAS was 77. After surgery (follow up mean 18 months, range 6–33) the mean VAS was 2 in 111 tendons (89%) from satisfied patients back in full Achilles tendon loading activity. Conclusions US+CD-guided scraping/tenolysis in the region with rich vascularity and innervation outside the ventral tendon shows good short term clinical results in midportion Achilles tendinopathy.
Cushing's syndrome associated with ectopic corticotropin production and small-cell lung cancer.
Authors: F A Shepherd, J Laskey, W K Evans, P E Goss, E Johansen, F Khamsi
Journal: Journal of Clinical Oncology (1992)

PURPOSE This study was undertaken to review the clinical and laboratory features and response to treatment of patients with Cushing's syndrome associated with ectopic corticotropin (adrenocorticotropic hormone; ACTH) production and small-cell lung cancer (SCLC). PATIENTS AND METHODS We undertook a retrospective chart review of 545 patients with SCLC seen at Toronto General Hospital between 1980 and 1990 and identified 23 patients (4.5%) with Cushing's syndrome and ectopic ACTH production. RESULTS There were 17 male and six female patients, with a median age of 60 years. The syndrome was diagnosed at the time of initial presentation of SCLC in 13 patients and at relapse in 10 patients. Seven patients had limited disease and 16 had extensive disease at their initial diagnosis of SCLC, but 20 of 23 had extensive disease at the time of diagnosis of Cushing's syndrome. Ten patients had bone marrow involvement. The most frequent physical findings included edema (83%) and proximal myopathy (61%). All patients had elevated plasma and urinary free cortisol levels; 22 had a hypokalemic alkalosis, and 13 had hyperglycemia. Only one patient had a normal ACTH level. The response rate (complete plus partial) to chemotherapy for patients who had the syndrome diagnosed at initial presentation of SCLC was only 46%, and their median survival was only 3.57 months. Only two patients achieved complete normalization of all hormone parameters, and neither experienced hormone relapse at the time of SCLC relapse. Complications of therapy included gastrointestinal (GI) ulceration (six patients), GI bleeding (four), perforation of a duodenal ulcer (one), pneumonia (10), septic shock (three), and fungal infections (five). CONCLUSION Ectopic ACTH production is associated with a low response to chemotherapy, short survival, and a high rate of complication to therapy.
The Development of Clinical Practice Guidelines and Guidance Statements of the American College of Physicians: Summary of Methods
Authors: Amir Qaseem
Journal: Annals of Internal Medicine (2010)

The American College of Physicians (ACP) established its evidence-based clinical practice guidelines program in 1981. The ACP's Guidelines Committee and the staff of the Clinical Programs and Quality of Care Department develop the clinical recommendations. The ACP develops 2 different types of clinical recommendations: clinical practice guidelines and clinical guidance statements. The ACP clinical practice guidelines and guidance statements follow a multistep development process that includes a systematic review of the evidence, deliberation of the evidence by the committee, summary recommendations, and evidence and recommendation grading. All ACP clinical practice guidelines and clinical guidance statements, if not updated, are considered automatically withdrawn or invalid 5 years after publication or once an update has been issued.
Circulating C reactive protein in osteoarthritis: a systematic review and meta-analysis
Authors: Xingzhong Jin, Julieta Ruiz Beguerie, Weiya Zhang, Leigh Blizzard, Petr Otahal, Graeme Jones, Changhai Ding
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> There is emerging evidence that the development and progression of osteoarthritis (OA) is associated with inflammation. C reactive protein (CRP), a systemic marker for inflammation, may be elevated in OA patients but the evidence is conflicting. <h3>Objective</h3> To systematically review the literature for the relationship between serum CRP levels measured by a high sensitivity method (high sensitive CRP (hs-CRP)) and OA, as well as the correlation between circulating CRP levels and OA phenotypes. <h3>Methods</h3> MEDLINE, EMBASE and CINAHL databases were systematically searched from January 1992 to December 2012. Studies were included when they met the inclusion criteria and data from studies were extracted. Two independent reviewers assessed study quality using a modified Newcastle-Ottawa Quality Assessment Scale. Meta-analyses were performed to pool available data from included studies. <h3>Results</h3> 32 studies met the inclusion criteria. Serum hs-CRP levels in OA were modestly but statistically significantly higher than controls (mean difference=1.19 mg/L, 95% CI 0.64 to 1.73, p&lt;0.001) with significant heterogeneity between studies. Levels were significantly associated with pain (r=0.14, 95% CI 0.09 to 0.20, p&lt;0.001) and decreased physical function (r=0.25, 95% CI 0.13 to 0.39, p&lt;0.001). No significant associations were found between hs-CRP levels and radiographic OA. <h3>Conclusions</h3> Low-grade systemic inflammation may play a greater role in symptoms rather than radiographic changes in OA.
TCT-729 Four years durability of clinical and hemodynamic outcomes of transcatheter aortic valve implantation with self expanding CoreValve: A single center experience
Authors: Simona Gulino, Marco Barbanti, Wanda Deste, Sebastiano Immè, Emanuele Benvenuto, Letizia Santonoceto, Daria Liberto, Alessio Di Landro, Patrizia Aruta, Vera Bottari, Rita Sicuso, Andrea Sole, Claudia Tamburino, Denise Todaro, Emanuela Di Simone, Carmelo Sgroi, Corrado Tamburino
Journal: Journal of the American College of Cardiology (2014)
Pediatric Malignant Peripheral Nerve Sheath Tumor: The Italian and German Soft Tissue Sarcoma Cooperative Group
Authors: Modesto Carli, Andrea Ferrari, Adrian Mattke, Ilaria Zanetti, Michela Casanova, Gianni Bisogno, Giovanni Cecchetto, Rita Alaggio, Luigi De Sio, Eura Koscielniak, Guido Sotti, Joern Treuner
Journal: Journal of Clinical Oncology (2005)

To assess the value of chemotherapy and radiotherapy in children with malignant peripheral nerve sheath tumors (MPNSTs) and to identify risk factors associated with outcome.A total of 167 untreated eligible patients enrolled onto the Italian and German studies between 1975 and 1998 entered this analysis. Seventeen percent of patients had neurofibromatosis type 1 (NF1). Chemotherapy was administered to 74% of patients; radiotherapy was administered to 38% of patients.With a median follow-up of 7 years, 5-year overall survival (OS) and progression-free survival (PFS) were 51% and 37%, respectively. The 5-year OS and PFS by Intergroup Rhabdomyosarcoma Study (IRS) groupings were as follows: group I, 82% and 61%; group II, 62% and 37%; group III, 32% and 27%; group IV, 26% and 21%, respectively. Univariate analysis identified IRS groups, size, invasiveness, primary site, age, and presence of NF1 as prognostic factors; multivariate analysis identified absence of NF1, tumor invasiveness T1, IRS groups I to II and extremity of primary site as independent favorable factors for OS. A trend was observed toward a benefit from radiotherapy after initial gross resection. The overall response rate to primary chemotherapy, including minor responses, in group III patients was 45%.MPNST is an aggressive tumor for which complete surgical resection is the mainstay of successful treatment. Postoperative radiotherapy may have a role in improving local control in patients with minimal residual tumor. The reported responses to primary chemotherapy suggest that it may be effective in patients with tumor considered unresectable at diagnosis.
Key role of tuberculosis services funding mechanisms in tuberculosis control and elimination
Authors: Karapet Davtyan, Armen Hayrapetyan, Masoud Dara, Laura Gillini, Hayk Davtyan, Rosella Centis, Lia D’Ambrosio, Giovanni Sotgiu, Giovanni Battista Migliori
Journal: European Respiratory Journal (2014)

We read with interest the systematic review by Tanimura et al. [1], looking at the existing studies focusing on costs and income loss incurred by tuberculosis (TB) patients and their families in low- or middle-income countries, and the related editorial [2]. The TB-related "catastrophic expenditures" are one of the main reasons that prevent patients completing their treatment, thus making TB control challenging. Based on the new post-2015 strategy of the World Health Organization (WHO), the authors strongly advocate for universal health coverage and social protection. Co-ordination is crucial to find the best way to finance TB services to ensure quality care and cost-effectiveness <http://ow.ly/AkdQL>
Reproducibility of dynamically represented acoustic lung images from healthy individuals
Authors: T M Maher, M Gat, D Allen, A Devaraj, A U Wells, D M Geddes
Journal: Thorax (2007)

Background and aim: Acoustic lung imaging offers a unique method for visualising the lung. This study was designed to demonstrate reproducibility of acoustic lung images recorded from healthy individuals at different time points and to assess intra- and inter-rater agreement in the assessment of dynamically represented acoustic lung images. Methods: Recordings from 29 healthy volunteers were made on three separate occasions using vibration response imaging. Reproducibility was measured using quantitative, computerised assessment of vibration energy. Dynamically represented acoustic lung images were scored by six blinded raters. Results: Quantitative measurement of acoustic recordings was highly reproducible with an intraclass correlation score of 0.86 (very good agreement). Intraclass correlations for inter-rater agreement and reproducibility were 0.61 (good agreement) and 0.86 (very good agreement), respectively. There was no significant difference found between the six raters at any time point. Raters ranged from 88% to 95% in their ability to identically evaluate the different features of the same image presented to them blinded on two separate occasions. Conclusion: Acoustic lung imaging is reproducible in healthy individuals. Graphic representation of lung images can be interpreted with a high degree of accuracy by the same and by different reviewers.
Estimating Translational Selection in Eukaryotic Genomes
Authors: M. dos Reis, L. Wernisch
Journal: Molecular Biology and Evolution (2008)

Natural selection on codon usage is a pervasive force that acts on a large variety of prokaryotic and eukaryotic genomes. Despite this, obtaining reliable estimates of selection on codon usage has proved complicated, perhaps due to the fact that the selection coefficients involved are very small. In this work, a population genetics model is used to measure the strength of selected codon usage bias, S, in 10 eukaryotic genomes. It is shown that the strength of selection is closely linked to expression and that reliable estimates of selection coefficients can only be obtained for genes with very similar expression levels. We compare the strength of selected codon usage for orthologous genes across all 10 genomes classified according to expression categories. Fungi genomes present the largest S values (2.24–2.56), whereas multicellular invertebrate and plant genomes present more moderate values (0.61–1.91). The large mammalian genomes (human and mouse) show low S values (0.22–0.51) for the most highly expressed genes. This might not be evidence for selection in these organisms as the technique used here to estimate S does not properly account for nucleotide composition heterogeneity along such genomes. The relationship between estimated S values and empirical estimates of population size is presented here for the first time. It is shown, as theoretically expected, that population size has an important role in the operativity of translational selection.