tbuckley/cabot-search huggingface dataset:
Reconstructing A/B compartments as revealed by Hi-C using long-range correlations in epigenetic data
Authors: Jean-Philippe Fortin, Kasper D. Hansen
Journal: Genome biology (2015)

Analysis of Hi-C data has shown that the genome can be divided into two compartments called A/B compartments. These compartments are cell-type specific and are associated with open and closed chromatin. We show that A/B compartments can reliably be estimated using epigenetic data from several different platforms: the Illumina 450 k DNA methylation microarray, DNase hypersensitivity sequencing, single-cell ATAC sequencing and single-cell whole-genome bisulfite sequencing. We do this by exploiting that the structure of long-range correlations differs between open and closed compartments. This work makes A/B compartment assignment readily available in a wide variety of cell types, including many human cancers.
Effect of Ammonium Chloride on Incidence of Bladder Tumors Induced by 4-Ethylsulfonylnaphthalene-1-Sulfonamide
Authors: Antonia Flaks, John M. Hamilton, David B. Clayson
Journal: JNCI Journal of the National Cancer Institute (1973)

Treatment of female (IF × C57)F1 mice with 4-ethylsulfonylnaphthalene-1-sulfonamide (ENS) produced an alkaline urine associated with the formation of calculi in the bladder and with hydronephrosis. Extensive epithelial hyperplasia and, in some mice, tumors were noted in the bladders. If, however, the urine was made acid through the addition of ammonium chloride (NH4Cl) to the drinking water, neither calculi nor tumors of the bladder were present, though a mild epithelial hyperplasia persisted. Mice treated with NH4CI alone and untreated controls had no histopathologic changes. Physical injury by calculi and/or elevated pH of the urine induced by ENS are essential for bladder tumors to develop. A thorough examination for bladder calculi is necessary for assessment of the environmental significance of bladder tumors in rodents.
Effects of Levamisole on In Vivo and In Vitro Murine Host Response to Syngeneic Transplantable Tumor2
Authors: Isaiah J. Fidler, Lynn E. Spitler
Journal: JNCI Journal of the National Cancer Institute (1975)

The effects of levamisole were studied in vivo and in vitro on two murine tumors, B16 melanoma and adenocarcinoma 15091, syngeneic to the mouse strains used. Administration of levamisole before tumor transplantation enhanced the early appearance of neoplasms but did not affect the overall incidence or course of tumor growth as compared with that observed in controls given saline injections or animals given levamisole with lethally X-irradiated tumor cells. Administration of the drug 1 day before iv injection of tumor cells significantly reduced the incidence of pulmonary nodules, but if the drug was given 3 or 5 days before tumor challenge, the incidence of nodules was increased. Lymphocytes or macrophages from normal mice given levamisole had no effect on tumor cells in vitro, whereas lymphocytes incubated with levamisole in vitro enhanced tumor cell growth. When lymphocytes and tumor cells were mixed in vitro, lymphocytes from animals treated with the drug formed larger multicell clumps with tumor cells than did those from normal controls. We concluded that levamisole did not protect the mice against the tested tumors.
Helminth extract from opisthorchis felineus suppresses allergic inflammation through modulation of dendritic cells phenotype
Authors: Natalia Kirillova, Elena Kremer, Evgenij Kulikov, Ludmila Ogorodova, Sergey Logvinov, Tatyana Perevozchikova, Elena Fajt
Journal: European Respiratory Journal (2012)

Background. Recent epidemiological and experimental reports have suggested that helminth infection could induce suppression of allergic Th2 responses [Jeong Y. et al., 2011]. Opisthorchiasis caused by Opisthorchis felineus (O.f.) is the major public health problems of Western Siberia in Russian Federation. Dendritic cells (DCs) are critical for controlling the immune response to various types of antigens so we established them to study the effects of O.f. on the development of airway inflammation.  Aim and objectives. To investigate DC immune phenotype during the treatment with O. f. extract in patients with bronchial asthma (BA).  Methods. Mature DCs were cultured from peripheral blood monocytes of healthy control (n=17) and asthmatic patients (mild BA, n=19; severe BA, n=24) using IL-4 and GM-CSF during 6 days. DCs were stimulated with O.f. extract and LPS on 4 day of incubation. After culturing DCs were harvested and labeled for CD86, CD83, CD209 and analyzed using flow cytometry.  Results. O. f. inhibited the expression of co-stimulatory molecules as CD86 in mature DCs. Number of CD86+CD209+ DC was significantly decreased in different severity of BA compared to healthy donors. Patients with mild and severe BA had increased levels of CD209+ DCs compared to control.  Conclusions. Our findings suggest that levels of co-stimulatory molecules expression on DC are important in immune response balancing and polarization. Increased levels of co-stimulatory molecules as CD86 on DC after helminth stimulation with O.f. might suppress airway inflammation in BA.
Factors affecting physical activity in patients with air pollution-related illness compared to patients with COPD
Authors: Naomi Miyamoto, Naoto Rikitomi, Chika Kitagawa, Hideaki Senjyu
Journal: European Respiratory Journal (2012)

Background: The survival of chronic obstructive pulmonary disease (COPD) patients has been reported to be associated with physical activity (PA). However, there have been no reports concerning PA in patients with air pollution-related illness (API), who have symptoms of dyspnea similar to COPD patients.

Objective: We investigated the factors affecting PA in patients with API compared with COPD patients.

Methods: The study subjects were 30 patients with API and 38 COPD patients. The MRC dyspnea scale (MRC), pulmonary function, muscle strength, six minute walking test (6MWT), incremental shuttle walking test (ISWT), ADL score, SGRQ, CES-D and PA were measured. PA was assessed using a multisensor accelerometer that records steps and energy expenditure for 7 consecutive days after admission for pulmonary rehabilitation. An analysis was performed to examine the differences between the two groups in order to identify the factors that influence PA in patients with API.

Results: Patients with API had significantly better pulmonary function compared with COPD patients (p<0.001). However, their leg strength, exercise tolerance and QOL were significantly worse (p<0.01), and a higher incidence of depression symptoms were seen in patients with API (p<0.05). On the other hand, the differences of MRC and PA were not significant between the two groups. PA of patients with API was correlated with the MRC, %VC, ISWT and ADL score, while PA of COPD patients was correlated with age, MRC, BMI, 6MWT, ISWT and ADL score.

Conclusions: To improve MRC, ISWT and ADL that influence PA, pulmonary rehabilitation as well as other treatments may therefore be useful in treating patients with API.
Enhanced surveillance during a large outbreak of bloody diarrhoea and haemolytic uraemic syndrome caused by Shiga toxin/verotoxin-producing Escherichia coli in Germany, May to June 2011
Authors: M Wadl, T Rieck, M Nachtnebel, B Greutélaers, M an der Heiden, D Altmann, W Hellenbrand, M Faber, C Frank, B Schweickert, G Krause, J Benzler, T Eckmanns, Collective on behalf of the HUS surveillance and laboratory team
Journal: Eurosurveillance (2011)

Germany has a well established broad statutory surveillance system for infectious diseases. In the context of the current outbreak of bloody diarrhoea and haemolytic uraemic syndrome caused by Shiga toxin/ verotoxin-producing Escherichia coli in Germany it became clear that the provisions of the routine surveillance system were not sufficient for an adequate response. This article describes the timeline and concepts of the enhanced surveillance implemented during this public health emergency.
Effectiveness of interferon alfa-2a combined with phototherapy for mycosis fungoides and the Sézary syndrome.
Authors: T M Kuzel, H H Roenigk, E Samuelson, J J Herrmann, A Hurria, A W Rademaker, S T Rosen
Journal: Journal of Clinical Oncology (1995)

PURPOSE To investigate the efficacy of combined topical therapy and systemic interferon alfa-2a in patients with mycosis fungoides (MF) and the Sézary syndrome (SS). PATIENTS AND METHODS Between December 1987 and April 1993, 39 patients with all stages of MF and SS were treated with combined phototherapy and systemic interferon alfa-2a as part of two institutional studies. The initial phase I study of 15 patients established the maximum-tolerated dose of interferon and has been previously reported. Subsequently, 24 patients have been entered onto a phase II trial. Long-term follow-up data are provided for both studies. RESULTS The median follow-up duration for the entire cohort is 28 months. Patients with all stages of disease were enrolled (stage IB, n = 14; IIA, n = 5; IIB, n = 6; III, n = 8; IVA, n = 5; IVB, n = 1). Thirty-four patients had received previous therapy. Overall, 36 of 39 patients achieved a complete response (CR; 62%) or partial response (28%) to therapy. The median response duration is 28 months (range, 1 to 64). Twenty-nine of 39 patients are alive, with a median survival duration of 62 months (range, 1 to 66). CONCLUSION Interferon alfa-2a combined with phototherapy is an effective, safe, durable therapy for MF and SS.
Diagnostic value of real-time endobronchial ultrasound-guided transbronchial needle aspiration for non-malign diseases
Authors: Mediha Gönenç Ortaköylü, Ayse Bahadir, Asuman Aslan, Figen Alkan, Halide Nur Ürer, Emel Çaglar
Journal: European Respiratory Journal (2013)

Background : Real-time endobronchial ultrasound (EBUS) guidance is a new method of TBNA. A descriptive study was conducted to test this new method for non-malign diseases.

Methods : 82 patients with enlarged hilar and/or mediastinal lymph nodes on computed tomography,were included in the study. Convex probe endobronchial ultrasonography integrated with a separate working channel was used for EBUS-TBNA. After the procedures, patients were followed up clinically and radiologically for 6-30 months.

Results : EBUS-TBNA was performed on a total of 140 lymph node stations in 82 patients (44 women and 38 men, mean age 50,2 years). The mean size of the enlarged lymph nodes, as measured by EBUS, was 13.9±4,46 mm. The most commonly sampled lymph node station (57 out of 140; 40,7%) was subcarinal. Final diagnosis was based on cytology, surgical results, and/or clinical follow-up. Diagnostic results are shown at the table.

View this table:

Table:Diagnosis obtained by EBUS-TBNA and other methods in patients





EBUS-TBNA was diagnostic in 59 (71,9%) patients. There were no complications associated with the procedures.

Conclusion : EBUS-TBNA proved to be a safe procedure with a high yield for the diagnoses of non-malign diseases.
Effects of inspiratory muscle training on electromyographic activity of inspiratory muscles in asthmatics
Authors: Ivanizia Silva, Renata Delgado, Victor Oliveira, Taina Fernandes, Italo Queiroz, Thaisy Silva, Nelson Lima Filho, Rafaela Pedrosa, Gardenia Ferreira
Journal: European Respiratory Journal (2014)

Background: Electromyographic evaluation provides quantitative information about the specific function of each muscle. Thus it can be used to justify the effect of inspiratory muscle training (IMT) on the inspiratory muscles. Objectives: To investigate the effects of IMT on surface electromyographic (sEMG) activity of inspiratory muscles in healthy and asthmatics adults. Methods: We performed a randomized controlled trial with blinding of outcome assessment. Ten healthy and 10 asthmatics were randomly divided into two groups (experimental and control). Participants performed 30 breaths, using a pressure threshold inspiratory muscle trainer (POWERbreathe®), twice a day, five days/week, for a total of six weeks at home. Training intensity was adjusted once a week. Experimental group trained at 50% MIP and control group at 15% MIP. sEMG activities of sternocleidomastoid (SCM) and diaphragm muscles were measured during basal respiration and maximum inspiratory pressure maneuver, before and after the six week of IMT. Results: Asthmatic experimental group demonstrated a significant increase in sEMG activity of diaphragm at 48,5% ( P <0,05) during basal respiration posttraining. Moreover the sEMG activity of SCM significant increases during maximum inspiratory pressure maneuver in healthy experimental group (1488%; P <0,05) and asthmatic experimental group (1186,4%; P <0,05) when compared with the baseline measurements. There were no statistically significant changes in the control groups. Conclusion: IMT was able to promote an increase in sEMG activity of diaphragm muscle in the asthmatics, and an increase SCM in healthy and asthmatic adults.
Bacterial Colonization Patterns in Mechanically Ventilated Patients with Traumatic and Medical Head Injury
Authors: SANTIAGO EWIG, ANTONI TORRES, MUSTAFA EL-EBIARY, NEUS FÀBREGAS, CARMEN HERNÁNDEZ, JULIÀ GONZÁLEZ, JOSE MARIA NICOLÁS, LUIS SOTO
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We prospectively evaluated the relation of upper airway, lower airway, and gastric colonization patterns with the development of pneumonia and its etiology in 48 patients with surgical (n = 25) and medical (n = 23) head injury. Initial colonization was assessed by cultures of nasal and pharyngeal swabs, tracheobronchial aspirates, gastric juice, and bronchoscopically retrieved protected specimen brush. Follow-up colonization was determined until the end points extubation, suspected ventilator-associated pneumonia (VAP), or death. The initial colonization rate at any site at ICU admission was 39/47 (83%). It mainly accounted for Group I pathogens (Streptococcus pneumoniae, Staphylococcus aureus, Hemophilus influenzae) of the upper and lower airways. At follow-up, colonization rates with Group II pathogens (Gram-negative enteric bacilli and Pseudomonas spp.) increased significantly. The high initial bacterial load with Group I pathogens of the upper airways and trachea decreased during Days 2 to 4, whereas that of Group II pathogens increased. Upper airway colonization was an independent predictor of follow-up tracheobronchial colonization (odds ratio [OR], 9.9; 95% confidence interval [CI], 1.8 to 56.3 for initial colonization with Group I pathogens; OR, 23.9; 95% CI, 3.8 to 153.3 for follow-up colonization with Group II pathogens). Previous (short-term) antibiotics had a protective effect against colonization with Group I pathogens of the lower respiratory tract (OR, 0.2; 95% CI, 0.05 to 0.86), but they were a risk factor for colonization with Group II pathogens (OR, 6.1; 95% CI, 1.3 to 29). Initial tracheobronchial colonization with Group I pathogens was associated with a higher probability of early onset pneumonia (OR, 4.1; 95% CI, 0.7 to 23.3), whereas prolonged antibiotic treatment ( > 24 h) independently predicted late-onset pneumonia (OR, 9.2; 95% CI, 1.7 to 51.3). We conclude that patients with head injury are colonized in the airways mainly by Group I pathogens early in the evolution of illness. The upper airways represent the main reservoir for subsequent lower airway colonization with Group I pathogens. Previous (short-term) antibiotic treatment is protective against initial tracheobronchial colonization with Group I pathogens, but it represents a risk factor for subsequent lower airway colonization by Group II pathogens.
Correlation Between Uracil and Dihydrouracil Plasma Ratio, Fluorouracil (5-FU) Pharmacokinetic Parameters, and Tolerance in Patients With Advanced Colorectal Cancer: A Potential Interest for Predicting 5-FU Toxicity and Determining Optimal 5-FU Dosage
Authors: E. Gamelin, M. Boisdron-Celle, V. Guérin-Meyer, R. Delva, A. Lortholary, F. Genevieve, F. Larra, N. Ifrah, J. Robert
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Patients with genetic fluorouracil (5-FU) catabolic deficiencies are at high risk for severe toxicity. To predict 5-FU catabolic deficiencies and toxic side effects, we conducted a prospective study of patients treated for advanced colorectal cancer by high-dose 5-FU. PATIENTS AND METHODS: Eighty-one patients were treated with weekly infusions of 5-FU and folinic acid. The initial 5-FU dose of 1,300 mg/m 2 was individually adjusted according to a dose-adjustment chart. Plasma concentrations of uracil (U) and its dihydrogenated metabolite, dihydrouracil (UH 2 ), were measured before treatment, and the ratio of UH 2 to U was calculated. Pharmacokinetic and pharmacodynamic studies were conducted to look for a relationship between the ratio of UH 2 to U and 5-FU metabolic outcome and tolerance. RESULTS: The UH 2 -U ratios were normally distributed (mean value, 2.82; range, 0.35 to 7.13) and were highly correlated to (1) 5-FU plasma levels after the first course of treatment (r = .58), (2) 5-FU plasma clearance (r = .639), and (3) individual optimal therapeutic 5-FU dose (r = .65). Toxic side effects were observed only in patients with initial UH 2 -U ratios of less than 1.8. No adverse effects were noted in patients with UH 2 -U ratios of greater than 2.25. CONCLUSION: The UH 2 -U ratio, easily determined before treatment, could help to identify patients with metabolic deficiency and, therefore, a risk of toxicity.
RTOG 0330: A pilot phase II study of preoperative radiation therapy/thalidomide for low-grade primary soft tissue sarcoma or preoperative MAID/thalidomide/radiation therapy for high/intermediate grade primary soft tissue sarcoma of the extremity or body wall
Authors: J. M. Kane III, J. Harris, W. G. Kraybill, D. C. Harmon, D. S. Ettinger, D. R. Lucas, T. F. DeLaney, D. Wang, W. J. Curran, B. L. Eisenberg
Journal: Journal of Clinical Oncology (2008)

10536 Background: Following RTOG 9514 (a phase II study of neoadjuvant chemoradiation for high-risk soft tissue sarcoma (STS) of the extremity/body wall), RTOG 0330 was developed to address the toxicity of 9514; the addition of thalidomide (THAL); low grade STS; and the development of biologic endpoints. Methods: Eligibility criteria were primary/recurrent STS of the extremity/trunk: ≥ 8 cm, intermediate/high grade (cohort A) or > 5 cm, low grade (cohort B). Cohort A received neoadjuvant mesna/doxorubicin/ifosfamide/DTIC (MAID) × 3 cycles, interdigitated THAL/concurrent 22 Gy radiation therapy (XRT) × 2 cycles, surgical resection, postoperative (postop) XRT boost if a positive margin, then 12 months adjuvant THAL. Cohort B received neoadjuvant THAL/concurrent 50 Gy XRT, surgical resection, postop XRT boost if a positive margin, then 6 months adjuvant THAL. Planned accrual was 44 patients (22 each cohort). The primary endpoint was treatment delivery/toxicity in each cohort. Results: From 2004–2007, 22 eligible primary STS patients were accrued (15 cohort A and 7 cohort B). For cohort A/B: median age was 49/47 years; median tumor size was 12.8/10 cm; male 53%/71%. All patients in both cohorts underwent 100% of the planned preoperative (preop) XRT, preop THAL, and surgical resection. Three cycles MAID were delivered in 93% of cohort A. Positive margins were present in 27% cohort A/ 29% cohort B and 50% received a 16 Gy boost. Adjuvant THAL was given in 60% cohort A/ 57% cohort B. Adverse events (AE) in cohort A were Grade 3 in 27%, Grade 4 in 53% and in cohort B were Grade 3 in 57%, Grade 4 in 0%. Grade 3/4 vascular AE occurred in 40% of cohort A (1 catheter thrombus and 5 DVT or PE) but in 0% of cohort B. RTOG 0330 was closed early (3/21/07) due to thromboembolic risk in cohort A (despite adding low-dose aspirin) and poor accrual in cohort B. Conclusions: Although the majority of RTOG 0330 patients were able to complete the planned treatment, the combination of neoadjuvant MAID with THAL/XRT was associated with an increased risk for thromboembolic events not seen with THAL/XRT alone. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis
Occupation-Related Risks for Colorectal Cancer
Authors: Donna Spiegelman, David H. Wegman
Journal: JNCI Journal of the National Cancer Institute (1985)

Several population data bases were used to generate hypotheses about associations between colorectal cancer and workplace exposures. The Third National Cancer Survey interview sample was used to select 343 male and 208 female cases and 626 male and 1,235 female cancer controls. Potential work exposures were assigned with the use of data from the National Institute for Occupational Safety and Health National Occupational Hazard Survey. Dietary factors were modeled from the National Health and Nutrition Examination Survey data. Work-related stress was considered with the use of a model based on the U.S. Department of Labor's Quality of Employment Survey. Other risk factors included age, race, ponderosity, and menopausal status. Logistic analysis yielded hypotheses for colon cancer risk in males with potentially high exposure to solvents, abrasives, and fuel oil and in those in jobs with high demand and low control (high "stress"). Hypotheses emerged for females with potentially high exposure to dyes, solvents, and grinding wheel dust.
Persistently Decreased Hepatic Levels of 5′-Deoxy-5′-methylthioadenosine During Regeneration of and Chemical Carcinogenesis in Rat Liver&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN4"&gt;4&lt;/xref&gt;
Authors: M E Ferioli, G Scalabrino
Journal: JNCI Journal of the National Cancer Institute (1986)

The hepatic levels of 5′-deoxy-5′-methylthioadenosine (MTA) were measured in the livers of adult male Sprague-Dawley rats a) killed at various times during the liver regeneration process, b) killed at times after partial hepatectomy when the liver mass had already been completely restored (hereafter called postregeneration livers), or c) continuously fed 3′-methyl-4-dimethylaminoazobenzene (CAS: 55-80-1) up to the full development of hepatoma and killed at regular intervals during hepatocarcinogenesis. Hepatic MTA levels were always significantly decreased, although to different degrees in both in vivo models of hepatic growth and at all times during the investigation. Astonishingly, the MTA levels were also significantly decreased in the post-regeneration livers, in which there was also a significant increase in the activity of adenosylmethionine decarboxylase (S-adenosyl-l-methionine decarboxylase; EC 4.1.1.50) with normal levels of activity of ornithine decarboxylase (EC 4.1.1.17). These results demonstrate that a) the MTA content is always decreased in rat liver whenever this organ is involved in a proliferative process (whether controlled or uncontrolled); b) the decrease in hepatic MTA content is a biochemical feature necessary for, but by no means by itself sufficient for, hepatocyte proliferation to occur, since this decrease remains long after complete restoration of the liver mass; and c) the return of the hepatocytes to the normal biochemical program after restoration of the liver mass is not complete, even though these cells become quiescent, because there are still some biochemical abnormalities in the post-regeneration livers.