tbuckley/cabot-search huggingface dataset:
MicroRNA‐494 is a master epigenetic regulator of multiple invasion‐suppressor microRNAs by targeting ten eleven translocation 1 in invasive human hepatocellular carcinoma tumors
Authors: Kuang‐Hsiang Chuang, Christa L. Whitney‐Miller, Chin‐Yi Chu, Zhongren Zhou, M. Katherine Dokus, Shannon Schmit, Christopher T. Barry
Journal: Hepatology (2015)

Vascular invasion provides a direct route for tumor metastasis. The degree to which microRNA (miRNA) expression plays a role in tumor vascular invasion is unclear. Here, we report that miR-494 is up-regulated in human hepatocellular carcinoma (HCC) tumors with vascular invasion and can promote HCC cell invasiveness by gene inactivation of multiple invasion-suppressor miRNAs. Our results show that ten eleven translocation (TET) methylcytosine dioxygenase, predominantly TET1 in HCC cells, is a direct target of miR-494. The reduced 5'-hydroxymethylcytosine levels observed in the proximal cytosine-phosphate-guanine (CpG) regions of multiple invasion-suppressor miRNA genes are strongly associated with their transcriptional repression upon miR-494 overexpression, whereas enforced DNA demethylation can abolish the repression. Furthermore, TET1 knockdown shows a similar effect as miR-494 overexpression. Conversely, miR-494 inhibition or enforced TET1 expression is able to restore invasion-suppressor miRNAs and inhibit miR-494-mediated HCC cell invasion.miR-494 can trigger gene silencing of multiple invasion-suppressor miRNAs by inhibiting genomic DNA demethylation by direct targeting of TET1, thereby leading to tumor vascular invasion.
Reducing inappropriate antibiotic use in lower respiratory tract infection (LRTI); a quality improvement study
Authors: Matthew S. Lloyd, Colin Murray, Arlene Shaw, Tom C. Fardon, Robin P. Smith, Stuart Schembri, James D. Chalmers
Journal: European Respiratory Journal (2013)

Introduction 

Prolonged courses of antibiotics result in adverse events for patients and lead to antibiotic resistance. We designed an intervention study to assess the benefits and safety of a new prescribing protocol for antibiotic duration for patients with LRTIs on a respiratory ward in a Scottish teaching hospital.

Methods 

We included all patients who received antibiotics for a LRTI identified over 1 year. In the initial phase we recorded mode and duration of antibiotic use. Outcome measures were: antibiotic related adverse effects, HDU/ITU admission, length of stay and death. The second phase followed implementation of an antibiotic protocol consisting of automatic stop dates, severity guided duration of antibiotics (duration 5 days for low risk CURB65 patients, 7 days for high severity patients) and pharmacist feedback. Antibiotic use was categorised into four therapeutic sub-groups; pneumonia (PN), acute exacerbations of COPD (AECOPD), exacerbations of asthma (ExA) and 'other' (O).

Results 

There were 281 pre and 221 post-intervention patients included. A significant decrease in antibiotic duration (days) was seen across all patients (8.3→6.8 p<0.001) and across each individual diagnostic sub-group (p<0.001); PN (9.3→7.1), AECOPD (7.7→6.2), ExA (6.3→5.0) and O (8.5→6.6). This was associated with a significant decrease in adverse events attributable to antibiotic use when comparing pre to post-intervention groups, from 31.3%→19.0% (p<0.0001). There was no significant effect of the intervention on mortality rate (8.9%→8.1% p=0.6).

Conclusion 

A multidisciplinary intervention can significantly reduce inappropriate antibiotic use and antibiotic associated adverse effects.
Hormonal Regulation of Rapidly Labeled RNA in Normal Preneoplastic and Neoplastic Tissues of Mouse Mammary Gland 2
Authors: D. N. Banerjee, M. R. Banerjee, R. G. Mehta
Journal: JNCI Journal of the National Cancer Institute (1973)

Linear sucrose-density gradient and polyacrylamide-gel electrophoresis were used to analyze patterns of rapidly labeled RNA synthesis in normal, preneoplastic, and neoplastic tissues of BALB/c mouse mammary gland. As measured by 5-3H-uridine incorporation, there was no synthesis of rapidly labeled, high molecular weight RNA in the mammary tissue of young virgin mice. Administration of estradiol-17β plus progesterone to intact or ovariectomized or adrenalectomized virgins induced a sharp rise of rapidly labeled RNA synthesis with patterns like those of the mammary tissue of pregnancy. The growth-promoting actions of the ovarian hormones in the mammary tissue thus appeared to involve induction of rapidly labeled, polydispersed RNA. The preneoplastic nodule outgrowth lines D1 and D8, carried in virgin hosts, actively synthesized rapidly labeled, high molecular weight RNA regardless of tumorigenic potential. RNA labeled with3H-methylmethionine showed that newly made RNA included both ribosomal precursor RNA and heterogeneous nuclear RNA. Ovariectomy and adrenalectomy or extended treatment with estradiol-17β plus progesterone failed to alter the patterns of rapidly labeled RNA synthesis in the preneoplastic tissues. A similar unaltered pattern of RNA synthesis was evident when the nodule tissue was carried in pregnant or lactating hosts. Therefore, RNA synthesis in nodule cells remained unresponsive to the ovarian hormonal regulation. Rapidly labeled RNA synthesis in the mammary tumors derived from these precancerous tissues showed a similar unresponsiveness to hormonal control; thus altered responsiveness to host hormonal control of preneoplastic nodule RNA may not be the ultimate metabolic abnormality leading to neoplastic transformation.
Induction of Neoplasms in Germfree Rodents by 3-Methylcholanthrene&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Morris Pollard, T. Matsuzawa, J. C. Salomon
Journal: JNCI Journal of the National Cancer Institute (1964)

Localized neoplasms were induced in two strains of germfree rats and in four strains of germfree mice by subcutaneous inoculation of sterile 3-methylcholanthrene in oil. The types, locations, and latent periods of the tumors in germfree animals were similar to those induced by the same agent in conventional control animals. Fragments of germfree fibrosarcomas were transplanted to germfree mice and rats of the same genetic strains. The germfree mice had no antibodies to polyoma virus, K virus, mouse adenovirus, and mouse hepatitis virus, and showed no immunity or tolerance to vaccinia or lymphocytic choriomeningitis viruses. Tissue cultures of whole fetuses and kidney tissues from the germfree mice and rats showed no cytopathic effects.
Phase I, Dose-Finding, and Pharmacokinetic Study of Raltitrexed Combined With Oxaliplatin in Patients With Advanced Cancer
Authors: Karim Fizazi, Michel Ducreux, Pierre Ruffié, Marc Bonnay, Catherine Daniel, Jean-Charles Soria, Catherine Hill, Abderrahim Fandi, Marc Poterre, Mark Smith, Jean-Pierre Armand
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of the raltitrexed plus oxaliplatin combination regimen, to explore its safety and pharmacokinetics, and to assess its antitumor activity in patients with advanced solid tumors. PATIENTS AND METHODS: Forty-eight patients received the combination of raltitrexed plus oxaliplatin. Raltitrexed was administered as a 15-minute infusion followed by oxaliplatin as a 2-hour infusion 1 hour later, repeated every 3 weeks. Seven dose levels were explored, ranging from 2 to 3.75 mg/m 2 and from 85 to 130 mg/m 2 for raltitrexed and oxaliplatin, respectively. The pharmacokinetics of both raltitrexed and oxaliplatin was assessed at the last three dose levels. RESULTS: Forty-six patients were assessable for toxicity. Severe toxicities usually occurred from dose level V (raltitrexed 3 mg/m 2 and oxaliplatin 130 mg/m 2 ). This combination was not myelosuppressive, eliciting only sporadic grades 3 and 4 neutropenia and/or thrombocytopenia without complications. There was no alopecia. DLTs were asthenia and nausea/vomiting, despite systematic antiemetic prophylaxis. Dose level VI (raltitrexed 3.5 mg/m 2 and oxaliplatin 130 mg/m 2 ) was deemed to be the MTD. Eight confirmed partial responses were observed: six patients with malignant mesothelioma (both pretreated and nonpretreated), one with fluorouracil-refractory pancreatic carcinoma, and one with renal carcinoma. Evaluation of the pharmacokinetics of both drugs did not suggest any drug interaction. CONCLUSION: The combination of raltitrexed and oxaliplatin given as consecutive short infusions every 3 weeks seems to be an acceptable regimen that allows a dose-intensity as high as the sum of the recommended doses of each agent given alone. The dose recommended for further phase II studies is raltitrexed 3 mg/m 2 and oxaliplatin 130 mg/m 2 every 3 weeks. Promising antitumor activity has been observed in patients with malignant mesothelioma.
A Multicenter Phase Ii Trial of Nab-Paclitaxel in Combination with Capecitabine in Patients (Pts) with Her-2 Negative and Triple Negative Advanced Breast Cancer (Abc): an Interim Analysis
Authors: M. Ciccarese, L. Orlando, P. Fedele, P. Schiavone, E. Maiello, P. Cilenti, M. Aieta, G. Bozza, M.R.C. Forcignanò, A. Febbraro, R. Bordonaro, S. Romito, A. Rinaldi, N. Borsellino, F. Riccardi, S. Pisconti, V. Lorusso, G. Colucci, S. Cinieri
Journal: Annals of Oncology (2014)
Expression of the Neurotrophin Receptor TrkB Is Associated With Unfavorable Outcome in Wilms’ Tumor
Authors: Angelika Eggert, Michael A. Grotzer, Naohiko Ikegaki, Huaqing Zhao, Avital Cnaan, Garrett M. Brodeur, Audrey E. Evans
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Neurotrophins and their receptors regulate the proliferation, differentiation, and death of neuronal cells, and they have been implicated in the pathogenesis and prognosis of neuroblastomas and medulloblastomas. Tyrosine kinase (Trk) receptors also are expressed in extraneural tissues. PATIENTS AND METHODS: To study the role of neurotrophin receptors and ligands in Wilms’ tumor (WT), we determined their expression by semiquantitative duplex reverse transcriptase polymerase chain reaction in 39 patients with primary WT. Comparison of mRNA expression levels with clinical variables was performed by use of Cox regression analysis. RESULTS: Children with WT that expressed high levels of full-length TrkB mRNA (TrkBfull) had a significantly greater risk of death than children whose tumors had little or no TrkBfull expression (hazard ratio, 9.7; P = .02). The 5-year relapse-free survival was 100% versus 65% for patients with low versus high tumor expression of TrkBfull (P &lt; .003). Conversely, children with tumors that expressed high mRNA levels of a functionally inactive truncated TrkB receptor (TrkBtrunc) had a greater chance of survival than children with low levels of TrkBtrunc (hazard ratio, 0.08; P = .005). The 5-year relapse-free survival was 95% versus 68% for patients with high versus low levels of TrkBtrunc (P = .01). The hazard ratios for TrkBfull and TrkBtrunc remained significant after they were adjusted for tumor stage (P = .01 and P = .017, respectively). All WTs with high levels of TrkB expression also expressed the brain-derived nerve growth factor ligand. CONCLUSION: Expression of TrkBfull in WT is associated with worse outcome, perhaps because it provides an autocrine survival pathway. Conversely, TrkBtrunc expression is associated with excellent outcome, perhaps as a result of a dominant negative effect.
Community acquired pneumonia in asthma patients
Authors: Adamantia Liapikou, Dimitra Bakali, Ioannis Pantazopoulos, Katerina Dimakou, Antonia Koutsoukou, Mina Gaga, Michalis Toumbis, Panos Demertzis
Journal: European Respiratory Journal (2013)

Background: Although asthma was the most common co-morbidity among patients hospitalized with pandemic influenza A (H1N1) infection, in community acquired pneumonia (CAP) there not data about the influence of asthma in its prognosis. The aim of this study was to compare the differences between asthma and non-asthma hospitalized patients with CAP.  Methods: A prospective study was performed to investigate the characteristics, severity and outcomes of asthma patients hospitalized with CAP, in 2 respiratory clinics and an ICU during 2 years period.  Results: During the study period 272 patients were recruited [median age 69.3 +/-9.5 years] and categorized in two groups: group A, asthma [n=19,age 55 +/- 20)] and group B non-asthma patients (n=251, age 65 +/-18years). Patients with asthma had more frequently comorbitidies (90% vs. 75%, p=0,15). They had received more often antibiotics before admission (56% vs. 40%, p=0,19) and presented earlier to the hospital (3,6 vs. 5,15 days, p=0,382), with lower CURB65 class (1,6 vs. 2,3, p=0, 15) and lower CRP levels (10,78 vs.16, 83, p=0,23). Two patients died, but were elderly (mean age 88 years) persons with other underline diseases  .  Conclusions: CAP patients with asthma presented earlier to the hospital and with less severe disease. More data are needed for further evaluation of this comorbidity in pneumonia’s course.
Can we assess COPD comorbidities by BODE index
Authors: Alexandru Corlateanu, Gloria Montanari, Victor Botnaru
Journal: European Respiratory Journal (2011)

Background:  COPD is characterized by a poorly reversible airflow limitation resulting from chronic inflammation, mainly due to tobacco exposure. The systemic inflammation induced by smoking may also cause extrapulmonary comorbidities, which may contribute to the clinical manifestations, natural history of COPD and significantly complicate the management and influence the prognosis.   The aim  of this study was to evaluate the possibility to assess comorbidities by GOLD/ATS/ERS classification and BODE.   Methods:  158 consecutive COPD patients were enrolled into the study. We analyzed age, gender, anthropometric, pack years, spirometric data (FEV1, FVC, FEV1/FVC), BODE index (BMI, FEV1, MRC, 6 MWD). Comorbidities were assessed by the Charlson Comorbidity Index (CCI).   Results:  158 COPD patients were studied, mean age 64.6±8.9 years. Patients across all stages GOLD/ATS/ERS classification had similar age and pack/years (p>0.01). As our data shows, the prevalence of comorbidities was similar when GOLD/ATS/ERS assessment of severity was applied. After the application of BODE classification the increase of comorbidities with severity of COPD was observed. There were no significant correlations between GOLD/ATS/ERS stage and comorbidities. Then Pearson correlation coefficient analysis demonstrated a significant positive correlation between the BODE and the comorbidities (r=0.29, p   Conclusion:  Comorbidity score correlates with BODE, this fact suggests that BODE is potentially able to measure COPD comorbidities. Further work is required to evaluate relationship between the BODE and COPD comorbidities.
Possible Carcinogenic Properties of a New Chromogen, Dicarboxydine (γ,γ′-3,3′-Benzidine Dioxydibutyric Acid), Tested in Rats and Mice
Authors: G B Pliss, N I Volfson
Journal: JNCI Journal of the National Cancer Institute (1979)

The carcinogenic properties of gamma,gamma'-3,3'-benzidine dioxydibutyric acid [dicarboxydine (DCD)] were studied in 208 rats and 127 mice by either sc administration or by feeding of the compound for 24 months. Tumors developed in 21 of the 99 DCD-treated rats that survived to the time of the first tumor appearance. In DCD-treated rats, tumors different from those in the controls were noted in the bladder, prostate gland, uterine body, and other organs, but in single cases only. Four rats had sarcomas at the site of DCD injection. DCD had no carcinogenic effect in mice. In view of the longer times of tumor induction and multiple tumor development only in rats given sc injections of DCD, the conclusion was reached that DCD is of dubious or negative carcinogenicity.
Specifications for signal processing and data handling used for infant pulmonary function testing
Authors: U Frey, J Stocks, P Sly, J Bates
Journal: European Respiratory Journal (2000)

The aim of this present paper is to define minimal performance criteria for the separate items comprising signal processing and data handling used to measure respiratory function in infants. These guidelines cover numerous aspects including: signal processing, data handling and subsequent analysis, reporting of results, demographics and handling of reference values. Adherence to these guidelines should ensure that infant lung function measurements can be performed with an acceptable degree of safety, precision, and reproducibility. Furthermore, they will facilitate multicentre collection of data and the performance of clinical investigations.
Black-White Differences in Social Background and Military Drug Abuse Patterns
Authors: RICHARD L. NAIL, E. K. ERIC GUNDERSON, RANSOM J. ARTHUR
Journal: American Journal of Psychiatry (1974)

The authors gathered data on the drug abuse patterns and social backgrounds of 833 Navy enlisted men (764 white and 69 black) admitted to a drug rehabilitation center. Black subjects reported better school adjustment, less delinquency, and fewer difficulties in their home lives than did whites. They had used heroin more frequently than whites but were less involved with hallucinogenic drugs. The authors suggest that different cultural patterns may underlie the drug abuse behaviors of the two groups. White users seem to be expressing new varieties of delinquent or antisocial behavior, while blacks are following long-established subcultural patterns of drug use.
The role of mast cells in functional GI disorders
Authors: Mira M Wouters, Maria Vicario, Javier Santos
Journal: Gut (2015)

Functional gastrointestinal disorders (FGIDs) are characterized by chronic complaints arising from disorganized brain-gut interactions leading to dysmotility and hypersensitivity. The two most prevalent FGIDs, affecting up to 16–26% of worldwide population, are functional dyspepsia and irritable bowel syndrome. Their etiopathogenic mechanisms remain unclear, however, recent observations reveal low-grade mucosal inflammation and immune activation, in association with impaired epithelial barrier function and aberrant neuronal sensitivity. These findings come to challenge the traditional view of FGIDs as pure functional disorders, and relate the origin to a tangible organic substrate. The mucosal inflammatory infiltrate is dominated by mast cells, eosinophils and intraepithelial lymphocytes in the intestine of FGIDs. It is well established that mast cell activation can generate epithelial and neuro-muscular dysfunction and promote visceral hypersensitivity and altered motility patterns in FGIDs, postoperative ileus, food allergy and inflammatory bowel disease. This review will discuss the role of mucosal mast cells in the gastrointestinal tract with a specific focus on recent advances in disease mechanisms and clinical management in irritable bowel syndrome and functional dyspepsia.
Discussing Genetic Testing With Patients With Breast Cancer in Developing Countries: Should We Be Judicious?
Authors: Abu Bakar Hafeez Bhatti
Journal: Journal of Clinical Oncology (2015)

TO THEEDITOR: Jagsietal 1 contributedtowardtheassessment of attitudes about genetic testing across various racial and/or ethnic backgrounds in the United States. Their study determined behavioral responses in patients with breast cancer over a reasonably protracted time and attempted to generate evidence that genetic testing should be discussed, even in patients with low-risk
Impact of Cardiovascular Events on Change in Quality of Life and Utilities in Patients After Myocardial Infarction
Authors: Eldrin F. Lewis, Yanhong Li, Marc A. Pfeffer, Scott D. Solomon, Kevin P. Weinfurt, Eric J. Velazquez, Robert M. Califf, Jean-Lucien Rouleau, Lars Kober, Harvey D. White, Kevin A. Schulman, Shelby D. Reed
Journal: JACC Heart Failure (2014)

The objective of this study was to determine the impact of nonfatal cardiovascular (CV) events on changes in health-related quality of life (HRQL). There is limited understanding of the impact of nonfatal CV events on long-term changes in HRQL in survivors of myocardial infarction (MI). The VALIANT (Valsartan In Acute Myocardial Infarction) trial enrolled 14,703 patients post-MI complicated by Killip class II or higher (scale measuring heart failure severity post-MI ranging from class I to IV) and/or reduced ejection fraction. The HRQL substudy included 2,556 (17.4%) patients who completed the EQ-5D with 5 questions, with responses mapped to utility weight on a scale of 0 to 1 and a visual analog scale (VAS) ranging from 0 (worst) to 100 (best) imaginable health state. EQ-5D was administered at baseline and 6, 12, 20, and 24 months. The trajectory of EQ-5D scores was developed by using linear mixed effects regression models with calculation of deviation from this trajectory after nonfatal CV events. Patients who died before the next EQ-5D assessment were excluded. Over a 2-year period, 597 patients experienced a nonfatal CV event and survived to have another EQ-5D assessment. Their baseline EQ-5D scores were lower than patients without a subsequent nonfatal CV event (VAS 61.0 ± 19 vs 68.2 ± 18 [p < 0.001] and US-based utility score 0.76 ± 0.22 vs 0.83 ± 0.17 [p < 0.001]). These patients with CV events experienced a trajectory-adjusted 6.6 point decrease (p < 0.001) in VAS scores and a 0.07 decrease (p < 0.001) in utility score after the nonfatal CV event. MI survivors suffering a CV event experienced significantly worse HRQL than their previous trajectory, suggesting that generic instruments can be responsive to nonfatal events. Reduction in nonfatal CV events may affect longitudinal changes in HRQL.
Pharmacological assessment of the effects of SB-705498 on capsaicin-induced responses in healthy volunteers and patients with non-allergic rhinitis
Authors: Carlijn Holland, Christine Segboer, Daphne Tsitoura, Amy Newlands, Philippe Bareille, Jane Denyer, Cornelis van Drunen, Wytske Fokkens
Journal: European Respiratory Journal (2011)

Rationale:  “Nasal hyper-responsiveness” has been proposed as a key mechanism driving nasal symptoms in patients with non-allergic rhinitits (NAR). Here, we explore the potential clinical use of the selective TRPV1 antagonist, SB-705498, for treatment of symptoms of rhinitis.   Methods:  Two clinical studies were conducted to assess the effect of SB-705498 on nasal responses to incrementally dosed, unilateral intranasal capsaicin challenge: In the first study, a single 400mg oral dose of SB-705498 was assessed in healthy volunteers (HVT). In the second study, 12mg of SB-705498 was administered topically to patients with non-allergic rhinitis. SB-705498 or placebo was administered according to a randomised, double blind, crossover (HVT) or parallel group (NAR) design. 1 hour post dosing, incremental capsaicin challenge (2.5, 12.5 and 50mg) was performed. Symptom scores, secretion weights, peak nasal inspiratory flow (PNIF) and mediators in nasal secretions were evaluated. Blood samples were collected for pharmacokinetic analysis.   Results:  Both studies showed a clear signal for effect of SB-705498 versus placebo on the clinical endpoints following intranasal challenge with capsaicin. The relative dose potency for TSS was 3.33 (1.45, 8.26 95% CI) in HVT and 2.81 (0.78, 10.7 95% CI) in NAR patients. All other clinical endpoints (satisfying parallelism) showed approximately 2-5 fold potency shift, except PNIF in NAR patients.   Conclusion:  SB-705498 inhibits capsaicin induced nasal responses in HVT and NAR. SB-705498 has potential for further development as a novel, topical intranasal medicine for treatment of rhinitis.