Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and safety of budesonide/formoterol single inhaler therapy versus a higher dose of budesonide in moderate to severe asthma

SUMMARY Objectives: This study evaluated the efficacy and safety of a novel asthma management strategy – budesonide/formoterol for both maintenance and symptom relief (Symbicort Single Inhaler Therapy*) – compared with a higher maintenance dose of budesonide in patients with moderate to severe asthma. Methods: This was a 12-month, randomised, double-blind, parallel-group study. Symptomatic patients with asthma (n = 1890; mean age 43 years [range 11 years–80 years], mean baseline forced expiratory volume in 1 s [FEV1] 70% of predicted, mean inhaled corticosteroid [ICS] dose 746 µg/day) received either budesonide (160 µg, 2 inhalations twice daily) plus terbutaline 0.4 mg as needed or a daily maintenance dose of budesonide/formoterol (160/4.5 µg, 2 inhalations once daily) with additional inhalations of budesonide/formoterol 160/4.5 µg as needed. Time to first severe exacerbation (hospitalisation/emergency room [ER] treatment or systemic steroids due to asthma worsening or a fall in morning peak expiratory flow [PEF] to ≤ 70% of baseline on 2 consecutive days) was the primary outcome variable. Results: A total of 1890 patients were randomised, of whom 1563 (83%) had severe asthma. The time to first severe exacerbation was prolonged by budesonide/formoterol single inhaler therapy ( p < 0.001) compared with a higher dose of budesonide. The risk of having a severe exacerbation was 39% lower with budesonide/ formoterol single inhaler therapy compared with budesonide ( p < 0.001). The number needed to treat to prevent one severe exacerbation per year with budesonide/formoterol compared with budesonide was 5. The budesonide/formoterol group had 45% fewer severe exacerbations requiring medical intervention per patient compared with the budesonide group ( p < 0.001). Budesonide/formoterol patients had fewer hospitalisations/ER treatments (15 vs 25 events, respectively [descriptive statistics]) and fewer treatment days with systemic steroids (1776 days vs 3177 days, respectively [descriptive statistics]) compared with budesonide patients. Budesonide/formoterol single inhaler therapy patients used less as-needed medication compared with budesonide patients (0.90 vs 1.42 inhalations/day; p < 0.001). The mean daily ICS dose was lower in the budesonide/formoterol group than in the budesonide group (466 µg/day vs 640 µg/day). Over the 12-month study period, the budesonide/formoterol group achieved asthma control sufficient to not require any additional as-needed medication on 60% of days. Overall, budesonide/formoterol single inhaler therapy gave 31 more asthma control days (a night and day with no asthma symptoms and no as-needed medication use) per patient-year and 12 additional undisturbed nights per patient-year compared with a higher dose of budesonide. Both treatments were well tolerated. Conclusion: Budesonide/formoterol single inhaler therapy has the potential to provide a complete asthma management approach with one inhaler, demonstrating a high level of efficacy in patients with moderate to severe asthma.
Influence of Forest Fragmentation on Community Structure of Frogs and Lizards in Northeastern Costa Rica

Abstract: To better understand responses of reptiles and amphibians to forest fragmentation in the lowland Neotropics, we examined community and population structure of frogs and lizards in the fragmented landscape surrounding La Selva Biological Station in the Sarapiquí region of northeastern Costa Rica. We used diurnal quadrats and nocturnal transects to sample frogs and lizards in nine forest fragments (1–7 ha each) and La Selva (1100 ha). Species richness in all fragments combined was 85% of that found in La Selva with comparable sampling effort. Richness varied from 10 to 24 species among forest fragments, compared with 36 species at La Selva. Lizard density was higher and frog density was lower in forest fragments than in La Selva. Community composition varied among sites and by fragment size class, and species occurrence was nested with respect to fragment area. Isolation and habitat variables did not significantly affect species richness, composition, or nestedness. We classified 34% of species as fragmentation sensitive because they were absent or occurred at low densities in fragments. Nevertheless, the relatively high diversity observed in the entire set of fragments indicates that preserving a network of small forest patches may be of considerable conservation value to the amphibians and reptiles of this region.
The adherence and invasion of human intestinal cells by Arcobacter species 1 and their virulence genotype

3 Arturo Levican, Aldukali Alkeskas, Claudia Günter, Stephen J Forsythe, and María José 4 Figueras 5 Unitat de Microbiologia, Departament de Ciències Mediques Bàsiques, Facultat de 6 Medicina i Ciències de la Salut. IISPV. Universitat Rovira i Virgili, Reus, Spain. 7 Pathogen Research Centre, School of Science and Technology, Nottingham Trent 8 University, Nottingham, UK. NG11 8NS. 9 10
Molecular screening of antibiotic-resistant determinants among multidrug-resistant clinical isolates of Proteus mirabilis from SouthWest Nigeria.

BACKGROUND Globally, and particularly in developing countries, the menace of anti-microbial resistance is an accelerating problem. In Nigeria, increase in bacterial resistance has been phenotypically established but due to high cost, few molecular studies have been reported. OBJECTIVES This study screened for presence of transferable resistance genes and mobile genetic elements (MGEs) such as integron among multi-drug resistant (MDR) P. mirabilis. METHODS A total of 108 P. mirabilis strains collected from five tertiary hospitals in SouthWest Nigeria were subjected to antibiotic susceptibility study using disc-diffusion method. Transferable resistance genes and MGEs were amplified using Polymerase chain reaction (PCR) analysis and amplicons sequenced. RESULTS Varied resistance was observed against all the antibiotics tested. About 56% of the isolates were MDR including those from 0-12 years old children. PCR analysis revealed the presence of aac(6')-Ib (33.3%), plasmid mediated quinolone resistance (PMQR) genes [qnrA (36.7%), acc(6')-Ib-cr (5%)], TEM (48.3%), CTX-M (6.7%) and integrons class 1 (58.3%) and class 2 (26.7%). Sequencing analysis revealed blaTEM-1, blaCTX-M-15 associated with ISEcp1 and eight different arrays of gene cassettes: aadA1, aadA1-qacH, aadB-aadA2, aadA5, dfrA7, dfrA15, dfrA17, dfrA17-aadA5. CONCLUSION Transferable resistance genes in association with MGEs are present in Nigerian P. mirabilis thus their potential in disseminating resistance.
Salivary Acinar Cells from Aquaporin 5-deficient Mice Have Decreased Membrane Water Permeability and Altered Cell Volume Regulation*

Aquaporins (AQPs) are channel proteins that regulate the movement of water through the plasma membrane of secretory and absorptive cells in response to osmotic gradients. In the salivary gland, AQP5 is the major aquaporin expressed on the apical membrane of acinar cells. Previous studies have shown that the volume of saliva secreted by AQP5-deficient mice is decreased, indicating a role for AQP5 in saliva secretion; however, the mechanism by which AQP5 regulates water transport in salivary acinar cells remains to be determined. Here we show that the decreased salivary flow rate and increased tonicity of the saliva secreted byAqp5 − /− mice in response to pilocarpine stimulation are not caused by changes in whole body fluid homeostasis, indicated by similar blood gas and electrolyte concentrations in urine and blood in wild-type and AQP5-deficient mice. In contrast, the water permeability in parotid and sublingual acinar cells isolated from Aqp5 − /− mice is decreased significantly. Water permeability decreased by 65% in parotid and 77% in sublingual acinar cells fromAqp5 − /− mice in response to hypertonicity-induced cell shrinkage and hypotonicity-induced cell swelling. These data show that AQP5 is the major pathway for regulating the water permeability in acinar cells, a critical property of the plasma membrane which determines the flow rate and ionic composition of secreted saliva.
Waist circumference as the best predictor of noninsulin dependent diabetes mellitus (NIDDM) compared to body mass index, waist/hip ratio and other anthropometric measurements in Mexican Americans--a 7-year prospective study.

Although a number of obesity-related variables are recognized risk factors for NIDDM, few studies have addressed which one is the best predictor. A cohort of 721 Mexican Americans aged 25-64 years who were free of NIDDM at baseline were followed for an average of 7.2 years; 105 new cases of NIDDM were diagnosed. Body weight, body mass index (BMI), waist and hip circumferences, waist/hip ratio (WHR), triceps and subscapular skinfolds were all positively predictive of NIDDM independent of age and sex. There were modest to strong correlations between these anthropometric variables, however, waist circumference was the strongest predictor of NIDDM. The predictive power of a single measurement of waist circumference was at least equal to that of WHR and BMI combined. The risk of NIDDM for those in the highest quartile of waist circumference was 11 times greater than for those in the lowest quartile (95% confidence interval: 4.2-28.8). The waist-NIDDM relation was stronger in subjects with BMI < or = 27 kg/m2 (OR: 6.0 for a 1 SD difference) than in subjects with BMI > 27 kg/m2 (OR: 1.7 for a 1 SD difference). In multivariate analysis, waist circumference was the only significant predictor of NIDDM in models that included other anthropometric variables either separately or simultaneously. WHR and BMI were independent predictors of NIDDM after adjustment for each other, however, their predictive abilities disappeared after adjustment for waist circumference. The data indicate that waist is the best obesity-related predictor of NIDDM. This finding suggests that the distribution of body fat, especially abdominal localization, is a more important determinant than the total amount of body fat of the development of NIDDM in Mexican Americans.
Treatment of EBV‐associated nodular sclerosing Hodgkin lymphoma in a patient with ataxia telangiectasia with brentuximab vedotin and reduced COPP plus rituximab

Patients with ataxia telangiectasia (AT) with malignancies face poor prognosis due to increased treatment‐related toxicity. Here, we report a 14‐year‐old male with AT and Hodgkin lymphoma (HL) who received brentuximab vedotin and reduced COPP plus rituximab courses. This treatment resulted in complete remission and showed no severe toxicity. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.
Processing of the S-cone signals in the early visual cortex of primates

Abstract The short-wavelength-sensitive (S) cones play an important role in color vision of primates, and may also contribute to the coding of other visual features, such as luminance and motion. The color signals carried by the S cones and other cone types are largely separated in the subcortical visual pathway. Studies on nonhuman primates or humans have suggested that these signals are combined in the striate cortex (V1) following a substantial amplification of the S-cone signals in the same area. In addition to reviewing these studies, this review describes the circuitry in V1 that may underlie the processing of the S-cone signals and the dynamics of this processing. It also relates the interaction between various cone signals in V1 to the results of some psychophysical and physiological studies on color perception, which leads to a discussion of a previous model, in which color perception is produced by a multistage processing of the cone signals. Finally, I discuss the processing of the S-cone signals in the extrastriate area V2.
Adult Undergraduates' Participation and Involvement: Future Directions for Theory and Research.

AUTHOR Donaldson, Joe F. ; Graham, Steven W. ; Kasworm, Carol; Dirkx, John M. TITLE Adult Undergraduates' Participation and Involvement: Future Directions for Theory and Research. PUB DATE 1999-04-00 NOTE 54p. ; Paper presented at the Annual Meeting of the American Educational Research Association (Montreal, Ontario, Canada, April 19-23, 1999). PUB TYPE Information Analyses (070) Speeches/Meeting Papers (150) EDRS PRICE MF01/PC03 Plus Postage. DESCRIPTORS *Adult Learning; *Adult Students; Andragogy; Higher Education; Nontraditional Students; Reentry Students; Research and Development; Research Needs; *Student Development; *Student Participation; *Theory Practice Relationship; *Undergraduate Students; Undergraduate Study
Targeting the c‐Myc coiled coil with interfering peptides

c‐Myc is one of the most frequently deregulated oncogenes in human cancers, and recent studies showed that even brief inactivation of Myc can be sufficient to induce tumor regression or loss. Consequently, inactivation of Myc provides a novel therapeutic opportunity and challenge, as the dimerization of Myc with Max is crucial for its function. We applied two strategies to specifically target this coiled coil mediated interaction with interfering peptides: a dominant‐negative human Max sequence (Max) and a peptide selected from a genetic library (Mip). Both peptides form coiled coils and were fused to an acidic extension interacting with the basic DNA‐binding region of human Myc. The genetic library was obtained by semi‐rational design randomizing residues important for interaction, and selection was carried out using a protein‐fragment complementation assay. The peptides Max and Mip easily outcompeted the human Myc:Max interaction and successfully interfered with the DNA binding of the complex. Both interfering peptides exhibited higher Tm (ΔTm = 13 and 15 °C) upon interaction with Myc compared to wt Max. The inhibitory effect of the two interfering peptides on human Myc:Max activity makes them promising molecules for analytical and therapeutic Myc‐directed research. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.
Clastogenic activity of 2-chlorodeoxyadenosine in mammalian somatic cells

The base analogue 2-chlorodeoxyadenosine (2-CdA) used for therapy in chronic resistant and advanced lymphoproliferative disorders, is cytotoxic for both dividing and non-dividing lymphocytes. The present work evaluated the clastogenic potential of this drug in vitro in human lymphocytes in culture and in vivo in BALB/c mice bone marrow cells. In human lymphocytes, the clastogenic effect of 2-CdA was studied in G1, S and G2 phases of the cell cycle, using three different concentrations (10, 20 and 40 mg/mL). The endpoints analyzed included mitotic index (MI), proliferation index (PI), sister chromatid exchange (SCE), and chromosomal aberration (CA). Statistical analysis by a variance (ANOVA) test showed a significant increase (p < 0.05) in CA frequencies for cells treated during the S phase, but the MI did not vary. The concentrations tested did not produce a significant increase in the mean frequency of SCEs, nor did they change the cell PI in the G1 and S phases. The concentrations in vivo tested were 0.25, 0.375 and 0.5 mg/kg body weight. In this assay, alterations in CA frequencies and MI were not observed at the dose levels tested. Therefore, the results indicate a clastogenic effect of 2-CdA in human lymphocyte cultures.
CNGC2 Is a Ca2+ Influx Channel That Prevents Accumulation of Apoplastic Ca2+ in the Leaf1

Arabidopsis CNGC2 is a Ca2+-permeable channel that mediates Ca2+ influx into mesophyll cells near minor veins but has no direct role in the hypersensitive response or leaf senescence. Ca2+ is absorbed by roots and transported upward through the xylem to the apoplastic space of the leaf, after which it is deposited into the leaf cell. In Arabidopsis (Arabidopsis thaliana), the tonoplast-localized Ca2+/H+ transporters CATION EXCHANGER1 (CAX1) and CAX3 sequester Ca2+ from the cytosol into the vacuole, but it is not known what transporter mediates the initial Ca2+ influx from the apoplast to the cytosol. Here, we report that Arabidopsis CYCLIC NUCLEOTIDE-GATED CHANNEL2 (CNGC2) encodes a protein with Ca2+ influx channel activity and is expressed in the leaf areas surrounding the free endings of minor veins, which is the primary site for Ca2+ unloading from the vasculature and influx into leaf cells. Under hydroponic growth conditions, with 0.1 mm Ca2+, both Arabidopsis cngc2 and cax1cax3 loss-of-function mutants grew normally. Increasing the Ca2+ concentration to 10 mm induced H2O2 accumulation, cell death, and leaf senescence and partially suppressed the hypersensitive response to avirulent pathogens in the mutants but not in the wild type. In vivo apoplastic Ca2+ overaccumulation was found in the leaves of cngc2 and cax1cax3 but not the wild type under the 10 mm Ca2+ condition, as monitored by Oregon Green BAPTA 488 5N, a low-affinity and membrane-impermeable Ca2+ probe. Our results indicate that CNGC2 likely has no direct roles in leaf development or the hypersensitive response but, instead, that CNGC2 could mediate Ca2+ influx into leaf cells. Finally, the in vivo extracellular Ca2+ imaging method developed in this study provides a new tool for investigating Ca2+ dynamics in plant cells.
Deep white matter hyperintensities affect verbal memory independent of PTSD symptoms in veterans with mild traumatic brain injury

Abstract Objective: Although white matter hyperintensity (WMH) pathology has been observed in the context of traumatic brain injury (TBI), the contribution of this type of macrostructural damage to cognitive and/or post-concussive symptomatology (PCS) remains unclear. Methods: Sixty-eight Veterans (mTBI = 46, Military Controls [MCs] = 22) with and without history of mild TBI (mTBI) underwent structural MRI and comprehensive cognitive and psychiatric assessment. WMH volume was identified as deep (DWMH) or periventricular (PVWMH) on fluid-attenuated inversion recovery (FLAIR) images. Results: Group analyses revealed that mTBI history was not associated with increased WMH pathology (p’s > 0.05). However, after controlling for post-traumatic stress disorder (PTSD) and intracranial volume, DWMH was associated with reduced short-and long-delayed memory performance within the mTBI group (p’s < 0.05). Additionally, after adjusting for PTSD and time since injury, regression analyses revealed that WMH was not associated with self-reported ratings of PCS (p’s > 0.05) in the mTBI group. Conclusions: The results demonstrate that, in relatively young Veterans with mTBI, DWMH differentially and negatively affects memory performance above and beyond the effects of PTSD symptoms. The findings may help to clarify prior mixed results as well as offer focused treatment implications for Veterans with history of neurotrauma and evidence of macrostructural white matter damage.
Is the asymmetric cost behavior affected by competition factors?*

Abstract Prior studies on the asymmetric cost behavior mainly focus on internal factors. However, managers consider both internal and external factors when making strategic cost decisions. In this paper, we investigate the relation between the asymmetric cost behavior and external competition factors. We find that Selling, General, and Administrative costs are more sticky for firms in different competition environments, proxied by higher product differentiation, higher entry costs, and larger market size. Overall, these findings suggest that the asymmetric cost behavior is affected by external factors as well as internal factors.
HYPEROXIA SUPPRESSES EXCESSIVE SUPEROXIDE ANION RADICAL GENERATION IN BLOOD, OXIDATIVE STRESS, EARLY INFLAMMATION, AND ENDOTHELIAL INJURY IN FOREBRAIN ISCHEMIA/REPERFUSION RATS: LABORATORY STUDY

This study used an electrochemical O2-· sensor to investigate the effects of hyperoxia on generation of the superoxide radical (O2-·) in the jugular vein during forebrain I/R in rats. Twenty-eight male Wistar rats were allocated to a sham group (n = 7; sham-treated rats with inspired oxygen fraction [FiO2] of 0.4), a hemorrhagic shock and reperfusion (HS/R) group (n = 7; HS without carotid artery occlusion and reperfusion with FiO2 of 0.4), a normoxia group (n = 7; forebrain ischemia produced by bilateral carotid arteries occlusion with HS and reperfusion with FiO2 of 0.4), and a hyperoxia group (n = 7; forebrain ischemia with FiO2 of 0.4 and reperfusion with FiO2 of 1.0). The jugular venous O2-· current was measured for 10 min during forebrain ischemia and for 120 min after reperfusion. The O2-· current increased gradually during forebrain ischemia in the three groups other than the sham group. Immediately after reperfusion, the current showed a marked increase in the normoxia group and a pronounced decrease in the hyperoxia group. Levels of brain and plasma malondialdehyde, high-mobility group box 1 protein, and intercellular adhesion molecule 1 were significantly attenuated in the hyperoxia group relative to those in the normoxia group. In conclusion, hyperoxia suppressed jugular venous O2-· generation and malondialdehyde, high-mobility group box 1, and intercellular adhesion molecule 1 in the brain and plasma in the acute phase of cerebral I/R. Thus, the administration of 100% oxygen immediately after reperfusion suppresses oxidative stress and early inflammation in cerebral I/R.
Local-regional control by conventional radiotherapy according to tumor volume in patients with squamous cell carcinoma of the pharyngolarynx.

BACKGROUND To estimate the effect of tumor volume on local-regional control of pharyngolaryngeal cancer by radiotherapy (RT). METHODS Definitive RT for 48 patients with squamous cell carcinoma of the lateral wall of the oropharynx, pyriform sinus and supraglottic larynx was reviewed. Tumor volume was estimated from computed tomography and it was expressed as the diameter of a sphere the volume of which is equal to the primary tumor (Td) and sum of the volumes of metastatic adenopathies (Nd). All patients received > or =60 Gy (median 66 Gy) to the gross tumor by conventional fractionation with or without chemotherapy. RESULTS A median period of follow-up for survivors was 32.7 months (range, 12.4-68.6). The 2 year local control rate for T1/2 (n = 30) and T3/4 (n = 18) patients was 72 and 65%, respectively (P= 0.966), however, the rates for Td < 4 cm tumors (n = 37) and Td > or = 4 cm tumors (n = 11) were significantly different (80% vs 27%, P < 0.001). The 2 year regional control rates for Nd < 3 cm lesions (n = 29) and Nd > or = 3 cm (n = 19) lesions were 85 and 42%, respectively (P < 0.001). The 2 year ultimate regional control rates for N2/3 disease with Nd < 4 cm (n = 11) and Nd > or = 4 cm (n = 11) were 100 and 42%, respectively (P = 0.004). CONCLUSIONS Conventional radiotherapy may allow organ preservation and ultimate local control in patients with Td < 4 cm and Nd < 4 cm disease, but larger volume tumors should be considered candidates for the most intensive chemoradiotherapy.
Fear and Loathing on the Campaign Trail: Did Immigration Cause Brexit?

Can large immigration inflows impact electoral outcomes and specifically, what impact did immigration have on the vote in favour of leaving the European Union (Brexit) in the United Kingdom? In particular, I focus on how the increase in Polish immigration, the major group of immigrants post 2004, affected votes in favour of leaving the EU. I find a percentage point increase in Polish immigration to the UK to have caused an increase in votes in favour of Brexit of about 2.72-3.12 percentage points, depending on the specification. To obtain exogenous variation in Polish immigration, I collect data from the archives that reveals the location of Polish War Resettlement Camps after Word War II, which location is plausibly exogenous to current political outcomes. Discussing potential mechanisms, I examine public opinion data in the British Election Study 2015 and find evidence of adversity towards immigration to be a root cause. Other considerations such as the National Health Service (NHS), incumbency and the general trust in politicians as well as the political institutions seem not to play a role.