Miracle-dz/UniFAR-FTUs huggingface dataset:
The Genetics of Carotid Dissection: Meta-Analysis of a MTHFR/C677T Common Molecular Variant

Background and Purpose: Carotid dissection is a recognized cause of stroke. An association has been reported between carotid dissection and elevated homocysteine levels. Homocysteine levels are partly determined by a thermolibile form of methyltetrahydrofolate reductase (MTHFR) which has a common C677T single nucleotide polymorphism (SNP). We sought to undertake a comprehensive genetic meta-analysis of this SNP and its association with carotid dissection. Methods: All case-control studies evaluating MTHFR/C677T in carotid dissection were identified. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) using both fixed and random effects were determined for both dominant and recessive genetic models. Analyses were also undertaken to compare the effects of the homogenous forms of MTHFR/C677T. Results: Four manuscripts analyzing a total of 420 individuals (183 cases and 237 controls) were identified. The pooled OR for the dominant MTHFR/T677 model was 1.36 (95% CI 0.89–2.08; p = 0.16) while the pooled OR for the recessive TT model was 1.07 (95% CI 0.61–1.89; p = 0.81). To ensure a subtle recessive effect was not being masked by the inclusion of the heterozygous genotype, comparison of the CC and TT genotypes in cases against controls was undertaken but no significant association was observed (OR 0.73; 95% CI 0.38–1.40; p = 0.34). Conclusions: Our data does not support an association between the MTHFR/C677T molecular variant and carotid dissection. As this SNP accounts for the majority of the genetic variance of homocysteine levels, our data suggests that homocysteine is unlikely to play a major role in this condition.
Exposure to myelotoxic agents and myelodysplasia: case–control study and correlation with clinicobiological findings

To better define the role of exposure to myelotoxic agents in the genesis of myelodysplastic syndrome (MDS), we carried out (a) a case–control study for the determination of the relative risk (RR) of developing MDS, including 178 consecutive patients and 178 sex‐ and age‐matched controls; (b) a study of clinicobiological features in MDS arising after occupational exposure to myelotoxic agents and in MDS in ‘non‐exposed’ patients. The definition of the ‘exposure’ status was based on a predetermined questionnaire, with calculation of an ‘exposure’ index (hours/day × days/year × years). Cumulative exposure to pesticides or to organic solvents, for >2400 h, was recorded in 48 and 25 MDS patients, respectively, compared to 27 and four controls (P < 0.00001; RR 3.74; 95% confidence interval 2.02–5.37). Older age and an excess of refractory anaemia with ringed sideroblasts and refractory anaemia with excess of blasts was noted among ‘exposed’ MDS‐patients (group 1), compared to non‐exposed MDS‐patients (group 2). 68.3% patients in group 1 had clonal chromosome changes, compared with 43.2% patients in group 2. Complex karyotypes, −7/7q−, −5/5q−, +8, 7p and 17p aberrations were seen more frequently in group 1, whereas a normal karyotype, isolated 5q− or 20q− occurred more frequently in group 2. The association of exposure to myelotoxic agents with older age at presentation and with unfavourable chromosome changes accounted for the shorter survival observed in ‘exposed’ patients. These data show that occupational exposure to pesticides and organic solvents in our region resulted in an increased RR of developing MDS and that a distinct cytogenetic profile was associated with MDS in ‘exposed’ patients. These findings provide strong indirect evidence that these agents may play a role in the pathogenesis of MDS, preferentially targeting some of the chromosome regions which are frequently involved in therapy‐related myeloid neoplasias.
Relationship between Ileal symbiont intracellularis and porcine proliferative enteritis

The relationship between Ileal symbiont (IS) intracellularis, formerly known as a Campylobacter-like organism, and porcine proliferative enteritis (PE) was studied by use of pigs with experimentally transmitted PE. Twenty one pigs were experimentally inoculated with homogenized ileal mucosa from a pig that died with PE, and 7 were maintained as uninoculated controls. Fecal samples were collected, and pigs were necropsied weekly postinoculation. Light microscopy and electron microscopy were used to examine tissues for lesions of PE and infectious agents. DNA was extracted from the fecal samples and assayed for the presence of sequences specific for IS intracellularis by dot blot hybridization and polymerase chain reaction amplification. IS intracellularis was detected by the polymerase chain reaction in the feces of 20 of 21 inoculated pigs but not in the feces of uninoculated pigs. Seven inoculated pigs but no uninoculated pigs were detected shedding IS intracellularis by dot blot hybridization. Shedding was detected 1 to 5 weeks after inoculation, and clinical signs were seen in the second to fifth weeks after inoculation. Few pigs without lesions of PE were found to shed IS intracellularis. There was a highly significant association between the presence of IS intracellularis in feces or tissue and the presence of microscopic proliferative lesions and between the severity of the lesions of PE and the percentage of IS intracellularis-infected intestinal crypts. Pigs that ceased shedding IS intracellularis were significantly less likely to have proliferative lesions. These and previous reports are consistent with the hypothesis that IS intracellularis is a necessary causative agent of PE.
Renewable Chemical Commodity Feedstocks from Integrated Catalytic Processing of Pyrolysis Oils

A Little Help from Hydrogen Biomass may one day displace petroleum as the chemical industry's primary feedstock. Currently, though, the primary hurdle for incorporating plant-derived material into existing process feeds is the high proportion of oxygen in its molecular frameworks. Rapid heating of the biomass followed by high-temperature treatment with zeolite catalysts can yield tractable quantities of useful commodity compounds such as ethylene and benzene, but much of the carbon is wasted in the process—diverted either toward gaseous CO and CO2, or solid coke. Vispute et al. (p. 1222) show that an intermediate step, in which hydrogen is catalytically incorporated into the heated material prior to zeolite treatment, can substantially raise the yield of useful products by reducing susceptibility to coking. The addition of hydrogen helps boost the yield of useful commodity compounds from pyrolized biomass. Fast pyrolysis of lignocellulosic biomass produces a renewable liquid fuel called pyrolysis oil that is the cheapest liquid fuel produced from biomass today. Here we show that pyrolysis oils can be converted into industrial commodity chemical feedstocks using an integrated catalytic approach that combines hydroprocessing with zeolite catalysis. The hydroprocessing increases the intrinsic hydrogen content of the pyrolysis oil, producing polyols and alcohols. The zeolite catalyst then converts these hydrogenated products into light olefins and aromatic hydrocarbons in a yield as much as three times higher than that produced with the pure pyrolysis oil. The yield of aromatic hydrocarbons and light olefins from the biomass conversion over zeolite is proportional to the intrinsic amount of hydrogen added to the biomass feedstock during hydroprocessing. The total product yield can be adjusted depending on market values of the chemical feedstocks and the relative prices of the hydrogen and biomass.
Soil surface acidity plays a determining role in the atmospheric-terrestrial exchange of nitrous acid

Significance Nitrous acid (HONO) emitted from soil plays an important role in regulating the oxidizing capacity of the atmosphere. Unexpectedly high emissions of HONO are observed from soils with close to neutral pH, where aqueous acid–base and Henry’s law equilibria would predict that nitrite is the dominant nitrogen species. We show that surface acidity of soil minerals rather than aqueous acid–base equilibria controls nitrite speciation in soil, implying that up to 70% of global soils are capable of emitting HONO due to their acidic or close to neutral pH; this suggests that soil nitrite, whether microbially derived or otherwise deposited, likely plays a more widespread role in terrestrial–atmospheric cycling of nitrogen affecting air pollution and climate than previously thought. Nitrous acid (HONO) is an important hydroxyl (OH) radical source that is formed on both ground and aerosol surfaces in the well-mixed boundary layer. Recent studies report the release of HONO from nonacidic soils, although it is unclear how soil that is more basic than the pKa of HONO (∼3) is capable of protonating soil nitrite to serve as an atmospheric HONO source. Here, we used a coated-wall flow tube and chemical ionization mass spectrometry (CIMS) to study the pH dependence of HONO uptake onto agricultural soil and model substrates under atmospherically relevant conditions (1 atm and 30% relative humidity). Experiments measuring the evolution of HONO from pH-adjusted surfaces treated with nitrite and potentiometric titrations of the substrates show, to our knowledge for the first time, that surface acidity rather than bulk aqueous pH determines HONO uptake and desorption efficiency on soil, in a process controlled by amphoteric aluminum and iron (hydr)oxides present. The results have important implications for predicting when soil nitrite, whether microbially derived or atmospherically deposited, will act as a net source or sink of atmospheric HONO. This process represents an unrecognized mechanism of HONO release from soil that will contribute to HONO emissions throughout the day.
Different apoptotic effects of [Pt(O,O′‐acac)(γ‐acac)(DMS)] and cisplatin on normal and cancerous human epithelial breast cells in primary culture

The aim of this study was to determine whether [platinum (Pt)(O,O′‐acetylacetonate (acac))(γ‐acac)(dimethylsulphide (DMS))] is differentially cytotoxic in normal and cancer cells, and to measure comparative levels of cytotoxicity compared with cisplatin in the same cells.
Oculo‐auriculo-vertebral spectrum and the CHARGE association: clinical evidence for a common pathogenetic mechanism

We describe two infants with features of both the oculo-auriculo-vertebral spectrum (OAVS) and the CHARGE association (CA) Both patients are more severely affected than the typical patient with the OAVS Each has facial asymmetry, mandibular hypoplasia, ear abnormalities, hearing impairment, microphthalmia, heart defects, and developmental delay. They, also have features that are not characteristic of either OAVS or CA including torticollis, plagiocephaly, and heminostril. Based on the findings of these patients and others reported in the literature, there appears to be a significant overlap of features between OAVS and CA. and we suggest that these conditions in fact may be produced by the same pathogenetic mechanism. One such mechanism to explain the overlap of these disorders is that both conditions are part of the axial mesodermal spectrum, and represent a dysblastogenetic process. This mechanism may also explain the presence of some of the additional features not normally seen in OAVs and CA but seen in these two infants.
Mathematical modelling of scanner-specific bowtie filters for Monte Carlo CT dosimetry

The purpose of bowtie filters in CT scanners is to homogenize the x-ray intensity measured by the detectors in order to improve the image quality and at the same time to reduce the dose to the patient because of the preferential filtering near the periphery of the fan beam. For CT dosimetry, especially for Monte Carlo calculations of organ and tissue absorbed doses to patients, it is important to take the effect of bowtie filters into account. However, material composition and dimensions of these filters are proprietary. Consequently, a method for bowtie filter simulation independent of access to proprietary data and/or to a specific scanner would be of interest to many researchers involved in CT dosimetry. This study presents such a method based on the weighted computer tomography dose index, CTDIw, defined in two cylindrical PMMA phantoms of 16 cm and 32 cm diameter. With an EGSnrc-based Monte Carlo (MC) code, ratios CTDIw/CTDI100,a were calculated for a specific CT scanner using PMMA bowtie filter models based on sigmoid Boltzmann functions combined with a scanner filter factor (SFF) which is modified during calculations until the calculated MC CTDIw/CTDI100,a matches ratios CTDIw/CTDI100,a, determined by measurements or found in publications for that specific scanner. Once the scanner-specific value for an SFF has been found, the bowtie filter algorithm can be used in any MC code to perform CT dosimetry for that specific scanner. The bowtie filter model proposed here was validated for CTDIw/CTDI100,a considering 11 different CT scanners and for CTDI100,c, CTDI100,p and their ratio considering 4 different CT scanners. Additionally, comparisons were made for lateral dose profiles free in air and using computational anthropomorphic phantoms. CTDIw/CTDI100,a determined with this new method agreed on average within 0.89% (max. 3.4%) and 1.64% (max. 4.5%) with corresponding data published by CTDosimetry (www.impactscan.org) for the CTDI HEAD and BODY phantoms, respectively. Comparison with results calculated using proprietary data for the PHILIPS Brilliance 64 scanner showed agreement on average within 2.5% (max. 5.8%) and with data measured for that scanner within 2.1% (max. 3.7%). Ratios of CTDI100,c/CTDI100, p for this study and corresponding data published by CTDosimetry (www.impactscan.org) agree on average within about 11% (max. 28.6%). Lateral dose profiles calculated with the proposed bowtie filter and with proprietary data agreed within 2% (max. 5.9%), and both calculated data agreed within 5.4% (max. 11.2%) with measured results. Application of the proposed bowtie filter and of the exactly modelled filter to human phantom Monte Carlo calculations show agreement on the average within less than 5% (max. 7.9%) for organ and tissue absorbed doses.
The impact of IFRS on financial report quality in Latin America and the Caribbean

This paper examines the impact generated for the application of International Financial Reporting Standards (IFRS) on financial report quality (accounting quality) for Latin American and Caribbean economies, by using five measurement proxies related to the magnitude of absolute discretionary accruals; accounting quality is assessed during the periods 2006 to 2014. At the same time, the effects of institutional factors and management incentives on the use of such accruals are examined as a mechanism for earnings management. The results show that during the period of application of IFRS, companies report lower magnitude of absolute discretionary accruals, indicating an inverse relationship between these two variables; these results suggest less earnings management, which is the same as higher financial report quality. It is intended to contribute to the literature by presenting generalized findings for the Latin and Caribbean region, by including in this study the majority of countries of the region over a wide period of application of IFRS, in addition to using different measurement metrics to give greater robustness to the findings.
Mutagenesis of Adeno-Associated Virus Type 2 Capsid Protein VP1 Uncovers New Roles for Basic Amino Acids in Trafficking and Cell-Specific Transduction

ABSTRACT The N termini of the capsid proteins VP1 and VP2 of adeno-associated virus (AAV) play important roles in subcellular steps of infection and contain motifs that are highly homologous to a phospholipase A2 (PLA2) domain and nuclear localization signals (NLSs). To more clearly understand how virion components influence infection, we have generated mutations in these regions and examined their effects on subcellular trafficking, capsid stability, transduction, and sensitivity to pharmacological enhancement. All mutants tested assembled into capsids; retained the correct ratio of VP1, VP2, and VP3; packaged DNA similarly to recombinant AAV2 (rAAV2); and displayed similar stability profiles when heat denatured. Confocal microscopy demonstrated that these mutants trafficked through a perinuclear region in the vicinity of the Golgi apparatus, with a subset of mutants displaying more-diffuse localization consistent with an NLS-deficient phenotype. When tested for viral transduction, two mutant classes emerged. Class I (BR1−, BR2−, and BR2+K) displayed partial transduction, whereas class II (VP3only, 75HD/AN, BR3−, and BR3+K) were severely defective. Surprisingly, one class II mutant (BR3+K) trafficked identically to rAAV2 and accumulated in the nucleolus, a step recently described by our laboratory that occurs with wild-type infection. The BR3+K mutant, containing an alanine-to-lysine substitution in the third basic region of VP1, was 10- to 100-fold-less infectious than rAAV2 in transformed cell lines (such as HEK-293, HeLa, and CV1-T cells), but in contrast, it was indistinguishable from rAAV2 in several nontransformed cell lines, as well as in tissues (liver, brain, and muscle) in vivo. Complementation studies with pharmacological adjuvants or adenovirus coinfection suggested that additional positive charges in NLS regions restrict mobilization in the nucleus and limit transduction in a transformed-cell-specific fashion. Remarkably, besides displaying cell-type-specific transduction, this is the first description of a capsid mutant indicating that nuclear entry is not sufficient for AAV-mediated transduction and suggests that additional steps (i.e., subnuclear mobilization or uncoating) limit successful AAV infection.
Fungal β-Glucan, a Dectin-1 Ligand, Promotes Protection from Type 1 Diabetes by Inducing Regulatory Innate Immune Response

β-Glucans are naturally occurring polysaccharides in cereal grains, mushrooms, algae, or microbes, including bacteria, fungi, and yeast. Immune cells recognize these β-glucans through a cell surface pathogen recognition receptor called Dectin-1. Studies using β-glucans and other Dectin-1 binding components have demonstrated the potential of these agents in activating the immune cells for cancer treatment and controlling infections. In this study, we show that the β-glucan from Saccharomyces cerevisiae induces the expression of immune regulatory cytokines (IL-10, TGF-β1, and IL-2) and a tolerogenic enzyme (IDO) in bone marrow–derived dendritic cells as well as spleen cells. These properties can be exploited to modulate autoimmunity in the NOD mouse model of type 1 diabetes (T1D). Treatment of prediabetic NOD mice with low-dose β-glucan resulted in a profound delay in hyperglycemia, and this protection was associated with increase in the frequencies of Foxp3+, LAP+, and GARP+ T cells. Upon Ag presentation, β-glucan–exposed dendritic cells induced a significant increase in Foxp3+ and LAP+ T cells in in vitro cultures. Furthermore, systemic coadministration of β-glucan plus pancreatic β cell Ag resulted in an enhanced protection of NOD mice from T1D as compared with treatment with β-glucan alone. These observations demonstrate that the innate immune response induced by low-dose β-glucan is regulatory in nature and can be exploited to modulate T cell response to β cell Ag for inducing an effective protection from T1D.
Endothelial cellular senescence is inhibited by nitric oxide: Implications in atherosclerosis associated with menopause and diabetes

Senescence may contribute to the pathogenesis of atherosclerosis. Although the bioavailability of nitric oxide (NO) is limited in senescence, the effect of NO on senescence and its relationship to cardiovascular risk factors have not been investigated fully. We studied these factors by investigating senescence-associated β-galactosidase (SA-β-gal) and human telomerase activity in human umbilical venous endothelial cells (HUVECs). Treatment with NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-aminoethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO) and transfection with endothelial NO synthase (eNOS) into HUVECs each decreased the number of SA-β-gal positive cells and increased telomerase activity. The NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME) abolished the effect of eNOS transfection. The physiological concentration of 17β-estradiol activated hTERT, decreased SA-β-gal-positive cells, and caused cell proliferation. However, ICI 182780, an estrogen receptor-specific antagonist, and l-NAME each inhibited these effects. Finally, we investigated the effect of NO bioavailability on high glucose-promoted cellular senescence of HUVECs. Inhibition by eNOS transfection of this cellular senescence under high glucose conditions was less pronounced. Treatment with l-arginine or l-citrulline of eNOS-transfected cells partially inhibited, and combination of l-arginine and l-citrulline with antioxidants strongly prevented, high glucose-induced cellular senescence. These data demonstrate that NO can prevent endothelial senescence, thereby contributing to the anti-senile action of estrogen. The ingestion of NO-boosting substances, including l-arginine, l-citrulline, and antioxidants, can delay endothelial senescence under high glucose. We suggest that the delay in endothelial senescence through NO and/or eNOS activation may have clinical utility in the treatment of atherosclerosis in the elderly.
Implementing culture change in health care: theory and practice.

OBJECTIVES To review some of the key debates relating to the nature of organizational culture and culture change care organizations and systems. METHODS A literature review was conducted that covered both theoretical contributions and published studies of the processes and outcomes of culture change programmes across a range of health and non-health care settings. RESULTS There is little consensus among scholars over the precise meaning of organizational culture. Competing claims exist concerning whether organizational cultures are capable of being shaped by external manipulation to beneficial effect. A range of culture change models has been developed. A number of underlying factors that commonly attenuate culture change programmes can be identified. Key factors that appear to impede culture change across a range of sectors include: inadequate or inappropriate leadership; constraints imposed by external stakeholders and professional allegiances; perceived lack of ownership; and subcultural diversity within health care organizations and systems. CONCLUSIONS Managing organizational culture is increasingly viewed as an essential part of health system reform. To transform the culture of a whole health system such as the UK National Health Service would be a complex, multi-level, and uncertain process, comprising a range of interlocking strategies and supporting tactics unfolding over a period of years.