bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosing and preventing iron overload
Authors: Ramanathan Ganesh , Olynyk John K. , Ferrari Paolo 
Published: March 2017

AbstractAbsolute or functional iron (Fe) deficiency is an important determinant of anemia in hemodialysis patients and parenteral Fe is routinely used to treat this condition in conjunction with erythropoiesis stimulating agents. While restoration of hemoglobin toward the target range is a good outcome of Fe replacement, it is well known that Fe overload and toxicity may be adverse consequences of this therapy. Dialysis clinical practice guidelines recommend tailoring Fe therapy based on transferrin saturation and serum ferritin levels. Unfortunately, serum Fe markers may not accurately reflect the amount of Fe in the body, because factors such as infections, inflammation, or malignancy can alter serum ferritin levels. Some recent trials in dialysis patients receiving high intravenous Fe doses have shown increased cardiovascular morbidity and mortality and studies using magnetic resonance imaging (MRI) in this population have shown excessive tissue liver iron content (LIC) suggesting Fe overload. While LIC measured by MRI correlates well with LIC quantitated by liver biopsy, it only represents a surrogate marker for total body Fe and its clinical relevance in dialysis patients in terms of mortality and morbidity remains to be demonstrated. Nevertheless, these recent findings challenge the use of current serum Fe markers recommended by clinical guidelines to guide safe Fe therapy in dialysis patients. While not yet established for the routine screening of dialysis patients for Fe overload, MRI should be considered in patients who have received a high cumulative dose of intravenous Fe, or have long cumulative dialysis vintage. Further studies are needed to assess how MRI will alter management.
Hypoacetylation of acetyl‐histone H3 (H3K9ac) as marker of poor prognosis in oral cancer
Authors: Webber Liana P , Wagner Vivian P , Curra Marina , Vargas Pablo A , Meurer Luise , Carrard Vinícius C , Squarize Cristiane H , Castilho Rogério M , Martins Manoela D 
Published: March 2017

AimsEpigenetics refers to changes in cell characteristics that occur independently of modifications to the DNA sequence. Oral carcinogenesis is influenced by modifications in epigenetic mechanisms, including changes in histones, which are proteins that support chromatin remodelling for the dynamic regulation of gene expression and silencing. The dysregulation of histone acetylation can lead to the uncontrolled activity of different genes, thereby triggering events associated with malignant transformation. The aim of this study was to analyse the expression of acetyl‐histone H3 at lys9 (H3K9ac) in oral leucoplakia (OL) and oral squamous cell carcinoma (OSCC) in addition to its association with cell proliferation, epithelial–mesenchymal transition (EMT) and clinical‐pathological findings.Methods and resultsSamples of normal oral mucosa (NOM), OL and OSCC were submitted to immunohistochemical analysis using anti‐H3K9ac, Ki67 and vimentin. Slides were submitted to quantitative analysis regarding the percentage of positive cells. OSCC presented less expression of H3K9ac in comparison to OL (P < 0.01), whereas Ki67 and vimentin levels increased from OL to OSCC (P < 0.001 and P = 0.03, respectively). OSCC patients with poor prognosis had less H3K9ac expression (P = 0.04). The Kaplan–Meier cumulative survival curves also revealed lower survival rates in patients with less H3K9ac expression (P < 0.01).ConclusionsThe present findings suggest that changes in H3K9ac occur during the process of oral carcinogenesis along with an increase in cell proliferation and EMT. The results demonstrate that H3K9ac may be a useful novel prognostic marker for OSCC.
Tumour epithelial and stromal characteristics of hepatocellular carcinomas with abundant fibrous stroma: fibrolamellar versus scirrhous hepatocellular carcinoma
Authors: Kim Young‐Joo , Rhee Hyungjin , Yoo Jeong Eun , Alves Venancio A F , Kim Gi Jeong , Kim Hye Min , Herman Paulo , Chagas Aline , Kim Haeryoung , Park Young Nyun 
Published: March 2017

AimsThe scirrhous variant of hepatocellular carcinoma (S‐HCC) and fibrolamellar HCC (FL‐HCC) are less common subtypes of HCC that are characterized by abundant fibrous stroma. Here, we aimed to investigate differences in the tumour microenvironment and the tumour epithelial cell characteristics of S‐HCC and FL‐HCC.Methods and resultsWhole tissue sections of 17 S‐HCCs and 9 FL‐HCCs were subjected to immunohistochemical stains for keratin 7 (K7), K19, EpCAM, CD56/NCAM, CD163, CD68, pSTAT3, FAP, CCN2 and Ki‐67. FL‐HCC patients were younger than S‐HCC patients (P < 0.001), and chronic liver disease was seen in the background of 88.2% of S‐HCC and in none of the FL‐HCC. CD68 and CD163‐positive tumour‐infiltrating macrophages, and FAP‐positive cancer‐associated fibroblasts (CAFs) were more abundant in the stroma of S‐HCCs compared to FL‐HCCs (all P < 0.05). Tumour epithelial K19 expression was more frequent in S‐HCCs compared to FL‐HCCs (P = 0.023). Significant positive correlations were seen between pSTAT3 expression status in tumour epithelial cells and CAFs, the extent of stromal CAF and macrophage infiltration and K19 expression status. No significant differences were seen for K7, EpCAM, CD56/NCAM, CCN2 expression and Ki‐67 labelling index between S‐HCCs and FL‐HCCs.ConclusionS‐HCC and FL‐HCC are subtypes of HCC with extensive fibrosis, and the nature of the fibrous stroma differs between them. While the stroma of FL‐HCC is composed of dense lamellated collagenous bands with sparse cellular components, S‐HCC demonstrates more abundant CAF and tumour‐infiltrating macrophages and stemness‐related marker expression, suggesting the presence of a complex tumour microenvironment that may influence the aggressive behaviour of S‐HCCs.
Lower urinary tract symptoms/benign prostatic hypertrophy and vascular function: Role of the nitric oxide–phosphodiesterase type 5–cyclic guanosine 3′,5′‐monophosphate pathway
Authors: Higashi Yukihito 
Published: March 2017

AbstractIt is well known that there is an association of lower urinary tract symptoms/benign prostatic hypertrophy with cardiovascular disease, suggesting that lower urinary tract symptoms/benign prostatic hypertrophy is a risk factor for cardiovascular events. Vascular function, including endothelial function and vascular smooth muscle function, is involved in the pathogenesis, maintenance and development of atherosclerosis, leading to cardiovascular events. Vascular dysfunction per se should also contribute to lower urinary tract symptoms/benign prostatic hypertrophy. Both lower urinary tract symptoms/benign prostatic hypertrophy and vascular dysfunction have cardiovascular risk factors, such as hypertension, dyslipidemia, diabetes mellitus, aging, obesity and smoking. Inactivation of the phosphodiesterase type 5–cyclic guanosine 3′,5′‐monophosphate–nitric oxide pathway causes lower urinary tract symptoms/benign prostatic hypertrophy through an enhancement of sympathetic nervous activity, endothelial dysfunction, increase in Rho‐associated kinase activity and vasoconstriction, and decrease in blood flow of pelvic viscera. Both endogenous nitric oxide and exogenous nitric oxide act as vasodilators on vascular smooth muscle cells through an increase in the content of cyclic guanosine 3′,5′‐monophosphate, which is inactivated by phosphodiesterase type 5. In a clinical setting, phosphodiesterase type 5 inhibitors are widely used in patients with lower urinary tract symptoms/benign prostatic hypertrophy. Phosphodiesterase type 5 inhibitors might have beneficial effects on vascular function through not only inhibition of cyclic guanosine 3′,5′‐monophosphate degradation, but also increases in testosterone levels and nitric oxide bioavailability, increase in the number and improvement of the function of endothelial progenitor cells, and decrease in insulin resistance. In the present review, the relationships between lower urinary tract symptoms/benign prostatic hypertrophy, the phosphodiesterase type 5–nitric oxide–cyclic guanosine 3′,5′‐monophosphate pathway, vascular function and cardiovascular outcomes are examined.
Cohort study of Gorlin syndrome with emphasis on standardised phenotyping and quality of life assessment
Authors: Huq Aamira J. , Bogwitz Michael , Gorelik Alexandra , Winship Ingrid M. , White Susan M. , Trainer Alison H. 
Published: March 2017

BackgroundGorlin syndrome (nevoid basal cell carcinoma syndrome) is a rare genetic predisposition to basal cell carcinomas (BCC), keratocysts of the jaw and calcification of the falx cerebri among other clinical features. With the advent of sonic hedgehog inhibitors for the treatment of BCC, it is timely to establish a cohort of individuals with Gorlin syndrome and collect standardised phenotypic information on these individuals. Moreover, the health‐related quality of life (QoL) in individuals with Gorlin syndrome is not well studied.AimTo establish a Victorian cohort of Gorlin syndrome and study the QoL in these individuals.MethodsPhenotypic data were obtained by reviewing medical records of individuals attending two major tertiary/quaternary genetic referral centres in Victoria, followed by telephone or face‐to‐face interviews where possible. QoL information was obtained utilising the AQoL‐6D quality of life survey form.ResultsThe median number of BCC in the 19 individuals studied was 17.5 (interquartile range 3–70). The number of patients with ≥100 BCC in this group was similar to a previously described national cohort (22.2 vs 27% respectively). A total of 58% of referrals to the genetics clinics originated from maxillofacial surgeons and 42% from dermatologists. Individuals with ≥100 BCC had worse median QoL scores compared to those with <100 BCC (36 vs 29, P‐value of 0.031).ConclusionThe clinical features in our cohort were congruent with those previously described in Australia. The QoL is adversely correlated with increased BCC burden.
What drives perceived work intensity in neonatal intensive care units? Empirical evidence from a longitudinal study
Authors: Sülz Sandra , Langhammer Kristina , Becker‐Peth Michael , Roth Bernhard 
Published: March 2017

AbstractAimTo investigate the drivers of perceived work intensity among neonatal intensive care unit nurses.BackgroundThe consequences of high work intensity have been studied extensively, yet setting‐specific drivers have received less attention.DesignProspective, longitudinal and monocentric study design.MethodsThe study combined data from standardized diary surveys and passive observations of study nurses. Data were collected over a period of 6 months in 2015. We considered two scenarios: (1) the perception of normal work intensity relative to non‐normal work intensity; and (2) the perception of high work intensity relative to non‐high work intensity. Perceived work intensity was then analysed using mixed‐effects probit regression models.ResultsWe found that when direct and indirect care were provided more frequently than administrative and other duties were performed, the evaluated nurses perceived their work intensity to be higher. We also found that nurses who more frequently provided care for sick and preterm infants were less likely to perceive their work intensity as normal and this effect was stronger among nurses who cared for infants under mechanical ventilation than nurses who cared for infants receiving non‐invasive respiratory support.ConclusionIn the interest of both nurses and infants and the pursuit of a reduction in perceived work intensity and the provision of better neonatal care, caution must be applied when assigning infants to nurses. Further research is needed to validate these findings using a multicentre study design.
A novel bispecific molecule delivered by recombinant AAV2 suppresses ocular inflammation and choroidal neovascularization
Authors: Li Yiming , Zhu Ping , Verma Amrisha , Prasad Tuhina , Deng Hongxin , Yu Dechao , Li Qiuhong 
Published: March 2017

AbstractElevated vascular endothelial growth factor (VEGF) and complement activation are implicated in the pathogenesis of different ocular diseases. The objective of this study was to investigate the hypothesis that dual inhibition of both VEGF and complement activation would confer better protection against ocular inflammation and neovascularization. In this study, we engineered a secreted chimeric VEGF inhibitor domain (VID), a complement inhibitor domain (CID) and a dual inhibitor (ACVP1). Vectors expressing these three inhibitors were constructed and packaged into AAV2 (sextY‐F) particles. The expression and secretion of the proteins were validated by Western blot. The effects of these inhibitors expressed from AAV2 vectors were examined in endotoxin‐induced uveitis (EIU), experimental autoimmune uveoretinitis (EAU) and choroidal neovascularization (CNV) mouse models. The AAV2 vectors expressing the CID‐ and ACVP1‐attenuated inflammation in EIU and EAU model, whereas the vector expressing VID showed improved retinal structure damaged by EAU, but not affect the infiltration of inflammatory cells in EAU or EIU eyes. Both VID and CID vectors improved laser‐induced retinal and choroid/RPE injuries and CNV, whereas ACVP1 vector provided significantly better protection. Our results suggest that gene therapy targeting VEGF and complement components could provide an innovative and long‐term strategy for ocular inflammatory and neovascular diseases.
Enhanced spatial resolution in vector potential photoelectron microscopy
Authors: BROWNING R. 
Published: March 2017

SummaryThe spatial resolution of the vector potential photoelectron microscope is determined by the maximum size of the cyclotron orbits of the imaged electrons at the surface of a sample. It is straightforward to calculate the spatial resolution for any imaged electron energy given the magnetic field strength. However, in low‐energy secondary photoelectron images from an aluminium–calcium metal matrix alloy, we find the apparent spatial resolution is significantly higher than expected. A possible explanation for the enhanced resolution is that the low‐energy cyclotron orbits are distorted when passing from one area of work function to another and the image is dependent on the surface field distribution.
Comparative genomic analyses of transport proteins encoded within the red algae Chondrus crispus, Galdieria sulphuraria, and Cyanidioschyzon merolae11
Authors: Lee Justin , Ghosh Shounak , Saier Milton H. 
Published: March 2017

Galdieria sulphuraria and Cyanidioschyzon merolae are thermo‐acidophilic unicellular red algal cousins capable of living in volcanic environments, although the former can additionally thrive in the presence of toxic heavy metals. Bioinformatic analyses of transport systems were carried out on their genomes, as well as that of the mesophilic multicellular red alga Chondrus crispus (Irish moss). We identified transport proteins related to the metabolic capabilities, physiological properties, and environmental adaptations of these organisms. Of note is the vast array of transporters encoded in G. sulphuraria capable of importing a variety of carbon sources, particularly sugars and amino acids, while C. merolae and C. crispus have relatively few such proteins. Chondrus crispus may prefer short chain acids to sugars and amino acids. In addition, the number of encoded proteins pertaining to heavy metal ion transport is highest in G. sulphuraria and lowest in C. crispus. All three organisms preferentially utilize secondary carriers over primary active transporters, suggesting that their primary source of energy derives from electron flow rather than substrate‐level phosphorylation. Surprisingly, the percentage of inorganic ion transporters encoded in C. merolae more closely resembles that of C. crispus than G. sulphuraria, but only C. crispus appears to signal via voltage‐gated cation channels and possess a Na+/K+‐ATPase and a Na+ exporting pyrophosphatase. The results presented in this report further our understanding of the metabolic potential and toxic compound resistances of these three organisms.
Estimation of Heritability for Growth‐related Traits in Paralichthys olivaceus Using a Microsatellite‐based Pedigree
Authors: Liu Yongxin , Yang Runqing , Liu Yi , Sun Zhaohui 
Published: March 2017

AbstractThis study estimated the heritabilities of growth‐related traits in Paralichthys olivaceus using a microsatellite‐based pedigree. A set of 48 microsatellite markers located at different regions of each linkage group were selected from the published genetic map. The flounders used here originated from the Bohai Sea and the broodstock was mated to produce 10 full‐sib families. The resulting fish were assayed to obtain the probabilities of exclusion (Excl 1 and Excl 2) for each marker. Sixteen markers showed low Excl 1 and Excl 2 values, eight had high probability values, and the remainder showed intermediate probability values. A marker‐based pedigree of four full‐factorial crosses (FFCs) was constructed using the eight markers with high Excl 1 and Excl 2 probabilities. Body measurements (such as body weight and total length) were determined in 752–943 individuals from the FFCs at 200, 400, and 500 d of age. An animal model was used for single‐trait analyses and estimated moderate heritabilities, ranging from 0.23 to 0.48. These results demonstrate that markers with high exclusion probabilities provide an efficient tool for parentage assignments and genetic analyses in Japanese flounder. Marker‐assisted estimation of heritability is an efficient approach to genetically improve growth traits in this species.
Identification Based on Difference‐in‐Differences Approaches with Multiple Treatments
Authors: Fricke Hans 
Published: March 2017

AbstractThis paper discusses identification based on difference‐in‐differences (DiD) approaches with multiple treatments. It shows that an appropriate adaptation of the common trend assumption underlying the DiD strategy for the comparison of two treatments restricts the possibility of effect heterogeneity for at least one of the treatments. The required assumption of effect homogeneity is likely to be violated because of non‐random assignment to treatment based on both observables and unobservables. However, this paper shows that, under certain conditions, the DiD estimate comparing two treatments identifies a lower bound in absolute values on the average treatment effect on the treated compared to the unobserved non‐treatment state, even if effect homogeneity is violated. This is possible if the treatments have ordered treatment effects, that is, in expectation, the effects of both treatments compared to no treatment have the same sign, and one treatment has a stronger effect than the other treatment on the respective recipients. Such assumptions are plausible if treatments are ordered or vary in intensity.
Naproxen Inhibits UVB‐induced Basal Cell and Squamous Cell Carcinoma Development in Ptch1+/−/SKH‐1 Hairless Mice
Authors: Chaudhary Sandeep C. , Waseem Mohammad , Rana Mehtab , Xu Hui , Kopelovich Levy , Elmets Craig A. , Athar Mohammad 
Published: March 2017

AbstractNaproxen possesses anti‐proliferative and pro‐apoptotic effects besides its known anti‐inflammatory functions. Here, we demonstrate the anticancer effects of naproxen against UVB‐induced basal cell carcinoma (BCCs) and squamous cell carcinoma (SCCs) in a highly susceptible murine model of UVB carcinogenesis. Naproxen significantly inhibited UVB‐induced BCCs and SCCs in this model. Tumor number and volume were significantly decreased (P < 0.005 and P < 0.05, respectively). Inhibition in UVB‐induced SCCs and BCCs was 77% and 86%, respectively, which was associated with reduced PCNA and cyclin D1 and increased apoptosis. As expected, inflammation‐related iNOS, COX‐2 and nuclear NFκBp65 were also diminished by naproxen treatment. Residual tumors excised from naproxen‐treated animal were less invasive and showed reduced expression of epithelial‐mesenchymal transition (EMT) markers N‐cadherin, Vimentin, Snail and Twist with increased expression of E‐cadherin. In BCC and SCC cells, naproxen‐induced apoptosis and activated unfolded protein response (UPR) signaling with increased expression of ATF4, p‐eIF2α and CHOP. Employing iRNA‐based approaches, we found that naproxen‐induced apoptosis was regulated by CHOP as sensitivity of these cutaneous neoplastic cells for apoptosis was significantly diminished by ablating CHOP. In summary, these data show that naproxen is a potent inhibitor of UVB‐induced skin carcinogenesis. ER stress pathway protein CHOP may play an important role in inducing apoptosis in cancer cells.
Reproductive performance of postpartum ewes treated with insulin or progesterone hormones in association with ram effect
Authors: Ferreira‐Silva JC , Basto SRL , Tenório Filho F , Moura MT , Silva Filho ML , Oliveira MAL 
Published: March 2017

ContentsThe reproductive performance of postpartum Santa Inês (SI) and Morada Nova (MN) ewes treated with insulin or progesterone hormones in association with ram effect was evaluated. Ewes from SI (n = 69) and MN (n = 69) breeds were randomly allocated to three groups of each breed (T1—ram effect only; T2—ram effect + insulin; T3—ram effect + progesterone). Progesterone concentrations (ηg/ml; mean ± SD) before and after introduction of rams (n = 6) were 0.51 ± 0.22 and 3.78 ± 0.68 (T1), 0.65 ± 0.21 and 3.77 ± 0.78 (T2) and 0.52 ± 0.21 and 3.84 ± 0.84 (T3) in SI ewes and 0.74 ± 0.19 and 3.71 ± 0.56 (T1), 0.70 ± 0.21 and 3.79 ± 0.75 (T2) and 0.81 ± 0.14 and 3.87 ± 0.80 (T3) in MN ewes, respectively. Thus, lower progesterone concentrations were found before the introduction of rams (p < .05). After the introduction of rams, preovulatory peaks of LH (ηg/ml) occurred at 28 (T1), 44 (T2) and 48 (T3) hr in SI ewes and at 64 (T1), 40 (T2) and 44 (T3) hr in MN ewes. The mean number of ovulations was similar between groups (p > .05), was 1.3 ± 0.51 (T1), 1.5 ± 0.54 (T2) and 1.6 ± 0.51 (T3) in SI ewes and 1.3 ± 0.51 (T1), 1.6 ± 0.51 (T2) and 1.6 ± 0.51 (T3) in MN ewes. In conclusion, the ram effect alone is effective at inducing and synchronizing oestrus in sheep under postpartum anoestrus, irrespective of hormone treatments.
Co‐morbidities in severe asthma: Clinical impact and management
Authors: Porsbjerg Celeste , Menzies‐Gow Andrew 
Published: March 2017

ABSTRACT
Patients with severe asthma represent a minority of the total asthma population, but carry a majority of the morbidity and healthcare costs. Achieving better asthma control in this group of patients is therefore of key importance. Systematic assessment of patients with possible severe asthma to identify treatment barriers and triggers of asthma symptoms, including co‐morbidities, improves asthma control and reduces healthcare costs and is recommended by international guidelines on management of severe asthma.This review provides the clinician with an overview of the prevalence and clinical impact of the most common co‐morbidities in severe asthma, including chronic rhinosinusitis, nasal polyposis, allergic rhinitis, dysfunctional breathing, vocal cord dysfunction, anxiety and depression, obesity, obstructive sleep apnoea syndrome (OSAS), gastroesophageal reflux disease (GERD), bronchiectasis, allergic bronchopulmonary aspergillosis (ABPA) and eosinophilic granulomatous with polyangiitis (EGPA). Furthermore, the review offers a summary of recommended diagnostic and management approaches for each co‐morbidity. Finally, the review links co‐morbid conditions to specific phenotypes of severe asthma, in order to guide the clinician on which co‐morbidities to look for in specific patients.