bluuebunny/crossref_metadata_2025_split huggingface dataset:
The SKN‐1/Nrf2 transcription factor can protect against oxidative stress and increase lifespan in C. elegans by distinct mechanisms
Authors: Tullet Jennifer M.A. , Green James W. , Au Catherine , Benedetto Alexandre , Thompson Maximillian A. , Clark Emily , Gilliat Ann F. , Young Adelaide , Schmeisser Kathrin , Gems David 
Published: June 2017

SummaryIn C. elegans, the skn‐1 gene encodes a transcription factor that resembles mammalian Nrf2 and activates a detoxification response. skn‐1 promotes resistance to oxidative stress (Oxr) and also increases lifespan, and it has been suggested that the former causes the latter, consistent with the theory that oxidative damage causes aging. Here, we report that effects of SKN‐1 on Oxr and longevity can be dissociated. We also establish that skn‐1 expression can be activated by the DAF‐16/FoxO transcription factor, another central regulator of growth, metabolism, and aging. Notably, skn‐1 is required for Oxr but not increased lifespan resulting from over‐expression of DAF‐16; concomitantly, DAF‐16 over‐expression rescues the short lifespan of skn‐1 mutants but not their hypersensitivity to oxidative stress. These results suggest that SKN‐1 promotes longevity by a mechanism other than protection against oxidative damage.
Rural specialists: The nature of their work and professional satisfaction by geographical location of work
Authors: O'Sullivan Belinda , McGrail Matthew , Russell Deborah 
Published: June 2017

AbstractObjectiveSystematically describe the characteristics of rural specialists, their work and job satisfaction by geographical location of work.DesignCross‐sectional.Setting and participantsThree thousand, four hundred and seventy‐nine medical specialists participating in the 2014 Medicine in Australia: Balancing Employment and Life (MABEL) survey of doctors.Main outcome measureLocation of practice, whether metropolitan, large (>50 000 population) or small regional centres (<50 000 population).ResultSpecialists working in large regional centres had similar characteristics to metropolitan specialists, however, those in small regional centres were more likely men, later career, overseas‐trained and less likely to work privately. Rural specialists had more on‐call requirements and poorer professional development opportunities. However, satisfaction with work hours, remuneration, variety of work, level of responsibility, opportunities to use abilities and overall satisfaction did not differ. Specialists in general medicine and general surgery were significantly more likely to work rurally compared with anaesthetists, particularly in small regional centres, whereas a range of other relevant specialists had lower than the average rural distribution and paediatricians and endocrinologists were significantly less likely to work in large regional centres.ConclusionRural specialists are just as satisfied as metropolitan counterparts reporting equivalent variety and responsibility at work. Better support for on‐call demands and access to professional development could attract more specialists to rural practice. Increased rural training opportunities and regional workforce planning is needed to develop and recruit relevant specialties. Specifically, targeted support is warranted for training and development of specialists in general medicine and general surgery and overseas‐trained specialists, who provide essential services in smaller regional centres.
The Urban Majority and Provisional Recompositions in Yangon
Authors: Simone AbdouMaliq 
Published: June 2017

AbstractYangon is a city where the now predominant modalities of urban transformation arrived late, and after a prolonged period of political repression. As the urban system has been “set loose” to articulate itself to a broader range of inputs and dispositions, many residents attempt to remake long‐honed yet fragile mechanisms of social interchange in provisional forms. This ethos and practice of provisionality emphasizes ensemble work aimed at recomposing the character of local district life in various locations across Yangon. Most importantly, it raises questions of how an urban majority—as a confluence of heterogeneous ways of life that has long been critical to making viable urban lives in the postcolony—have endured and can continue to endure in changing circumstances. The article draws from critical black thought as a means of generating heuristic concepts to explore the ways in which residents of several Yangon districts make productive use of the simultaneity of seemingly contradictory inclinations.
Systematic review: pharmacotherapy for high‐output enterostomies or enteral fistulas
Authors: de Vries F. E. E. , Reeskamp L. F. , van Ruler O. , van Arum I. , Kuin W. , Dijksta G. , Haveman J. W. , Boermeester M. A. , Serlie M. J. 
Published: June 2017

SummaryBackgroundHigh‐output enterocutaneous fistula or enterostomies can cause intestinal failure. There is a wide variety of options in medical management of patients with high output.AimTo systematically review the literature on available pharmacotherapy to reduce output and to propose an algorithm for standard of care.MethodsRelevant databases were systematically reviewed to identify studies on pharmacotherapy for reduction in (high‐) output enterostomies or fistula. Randomised controlled trials and within subjects controlled prospective trials were included. An algorithm for standard of care was generated based on the outcomes of the systematic review.ResultsTwo studies on proton pump inhibitors, six on anti‐motility agents, three on histamine receptor antagonists, one on an α2‐ receptor agonist and eight on somatostatin (analogues) were included. One study examined a proton pump inhibitor and a histamine receptor antagonist within the same patients. Overall, we found evidence for the following medical therapies to be effective: omeprazole, loperamide and codeine, ranitidine and cimetidine. On the basis of these outcomes and clinical experience, we proposed an algorithm for standard of care which consists of high‐dose proton pump inhibitors combined with high‐dose loperamide as the first step followed by addition of codeine in case of insufficient output reduction. So far, there is insufficient evidence for the standard use of somatostatin (analogues).ConclusionsThe available evidence on the efficacy of medication to reduce enterostomy or enterocutaneous fistula output is hampered by low quality studies. We propose an algorithm for standard of care output reduction in these patients.
Systematic review with meta‐analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis
Authors: Costello S. P. , Soo W. , Bryant R. V. , Jairath V. , Hart A. L. , Andrews J. M. 
Published: June 2017

SummaryBackgroundFaecal microbiota transplantation (FMT) is emerging as a novel therapy for ulcerative colitis (UC). Interpretation of efficacy of FMT for UC is complicated by differences among studies in blinding, FMT administration procedures, intensity of therapy and donor stool processing methods.AimTo determine whether FMT is effective and safe for the induction of remission in active UC.MethodsMedline (Ovid), Embase and the Cochrane Library were searched from inception through February 2017. Original studies reporting remission rates following FMT for active UC were included. All study designs were included in the systematic review and a meta‐analysis performed including only randomised controlled trials (RCTs).ResultsThere were 14 cohort studies and four RCTs that used markedly different protocols. In the meta‐analysis of RCTs, clinical remission was achieved in 39 of 140 (28%) patients in the donor FMT groups compared with 13 of 137 (9%) patients in the placebo groups; odds ratio 3.67 (95% CI: 1.82‐7.39, P<.01). Clinical response was achieved in 69 of 140 (49%) donor FMT patients compared to 38 of 137 (28%) placebo patients; odds ratio 2.48 (95% CI: 1.18‐5.21, P=.02). In cohort studies, 39 of 168 (24%; 95% CI: 11%‐40%) achieved clinical remission.ConclusionsDespite variation in processes, FMT appears to be effective for induction of remission in UC, with no major short‐term safety signals. Further studies are needed to better define dose frequency and preparation methods, and to explore its feasibility, efficacy and safety as a maintenance agent.
Diagnosis of inherited bleeding disorders in the genomic era
Authors: Sivapalaratnam Suthesh , Collins Janine , Gomez Keith 
Published: June 2017

SummaryInherited bleeding disorders affect between 1 in 1000 individuals for the most common disorder, von Willebrand Disease, to only 8 reported cases worldwide of alpha‐2‐antiplasmin deficiency. Those with an identifiable abnormality can be divided into disorders of coagulation factors (87%), platelet count and function (8%) and the fibrinolytic system (3%). Of the patients registered in the UK with a bleeding disorder, the remaining 2% are unclassifiable. In addition to bleeding symptoms, patients with an inherited bleeding disorder can manifest other abnormalities, making an accurate and complete diagnosis that reflects the underlying molecular pathology important. Although some inherited bleeding disorders can still be easily diagnosed through a combination of careful clinical assessment and laboratory assays of varying degrees of complexity, there are many where conventional approaches are inadequate. Improvements in phenotyping assays have enhanced our diagnostic armoury but genotyping now offers the most accurate and complete diagnosis for some of these conditions. The advent of next generation sequencing technology has meant that many genes can now be analysed routinely in clinical practice. Here, we discuss the different diagnostic tools currently available for inherited bleeding disorders and suggest that genotyping should be incorporated at an early stage in the diagnostic pathway.
Investigation of the dynamics of agricultural land at the urban fringe: A comparison of two peri‐urban areas in Canada
Authors: Wang Haoluan , Qiu Feng 
Published: June 2017

Key Messages

Disparities in the peri‐urbanization patterns in two study areas are associated with mixed factors.
Distance from a major city is negatively correlated to agricultural land development.
Road density is negatively associated with agricultural land abandonment.
Effects of Antimutagens on the Teratogenicity of N‐Methyl‐N'‐Nitro‐N‐Nitrosoguanidine in Mice
Authors: Morita Yasunobu , Mizutani Masahiro 
Published: June 2017

We examined whether vanillin (VA) and CoCl2∙6H2O(CoCl2), antimutagens, which have mutation suppressing effect, i.e., promotion of cellular repair function in vitro, can modify the teratogenicity in mice caused by N‐methyl‐N'‐nitro‐N‐nitrosoguanidine (MNNG), a direct‐acting monofunctional alkylating agent.ICR mice were treated with MNNG alone (single IP dose of 40 or 60 mg/kg) or in combination with the antimutagen on day 11 of gestation. Embryotoxicity and teratogenicity were examined at term. The incidence of MNNG‐induced syndactyly in the fore‐ and hindlimbs was significantly decreased by VA (50 mg/kg, IP) or CoCl2 (10 mg/kg, IV) and a tendency to decrease in the incidence of oligodactyly was noted as well. On the other hand, the incidence of MNNG‐induced brachydactyly was increased by VA or CoCl2.Though the mechanism of the modifying effects of both VA and CoCl2 on MNNG‐induced malformations could not be delineated in the present study, the results indicate that the antimutagens which stimulate DNA recombination repair in vitro modify the manifestation of malformations caused by teratogens that attack the fetal DNA in the initial teratogenic mechanism.
Two‐dimensional knowledge‐based volumetric reconstruction of the right ventricle documents short‐term improvement in pulmonary hypertension
Authors: Schwaiger Johannes P. , Knight Daniel S. , Kaier Thomas , Gallimore Adele , Denton Christopher P. , Schreiber Benjamin E. , Handler Clive , Coghlan John G. 
Published: June 2017

BackgroundData are scarce about short‐term right ventricular changes in pulmonary hypertension. Two‐dimensional knowledge‐based reconstruction of the right ventricle with 2D echocardiography (2DKBR) has been shown to be a valid alternative to Cardiac MRI.Patients and MethodsIn this longitudinal study 25 pulmonary hypertension patients underwent 2DKBR of the right ventricle, assessment of NT‐proBNP levels and functional class at baseline and after a mean follow‐up of 6.1 months. Patients were followed up clinically for a further mean of 8.2 months. The majority of patients had connective tissue disease (CTD) associated pulmonary arterial hypertension (n=15) or chronic thromboembolic pulmonary hypertension (CTEPH; n=6). A total of 15 patients underwent an intervention, either new targeted therapy, escalation of targeted therapy or pulmonary endarterectomy. A total of 10 clinically stable patients were routinely followed up without any change in therapy.ResultsThere were significant improvements in the right ventricular end‐diastolic volume index (111±29 mL/m² vs 100±36 mL/m²; P=.038), end‐systolic volume index (72±23 mL/m² vs 61±25 mL/m²; P=.001), and ejection fraction (35±10% vs 40±9%; P=.030). Changes in NT‐proBNP levels correlated strongest with changes in end‐systolic volume index (r=−.77; P=<.0001). Four patients experienced clinical worsening during extended follow‐up, dilatation of the right ventricle was associated with clinical worsening.ConclusionIn a CTD and CTEPH dominated patient population significant reverse remodeling and improvement of ejection fraction occurred despite a short follow‐up and was paralleled by significant changes in NT‐proBNP levels. Further right ventricular dilatation was associated with worse clinical outcome. 2DKBR is a feasible substitute for Cardiac MRI to follow‐up right ventricular indices in pulmonary hypertension.
Research and practice for ultra‐high risk for psychosis: A national survey of early intervention in psychosis services in England
Authors: Stain Helen J. , Mawn Lauren , Common Stephanie , Pilton Marie , Thompson Andrew 
Published: June 2017

BackgroundEvidence from meta‐analyses of randomized clinical trials show interventions for young people at ultra‐high risk (UHR) of developing psychosis are effective both clinically and economically. While research evidence has begun to be integrated into clinical guidelines, there is a lack of research on the implementation of these guidelines. This paper examines service provision for UHR individuals in accordance with current clinical guidelines within the National Health Service (NHS) in England.MethodA self‐report online survey was completed by clinical leaders of early intervention in psychosis (EIP) teams (N = 50) within the NHS across England.ResultsOf the 50 EIP teams responding (from 30 NHS trusts), 53% reported inclusion of the UHR group in their service mandate, with age range predominantly 14 to 35 years (81%) and service provided for at least 12 months (53%). Provision of services according to NICE clinical guidelines showed 50% of services offered cognitive behavioural therapy (CBT) for psychosis, and 42% offered family intervention. Contrary to guidelines, 50% of services offered antipsychotic medication. Around half of services provided training in assessment by Comprehensive Assessment of At Risk Mental States, psycho‐education, CBT for psychosis, family work and treatment for anxiety and depression.ConclusionsDespite clear evidence for the benefit of early intervention in this population, current provision for UHR within EIP services in England does not match clinical guidelines. While some argue this is due to a lack of allocated funding, it is important to note the similar variable adherence to clinical guidelines in the treatment of people with established schizophrenia.
Why mutualist partners vary in quality: mutation–selection balance and incentives to cheat in the fig tree–fig wasp mutualism
Authors: Jandér K. Charlotte , Steidinger Brian S. 
Published: June 2017

AbstractMutualisms between species are ecologically ubiquitous but evolutionarily puzzling. Host discrimination mechanisms that reduce the fitness of uncooperative symbionts can stabilise mutualism against collapse, but also present a paradox – if discrimination is effective, why do uncooperative symbionts persist? Here, we test whether mutations or fitness benefits of cheating best explain the prevalence of uncooperative wasps in the fig tree–fig wasp mutualism. By combining theory with field‐collected data we demonstrate that the proportions of pollen‐free wasps of strongly discriminating hosts are reached with reasonable mutation rates. In contrast, in weakly discriminating hosts, the required mutation rates, assuming a single locus, are untenably high, but the required cheater advantages fall within expected ranges. We propose that when discrimination is weak, uncooperative symbionts proliferate until they reach the equilibrium proportion that balances costs and benefits of cheating. Our results suggest that mechanisms that resolve the paradox of uncooperative symbionts differ among host species.
IgG subclasses of FVIII inhibitors in an argentine cohort of severe hemophilia A patients: Analysis by flow cytometry
Authors: Irigoyen M. B. , Primiani L. , Felippo M. , Candela M. , de Bracco M. M. E. , Galassi N. V. 
Published: June 2017

AbstractIntroductionFVIII inhibitors consist of a polyclonal population of antibodies. Previous studies have demonstrated different distribution of IgG subclasses. IgG4 was associated to high level of FVIII inhibitors and failure of immune tolerance induction (ITI) treatment. This study monitored the relative distribution of IgG subclasses of anti‐FVIII in patients with severe hemophilia A (SHA).MethodsAnti‐FVIII antibodies were measured employing an immunomethod, developed in our laboratory, that combines flow cytometry (FC) with microspheres coupled (FVIII‐m) or not (Control‐m) to FVIII. Seventy‐five patients with SHA were studied, 17 without inhibitors (Group I); 58 with inhibitor history, 13 low responders: (LR: Group II), and 45 high responders (HR: Group III). Eight patients undergoing ITI were also included.ResultsWe found anti‐FVIII antibodies in 11 of 27 patients (40%) without inhibitors and in 45 of 48 with inhibitors at the moment of the study. IgG4 was predominant only in the Group III: P=0.02 in patients with low level of inhibitors and P=0.0001 with high titer of inhibitors. Longitudinal analysis performed on patients undergoing ITI showed a gradual decrease of IgG4 values that was associated to improvement of clinical parameters during treatment.ConclusionWe suggest the use of the FC method to supplement functional traditional assays and to help to improve the management of patients with SHA.
PTPRS and PER3 methylation levels are associated with childhood obesity: results from a genome‐wide methylation analysis
Authors: Samblas M. , Milagro F. I. , Mansego M. L. , Marti A. , Martinez J. A. ,   GENOI members
Published: June 2017

SummaryBackgroundThe global prevalence of childhood overweight and obesity has increased in the last years. Epigenetic dysregulation affecting gene expression could be a determinant in early‐life obesity onset and accompanying complications.ObjectiveThe aim of the present investigation was to analyse the putative association between DNA methylation and childhood obesity.MethodsDNA was isolated from white blood cells of 24 children obtained from the GENOI study and was hybridized in a 450K methylation array. Two CpG sites associated with obesity were validated in 91 children by MassArray® EpiTyper™ technology.ResultsGenome‐wide analysis identified 734 CpGs (783 genes) differentially methylated between cases (n = 12) and controls (n = 12). Ingenuity Pathway Analysis showed that these genes were involved in oxidative stress and circadian rhythm signalling pathways. Moreover, the DNA methylation levels of VIPR2, GRIN2D, ADCYAP1R1, PER3 and PTPRS regions correlated with the obesity trait. EpiTyper™ validation also identified significant correlations between methylation levels of CpG sites on PTPRS and PER3 with BMI z‐score.ConclusionsThis study identified several CpG sites and specifically several CpGs in the PTPRS and PER3 genes differentially methylated between obese and non‐obese children, suggesting a role for DNA methylation concerning development of childhood obesity.
Texture, microstructures, and mechanical properties of AlN‐based ceramics with Si3N4–Y2O3 additives
Authors: Liu Cong , Guo Wei‐Ming , Sun Shi‐Kuan , Zou Ji , Wu Shang‐Hua , Lin Hua‐Tay 
Published: June 2017

AbstractTextured AlN‐based ceramics with improved mechanical properties were prepared by hot pressing using Si3N4 and Y2O3 as additives. The introduction of Si3N4–Y2O3 into AlN matrix led to the formation of secondary Y3AlSi2O7N2 and fiber‐like 2Hδ AlN‐polytypoid phases, the partial texture of all crystalline phases, and the fracture mode change from intergranular to transgranular. Consequently, Vickers hardness, fracture toughness and flexural strength of AlN‐based ceramics by the replacement of Y2O3 by Si3N4–Y2O3 increased significantly from 10.4±0.3 GPa, 2.4±0.3 MPa m½ and 333.3±10.3 MPa to 14.2±0.4 GPa, 3.4±0.1 MPa m½ and 389.5±45.5 MPa, respectively.
Regular exercise behavior is related to lower extremity muscle strength in patients with type 2 diabetes: Data from the Multicenter Survey of the Isometric Lower Extremity Strength in Type 2 Diabetes study
Authors: Nomura Takuo , Ishiguro Tomoyasu , Ohira Masayoshi , Ikeda Yukio 
Published: June 2017

AbstractOwing to several contributing factors, continuation of exercise therapy is difficult for patients with type 2 diabetes. One potential factor that has not been well examined is the influence of muscle strength on regular exercise behavior. We examined the relationship between regular exercise behavior and knee extension force (KEF) in 1,442 patients with type 2 diabetes. In sex‐specific univariate analysis, KEF was significantly higher in patients who regularly exercised than in patients who did not regularly exercise. However, age, but not exercise behavior, was significantly different between KEF quartiles. Accordingly, KEF and age might strongly influence exercise behavior. In the multivariate analyses using age and other parameters as covariates, KEF was a significant explanatory variable of regular exercise in both men and women, suggesting that muscle strength could influence regular exercise behavior.
Evaluation of the added value of imaging the pelvis in patients with hepatocellular cancer
Authors: Szklaruk Janio , Kaya Diana , Wei Wei 
Published: June 2017

AbstractBackground and AimThe study aims to evaluate added value of the pelvic portion of the computed tomography (CT) and magnetic resonance imaging (MRI) examination in patients with a primary diagnosis of hepatocellular cancer (HCC).MethodsThe study reviewed the medical records of 478 patients with 881 examinations of the abdomen and pelvis who underwent treatment at our institution between March 2015 and March 2016. These patients were reviewed for presence of pathology in the pelvis, which were classified into two categories as new or old (already known on prior imaging).ResultsOf 478 patients, 230 underwent MRI examination of the abdomen and pelvis, and the other 248 underwent CT scans of these regions. There were no findings on the CT or MRI of the pelvis in 80.5% of patients (n = 385), including 81.5% of those who had CT and 79.6% of those who had MRI. Ninety‐three patients had findings in the pelvis, the most common of which were bone metastases (31 patients), ascites (27 patients), implants (seven patients), and bladder wall thickening (five patients). In only 7.9% of patients, the findings were related to metastatic disease. In 5.4% of all imaging studies revealed a new finding in the pelvis.ConclusionImaging of the pelvis (CT or MRI) does not seem to provide additional information in the majority of cases with HCC. The results suggest that the follow‐up evaluation of patients with HCC may not include a pelvis exam.