bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Ueno method for substaging pT1 colorectal adenocarcinoma by depth and width measurement: an interobserver study
Authors: Wang L. M. , Guy R. , Fryer E. , Kartsonaki C. , Gill P. , Hughes C. , Szuts A. , Perera R. , Chetty R. , Mortensen N. 
Published: January 2015

AbstractAimEarly pT1 polyp colorectal cancers (CRCs) present challenges for accurate pathology substaging. Haggitt and Kikuchi stages depend on polyp morphology and are often difficult to apply due to suboptimal orientation or fragmentation, or absence of the muscularis propria in polypectomy or submucosal resection specimens. European guidelines for quality assurance suggest using Ueno's more objective approach, using depth and width measurements beyond muscularis mucosae. We have investigated interobserver variation using Ueno's approach.MethodTen consecutive pT1 polyp CRCs were identified and the slides assessed by six gastrointestinal pathologists for depth and width of invasion. A further 60 polyps were studied by a group of specialist and general pathologists. Agreement was assessed by analysis of variance. A polyp CRC is classified as high risk if it has a depth ≥ 2000 μm or a width ≥ 4000 μm and low risk with a depth < 2000 μm or a width < 4000 μm. Concordance for the dichotomized values was assessed using the kappa statistic.ResultsThe intraclass correlation coefficient (ICC) for depth was 0.83 and for width 0.56 in the 10‐polyp group. The ICC for the 60‐polyp CRCs was 0.67 for depth and 0.37 for width. In both groups, when polyp CRCs are divided into high‐ and low‐risk categories based on depth, there was substantial and moderate agreement (κ = 0.80 and 0.47) but only fair agreement when based on width (κ = 0.34 and 0.35).ConclusionUeno's method has the advantage of being independent of polyp morphology. Our study shows better concordance for depth measurement and reproducibility in nonfragmented specimens, with poorer agreement when based on width.
Daily fluid intake and outcomes in kidney recipients: post hoc analysis from the randomized ABCAN trial
Authors: Weber M. , Berglund D. , Reule S. , Jackson S. , Matas A.J. , Ibrahim H.N. 
Published: January 2015

AbstractGenerous and even excessive fluid intake is routinely recommended to kidney transplant recipients despite minimal evidence to support this practice. We hypothesized that increased fluid intake, ascertained by 24‐h urine volume output, may adversely affect graft outcomes as it would impose an extra workload on a limited number of nephrons. Kidney transplant recipients who were randomized to losartan vs. placebo in the Angiotensin II Blockade for Chronic Allograft Nephropathy (ABCAN) trial (n = 153) underwent baseline, five‐yr biopsies, and annual iothalamate glomerular filtration rate assessment. Recipients with higher urine volume at randomization had higher urinary sodium and also higher urinary protein. The proportion using diuretics or CNI based regimens were similar across urinary volume tertiles. The highest urinary volume tertile (>2.56 L/d) did not predict the development of interstitial volume doubling or end‐stage renal disease (ESRD) from interstitial fibrosis/tubular atrophy (OR = 3.52, 95% CI 0.4, 31.24, p = 0.26), interstitial volume doubling or all‐cause ESRD (OR = 7.04, 95% CI 0.66, 74.87, p = 0.11), and was not associated with the conventional endpoint of doubling serum creatinine, all‐cause ESRD, or death (OR = 0.89, 95% CI 0.21, 3.71, p = 0.87). These results suggest that the current practice of liberal fluid intake may not be beneficial in low risk and mostly Caucasian transplant recipients.
‘Dopamine‐first’ mechanism enables the rational engineering of the norcoclaurine synthase aldehyde activity profile
Authors: Lichman Benjamin R. , Gershater Markus C. , Lamming Eleanor D. , Pesnot Thomas , Sula Altin , Keep Nicholas H. , Hailes Helen C. , Ward John M. 
Published: January 2015

Norcoclaurine synthase (NCS) (EC 4.2.1.78) catalyzes the Pictet–Spengler condensation of dopamine and an aldehyde, forming a substituted (S)‐tetrahydroisoquinoline, a pharmaceutically important moiety. This unique activity has led to NCS being used for both in vitro biocatalysis and in vivo recombinant metabolism. Future engineering of NCS activity to enable the synthesis of diverse tetrahydroisoquinolines is dependent on an understanding of the NCS mechanism and kinetics. We assess two proposed mechanisms for NCS activity: (a) one based on the holo X‐ray crystal structure and (b) the ‘dopamine‐first’ mechanism based on computational docking. Thalictrum flavum NCS variant activities support the dopamine‐first mechanism. Suppression of the non‐enzymatic background reaction reveals novel kinetic parameters for NCS, showing it to act with low catalytic efficiency. This kinetic behaviour can account for the ineffectiveness of recombinant NCS in in vivo systems, and also suggests NCS may have an in planta role as a metabolic gatekeeper. The amino acid substitution L76A, situated in the proposed aldehyde binding site, results in the alteration of the enzyme's aldehyde activity profile. This both verifies the dopamine‐first mechanism and demonstrates the potential for the rational engineering of NCS activity.
Multiphase flow simulation through porous media with explicitly resolved fractures
Authors: Su K. , Latham J.‐P. , Pavlidis D. , Xiang J. , Fang F. , Mostaghimi P. , Percival J. R. , Pain C. C. , Jackson M. D. 
Published: January 2015

AbstractAccurate simulation of multiphase flow in fractured porous media remains a challenge. An important problem is the representation of the discontinuous or near discontinuous behaviour of saturation in real geological formations. In the classical continuum approach, a refined mesh is required at the interface between fracture and porous media to capture the steep gradients in saturation and saturation‐dependent transport properties. This dramatically increases the computational load when large numbers of fractures are present in the numerical model. A discontinuous finite element method is reported here to model flow in fractured porous media. The governing multiphase porous media flow equations are solved in the adaptive mesh computational fluid dynamics codeIC‐FERSTon unstructured meshes. The method is based on a mixed control volume – discontinuous finite element formulation. This is combined with thePN+1DG‐PNDGelement pair, which has discontinuous (orderN+1) representation for velocity and discontinuous (orderN) representation for pressure. A number of test cases are used to evaluate the method's ability to model fracture flow. The first is used to verify the performance of the element pair on structured and unstructured meshes of different resolution. Multiphase flow is then modelled in a range of idealised and simple fracture patterns. Solutions with sharp saturation fronts and computational economy in terms of mesh size are illustrated.
Regímenes de producción y relaciones laborales en el sector chino del automóvil
Authors: LÜTHJE Boy 
Published: January 2015

ResumenLas huelgas en el sector del automóvil acaecidas en China en 2010 suscitaron reformas sustanciales de las relaciones laborales en la provincia de Guangdong. A partir de una investigación empírica exhaustiva en empresas líderes de ensamblaje y en sus suministradoras, el autor construye una tipología de los regímenes de producción para analizar los cambios actuales de las relaciones laborales. Este marco ayuda a entender y a conceptualizar la diversidad creciente de regímenes en la industria china automotriz y la segmentación de la fuerza de trabajo a lo largo de la cadena de suministro. Se concluye con un análisis de las perspectivas de reforma ulterior.
Consulta colectiva y gestión por cuotas en el modelo chino gubernamental de relaciones laborales
Authors: WU Qingjun , SUN Zhaoyang 
Published: January 2015

ResumenEl sistema chino de relaciones laborales consiste en un modelo de consulta colectiva dirigida por el Gobierno y un método de gestión por cuotas heredado de la economía planificada. Gobierno y sindicatos colaboran para lograr cuotas de cobertura, sobre todo a nivel empresarial. Aunque consiguen salvar las reticencias empresariales, la ausencia de verdadera negociación colectiva priva de sustancia los convenios firmados. A partir de entrevistas y de fuentes documentales, los autores concluyen que el Gobierno pretende institucionalizar un marco de relaciones laborales para contener el creciente descontento laboral pero posponiendo pragmáticamente la auténtica negociación colectiva en aras de la estabilidad y el crecimiento.
Safety, Tolerability, and Efficacy of Azilsartan Medoxomil With or Without Chlorthalidone During and After 8 Months of Treatment for Hypertension
Authors: Kipnes Mark S. , Handley Alison , Lloyd Eric , Barger Bruce , Roberts Andrew 
Published: January 2015

A phase 3, 26‐week, open‐label, titrate‐to‐target study (n=418) assessed the safety of azilsartan medoxomil (AZL‐M) alone and with chlorthalidone (CLD), followed by a 6‐week, double‐blind, placebo‐controlled reversal phase with change in clinic diastolic blood pressure (DBP) as the primary endpoint. Target blood pressure (BP) was <140/90 mm Hg (<130/80 mm Hg with diabetes/chronic kidney disease). AZL‐M was initiated at 40 mg once a day (QD), force‐titrated to 80 mg at week 4. CLD 25 mg QD could be added (weeks 8–22), if required, to reach target, followed by additional antihypertensives from week 12. At the end of the open‐label phase, mean change in systolic BP (SBP)/DBP from baseline was −23/−16 mm Hg. The most common adverse events, irrespective of treatment, were dizziness (8.9%) and headache (7.2%). Serious AEs were reported in eight patients (1.9%). Consecutive creatinine elevations ≥50% with values exceeding the upper limit of normal (ULN) were reported in nine (2.2%) patients. All returned to below the 50% threshold; most also returned to below the ULN after drug discontinuation. Mean DBP was maintained through the reversal phase in patients receiving AZL‐M, but increased with placebo (difference: −7.8 mm Hg, 95% confidence interval, −9.8 to −5.8; P<.001). AZL‐M alone or with CLD showed good long‐term safety and stable BP improvements in a titrate‐to‐target approach. BP improvements caused by AZL‐M therapy were safely reversible upon AZL‐M withdrawal.
Facial dynamics and emotional expressions in facial aging treatments
Authors: Michaud Thierry , Gassia Véronique , Belhaouari Lakhdar 
Published: January 2015

SummaryFacial expressions convey emotions that form the foundation of interpersonal relationships, and many of these emotions promote and regulate our social linkages. Hence, the facial aging symptomatological analysis and the treatment plan must of necessity include knowledge of the facial dynamics and the emotional expressions of the face. This approach aims to more closely meet patients' expectations of natural‐looking results, by correcting age‐related negative expressions while observing the emotional language of the face. This article will successively describe patients' expectations, the role of facial expressions in relational dynamics, the relationship between facial structures and facial expressions, and the way facial aging mimics negative expressions. Eventually, therapeutic implications for facial aging treatment will be addressed.
Is tolvaptan indicated for refractory oedema in nephrotic syndrome?
Authors: Park Eun‐Sik , Huh Youn‐sung , Kim Gheun‐Ho 
Published: January 2015

AbstractTolvaptan is useful for correcting dilutional hyponatraemia because of its aquaretic effect. On the other hand, there is a distinct lack of data regarding tolvaptan‐induced natriuresis, although previous studies have demonstrated improvement of congestive symptoms and signs in heart failure patients following tolvaptan treatment. Here, we report the case of a 47‐year‐old man diagnosed with minimal change nephrotic syndrome and whose refractory oedema was immediately controlled by tolvaptan before steroid response was induced. With tolvaptan treatment, patient urine output increased dramatically to approximately 5.5 L/day and body weight decreased by 9 kg over 5 days. Interestingly, urine sodium concentration, fractional excretion of sodium and urine osmolality all increased in response to tolvaptan administration. However, serum sodium concentration was maintained within the normal range, and mild azotaemia was corrected. Tolvaptan was discontinued after 11 days when heavy proteinuria and generalized oedema had been resolved. We discuss the potential mechanisms by which V2 receptor antagonists may stimulate natriuresis in the kidney. In conclusion, tolvaptan may be useful as an adjunctive treatment for oedematous disorders.
Is renal tissue oxygen desaturation during severe hypoxia underestimated? An observational study in term newborn piglets
Authors: Pichler Gerhard , Cheung Po‐Yin , Tze‐Fun Lee , Li Elliott S , Schmölzer Georg M 
Published: January 2015

AbstractThe kidney is an organ highly susceptible to injury by regional tissue oxygen desaturation during hypoxic episodes. Transcutaneous monitoring of renal tissue oxygen saturation is therefore of increasing interest. The aim of the present study was to compare renal tissue oxygen saturation measured by near‐infrared spectroscopy (NIRS) during acute hypoxia in neonates directly on the kidney and transcutaneously. We hypothesized that transcutaneous renal tissue oxygen saturation measurements would be influenced by superficial tissue. Five term newborn piglets were anesthetized, instrumented and exposed to normocapnic hypoxia at an inspired oxygen concentration of 0.14. Regional tissue oxygen saturation (rSO2) was simultaneously measured for comparison with the sensor of NIRS (Invos 5100, Somanetics Corp., Troy, MI, USA) applied directly on the left kidney (renaldirectrSO2) and on the skin of right flank above the right kidney (renalskinrSO2). Cerebral regional tissue oxygenation (cerebralskinrSO2), arterial oxygen saturation, heart rate (HR) and mean arterial pressure (MAP) were also monitored. NIRS parameters were analyzed in 5 s intervals during first 2 min of hypoxia. Hypoxia was achieved with an arterial oxygen desaturation from median (range) 95.3% (86.8–98.0) to 23.5% (13.0–41.0) after 2 min. HR and MAP did not change significantly during hypoxia. There were pronounced and lower renaldirectrSO2 readings when compared with those of renalskinrSO2 with significant differences from 25 to 55 s after initiation of hypoxia. Changes of cerebralskinrSO2 and renalskinrSO2 were similar. Transcutaneous monitoring of renal tissue oxygen saturation may underestimate acute oxygen desaturation of the kidney during hypoxia in neonates.
The rural–urban enigma of allergy: What can we learn from studies around the world?
Authors: Schröder Paul C. , Li Jing , Wong Gary W. K. , Schaub Bianca 
Published: January 2015

AbstractChildhood asthma and related allergic conditions have become the most common chronic disorders in the Western world. Many studies from around the world have demonstrated an increasing trend of asthma prevalence over the last few decades (Lancet, 368, 2004, 733). A few recent reports also suggested that childhood asthma prevalence may be showing a plateau or even a decline in few developed countries. Given the rapid changes in the prevalence over a short period of time, environmental factors are the more likely candidates explaining such trend. One of the most consistent epidemiological findings was that subjects living in the rural areas had lower prevalence of allergies when compared to those from urban areas (Clin Exp Allergy 30, 2000, 187; Pediatr Pulmonol 44, 2009, 793). Clear understanding of the mechanisms of how the environmental determinants in the rural environment may affect the early immune system resulting in lower risk of allergies and asthma will facilitate the development of future primary preventive strategies. In this study, we review recent data from around the world and explore the epidemiology and mechanistic studies that may explain the rural–urban difference of allergies.
Anthroposophic lifestyle and salivary cortisol are associated with a lower risk of sensitization during childhood
Authors: Swartz Jackie , Lindblad Frank , Arinell Hans , Theorell Töres , Alm Johan 
Published: January 2015

AbstractBackgroundInfants from anthroposophic families have low cortisol levels and low risk of IgE‐sensitization during first 2 years of life. Our aim was to study the impact of an anthroposophic lifestyle and cortisol levels at 6 months on allergy sensitization up to age 5 years.MethodsA total of 507 families participated from maternal healthcare centers. Parental lifestyle was categorized as anthroposophic, partly anthroposophic, or non‐anthroposophic. Blood samples for analyzes of sensitization were obtained from parents at inclusion and from children at 6, 12, 24, and 60 months. Salivary samples were collected at home at 6 months.ResultsSensitization increased from 2.9% to 26.0% in the anthroposophic group, from 8.4% to 26.8% in the partly anthroposophic group, and from 19.1% to 44.1% in the non‐anthroposophic group. Children from anthroposophic families had lower cortisol levels in the morning, afternoon, and evening. The odds ratio (OR) for anthroposophic lifestyle was always <1 and lowest at 12 months (OR, 0.10; 95% CI, 0.03–0.36). Adjusting for cortisol levels at 6 months increased these ORs at 12 and 24 months. At the same ages, ORs for sensitization were elevated also for cortisol levels at 6 months. Analyzes in children not sensitized at 6 months confirmed the cortisol‐related risk of sensitization.ConclusionsChildren from families with an anthroposophic lifestyle have lower risk than comparisons of developing sensitization up to 5 years. This risk is partially explained by low cortisol levels during infancy. High cortisol levels at 6 months predict sensitization up to 24 months.
Epichloae infection in a native South African grass, Festuca costata Nees
Authors: McGranahan D. A. , Burgdorf R. , Kirkman K. P. 
Published: January 2015

AbstractFungal endophytes have been documented in almost all terrestrial plant groups. Although the endophyte infection syndrome in agronomic cultivars is well studied, relatively little work addresses questions of spatial ecology and fire effects on epichloae endophyte infection in native grasses, and none, to our knowledge, in sub‐Saharan Africa. We sampled seven populations of the native Festuca costata Nees along the spline of the Drakensberg range in South Africa at several spatial scales, including both recently burned and unburned stands. We tested epichloae presence and prevalence with immunoblot assays, PCR and genetic sequencing. We found epichloae endophytes were present and prevalent (38–98% infection rates depending on location). Variation in infection rates occurred primarily among locations, but also among bunches. There was little evidence that endophyte infection rates varied with fire. Novel evidence of epichloae infection of a native Festuca in South Africa opens the door to several new research questions, from the phylogenetic relationship between epichloae of sub‐Saharan Africa and other continents to the ecological advantages or disadvantages that endophytes confer upon their hosts, especially in a fire‐prone ecosystem vulnerable to global environmental change.
High light‐induced hydrogen peroxide production in Chlamydomonas reinhardtii is increased by high CO2 availability
Authors: Roach Thomas , Na Chae Sun , Krieger‐Liszkay Anja 
Published: January 2015

SummaryThe production of reactive oxygen species (ROS) is an unavoidable part of photosynthesis. Stress that accompanies high light levels and low CO2 availability putatively includes enhanced ROS production in the so‐called Mehler reaction. Such conditions are thought to encourage O2 to become an electron acceptor at photosystem I, producing the ROS superoxide anion radical () and hydrogen peroxide (H2O2). In contrast, here it is shown in Chlamydomonas reinhardtii that CO2 depletion under high light levels lowered cellular H2O2 production, and that elevated CO2 levels increased H2O2 production. Using various photosynthetic and mitochondrial mutants of C. reinhardtii, the chloroplast was identified as the main source of elevated H2O2 production under high CO2 availability. High light levels under low CO2 availability induced photoprotective mechanisms called non‐photochemical quenching, or NPQ, including state transitions (qT) and high energy state quenching (qE). The qE‐deficient mutant npq4 produced more H2O2 than wild‐type cells under high light levels, although less so under high CO2 availability, whereas it demonstrated equal or greater enzymatic H2O2‐degrading capacity. The qT‐deficient mutant stt7‐9 produced the same H2O2 as wild‐type cells under high CO2 availability. Physiological levels of H2O2 were able to hinder qT and the induction of state 2, providing an explanation for why under high light levels and high CO2 availability wild‐type cells behaved like stt7‐9 cells stuck in state 1.
The Arabidopsis ceramidase AtACER functions in disease resistance and salt tolerance
Authors: Wu Jian‐Xin , Li Jian , Liu Zhe , Yin Jian , Chang Zhen‐Yi , Rong Chan , Wu Jia‐Li , Bi Fang‐Cheng , Yao Nan 
Published: January 2015

SummaryCeramidases hydrolyze ceramide into sphingosine and fatty acids. In mammals, ceramidases function as key regulators of sphingolipid homeostasis, but little is known about their roles in plants. Here we characterize the Arabidopsis ceramidase AtACER, a homolog of human alkaline ceramidases. The acer‐1 T‐DNA insertion mutant has pleiotropic phenotypes, including reduction of leaf size, dwarfing and an irregular wax layer, compared with wild‐type plants. Quantitative sphingolipid profiling showed that acer‐1 mutants and the artificial microRNA‐mediated silenced line amiR‐ACER‐1 have high ceramide levels and decreased long chain bases. AtACER localizes predominantly to the endoplasmic reticulum, and partially to the Golgi complex. Furthermore, we found that acer‐1 mutants and AtACER RNAi lines showed increased sensitivity to salt stress, and lines overexpressing AtACER showed increased tolerance to salt stress. Reduction of AtACER also increased plant susceptibility to Pseudomonas syringae. Our data highlight the key biological functions of ceramidases in biotic and abiotic stresses in plants.