bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human UDP‐Glucuronosyltransferases 1A1, 1A3, 1A9, 2B4 and 2B7 are Inhibited by Diethylstilbestrol
Authors: Zhu Liangliang , Xiao Ling , Li Wenjuan , Zhang Yuan , Han Wenwen , Zhu Yu , Ge Guangbo , Yang Ling 
Published: May 2016

AbstractInhibition of UDP‐glucuronosyltransferases (UGTs) can result in many undesired side effects. Diethylstilbestrol (DES), a synthetic oestrogen famous for its multiple toxicities, was once widely administered to women in high dosages and now still gains application in clinics. This study investigated in vitro inhibitory effects of DES on catalytic activities of human UGTs, aiming at disclosing new potential toxic mechanisms on the basis of interactions between DES and metabolizing enzymes. DES (10 μM) could decrease activities of UGT1A1, 1A3, 1A9, 2B4 and 2B7 in catalysing 4‐methylumbelliferone (4‐Mu) glucuronidation. Further kinetic analyses showed that inhibition of these UGTs followed competitive (UGT1A1 and 1A9), mixed (UGT1A3 and 2B4) and non‐competitive (UGT2B7) mechanisms, with Ki values ranging from 0.91 to 4.1 μM. The inhibition potentials of UGT1A9 and 2B7 in human liver microsomes (HLM) were further tested by employing propofol and zidovudine as probe substrates, respectively. The inhibition of human liver microsomal UGT1A9 followed mixed mechanism, with the Ki value of 3.5 μM and α of 4.1. On the other hand, DES displayed non‐competitive inhibition against UGT2B7 in HLM, with the Ki value of 9.8 μM. The risks of in vivo inhibition of human UGTs were also predicted by calculation of plasma C/Ki values. Results suggest that DES can trigger in vivo inhibition of UGT1A1, 1A3, 1A9, 2B4 and 2B7 after the intravenous administration in high doses.
Comparative analysis between RQ‐PCR and digital‐droplet‐PCR of immunoglobulin/T‐cell receptor gene rearrangements to monitor minimal residual disease in acute lymphoblastic leukaemia
Authors: Della Starza Irene , Nunes Vittorio , Cavalli Marzia , De Novi Lucia Anna , Ilari Caterina , Apicella Valerio , Vitale Antonella , Testi Anna Maria , Del Giudice Ilaria , Chiaretti Sabina , Foà Robin , Guarini Anna 
Published: May 2016

SummaryReal‐time quantitative polymerase chain reaction (RQ‐PCR) is a standardized tool for minimal residual disease (MRD) monitoring in acute lymphoblastic leukaemia (ALL). The applicability of this technology is limited by the need of a standard curve based on diagnostic DNA. The digital droplet PCR (ddPCR) technology has been recently applied to various medical fields, but its use in MRD monitoring is under investigation. In this study, we analysed 50 ALL cases by both methods in two phases: in the first, we established analytical parameters to investigate the applicability of this new technique; in the second, we analysed MRD levels in 141 follow‐up (FU) samples to investigate the possible use of ddPCR for MRD monitoring in ALL patients. We documented that ddPCR has sensitivity and accuracy at least comparable to those of RQ‐PCR. Overall, the two methods gave concordant results in 124 of the 141 analysed MRD samples (88%, P = 0·94). Discordant results were found in 12% borderline cases.The results obtained prove that ddPCR is a reliable method for MRD monitoring in ALL, with the advantage of quantifying without the need of the calibration curves. Its application in a cohort of patients with a longer FU will conclusively define its clinical predictive value.
Women on the edge: Workplace stress at universities in North America
Authors: Mountz Alison 
Published: May 2016

Key Messages

There is an important, under‐explored relationship between deteriorating work conditions in the neoliberal university and the deteriorating well‐being and health of women working at universities.
Women faculty struggle with fertility, mental health and well‐being, and other physical manifestations of stress.
There are many strategies that universities, departments, and individuals can pursue to improve work conditions for all university faculty.
Cognitive Architecture of Belief Reasoning in Children and Adults: A Primer on the Two‐Systems Account
Authors: Low Jason , Apperly Ian A. , Butterfill Stephen A. , Rakoczy Hannes 
Published: May 2016

AbstractCharacterizing the cognitive architecture of human mindreading forces us to address two puzzles in people's attributions of belief: Why children show inconsistent expectations about others' belief‐based actions, and why adults' reasoning about belief is sometimes automatic and sometimes not. The seemingly puzzling data suggest that humans have many mindreading systems that use different models of mental representations. The efficient system is shared by infants, children, and adults, and uses a minimal model of the mind, which enables belief‐like states to be tracked. The flexible system develops late and uses a canonical model, which incorporates propositional attitudes. A given model's operation has signature limits that produce performance contrasts, in children as well as adults, between certain types of mindreading tasks.
Tea tree oil: contact allergy and chemical composition
Authors: de Groot Anton C. , Schmidt Erich 
Published: May 2016

SummaryIn this article, contact allergy to, and the chemical composition of, tea tree oil (TTO) are reviewed. This essential oil is a popular remedy for many skin diseases, and may be used as neat oil or be present in cosmetics, topical pharmaceuticals and household products. Of all essential oils,TTOhas caused most (published) allergic reactions since the first cases were reported in 1991. In routine testing, prevalences of positive patch test reactions have ranged from 0.1% to 3.5%. Nearly 100 allergic patients have been described in case reports and case series. The major constituents of commercialTTOare terpinen‐4‐ol, γ‐terpinene, 1,8‐cineole, α‐terpinene, α‐terpineol,p‐cymene, and α‐pinene. FreshTTOis a weak to moderate sensitizer, but oxidation increases its allergenic potency. The major sensitizers appear to be ascaridole, terpinolene, α‐terpinene, 1,2,4‐trihydroxymenthane, α‐phellandrene, and limonene. The clinical picture of allergic contact dermatitis caused byTTOdepends on the products used. Most reactions are caused by the application of pure oil; cosmetics are the culprits in a minority of cases. Patch testing may be performed with 5% oxidizedTTO. Co‐reactivity to turpentine oil is frequent, and there is an overrepresentation of reactions to fragrance mixI,Myroxylon pereirae, colophonium, and other essential oils.
Dealing with Cumulative Biodiversity Impacts in Strategic Environmental Assessment: A New Frontier for Conservation Planning
Authors: Whitehead Amy L. , Kujala Heini , Wintle Brendan A. 
Published: May 2016

AbstractBiodiversity impact assessments under threatened species legislation often focus on individual development proposals at a single location, usually for a single species, leading to inadequate assessments of multiple impacts that accumulate over large spatial scales for multiple species. Regulations requiring ad‐hoc assessments can lead to “death by a thousand cuts,” where biodiversity is degraded by many small impacts that individually do not appear to threaten species’ persistence. Spatial prioritization methods can improve the efficiency of decision‐making by explicitly considering cumulative impacts of multiple proposed developments on multiple species over large spatial scales. We present an assessment approach and a unique case study in which spatial prioritization tools were used to support strategic assessment of a large development plan in Western Australia. The application of the approach helped identify relatively minor alterations to development plans that resulted in reductions in biodiversity impacts and informed expansion of the protected area network. Using these tools to assess trade‐offs between conservation and development will help identify planning footprints that minimize biodiversity losses.
Overweight and obesity: a remaining problem in women treated for severe gestational diabetes
Authors: Hildén K. , Hanson U. , Persson M. , Fadl H. 
Published: May 2016

AbstractAimTo analyse the impact of overweight and obesity on the risk of adverse maternal outcomes and fetal macrosomia in pregnancies of women treated for severe gestational diabetes.MethodsThis was a population‐based cohort study including all singleton pregnancies in Sweden without pre‐existing diabetes in the period 1998–2012. Only mothers with an early‐ pregnancy BMI of ≥ 18.5 kg/m² were included. Logistic regression analysis was used to determine odds ratios with 95% CIs for maternal outcomes and fetal growth. Analyses were stratified by maternal gestational diabetes/non‐gestational diabetes to investigate the impact of overweight/obesity in each group.ResultsOf 1 249 908 singleton births, 13 057 were diagnosed with gestational diabetes (1.0%). Overweight/obesity had the same impact on the risks of caesarean section and fetal macrosomia in pregnancies with and without gestational diabetes, but the impact of maternal BMI on the risk of preeclampsia was less pronounced in women with gestational diabetes. Normal‐weight women with gestational diabetes had an increased risk of caesarean section [odds ratio 1.26 (95% CI 1.16–1.37)], preeclampsia [odds ratio 2.03 (95% CI 1.71–2.41)] and large‐for‐gestational‐age infants [odds ratio 2.25 (95% CI 2.06–2.46)]. Risks were similar in the overweight group without gestational diabetes, caesarean section [odds ratio 1.34 (1.33–1.36)], preeclampsia odds ratio [1.76 (95% CI 1.72–1.81)], large‐for‐gestational‐age [odds ratio 1.76 (95% CI 1.74–1.79)].ConclusionsMaternal overweight and obesity is associated with similar increments in risks of adverse maternal outcomes and delivery of large‐for‐gestational‐age infants in women with and without gestational diabetes. Obese women with gestational diabetes are defined as a high‐risk group. Normal‐weight women with gestational diabetes have similar risks of adverse outcomes to overweight women without gestational diabetes.
Involvement of GATOR complex genes in familial focal epilepsies and focal cortical dysplasia
Authors: Weckhuysen Sarah , Marsan Elise , Lambrecq Virginie , Marchal Cécile , Morin‐Brureau Mélanie , An‐Gourfinkel Isabelle , Baulac Michel , Fohlen Martine , Kallay Zetchi Christine , Seeck Margitta , de la Grange Pierre , Dermaut Bart , Meurs Alfred , Thomas Pierre , Chassoux Francine , Leguern Eric , Picard Fabienne , Baulac Stéphanie 
Published: May 2016

SummaryObjectiveThe discovery of mutations in DEPDC5 in familial focal epilepsies has introduced a novel pathomechanism to a field so far dominated by ion channelopathies. DEPDC5 is part of a complex named GAP activity toward RAGs (GATOR) complex 1 (GATOR1), together with the proteins NPRL2 and NPRL3, and acts to inhibit the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) pathway. GATOR1 is in turn inhibited by the GATOR2 complex. The mTORC1 pathway is a major signaling cascade regulating cell growth, proliferation, and migration. We aimed to study the contribution of GATOR complex genes to the etiology of focal epilepsies and to describe the associated phenotypical spectrum.MethodsWe performed targeted sequencing of the genes encoding the components of the GATOR1 (DEPDC5, NPRL2, and NPRL3) and GATOR2 (MIOS, SEC13, SEH1L, WDR24, and WDR59) complex in 93 European probands with focal epilepsy with or without focal cortical dysplasia. Phospho‐S6 immunoreactivity was used as evidence of mTORC1 pathway activation in resected brain tissue of patients carrying pathogenic variants.ResultsWe identified four pathogenic variants in DEPDC5, two in NPRL2, and one in NPRL3. We showed hyperactivation of the mTORC1 pathway in brain tissue from patients with NPRL2 and NPRL3 mutations. Collectively, inactivating mutations in GATOR1 complex genes explained 11% of cases of focal epilepsy, whereas no pathogenic mutations were found in GATOR2 complex genes. GATOR1‐related focal epilepsies differ clinically from focal epilepsies due to mutations in ion channel genes by their association with focal cortical dysplasia and seizures emerging from variable foci, and might confer an increased risk of sudden unexplained death in epilepsy (SUDEP).SignificanceGATOR1 complex gene mutations leading to mTORC1 pathway upregulation is an important cause of focal epilepsy with cortical malformations and represents a potential target for novel therapeutic approaches.
Passerines may be sufficiently plastic to track temperature‐mediated shifts in optimum lay date
Authors: Phillimore Albert B. , Leech David I. , Pearce‐Higgins James W. , Hadfield Jarrod D. 
Published: May 2016

AbstractProjecting the fates of populations under climate change is one of global change biology's foremost challenges. Here, we seek to identify the contributions that temperature‐mediated local adaptation and plasticity make to spatial variation in nesting phenology, a phenotypic trait showing strong responses to warming. We apply a mixed modeling framework to a Britain‐wide spatiotemporal dataset comprising >100 000 records of first egg dates from four single‐brooded passerine bird species. The average temperature during a specific time period (sliding window) strongly predicts spatiotemporal variation in lay date. All four species exhibit phenological plasticity, advancing lay date by 2–5 days °C−1. The initiation of this sliding window is delayed further north, which may be a response to a photoperiod threshold. Using clinal trends in phenology and temperature, we are able to estimate the temperature sensitivity of selection on lay date (B), but our estimates are highly sensitive to the temporal position of the sliding window. If the sliding window is of fixed duration with a start date determined by photoperiod, we findBis tracked by phenotypic plasticity. If, instead, we allow the start and duration of the sliding window to change with latitude, we find plasticity does not trackB, although in this case, at odds with theoretical expectations, our estimates ofBdiffer across latitude vs. longitude. We argue that a model combining photoperiod and mean temperature is most consistent with current understanding of phenological cues in passerines, the results from which suggest that each species could respond to projected increases in spring temperatures through plasticity alone. However, our estimates ofBrequire further validation.
Climate change amplifies gross nitrogen turnover in montane grasslands of Central Europe in both summer and winter seasons
Authors: Wang Changhui , Chen Zhe , Unteregelsbacher Sebastian , Lu Haiyan , Gschwendtner Silvia , Gasche Rainer , Kolar Allison , Schloter Michael , Kiese Ralf , Butterbach‐Bahl Klaus , Dannenmann Michael 
Published: May 2016

AbstractThe carbon‐ and nitrogen‐rich soils of montane grasslands are exposed to above‐average warming and to altered precipitation patterns as a result of global change. To investigate the consequences of climatic change for soil nitrogen turnover, we translocated intact plant–soil mesocosms along an elevational gradient, resulting in an increase of the mean annual temperature by approx. 2 °C while decreasing precipitation from approx. 1500 to 1000 mm. Following three years of equilibration, we monitored the dynamics of gross nitrogen turnover and ammonia‐oxidizing bacteria (AOB) and archaea (AOA) in soils over an entire year. Gross nitrogen turnover and gene levels of AOB and AOA showed pronounced seasonal dynamics. Both summer and winter periods equally contributed to cumulative annual N turnover. However, highest gross N turnover and abundance of ammonia oxidizers were observed in frozen soil of the climate change site, likely due to physical liberation of organic substrates and their rapid turnover in the unfrozen soil water film. This effect was not observed at the control site, where soil freezing did not occur due to a significant insulating snowpack. Climate change conditions accelerated gross nitrogen mineralization by 250% on average. Increased N mineralization significantly stimulated gross nitrification by AOB rather than by AOA. However, climate change impacts were restricted to the 2–6 cm topsoil and rarely occurred at 12–16 cm depth, where generally much lower N turnover was observed. Our study shows that significant mineralization pulses occur under changing climate, which is likely to result in soil organic matter losses with their associated negative impacts on key soil functions. We also show that N cycling processes in frozen soil can be hot moments for N turnover and thus are of paramount importance for understanding seasonal patterns, annual sum of N turnover and possible climate change feedbacks.
Evaluating confidence in climate‐based predictions of population change in a migratory species
Authors: Saunders Sarah P. , Ries Leslie , Oberhauser Karen S. , Zipkin Elise F. 
Published: May 2016

AbstractAimForecasting ecological responses to climate change is a common objective, but there are few methods for evaluating confidence in such predictions. For migratory species, in particular, it is also essential to consider the extent of spatial synchrony among separate breeding populations in range‐wide predictions. We develop a quantitative method to evaluate the accuracy of climate‐based ecological predictions and use this approach to assess the extent of spatio‐temporal synchrony among distinct regions within the breeding range of a single migratory population.LocationWe model weekly site‐specific summer abundances (1996–2011) of monarch butterflies (Danaus plexippus) in the Midwestern USA as a function of climate conditions experienced during a shared spring migration/breeding phase in Texas and separate summer recruitment periods in Ohio and Illinois.MethodsUsing negative binomial regression models, we evaluate spatio‐temporal synchrony between monarchs in the two states and develop a novel quantitative assessment approach to determine the temporal predictive strength of our model with BayesianP‐values.ResultsMonarchs breeding in the Midwest exhibit spatio‐temporal synchrony in Ohio and Illinois; cooler spring temperatures, average to above average precipitation in Texas and cooler than average summer temperatures are associated with higher population abundances in both states. At least 10 years of data are needed for adequate model predictability of average future counts. Because annual spring weather conditions in Texas primarily drive yearly abundances, as opposed to localized summer effects, year‐specific counts are often difficult to predict reliably, specifically when predictive spring conditions are outside the range of typical regional conditions.Main conclusionsOur assessment method can be used in similar analyses to more confidently interpret ecological responses to climate change. Our results demonstrate the relative importance of climatic drivers in predicting abundances of a migratory species and the difficulties in producing reliable predictions of animal populations in the face of climate change.
Serum antinuclear antibody in adult Thais
Authors: Prapinjumrune Chanwit , Prucktrakul Chalakorn , Sooktonglarng Trakarn , Thongprasom Kobkan 
Published: May 2016

ObjectiveThis study investigated the presence of antinuclear antibody (ANA) in older Thais compared with middle‐age and younger participants.BackgroundAntinuclear antibody represents the first step in the diagnostic testing for lupus erythematosus (LE) and other autoimmune diseases. Due to the lack of reference ANA levels in older, middle‐age and younger Thais healthy participants, this study will be useful for determining the proper diagnostic and treatment criteria.MethodsThere were 28 older (60–76 years), 17 middle‐age (41–59 years) and 13 younger (24–40 years) participants in this study. Immunofluorescence was performed to analyse the ANA staining pattern and titre levels in the participants' blood samples.ResultsThe presence of serum ANA was found in 18 of 28 cases (64.3%), four of 17 (23.5%) and one of 13 cases (7.7%) of the older, middle‐age and younger participants, respectively. The difference in the number of serum ANA‐positive participants between the older, middle‐age and younger groups was statistically significant (p < 0.05). Interestingly, the ANA positive in older participants presented more than one staining pattern. The speckled pattern was the most commonly detected ANA staining pattern in the older group, being found in 12 cases followed by cytoplasmic pattern (10 cases), homogeneous pattern (nine cases) and nucleolar pattern (five cases). In the middle‐age group, the speckled pattern was found in four cases, whereas one younger participant presented a nucleolar pattern.ConclusionSerum ANA positive was significantly higher in the older group compared with the middle‐age and younger groups. There were variations of the serum ANA staining patterns in the older group.
Routine Anti‐Helicobacter Immunohistochemical Staining is Significantly Superior to Reflex Staining Protocols for the Detection of Helicobacter in Gastric Biopsy Specimens
Authors: Lash Richard H. , Genta Robert M. 
Published: May 2016

AbstractBackgroundThe role of special stains in the detection of H. pylori is controversial; some pathologists claim that hematoxylin and eosin staining alone is adequate to detect bacteria, while others maintain that immunohistochemical staining must be used on all gastric biopsies. This study was designed to test the hypothesis that hematoxylin and eosin and histochemical special stains have similar sensitivity and that immunohistochemical staining only marginally enhances the detection rate of the organisms.Materials and MethodsRecords of all gastric biopsies examined in a large pathology laboratory between January 1, 2010 and December 31, 2014 were extracted and stratified according to the stain used for the detection of Helicobacter (1. hematoxylin and eosin only; 2. Upfront HP Blue; 3. Upfront HP Blue including reflex immunohistochemistry; 4. Upfront anti‐Helicobacter immunohistochemical staining.ResultsGastric biopsies from 794,859 endoscopies obtained from 622,945 unique patients were analyzed. The basic demographics of the patients in different staining groups were identical. A total of 56,955 gastric biopsy sets were stained with histochemical stains only, and 731,193 with anti‐Helicobacter immunohistochemical stain; in 4409 of these, an immunohistochemical stain was also performed. In 2302 cases, only hematoxylin and eosin were performed. In this latter group, 7.0% of patients were Helicobacter‐positive; in the upfront HP Blue, the prevalence was 7.8%, whereas patients with upfront immunohistochemistry had a prevalence of 10.2% (p < .0001, compared to hematoxylin and eosin only).ConclusionsThere was a dramatic improvement in detection of H. pylori infection through the use of upfront immunohistochemical stains. Therefore, we contend that the routine use of IHC for all gastric biopsies is an appropriate protocol to ensure that every patient gets the right answer.