bluuebunny/crossref_metadata_2025 huggingface dataset:
Move out or dig in? Risk awareness and mobility plans in disaster‐affected communities
Authors: Haney Timothy J.
Published: December 2018

Post‐disaster migration patterns have been thoroughly studied from a demographic standpoint, but affected community residents’ perceptions of ongoing risks and their willingness to remain in an affected community remain under‐researched. Using data generated by 407 surveys and 40 interviews with residents impacted by the 2013 Calgary flood, this study analyses the effects of flood experience on residents’ worry about future floods and their ensuing short‐term and medium‐term mobility plans. The results indicate that home flooding and evacuation orders are both predictive of worry about future floods. In turn, worry about future floods as well as age, homeownership, and place attachment are all predictive of post‐disaster mobility plans. Residents discuss how the flood either strengthened or weakened their place attachment. The paper concludes by discussing the implications for social science research and for public policy that aims to mitigate disaster risk.
Systematic review of sociodemographic representation and cultural responsiveness in psychosocial and behavioral interventions with adolescents with type 1 diabetes
Authors: Morone Jennifer
Published: December 2018

Background

The increasing incidence of type 1 diabetes (T1D) in youth aged less than 20 years in the USA is a mounting public health concern. Specific sociodemographic characteristics—racial/ethnic minority, low socioeconomic status (SES), single‐parent home and underinsured—have been associated with increased risk for poor glycemic control and poor self‐management in adolescents with T1D.

Methods

Sample demographic and cultural responsiveness methods in psychosocial and behavioral interventions focused on improving self‐management and glycemic control in adolescents with T1D were systematically evaluated, to identify if studies were targeting these high‐risk groups. Keyword searches of PsychInfo, PubMed and CINAHL identified 259 studies published between 2006 and 2016, of adolescents (13‐18 years old) with T1D; 28 studies met inclusion criteria.

Results

Samples focused predominantly on White adolescents with fair glycemic control, from middle‐high income, two‐parent households with private insurance. The majority of studies scored poorly in cultural responsiveness and moderately in culturally responsive reporting. Studies lacked descriptions of culturally inclusive recruitment and sampling methods, and use of culturally responsive assessments for diverse groups. The majority of studies recruited and enrolled homogeneous adolescent samples from the lowest risk groups.

Conclusion

T1D intervention researchers must increase targeted recruitment and sampling methods to include more high‐risk pediatric T1D groups, expand sociodemographic reporting, and increase the use of culturally responsive recruitment and sampling methods, such as those used in community‐based participatory research. Such efforts have the potential to reduce T1D disparities by making interventions more relevant to the unique needs, goals and priorities of highest risk groups.
Cryptic diversity in the Mexican highlands: Thousands of UCE loci help illuminate phylogenetic relationships, species limits and divergence times of montane rattlesnakes (Viperidae: Crotalus)
Authors: Blair Christopher , Bryson Robert W. , Linkem Charles W. , Lazcano David , Klicka John , McCormack John E.
Published: December 2018

With the continued adoption of genome‐scale data in evolutionary biology comes the challenge of adequately harnessing the information to make accurate phylogenetic inferences. Coalescent‐based methods of species tree inference have become common, and concatenation has been shown in simulation to perform well, particularly when levels of incomplete lineage sorting are low. However, simulation conditions are often overly simplistic, leaving empiricists with uncertainty regarding analytical tools. We use a large ultraconserved element data set (>3,000 loci) from rattlesnakes of the Crotalus triseriatus group to delimit lineages and estimate species trees using concatenation and several coalescent‐based methods. Unpartitioned and partitioned maximum likelihood and Bayesian analysis of the concatenated matrix yield a topology identical to coalescent analysis of a subset of the data in bpp. ASTRAL analysis on a subset of the more variable loci also results in a tree consistent with concatenation and bpp, whereas the SVDquartets phylogeny differs at additional nodes. The size of the concatenated matrix has a strong effect on species tree inference using SVDquartets, warranting additional investigation on optimal data characteristics for this method. Species delimitation analyses suggest up to 16 unique lineages may be present within the C. triseriatus group, with divergences occurring during the Neogene and Quaternary. Network analyses suggest hybridization within the group is relatively rare. Altogether, our results reaffirm the Mexican highlands as a biodiversity hotspot and suggest that coalescent‐based species tree inference on data subsets can provide a strongly supported species tree consistent with concatenation of all loci with a large amount of missing data.
A robust, cost‐effective method for DNA, RNA and protein co‐extraction from soil, other complex microbiomes and pure cultures
Authors: Thorn Camilla E. , Bergesch Christian , Joyce Aoife , Sambrano Gustavo , McDonnell Kevin , Brennan Fiona , Heyer Robert , Benndorf Dirk , Abram Florence
Published: December 2018

The soil microbiome is inherently complex with high biological diversity, and spatial heterogeneity typically occurring on the submillimetre scale. To study the microbial ecology of soils, and other microbiomes, biomolecules, that is, nucleic acids and proteins, must be efficiently and reliably co‐recovered from the same biological samples. Commercial kits are currently available for the co‐extraction of DNA, RNA and proteins but none has been developed for soil samples. We present a new protocol drawing on existing phenol–chloroform‐based methods for nucleic acids co‐extraction but incorporating targeted precipitation of proteins from the phenol phase. The protocol is cost‐effective and robust, and easily implemented using reagents commonly available in laboratories. The method is estimated to be eight times cheaper than using disparate commercial kits for the isolation of DNA and/or RNA, and proteins, from soil. The method is effective, providing good quality biomolecules from a diverse range of soil types, with clay contents varying from 9.5% to 35.1%, which we successfully used for downstream, high‐throughput gene sequencing and metaproteomics. Additionally, we demonstrate that the protocol can also be easily implemented for biomolecule co‐extraction from other complex microbiome samples, including cattle slurry and microbial communities recovered from anaerobic bioreactors, as well as from Gram‐positive and Gram‐negative pure cultures.
Fertilisation practice changes rhizosphere microbial community structure in the agroecosystem
Authors: Guo Zhibin , Liu Hui , Wan Shuixia , Hua Keke , Wang Daozhong , Guo Xisheng , He ChuanLong
Published: December 2018

Rhizosphere microbial community is important for the acquisition of soil nutrients and closely related to plant species. Fertilisation practice changed soil quality. With the hypothesis of stronger rhizosphere effect of plant on rhizosphere microbial community than fertilisation management, we designed this research based on a long‐term field experiment (1982–present). This study consists of no fertilisation (NF), mineral fertilisers (NPK), mineral fertilisers plus 7,500 kg/ha of wheat straw addition (WS) and mineral fertilisers plus 30,000 kg/ha of cow manure (CM). After analysing, we found that fertilisation management not only elevated crop yield but also affected crop rhizosphere microbial community structure. The influence of fertilisation practice on wheat rhizosphere microbial structure was stronger than that of wheat. For wheat rhizosphere bacterial community, it was significantly affected by soil water content (SWC), nitrogen (TN), phosphorus (TP), pH, available phosphorus (AVP) and nitrogen (AVN), dissolved organic nitrogen (DON) and carbon (DOC). Besides SWC, pH, AVP, AVN, TN, TP and DOC, the wheat rhizosphere fungi community was also significantly affected by soil organic matter (SOM) and available potassium (AVK). Moreover, compared to rhizosphere bacterial community, the influences of soil physiochemical properties on rhizosphere fungal community was stronger. In conclusion, fertilisation practice was the primary factor structuring rhizosphere microbial community by changing soil nutrients availabilities in the agroecosystem.
Output and input bias effects of U.S. direct payments
Authors: Haque Samiul , Foster Kenneth A. , Keeney Roman , Boys Kathryn A. , Narayanan Badri G.
Published: December 2018

This study examines the national effect of U.S. direct payments on the extent and direction of biased technical change on U.S. agriculture. We also assess the economic significance of the estimated bias effects for economic policy modeling endeavors involving a reduction of domestic support payments. A two outputs (livestock and crops) and four inputs (labor, capital, land, and material) translog cost function was estimated from national time series (1948–2011) data. Results indicate that payments do not induce output‐biased technical change. We do find evidence of Hicksian bias that is land using and material input saving attributable to support payments. Global computable general equilibrium simulations suggest that price and output effects of discontinuing direct payments are 1/4 to 1/3 the size once the bias effects are incorporated.
Corridors of Power: AssemblingUSEnvironmental Foreign Aid
Authors: Corson Catherine
Published: December 2018

Using theUSAgency for International Development's environmental program in Madagascar as a lens, I offer a historically grounded, relational, and multi‐sited methodology for understanding the transnational processes that constitute political forests in the contemporary era. I argue that neoliberal reforms conditioned the emergence of a public–private–non‐profit alliance, which promoted biodiversity conservation as aUSforeign aid priority. As these reforms weakened state capacity and liberalised economies, the downsized Madagascar andUSgovernments became reliant on conservation actors to mobilise political support for their programs. This reinforced the need to maintain strategic relationships with capital‐city actors, undermining prior efforts to devolve forest management to local communities. By isolating deforestation as a peasant problem “over there” and by expanding protected areas to meet global biodiversity targets, the conservation alliance created an avenue to be green that did not threaten extractive industries or key constituents. In this manner, saving the environment via protected areas expansion offered politicians a pathway through the inherent contradictions of green neoliberalism.
Effects of supplementary mother liquor, by‐product of monosodium glutamate, on in vitro ruminal fermentation characteristics
Authors: Sato Yoshiaki , Nakanishi Takashi , Takeda Motoharu , Oishi Kazato , Hirooka Hiroyuki , Kumagai Hajime
Published: December 2018

Mother liquor (ML) is monosodium glutamate by‐product and contains much crude protein (CP). The objective of this study was to investigate the effect of supplementation of two types of MLs having different chemical compositions on in vitro ruminal fermentation characteristics. ML1 had 74% organic matter (OM) and 70% CP and ML2 had 85% OM and 83% CP on a dry matter (DM) basis. The experiments were conducted using 0.5 gDM rolled barley or ryegrass straw as substrates. Urea and freeze‐dried MLs were added at three levels of nitrogen to be isonitrogenous. The ML1 treatment increased gas production compared with the ML2 treatment in barley substrate condition (p < 0.05). The supplementary ML2 increased gas production compared with the supplementary urea, and the digestibilities of DM and neutral detergent fiber expressed exclusive of residual ash (NDFom) were higher for the supplementary ML2 than for the supplementary ML1 in straw substrate condition (p < 0.05). In both the conditions, ammonia nitrogen concentrations of the ML1 and ML2 treatments were lower than that of the urea treatment (p < 0.05). The results indicated that the supplementary ML1 and ML2 activated in vitro ruminal fermentation particularly in concentrate and roughage substrate conditions respectively.
Comparison on predictors of mental health service use among Asian older adults
Authors: Hong Seokho
Published: December 2018

Studies have mostly examined mental health service use of older Asian immigrant combining all Asian Americans into one group whereas immigration backgrounds and socioeconomic status of each Asian minority group are different. Therefore, this study aimed to identify predictors of mental health service use within specific ethnic groups among older Asian adults focusing on Chinese, Japanese, Korean, Filipino, and Vietnamese in California. The Behavioral Model for Vulnerable Populations (BMVP) is used to guide the secondary data analysis of a sample of 3,453 older Asian immigrants from the California Health Interview Survey (CHIS). Logistic and linear regression analyses are performed to examine predictors of mental health service use and the frequency of mental health service use, respectively. As results, mental health‐seeking patterns differ by ethnicity within the older Asian immigrant sample, not being married (Korean), higher levels of acculturation (Filipino), lower levels of neighborhood cohesion (Korean and Vietnamese), higher levels of perceived safety (Korean) and lower levels of perceived safety (Vietnamese), higher levels of mental distress (Korean and Filipino), and having perceived need (all) were related to more visits for mental health services. The study findings highlight the necessity of cultural competency services and programs for each Asian ethnicity.
Target engagement and cellular fate of otelixizumab: a repeat dose escalation study of an anti‐CD3ε mAb in new‐onset type 1 diabetes mellitus patients
Authors: Vlasakakis Georgios , Napolitano Antonella , Barnard Ruth , Brown Kim , Bullman Jonathan , Inman David , Keymeulen Bart , Lanham David , Leirens Quentin , MacDonald Alexander , Mezzalana Enrica , Page Kevin , Patel Minesh , Savage Caroline O. , Zamuner Stefano , van Maurik Andre
Published: December 2018

Aims

This paper describes the pharmacological findings from a study where otelixizumab, an anti‐CD3ɛ mAb, was dosed in new onset Type 1 diabetes mellitus (NOT1DM) patients. This is the first time that the full dose–response of an anti‐CD3ɛ mAb has been investigated in the clinic. The data have been validated using a previously developed pharmacokinetic/pharmacodynamic (PK/PD) model of otelixizumab to simulate the interplay between drug administration, CD3ɛ target engagement and downmodulation.

Methods

Patients were randomized to control or active treatment with otelixizumab (1:4), administered via infusion over 6 days, in a dose‐ascending study consisted of three cohorts (n = 10 per cohort) at doses of 9, 18 or 27 mg respectively. The study allowed quantification of otelixizumab PK, CD3ɛ target engagement and its pharmacodynamic effect (CD3ε/TCR modulation on circulating T lymphocytes).

Results

Otelixizumab concentrations increased and averaged to 364.09 (54.3), 1625.55 (72.5) and 2781.35 (28.0) ng ml−1 (Geom.mean, %CV) at the 9, 18 and 27 mg dose respectively. CD3ɛ target engagement was found to be rapid (within the first 30 min), leading to a receptor occupancy of ~60% within 6 h of dosing in all three doses. A dose–response relationship was observed with the two highest doses achieving a ~90% target engagement and consequential CD3ɛ/TCR downmodulation by Day 6.

Conclusions

Data from this study revealed maximum target engagement and CD3ɛ/TCR modulation is achieved at doses of 18, 27 mg of otelixizumab. These findings can be useful in guiding dose selection in clinical trials with anti‐CD3ɛ mAbs.
PERFORMANCE‐BASED FEE CONTRACT AND RISK‐TAKING STRATEGY IN ASSET MANAGEMENT TOURNAMENT
Authors: Sheng Jiliang , Wang Xiaoting , Yang Jun , Li Miao
Published: December 2018

This paper investigates how performance‐based fee (PBF) contracts affect strategic risk‐taking behaviours of fund managers in an asset management tournament. In the perfect equilibrium, managers with better mid‐year performance will hold the risky asset with a higher probability in the remaining of the year, compared to managers with poorer mid‐year performance. If the volume of the cash flow into the winner fund is contingent on its level of success, the winning fund will take a more aggressive approach. When the PBF contract pays more heed to relative performance against the benchmark, managers are more likely to adopt aggressive strategies.
Cost‐effectiveness of intensification with sodium‐glucose co‐transporter‐2 inhibitors in patients with type 2 diabetes on metformin and sitagliptin vs direct intensification with insulin in the United Kingdom
Authors: Pawaskar Manjiri , Bilir S. Pinar , Kowal Stacey , Gonzalez Claudio , Rajpathak Swapnil , Davies Glenn
Published: December 2018

Aim

To evaluate the long‐term cost‐effectiveness of an intensification strategy with sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors (pathway 1) compared with NPH insulin (pathway 2) in patients with type 2 diabetes (T2D) in the United Kingdom who were not at goal on metformin and sitagliptin.

Methods

Cost‐effectiveness analysis was performed using the well‐established, validated IQVIA CORE Diabetes Model from the payer perspective over a patient's lifetime. Randomized clinical trials informed treatment effect measures, while public or published sources informed economic inputs. Scenario analyses of glycated haemoglobin (HbA1c), hypoglycaemia rate, body mass index effects, SGLT2 inhibitor cardiovascular protective effects, and population characteristics were conducted to assess the robustness of results.

Results

Pathway 1 increased life‐years and quality‐adjusted life‐years (QALYs) compared with pathway 2 (13.49 vs. 13.37, and 9.40 vs. 9.22, respectively). Additional drug costs in pathway 1 were offset by diabetes‐related complication decreases, leading to slightly lower direct medical costs for pathway 1 (£25747 vs £26095). Pathway 1 was therefore cost‐neutral (no interpretable incremental cost‐effectiveness ratio), while improving clinical outcomes. Scenario analyses consistently showed cost‐neutrality or cost‐effectiveness of pathway 1. The highest result remained less than £3000/QALY, reflecting older patients (≥65 years) with lower baseline HbA1c (7%).

Conclusions

For UK patients with T2D not at goal on metformin and sitagliptin therapy, treatment intensification with SGLT2 inhibitors prior to NPH insulin is cost‐neutral or cost‐effective compared with immediate NPH insulin intensification.
MANAGING RISK TAKING WITH INTEREST RATE POLICY AND MACROPRUDENTIAL REGULATIONS
Authors: Cociuba Simona E. , Shukayev Malik , Ueberfeldt Alexander
Published: December 2018

We develop a model in which a financial intermediary's investment in risky assets—risk taking—is excessive due to limited liability and deposit insurance, and characterize the policies that implement efficient risk taking. In the calibrated model, combining interest rate policy with state‐contingent macroprudential regulations—either capital or leverage regulation, and a tax on profits—achieves efficiency. Interest rate policy mitigates excessive risk taking by altering the return and the supply of collateralizable safe assets. In contrast to commonly used capital regulation, leverage regulation has stronger effects on risk taking and calls for higher interest rates. (JEL E44, E52, G11, G18)
Seasonal changes in the density of the symbionts Buchnera and Wolbachia of the aphid Tuberculatus macrotuberculatus on Quercus dentata
Authors: Yao Izumi
Published: December 2018

Seasonal changes in leaf traits and tannins, including hydrolysable tannins (HTs) and condensed tannins (CTs), affect aphid body size and demographic patterns. The aphid Tuberculatus macrotuberculatus Essig & Kuwana (Hemiptera: Aphididae) feeds on the leaves of the daimyo oak, Quercus dentata Thunberg (Fagaceae), does not alternate hosts, and is attended continuously by ants. Buchnera aphidicola Munson et al. (a γ‐proteobacterium, hereafter Buchnera) is the primary symbiont of most aphid species. It provides essential amino acids to host aphids. Wolbachia sp. (an α‐proteobacterium) is present in some aphid species. This study investigated the effects of seasonal tannin and leaf trait fluctuations in Q. dentata on aphid performance and Buchnera and Wolbachia densities in T. macrotuberculatus. As the season progressed, the water content and HT concentration in Q. dentata leaves decreased, CT concentration in Q. dentata leaves increased, and T. macrotuberculatus performance decreased. Buchnera density varied in accordance with host aphid performance, whereas Wolbachia density did not vary throughout the season, suggesting that although Buchnera depends on the host plant and host aphid performance for growth, Wolbachia may have a high tolerance for oligotrophic environments and may exist independent of the nutritional metabolism of the host aphid. Although the role of Wolbachia in T. macrotuberculatus remains unclear, it may be associated with resistance to parasitoid wasps and plant secondary metabolites.
Impaired cocaine‐induced behavioral plasticity in the male offspring of cocaine‐experienced sires
Authors: Wimmer Mathieu E. , Vassoler Fair M. , White Samantha L. , Schmidt Heath D. , Sidoli Simone , Han Yumiao , Garcia Benjamin A. , Pierce R. Christopher
Published: December 2018

Our previous work indicated that male, but not female, offspring of cocaine‐experienced sires display blunted cocaine self‐administration. We extended this line of investigation to examine behavioral sensitization, a commonly used model of cocaine‐induced behavioral and neuronal plasticity. Results indicated that male, but not female, offspring of cocaine‐taking sires showed deficits in the ability of repeated systemic cocaine injections to induce augmented locomotor activity. The reduced cocaine sensitization phenotype in male progeny was associated with changes in histone post‐translational modifications, epigenetic processes that regulate gene expression by controlling the accessibility of genes to transcriptional machinery, in the nucleus accumbens of first‐generation male progeny. Thus, five histone post‐translational modifications were significantly altered in the male progeny of cocaine‐exposed sires. In contrast, self‐administration of nicotine was unaltered in male and female offspring suggesting that the intergenerational effects of paternal cocaine taking may be drug‐specific. Interestingly, the reduced sensitivity to cocaine previously observed in the male offspring of cocaine‐taking sires dissipated in the grand‐offspring. Both male and female grand‐progeny of cocaine‐exposed sires showed unaltered cocaine‐induced behavioral sensitization and cocaine self‐administration. Taken together, these findings indicate that paternal cocaine taking produces changes in multiple cocaine addiction‐related behaviors in male progeny, which do not persist beyond the first generation of offspring. Moreover, the altered sensitivity to cocaine in first‐generation male progeny of cocaine‐sired male offspring was associated with epigenetic modifications in the nucleus accumbens, a nucleus that plays a critical role in cocaine‐associated behavioral plasticity.
Donepezil for gait and falls in mild cognitive impairment: a randomized controlled trial
Authors: Montero‐Odasso M. , Speechley M. , Chertkow H. , Sarquis‐Adamson Y. , Wells J. , Borrie M. , Vanderhaeghe L. , Zou G. Y. , Fraser S. , Bherer L. , Muir‐Hunter S. W.
Published: December 2018

Background and purpose

Cognitive enhancers are commonly prescribed to people with Alzheimer's disease and related dementias to improve cognition and function. However, their effectiveness for individuals in the pre‐stages of dementia, particularly in functional motor outcomes, remains unknown. We aimed to determine the efficacy of donepezil, a cognitive enhancer that improves cholinergic neurotransmission, on gait performance in mild cognitive impairment (MCI).

Methods

This was a double‐blind, placebo‐controlled trial including 60 older adults with MCI, randomized to receive donepezil (10 mg/daily, maximal dose) or placebo. Primary outcome was gait speed (cm/s) under single and three dual‐task conditions (counting backwards by 1 or 7 and naming animals) measured using an electronic walkway. Dual‐task gait cost (DTC), a valid measure of motor–cognitive interaction, was calculated as the percentage change between single (S) and dual‐task (D) gait speeds: [(S − D)/S] × 100. Secondary outcomes included attention, executive function, balance and falls.

Results

After 6 months, the donepezil group experienced an improvement in dual‐task gait speed (range 4–11 cm/s), although this was not statistically significant. The donepezil group showed a significant reduction in DTC (improvement) by counting backwards by 1 and 7 compared with placebo (10.25% vs. 1.75%, P = 0.048; 21.38% vs. 14.64%, P = 0.037, intention‐to‐treat analysis). Per‐protocol analyses showed that all three DTCs improved in the donepezil group, along with a non‐significant reduction of rate of falls.

Conclusions

Donepezil treatment improved dual‐task gait speed and DTC in elderly patients with MCI. Our results support the concept of reducing falls in MCI by targeting the motor–cognitive interface.
Chorioamnionitis exposure remodels the unique histone modification landscape of neonatal monocytes and alters the expression of immune pathway genes
Authors: Bermick Jennifer , Gallagher Katherine , denDekker Aaron , Kunkel Steve , Lukacs Nicholas , Schaller Matthew
Published: December 2018

Chorioamnionitis is an intrauterine infection involving inflammation of the chorion, amnion, and placenta. It leads to a fetal systemic inflammatory response that can alter the transcription of neonatal immune genes. We have previously shown that neonatal monocytes gain the activating histone tail modification H3K4me3 at promoter sites of immunologically important genes as development progresses from preterm neonate to adult. In this study, we applied ChIP‐seq and RNA‐seq to evaluate the impact of chorioamnionitis on the neonatal monocyte H3K4me3 histone modification landscape over the course of fetal and neonatal immune system development. Chorioamnionitis exposure in neonatal monocytes resulted in a net increase in total monocyte H3K4me3, primarily in introns and intergenic regions. Immune gene expression was decreased in chorioamnionitis‐exposed monocytes, with the majority of enriched transcripts falling into pathways that are not linked to the immune system. Over half of all neonatal monocyte H3K4me3 peaks, independent of their location, were associated with active gene transcription. Overall, chorioamnionitis exposure resulted in the global remodeling of the neonatal monocyte H3K4me3 landscape and changes in the expression of known immune genes. These changes resulted in a less robust inflammatory response upon exposure to a secondary challenge, which may explain why chorioamnionitis‐exposed neonates have an increased risk of sepsis.

Database

ChIP‐seq data for U30/O30/Term: GEO GSE81957

ChIP‐seq data for U30C/O30C/TermC: GEO GSE111873

RNA‐seq data for U/L/CU/CL: GEO GSE111927
Structural and thermodynamic characterization of the binding of isoliquiritigenin to the first bromodomain of BRD4
Authors: Yokoyama Takeshi , Matsumoto Kazunori , Ostermann Andreas , Schrader Tobias E. , Nabeshima Yuko , Mizuguchi Mineyuki
Published: December 2018

Bromodomain‐containing protein 4 (BRD4) recognizes the acetylated lysine of histone H4 via its bromodomains, leading to the recruitment of positive transcription elongation factor b. Small molecules that inhibit BRD4 have potential as anticancer agents by leading to the downregulation of specific oncogenes. Using X‐ray crystallographic screening, we identified the BRD4 inhibitory activity of isoliquiritigenin (ISL), a natural chalcone found in licorice. Structural analysis revealed that ISL bound to BRD4 with a novel binding mode and squeezed out one of the six conserved water molecules that form a strong hydrogen bond network. The thermodynamic analysis revealed that the binding of ISL is enthalpy driven, suggesting that strong hydrogen bonds would compensate for the desolvation penalty. Neutron protein crystallography further suggested that the favorable binding enthalpy originates from the stabilization and optimization of the hydrogen bond network of the conserved water molecules. Here, we describe the novelty and potential of ISL as a template for new BRD4 inhibitors.
Silage additives to reduce protein degradation during ensiling and evaluation of in vitro ruminal nitrogen degradability
Authors: Herremans Sophie , Decruyenaere Virginie , Beckers Yves , Froidmont Eric
Published: December 2018

Despite the high degradability of their proteins, grass and legume silages represent an important option to reach more sustainable livestock systems. To improve the nitrogen use efficiency of these crops, this study assessed the potential of several additives (chestnut tannins, oak tannins, zeolite, erythritol by‐product solution and wood molasses) to reduce proteolysis in the silo and in vitro nitrogen degradability. Ryegrass (Lolium multiflorum) and red clover (Trifolium pratense) were ensiled in varying proportions in laboratory‐scale silos made of vacuum‐packed plastic bags. Dry‐matter content, chemical composition, pH, ammonia and volatile fatty acids content were analysed after 34 days of ensiling. Ruminal nitrogen degradability was assessed in vitro (Aufrère & Cartailler, ). We observed that the proportion of ammonia in silage was reduced by the addition of oak tannin (−12%) and zeolite (−16%). The addition of zeolite lowered in vitro organic matter digestibility. Rapidly degradable nitrogen (1‐hr degradability) was reduced in vitro by both tannins (−6.8% for chestnut and −6.6% for oak) and zeolite (−5.8%), but total degradable nitrogen (24‐hr degradability) was only reduced by oak (−6.5%) and chestnut tannins (−7.3%). It suggests that tannins protected proteins from plant and bacterial enzymes by forming a complex that better resists silage fermentations and in vitro protease action. The reduction effects on proteolysis in the silo and on in vitro ruminal nitrogen degradability are limited individually but could be cumulative. Erythritol by‐product solution and wood molasses had no effect on silo or in vitro proteolysis.
Mucin 5B, carbonic anhydrase 9 and claudin 18 are potential theranostic markers of gallbladder carcinoma
Authors: Espinoza Jaime A , Riquelme Ismael , Sagredo Eduardo A , Rosa Lorena , García Patricia , Bizama Carolina , Apud‐Bell María , Leal Pamela , Weber Helga , Benavente Felipe , Vargas Sergio , Romero Diego , Kalergis Alexis M , Roa Juan Carlos
Published: December 2018

Aims

Gallbladder cancer (GBC) is an aggressive tumour that is usually diagnosed at advanced stages and is characterised by a poor prognosis. Using public data of normal human tissues, we found that mRNA and protein levels of mucin 5B (MUC5B) and carbonic anhydrase 9 (CA9) were highly increased in gallbladder tissues. In addition, previous evidence has shown that claudin 18 (CLDN18) protein expression is higher in GBC. The aim of this study was to perform an analysis of these cell surface proteins during the histological progression of GBC in order to identify their theranostic potential.

Methods and results

MUC5B expression, CA9 expression and CLDN18 expression were examined by immunohistochemistry in a series of 179 chronic cholecystitis (including 16 metaplastic tissues), 15 dysplasia and 217 GBC samples by the use of tissue microarray analysis. A composite staining score was calculated from staining intensity and percentage of positive cells. Immunohistochemical analysis showed high expression of MUC5B and CA9 among normal epithelium, metaplastic tissues, and dysplastic tissues. However, expression of both proteins was observed in roughly 50% of GBC samples. In contrast, CLDN18 was absent in normal epithelium, but its expression was higher in metaplastic cells. Among GBC cases, approximately half showed high CLDN18 expression. No associations were found between MUC5B, CA9 and CLDN18 expression and any clinicopathological features.

Conclusions

CLDN18 is a new metaplasia marker in gallbladder tissues, and is conserved in approximately half of GBC cases. MUC5B and CA9 are highly conserved during GBC histological progression. The three markers are potential theranostic markers, in particular CA9 and CLDN18, for which there are already targeted therapies available.
Heparin is biocompatible and can induce differentiation of human dental pulp cells
Authors: Rodrigues E. M. , Cornélio A. L. G. , Godoi P. H. , da Costa P. I. , Rossa‐Junior C. , Faria G. , Guerreiro Tanomaru J. M. , Tanomaru‐Filho M.
Published: December 2018

Aim

To investigate the biocompatibility, osteogenic bioactivity and mRNA expression of the osteo/odontogenic markers bone morphogenetic protein 2 (BMP‐2), osteocalcin (OC) and alkaline phosphatase (ALP), induced by heparin in human dental pulp cells (hDPCs).

Methodology

hDPCs were exposed to the heparin, and cell viability was assessed by 3‐(4,5‐dimethylthiazol)‐2,5‐diphenyltetrazolium bromide (MTT), and cell death was evaluated by flow cytometry. Osteogenic bioactivity was evaluated by the alkaline phosphatase (ALP) assay, and the detection of calcium deposits by alizarin red staining (ARS). The gene expression of BMP‐2, OC and ALP was quantified with real‐time PCR. Statistical analysis was performed with ANOVA and Bonferroni or Tukey post‐test and t‐test (α = 0.05).

Results

Heparin had no cytotoxic effect and did not induce apoptosis. After 3 days, heparin had significantly higher ALP activity in comparison with the control (P < 0.05). Heparin had a significant (P < 0.05) stimulatory effect on the formation of mineralized nodules. BMP‐2 and OC mRNA expressions were significantly higher in cells exposed to heparin than control group after 1 day (P < 0.05).

Conclusions

Heparin was biocompatible in hDPCs, induced osteogenic bioactivity and enhanced mRNA expression of osteo/odontogenic markers BMP‐2 and OC. These results suggest that heparin has potential to induce osteo/odontogenic cell differentiation of hDPCs.
Recovery of phytochemical compounds from natural and blanched green broccoli using non‐isothermal autohydrolysis
Authors: González‐Muñoz María Jesús , Conde Enma , Domínguez Herminia , Torres María Dolores
Published: December 2018

The temperature effect during autohydrolysis of natural and blanched broccoli was studied. For this purpose, the extraction yield, total phenolic content, antioxidant capacity and glucosinolates type and content of the autohydrolysis liquors have been determined. The development of alginate based hydrogels using the autohydrolysis liquid phase as solvent and the corresponding textural characterisation was also evaluated. In all cases, extraction yields rose with the autohydrolysis temperature up to 150 °C and then decreased. For liquors from natural samples, total phenolic content and antioxidant capacity increased with increasing operation temperature. The opposite trend was identified for blanched samples. Comparable values were obtained at 150 °C for liquors from natural samples and those blanched treated at 100 °C. Glucosinolates content decreased with increasing temperature. Glucoiberin, glucoraphanin, gluconapin, glucobrassicin and gluconasturniin were detected. Hydrogels with suitable textural properties were formulated with the extracted liquors at 100 and 150 °C, independently of the blanching treatment.
Chromosome 22q11.2 deletion syndrome and DiGeorge syndrome
Authors: Sullivan Kathleen E.
Published: December 2018

Chromosome 22q11.2 deletion syndrome is the most common microdeletion syndrome in humans. The effects are protean and highly variable, making a unified approach difficult. Nevertheless, commonalities have been identified and white papers with recommended evaluations and anticipatory guidance have been published. This review will cover the immune system in detail and discuss both the primary features and the secondary features related to thymic hypoplasia. A brief discussion of the other organ system involvement will be provided for context. The immune system, percolating throughout the body can impact the function of other organs through allergy or autoimmune disease affecting organs in deleterious manners. Our work has shown that the primary effect of thymic hypoplasia is to restrict T cell production. Subsequent homeostatic proliferation and perhaps other factors drive a Th2 polarization, most obvious in adulthood. This contributes to atopic risk in this population. Thymic hypoplasia also contributes to low regulatory T cells and this may be part of the overall increased risk of autoimmunity. Collectively, the effects are complex and often age‐dependent. Future goals of improving thymic function or augmenting thymic volume may offer a direct intervention to ameliorate infections, atopy, and autoimmunity.
Identifying ecological drivers of interspecific variation in song complexity in songbirds (Passeriformes, Passeri)
Authors: Crouch Nicholas M. A. , Mason‐Gamer Roberta J.
Published: December 2018

A diversity of selective pressures and stochastic processes have likely created substantial variation in song structure, creating difficulties in quantifying the influence of specific ecological factors. This problem is further compounded by differences in study taxa and methods of data analysis between studies. Large comparative studies offer the potential to mitigate some of these methodological difficulties by maximizing the power of statistical analyses and minimizing the probability of misidentifying the magnitude and direction of relationships between independent and dependent variables. In this study, we quantified song complexity for 367 species of globally distributed songbirds (Passeriformes, Passeri). We quantified eight individual acoustic variables that have previously been linked to audio complexity which we analyzed independently, and after applying multivariate statistics to the variables. We used Bayesian linear mixed effect models to test multiple hypotheses regarding song complexity: that it should be greater in open habitats, in migratory species, for sexually monomorphic species, at higher latitudes and altitudes, and that it should co‐vary with clutch size characteristics. Our results challenge perceptions of the effect of habitat structure on song complexity; for instance, counter to expectation, we found songs in closed environments to have reduced syllable diversity. Additionally, our results suggest song complexity may not be ubiquitously a means of communicating male quality, with no significant difference between recordings from monomorphic and dimorphic species. By estimating song complexity in multiple ways, and quantifying these over large taxonomic and spatial scales, we are able to gain a more nuanced understanding of how song complexity is potentially affected by a range of biotic and abiotic factors. Our results also suggest that caution is required when making generalized statements about the relative influence of different factors on song complexity; more densely‐sampled, group‐specific studies are necessary complements to this taxonomically broad analysis.
Cognitive‐behavioural outreach for an adolescent experiencing social anxiety, panic and agoraphobia: A single‐case experimental design
Authors: Waldron Samuel M. , Maddern Lynn , Wynn Amber
Published: December 2018

Problem

Previous research suggests that the adult‐focussed Clark and Wells (1995) model of social anxiety disorder (SAD) can be used to guide clinic‐based treatment for adolescents. This single‐case study (N = 1) investigated whether this model could also guide community‐based outreach work for a 16‐year‐old female who was unable to attend clinic‐based appointments due to social anxiety comorbid with panic and agoraphobia.

Methods

An experimental A‐B‐A design was used with three assessment–formulation sessions and 12 intervention sessions, focussing on exposure, cognitive restructuring, attention training, behavioural experiments and imagery rescripting. The Revised Child Anxiety and Depression Scale (RCADS), the Session Rating Scale (SRS) and the Goal Based Outcome form were administered at regular intervals.

Findings and Conclusions

Social anxiety and panic scores reduced below the clinical threshold and the young person was able to leave home, travel independently (short‐term goal) and re‐engage with her social–family life (medium‐term goal). SRS scores suggest that the intervention was acceptable and the therapeutic alliance was maintained throughout. In summary, this case study suggests that the Clark and Wells (1995) model of SAD can be used to guide community‐based outreach work with adolescents unable to leave their home. Limitations and ideas for future research are discussed.
Organotypic slice culture based on in ovo electroporation for chicken embryonic central nervous system
Authors: Yang Ciqing , Li Xiaoying , Li Shuanqing , Chai Xuejun , Guan Lihong , Qiao Liang , Li Han , Lin Juntang
Published: December 2018

Organotypic slice culture is a living cell research technique which blends features of both in vivo and in vitro techniques. While organotypic brain slice culture techniques have been well established in rodents, there are few reports on the study of organotypic slice culture, especially of the central nervous system (CNS), in chicken embryos. We established a combined in ovo electroporation and organotypic slice culture method to study exogenous genes functions in the CNS during chicken embryo development. We performed in ovo electroporation in the spinal cord or optic tectum prior to slice culture. When embryonic development reached a specific stage, green fluorescent protein (GFP)‐positive embryos were selected and fluorescent expression sites were cut under stereo fluorescence microscopy. Selected tissues were embedded in 4% agar. Tissues were sectioned on a vibratory microtome and 300 μm thick sections were mounted on a membrane of millicell cell culture insert. The insert was placed in a 30‐mm culture dish and 1 ml of slice culture media was added. We show that during serum‐free medium culture, the slice loses its original structure and propensity to be strictly regulated, which are the characteristics of the CNS. However, after adding serum, the histological structure of cultured‐tissue slices was able to be well maintained and neuronal axons were significantly longer than that those of serum‐free medium cultured‐tissue slices. As the structure of a complete single neuron can be observed from a slice culture, this is a suitable way of studying single neuronal dynamics. As such, we present an effective method to study axon formation and migration of single neurons in vitro.
Expert consensus for respiratory physiotherapy management of mechanically ventilated adults with community‐acquired pneumonia: A Delphi study
Authors: van der Lee Lisa , Hill Anne‐Marie , Patman Shane
Published: December 2018

Rationale and aims

Patients with community‐acquired pneumonia (CAP) are frequently admitted to an intensive care unit. Physiotherapy may be provided to optimize respiratory function; however, there is significant variability in clinical practice and limited research directing best practice for this cohort. This study aimed to determine expert consensus for best physiotherapy practice for invasively ventilated adults with CAP.

Method

A modified Delphi technique involved an international expert panel completing three rounds of an online questionnaire. The initial 35‐statement questionnaire, based on a systematic literature review and survey of current clinical practice, covered physiotherapy assessment and treatment of intubated patients with CAP. Quantitative data using Likert scales determined level of agreement, with qualitative data collected through open‐ended responses. Consensus threshold was set a priori at 70%. Items not achieving consensus were modified and new items added based on themes from qualitative data. Quantitative data were analysed descriptively, with thematic analysis used on qualitative data.

Results

The panel comprised 29 international clinical and academic experts in critical care physiotherapy. Response rate was more than 95% for each round. Outcome achieved was 38 consensus statements covering assessment and treatment, with 28 statements (74%) providing consensus on recommended clinical practice, two consensus disagreement statements (7%) for what practice is not recommended, and eight statements (21%) indicating which treatments may be beneficial.

Conclusion

Expert consensus regarding physiotherapy for intubated adults with CAP patients provides an evidence‐based approach to guide clinical practice. The consensus statements can also be used to guide research evaluating physiotherapy interventions for patients with CAP.
Nutritionally improved third generation snacks produced by supercritical CO2 extrusion I. Physical and sensory properties
Authors: Panak Balentić Jelena , Jozinović Antun , Ačkar Đurđica , Babić Jurislav , Miličević Borislav , Benšić Mirta , Jokić Stela , Šarić Antonija , Šubarić Drago
Published: December 2018

This study was aimed at investigating the possible application of defatted hazelnut, camelina, pumpkin, and hemp cakes (by‐products of edible oil production) in the production of corn snack products, and to use supercritical CO2 as a blowing agent in indirectly expanded snack products. Cakes were added in 3, 6, and 9% proportions. Extrusion was performed in a laboratory single screw extruder and expanded by microwave. The obtained extrudates were evaluated for their physical and sensory properties. For comparison, directly expanded products without supercritical CO2, were produced with the same raw materials. The addition of the by‐product had a significant influence on the expansion ratio, bulk density, fracturability, and crispiness, and all four by‐products were successfully incorporated in the production of sensory acceptable, indirectly expanded snack products, produced by supercritical fluid extrusion. This type of products is interesting for consumers since it can be home‐made and produced without additives or any chemical substances.

Practical applications

By‐products of oil production (defatted press cake from pumpkin seeds, hazelnuts, camelina seeds, and hemp seeds), known as high‐fiber and high‐protein ingredients, were added in the corn grits with the aim to increase nutritional value of the product and to reduce the waste of the food industry.

For production of indirectly expanded corn snacks, supercritical CO2 is used as blowing agent, and pellets are expanded by microwave heating in few seconds. This is a good example of new products, which is interesting for consumers since it can be home‐made and it is without additives or any chemical substances.