bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of changing urine testing orderables and clinician order sets on inpatient urine culture testing: Analysis from a large academic medical center
Authors: Munigala Satish , Rojek Rebecca , Wood Helen , Yarbrough Melanie L. , Jackups Ronald R. , Burnham Carey-Ann D. , Warren David K.
Published: February 2019

Objective:

To evaluate the impact of changes to urine testing orderables in computerized physician order entry (CPOE) system on urine culturing practices.

Design:

Retrospective before-and-after study.

Setting:

A 1,250-bed academic tertiary-care referral center.

Patients:

Hospitalized adults who had ≥1 urine culture performed during their stay.

Intervention:

The intervention (implemented in April 2017) consisted of notifications to providers, changes to order sets, and inclusion of the new urine culture reflex tests in commonly used order sets. We compared the urine culture rates before the intervention (January 2015 to April 2016) and after the intervention (May 2016 to August 2017), adjusting for temporal trends.

Results:

During the study period, 18,954 inpatients (median age, 62 years; 68.8% white and 52.3% female) had 24,569 urine cultures ordered. Overall, 6,662 urine cultures (27%) were positive. The urine culturing rate decreased significantly in the postintervention period for any specimen type (38.1 per 1,000 patient days preintervention vs 20.9 per 1,000 patient days postintervention; P < .001), clean catch (30.0 vs 18.7; P < .001) and catheterized urine (7.8 vs 1.9; P < .001). Using an interrupted time series model, urine culture rates decreased for all specimen types (P < .05).

Conclusions:

Our intervention of changes to order sets and inclusion of the new urine culture reflex tests resulted in a 45% reduction in the urine cultures ordered. CPOE system format plays a vital role in reducing the burden of unnecessary urine cultures and should be implemented in combination with other efforts.
Integrating bedside nurses into antibiotic stewardship: A practical approach
Authors: Monsees Elizabeth A. , Tamma Pranita D. , Cosgrove Sara E. , Miller Melissa A. , Fabre Valeria
Published: February 2019

Nurses view patient safety as an essential component of their work and have reported a general interest in embracing an antibiotic steward role. However, antibiotic stewardship (AS) functions have not been formally integrated into nursing practice despite nurses’ daily involvement in clinical activities that impact antibiotic decisions (e.g., obtaining specimens for cultures, blood drawing for therapeutic drug monitoring). Recommendations to expand AS programs to include bedside nurses are generating support at a national level, yet a practical guidance on how nurses can be involved in AS activities is lacking. In this review, we provide a framework identifying selected practices where nurses can improve antibiotic prescribing practices through appropriate obtainment of Clostridioides difficile tests, appropriate urine culturing practices, optimal antibiotic administration, accurate and detailed documentation of penicillin allergy histories and through the prompting of antibiotic time outs. We identify reported barriers to engagement of nurses in AS and offer potential solutions that include patient safety principles and quality improvement strategies that can be used to mitigate participation barriers. This review will assist AS leaders interested in advancing the contributions of nurses into their AS programs by discussing education, communication, improvement models, and workflow integration enhancements that strengthen systems to support nurses as valued partners in AS efforts.
ESBL-colonization at ICU admission: impact on subsequent infection, carbapenem-consumption, and outcome
Authors: Martinez Aurélien Emmanuel , Widmer Andreas , Frei Reno , Pargger Hans , Tuchscherer Daniel , Marsch Stephan , Egli Adrian , Tschudin-Sutter Sarah
Published: February 2019

Objective:

To determine whether colonization with extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-PE) predicts the risk for subsequent infection and impacts carbapenem-consumption and outcome in intensive care unit (ICU) patients.

Design:

Prospective cohort study.

Setting:

The 2 ICUs in the University Hospital Basel in Switzerland.

Patients:

All patients admitted to the 2 ICUs providing mechanical ventilation and an expected ICU stay >48 hours.

Methods:

Patients were routinely screened for ESBL-PE carriage by rectal swab on admission. Competing risk regression analyses were applied to calculate hazard ratios (HRs) for infection with ESBL-PE and mortality. Length of hospital stay, length of ICU stay, and duration of carbapenem exposure were compared using the Mann-Whitney U test.

Results:

Among 302 patients, 24 (8.0%) were colonized with ESBL-PE on ICU admission. Infections with ESBL-PE occurred in 4 patients, of whom 3 (75%) were identified as ESBL-PE colonized on admission. ESBL-PE colonization on admission was associated with subsequent ESBL-PE infection (hazard ratio [HR], 25.52; 95% confidence interval [CI], 2.40–271.41; P = .007) and exposure to carbapenems (HR, 2.42; 95% CI, 1.01–5.79; P = .047), whereas duration of carbapenem exposure did not differ in relation to ESBL-PE colonization (median, 7 days [IQR, 3–8 days] vs median, 6 days [IQR 3–9 days]; P = 0.983). Patients colonized with ESBL-PE were not at increased risk for death overall (HR, 1.00; 95% CI, 0.44–2.30; P = .993) or death attributable to infection (HR, 1.20; 95% CI, 0.28–5.11; P = .808).

Conclusions:

Screening strategies for detection of ESBL-PE colonization on ICU admission may allow the identification of patients at highest risk for ESBL-PE infection and the correct allocation of empiric carbapenem treatment.
Association between vegetarian diets and cardiovascular risk factors in non-Hispanic white participants of the Adventist Health Study-2
Authors: Matsumoto Seiji , Beeson W. Lawrence , Shavlik David J. , Siapco Gina , Jaceldo-Siegl Karen , Fraser Gary , Knutsen Synnove F.
Published: February 2019

The association between dietary patterns and CVD risk factors among non-Hispanic whites has not been fully studied. Data from 650 non-Hispanic white adults who participated in one of two clinical sub-studies (about 2 years after the baseline) of the Adventist Health Study-2 (AHS-2) were analysed. Four dietary patters were identified using a validated 204-item semi-quantitative FFQ completed at enrolment into AHS-2: vegans (8·3 %), lacto-ovo-vegetarians (44·3 %), pesco-vegetarians (10·6 %) and non-vegetarians (NV) (37·3 %). Dietary pattern-specific prevalence ratios (PR) of CVD risk factors were assessed adjusting for confounders with or without BMI as an additional covariable. The adjusted PR for hypertension, high total cholesterol and high LDL-cholesterol were lower in all three vegetarian groups. Among the lacto-ovo-vegetarians the PR were 0·57 (95 % CI 0·45, 0·73), 0·72 (95 % CI 0·59, 0·88) and 0·72 (95 % CI 0·58, 0·89), respectively, which remained significant after additionally adjusting for BMI. The vegans and the pesco-vegetarians had similar PR for hypertension at 0·46 (95 % CI 0·25, 0·83) and 0·62 (95 % CI 0·42, 0·91), respectively, but estimates were attenuated and marginally significant after adjustment for BMI. Compared with NV, the PR of obesity and abdominal adiposity, as well as other CVD risk factors, were significantly lower among the vegetarian groups. Similar results were found when limiting analyses to participants not being treated for CVD risk factors, with the vegans having the lowest mean BMI and waist circumference. Thus, compared with the diet of NV, vegetarian diets were associated with significantly lower levels of CVD risk factors among the non-Hispanic whites.
Finding a High-Quality Initial Solution for the RRTs Algorithms in 2D Environments
Authors: Wang Jiankun , Chi Wenzheng , Shao Mingjie , Meng Max Q.-H.
Published: February 2019

In this paper, we propose a bioinspired path planning algorithm for finding a high-quality initial solution based on the pipeline of the Rapidly exploring Random Tree (RRT) method by modifying the sampling process. The modification mainly includes controlling the sampling space and using the probabilistic sampling with the two-dimensional Gaussian mixture model. Inspired by the tropism of plants, we use a Gaussian mixture model to imitate the tree’s growth in nature. In a 2D environment, we can get an approximate moving point’s probabilistic distribution, and the initial path can be found much quickly guided by the probabilistic heuristic. At the same time, only a small number of nodes are generated, which can reduce the memory usage. As a meta-algorithm, it can be applicable to other RRT methods and the performance of underlying algorithm is improved dramatically. We also prove that the probabilistic completeness and the asymptotic optimality depend on the original algorithm (other RRTs). We demonstrate the application of our algorithm in different simulated 2D environments. On these scenarios, our algorithm outperforms the RRT and the RRT* methods on finding the initial solution. When embedded into post-processing algorithms like the Informed RRT*, it also promotes the convergence speed and saves the memory usage.
A Fast Rotating Partition Satellite Selection Algorithm Based on Equal Distribution of Sky
Authors: Li Fangchao , Li Zengke , Gao Jingxiang , Yao Yifei
Published: February 2019

To achieve fast satellite selection for a multi-Global Navigation Satellite System (GNSS), thereby reducing the burden on a receiver's processing element and the cost of hardware, and improving the utilisation ratio of receiver signal channels, the relationship between the number of satellites and Geometric Dilution Of Precision (GDOP), the number of satellites selected and the computation time is analysed. A fast rotating partition algorithm for satellite selection based on equal distribution of the sky is proposed. The algorithm divides the satellite selection process into two parts: rough selection and detailed selection. Unhealthy satellites, according to a health identifier, and low elevation angle satellites with a large troposphere delay are eliminated during the rough selection process. During the detailed satellite selection process, the satellite sky is divided and rotated to match satellites based on the average angle distance between the satellite and central partition line. Static data from the International GNSS Service (IGS) station and dynamic data collected at China University of Mining and Technology were used to verify the algorithm, and the results demonstrated that an inverse matrix could be avoided to reduce computation complexity. Additionally, the new satellite selection algorithm has the merit that there is little effect on the computation when the selected satellites and number of satellites in the field increased. A single system of the Global Positioning System (GPS) and double system of GPS/Globalnaya Navigazionnaya Sputnikovaya Sistema (GLONASS) both passed the hypothesis test for each epoch. By including BeiDou Navigation Satellite System (BDS) data, data utilisation increased to more than 95% using the rotating partition algorithm. Also, the GDOP and positioning performance of a rotating partition algorithm and an optimal Dilution Of Precision (DOP) algorithm are compared in this paper, and the analysis result shows that both of the algorithms have only a small difference of GDOP and have comparable positioning performance.
A NOTE ON OPTIMAL DEBT REDUCTION POLICIES
Authors: la Torre Davide , Marsiglio Simone
Published: February 2019

We analyze the optimal debt reduction problem in an uncertainty context. The social planner has a finite horizon and seeks to minimize the social costs associated with debt repayment by taking into account not only the short-run costs of the policy, but also the long-run costs associated with the outstanding level of debt. We characterize the optimal policy and the dynamics of the debt-to-GDP ratio, showing that it will decrease over time if economic policy is effective enough. We characterize how the evolution of the debt-to-GDP ratio depends on the main parameters and we present a simple calibration based on Greek data to illustrate the implications of our analysis in real-world setups.
Midsummer Dreams: Felix Mendelssohn’s Swedish Connections
Authors: Santos Rutschman Kirsten
Published: February 2019

Two years after completing his overture toA Midsummer Night’s Dream(1826), Felix Mendelssohn-Bartholdy began to write of another vision: visiting his friend, the composer Adolf Fredrik Lindblad, in Sweden. Over the coming years, as Mendelssohn continually returned to this idea, additional reasons to make such a journey presented themselves: performances of his works in that city, including the Shakespearean overture, were well received; he became personally acquainted with Crown Prince Oscar, to whom he dedicated the op. 44 string quartets; he was elected to the Royal Swedish Academy of Music; his first cousin, Josephine (‘Peppi’) Benedicks, lived in Stockholm; and his friendship with Jenny Lind in the last years of his life only strengthened his interest in the north.

While Mendelssohn’s letters to Lindblad have long been known to scholars, the Gegenbriefe from Lindblad remain unpublished. For the first time, his voice is now fully restored to the conversation in an extensive correspondence that contributes to knowledge of Mendelssohn’s interpretations of his own music and his early reverence for the late Beethoven string quartets. In addition, this article also uncovers epistolary evidence of a cluster of related compositions by Mendelssohn and Lindblad spawned by Mendelssohn’s interest in the quartet in F Major (op. 135), including a little-known song that Lindblad dedicated to Felix on the occasion of his marriage.

Mendelssohn’s journeys to Scotland and Italy inspired his musical imagination in ways that have richly benefitted the concert repertoire. How might he have translated his impressions of Nordic history, culture and geography into new aural atmospheres, had he followed his dream to travel northwards?
CPW fed rectangular rings-based patch antenna with DGS for WLAN/UNII applications
Authors: Singla Geetanjali , Khanna Rajesh , Parkash Davinder
Published: February 2019

The spectral congestion in existing Industrial, Scientific, and Medical (ISM) Wireless Local Area Network (WLAN) bands has led to the emergence of new ISM bands (Unlicensed National Information Infrastructure (UNII)) from 5.150 to 5.710 GHz. In this paper, a simple uniplanar, high gain, microstrip antenna is designed, fabricated, and tested for existing WLAN and new UNII standards. The proposed antenna provides dualband operation by joining two rectangular rings and cutting Defected Ground Structure in the Coplanar Wave Guide (CPW) feed. The experimental and simulation results show good return loss characteristics and stable radiation pattern over the desired frequency bands ranging from 2.20 to 2.65 GHz (WLAN band) at a lower frequency and from 5.0 to 5.45 GHz (UNII-1/UNII-2 bands). The measured peak gains are 5.5 and 4.9 dBi at 2.45 GHz (WLAN band) and 5.15 GHz (UNII band), respectively.
“Friends-and-Neighbors” Mobilization: A Field Experimental Replication and Extension
Authors: Panagopoulos Costas , Bailey Kendall
Published: February 2019

Key [1949. Southern Politics in State and Nation. New York: A.A. Knopf] observed voters tend to support local candidates at higher rates, a phenomenon he termed “friends-and-neighbors” voting. In a recent study, Panagopoulos et al. [2017. Political Behavior 39(4): 865–82] deployed a nonpartisan randomized field experiment to show that voters in the September 2014 primary election for state senate in Massachusetts were mobilized on the basis of shared geography. County ties and, to a lesser extent, hometown ties between voters and candidates have the capacity to drive voters to the polls. We partnered with a national party organization to conduct a similar, partisan experiment in the November 2014 general election for the Pennsylvania state senate. We find localism cues can stimulate voting in elections, including in neighboring communities that lie beyond the towns and counties in which the target candidate resided, at least among voters favorably disposed to a candidate and even when voters reside in the home county of the opponent.
Association Between Bat Vitamin D Receptor 3′ Haplotypes and Vitamin D Levels at Baseline and a Lower Response After Increased Vitamin D Supplementation and Exposure to Sunlight
Authors: Pérez-Alonso María , Briongos Laisa-Socorro , Ruiz-Mambrilla Marta , Velasco Eladio A. , Olmos José M. , de Luis Daniel , Dueñas-Laita Antonio , Pérez-Castrillón José-Luis
Published: February 2019

Abstract. Objective: The aim of this study was to evaluate the relationship between vitamin D levels at baseline and after 12 weeks of supplementation/exposure to sunlight and VDR genotypes (BsmI, TaqI and ApaI) and haplotypes in a homogeneous population of postmenopausal women.

Methods: We made a prospective study in which 151 women were randomized to two groups: One with 1000 mg of calcium and 800 IU vitamin D supplementation (102 women) and a placebo group with neither calcium or vitamin D supplementation (49 women). The follow-up was from May to September 2012.Vitamin D was determined by chemiluminescent immunoassay. Genotypes were determined using the Sequenomi Plexplatform and haplotypes using PHASE software.

Results: Baseline (25 ± 10 ng/ml vs.23 ± 9 ng/ml, p > 0.05) and 12-week (32 ± 8 ng/ml vs.29 ± 10 ng/ml, p > 0.05) vitamin D levels were similar between the two groups. The genetic study was made in the total population. There were no differences in baseline and final levels of vitamin D in terms of genotypes and haplotypes, except for the Bat haplotype, whose baseline values were lower (25OHD: 21 ± 10 ng/ml vs. 21 ± 10 ng/ml, p = 0.038). The rate of nonresponders in this group was 15 % (p = 0.001), compared with 9 %, 2 % and 3 % in the other groups.

Conclusions: The Bat haplotype was associated with lower baseline levels of vitamin D and a worse response to supplementation and, therefore, may be a risk factor for vitamin D deficiency.
Relationship between vitamin D level and Bechcet’s disease activity: A systematic review and meta-analysis
Authors: Khabbazi Alireza , Ghojazadeh Morteza , Hajebrahimi Sakineh , Nikniaz Zeinab
Published: February 2019

Abstract. Aim: In the present study, the evidence about the association between vitamin D deficiency and Behcet’s disease activity was systematically reviewed and meta-analyzed.

Method: We searched the English and Persian databases of Medline (Ovid), CINHAL, Scopus, Proquest, the Cochrane library and SID, IranDoc, Magiran, Iran Medex for articles published up until May 2018 with the keywords were related to serum vitamin D and active and inactive Behcet’s disease in adults. Meta-analysis was done using the CMA software.

Results: A total of 138 titles were retrieved and reduced to 80 titles after deletion of duplicates and finally after close assessing of titles and abstracts eight eligible studies including a total of 939 participants were identified for systematic review and meta-analysis. According to the results of the meta-analysis, the pooled effect size of the differences in the serum level of vitamin D in patients with inactive Behçet’s Disease and healthy controls was [OR:−0.05; 95% CI:−2.05, 1.94; p = 0.95]. The serum vitamin D level was significantly lower in active patients compared with healthy controls [OR:1.21; 95%CI: −0.12, 2.31; p = 0.03]. The pooled effect size of the differences in the serum level of vitamin D in active and inactive Behçet’s Disease was [OR:−0.71; 95%CI: −1.41, −0.007; p = 0.04]

Conclusion: There is an association between vitamin D deficiency and active Behçet’s Disease. Future studies investigating the association of vitamin D deficiency and Behçet’s Disease needs to involve following information: dietary intake of calcium and vitamin D, measuring of sun exposure, report of drug consumption and physical activity level.
The Impact of Strong El Niño and La Niña Events on the North Atlantic
Authors: Hardiman S. C. , Dunstone N. J. , Scaife A. A. , Smith D. M. , Ineson S. , Lim J. , Fereday D.
Published: February 2019

The impact of strong La Niña events on January–February North Atlantic mean sea level pressure is unknown, as these events have never been observed. Using large ensembles from the Met Office decadal prediction system, examples of strong La Niña events are simulated and the Atlantic response to these is found to be a positive North Atlantic Oscillation. This is very different to the wavelike response observed and simulated for strong El Niño events. The reason for this difference is traced to the fact that the December‐January‐February mean tropospheric teleconnection of El Niño–Southern Oscillation to the North Atlantic dominates for strong El Niño events, while the stratospheric teleconnection dominates for strong La Niña events. The strength of the tropospheric pathway grows linearly and symmetrically with El Niño–Southern Oscillation. The stratospheric pathway is the source of the asymmetry between January and February surface responses to strong El Niño and strong La Niña events.
Does the Solar Wind Electric Field Control the Reconnection Rate at Earth's Subsolar Magnetopause?
Authors: Dorelli John C.
Published: February 2019

We demonstrate that the reconnection rate at the subsolar magnetopause is strongly controlled by the solar wind electric field and depends weakly on the local properties of the dissipation region. Our approach is to match the solar wind and magnetospheric states in an internal boundary layer described by the Cassak and Shay (2007, https://doi.org/10.1063/1.2795630) expression for two‐dimensional asymmetric reconnection. Faraday's law along the Sun‐Earth line determines the variation of the solar wind electric field from the bow shock to the magnetopause. While the magnetospheric plasma exerts some control over the reconnection rate, magnetic flux pileup in the sheath partially compensates for any local reduction in the reconnection rate. For a fixed magnetospheric state, the reconnection rate is shown to be directly proportional to the solar wind electric field, thus explaining why the solar wind electric field correlates well with geomagnetic indices.
Tectonothermal Evolution of the Broadly Rifted Zone, Ethiopian Rift
Authors: Boone S. C. , Balestrieri M.‐L. , Kohn B. P. , Corti G. , Gleadow A. J. W. , Seiler C.
Published: February 2019

The Broadly Rifted Zone (BRZ) of southern Ethiopia is a long‐lived and structurally complex segment of the East African Rift System. However, due to poor surface exposure of early synrift strata and a dearth of subsurface data, the evolution of the BRZ remains poorly understood. We present new apatite (U‐Th‐Sm)/He and augmented apatite fission track low‐temperature thermochronology data from the Beto and Galana basin boundary fault systems to constrain the tectonothermal evolution of the western and eastern BRZ, respectively. Time‐temperature reconstructions suggest that East African Rift System‐related extension began concurrently across the BRZ in the early Miocene (20–17 Ma), at least 6 Myr prior to faulting in the Main Ethiopian Rift further north. Increased time‐temperature resolution provided by multithermochronometer analyses reveals contrasting along‐strike spatiotemporal variations in Beto and Galana margin cooling histories, which appear to mirror the disparate structural geometries of their basin‐bounding normal fault arrays. Longitudinal contrasts in basin architecture and rift‐related cooling histories across the BRZ may reflect the region's heterogeneous distribution of preexisting basement fabrics, namely, the presence of a previously reported N‐NNE trending Neoproterozoic suture zone beneath the eastern BRZ. Its influence may explain both the development of long, curvilinear faults and the gradual basinward migration of strain exhibited by the easternmost BRZ, absent further west. The anomalous evolution of the BRZ compared to the greater Ethiopian Rift, both in its earlier onset and its wider deformation zone, likely results from its inheritance of preattenuated lithosphere, thermomechanically modified by earlier Cretaceous‐Paleogene Anza‐South Sudan rifting and/or Eocene plume impingement.
Late Quaternary Activity of the La Rinconada Fault Zone, San Juan, Argentina
Authors: Rimando Jeremy M. , Schoenbohm Lindsay M. , Costa Carlos H. , Owen Lewis A. , Cesta Jason M. , Richard Andres D. , Gardini Carlos E.
Published: February 2019

Most of the permanent deformation in the Pampean Flat slab segment of the central Andes is taken up at the Andean Orogenic Front in Argentina, a narrow zone between the Eastern Precordillera and Sierras Pampeanas that comprises one of the world's most seismically active thrust zones. Active faults and folds in the region have been extensively mapped but still largely lack information on style and rates of deformation, which is essential for understanding the distribution of regional strain and estimating the seismic potential of individual faults. Structural, geomorphic, and36Cl cosmogenic radionuclide surface exposure age methods are used to focus on key sites along the 30‐km‐long La Rinconada Fault Zone in this region of west‐central Argentina, which is ~15 km away from the highly populated (~500,000) city of San Juan, to define a late Quaternary average shortening rate of 0.41 ± 0.01 mm/year. This slip rate is the same order of magnitude, but slightly lower than nearby similar east dipping Eastern Precordillera faults including the La Laja and Las Tapias Faults. Relatively low slip rates are interpreted as being a consequence of distributed deformation between the latitude of the La Rinconada Fault Zone (31 and 32°S), as compared to between latitudes 32 to 33°S where deformation appears to be focused on fewer structures, including the Las Peñas and La Cal Thrust Faults. The La Rinconada Fault Zone is capable of generating earthquakes ofMw6.6–7.2, but further investigations are required to determine timing and recurrence intervals of discrete events.
Fluid Geochemistry Contribution to the Interpretation of the 2011–2012 Unrest of Santorini, Greece, in the Frame of the Dynamics of the Aegean Volcanic Arc
Authors: Tarchini L. , Carapezza M. L. , Ranaldi M. , Sortino F. , Gattuso A. , Acocella V.
Published: February 2019

Tectonic and magmatic activity may couple at volcanic arcs, even though any relationship is less defined in smaller arcs, experiencing limited activity. Here we use gas geochemistry data collected during the 2011–2012 unrest at Santorini (Greece) to understand better the dynamics of the Aegean Volcanic Arc with regard to its tectonic setting. Since the most recent eruption in 1950 and before the unrest, minor seismicity and CO2 degassing (mainly from the fumaroles of Nea Kameni islet) were observed at Santorini. On January 2011, anomalous seismicity along the NE‐SW trending Kameni Line was accompanied by an inflation north of Nea Kameni. Fumarolic gas composition changed and gas release notably increased. We carried out geochemical study on both Kameni and Thera islands from January 2012 to June 2013. We repeated surveys of diffuse soil CO2 degassing and of in‐soil gas concentration, and we analyzed fumaroles and gas dissolved in thermal waters for chemical and isotopic composition. In agreement with previous studies, our geochemical data, particularly the diffuse soil CO2 flux increase, the increase of H2 content, and of CO2/CH4 and 3He/4He ratios in fumarolic gases, support geophysical data in indicating that unrest was associated with the emplacement of new mafic magma. This unrest had limited effect on the regional setting, with gas emissions focusing along the regional NE‐SW structures, without triggering by any seismic event, conversely to the 1950 eruption, which probably occurred in a frame of general tectonic reorganization of the Aegean microplate.
Characterization of a novel murine Sost ERT2 Cre model targeting osteocytes
Authors: Maurel Delphine B. , Matsumoto Tsutomu , Vallejo Julian A. , Johnson Mark L. , Dallas Sarah L. , Kitase Yukiko , Brotto Marco , Wacker Michael J. , Harris Marie A. , Harris Stephen E. , Bonewald Lynda F.
Published: February 2019

Transgenic mice are widely used to delete or overexpress genes in a cell specific manner to advance knowledge of bone biology, function and disease. While numerous Cre models exist to target gene recombination in osteoblasts and osteoclasts, few target osteocytes specifically, particularly mature osteocytes. Our goal was to create a spatial and temporal conditional Cre model using tamoxifen to induce Cre activity in mature osteocytes using a Bac construct containing the 5’ and 3’ regions of the Sost gene (Sost ERT2 Cre). Four founder lines were crossed with the Ai9 Cre reporter mice. One founder line showed high and specific activity in mature osteocytes. Bones and organs were imaged and fluorescent signal quantitated. While no activity was observed in 2 day old pups, by 2 months of age some osteocytes were positive as osteocyte Cre activity became spontaneous or ‘leaky’ with age. The percentage of positive osteocytes increased following tamoxifen injection, especially in males, with 43% to 95% positive cells compared to 19% to 32% in females. No signal was observed in any bone surface cell, bone marrow, nor in muscle with or without tamoxifen injection. No spontaneous signal was observed in any other organ. However, with tamoxifen injection, a few positive cells were observed in kidney, eye, lung, heart and brain. All other organs, 28 in total, were negative with tamoxifen injection. However, with age, a muscle phenotype was apparent in the Sost-ERT2 Cre mice. Therefore, although this mouse model may be useful for targeting gene deletion or expression to mature osteocytes, the muscle phenotype may restrict the use of this model to specific applications and should be considered when interpreting data.
BCL-2 family isoforms in apoptosis and cancer
Authors: Warren Chloe F. A. , Wong-Brown Michelle W. , Bowden Nikola A.
Published: February 2019

The BCl-2 family has long been identified for its role in apoptosis. Following the initial discovery of BCL-2 in the context of B-cell lymphoma in the 1980s, a number of homologous proteins have since been identified. The members of the Bcl-2 family are designated as such due to their BCL-2 homology (BH) domains and involvement in apoptosis regulation. The BH domains facilitate the family members’ interactions with each other and can indicate pro- or anti-apoptotic function. Traditionally, these proteins are categorised into one of the three subfamilies; anti-apoptotic, BH3-only (pro-apoptotic), and pore-forming or ‘executioner’ (pro-apoptotic) proteins. Each of the BH3-only or anti-apoptotic proteins has a distinct pattern of activation, localisation and response to cell death or survival stimuli. All of these can vary across cell or stress types, or developmental stage, and this can cause the delineation of the roles of BCL-2 family members. Added to this complexity is the presence of relatively uncharacterised isoforms of many of the BCL-2 family members. There is a gap in our knowledge regarding the function of BCL-2 family isoforms. BH domain status is not always predictive or indicative of protein function, and several other important sequences, which can contribute to apoptotic activity have been identified. While therapeutic strategies targeting the BCL-2 family are constantly under development, it is imperative that we understand the molecules, which we are attempting to target. This review, discusses our current knowledge of anti-apoptotic BCL-2 family isoforms. With significant improvements in the potential for splicing therapies, it is important that we begin to understand the distinctions of the BCL-2 family, not limited to just the mechanisms of apoptosis control, but in their roles outside of apoptosis.
Angiomotin-p130 inhibits β-catenin stability by competing with Axin for binding to tankyrase in breast cancer
Authors: Yang Jiao , Zhang Xiaoman , Chen Zheling , Shen Yanwei , Wang Fan , Wang Yaochun , Liu Yu , Liu Peijun , Yang Jin
Published: February 2019

Growing evidence indicates that Angiomotin (Amot)-p130 and Amot-p80 have different physiological functions. We hypothesized that Amot-p130 is a tumor suppressor gene in breast cancer, in contrast with the canonical oncogenicity of Amot-p80 or total Amot. To clarify the role of Amot-p130 in breast cancer, we performed real-time quantitative PCR, western blotting, flow cytometry, microarray, immunofluorescence, immunoprecipitation, and tumor sphere-formation assays in vitro, as well as tumorigenesis and limited-dilution analysis in vivo. In this study, we showed that Amot-p130 inhibited the proliferation, migration, and invasion of breast cancer cells. Interestingly, transcriptional profiles indicated that genes differentially expressed in response to Amot-p130 knockdown were mostly related to β-catenin signaling in MCF7 cells. More importantly, most of the downstream partners of β-catenin were associated with stemness. In a further validation, Amot-p130 inhibited the cancer stem cell potential of breast cancer cells both in vitro and in vivo. Mechanistically, Amot-p130 decreased β-catenin stability by competing with Axin for binding to tankyrase, leading to a further inhibition of the WNT pathway. In conclusions, Amot-p130 functions as a tumor suppressor gene in breast cancer, disrupting β-catenin stability by competing with Axin for binding to tankyrase. Amot-p130 was identified as a potential target for WNT pathway-targeted therapies in breast cancer.
Potassium channel activity controls breast cancer metastasis by affecting β-catenin signaling
Authors: Breuer Eun-Kyoung , Fukushiro-Lopes Daniela , Dalheim Annika , Burnette Miranda , Zartman Jeremiah , Kaja Simon , Wells Claire , Campo Loredana , Curtis Kimberly J. , Romero-Moreno Ricardo , Littlepage Laurie E. , Niebur Glen L. , Hoskins Kent , Nishimura Michael I. , Gentile Saverio
Published: February 2019

Potassium ion channels are critical in the regulation of cell motility. The acquisition of cell motility is an essential parameter of cancer metastasis. However, the role of K+ channels in cancer metastasis has been poorly studied. High expression of the hG1 gene, which encodes for Kv11.1 channel associates with good prognosis in estrogen receptor-negative breast cancer (BC). We evaluated the efficacy of the Kv11.1 activator NS1643 in arresting metastasis in a triple negative breast cancer (TNBC) mouse model. NS1643 significantly reduces the metastatic spread of breast tumors in vivo by inhibiting cell motility, reprogramming epithelial–mesenchymal transition via attenuation of Wnt/β-catenin signaling and suppressing cancer cell stemness. Our findings provide important information regarding the clinical relevance of potassium ion channel expression in breast tumors and the mechanisms by which potassium channel activity can modulate tumor biology. Findings suggest that Kv11.1 activators may represent a novel therapeutic approach for the treatment of metastatic estrogen receptor-negative BC. Ion channels are critical factor for cell motility but little is known about their role in metastasis. Stimulation of the Kv11.1 channel suppress the metastatic phenotype in TNBC. This work could represent a paradigm-shifting approach to reducing mortality by targeting a pathway that is central to the development of metastases.
CXCL5 induces tumor angiogenesis via enhancing the expression of FOXD1 mediated by the AKT/NF-κB pathway in colorectal cancer
Authors: Chen Chun , Xu Zhuo-Qing , Zong Ya-Ping , Ou Bao-Chi , Shen Xiao-Hui , Feng Hao , Zheng Min-Hua , Zhao Jing-Kun , Lu Ai-Guo
Published: February 2019

The mechanisms underlying the role of CXCL5 in tumor angiogenesis have not been fully defined. Here, we examined the effect of CXCL5 on tumor angiogenesis in colorectal cancer (CRC). Immunohistochemistry was used to monitor the expression of CXCL5 and CD31 in CRC patients’ tissues. HUVEC cell lines stably transfected with shCXCR2 and shFOXD1 lentivirus plasmids were used in an in vitro study. Based on some molecular biological experiments in vitro and in vivo, we found that CXCL5 was upregulated in tumor tissues and that its level positively correlated with the expression of CD31. Next, we used recombinant human CXCL5 (rhCXCL5) to stimulate HUVECs and found that their tube formation ability, proliferation, and migration were enhanced by the activation of the AKT/NF-κB/FOXD1/VEGF-A pathway in a CXCR2-dependent manner. However, silencing of CXCR2 and FOXD1 or inhibition of the AKT and NF-κB pathways could attenuate the tube formation ability, proliferation, and migration of rhCXCL5-stimulated HUVECs in vitro. rhCXCL5 can promote angiogenesis in vivo in Matrigel plugs, and the overexpression of CXCL5 can also increase microvessel density in vivo in a subcutaneous xenotransplanted tumor model in nude mice. Taken together, our findings support CXCL5 as an angiogenic factor that can promote cell metastasis through tumor angiogenesis in CRC. Furthermore, we propose that FOXD1 is a novel regulator of VEGF-A. These observations open new avenues for therapeutic application of CXCL5 in tumor anti-angiogenesis.
Polygyny is linked to accelerated birdsong evolution but not to larger song repertoires
Authors: Snyder Kate T. , Creanza Nicole
Published: February 2019

Non-monogamous mating behaviors including polygyny or extra-pair paternity are theorized to amplify sexual selection, since some males attract multiple mates or copulate with paired females. In several well-studied songbird species, females prefer more complex songs and larger repertoires; thus, non-monogamous mating behaviors are predicted to accelerate song evolution, particularly toward increased complexity. However, studies within songbird clades have yielded mixed results, and the effect of non-monogamy on song evolution remains unclear. Here, we construct a large-scale database synthesizing mating system, extra-pair paternity, and song information and perform comparative analyses alongside songbird genetic phylogenies. Our results suggest that polygyny drives faster evolution of syllable repertoire size (measured as average number of unique syllables), but this rapid evolution does not produce larger repertoires in polygynous species. Instead, both large and small syllable repertoires quickly evolve toward moderate sizes in polygynous lineages. Contrary to expectation, high rates of extra-pair paternity coincide with smaller repertoires.
Auxin Response Factors promote organogenesis by chromatin-mediated repression of the pluripotency gene SHOOTMERISTEMLESS
Authors: Chung Yuhee , Zhu Yang , Wu Miin-Feng , Simonini Sara , Kuhn Andre , Armenta-Medina Alma , Jin Run , Østergaard Lars , Gillmor C. Stewart , Wagner Doris
Published: February 2019

Specification of new organs from transit amplifying cells is critical for higher eukaryote development. In plants, a central stem cell pool maintained by the pluripotency factor SHOOTMERISTEMLESS (STM), is surrounded by transit amplifying cells competent to respond to auxin hormone maxima by giving rise to new organs. Auxin triggers flower initiation through Auxin Response Factor (ARF) MONOPTEROS (MP) and recruitment of chromatin remodelers to activate genes promoting floral fate. The contribution of gene repression to reproductive primordium initiation is poorly understood. Here we show that downregulation of the STM pluripotency gene promotes initiation of flowers and uncover the mechanism for STM silencing. The ARFs ETTIN (ETT) and ARF4 promote organogenesis at the reproductive shoot apex in parallel with MP via histone-deacetylation mediated transcriptional silencing of STM. ETT and ARF4 directly repress STM, while MP acts indirectly, through its target FILAMENTOUS FLOWER (FIL). Our data suggest that – as in animals- downregulation of the pluripotency program is important for organogenesis in plants.
Multi-band mass enhancement towards critical doping in a pnictide superconductor
Authors: Moir Camilla Margaret , Riggs Scott Chandler , Galvis Jose Augusto , Lian Xiujun , Giraldo-Gallo Paula , Chu Jiun-Haw , Walmsley Philip , Fisher Ian Randal , Shekhter Arkady , Boebinger Gregory Scott
Published: February 2019

Near critical doping, high-temperature superconductors exhibit multiple anomalies associated with enhanced electronic correlations and quantum criticality. Quasiparticle mass enhancement approaching optimal doping has been reported in quantum oscillation measurements in both cuprate and pnictide superconductors. Although the data are suggestive of enhanced interactions, the microscopic theory of quantum oscillation measurements near a quantum critical point is not yet firmly established. It is therefore desirable to have a direct thermodynamic measurement of quasiparticle mass. Here we report high-magnetic field measurements of heat capacity in the doped pnictide superconductor BaFe2(As1−xPx)2. We observe saturation of the specific heat at high magnetic field in a broad doping range above optimal doping which enables a direct determination of the electronic density of states recovered when superconductivity is suppressed. Our measurements find a strong total mass enhancement in the Fermi pockets that superconduct. This mass enhancement extrapolates to a mass divergence at a critical doping of x = 0.28.
Association of IL1RAP-related genetic variation with cerebrospinal fluid concentration of Alzheimer-associated tau protein
Authors: Zettergren Anna , Höglund Kina , Kern Silke , Thorvaldsson Valgeir , Johan Skoog Msc , Hansson Oskar , Andreasen Niels , Bogdanovic Nenad , Blennow Kaj , Skoog Ingmar , Zetterberg Henrik
Published: February 2019

A possible involvement of the gene IL1RAP (interleukin-1 receptor-associated protein) in the pathogenesis of Alzheimer’s disease (AD) has been suggested in GWASs of cerebrospinal fluid (CSF) tau levels and longitudinal change in brain amyloid burden. The aim of this study was to examine previously implicated genetic markers in and near IL1RAP in relation to AD risk, CSF tau and Aβ biomarkers, as well as cognitive decline, in a case (AD)-control study and an age homogenous population-based cohort. Genotyping of IL1RAP-related single nucleotide polymorphisms (SNPs), selected based on previous GWAS results, was performed. 3446 individuals (1154 AD cases and 2292 controls) were included in the analyses of AD risk, 1400 individuals (cognitively normal = 747, AD = 653) in the CSF biomarker analyses, and 861 individuals in the analyses of cognitive decline. We found no relation between IL1RAP-related SNPs and AD risk. However, CSF total-tau and phospho-tau were associated with the SNP rs9877502 (p = 6 × 10−3 and p = 5 × 10−4). Further, nominal associations (p = 0.03–0.05) were found between three other SNPs and CSF biomarker levels, or levels of cognitive performance and decline in a sub-sample from the general population. These results support previous studies suggesting an association of IL1RAP with disease intensity of AD.
Comparative transcriptome analysis reveals differentially expressed genes related to the tissue-specific accumulation of anthocyanins in pericarp and aleurone layer for maize
Authors: Li Tingchun , Zhang Wei , Yang Huaying , Dong Qing , Ren Jie , Fan Honghong , Zhang Xin , Zhou Yingbing
Published: February 2019

Purple corn is a rich source of anthocyanins. In the experiment, two anthocyanins-enriched purple corn lines Ha0414 and Ha6130 were identified. The anthocyanins were respectively accumulated in the pericarp of Ha0414 and the aleurone layer of Ha6130 with different composition and content. Transcriptome analysis of the two tissues in both lines identified 16 and 14 differentially expressed genes belonging to anthocyanin metabolism pathway in pericarp and the aleurone layer, individually. Of these genes, two genes encoding 2-oxoglutarate (2OG) and Fe (II)-dependent oxygenase superfamily proteins, and one gene annotated as UDP-glycosyltransferase superfamily protein exhibited increased transcript abundance in both the colored pericarp and aleurone layer. Otherwise, one gene annotated as flavonoid 3′, 5′-hydroxylase, and another gene encoding flavonoid 3′-monooxygenase displayed increased transcript abundance in the aleurone layer of Ha6130. Moreover, 36 transcription factors were identified with increased transcript abundance in the pericarp of Ha0414, such as bHLH transcription factors, WRKY transcription factors, and HB transcription factors. And 79 transcription factors were isolated with an increased expression level in the aleurone layer of Ha6130, including MYB transcription factors, MYB-related transcription factors, and bHLH transcription factors. These genes expression may result in the tissue-specific accumulation of anthocyanins in pericarp and aleurone layer.
The effect of prebiotic fortified infant formulas on microbiota composition and dynamics in early life
Authors: Borewicz Klaudyna , Suarez-Diez Maria , Hechler Christine , Beijers Roseriet , de Weerth Carolina , Arts Ilja , Penders John , Thijs Carel , Nauta Arjen , Lindner Cordula , Van Leusen Ellen , Vaughan Elaine E. , Smidt Hauke
Published: February 2019

Gastrointestinal (GI) microbiota composition differs between breastfed and formula-fed infants. Today’s infant formulas are often fortified with prebiotics to better mimic properties of human milk with respect to its effect on GI microbiota composition and function. We used Illumina HiSeq sequencing of PCR-amplified 16S rRNA gene fragments to investigate the composition of faecal microbiota in 2–12 week old infants receiving either breastmilk, infant formulas fortified with prebiotics, or mixed feeding. We compared these results with results from infants fed traditional formulas used in the Netherlands in 2002–2003, which contained no added prebiotics. We showed that today’s formulas supplemented with either scGOS (0.24–0.50 g/100 ml) or scGOS and lcFOS (at a 9:1 ratio; total 0.6 g/100 ml) had a strong bifidogenic effect as compared to traditional formulas, and they also resulted in altered patterns of microbial colonisation within the developing infant gastrointestinal tract. We identified three microbial states (or developmental stages) in the first 12 weeks of life, with a gradual transition pattern towards a bifidobacteria dominated state. In infants receiving only fortified formulas, this transition towards the bifidobacteria dominated state was accelerated, whereas in infants receiving mixed feeding the transition was delayed, as compared to exclusively breastfed infants.
Cooling of atoms using an optical frequency comb
Authors: Šantić N. , Buhin D. , Kovačić D. , Krešić I. , Aumiler D. , Ban T.
Published: February 2019

We report on laser cooling of neutral rubidium atoms by using a single mode of a frequency comb. Cooling is achieved on a dipole-allowed transition at 780 nm in a one-dimensional retro-reflected beam geometry. Temperatures are measured using standard time-of-flight imaging. We show the dependence of the temperature on the cooling time, intensity and detuning of the frequency comb. The lowest temperature achieved is approximately equal to the Doppler temperature and is limited by the intensity of the comb mode driving the cooling transition. Additionally, we verify the analogy between frequency comb and continuous-wave laser cooling. Our work is a step towards laser cooling of atoms with strong cycling transitions in the vacuum ultraviolet, such as hydrogen, deuterium and antihydrogen, where generation of continuous-wave laser light is limited by current laser technology. Achieving efficient cooling at these wavelengths would significantly improve the precision of optical frequency standards, enable measurements of fundamental constants with unprecedented accuracy, improve tests of charge, parity, and time reversal symmetry, and open the way to achieving quantum degeneracy width new atomic species.