bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementing a course-based undergraduate research experience to grow the quantity and quality of undergraduate research in an animal science curriculum1
Authors: Jones Cassandra K , Lerner Annie B
Published: October 2019

Undergraduate research involves experiential learning methods that helps animal science students gain critical thinking skills. There is high demand for these opportunities. For example, 77.9% of incoming freshmen in the Department of Animal Sciences & Industry at Kansas State University in Fall 2017 and Fall 2018 planned to conduct research sometime during their undergraduate career (422 of 542 students). Conventional, one-on-one mentoring methods in the department were only serving 1.7% of the undergraduate population (21 of 1,212 students). This creates a unique challenge of increasing the number of undergraduate research opportunities, while maintaining the impact of individualized experiential learning. One method to address this challenge is the incorporation of a course-based research program. In this model, research projects are conducted during a conventional semester during scheduled classroom hours, with project components divided into 3 sections: (1) research preparation, including compliance requirements, hypothesis testing, experimental design, and protocol development; (2) data collection; and (3) data interpretation and dissemination. Students collect data as a team, but individually develop their own research abstract and poster to maintain a high level of experiential learning. By teaching multiple sections of this course per semester and incorporating the concepts into existing laboratories, 13.5% of students in the department completed undergraduate research in the 2018–2019 academic year (162 of 1,197 students). To monitor the quality of these experiences, student critical thinking ability was assessed using the online Critical Thinking Basic Concepts & Understanding Test (Foundation for Critical Thinking, Tomales, CA). Undergraduate research experiences increased (P = 0.028) the growth in student critical thinking score, but the type of research experience did not influence assessed skills (P > 0.281). Thus, course-based undergraduate research experiences may be an option for growing the quantity and quality of undergraduate research experience in animal science.
Sustained maternal inflammation during the early third-trimester yields intrauterine growth restriction, impaired skeletal muscle glucose metabolism, and diminished β-cell function in fetal sheep1,2
Authors: Cadaret Caitlin N , Merrick Elena M , Barnes Taylor L , Beede Kristin A , Posont Robert J , Petersen Jessica L , Yates Dustin T
Published: October 2019

Maternal inflammation causes fetal intrauterine growth restriction (IUGR), but its impact on fetal metabolism is not known. Thus, our objective was to determine the impact of sustained maternal inflammation in late gestation on fetal inflammation, skeletal muscle glucose metabolism, and insulin secretion. Pregnant ewes were injected every third day from the 100th to 112th day of gestation (term = 150 d) with saline (controls) or lipopolysaccharide (LPS) to induce maternal inflammation and IUGR (MI-IUGR). Fetal femoral blood vessels were catheterized on day 118 to assess β-cell function on day 123, hindlimb glucose metabolic rates on day 124, and daily blood parameters from days 120 to 125. Fetal muscle was isolated on day 125 to assess ex vivo glucose metabolism. Injection of LPS increased (P < 0.05) rectal temperatures, circulating white blood cells, and plasma tumor necrosis factor α (TNFα) concentrations in MI-IUGR ewes. Maternal leukocytes remained elevated (P < 0.05) and TNFα tended to remain elevated (P < 0.10) compared with controls almost 2 wk after the final LPS injection. Total white blood cells, monocytes, granulocytes, and TNFα were also greater (P < 0.05) in MI-IUGR fetuses than controls over this period. MI-IUGR fetuses had reduced (P < 0.05) blood O2 partial pressures and greater (P < 0.05) maternofetal O2 gradients, but blood glucose and maternofetal glucose gradients did not differ from controls. Basal and glucose-stimulated insulin secretion were reduced (P < 0.05) by 32% and 42%, respectively, in MI-IUGR fetuses. In vivo hindlimb glucose oxidation did not differ between groups under resting conditions but was 47% less (P < 0.05) in MI-IUGR fetuses than controls during hyperinsulinemia. Hindlimb glucose utilization did not differ between fetal groups. At day 125, MI-IUGR fetuses were 22% lighter (P < 0.05) than controls and tended to have greater (P < 0.10) brain/BW ratios. Ex vivo skeletal muscle glucose oxidation did not differ between groups in basal media but was less (P < 0.05) for MI-IUGR fetuses in insulin-spiked media. Glucose uptake rates and phosphorylated-to-total Akt ratios were less (P < 0.05) in muscle from MI-IUGR fetuses than controls regardless of media. We conclude that maternal inflammation leads to fetal inflammation, reduced β-cell function, and impaired skeletal muscle glucose metabolism that persists after maternal inflammation ceases. Moreover, fetal inflammation may represent a target for improving metabolic dysfunction in IUGR fetuses.
Effects of Silica-Based CimeXa and Drione Dusts Against Lone Star Tick (Ixodida: Ixodidae) on Cattle
Authors: Showler Allan T , Harlien Jessica L
Published: October 2019

Ixodid ticks vector pathogens of humans, livestock, and wildlife, and occur in tropical and temperate regions worldwide. We used the lone star tick, Amblyomma americanum (L.) (Ixodida: Ixodidae), as a model for other ixodid species, including the southern cattle fever tick, Rhipicephalus (Boophilus) microplus (Canestrini) (Ixodida: Ixodidae). We assessed the lethality of CimeXa, an inert silica-based desiccant dust, and Drione, a silica-based desiccant dust with pyrethrin and piperonyl butoxide (PBO), against A. americanum larvae and nymphs on calves. CimeXa was highly lethal to larvae released onto shaved calf skin 72–96 h previously, and moderately toxic to nymphs. It did not affect immature life stages treated after they began feeding because desiccation was offset by ingestion of blood. Being inert, CimeXa can protect cattle from infestation before feeding occurs for a potentially indefinite period of time. Drione killed immatures within 24 h when released on treated skin and when applied to feeding ixodids because of the pyrethrin and PBO (PBO will also reduce resistance to pyrethrin if it develops). When CimeXa was applied to calves with the hair intact, ≈90% and ≈70% of A. americanum larvae and nymphs, respectively, were killed within 24 h and Drione killed 100% of each life stage. Drione also prevented and drastically reduced egg production and hatching. While CimeXa protects against infestation by immatures, Drione will also control ticks that are feeding. When pyrethrin and PBO in Drione eventually degrade, the silica aerogel carrier can continue to protect against infestation indefinitely.
An insight into the extragalactic transient and variable microJy radio sky across multiple decades
Authors: Radcliffe Jack F , Beswick Robert J , Thomson A P , Garrett Michael A , Barthel Peter D , Muxlow Thomas W B
Published: October 2019

The mJy variable extragalactic radio sky is known to be broadly non-changing with approximately $3{{\ \rm per\ cent}}$ of persistent radio sources exhibiting variability that is largely active galactic nucleus-related (AGN). In the faint (<mJy) flux density regime, it is widely accepted that the radio source population begins to change from AGN dominated to star formation dominated, together with an emergent radio-quiet AGN component. Very little is known about the variable source component in this sub-mJy regime. In this paper, we provide the first insight into the μJy variable sky by performing a careful analysis using the deep VLA data in the well-studied GOODS-N field. Using five epochs spread across 22 yr, we investigate approximately 480 radio sources finding 10 that show signs of variability. We attribute this variability to the presence of an AGN in these systems. We confirm and extend the results of previous surveys, finding that variability in the faint radio sky is rather modest with only ≤2 per cent of sources exhibiting significant variability between any two epochs. We find that 70 per cent of variable sources show variability on time-scales of a few days while on longer decadal time-scales, the fraction of variable sources decreases to $\lt 1{{\ \rm per\ cent}}$. This suggests that the radio variability peaks on shorter time-scales as suggested by other studies. We find that 80 per cent of variable sources have VLBI counterparts, and we use multiwavelength data to infer that these may well be core-dominated FR-I sources as postulated by the wide-field VLBI surveys and semi-empirical simulations.
REBOUNDx: a library for adding conservative and dissipative forces to otherwise symplectic N-body integrations
Authors: Tamayo Daniel , Rein Hanno , Shi Pengshuai , Hernandez David M
Published: October 2019

Symplectic methods, in particular the Wisdom–Holman map, have revolutionized our ability to model the long-term, conservative dynamics of planetary systems. However, many astrophysically important effects are dissipative. The consequences of incorporating such forces into otherwise symplectic schemes are not always clear. We show that moving to a general framework of non-commutative operators (dissipative or not) clarifies many of these questions, and that several important properties of symplectic schemes carry over to the general case. In particular, we show that explicit splitting schemes generically exploit symmetries in the applied external forces, which often strongly suppress integration errors. Furthermore, we demonstrate that so-called ‘symplectic correctors’ (which reduce energy errors by orders of magnitude at fixed computational cost) apply equally well to weakly dissipative systems and can thus be more generally thought of as ‘weak splitting correctors’. Finally, we show that previously advocated approaches of incorporating additional forces into symplectic methods work well for dissipative forces, but give qualitatively wrong answers for conservative but velocity-dependent forces like post-Newtonian corrections. We release REBOUNDx, an open-source C library for incorporating additional effects into REBOUNDN-body integrations, together with a convenient python wrapper. All effects are machine independent and we provide a binary format that interfaces with the SimulationArchive class in REBOUND to enable the sharing and reproducibility of results. Users can add effects from a list of pre-implemented astrophysical forces, or contribute new ones.
Resolving accretion flows in nearby active galactic nuclei with the Event Horizon Telescope
Authors: Bandyopadhyay Bidisha , Xie Fu-Guo , Nagar Neil M , Schleicher Dominik R G , Ramakrishnan Venkatessh , Arévalo Patricia , López Elena , Diaz Yaherlyn
Published: October 2019

The Event Horizon Telescope (EHT), now with its first ever image of the photon ring around the supermassive black hole of M87, provides a unique opportunity to probe the physics of supermassive black holes through Very Long Baseline Interferometry (VLBI), such as the existence of the event horizon, the accretion processes as well as jet formation in low-luminosity AGNs (LLAGNs). We build a theoretical model that includes an advection dominated accretion flow (ADAF) with emission from thermal and non-thermal electrons in the flow and a simple radio jet outflow. The predicted spectral energy distribution (SED) of this model is compared to sub-arcsec resolution observations to get the best estimates of the model parameters. The model-predicted radial emission profiles at different frequency bands are used to predict whether the inflow can be resolved by the EHT or with telescopes such as the Global 3-mm VLBI array (GMVA). In this work the model is initially tested with high-resolution SED data of M87 and then applied to our sample of five galaxies (Cen A, M84, NGC 4594, NGC 3998, and NGC 4278). The model then allows us to predict if one can detect and resolve the inflow for any of these galaxies using the EHT or GMVA within an 8 h integration time.
A multidimensional implementation of the Advanced Spectral neutrino Leakage scheme
Authors: Gizzi D , O’Connor E , Rosswog S , Perego A , Cabezón R M , Nativi L
Published: October 2019

We present a new, multidimensional implementation of the Advanced Spectral Leakage (ASL) scheme with the purpose of modelling neutrino–matter interactions in neutron star mergers. A major challenge is the neutrino absorption in the semitransparent regime, which is responsible for driving winds from the merger remnant. The composition of such winds is crucial in the understanding of the electromagnetic emission in the recently observed macronova following GW170817. Compared to the original version, we introduce an optical-depth-dependent flux factor to model the average angle of neutrino propagation, and a modulation that accounts for flux anisotropies in non-spherical geometries. We scrutinize our approach by first comparing the new scheme against the original one for a spherically symmetric core-collapse supernova snapshot, both in 1D and in 3D, and additionally against a two-moment (M1) scheme as implemented in 1D into the code GR1D. The luminosities and mean energies agree to a few per cents in most tests. Finally, for the case of a binary merger remnant snapshot we compare the new ASL scheme with the M1 scheme that is implemented in the Eulerian adaptive mesh refinement code flash. We find that the neutrino absorption distribution in the semitransparent regime is overall well reproduced. Both approaches agree to within $\lesssim 15{{\ \rm per\ cent}}$ for the average energies and to better than $\sim 35 {{\ \rm per\ cent}}$ in the total luminosities.
Inclined jets inside a common envelope of a triple stellar system
Authors: Schreier Ron , Hillel Shlomi , Soker Noam
Published: October 2019

We conduct a three-dimensional hydrodynamical simulation to study the interaction of two opposite inclined jets inside the envelope of a giant star, and find that the jets induce many vortexes inside the envelope and that they efficiently remove mass from the envelope and form a very clumpy outflow. We assume that this very rare type of interaction occurs when a tight binary system enters the envelope of a giant star, and that the orbital plane of the tight binary system and that of the triple stellar system are inclined to each other. We further assume that one of the stars of the tight binary system accretes mass and launches two opposite jets and that the jets’ axis is inclined to the angular momentum axis of the triple stellar system. The many vortexes that the jets induce along the orbit of the tight binary system inside the giant envelope might play an important role in the common envelope evolution (CEE) by distributing energy in the envelope. The density fluctuations that accompany the vortexes lead to an outflow with many clumps that might facilitate the formation of dust. This outflow lacks any clear symmetry, and it might account for very rare types of ‘messy’ planetary nebulae and ‘messy’ nebulae around massive stars. On a broader scope, our study adds to the notion that jets can play important roles in the CEE, and that they can form a rich variety of shapes of nebulae around evolved stars.
Cosmological constraints from galaxy–lensing cross-correlations using BOSS galaxies with SDSS and CMB lensing
Authors: Singh Sukhdeep , Mandelbaum Rachel , Seljak Uroš , Rodríguez-Torres Sergio , Slosar Anže
Published: October 2019

We present cosmological parameter constraints based on a joint modelling of galaxy–lensing cross-correlations and galaxy clustering measurements in the SDSS, marginalizing over small-scale modelling uncertainties using mock galaxy catalogues, without explicit modelling of galaxy bias. We show that our modelling method is robust to the impact of different choices for how galaxies occupy dark matter haloes and to the impact of baryonic physics (at the $\sim 2{{\ \rm per\ cent}}$ level in cosmological parameters) and test for the impact of covariance on the likelihood analysis and of the survey window function on the theory computations. Applying our results to the measurements using galaxy samples from BOSS and lensing measurements using shear from SDSS galaxies and CMB lensing from Planck, with conservative scale cuts, we obtain $S_8\equiv \left(\frac{\sigma _8}{0.8228}\right)^{0.8}\left(\frac{\Omega _\mathrm{ m}}{0.307}\right)^{0.6}=0.85\pm 0.05$ (stat.) using LOWZ × SDSS galaxy lensing, and S8 = 0.91 ± 0.1 (stat.) using combination of LOWZ and CMASS × Planck CMB lensing. We estimate the systematic uncertainty in the galaxy–galaxy lensing measurements to be $\sim 6{{\ \rm per\ cent}}$ (dominated by photometric redshift uncertainties) and in the galaxy–CMB lensing measurements to be $\sim 3{{\ \rm per\ cent}}$, from small-scale modelling uncertainties including baryonic physics.
Parameter inference and model comparison using theoretical predictions from noisy simulations
Authors: Jeffrey Niall , Abdalla Filipe B
Published: October 2019

When inferring unknown parameters or comparing different models, data must be compared to underlying theory. Even if a model has no closed-form solution to derive summary statistics, it is often still possible to simulate mock data in order to generate theoretical predictions. For realistic simulations of noisy data, this is identical to drawing realizations of the data from a likelihood distribution. Though the estimated summary statistic from simulated data vectors may be unbiased, the estimator has variance that should be accounted for. We show how to correct the likelihood in the presence of an estimated summary statistic by marginalizing over the true summary statistic in the framework of a Bayesian hierarchical model. For Gaussian likelihoods where the covariance must also be estimated from simulations, we present an alteration to the Sellentin–Heavens corrected likelihood. We show that excluding the proposed correction leads to an incorrect estimate of the Bayesian evidence with Joint Light-Curve Analysis data. The correction is highly relevant for cosmological inference that relies on simulated data for theory (e.g. weak lensing peak statistics and simulated power spectra) and can reduce the number of simulations required.
Lynx canadensis (Carnivora: Felidae)
Authors: Lavoie Maxime , Renard Aurélie , Larivière Serge
Published: October 2019

Lynx canadensis Kerr, 1792, commonly called the Canada lynx, is a medium size felid and is the second largest of the four species in the genus Lynx. It is distributed throughout the boreal forest of most of Canada and Alaska and across portions of the northern United States. It prefers dense, regenerating coniferous forests with moderate canopy and understory cover. L. canadensis is a snowshoe hare specialist, and its ecology, morphology, and behavior closely reflect that of its main prey. It is listed as “Least Concern” by the International Union for Conservation of Nature and Natural Resources, is on Appendix II of the Convention on International Trade in Endangered Species of Wild Fauna and Flora, and its population size trend is considered stable. However, the status of United States subpopulations, being largely peripheral to the Canadian population, is more tenuous and the species is protected.
JASPAR 2020: update of the open-access database of transcription factor binding profiles
Authors: Fornes Oriol , Castro-Mondragon Jaime A , Khan Aziz , van der Lee Robin , Zhang Xi , Richmond Phillip A , Modi Bhavi P , Correard Solenne , Gheorghe Marius , Baranašić Damir , Santana-Garcia Walter , Tan Ge , Chèneby Jeanne , Ballester Benoit , Parcy François , Sandelin Albin , Lenhard Boris , Wasserman Wyeth W , Mathelier Anthony
Published: October 2019

JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) for TFs across multiple species in six taxonomic groups. In this 8th release of JASPAR, the CORE collection has been expanded with 245 new PFMs (169 for vertebrates, 42 for plants, 17 for nematodes, 10 for insects, and 7 for fungi), and 156 PFMs were updated (125 for vertebrates, 28 for plants and 3 for insects). These new profiles represent an 18% expansion compared to the previous release. JASPAR 2020 comes with a novel collection of unvalidated TF-binding profiles for which our curators did not find orthogonal supporting evidence in the literature. This collection has a dedicated web form to engage the community in the curation of unvalidated TF-binding profiles. Moreover, we created a Q&A forum to ease the communication between the user community and JASPAR curators. Finally, we updated the genomic tracks, inference tool, and TF-binding profile similarity clusters. All the data is available through the JASPAR website, its associated RESTful API, and through the JASPAR2020 R/Bioconductor package.
Intrathecal liposomal cytarabine plus systemic therapy versus systemic chemotherapy alone for newly diagnosed leptomeningeal metastasis from breast cancer
Authors: Le Rhun Emilie , Wallet Jennifer , Mailliez Audrey , Le Deley Marie Cecile , Rodrigues Isabelle , Boulanger Thomas , Lorgis Veronique , Barrière Jerome , Robin Yves Marie , Weller Michael , Bonneterre Jacques
Published: October 2019

Background

DEPOSEIN (NCT01645839) was a randomized open-label phase III study to explore the role of intrathecal chemotherapy in patients with newly diagnosed leptomeningeal metastasis (LM), a common manifestation of breast cancer.

Methods

Patients with newly diagnosed LM defined by tumor cells in the cerebrospinal fluid or combination of clinical and neuroimaging signs of LM were randomized to receive systemic therapy alone (control group) or systemic therapy plus intrathecal liposomal cytarabine (experimental group). Progression-free survival related to LM (LM-PFS) was the primary endpoint.

Results

Thirty-seven and 36 patients were assigned to the control and the experimental groups. Median number of liposomal cytarabine injections in the experimental group was 5 (range 1–20). Focal radiotherapy was performed in 6 (16%) and 3 (8%) patients in the control and experimental groups. In the intent-to-treat population, median LM-PFS was 2.2 months (95% CI: 1.3–3.1) in the control versus 3.8 months (95% CI: 2.3–6.8) in the experimental group (hazard ratio 0.61, 95% CI: 0.38–0.98) (P = 0.04). Seventy-one patients have died. Median overall survival was 4.0 months (95% CI: 2.2–6.3) in the control versus 7.3 months (95% CI: 3.9–9.6) in the experimental group (hazard ratio 0.85, 95% CI: 0.53–1.36) (P = 0.51). Serious adverse events were reported in 22 and 30 patients, respectively. Quality of life until progression did not differ between groups.

Conclusion

The addition of intrathecal liposomal cytarabine to systemic treatment improves LM-related PFS. Confirmatory trials with optimized patient selection criteria and more active drugs may be required to demonstrate a survival benefit from intrathecal pharmacotherapy.
Incorporating New Technology Into a Surgical Technique: The Learning Curve of a Single Surgeon's Stereo-Electroencephalography Experience
Authors: McGovern Robert A , Butler Robert S , Bena James , Gonzalez-Martinez Jorge
Published: October 2019

BACKGROUND

Technological improvements frequently outpace the publication of randomized, controlled trials in surgical patients. This makes the application of new surgical techniques difficult as surgeons solely use clinical experience to guide changes in their practice.

OBJECTIVE

To quantitatively examine the learning curve of incorporating new technology into a surgical technique and discuss the clinical significance of incorporating this new technology into daily practice. To identify areas of improvement for operative efficiency and safety.

METHODS

A retrospective observational study examining quantitative measures of operative efficiency and safety from 2009 to 2017 in 454 consecutive patients undergoing stereo-electroencephalography depth electrode implantations.

RESULTS

The transition to a new robotic technique significantly improved operative times (196 min [95% CI 173-219] vs 115 min [95% CI 111-118], P < .0001). Cumulative sum (CUSUM) analysis demonstrated that mastery of the robotic technique took much longer than the frame-based technique (operative time peak at case 75 vs case 25, plateau of 150 vs 10 cases). Although hemorrhage rates using different vascular imaging techniques did not appear to differ using traditional statistical analysis (magnetic resonance imaging, MRI 22.3%, computed tomography angiography, CTA 17.9%, angiogram 18.1%, likelihood ratio χ2 = 4.84, P = .30), CUSUM analysis suggested MRI as the vascular imaging modality leading to higher hemorrhage and symptomatic hemorrhage rates at our center.

CONCLUSION

This experience demonstrates an improvement in operative efficiency through a series of changes made using clinical experience and intuition while transitioning to a completely new paradigm. CUSUM analysis identified potential areas for improvement in both operative efficiency and safety if used in a prospective manner.
ASSESSMENT OF DOSE DUE TO AMBIENT Rn222/Rn220 PROGENY IN DIFFERENT DWELLINGS OF JAMMU AND KASHMIR STATE, INDIA
Authors: Sharma S , Kumar A , Mehra R , Mishra R
Published: October 2019

The un-attached part of radon (222Rn) progeny is one of the imperative variables for the definitive evaluation of the effective dose from the radon exposure perspective, and it might fluctuate enormously in various ecological conditions. Therefore, estimate dispersion of 222Rn/220Rn progeny, un-attached part and aerosol concentration was estimated in an indoor domain of Jammu and Kashmir State, India utilizing progeny deposition based sensors. Distinctive sorts of residence were picked up for this exploratory examination and maximum 222Rn and thoron (220Rn) descendants concentration was found in working environments or workplaces when contrasted from other abodes because of low ventilation rate. The average evaluated portions of an unattached for 222Rn and 220Rn are 0.29 and 0.26 and in addition, observed to be most extreme in work environments. The age-dependent dose has furthermore been determined utilizing attached and un-attached 222Rn/220Rn progeny concentrations. The dose to trachea-bronchial region and aerosol concentrations has additionally been estimated.
Effects of amino acid biomass or feed-grade amino acids on growth performance of growing swine and poultry12
Authors: Wensley Madie R , Woodworth Jason C , Derouchey Joel M , Dritz Steve S , Tokach Mike D , Goodband Robert D , Walters Hunter G , Leopold Bryce A , Coufal Craig D , Haydon Keith D , Lee Jason T
Published: October 2019

Three experiments were conducted to determine the effect of three fermented amino acids (AA) with their respective biomass compared to crystalline AA on the growth performance of swine and poultry. In experiment 1, 315 barrows (DNA 200 × 400, initially 11.3 ± 0.69 kg) were allotted to 1 of 4 dietary treatments with 5 pigs per pen and 15 or 16 pens per treatment. Dietary treatments included a negative control (16% standardized ileal digestible [SID] Tryptophan:lysine [Trp:Lys] ratio), positive control (21% SID Trp:Lys ratio from crystalline Trp), or diets containing Trp with biomass to provide 21 or 23.5% SID Trp:Lys ratios, respectively. Pigs fed the positive control or low Trp with biomass diet had increased (P < 0.05) ADG compared to pigs fed the negative control diet, with pigs fed the high Trp with biomass diet intermediate. Pigs fed the low Trp with biomass diet had increased (P < 0.05) G:F compared to the negative control diet, with others intermediate. In experiment 2, 1,320 1-d-old male broilers (Cobb 500, initially 45.2 g) were allotted to one of four dietary treatments with 33 birds per pen and 10 pens per treatment. Dietary treatments included a negative control (58/58% Threonine:lysine [Thr:Lys] ratio), positive control (65/66% Thr:Lys ratio from crystalline Thr), or diets containing Thr with biomass to provide 65/66 or 69/70% Thr:Lys ratios in starter and grower diets, respectively. Broilers fed the positive control or Thr with biomass diets had increased (P < 0.05) ADG compared to broilers fed the negative control diet. Broilers fed the positive control or the low Thr with biomass diet had increased (P < 0.05) G:F compared to the negative control and high Thr with biomass treatments. In experiment 3, 2,100 one-day-old male broilers (Cobb 500, initially 39.4 g) were allotted to one of four dietary treatments with 35 birds per pen and 15 pens per treatment. Dietary treatments included a negative control (59/63% Valine:lysine [Val:Lys] ratio), positive control (75/76% Val:Lys ratio from crystalline Val), or diets containing Val with biomass to provide 75/76 or 84/83% Val:Lys ratios in starter and grower diets, respectively. Broilers fed the positive control or Val with biomass diets had increased (P < 0.05) ADG, ADFI, and G:F compared to those fed the negative control diet. In conclusion, Trp, Thr, or Val with their respective biomass appear to be equally bioavailable and a suitable alternative to crystalline AA in swine and poultry diets.
Development of a Generic Physiologically Based Kinetic Model to Predict In Vivo Uterotrophic Responses Induced by Estrogenic Chemicals in Rats Based on In Vitro Bioassays
Authors: Zhang Mengying , van Ravenzwaay Bennard , Rietjens Ivonne M C M
Published: October 2019

The present study assessed the potential of a generic physiologically based kinetic (PBK) model to convert in vitro data for estrogenicity to predict the in vivo uterotrophic response in rats for diethylstibestrol (DES), ethinylestradiol (EE2), genistein (GEN), coumestrol (COU), and methoxychlor (MXC). PBK models were developed using a generic approach and in vitro concentration-response data from the MCF-7 proliferation assay and the yeast estrogen screening assay were translated into in vivo dose-response data. Benchmark dose analysis was performed on the predicted data and available in vivo uterotrophic data to evaluate the model predictions. The results reveal that the developed generic PBK model adequate defines the in vivo kinetics of the estrogens. The predicted dose-response data of DES, EE2, GEN, COU, and MXC matched the reported in vivo uterus weight response in a qualitative way, whereas the quantitative comparison was somewhat hampered by the variability in both in vitro and in vivo data. From a safety perspective, the predictions based on the MCF-7 proliferation assay would best guarantee a safe point of departure for further risk assessment although it may be conservative. The current study indicates the feasibility of using a combination of in vitro toxicity data and a generic PBK model to predict the relative in vivo uterotrophic response for estrogenic chemicals.
On the stability of sequences inserted into viral genomes
Authors: Willemsen Anouk , Zwart Mark P
Published: October 2019

Viruses are widely used as vectors for heterologous gene expression in cultured cells or natural hosts, and therefore a large number of viruses with exogenous sequences inserted into their genomes have been engineered. Many of these engineered viruses are viable and express heterologous proteins at high levels, but the inserted sequences often prove to be unstable over time and are rapidly lost, limiting heterologous protein expression. Although virologists are aware that inserted sequences can be unstable, processes leading to insert instability are rarely considered from an evolutionary perspective. Here, we review experimental work on the stability of inserted sequences over a broad range of viruses, and we present some theoretical considerations concerning insert stability. Different virus genome organizations strongly impact insert stability, and factors such as the position of insertion can have a strong effect. In addition, we argue that insert stability not only depends on the characteristics of a particular genome, but that it will also depend on the host environment and the demography of a virus population. The interplay between all factors affecting stability is complex, which makes it challenging to develop a general model to predict the stability of genomic insertions. We highlight key questions and future directions, finding that insert stability is a surprisingly complex problem and that there is need for mechanism-based, predictive models. Combining theoretical models with experimental tests for stability under varying conditions can lead to improved engineering of viral modified genomes, which is a valuable tool for understanding genome evolution as well as for biotechnological applications, such as gene therapy.
A Machine Learning Algorithm to Predict the Probability of (Occult) Posterior Malleolar Fractures Associated With Tibial Shaft Fractures to Guide “Malleolus First” Fixation
Authors: Hendrickx Laurent A. M. , Sobol Garret L. , Langerhuizen David W. G. , Bulstra Anne Eva J. , Hreha Jeremy , Sprague Sheila , Sirkin Michael S. , Ring David , Kerkhoffs Gino M. M. J. , Jaarsma Ruurd L. , Doornberg Job N. ,   Machine Learning Consortium
Published: October 2019

Objectives:

To develop an accurate machine learning (ML) predictive model incorporating patient, fracture, and trauma characteristics to identify individual patients at risk of an (occult) PMF.

Methods:

Databases of 2 studies including patients with TSFs from 2 Level 1 trauma centers were combined for analysis. Using ten-fold cross-validation, 4 supervised ML algorithms were trained in recognizing patterns associated with PMFs: (1) Bayes point machine; (2) support vector machine; (3) neural network; and (4) boosted decision tree. Performance of each ML algorithm was evaluated and compared based on (1) C-statistic; (2) calibration slope and intercept; and (3) Brier score. The best-performing ML algorithm was incorporated into an online open-access prediction tool.

Results:

Total data set included 263 patients, of which 28% had a PMF. Training of the Bayes point machine resulted in the best-performing prediction model reflected by good C-statistic, calibration slope, calibration intercept, and Brier score of 0.89, 1.02, −0.06, and 0.106, respectively. This prediction model was deployed as an open-access online prediction tool.

Conclusion:

A ML-based prediction model accurately predicted the probability of a (occult) PMF in patients with a TSF based on patient- and fracture-specific characteristics. This prediction model can guide surgeons in their diagnostic workup and preoperative planning. Further research is required to externally validate the model before implementation in clinical practice.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Mitochondrial metabolism: a common link between neuroinflammation and neurodegeneration
Authors: Garabadu Debapriya , Agrawal Nidhi , Sharma Anjali , Sharma Sahil
Published: October 2019

Neurodegenerative disorders have been considered as a growing health concern for decades. Increasing risk of neurodegenerative disorders creates a socioeconomic burden to both patients and care givers. Mitochondria are organelle that are involved in both neuroinflammation and neurodegeneration. There are few reports on the effect of mitochondrial metabolism on the progress of neurodegeneration and neuroinflammation. Therefore, the present review summarizes the potential contribution of mitochondrial metabolic pathways in the pathogenesis of neuroinflammation and neurodegeneration. Mitochondrial pyruvate metabolism plays a critical role in the pathogenesis of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. However, there its potential contribution in other neurodegenerative disorders is as yet unproven. The mitochondrial pyruvate carrier and pyruvate dehydrogenase can modulate mitochondrial pyruvate metabolism to attenuate neuroinflammation and neurodegeneration. Further, it has been observed that the mitochondrial citric acid cycle can regulate the pathogenesis of neuroinflammation and neurodegeneration. Additional research should be undertaken to target tricarboxylic acid cycle enzymes to minimize the progress of neuroinflammation and neurodegeneration. It has also been observed that the mitochondrial urea cycle can potentially contribute to the progression of neurodegenerative disorders. Therefore, targeting this pathway may control the mitochondrial dysfunction-induced neuroinflammation and neurodegeneration. Furthermore, the mitochondrial malate-aspartate shuttle could be another target to control mitochondrial dysfunction-induced neuroinflammation and neurodegeneration in neurodegenerative disorders.
A Cluster of Bacillus cereus Infections in the Neonatal Intensive Care Unit
Authors: Bar-Meir Maskit , Kashat Livnat , Zeevi David A. , Well Yonit Wiener , Assous Marc V.
Published: October 2019

Bacillus cereus isolates causing an outbreak in the neonatal intensive care unit were investigated using whole-genome sequencing. The outbreak coincided with construction work performed adjacent to the neonatal intensive care unit and ceased after strict sealing of the construction area. We found the outbreak to be polyclonal, however, the clonality did not correlate with the virulence in vivo. Genotypically similar isolates were associated with both lethal/severe infection and colonization/environmental contamination. Environmental bacterial load may be a major determinant of infection, especially in high-risk patients. Clinicians should be alert to unusual increase in B. cereus isolations from clinical cultures to facilitate early recognition and investigations of Bacillus outbreaks and pseudo-outbreaks. The integration of genomics into the classical infectious disease work can augment our understanding of pathogen transmission and virulence, and can rapidly assist our response to unusual disease trends.
Identification of predictors for acute postoperative pain after gynecological laparoscopy (STROBE-compliant article)
Authors: Joo Jin , Moon Hyun Kyung , Moon Young Eun
Published: October 2019

While the pain after gynecological laparoscopy is assumed to be minor, many women suffer from unexpected postoperative pain in the post-anesthesia care unit (PACU). Prior identification of these patients is significant for effective analgesia. Therefore, we sought to determine the predictors for acute postoperative pain after gynecological laparoscopy. The data of 280 patients undergoing gynecological laparoscopy were analyzed. Data included demographic characteristics, previous obstetric/gynecologic surgical history, menstruation pattern including dysmenorrhea severity, gynecological hormone administration history, and surgical data (surgical time, endometriosis severity, adhesion, drainage insertion, and surgery type). Univariate analysis and binary logistic regression were used to evaluate predictors for substantial pain in the PACU after gynecologic laparoscopy. Among the 280 patients, 115 (41%) suffered from substantial postoperative pain in the PACU. Whenever the level of dysmenorrhea became more severe (none → mild → moderate → severe), the risk of substantial pain in the PACU increased 2.9-fold (odds ratio [OR] 2.92, 95% confidence interval [CI] 2.11–4.03, P < .001). Moreover, patients undergoing laparoscopy for ectopic pregnancy had a higher risk of substantial pain compared with the others (OR 3.11, 95% CI 1.36–7.12, P = .007). Other factors did not show a significant association with substantial pain. Patients with preoperative severe dysmenorrhea and those undergoing laparoscopy for ectopic pregnancy should be considered to have a high risk of substantial postoperative pain in the PACU so that they receive prompt and aggressive analgesic intervention. In particular, dysmenorrhea severity is clinically valuable as a useful predictor for substantial pain after gynecological laparoscopy.
How well do revegetation plantings capture genetic diversity?
Authors: Jordan Rebecca , Breed Martin F. , Prober Suzanne M. , Miller Adam D. , Hoffmann Ary A.
Published: October 2019

Revegetation plantings are a key management tool for ecological restoration. Revegetation success is usually measured using ecological traits, however, genetic diversity should also be considered as it can influence fitness, adaptive capacity and long-term viability of revegetation plantings and ecosystem functioning. Here we review the global literature comparing genetic diversity in revegetation plantings to natural stands. Findings from 48 studies suggest variable genetic outcomes of revegetation, with 46% demonstrating higher genetic diversity in revegetation than natural stands and 52% demonstrating lower diversity. Levels of genetic diversity were most strongly associated with the number of source sites used—where information was available, 69% of studies showing higher genetic diversity in revegetation reported using multiple provenances, compared with only 33% for those with lower diversity. However, with a few exceptions, it was unclear whether differences in genetic diversity between revegetation and natural stands were statistically significant. This reflected insufficient reporting of statistical error and metadata within the published studies, which limited conclusions about factors contributing to patterns. Nonetheless, our findings indicate that mixed seed sourcing can contribute to higher genetic diversity in revegetation. Finally, we emphasize the type of metadata needed to determine factors influencing genetic diversity in revegetation and inform restoration efforts.
Sustained scleral stiffening in rats after a single genipin treatment
Authors: Hannon Bailey G. , Schwaner Stephen A. , Boazak Elizabeth M. , Gerberich Brandon G. , Winger Erin J. , Prausnitz Mark R. , Ethier C. Ross
Published: October 2019

Scleral stiffening has been proposed as a therapy for glaucoma and myopia. Previous
in vivo
studies have evaluated the efficacy of scleral stiffening after multiple treatments with a natural collagen crosslinker, genipin. However, multiple injections limit clinical translatability. Here, we examined whether scleral stiffening was maintained after four weeks following a single genipin treatment. Eyes from brown Norway rats were treated
in vivo
with a single 15 mM genipin retrobulbar injection, sham retrobulbar injection, or were left naive. Eyes were enucleated either 1 day or four weeks post-injection and underwent whole globe inflation testing. We assessed first principal Lagrange strain of the posterior sclera using digital image correlation as a proxy for scleral stiffness. Four weeks post-injection, genipin treatment resulted in a 58% reduction in scleral strain as compared to controls (
p
= 0.005). We conclude that a single
in vivo
injection of genipin effectively stiffened rat sclera for at least four weeks which motivates further functional studies and possible clinical translation of genipin-induced scleral stiffening.
Condensin locates at transcriptional termination sites in mitosis, possibly releasing mitotic transcripts
Authors: Nakazawa Norihiko , Arakawa Orie , Yanagida Mitsuhiro
Published: October 2019

Condensin is an essential component of chromosome dynamics, including mitotic chromosome condensation and segregation, DNA repair, and development. Genome-wide localization of condensin is known to correlate with transcriptional activity. The functional relationship between condensin accumulation and transcription sites remains unclear, however. By constructing the auxin-inducible degron strain of condensin, herein we demonstrate that condensin does not affect transcription itself. Instead, RNA processing at transcriptional termination appears to define condensin accumulation sites during mitosis, in the fission yeastSchizosaccharomyces pombe. Combining the auxin-degron strain with thenda3β-tubulin cold-sensitive (cs) mutant enabled us to inactivate condensin in mitotically arrested cells, without releasing the cells into anaphase. Transcriptional activation and termination were not affected by condensin's degron-mediated depletion, at heat-shock inducible genes or mitotically activated genes. On the other hand, condensin accumulation sites shifted approximately 500 bp downstream in the auxin-degron of 5′-3′ exoribonuclease Dhp1, in which transcripts became aberrantly elongated, suggesting that condensin accumulates at transcriptionally terminated DNA regions. Growth defects in mutant strains of 3′-processing ribonuclease and polyA cleavage factors were additive in condensin temperature-sensitive (ts) mutants. Considering condensin'sin vitroactivity to form double-stranded DNAs from unwound, single-stranded DNAs or DNA-RNA hybrids, condensin-mediated processing of mitotic transcripts at the 3′-end may be a prerequisite for faithful chromosome segregation.
Modes of phase separation affecting chromatin regulation
Authors: Palikyras Spiros , Papantonis Argyris
Published: October 2019

It has become evident that chromatin in cell nuclei is organized at multiple scales. Significant effort has been devoted to understanding the connection between the nuclear environment and the diverse biological processes taking place therein. A fundamental question is how cells manage to orchestrate these reactions, both spatially and temporally. Recent insights into phase-separated membraneless organelles may be the key for answering this. Of the two models that have been proposed for phase-separated entities, one largely depends on chromatin–protein interactions and the other on multivalent protein–protein and/or protein–RNA ones. Each has its own characteristics, but both would be able to, at least in part, explain chromatin and transcriptional organization. Here, we attempt to give an overview of these two models and their studied examples to date, before discussing the forces that could govern phase separation and prevent it from arising unrestrainedly.
Implications of kappa-casein evolutionary diversity for the self-assembly and aggregation of casein micelles
Authors: Manguy Jean , Shields Denis C.
Published: October 2019

Milk alpha-, beta- and kappa-casein proteins assemble into casein micelles in breast epithelial cells. The glycomacropeptide (GMP) tails of kappa-casein that extend from the surface of the micelle are key to assembly and aggregation. Aggregation is triggered by stomach pepsin cleavage of GMP from para-kappa-casein (PKC). While one casein micelle model emphasizes the importance of hydrophobic interactions, another focuses on polar residues. We performed an evolutionary analysis of kappa-casein primary sequence and predicted features that potentially impact on protein interactions. We noted more rapid change in the earlier period (166 to 60 Ma). Pepsin and plasmin cleavage sites were avoided in the GMP, which may partly explain its amino acid composition. Short tandem repeats have led to modest expansions of PKC, and to large GMP expansions, suggesting the GMP is less length constrained. Amino acid compositional constraints were assessed across species. Polarity and hydrophobicity properties were insufficient to explain differences between PKC and GMP. Among polar residues, threonine dominates the GMP, compared to serine, probably reflecting its preference for O-glycosylation over phosphorylation. Glutamine, enriched in the bovine PQ-rich region, is not positionally conserved in other species. Among hydrophobic residues, isoleucine is clearly preferred over leucine in the GMP, and patches of hydrophobicity are not markedly positionally conserved. PKC tyrosine and charged residues showed stronger conservation of position, suggesting a role for pi-interactions, seen in other structurally dynamic protein membraneless assemblies. Independent acquisitions of cysteines are consistent with a trend of increasing stabilization of multimers by covalent disulphide bonds, over evolutionary time. In conclusion, kappa-casein compositional and positional constraints appear to be influenced by modification preferences, protease evasion and protein–protein interactions.