bluuebunny/crossref_metadata_2025 huggingface dataset:
The combination of nutraceuticals and functional feeds as additives modulates gut microbiota and blood markers associated with immune response and health in weanling piglets
Authors: Lo Verso Luca , Talbot Guylaine , Morissette Bruno , Guay Frédéric , Matte J Jacques , Farmer Chantal , Gong Joshua , Wang Qi , Bissonnette Nathalie , Beaulieu Carole , Lessard Martin
Published: August 2020

This study aimed to evaluate the effects of a combination of feed additives with complementary functional properties on the intestinal microbiota, homocysteine, and vitamins E and B status as well as systemic immune response of weanling piglets. At weaning, 32 litters were assigned to one of the following dietary treatments (DT): 1) conventional diet (CTRL); 2) CTRL diet supplemented with antibiotics (ATB); 3) a cocktail of feed additives containing cranberry extract, encapsulated carvacrol, yeast-derived products, and extra vitamins A, D, E, and B complex (CKTL); or 4) CKTL diet with bovine colostrum in replacement of plasma proteins (CKTL + COL). Within each litter, the piglets with lowest and highest birth weights (LBW and HBW, respectively) and two piglets of medium birth weight (MBW) were identified. The MBW piglets were euthanized at 42 d of age in order to characterize the ileal and colonic microbiota. Blood samples were also collected at weaning and at 42 d of age from LBW and HBW piglets to measure insulin-like growth factor-1 (IGF-1), cysteine, homocysteine, and vitamins E, B6, and B12, and to characterize the leukocyte populations. At 42 d of age, cytokine production by stimulated peripheral blood mononuclear cells was also measured. In a second experiment, piglets were reared under commercial conditions to evaluate the effects of the DT on the growth performance. At the indicator species analysis, the highest indicator value (IV) for Succinivibrio dextrinosolvens was found in the CKTL group, whereas the highest IV for Lactobacillus reuteri and Faecalibacterium prausnitzii was evidenced in the CKTL + COL group (P < 0.05). Compared with the other DT, CTRL piglets had higher concentrations of homocysteine, whereas the CKTL and CKTL + COL supplementations increased the concentrations of vitamins E and B12 (P < 0.05). DT had no effect on IGF-1 concentration and on blood leukocytes populations; however, compared with HBW piglets, LBW animals had lower values of IGF-1, whereas the percentages of γδ T lymphocytes and T helper were decreased and increased, respectively (P < 0.05). CKTL + COL also improved the growth performance of piglets reared under commercial conditions (P < 0.05). This study highlights the impact of birth weight on piglet systemic immune defenses and the potential of weaning diet supplemented with feed additives and bovine colostrum to modulate the homocysteine metabolism and the intestinal microbiota.
A Structured Review to Assess the Current Status of Cost-Based Burns Research in Nepal
Authors: Lowin Julia L , Poudel Ak Narayan , Price Patricia E , Potokar Tom S
Published: August 2020

The management of burns is costly and complex. The problem is compounded in low and middle income countries (LMICs) where the incidence of burn injuries is high but infrastructure and funding for management and prevention is limited. Cost of illness studies allows for quantification of the costs associated with public health problems. Without cost quantification, focus and allocation of funding is challenging. The authors explored the availability of cost-focused burns research data in a target LMIC. The focus of their research was Nepal. A structured literature review including published papers, Ministry of Health (MOH) and World Health Organization (WHO) statistics was conducted to identify cost of illness studies or evidence relating to burn-related resource and costs. Gaps in the evidence base were highlighted. Research methodologies from other LMICs were reviewed. We found 32 papers related to burn injury in Nepal, one key MOH document and one relevant WHO data source. Most research focused on the epidemiology and etiology of burns in Nepal. Of the papers, only 14 reported any type of burn-related resource use and only 1 paper directly reported (limited) cost data. No studies attempted an overall quantification of the cost of burns. MOH statistics provided no additional insight into costs. Our study found an almost complete lack of cost-focused burns research in Nepal. Primary research is needed to quantify the cost of burns in Nepal. Initial focus could usefully be on the cost of care in tertiary hospitals. A full cost of burns for Nepal remains some way off.
A new pinnotherid crab of the genusPinnixulalaPalacios Theil, Cuesta & Felder, 2016 from uncertain infaunal hosts in the northern Gulf of Mexico, with a rediagnosis and updated synonymy for the polychaete symbiontPinnixulala retinens(Rathbun, 1918) (Decapoda: Brachyura: Pinnotheridae)
Authors: Felder Darryl L , Palacios Theil Emma
Published: August 2020

A new infaunal pinnotherid crab, Pinnixulala heardin. sp., is described from muddy substrates of the middle to inner continental shelf of the northern Gulf of Mexico. Molecular genetic analysis supports its separation from P. retinens (Rathbun, 1918), the only other western Atlantic member of the genus and a species most commonly found living as a symbiont of large polychaete worms. Both western Atlantic species are clearly separated from several described and undescribed populations of congeners occurring along shorelines of the eastern Pacific. We herein include a rediagnosis of P. retinens to facilitate morphological comparisons with P. heardin. sp. Unlike P. retinens, which is more common in shallow inshore waters and reaches larger sizes, the new species lacks development of a strong distally directed spine on the fourth pereopod ischium and has chelae that are at least as heavily developed as the second and third pereopods. In addition, the mature male first gonopods in P. heardin. sp. are tapered over their terminal one-third and directed distally, rather than being curved in their terminal one-third with the tips directed mesially, as they are in P. retinens. The new species is invariably collected from samples including infaunal worms and other invertebrates, but the specific hosts remain to be determined
The current state of immunotherapy for primary and secondary brain tumors: similarities and differences
Authors: Nejo Takahide , Mende Abigail , Okada Hideho
Published: August 2020

Treatment and resolution of primary and metastatic brain tumors have long presented a challenge to oncologists. In response to the dismal survival outcomes associated with conventional therapies, various immunotherapy modalities, such as checkpoint inhibitors, vaccine, cellular immunotherapy and viral immunotherapy have been actively explored over the past couple of decades. Although improved patient survival has been more frequently noted in treatment of brain metastases, little progress has been made in improving patient survival in cases of primary brain tumors, specifically glioblastoma, which is the representative primary brain tumor discussed in this review. Herein, we will first overview the findings of recent clinical studies for treatment of primary and metastatic brain tumors with immunotherapeutic interventions. The clinical efficacy of these immunotherapies will be discussed in the context of their ability or inability to overcome inherent characteristics of the tumor as well as restricted antigen presentation and its immunosuppressive microenvironment. Additionally, this review aims to briefly inform clinicians in the field of neuro-oncology on the relevant aspects of the immune system as it pertains to the central nervous system, with special focus on the differing modes of antigen presentation and tumor microenvironment of primary and metastatic brain tumors and the role these differences may play in the efficacy of immunotherapy in eradicating the tumor.
Opioid Use Disorder and Overdose in Older Adults With Breast, Colorectal, or Prostate Cancer
Authors: Roberts Andrew W , Eiffert Samantha , Wulff-Burchfield Elizabeth M , Dusetzina Stacie B , Check Devon K
Published: August 2020

Background

Despite high rates of opioid therapy, evidence about the risk of preventable opioid harms among cancer survivors is underdeveloped. Our objective was to estimate the odds of opioid use disorder (OUD) and overdose following breast, colorectal, or prostate cancer diagnosis among Medicare beneficiaries.

Methods

We conducted a retrospective cohort study using 2007-2014 Surveillance, Epidemiology, and End Results-Medicare data for cancer survivors with a first cancer diagnosis of stage 0-III breast, colorectal, or prostate cancer at age 66-89 years between 2008 and 2013. Cancer survivors were matched to up to 2 noncancer controls on age, sex, and Surveillance, Epidemiology, and End Results region. Using Firth logistic regression, we estimated adjusted 1-year odds of OUD or nonfatal opioid overdose associated with a cancer diagnosis. We also estimated adjusted odds of OUD and overdose separately and by cancer stage, prior opioid use, and follow-up time.

Results

Among 69 889 cancer survivors and 125 007 controls, the unadjusted rates of OUD or nonfatal overdose were 25.2, 27.1, 38.9, and 12.4 events per 10 000 patients in the noncancer, breast, colorectal, and prostate samples, respectively. There was no association between cancer and OUD. Colorectal survivors had 2.3 times higher odds of opioid overdose compared with matched controls (adjusted odds ratio = 2.33, 95% confidence interval  = 1.49 to 3.67). Additionally, overdose risk was greater in those with more advanced disease, no prior opioid use, and preexisting mental health conditions.

Conclusions

Opioid overdose was a rare, but statistically significant, outcome following stage II-III colorectal cancer diagnosis, particularly among previously opioid-naïve patients. These patients may require heightened screening and intervention to prevent inadvertent adverse opioid harms.
Haemophilus haemolyticus: an atypical pathogen of septic arthritis of the knee joint
Authors: Weber Sabrina , Kabelitz Method , Kabelitz Nina , Schoenborn Veit
Published: August 2020

Septic knee arthritis is a common disease, mostly due to bacterial infections. We describe a rare case of Haemophilus haemolyticus causing unilateral septic arthritis of a native knee. The affected patient presented with persistent severe knee pain after repeated intra-articular injections. Patient history included knee arthroscopy and a known rheumatoid arthritis treated by steroids. Since conservative treatment was ineffective and infection could not be excluded, diagnostic arthroscopy was performed. Synovial fluid and biopsies verified the uncommon microorganism and antibiotic therapy was initiated. Clinical findings and blood results showed rapid improvement. The patient was discharged in a good condition after 6 weeks. A review of the current literature describes only one joint infection with H. haemolyticus as underlying cause. In immunocompromised patients with septic knee arthritis also atypical pathogens must be considered. Nevertheless, the established treatment algorithm with arthroscopy and anti-infective therapy seems to be effective leading to satisfactory results.
What does it take to be antiviral? An Argonaute-centered perspective on plant antiviral defense
Authors: Silva-Martins Guilherme , Bolaji Ayooluwa , Moffett Peter
Published: August 2020

RNA silencing is a major mechanism of constitutive antiviral defense in plants, mediated by a number of proteins, including the Dicer-like (DCL) and Argonaute (AGO) endoribonucleases. Both DCL and AGO protein families comprise multiple members. In particular, the AGO protein family has expanded considerably in different plant lineages, with different family members having specialized functions. Although the general mode of action of AGO proteins is well established, the properties that make different AGO proteins more or less efficient at targeting viruses are less well understood. In this report, we review methodologies used to study AGO antiviral activity and current knowledge about which AGO family members are involved in antiviral defense. In addition, we discuss what is known about the different properties of AGO proteins thought to be associated with this function.
Effect of Addition of WZB117 as an Inhibitor of Glucose Transporter 1 for Venous Blood Glucose Determination
Authors: Zhang Lei , Ran Yaqiong , Zhu Yan , Zhen Qianna
Published: August 2020

Objective

Sodium fluoride (NaF) has been applied to inhibit glycolysis in venous specimens for decades. However, it has had little effect on the rate of glycolysis in the first 1 to 2 hours, resulting in a decrease of glucose, so a more efficient method is needed. Recently, we discovered that WZB117, a specific Glut1 inhibitor, restricts glycolysis by inhibiting the passive sugar transport of human red blood cells and cancer cells. The purpose of this study was to evaluate the results of intravenous blood glucose determination after the addition of WZB117.

Methods

Venous specimens from 40 pairs of healthy volunteers were collected for several days and placed in tubes containing NaF plus EDTA-disodium (Na2) without WZB117 (the A group); citric acid, trisodium citrate, and EDTA-Na2 without WZB117 (B group); and NaF plus EDTA-Na2 with WZB117 (C group). The glucose concentration was measured after venipuncture and compared with test tubes treated for 1 hour, 2 hours, and 3 hours before centrifugation. Glucose level was determined by the hexokinase method. The paired t-test was used to examine differences in glucose values at baseline and at different time points. The number of misdiagnoses and the misdiagnosis rate were calculated at 2 diagnostic stages: high risk of diabetes (glucose level of 6.1 mmol/L) and diagnosis of diabetes (glucose level of 7.0 mmol/L).

Results

Glucose levels decreased by 1.0% at 1 hour and by 2.1% at 3 hours in the C group tubes and simultaneously decreased by 1.7% at 1 hour and by 2.5% at 3 hours in the B group tubes. In contrast, glucose levels decreased by 4.1% at 1 hour and by 6.3% at 3 hours in the A group tubes. There was a statistically significant difference in glucose levels measured in the A group tubes and B group tubes at 1 hour, 2 hours, and 3 hours. The misdiagnosis rate of clinical diagnosis in diabetes was highest in the A group tubes (7.0‰ at 1 hour, 0.1‰ at 3 hours at 7.0 mmol/L point; 14.6‰ at 1 hour, 0.4‰ at 3 hours at 6.1 mmol/L point) and lowest in the C group tubes (2.95‰ at 1 hour, 0‰ at 3 hours at 7.0 mmol/L point; 4.8‰ at 1 hour, 0.1‰ at 3 hours at 6.1 mmol/L point).

Conclusion

The tube addition of WZB117 is more suitable for minimizing glycolysis and has no effect on glucose levels even if specimens are left uncentrifuged for up to 3 hours.
Multiwavelength modelling of the circumstellar environment of the massive protostar AFGL 2591 VLA 3
Authors: Olguin F A , Hoare M G , Johnston K G , Motte F , Chen H-R V , Beuther H , Mottram J C , Ahmadi A , Gieser C , Semenov D , Peters T , Palau A , Klaassen P D , Kuiper R , Sánchez-Monge Á , Henning Th
Published: August 2020

We have studied the dust density, temperature, and velocity distributions of the archetypal massive young stellar object (MYSO) AFGL 2591. Given its high luminosity ($L=2\times 10^5\, \mbox{L$_{\odot}$}$) and distance (d = 3.3 kpc), AFGL 2591 has one of the highest $\sqrt{L}/d$ ratio, giving better resolved dust emission than any other MYSO. As such, this paper provides a template on how to use resolved multiwavelength data and radiative transfer to obtain a well-constrained 2D axisymmetric analytic rotating infall model. We show for the first time that the resolved dust continuum emission from Herschel 70- μm observations is extended along the outflow direction, whose origin is explained in part from warm dust in the outflow cavity walls. However, the model can only explain the kinematic features from CH3CN observations with unrealistically low stellar masses (<15 M⊙), indicating that additional physical processes may be playing a role in slowing down the envelope rotation. As part of our three-step continuum and line fitting, we have identified model parameters that can be further constrained by specific observations. High-resolution mm visibilities were fitted to obtain the disc mass (6 M⊙) and radius (2200 au). A combination of SED and near-infrared observations were used to estimate the luminosity and envelope mass together with the outflow cavity inclination and opening angles.
Ly α blobs from cold streams undergoing Kelvin–Helmholtz instabilities
Authors: Mandelker Nir , van den Bosch Frank C , Nagai Daisuke , Dekel Avishai , Birnboim Yuval , Aung Han
Published: August 2020

We present an analytic toy model for the radiation produced by the interaction between cold streams thought to feed massive haloes at high redshift and their hot CGM. We begin by deriving cosmologically motivated parameters for the streams, as they enter the halo virial radius, Rv, as a function of halo mass and redshift. For $10^{12}\, {\rm M}_\odot$ haloes at z = 2, we find the stream density to be $n_{\rm H,s}\sim (0.1{\!-\!}5)\times 10^{-2}\, {\rm cm}^{-3}$, a factor of δ ∼ (30–300) times denser than the hot CGM, while stream radii are in the range Rs ∼ (0.03−0.50)Rv. As streams accelerate towards the halo centre, they become denser and narrower. The stream–CGM interaction induces Kelvin–Helmholtz instability (KHI), which leads to entrainment of CGM mass by the stream and to stream deceleration by momentum conservation. Assuming the entrainment rates derived by Mandelker et al. (2020) in the absence of gravity can be applied locally at each halocentric radius, we derive equations of motion for the stream in the halo. Using these, we derive the net acceleration, mass growth, and energy dissipation induced by the stream–CGM interaction, as a function of halo mass and redshift, for different CGM density profiles. For the range of model parameters considered, we find that the interaction induces dissipation luminosities Ldiss > 1042 erg s−1 within ≲0.6Rv of haloes with $M_{\rm v}\gt 10^{12}\, {\rm M}_\odot$ at z = 2. The emission scales with halo mass and redshift approximately as $\propto M_{\rm v}\, (1+z)^2$. The magnitude and spatial extent of the emission are consistent with observed Ly α blobs, though better treatment of the UV background and self-shielding is needed to solidify this conclusion.
Probing the atmosphere of HD189733b with the Na i and K i lines
Authors: Keles E , Kitzmann D , Mallonn M , Alexoudi X , Fossati L , Pino L , Seidel J V , Carroll T A , Steffen M , Ilyin I , Poppenhäger K , Strassmeier K G , von Essen C , Nascimbeni V , Turner J D
Published: August 2020

High spectral resolution transmission spectroscopy is a powerful tool to characterize exoplanet atmospheres. Especially for hot Jupiters, this technique is highly relevant, due to their high-altitude absorption, e.g. from resonant sodium (Na i) and potassium (K i) lines. We resolve the atmospheric K i absorption on HD189733b with the aim to compare the resolved K i line and previously obtained high-resolution Na i-D line observations with synthetic transmission spectra. The line profiles suggest atmospheric processes leading to a line broadening of the order of ∼10 km/s for the Na i-D lines and only a few km/s for the K i line. The investigation hints that either the atmosphere of HD189733b lacks a significant amount of K i or the alkali lines probe different atmospheric regions with different temperature, which could explain the differences we see in the resolved absorption lines.
A search for transiting planets around FGKM dwarfs and subgiants in the TESS full frame images of the Southern ecliptic hemisphere
Authors: Montalto M , Borsato L , Granata V , Lacedelli G , Malavolta L , Manthopoulou E E , Nardiello D , Nascimbeni V , Piotto G
Published: August 2020

In this work, we present the analysis of 976 814 FGKM dwarf and subgiant stars in the Transiting Exoplanet Survey Telescope (TESS) full frame images (FFIs) of the Southern ecliptic hemisphere. We present a new pipeline, DIAmante, developed to extract optimized, multisector photometry from TESS FFIs and a classifier, based on the Random Forest technique, trained to discriminate plausible transiting planetary candidates from common false positives. A new statistical model was developed to provide the probability of correct identification of the source of variability. We restricted the planet search to the stars located in the least crowded regions of the sky and identified 396 transiting planetary candidates among which 252 are new detections. The candidates’ radius distribution ranges between 1 R⊕ and 2.6 RJ with median value of 1 RJ and the period distribution ranges between 0.25 and 105 d with median value of 3.8 d. The sample contains four long period candidates (P > 50 d), one of which is new, and 64 candidates with periods between 10 and 50 d (42 new ones). In the small planet radius domain (4R < R⊕), we found 39 candidates among which 15 are new detections. Additionally, we present 15 single transit events (14 new ones), a new candidate multiplanetary system, and a novel candidate around a known TOI. By using Gaia dynamical constraints, we found that 70 objects show evidence of binarity. We release a catalogue of the objects we analysed and the corresponding light curves and diagnostic figures through the MAST and ExoFOP portals.
Quantifying excess power from radio frequency interference in Epoch of Reionization measurements
Authors: Wilensky Michael J , Barry Nichole , Morales Miguel F , Hazelton Bryna J , Byrne Ruby
Published: August 2020

We quantify the effect of radio frequency interference (RFI) on measurements of the 21-cm power spectrum during the Epoch of Reionization (EoR). Specifically, we investigate how the frequency structure of RFI source emission generates contamination in higher order wave modes, which is much more problematic than smooth-spectrum foreground sources. Using a relatively optimistic EoR model, we find that even a single relatively dim RFI source can overwhelm the EoR power spectrum signal of $\sim 10\, {\rm mK}^2$ for modes $0.1 \ \lt k \lt 2 \, h\, {\rm Mpc}^{-1}$. If the total apparent RFI flux density in the final power spectrum integration is kept below 1 mJy, an EoR signal resembling this optimistic model should be detectable for modes $k \lt 0.9\, h\, {\rm Mpc}^{-1}$, given no other systematic contaminants and an error tolerance as high as 10 per cent. More pessimistic models will be more restrictive. These results emphasize the need for highly effective RFI mitigation strategies for telescopes used to search for the EoR.
Physicochemical models: source-tailored or generic?
Authors: Kulterer Beatrice M , Drozdovskaya Maria N , Coutens Audrey , Manigand Sébastien , Stéphan Gwendoline
Published: August 2020

Physicochemical models can be powerful tools to trace the chemical evolution of a protostellar system and allow to constrain its physical conditions at formation. The aim of this work is to assess whether source-tailored modelling is needed to explain the observed molecular abundances around young, low-mass protostars or if, and to what extent, generic models can improve our understanding of the chemistry in the earliest stages of star formation. The physical conditions and the abundances of simple, most abundant molecules based on three models are compared. After establishing the discrepancies between the calculated chemical output, the calculations are redone with the same chemical model for all three sets of physical input parameters. With the differences arising from the chemical models eliminated, the output is compared based on the influence of the physical model. Results suggest that the impact of the chemical model is small compared to the influence of the physical conditions, with considered time-scales having the most drastic effect. Source-tailored models may be simpler by design; however, likely do not sufficiently constrain the physical and chemical parameters within the global picture of star-forming regions. Generic models with more comprehensive physics may not provide the optimal match to observations of a particular protostellar system, but allow a source to be studied in perspective of other star-forming regions.
The nearby extreme accretion and feedback system PDS 456: finding a complex radio-emitting nucleus
Authors: Yang Jun , Paragi Zsolt , Nardini Emanuele , Baan Willem A , Fan Lulu , Mohan Prashanth , Varenius Eskil , An Tao
Published: August 2020

When a black hole accretes close to the Eddington limit, the astrophysical jet is often accompanied by radiatively driven, wide-aperture and mildly relativistic winds. Powerful winds can produce significant non-thermal radio emission via shocks. Among the nearby critical accretion quasars, PDS 456 has a very massive black hole (about 1 billion solar masses), shows a significant star-forming activity (about 70 solar masses per year), and hosts exceptionally energetic X-ray winds (power up to 20 per cent of the Eddington luminosity). To probe the radio activity in this extreme accretion and feedback system, we performed very long baseline interferometric (VLBI) observations of PDS 456 at 1.66 GHz with the European VLBI Network and the enhanced Multi-Element Remotely Linked Interferometry Network. We find a rarely seen complex radio-emitting nucleus consisting of a collimated jet and an extended non-thermal radio emission region. The diffuse emission region has a size of about 360 pc and a radio luminosity about three times higher than that of the nearby extreme starburst galaxy Arp 220. The powerful nuclear radio activity could result either from a relic jet with a peculiar geometry (nearly along the line of sight) or more likely from diffuse shocks formed naturally by the existing high-speed winds impacting on high-density star-forming regions.
Optimal probabilistic catalogue matching for radio sources
Authors: Fan Dongwei , Budavári Tamás , Norris Ray P , Basu Amitabh
Published: August 2020

Cross-matching catalogues from radio surveys to catalogues of sources at other wavelengths is extremely hard, because radio sources are often extended, often consist of several spatially separated components, and often no radio component is coincident with the optical/infrared host galaxy. Traditionally, the cross-matching is done by eye, but this does not scale to the millions of radio sources expected from the next generation of radio surveys. We present an innovative automated procedure, using Bayesian hypothesis testing, that models trial radio-source morphologies with putative positions of the host galaxy. This new algorithm differs from an earlier version by allowing more complex radio-source morphologies, and performing a simultaneous fit over a large field. We show that this technique performs well in an unsupervised mode.
Kraken reveals itself – the merger history of the Milky Way reconstructed with the E-MOSAICS simulations
Authors: Kruijssen J M Diederik , Pfeffer Joel L , Chevance Mélanie , Bonaca Ana , Trujillo-Gomez Sebastian , Bastian Nate , Reina-Campos Marta , Crain Robert A , Hughes Meghan E
Published: August 2020

Globular clusters (GCs) formed when the Milky Way experienced a phase of rapid assembly. We use the wealth of information contained in the Galactic GC population to quantify the properties of the satellite galaxies from which the Milky Way assembled. To achieve this, we train an artificial neural network on the E-MOSAICS cosmological simulations of the co-formation and co-evolution of GCs and their host galaxies. The network uses the ages, metallicities, and orbital properties of GCs that formed in the same progenitor galaxies to predict the stellar masses and accretion redshifts of these progenitors. We apply the network to Galactic GCs associated with five progenitors: Gaia-Enceladus, the Helmi streams, Sequoia, Sagittarius, and the recently discovered ‘low-energy’ GCs, which provide an excellent match to the predicted properties of the enigmatic galaxy ‘Kraken’. The five galaxies cover a narrow stellar mass range [M⋆ = (0.6–4.6) × 108 M⊙], but have widely different accretion redshifts ($\mbox{$z_{\rm acc}$}=0.57\!-\!2.65$). All accretion events represent minor mergers, but Kraken likely represents the most major merger ever experienced by the Milky Way, with stellar and virial mass ratios of $\mbox{$r_{M_\star }$}=1$:$31^{+34}_{-16}$ and $\mbox{$r_{M_{\rm h}}$}=1$:$7^{+4}_{-2}$, respectively. The progenitors match the z = 0 relation between GC number and halo virial mass, but have elevated specific frequencies, suggesting an evolution with redshift. Even though these progenitors likely were the Milky Way’s most massive accretion events, they contributed a total mass of only log (M⋆, tot/M⊙) = 9.0 ± 0.1, similar to the stellar halo. This implies that the Milky Way grew its stellar mass mostly by in-situ star formation. We conclude by organizing these accretion events into the most detailed reconstruction to date of the Milky Way’s merger tree.
Life and Death of Selfish Genes: Comparative Genomics Reveals the Dynamic Evolution of Cytoplasmic Incompatibility
Authors: Martinez Julien , Klasson Lisa , Welch John J , Jiggins Francis M
Published: August 2020

Cytoplasmic incompatibility is a selfish reproductive manipulation induced by the endosymbiont Wolbachia in arthropods. In males Wolbachia modifies sperm, leading to embryonic mortality in crosses with Wolbachia-free females. In females, Wolbachia rescues the cross and allows development to proceed normally. This provides a reproductive advantage to infected females, allowing the maternally transmitted symbiont to spread rapidly through host populations. We identified homologs of the genes underlying this phenotype, cifA and cifB, in 52 of 71 new and published Wolbachia genome sequences. They are strongly associated with cytoplasmic incompatibility. There are up to seven copies of the genes in each genome, and phylogenetic analysis shows that Wolbachia frequently acquires new copies due to pervasive horizontal transfer between strains. In many cases, the genes have subsequently acquired loss-of-function mutations to become pseudogenes. As predicted by theory, this tends to occur first in cifB, whose sole function is to modify sperm, and then in cifA, which is required to rescue the cross in females. Although cif genes recombine, recombination is largely restricted to closely related homologs. This is predicted under a model of coevolution between sperm modification and embryonic rescue, where recombination between distantly related pairs of genes would create a self-incompatible strain. Together, these patterns of gene gain, loss, and recombination support evolutionary models of cytoplasmic incompatibility.
Effective Population Size Predicts Local Rates but Not Local Mitigation of Read-through Errors
Authors: Ho Alexander T , Hurst Laurence D
Published: August 2020

In correctly predicting that selection efficiency is positively correlated with the effective population size (Ne), the nearly neutral theory provides a coherent understanding of between-species variation in numerous genomic parameters, including heritable error (germline mutation) rates. Does the same theory also explain variation in phenotypic error rates and in abundance of error mitigation mechanisms? Translational read-through provides a model to investigate both issues as it is common, mostly nonadaptive, and has good proxy for rate (TAA being the least leaky stop codon) and potential error mitigation via “fail-safe” 3′ additional stop codons (ASCs). Prior theory of translational read-through has suggested that when population sizes are high, weak selection for local mitigation can be effective thus predicting a positive correlation between ASC enrichment and Ne. Contra to prediction, we find that ASC enrichment is not correlated with Ne. ASC enrichment, although highly phylogenetically patchy, is, however, more common both in unicellular species and in genes expressed in unicellular modes in multicellular species. By contrast, Ne does positively correlate with TAA enrichment. These results imply that local phenotypic error rates, not local mitigation rates, are consistent with a drift barrier/nearly neutral model.
Structural basis for DNA recognition and allosteric control of the retinoic acid receptors RAR–RXR
Authors: Osz Judit , McEwen Alastair G , Bourguet Maxime , Przybilla Frédéric , Peluso-Iltis Carole , Poussin-Courmontagne Pierre , Mély Yves , Cianférani Sarah , Jeffries Cy M , Svergun Dmitri I , Rochel Natacha
Published: August 2020

Retinoic acid receptors (RARs) as a functional heterodimer with retinoid X receptors (RXRs), bind a diverse series of RA-response elements (RAREs) in regulated genes. Among them, the non-canonical DR0 elements are bound by RXR–RAR with comparable affinities to DR5 elements but DR0 elements do not act transcriptionally as independent RAREs. In this work, we present structural insights for the recognition of DR5 and DR0 elements by RXR–RAR heterodimer using x-ray crystallography, small angle x-ray scattering, and hydrogen/deuterium exchange coupled to mass spectrometry. We solved the crystal structures of RXR–RAR DNA-binding domain in complex with the Rarb2 DR5 and RXR–RXR DNA-binding domain in complex with Hoxb13 DR0. While cooperative binding was observed on DR5, the two molecules bound non-cooperatively on DR0 on opposite sides of the DNA. In addition, our data unveil the structural organization and dynamics of the multi-domain RXR–RAR DNA complexes providing evidence for DNA-dependent allosteric communication between domains. Differential binding modes between DR0 and DR5 were observed leading to differences in conformation and structural dynamics of the multi-domain RXR–RAR DNA complexes. These results reveal that the topological organization of the RAR binding element confer regulatory information by modulating the overall topology and structural dynamics of the RXR–RAR heterodimers.
Decrease of respiratory diseases in one social children welfare institute in Shanxi Province during COVID-19
Authors: B Liu , QF Han , WP Liang , XY Shi , JJ Wei
Published: August 2020

Background

To assess the impact of disinfection measures on the incidence of common diseases in children welfare institute during the epidemic of Corona Virus Disease 2019 (COVID-19), and provide a basis for the daily disinfection management of children welfare institute.

Methods

This study surveyed and analyzed common diseases among children under the age of 14 in one social children welfare institute in Shanxi Province from January to May in 2018–2020 by the year-on-year method.

Results

The prevalence rate of respiratory diseases in 2020 was a significantly negative growth compared with 2018 and 2019. There was no obvious pattern of changes in digestive diseases group.

Conclusion

In view of the above anti-epidemic measures, it indicates that the children gathering institutions should strengthen effective personal protection and public health management to reduce infectious disease among children.
Stress hyperglycaemia is associated with poor functional outcomes in patients with acute ischaemic stroke after intravenous thrombolysis
Authors: Ngiam J N , Cheong C W S , Leow A S T , Wei Y -T , Thet J K X , Lee I Y S , Sia C -H , Tan B Y Q , Khoo C -M , Sharma V K , Yeo L L L
Published: August 2020

Background

Transient hyperglycaemia in the context of illness with or without known diabetes has been termed as ‘stress hyperglycaemia’. Stress hyperglycaemia can result in poor functional outcomes in patients with acute ischaemic stroke (AIS) who underwent mechanical thrombectomy. We investigated the association between stress hyperglycaemia and clinical outcomes in AIS patients undergoing intravenous thrombolysis (IVT).

Methods

We examined 666 consecutive patients with AIS who underwent IVT from 2006 to 2018. All patients had a glycated haemoglobin level (HbA1c) and fasting venous blood glucose measured within 24 h of admission. Stress hyperglycaemia ratio (SHR) was defined as the ratio of the fasting glucose to the HbA1c. Univariate and multivariate analyses were employed to identify predictors of poor functional outcomes (modified Rankin Scale 3–6 at 3 months) after IVT.

Results

Three-hundred and sixty-one patients (54.2%) had good functional outcomes. These patients tended to be younger (60.7 ± 12.7 vs. 70 ± 14.4 years, P < 0.001), male (70.7% vs. 51.5%, P < 0.001), had lower prevalence of atrial fibrillation (13.0% vs. 20.7%, P = 0.008) and lower SHR (0.88 ± 0.20 vs. 0.99 ± 26, P < 0.001). Patients with high SHR (≥0.97) were slightly older than those with low SHR (<0.97) and were more likely to have diabetes mellitus. On multivariate analysis, higher SHR was independently associated with poor functional outcomes (adjusted odds ratio 3.85, 95% confidence interval 1.59–9.09, P = 0.003).

Conclusion

SHR appears to be an important predictor of functional outcomes in patients with AIS undergoing IVT. This may have important implications on the role of glycaemic control in the acute management of ischaemic stroke.
Incidence, risk factors and validation of the RABBIT score for serious infections in a cohort of 1557 patients with rheumatoid arthritis
Authors: Thomas Konstantinos , Lazarini Argyro , Kaltsonoudis Evripidis , Voulgari Paraskevi V , Drosos Alexandros A , Repa Argyro , Sali Ainour Molla Ismail , Sidiropoulos Prodromos , Tsatsani Panagiota , Gazi Sousana , Evangelia Argyriou , Boki Kyriaki A , Katsimbri Pelagia , Boumpas Dimitrios , Fragkiadaki Kalliopi , Tektonidou Maria G , Sfikakis Petros P , Karagianni Konstantina , Sakkas Lazaros I , Grika Eleftheria P , Vlachoyiannopoulos Panagiotis G , Evangelatos Gerasimos , Iliopoulos Alexios , Dimitroulas Theodoros , Garyfallos Alexandros , Melissaropoulos Konstantinos , Georgiou Panagiotis , Areti Maria , Georganas Constantinos , Vounotrypidis Periklis , Georgiopoulos Georgios , Kitas George D , Vassilopoulos Dimitrios
Published: August 2020

Objectives

Predicting serious infections (SI) in patients with rheumatoid arthritis (RA) is crucial for the implementation of appropriate preventive measures. Here we aimed to identify risk factors for SI and to validate the RA Observation of Biologic Therapy (RABBIT) risk score in real-life settings.

Methods

A multi-centre, prospective, RA cohort study in Greece. Demographics, disease characteristics, treatments and comorbidities were documented at first evaluation and one year later. The incidence of SI was recorded and compared with the expected SI rate using the RABBIT risk score.

Results

A total of 1557 RA patients were included. During follow-up, 38 SI were recorded [incidence rate ratio (IRR): 2.3/100 patient-years]. Patients who developed SI had longer disease duration, higher HAQ at first evaluation and were more likely to have a history of previous SI, chronic lung disease, cardiovascular disease and chronic kidney disease. By multivariate analysis, longer disease duration (IRR: 1.05; 95% CI: 1.005, 1.1), history of previous SI (IRR: 4.15; 95% CI: 1.7, 10.1), diabetes (IRR: 2.55; 95% CI: 1.06, 6.14), chronic lung disease (IRR: 3.14; 95% CI: 1.35, 7.27) and daily prednisolone dose ≥10 mg (IRR: 4.77; 95% CI: 1.47, 15.5) were independent risk factors for SI. Using the RABBIT risk score in 1359 patients, the expected SI incidence rate was 1.71/100 patient-years, not different from the observed (1.91/100 patient-years; P = 0.97).

Conclusion

In this large real-life, prospective study of RA patients, the incidence of SI was 2.3/100 patient-years. Longer disease duration, history of previous SI, comorbidities and high glucocorticoid dose were independently associated with SI. The RABBIT score accurately predicted SI in our cohort.
The Effects of Erratic Ratings on Placebo Response and Signal Detection in the Roche Bitopertin Phase 3 Negative Symptom Studies—A Post Hoc Analysis
Authors: Umbricht Daniel , Kott Alan , Daniel David G
Published: August 2020

Objective

In the current post hoc analyses, we assessed the impact of erratic ratings, a marker of questionable measurement quality, on placebo and drug response and drug-placebo separation in schizophrenia negative symptom trials.

Methods

Data were obtained from three phase 3, multi-center, 24-week, randomized, double-blind, placebo-controlled trials with bitopertin in the treatment of negative symptoms of schizophrenia. Erratic ratings were operationally defined as at least one occurrence of at least a 20% change in negative symptom factor score in the opposite direction at consecutive visits. The effect of erratic ratings on placebo and drug response and drug-placebo separation was assessed by the protocol on a subject and site-level using a mixed model repeated measures analysis.

Results

Placebo response was significantly increased in the presence of erratic ratings, both at the subject and site levels. Treatment response in the presence of erratic ratings was mixed and inconsistent across doses and protocols. In most cases removing data generated by subjects and sites with erratic ratings resulted in a numerical increase of drug-placebo difference favoring treatment. Additionally, in this post hoc analysis, 10 mg of bitopertin separated statistically significantly from placebo at the end of study in one of the protocols.

Discussion

Erratic rating patterns appear to be consistently associated with increased response to placebo and a mixed response to treatment in the bitopertin negative symptoms trials and to have degraded drug-placebo separation. As a quality indicator, they may flag the need for enhanced quality control of affected sites in clinical trials.
Fiber degrading enzymes increased monosaccharides release and fermentation in corn distillers dried grains with solubles and wheat middlings steeped without or with protease
Authors: Rho Youngji , Patterson Rob , Joye Iris , Martinez Mario , Squires E James , Kiarie Elijah G
Published: August 2020

Treating fibrous feed ingredients with exogenous feed enzymes may improve their utilization in monogastric animals. An in vitro study was conducted to determine the effects of steeping corn distillers dried grains with solubles (DDGS) or wheat middlings (WM) with exogenous feed enzymes. Four treatments were arranged as follows: 1) co-product steeped with water (CON), 2) CON plus 0.5-g fiber degrading enzymes (FDE), 3) CON plus 0.5-g protease (PRO), and 4) CON plus 0.5-g FDE and 0.5 g PRO (FDEPRO). The FDE contained about 62,000, 37,000, and 8,000 U/g of xylanase, cellulase, and β-glucanase, respectively, whereas activities in PRO amounted to 2,500,000, 1,300,000, and 800,000 U/g of acid, alkaline, and neutral proteases, respectively. Briefly, 50 g of DDGS or WM samples (n = 8) were mixed with 500-mL water with or without enzymes and steeped for 0 to 72 h at 37 °C with continuous agitation. The pH, concentration of monosaccharides, and organic acids in the supernatant and apparent disappearance (AD) of fiber in solids were measured at 0, 12, 24, 48, and 72 h. There was treatment and time interaction (P < 0.005) on monosaccharides concentration. At 12 h, arabinose and glucose concentrations were similar (P > 0.05) between FDE and FDEPRO but higher (P = 0.002) than for CON in DDGS. For WM, FDE, and FDEPRO had higher (P < 0.001) xylose concentration than CON and PRO, whereas glucose concentration was higher (P < 0.001) for enzymes than CON at 12 h. However, FDEPRO had higher (P < 0.001) xylose concentration than CON, whereas xylose concentration for FDE and PRO was intermediate at 24 h. There was an interaction (P < 0.05) between treatment and time effect on lactic acid concentration in DDGS and WM (P < 0.005), and acetic acid concentration in WM (P < 0.001). In general, monosaccharide concentration was higher between 12 and 24 h and decreased after 48 h, whereas the pH decreased, and concentration of organic acids increased continuously over time (P < 0.05). The AD of NDF and ADF in DDGS was greater (P = 0.001) for FDE and FDEPRO than CON and PRO at 72 h. In WM, enzymes increased (P = 0.007) AD of NDF relative to CON at 72 h. Nonetheless, greater (P < 0.05) AD of fiber was observed between 48 and 72 h. In conclusion, although there were differences in responses among co-products, fiber degrading enzymes increased release of fermentable monosaccharides from co-products at 12 to 24 h of steeping and these effects were not extended with the addition of protease.
Hydraulic traits of Neotropical canopy liana and tree species across a broad range of wood density: implications for predicting drought mortality with models
Authors: De Guzman Mark E , Acosta-Rangel Aleyda , Winter Klaus , Meinzer Frederick C , Bonal Damien , Santiago Louis S
Published: August 2020

Wood density (WD) is often used as a proxy for hydraulic traits such as vulnerability to drought-induced xylem cavitation and maximum water transport capacity, with dense-wooded species generally being more resistant to drought-induced xylem cavitation, having lower rates of maximum water transport and lower sapwood capacitance than light-wooded species. However, relationships between WD and the hydraulic traits that they aim to predict have not been well established in tropical forests, where modeling is necessary to predict drought responses for a high diversity of unmeasured species. We evaluated WD and relationships with stem xylem vulnerability by measuring cavitation curves, sapwood water release curves and minimum seasonal water potential (Ψmin) on upper canopy branches of six tree species and three liana species from a single wet tropical forest site in Panama. The objective was to better understand coordination and trade-offs among hydraulic traits and the potential utility of these relationships for modeling purposes. We found that parameters from sapwood water release curves such as capacitance, saturated water content and sapwood turgor loss point (Ψtlp,x) were related to WD, whereas stem vulnerability curve parameters were not. However, the water potential corresponding to 50% loss of hydraulic conductivity (P50) was related to Ψtlp,x and sapwood osmotic potential at full turgor (πo,x). Furthermore, species with lower Ψmin showed lower P50, Ψtlp,x and πo,x suggesting greater drought resistance. Our results indicate that WD is a good easy-to-measure proxy for some traits related to drought resistance, but not others. The ability of hydraulic traits such as P50 and Ψtlp,x to predict mortality must be carefully examined if WD values are to be used to predict drought responses in species without detailed physiological measurements.