bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting dry matter intake using conceptual models for cattle kept under tropical and subtropical conditions1
Authors: Bateki Christian A , Dickhoefer Uta
Published: July 2019

Using empirical models to predict voluntary dry matter intake (VDMI) of cattle across production systems in the (Sub-)Tropics often yields VDMI estimates with low adequacy (i.e., accuracy and precision). Thus, we investigated whether semimechanistic conceptual mathematical models (CMM) developed for cattle in temperate areas could be adopted and adjusted to adequately predict VDMI of stall-fed cattle in the (Sub-)Tropics. The CMM of Conrad et al. (1964) (C1) and Mertens (1987) (M1) were identified and adopted for their simplicity in reflecting physicophysiological VDMI regulation. Both CMM use 2 equations that estimate the physiologically and physically regulated VDMI and retain the lower VDMI prediction as actual VDMI. Furthermore, C1 was modified by increasing the daily average fecal dry matter output from 0.0107 to 0.0116 kg/kg body weight, yielding the modified model C2. For M1, the daily neutral detergent fiber intake capacity was increased from 0.012 to 0.0135 kg/kg body weight and the daily metabolizable energy requirements for maintenance from 0.419 to 0.631 MJ/kg0.75 body weight, whereas the metabolizable energy requirements for gain was reduced from 32.5 to 24.3 MJ/kg body weight gain, yielding the modified model M2. Last, also the mean of the physically and physiologically regulated VDMI rather than the lower of both estimates was retained as actual VDMI to generate the models C3 (from C1), C4 (from C2), M3 (from M1), and M4 (from M2). The 8 CMM were then evaluated using a data set summarizing results from 52 studies conducted under (sub)tropical conditions. The mean bias, root mean square error of prediction (RMSEP) and concordance correlation coefficient (CCC) were used to evaluate adequacy and robustness of all CMM. The M4, C2, and C1 were the most adequate CMM [i.e., lowest mean biases (0.07, −0.22, and 0.14 kg/animal and day, respectively), RMSEP (1.62, 1.93, and 2.0 kg/animal and day, respectively), and CCC (0.91, 0.86, and 0.85, respectively)] and robust of the 8 CMM. Hence, CMM can adequately predict VDMI across diverse stall-fed cattle systems in the (Sub-)Tropics. Adjusting CMM to reflect the differences in feed quality and animal physiology under typical husbandry conditions in the (Sub-)Tropics and those in temperate areas improves the adequacy of their VDMI predictions.
Ruminal microbes of adult steers do not degrade extracellular L-citrulline and have a limited ability to metabolize extracellular L-glutamate1,2
Authors: Gilbreath Kyler R , Nawaratna Gayan I , Wickersham Tryon A , Satterfield M Carey , Bazer Fuller W , Wu Guoyao
Published: July 2019

The microbial population within the rumen has long been considered to have the capability of extensively degrading all dietary AA. Results from our feeding trials revealed that this dogma is not correct. In vitro studies were conducted to test the hypothesis that certain AA undergo little degradation by ruminal microbes. Whole ruminal fluid (3 mL, containing microorganisms) from cannulated adult steers (~500 kg, n = 6) was incubated at 37 °C with 5 mM l-glutamine, l-glutamate, l-arginine, or l-citrulline for 0, 0.5, 1, and 2 h to determine time-dependent changes in the metabolism of these AA. Additional ruminal fluid was incubated with 0, 0.5, 2 or 5 mM l-glutamine, l-glutamate, l-arginine, or l-citrulline for 2 h to determine dose-dependent changes in their metabolism. An aliquot (50 µL) of the incubation solution was collected at the predetermined time points for AA analyses. There was extensive hydrolysis of l-glutamine into l-glutamate and ammonia, and l-arginine into l-ornithine, l-proline, and ammonia, but the near absence of catabolism of extracellular l-glutamate and no degradation of extracellular l-citrulline by ruminal microbes. There was little uptake of 14C-labeled l-glutamate and no detectable uptake of 14C-labeled l-citrulline by the cells. These results indicate, for the first time, that ruminal microbes of adult steers do not degrade extracellular l-citrulline and that metabolism of extracellular l-glutamate is negligible compared with their ability to extensively catabolize extracellular l-arginine and l-glutamine.
Growth in the northern stone crab Lithodes maja Linnaeus, 1758 (Decapoda: Anomura: Lithodidae), a potential fishery target, in the laboratory
Authors: Brown Alastair , Thatje Sven
Published: July 2019

Data are presented on growth in early juvenile (N = 36; 2.05–3.95 mm carapace length) Lithodes maja Linnaeus, 1758 reared at 6 °C in the laboratory, and on growth in males (N = 24; 45.9–113.3 mm carapace length) and females (N = 9; 61.0–81.3 mm carapace length) maintained at 6 °C in the laboratory. Growth rate did not differ significantly among early juvenile, males, or females, and therefore appeared linear across the size range examined. Intermoult period increased with increasing size. Growth and intermoult period models were combined to estimate size at age. Age at maturity appears greater in L. maja than in other species of Lithodes, suggesting that L. maja may be more vulnerable to fisheries overexploitation.
Positional Portfolio Management
Authors: Gagliardini P , Gourieroux C , Rubin M
Published: July 2019

We study positional portfolio management strategies in which the manager maximizes an expected utility function written on the cross-sectional rank (position) of the portfolio return. The objective function reflects the manager’s goal to be well-ranked among competitors. To implement positional allocation strategies, we specify a nonlinear unobservable factor model for the asset returns which disentangles the dynamics of the cross-sectional distribution and the dynamics of the ranks of the individual assets. Using a large dataset of stocks returns we find that positional strategies outperform standard momentum, reversal and mean-variance allocation strategies, as well as equally weighted portfolio for criteria based on position.
Racial Comparisons in Timeliness of Colon Cancer Treatment in an Equal-Access Health System
Authors: Eaglehouse Yvonne L , Georg Matthew W , Shriver Craig D , Zhu Kangmin
Published: July 2019

Background

Non-Hispanic black (NHB) adults with cancer may have longer time-to-treatment than non-Hispanic whites (NHW) in the United States. Unequal access to medical care may partially account for this racial disparity. This study aimed to investigate whether there were racial differences in time-to-treatment and in treatment delays for patients diagnosed with colon cancer in the equal-access Military Health System (MHS).

Methods

Patients age 18–79 years diagnosed with colon adenocarcinoma between January 1, 1998, and December 31, 2014, were identified in the Department of Defense Central Cancer Registry and the MHS Data Repository–linked databases. Median time-to-treatment (surgery and chemotherapy) and 95% confidence intervals were compared between NHBs and NHWs in multivariable quantile regression models. Odds ratios and 95% confidence intervals of receiving delayed treatment defined by guidelines for NHBs relative to NHWs were estimated using multivariable logistic regression.

Results

Patients (n = 3067) had a mean age at diagnosis of 58.4 (12.2) years and the racial distribution was 76.7% NHW and 23.3% NHB. Median adjusted time-to-treatment was similar for NHB compared to NHW patients. The likelihood of receiving delayed treatment was similar between NHB and NHW patients.

Conclusions

In the MHS, there was no evidence of treatment delays for NHBs compared to NHWs, suggesting the role of equal access to medical care and insurance coverage in reducing racial disparities in colon cancer treatment.
Methylcitrate cycle gene MCD is essential for the virulence of Talaromyces marneffei
Authors: Feng Jiao , He Liya , Xiao Xing , Chen Zhiwen , Chen Chunmei , Chu Jieming , Lu Sha , Li Xiqing , Mylonakis Eleftherios , Xi Liyan
Published: July 2019

Talaromyces marneffei (T. marneffei), which used to be known as Penicillium marneffei, is the causative agent of the fatal systemic mycosis known as talaromycosis. For the purpose of understanding the role of methylcitrate cycle in the virulence of T. marneffei, we generated MCD deletion (ΔMCD) and complementation (ΔMCD+) mutants of T. marneffei. Growth in different carbon sources showed that ΔMCD cannot grow on propionate media and grew slowly on the valerate, valine, methionine, isoleucine, cholesterol, and YNB (carbon free) media. The macrophage killing assay showed that ΔMCD was attenuated in macrophages of mice in vitro, especially at the presence of propionate. Finally, virulence studies in a murine infection experiment revealed attenuated virulence of the ΔMCD, which indicates MCD is essential for T. marneffei virulence in the host. This experiment laid the foundation for the further study of the specific mechanisms underlying the methylcitrate cycle of T. marneffei and may provide suitable targets for new antifungals.
Thermal tides in rotating hot Jupiters
Authors: Lee Umin , Murakami Daiki
Published: July 2019

We calculate tidal torque due to semidiurnal thermal tides in rotating hot Jupiters, taking account of the effects of radiative cooling in the envelope and of the planets rotation on the tidal responses. We use a simple Jovian model composed of a nearly isentropic convective core and a thin radiative envelope. To represent the tidal responses of rotating planets, we employ series expansions in terms of spherical harmonic functions $Y_l^m$ with different ls for a given m. For low-forcing frequency, there occurs frequency resonance between the forcing and the g- and r-modes in the envelope and inertial modes in the core. We find that the resonance enhances the tidal torque, and that the resonance with the g- and r-modes produces broad peaks and that with the inertial modes very sharp peaks, depending on the magnitude of the non-adiabatic effects associated with the oscillation modes. We also find that the behaviour of the tidal torque as a function of the forcing frequency (or period) is different between prograde and retrograde forcing, particularly for long forcing periods because the r-modes, which have long periods, exist only on the retrograde side.
High efficiency photospheric emission entailed by formation of a collimation shock in gamma-ray bursts
Authors: Gottlieb Ore , Levinson Amir , Nakar Ehud
Published: July 2019

The primary dissipation mechanism in jets of gamma-ray bursts (GRBs), and the high efficiency of the prompt emission are long-standing issues. One possibility is strong collimation of a weakly magnetized relativistic jet by the surrounding medium, which can considerably enhance the efficiency of the photospheric emission. We derive a simple analytic criterion for the radiative efficiency of a collimated jet showing that it depends most strongly on the baryon loading. We confirm this analytic result by 3D numerical simulations, and further find that mixing of jet and cocoon material at the collimation throat leads to a substantial stratification of the outflow as well as sporadic loading, even if the injected jet is uniform and continuous. One consequence of this mixing is a strong angular dependence of the radiative efficiency. Another is large differences in the Lorentz factor of different fluid elements that lead to formation of internal shocks. Our analysis indicates that in both long and short GRBs a prominent photospheric component cannot be avoided when observed within an angle of a few degrees to the axis, unless the asymptotic Lorentz factor is limited by baryon loading at the jet base to Γ∞ < 100 (with a weak dependence on outflow power). Photon generation by newly created pairs behind the collimation shock regulates the observed temperature at $\sim 50~\theta _0^{-1}$ keV, where θ0 is the initial jet opening angle, in remarkable agreement with the observed peak energies of prompt emission spectra. Further consequences for the properties of the prompt emission are discussed at the end.
GASP – XX. From the loose spatially resolved to the tight global SFR–mass relation in local spiral galaxies
Authors: Vulcani Benedetta , Poggianti Bianca M , Moretti Alessia , Franchetto Andrea , Gullieuszik Marco , Fritz Jacopo , Bettoni Daniela , Tonnesen Stephanie , Radovich Mario , Jaffé Yara L , McGee Sean , Bellhouse Callum , Fasano Giovanni
Published: July 2019

Exploiting the sample of 30 local star-forming, undisturbed late-type galaxies in different environments drawn from the GAs Stripping Phenomena in galaxies with MUSE (GASP), we investigate the spatially resolved star formation rate–mass ($\rm \Sigma _{SFR}$–$\rm \Sigma _\ast$) relation. Our analysis includes also the galaxy outskirts (up to >4 effective radii, re), a regime poorly explored by other Integral Field Spectrograph surveys. Our observational strategy allows us to detect H α out to more than 2.7re for 75 per cent of the sample. Considering all galaxies together, the correlation between the $\rm \Sigma _{SFR}$ and $\rm \Sigma _\ast$ is quite broad, with a scatter of 0.3 dex. It gets steeper and shifts to higher $\rm \Sigma _\ast$ values when external spaxels are excluded and moving from less to more massive galaxies. The broadness of the overall relation suggests galaxy-by-galaxy variations. Indeed, each object is characterized by a distinct $\rm \Sigma _{SFR}$ –$\rm \Sigma _\ast$ relation and in some cases the correlation is very loose. The scatter of the relation mainly arises from the existence of bright off-centre star-forming knots whose $\rm \Sigma _{SFR}$–$\rm \Sigma _\ast$ relation is systematically broader than that of the diffuse component. The $\rm \Sigma _{SFR}$–$\rm \Sigma _{tot \, gas}$ (total gas surface density) relation is as broad as the $\rm \Sigma _{SFR}$–$\rm \Sigma _\ast$ relation, indicating that the surface gas density is not a primary driver of the relation. Even though a large galaxy-by-galaxy variation exists, mean $\rm \Sigma _{SFR}$ and $\rm \Sigma _\ast$ values vary of at most 0.7 dex across galaxies. We investigate the relationship between the local and global SFR–M* relation, finding that the latter is driven by the existence of the size–mass relation.
The largest Crab glitch and the vortex creep model
Authors: Gügercinoğlu Erbil , Alpar M Ali
Published: July 2019

The Crab pulsar displayed its largest glitch on 2017 November. An extended initial spin-up phase of this largest glitch was resolved, for the first time with high cadence of observations both in radio and X-rays on a time-scale of 2 d. A combination of crustquake and vortex unpinning models is invoked to account for the extended spin-up, magnitude, and post-glitch relaxation characteristics of this glitch. We evaluate the extended spin-up followed by the familiar spin-down as due to the creep response to the initial induced inward motion of some vortex lines pinned to broken crustal plates moving inward towards the rotation axis, together with the common and familiar post-glitch creep response to the sudden outward motion of vortices unpinned at the glitch. Our analysis confirms that the number of unpinned vortices participating in glitches are similar in all Crab glitches, and within an order of magnitude in all glitches from all pulsars. This typical number of unpinned vortices is related to the broken plate size in quakes as triggers for vortex unpinning avalanches. The physical determinant of this universal broken plate size is in turn the critical strain angle in the neutron star crust. Occurrence of this largest Crab glitch after a relatively long inactive period is consistent with accumulation of the pinned vorticity to be tapped.
Barred galaxies in cosmological zoom-in simulations: the importance of feedback
Authors: Zana Tommaso , Capelo Pedro R , Dotti Massimo , Mayer Lucio , Lupi Alessandro , Haardt Francesco , Bonoli Silvia , Shen Sijing
Published: July 2019

Bars are a key factor in the long-term evolution of spiral galaxies, in their unique role in redistributing angular momentum and transporting gas and stars on large scales. The Eris-suite simulations are cosmological zoom-in, N-body, smoothed-particle hydrodynamic simulations built to follow the formation and evolution of a Milky-Way-sized galaxy across the build-up of the large-scale structure. Here we analyse and describe the outcome of two particular simulations taken from the Eris suite – ErisBH and Eris2k – which mainly differ in the prescriptions employed for gas cooling, star formation, and feedback from supernovae and black holes. Our study shows that the enhanced effective feedback in Eris2k, due to the collective effect of the different micro-physics implementations, results in a galaxy that is less massive than its ErisBH counterpart till z ∼ 1. However, when the stellar content is large enough so that global dynamical instabilities can be triggered, the galaxy in Eris2k develops a stronger and more extended bar with respect to ErisBH. We demonstrate that the structural properties and time evolution of the two bars are very different. Our results highlight the importance of accurate sub-grid prescriptions in cosmological zoom-in simulations of the process of galaxy formation and evolution, and the possible use of a statistical sample of barred galaxies to assess the strength of the stellar feedback.
Dark-matter-deficient galaxies in hydrodynamical simulations
Authors: Jing Yingjie , Wang Chunxiang , Li Ran , Liao Shihong , Wang Jie , Guo Qi , Gao Liang
Published: July 2019

Low-mass galaxies are expected to be dark-matter-dominated even within their central regions. Recently, two observations reported two dwarf galaxies in a group environment with very little dark matter in their central regions. We explore the population and origins of dark-matter-deficient galaxies (DMDGs) using two state-of-the-art hydrodynamical simulations, the EAGLE and Illustris projects. For all satellite galaxies with 109 < M* < 1010 M$\odot$ in groups with M200 > 1013 M$\odot$, we find that about $2.6\, {\rm per\, cent}$ of them in EAGLE, and $1.5\, {\rm per\, cent}$ in Illustris are DMDGs with dark matter fractions below $50\, {\rm per\, cent}$ inside two times the half-stellar-mass radius. We demonstrate that DMDGs are highly tidally disrupted galaxies, and that because dark matter has a higher binding energy than stars, mass loss of the dark matter is much more rapid than that of stars in DMDGs during tidal interactions. If DMDGs were confirmed in observations, they are expected in current galaxy formation models.
Placental creatine metabolism in cases of placental insufficiency and reduced fetal growth
Authors: Ellery Stacey J , Murthi Padma , Davies-Tuck Miranda L , Della Gatta Paul A , May Anthony K , Kowalski Greg M , Callahan Damien L , Bruce Clinton R , Alers Nicole O , Miller Suzanne L , Erwich Jan Jaap H M , Wallace Euan M , Walker David W , Dickinson Hayley , Snow Rod J
Published: July 2019

Creatine is a metabolite involved in cellular energy homeostasis. In this study, we examined placental creatine content, and expression of the enzymes required for creatine synthesis, transport and the creatine kinase reaction, in pregnancies complicated by low birthweight. We studied first trimester chorionic villus biopsies (CVBs) of small for gestational age (SGA) and appropriately grown infants (AGA), along with third trimester placental samples from fetal growth restricted (FGR) and healthy gestation-matched controls. Placental creatine and creatine precursor (guanidinoacetate—GAA) levels were measured. Maternal and cord serum from control and FGR pregnancies were also analyzed for creatine concentration. mRNA expression of the creatine transporter (SLC6A8); synthesizing enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT); mitochondrial (mtCK) and cytosolic (BBCK) creatine kinases; and amino acid transporters (SLC7A1 & SLC7A2) was assessed in both CVBs and placental samples. Protein levels of AGAT (arginine:glycine aminotransferase), GAMT, mtCK and BBCK were also measured in placental samples. Key findings; total creatine content of the third trimester FGR placentae was 43% higher than controls. The increased creatine content of placental tissue was not reflected in maternal or fetal serum from FGR pregnancies. Tissue concentrations of GAA were lower in the third trimester FGR placentae compared to controls, with lower GATM and GAMT mRNA expression also observed. No differences in the mRNA expression of GATM, GAMT or SLC6A8 were observed between CVBs from SGA and AGA pregnancies. These results suggest placental creatine metabolism in FGR pregnancies is altered in late gestation. The relevance of these changes on placental bioenergetics should be the focus of future investigations.
Inositol pyrophosphates impact phosphate homeostasis via modulation of RNA 3′ processing and transcription termination
Authors: Sanchez Ana M , Garg Angad , Shuman Stewart , Schwer Beate
Published: July 2019

Fission yeast phosphate acquisition genes pho1, pho84, and tgp1 are repressed in phosphate-rich medium by transcription of upstream lncRNAs. Here, we show that phosphate homeostasis is subject to metabolite control by inositol pyrophosphates (IPPs), exerted through the 3′-processing/termination machinery and the Pol2 CTD code. Increasing IP8 (via Asp1 IPP pyrophosphatase mutation) de-represses the PHO regulon and leads to precocious termination of prt lncRNA synthesis. pho1 de-repression by IP8 depends on cleavage-polyadenylation factor (CPF) subunits, termination factor Rhn1, and the Thr4 letter of the CTD code. pho1 de-repression by mutation of the Ser7 CTD letter depends on IP8. Simultaneous inactivation of the Asp1 and Aps1 IPP pyrophosphatases is lethal, but this lethality is suppressed by mutations of CPF subunits Ppn1, Swd22, Ssu72, and Ctf1 and CTD mutation T4A. Failure to synthesize IP8 (via Asp1 IPP kinase mutation) results in pho1 hyper-repression. Synthetic lethality of asp1Δ with Ppn1, Swd22, and Ssu72 mutations argues that IP8 plays an important role in essential 3′-processing/termination events, albeit in a manner genetically redundant to CPF. Transcriptional profiling delineates an IPP-responsive regulon composed of genes overexpressed when IP8 levels are increased. Our results establish a novel role for IPPs in cell physiology.
KDM2 proteins constrain transcription from CpG island gene promoters independently of their histone demethylase activity
Authors: Turberfield Anne H , Kondo Takashi , Nakayama Manabu , Koseki Yoko , King Hamish W , Koseki Haruhiko , Klose Robert J
Published: July 2019

CpG islands (CGIs) are associated with the majority of mammalian gene promoters and function to recruit chromatin modifying enzymes. It has therefore been proposed that CGIs regulate gene expression through chromatin-based mechanisms, however in most cases this has not been directly tested. Here, we reveal that the histone H3 lysine 36 (H3K36) demethylase activity of the CGI-binding KDM2 proteins contributes only modestly to the H3K36me2-depleted state at CGI-associated gene promoters and is dispensable for normal gene expression. Instead, we discover that KDM2 proteins play a widespread and demethylase-independent role in constraining gene expression from CGI-associated gene promoters. We further show that KDM2 proteins shape RNA Polymerase II occupancy but not chromatin accessibility at CGI-associated promoters. Together this reveals a demethylase-independent role for KDM2 proteins in transcriptional repression and uncovers a new function for CGIs in constraining gene expression.
Identifying critically important vascular access outcomes for trials in haemodialysis: an international survey with patients, caregivers and health professionals
Authors: Viecelli Andrea K , Howell Martin , Tong Allison , Teixeira-Pinto Armando , O’Lone Emma , Ju Angela , Craig Jonathan C , Hooi Lai-Seong , Lee Timmy , Lok Charmaine E , Polkinghorne Kevan R , Quinn Robert R , Vachharajani Tushar J , Vanholder Raymond , Zuo Li , Tordoir Jan , Pecoits-Filho Roberto , Yuo Theodore , Kopperschmidt Pascal , Smith Rob , Irish Ashley B , Mori Trevor A , Pascoe Elaine M , Johnson David W , Hawley Carmel M
Published: July 2019

Background

Vascular access outcomes reported across haemodialysis (HD) trials are numerous, heterogeneous and not always relevant to patients and clinicians. This study aimed to identify critically important vascular access outcomes.

Method

Outcomes derived from a systematic review, multi-disciplinary expert panel and patient input were included in a multilanguage online survey. Participants rated the absolute importance of outcomes using a 9-point Likert scale (7–9 being critically important). The relative importance was determined by a best–worst scale using multinomial logistic regression. Open text responses were analysed thematically.

Results

The survey was completed by 873 participants [224 (26%) patients/caregivers and 649 (74%) health professionals] from 58 countries. Vascular access function was considered the most important outcome (mean score 7.8 for patients and caregivers/8.5 for health professionals, with 85%/95% rating it critically important, and top ranked on best–worst scale), followed by infection (mean 7.4/8.2, 79%/92% rating it critically important, second rank on best–worst scale). Health professionals rated all outcomes of equal or higher importance than patients/caregivers, except for aneurysms. We identified six themes: necessity for HD, applicability across vascular access types, frequency and severity of debilitation, minimizing the risk of hospitalization and death, optimizing technical competence and adherence to best practice and direct impact on appearance and lifestyle.

Conclusions

Vascular access function was the most critically important outcome among patients/caregivers and health professionals. Consistent reporting of this outcome across trials in HD will strengthen their value in supporting vascular access practice and shared decision making in patients requiring HD.
Immunostaining for galactose-deficient immunoglobulin A is not specific for primary immunoglobulin A nephropathy
Authors: Cassol Clarissa A , Bott Cherri , Nadasdy Gyongyi M , Alberton Valeria , Malvar Ana , Nagaraja Haikady N , Nadasdy Tibor , Rovin Brad H , Satoskar Anjali A
Published: July 2019

Background

Primary immunoglobulin A nephropathy (IgAN) is characterized by IgA1-dominant or codominant glomerular deposits, postulated to be galactose deficient (Gd). However, glomerular IgA deposition can also occur in nonrenal diseases such as liver cirrhosis, psoriasis and inflammatory bowel disease (‘secondary IgAN’) or be an incidental finding in biopsies with other pathologies. A glomerulonephritis resembling IgAN can develop in patients with bacterial, mainly staphylococcal infections [staphylococcal infection-associated glomerulonephritis (SAGN)]. There are no specific histological features to distinguish between these, but differentiation is critical for appropriate management. The aim of this study was to investigate whether a recently described antibody to Gd-IgA1 (KM-55) could aid in differentiating primary IgAN from other conditions with glomerular IgA deposition, especially SAGN.

Methods

We performed a retrospective cohort study of patients who underwent kidney biopsy for clinical indications and were found to have glomerular IgA deposits.

Results

We evaluated 100 biopsies, including primary IgAN (n = 44), secondary IgAN (n = 27), SAGN (n = 13), incidental IgA deposition (n = 8) and lupus nephritis (n = 8). There was no difference in Gd-IgA staining intensity or the proportion of positive cases between primary and secondary IgAN. SAGN and cases with incidental IgA deposits had significantly lower Gd-IgA staining intensity than primary IgAN, but up to 69% of SAGN cases were positive (albeit weaker).

Conclusions

Gd-IgA staining is present not only in primary IgAN, but also in biopsies with secondary IgAN, SAGN and incidental IgA. Weak or negative staining may favor SAGN, especially in the setting of infection, or incidental IgA in the absence of nephritic symptoms or in the presence of other unrelated glomerular pathologies. However, positive staining for Gd-IgA alone is not specific enough for a diagnosis of primary IgAN.
Targeting hypoxia downstream signaling protein, CAIX, for CAR T-cell therapy against glioblastoma
Authors: Cui Jing , Zhang Qi , Song Qi , Wang Herui , Dmitriev Pauline , Sun Mitchell Y , Cao Xiaoyu , Wang Yang , Guo Liemei , Indig Iris H , Rosenblum Jared S , Ji Chunxia , Cao Dongqing , Yang Kaiyong , Gilbert Mark R , Yao Yu , Zhuang Zhengping
Published: July 2019

Background

Glioblastoma survival remains unchanged despite continuing therapeutic innovation. Herein, we aim to (i) develop chimeric antigen receptor (CAR) T cells with a specificity to a unique antigen, carbonic anhydrase IX (CAIX), which is expressed in the hypoxic microenvironment characteristic of glioblastoma, and (ii) demonstrate its efficacy with limited off-target effects.

Methods

First we demonstrated expression of CAIX in patient-derived glioblastoma samples and available databases. CAR T cells were generated against CAIX and efficacy was assessed in 4 glioblastoma cell lines and 2 glioblastoma stem cell lines. Cytotoxicity of anti-CAIX CAR T cells was assessed via interferon gamma, tumor necrosis factor alpha, and interleukin-2 levels when co-cultured with tumor cells. Finally, we assessed efficacy of direct intratumoral injection of the anti-CAIX CAR T cells on an in vivo xenograft mouse model using the U251 luciferase cell line. Tumor infiltrating lymphocyte analyses were performed.

Results

We confirm that CAIX is highly expressed in glioblastoma from patients. We demonstrate that CAIX is a suitable target for CAR T-cell therapy using anti-CAIX CAR T cells against glioblastoma in vitro and in vivo. In our mouse model, a 20% cure rate was observed without detectable systemic effects.

Conclusions

By establishing the specificity of CAIX under hypoxic conditions in glioblastoma and highlighting its efficacy as a target for CAR T-cell therapy, our data suggest that anti-CAIX CAR T may be a promising strategy to treat glioblastoma. Direct intratumoral injection increases anti-CAIX CAR T-cell potency while limiting its off-target effects.
Acyl chain that matters: introducing sn-2 acyl chain preference to a phospholipase D by protein engineering
Authors: Damnjanović Jasmina , Nakano Hideo , Iwasaki Yugo
Published: July 2019

Phospholipase D (PLD) is an enzyme widely used for enzymatic synthesis of structured phospholipids (PLs) with modified head groups. These PLs are mainly used as food supplements and liposome ingredients. Still, there is a need for an enzyme that discriminates between PLs and lysoPLs, for specific detection of lysoPLs in various specimens and enzymatic synthesis of certain PLs from a mixed substrate. To meet this demand, we aimed at altering sn-2 acyl chain recognition of a PLD, leading to a variant enzyme preferably reacting on lysoPLs, by protein engineering. Based on the crystal structure of Streptomyces antibioticus PLD, W166 was targeted for saturation mutagenesis due to its strong interaction with the sn-2 acyl chain of the PL. Screening result pointed at W166R and W166K PLDs to selectively react on lysophosphatidylcholine (lysoPC), while not on PC. These variants showed a negative correlation between activity and sn-2 chain length of PL substrates. This behavior was not observed in the wild-type (WT)-PLD. Kinetic analysis revealed that the W166R and W166K variants have 7–10 times higher preference to lysoPC compared to the WT-PLD. Additionally, W166R PLD showed detectable activity toward glycero-3-phosphocholine, unlike the WT-PLD. Applicability of the lysoPC-preferring PLD was demonstrated by detection of lysoPC in the mixed PC/lysoPC sample and by the synthesis of cyclic phosphatidic acid. Structure model analyses supported the experimental findings and provided a basis for the structure model-based hypothesis on the observed behavior of the enzymes.
Inequality in access to hearing care for older adults in residential homes
Authors: White J D , Johnson C , Deplacido C G , Matthews B , Steenkamp E H
Published: July 2019

Background

The population of older people in residential homes is projected to rise. There are unrecognized hearing difficulties among residents and prevalence of hearing loss in this population is underreported. This can result in an overestimation of levels of cognitive impairment. Untreated hearing loss is associated with social isolation, depression, disruptive behaviour and cognitive decline. This study aimed to explore the provision of hearing care (hearing assessment, rehabilitation and staff training) in Scottish care homes for older people.

Methods

A survey comprising 18 questions was distributed to the managers (or designated staff members) of 659 care homes across Scotland.

Results

Responses were obtained from 154 care homes. The results support existing evidence that hearing is not assessed in the majority of homes, resulting in under detection of hearing loss. Staff lack training in supporting residents’ hearing needs. Access to hearing care in residential homes differs across health board areas.

Conclusions

There is an urgent requirement for hearing assessment of older adults on admission to residential care. Care providers require this information to construct effective care plans and mitigate the effects of hearing loss. Those responsible for providing hearing rehabilitation services require information about service users to address any unmet need.
Analysing the determinants of higher education systems’ performance–a structural equation modelling approach
Authors: Agasisti Tommaso , Bertoletti Alice
Published: July 2019

This article deals with the relationships between the performance of higher education systems (HESs) and their potential determinants. The research employed data relating to twenty-nine European countries, within a time span of 15 years. The empirical work is based on a conceptual framework that has been tested through Structural Equation Modelling. The data was selected from a novel data set that we have built by gathering HES indicators from the major international databases. Among the more noteworthy results, we found no statistically significant correlation between graduation rates and research performance. Additionally, we found a moderate effect of public expenditure on HES performance. The article addresses the issue of the lack of a comprehensive set of systemic indicators for HES performance, providing a holistic picture of the relationship between HES determinants and performance, which, in turn, could help to provide an adequate evaluation of the policies in the field of higher education.
Governing research through affects: The case of ecosystem services science
Authors: Brunet Lucas , Arpin Isabelle , Peltola Taru
Published: July 2019

Despite the abundant literature on transformation of research and the affective dimension of research practice, affective governing of research has not been documented to the same extent. To address this gap, we examine how scientific research can be affectively governed by research institutions. We focus on the case of ecosystem services science, an interdisciplinary field of research expected to lead to decisions capable of halting environmental degradation. Drawing on theoretical discussions bridging the concept of affect and the Foucauldian concept of government, we argue that affects can be mobilised as a technology of government in governing scientific practice. We identify three affective techniques used to govern ecosystem service research and discuss the limits of governing research through affects. Our analysis deepens the understanding of how academic work is transformed in the context of redefined relations between science and society.
R&D and innovation policy in the Western Balkans: Are there additionality effects?
Authors: Orlic Edvard , Radicic Dragana , Balavac Merima
Published: July 2019

This article examines three types of additionality—input, output, and behavioural—in a cross-country framework. Besides conducting a systemic evaluation, which is scarce even in developed economies, this is among the first studies to investigate the effectiveness of R&D and innovation policy in transition economies. We estimate treatment effects for small and medium-sized firms in six Western Balkan countries. Empirical findings from matching estimators indicate no input and output additionality, while we find evidence of behavioural additionality. These results highlight the importance of conducting a systemic evaluation of innovation public support. We discuss theoretical and policy implications stemming from our empirical findings.
Cadmium Exposure Impairs Adult Hippocampal Neurogenesis
Authors: Wang Hao , Abel Glen M , Storm Daniel R , Xia Zhengui
Published: July 2019

Cadmium (Cd) is an environmental pollutant of considerable interest throughout the world and potentially a neurotoxicant. Our recent data indicate that Cd exposure induces impairment of hippocampus-dependent learning and memory in mice. However, the underlying mechanisms for this defect are not known. The goal of this study was to determine if Cd inhibits adult neurogenesis and to identify underlying signaling pathways responsible for this impairment. Adult hippocampal neurogenesis is a process in which adult neural progenitor/stem cells (aNPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG) generate functional new neurons in the hippocampus which contributes to hippocampus-dependent learning and memory. However, studies concerning the effects of neurotoxicants on adult hippocampal neurogenesis and the underlying signaling mechanisms are limited. Here, we report that Cd significantly induces apoptosis, inhibits proliferation, and impairs neuronal differentiation in primary cultured aNPCs derived from the SGZ. In addition, the c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase signaling pathways are activated by Cd and contribute to its toxicity. Furthermore, we exposed 8-week-old male C57BL/6 mice to Cd through drinking water for 13 weeks to assess the effects of Cd on adult hippocampal neurogenesis in vivo. Cd treatment reduced the number of 5-week-old adult-born cells in the DG and impaired the differentiation of adult-born hippocampal neurons. These results suggest that Cd exposure impairs adult hippocampal neurogenesis both in vitro and in vivo. This may contribute to Cd-mediated inhibition of hippocampus-dependent learning and memory.
Polycystic ovary syndrome
Authors: Pfieffer Mary Lauren
Published: July 2019

Polycystic ovary syndrome (PCOS) is a common endocrine disorder. Patients may present with a combination of hyperandrogenism symptoms, menstrual irregularities, metabolic syndrome, infertility, acne, and obesity. PCOS diagnosis is based on three diagnostic guidelines. Treatment options include oral contraceptive pills, antiandrogens, and metformin.
Validity of the Budapest Criteria For Poststroke Complex Regional Pain Syndrome
Authors: Oh Sang-Wook , Choi Seong-Uk , Park Mina , Shin Joon-Ho
Published: July 2019

Objectives:

Complex regional pain syndrome-1 is a chronic neuropathic disorder, and poststroke complex regional pain syndrome (PS-CRPS) is not a rare complication. There is a lack of study implementing the Budapest criteria for PS-CRPS diagnosis. Thus, the present study investigated the validity of the Budapest criteria for PS-CRPS diagnosis and assessed the PS-CRPS–related factors in stroke patients with an affected upper extremity.

Methods:

The study included 72 patients with first-ever stroke resulting in hemiplegia. The prevalence of PS-CRPS and diagnostic validity were compared among the Budapest clinical criteria, Budapest research criteria, modified Budapest criteria (removal of the motor factor from the motor/trophic category), and International Association for the Study of Pain (IASP) criteria in patients diagnosed with PS-CRPS according to the Budapest clinical criteria.

Results:

PS-CRPS was diagnosed in 6 (8.3%), 1 (1.4%), 6 (8.3%), and 11 patients (15.3%) according to the Budapest clinical criteria, Budapest research criteria, modified Budapest criteria, and IASP criteria, respectively. The Budapest criteria and IASP criteria had sensitivities of 0.99 and 1.00, respectively, and specificities of 0.68 and 0.41, respectively, for PS-CRPS diagnosis. There were no differences in risk factors between PS-CRPS patients and non–PS-CRPS patients when the diagnosis was based on the Budapest clinical criteria. However, there were differences in muscle strength and Brunnstrom stage between PS-CRPS patients and non–PS-CRPS patients when the diagnosis was based on the IASP criteria.

Discussion:

Our findings indicate that the diagnostic validity of the current Budapest clinical criteria for PS-CRPS is low. Thus, the current Budapest criteria might not be appropriate for PS-CRPS diagnosis.
Use of Potassium Hydroxide (KOH) Test Reduces Antifungal Medication Prescription for Suspected Monilial Diaper Dermatitis in the Neonatal Intensive Care Unit
Authors: Campbell Julie , MacConnell Valerie , Sacco Lauren , Zuill Ramona , Bosque Elena
Published: July 2019

Background:

Despite availability of rapid fungal potassium hydroxide (KOH) tests, many care providers rely on visual assessment to determine the diagnosis of monilial diaper dermatitis (MDD).

Purpose:

To determine whether a KOH test, when MDD is suspected, would result in more accurate diagnoses, with decreased antifungal medication prescription and exposure.

Methods:

Quality improvement project from 2016 through 2017 with protocol implemented in 2017 for treatment of MDD after positive KOH testing. If monilial rash suspected, after 2 negative KOH tests, then antifungal ordered (considered false negative). χ2testing and cost determination were performed.

Sample:

Neonates in 2 level III neonatal intensive care units.

Outcome Variables:

KOH test results, use of antifungal medication, and cost.

Results:

The patient census included 1051 and 1015 patients in the year before and after the protocol initiation. The medical orders for antifungal medication decreased from 143 to 36 (P< .001; 95% odds ratio confidence interval, 2.24-4.38). There was a 75% reduction in both use and cost, as charged, of antifungal agents. Overall charges, including KOH test costs, decreased by 12%. Three infants received multiple negative KOH tests, then a positive one. These met the definition of false-negative tests, per protocol. There were no cases of fungal sepsis.

Implications for Practice:

Use of a quality improvement protocol, in which the use of KOH testing is required, before antifungal agents are prescribed, results in decreased exposure and costs.

Implications for Research:

To test the feasibility of bedside “point-of-care” KOH testing, and whether KOH testing and reduced antifungal medication use affects antimicrobial resistance or invasive fungal sepsis.
Zika autoimmunity and Guillain–Barré syndrome
Authors: Katz Itai , Gilburd Boris , Shovman Ora
Published: July 2019

Purpose of review

To summarize the recent data regarding Guillain–Barré syndrome (GBS) as an autoimmune disorder following infection with Zika virus (ZIKV) infection, including the proposed pathogenic mechanisms and the role of autoantibodies.

Recent findings

The loss of self-tolerance that leads to autoimmune diseases is a multifactorial process that may be illustrated as ‘the mosaic of autoimmunity’. Infectious agents may contribute to the development of autoimmunity by several proposed mechanisms. One of the central mechanisms is molecular mimicry, which is also the most plausible mechanism in the case of ZIKV-induced autoimmune disorders.

A recent meta-analysis found a low prevalence of GBS associated with ZIKV infection. Nevertheless, the estimated cost of illness for patients with GBS associated with ZIKV are tremendous and exceed 4.7 million dollars per year in Brazil alone.

Currently, there is sufficient data to indicate that ZIKV infection is one of many triggers and factors that may contribute to the development GBS. Thus, it is advised to evaluate and determine ZIKV exposure and infection in the management of potential GBS patients.
Cutaneous Nodular Amyloidosis: A Disfiguring Aspect of the Face
Authors: Dupont Letícia , Martins Souza Paulo Ricardo , Damiani Leandro , Boff Ana Letícia
Published: July 2019

Primary localized cutaneous nodular amyloidosis is a rare plasma cell dyscrasia in which an amorphous material consisting of light chain amyloid is produced and deposited in the dermis, with varied clinical presentation. We describe the case with unusual and tumor lush clinical presentation in the face with no progression to systemic disease and no evidence of extracutaneous commitment.
Melanotic Schwannoma of the Vulva: A Case Report and Review of the Literature
Authors: Cohen Jarish N. , Yeh Iwei , LeBoit Philip E.
Published: July 2019

Melanotic schwannoma is a pigmented tumor of peripheral nerve differentiation. Primary cutaneous presentations are extremely rare, as the bulk of melanotic schwannomas tend to develop in paraspinal and axial sites. Tumors arise sporadically and in the setting of the Carney complex. Alterations in the gene encoding protein kinase A regulatory subunit-α (PRKAR1A) underlie most patients with the Carney complex and mediate melanotic schwannoma tumorigenesis. Melanotic schwannomas from noncutaneous sites can locally recur and metastasize widely, leading to a recent proposal to change the nomenclature to “malignant melanotic schwannian tumor.” However, the clinicopathologic features of primary cutaneous melanotic schwannomas are relatively unexplored. We present a case of a nodule arising on the vulva of a 34-year-old woman. Microscopically, a dermal-based, heavily pigmented proliferation of plump spindled and epithelioid cells arrayed in nodules and fascicles was seen. Lesional cells stained positively for S100, Melan-A, and BAP1 but were negative for Prkar1α. Next-generation sequencing of a panel of 480 cancer-associated genes revealed that the tumor harbored a PRKAR1A p.S299fs truncating mutation and copy neutral loss of heterozygosity of chromosome 17q, the locus at which PRKAR1A resides. Importantly, no other genetic abnormalities or chromosomal copy number changes were identified. On the basis of combined histopathologic, immunohistochemical, and genetic features, a diagnosis of melanotic schwannoma was rendered. Overall, we present the first clinicopathologic description of a vulvar melanotic schwannoma, review the literature concerning cutaneous presentations of melanotic schwannoma, and propose that melanotic schwannian tumors native to skin may behave more indolently than their noncutaneous counterparts.
Sarcomatoid Variant of Primary Cutaneous Anaplastic Large Cell Lymphoma
Authors: Natsuaki Yohei , Muto Ikko , Kawamura Miyuki , Saruta Hiroshi , Teye Kwesi , Ohshima Koichi , Nakama Takekuni , Ohata Chika
Published: July 2019

Sarcomatoid variant of primary cutaneous anaplastic large cell lymphoma is rare and is a diagnostic challenge. Clinical manifestation often mimics that of an infectious disease. Predominance of spindle cells in the biopsy specimen prevents from suspecting lymphoma. Here, we report the fourth case of this entity with good prognosis. A 30-year-old woman presented with several nodules on the whole body. The biopsy revealed infiltration of spindle cells in the dermis with myxomatous background. The spindle cells were positive for CD4 and CD30 and negative for CD3, CD8, CD20, and anaplastic lymphoma kinase. Although most of the skin lesions spontaneously resolved, a new red nodule progressively expanded on the left axilla. Finally, the patient received chemotherapy, which resulted in complete remission. The patient is free of disease for 18 months.