bluuebunny/crossref_metadata_2025 huggingface dataset:
D-Dimer Combined With CRP Can Improve the Differential Value of Bacterial Meningitis and Tuberculous Meningitis
Authors: Lu Liuyi , Qi Yunwei , Chen Huaping , Hu Zuojian , Yang Sitao , Qin Simeng , Zhang Linyan , Chen Mingxing , Qin Xue
Published: January 2021

Objective

To explore the diagnostic value of the coagulation marker D-dimer and its combination with the traditional marker C-reactive protein (CRP) in distinguishing bacterial meningitis (BM) from tuberculous meningitis (TM).

Methods

We performed a retrospective study on specimens from 173 patients with meningitis who were hospitalized at the First Affiliated Hospital of Guangxi Medical University, Guangxi, China, from 2012 through 2020. The patient records were divided into the BM group and the TM group, and hematological parameters D-dimer and CRP were evaluated for the 2 groups.

Results

The levels of D-dimer and CRP in the BM group were significantly higher than those levels in the TM group (P ˂.001 for each), and the sensitivity and specificity of the combined detection of the 2 markers was 86.3% to 100%; the area under the receiver operating characteristic (ROC) curve reached 0.983 (95% confidence interval [CI], 0.966–0.999).

Conclusion

D-dimer testing has high specificity in distinguishing between BM and TM; CRP testing also has high sensitivity. The combined diagnosis of the 2 biomarkers helps to distinguish TM from BM.
On the Moralization of Moral Theory
Authors: Baz Avner
Published: January 2021

In the concluding lines of Part Three of The Claim of Reason, Stanley Cavell writes: ‘If the moralist is the human being who best grasps the human position, teaches us what our human position is, better than we know, in ways we cannot escape but through distraction and muddle, then our first task in subjecting ourselves to judgment is to tell the moralist from the moralizer’ (Cavell 1979, hereafter ‘CR’, p. 326). Cavell then proceeds to characterize the moralizer as one who is ‘speaking in the name of a position one does not occupy, confronting others in positions of which one will not imagine the acknowledgement’ (CR, p. 326). Beginning with an exposition of Cavell’s notion of ‘moral position’, I will offer an interpretation of the distinction he draws between the moralist and the moralizer; I will then explain how the moral philosopher’s (attempted) use of morally significant words may come to resemble the moralizer’s; and then I will argue that contemporary English-speaking moral philosophy as represented by the recent debates concerning ‘moral testimony’, or ‘moral deference’, has been failing its moralist aspirations, and that, by Cavell’s lights, the morality reflected in those debates is, in essence, that of the moralizer.
On the radial abundance gradients of nitrogen and oxygen in the inner Galactic disc
Authors: Arellano-Córdova K Z , Esteban C , García-Rojas J , Méndez-Delgado J E
Published: January 2021

We present optical spectra of nine Galactic H ii regions observed with the 10.4 m Gran Telescopio Canarias telescope and located at Galactocentric distances (RG) from 4 to 8 kpc. The distances of the objects have been revised using Gaia DR2 parallaxes. We determine the electron temperature for all the nebulae, which allows a precise computation of their ionic abundances. We have included published data of an additional sample of Galactic H ii regions, providing a final data set of 42 objects. The shape of the radial gradients of O/H and N/H is linear and constant, discarding any substantial change of the slope, at least for RG between 4 and 17 kpc. The small dispersion of the O/H and N/H values with respect to the computed gradients imply the absence of significant azimuthal variations of the chemical abundances, at least in the quadrant covered by our observations. We find an almost flat N/O versus O/H diagram relation. This result is not observed in other nearby spiral galaxies except M31. Finally, we compare our computed gradients with those obtained using far-infrared (FIR) spectra. We confirm the significant offset in the N/O distribution between the optical and FIR observations. Possible explanations involve ionization correction factors and the strong dependence on density of the abundance determinations based on FIR lines.
A NuSTAR confirmation of the 36 ks hard X-ray pulse-phase modulation in the magnetar 1E 1547.0 − 5408
Authors: Makishima Kazuo , Enoto Teruaki , Yoneda Hiroki , Odaka Hirokazu
Published: January 2021

This paper describes an analysis of the NuSTAR data of the fastest-rotating magnetar 1E 1547 − 5408, acquired in 2016 April for a time lapse of 151 ks. The source was detected with a 1–60 keV flux of 1.7 × 10−11 erg s−1 cm−2, and its pulsation at a period of 2.086710(5) s. In 8–25 keV, the pulses were phase-modulated with a period of T = 36.0 ± 2.3 ks, and an amplitude of ∼0.2 s. This reconfirms the Suzaku discovery of the same effect at $T=36.0 ^{+4.5}_{-2.5}$ ks, made in the 2009 outburst. These results strengthen the view derived from the Suzaku data, that this magnetar performs free precession as a result of its axial deformation by ∼0.6 × 10−4, possibly caused by internal toroidal magneti fields (MFs) reaching ∼1016 G. Like in the Suzaku case, the modulation was not detected in energies below ∼8 keV. Above 10 keV, the pulse-phase behaviour, including the 36 ks modulation parameters, exhibited complex energy dependencies: at ∼22 keV, the modulation amplitude increased to ∼0.5 s, and the modulation phase changed by ∼65° over 10–27 keV, followed by a phase reversal. Although the pulse significance and pulsed fraction were originally very low in >10 keV, they both increased noticeably, when the arrival times of individual photons were corrected for these systematic pulse-phase variations. Possible origins of these complex phenomena are discussed, in terms of several physical processes that are specific to ultrastrong MFs.
Dual polarization measurements of MWA beampatterns at 137 MHz
Authors: Chokshi A , Line J L B , Barry N , Ung D , Kenney D , McPhail A , Williams A , Webster R L
Published: January 2021

The wide adoption of low-frequency radio interferometers as a tool for deeper and higher resolution astronomical observations has revolutionized radio astronomy. Despite their construction from static, relatively simple dipoles, the sheer number of distinct elements introduces new, complicated instrumental effects. Their necessary remote locations exacerbate failure rates, while electronic interactions between the many adjacent receiving elements can lead to non-trivial instrumental effects. The Murchison Widefield Array (MWA) employs phased array antenna elements (tiles), which improve collecting area at the expense of complex beam shapes. Advanced electromagnetic simulations have produced the fully embedded element (FEE) simulated beam model which has been highly successful in describing the ideal beam response of MWA antennas. This work focuses on the relatively unexplored aspect of various in-situ, environmental perturbations to beam models and represents the first large-scale, in-situ, all-sky measurement of MWA beam shapes at multiple polarizations and pointings. Our satellite based beam measurement approach enables all-sky beam response measurements with a dynamic range of ∼50 dB, at 137 MHz.
Massive black holes in high-redshift Lyman Break Galaxies
Authors: Orofino M C , Ferrara A , Gallerani S
Published: January 2021

Several evidences indicate that Lyman Break Galaxies (LBGs) in the Epoch of Reionization (redshift z > 6) might host massive black holes (MBHs). We address this question by using a merger-tree model combined with tight constraints from the 7 Ms Chandra survey and the known high-z super-MBH population. We find that a typical LBG with MUV = −22 residing in an Mh ≈ 1012 M⊙ halo at z = 6 host an MBH with mass M• ≈ 2 × 108 M⊙. Depending on the fraction, fseed, of early haloes planted with a direct collapse black hole seed (Mseed = 105M⊙), the model suggests two possible scenarios: (i) if fseed = 1, MBHs in LBGs mostly grow by merging and must accrete at a low (λE ≃ 10−3) Eddington ratio not to exceed the experimental X-ray luminosity upper bound $L_\mathrm{ X}^* = 10^{42.5} {\rm erg\, s}^{-1}$; (ii) if fseed = 0.05, accretion dominates (λE ≃ 0.22) and MBH emission in LBGs must be heavily obscured. In both scenarios the UV luminosity function is largely dominated by stellar emission up to very bright mag, $M_{\rm UV} \lower.5ex\hbox{$\,\, \buildrel\gt \over \sim \,\,$}-23$, with BH emission playing a subdominant role. Scenario (i) poses extremely challenging, and possibly unphysical, requirements on DCBH formation. Scenario (ii) entails testable implications on the physical properties of LBGs involving the FIR luminosity, emission lines, and the presence of outflows.
A machine learning approach to galaxy properties: joint redshift–stellar mass probability distributions with Random Forest
Authors: Mucesh S , Hartley W G , Palmese A , Lahav O , Whiteway L , Bluck A F L , Alarcon A , Amon A , Bechtol K , Bernstein G M , Carnero Rosell A , Carrasco Kind M , Choi A , Eckert K , Everett S , Gruen D , Gruendl R A , Harrison I , Huff E M , Kuropatkin N , Sevilla-Noarbe I , Sheldon E , Yanny B , Aguena M , Allam S , Bacon D , Bertin E , Bhargava S , Brooks D , Carretero J , Castander F J , Conselice C , Costanzi M , Crocce M , da Costa L N , Pereira M E S , De Vicente J , Desai S , Diehl H T , Drlica-Wagner A , Evrard A E , Ferrero I , Flaugher B , Fosalba P , Frieman J , García-Bellido J , Gaztanaga E , Gerdes D W , Gschwend J , Gutierrez G , Hinton S R , Hollowood D L , Honscheid K , James D J , Kuehn K , Lima M , Lin H , Maia M A G , Melchior P , Menanteau F , Miquel R , Morgan R , Paz-Chinchón F , Plazas A A , Sanchez E , Scarpine V , Schubnell M , Serrano S , Smith M , Suchyta E , Tarle G , Thomas D , To C , Varga T N , Wilkinson R D ,   (DES Collaboration)
Published: January 2021

We demonstrate that highly accurate joint redshift–stellar mass probability distribution functions (PDFs) can be obtained using the Random Forest (RF) machine learning (ML) algorithm, even with few photometric bands available. As an example, we use the Dark Energy Survey (DES), combined with the COSMOS2015 catalogue for redshifts and stellar masses. We build two ML models: one containing deep photometry in the griz bands, and the second reflecting the photometric scatter present in the main DES survey, with carefully constructed representative training data in each case. We validate our joint PDFs for 10 699 test galaxies by utilizing the copula probability integral transform and the Kendall distribution function, and their univariate counterparts to validate the marginals. Benchmarked against a basic set-up of the template-fitting code bagpipes, our ML-based method outperforms template fitting on all of our predefined performance metrics. In addition to accuracy, the RF is extremely fast, able to compute joint PDFs for a million galaxies in just under 6 min with consumer computer hardware. Such speed enables PDFs to be derived in real time within analysis codes, solving potential storage issues. As part of this work we have developed galpro1, a highly intuitive and efficient python package to rapidly generate multivariate PDFs on-the-fly. galpro is documented and available for researchers to use in their cosmology and galaxy evolution studies.
Cosmology with the Einstein telescope: No Slip Gravity model and redshift specifications
Authors: Mitra Ayan , Mifsud Jurgen , Mota David F , Parkinson David
Published: January 2021

The Einstein telescope and other third-generation interferometric detectors of gravitational waves are projected to be operational post 2030. The cosmological signatures of gravitational waves would undoubtedly shed light on any departure from the current gravitational framework. We here confront a specific modified gravity model, the No Slip Gravity model, with forecast observations of gravitational waves. We compare the predicted constraints on the dark energy equation of state parameters $w_0^{}-w_a^{}$, between the modified gravity model and that of Einstein gravity. We show that the No Slip Gravity model mimics closely the constraints from the standard gravitational theory, and that the cosmological constraints are very similar.

The use of spectroscopic redshifts, especially in the low–redshift regime, lead to significant improvements in the inferred parameter constraints. We test how well such a prospective gravitational wave dataset would function at testing such models, and find that there are significant degeneracies between the modified gravity model parameters, and the cosmological parameters that determine the distance, due to the gravitational wave dimming effect of the modified theory.
Statistical modelling of the cosmological dispersion measure
Authors: Takahashi Ryuichi , Ioka Kunihito , Mori Asuka , Funahashi Koki
Published: January 2021

We have investigated the basic statistics of the cosmological dispersion measure (DM)—such as its mean, variance, probability distribution, angular power spectrum, and correlation function—using the state-of-the-art hydrodynamic simulations, IllustrisTNG300, for the fast radio burst cosmology. To model the DM statistics, we first measured the free-electron abundance and the power spectrum of its spatial fluctuations. The free-electron power spectrum turns out to be consistent with the dark matter power spectrum at large scales, but it is strongly damped at small scales (≲  Mpc) owing to the stellar and active galactic nucleus feedback. The free-electron power spectrum is well modelled using a scale-dependent bias factor (the ratio of its fluctuation amplitude to that of the dark matter). We provide analytical fitting functions for the free-electron abundance and its bias factor. We next constructed mock sky maps of the DM by performing standard ray-tracing simulations with the TNG300 data. The DM statistics are calculated analytically from the fitting functions of the free-electron distribution, which agree well with the simulation results measured from the mock maps. We have also obtained the probability distribution of source redshift for a given DM, which helps in identifying the host galaxies of FRBs from the measured DMs. The angular two-point correlation function of the DM is described by a simple power law, $\xi (\theta) \approx 2400 (\theta /{\rm deg})^{-1} \, {\rm pc}^2 \, {\rm cm}^{-6}$, which we anticipate will be confirmed by future observations when thousands of FRBs are available.
A unique arginine cluster in PolDIP2 enhances nucleotide binding and DNA synthesis by PrimPol
Authors: Kasho Kazutoshi , Stojkovič Gorazd , Velázquez-Ruiz Cristina , Martínez-Jiménez Maria Isabel , Doimo Mara , Laurent Timothée , Berner Andreas , Pérez-Rivera Aldo E , Jenninger Louise , Blanco Luis , Wanrooij Sjoerd
Published: January 2021

Replication forks often stall at damaged DNA. To overcome these obstructions and complete the DNA duplication in a timely fashion, replication can be restarted downstream of the DNA lesion. In mammalian cells, this repriming of replication can be achieved through the activities of primase and polymerase PrimPol. PrimPol is stimulated in DNA synthesis through interaction with PolDIP2, however the exact mechanism of this PolDIP2-dependent stimulation is still unclear. Here, we show that PrimPol uses a flexible loop to interact with the C-terminal ApaG-like domain of PolDIP2, and that this contact is essential for PrimPol's enhanced processivity. PolDIP2 increases primer-template and dNTP binding affinities of PrimPol, which concomitantly enhances its nucleotide incorporation efficiency. This stimulation is dependent on a unique arginine cluster in PolDIP2. Since the polymerase activity of PrimPol alone is very limited, this mechanism, where the affinity for dNTPs gets increased by PolDIP2 binding, might be critical for the in vivo function of PrimPol in tolerating DNA lesions at physiological nucleotide concentrations.
Environmental Control of Phosphorus Acquisition: A Piece of the Molecular Framework Underlying Nutritional Homeostasis
Authors: Ueda Yoshiaki , Sakuraba Yasuhito , Yanagisawa Shuichi
Published: January 2021

Homeostasis of phosphorus (P), an essential macronutrient, is vital for plant growth under diverse environmental conditions. Although plants acquire P from the soil as inorganic phosphate (Pi), its availability is generally limited. Therefore, plants employ mechanisms involving various Pi transporters that facilitate efficient Pi uptake against a steep concentration gradient across the plant–soil interface. Among the different types of Pi transporters in plants, some members of the PHOSPHATE TRANSPORTER 1 (PHT1) family, present in the plasma membrane of root epidermal cells and root hairs, are chiefly responsible for Pi uptake from the rhizosphere. Therefore, accurate regulation of PHT1 expression is crucial for the maintenance of P homeostasis. Previous investigations positioned the Pi-dependent posttranslational regulation of PHOSPHATE STARVATION RESPONSE 1 (PHR1) transcription factor activity at the center of the regulatory mechanism controlling PHT1 expression and P homeostasis; however, recent studies indicate that several other factors also regulate the expression of PHT1 to modulate P acquisition and sustain P homeostasis against environmental fluctuations. Together with PHR1, several transcription factors that mediate the availability of other nutrients (such as nitrogen and zinc), light, and stress signals form an intricate transcriptional network to maintain P homeostasis under highly diverse environments. In this review, we summarize this intricate transcriptional network for the maintenance of P homeostasis under different environmental conditions, with a main focus on the mechanisms identified in Arabidopsis.
Phosphate Uptake and Transport in Plants: An Elaborate Regulatory System
Authors: Wang Yan , Wang Fei , Lu Hong , Liu Yu , Mao Chuanzao
Published: January 2021

Phosphorus (P) is an essential macronutrient for plant growth and development. Low inorganic phosphate (Pi) availability is a limiting factor for plant growth and yield. To cope with a complex and changing environment, plants have evolved elaborate mechanisms for regulating Pi uptake and use. Recently, the molecular mechanisms of plant Pi signaling have become clearer. Plants absorb Pi from the soil through their roots and transfer Pi to various organs or tissues through phosphate transporters, which are precisely controlled at the transcript and protein levels. Here, we summarize recent progress on the molecular regulatory mechanism of phosphate transporters in Arabidopsis and rice, including the characterization of functional transporters, regulation of transcript levels, protein localization and turnover of phosphate transporters. A more in-depth understanding of plant adaptation to a changing Pi environment will facilitate the genetic improvement of plant P efficiency.
UGT84F9 is the major flavonoid UDP-glucuronosyltransferase inMedicago truncatula
Authors: Adiji Olubu A , Docampo-Palacios Maite L , Alvarez-Hernandez Anislay , Pasinetti Giulio M , Wang Xiaoqiang , Dixon Richard A
Published: January 2021

Mammalian phase II metabolism of dietary plant flavonoid compounds generally involves substitution with glucuronic acid. In contrast, flavonoids mainly exist as glucose conjugates in plants, and few plant UDP-glucuronosyltransferase enzymes have been identified to date. In the model legume Medicago truncatula, the major flavonoid compounds in the aerial parts of the plant are glucuronides of the flavones apigenin and luteolin. Here we show that the M. truncatula glycosyltransferase UGT84F9 is a bi-functional glucosyl/glucuronosyl transferase in vitro, with activity against a wide range of flavonoid acceptor molecules including flavones. However, analysis of metabolite profiles in leaves and roots of M. truncatula ugt84f9 loss of function mutants revealed that the enzyme is essential for formation of flavonoid glucuronides, but not most flavonoid glucosides, in planta. We discuss the use of plant UGATs for the semi-synthesis of flavonoid phase II metabolites for clinical studies.
Lipoxygenase functions in 1O2 production during root responses to osmotic stress
Authors: Chen Tomer , Cohen Dekel , Itkin Maxim , Malitsky Sergey , Fluhr Robert
Published: January 2021

Drought induces osmotic stress in roots, a condition simulated by the application of high-molecular-weight polyethylene glycol. Osmotic stress results in the reduction of Arabidopsis thaliana root growth and production of 1O2 from an unknown non-photosynthetic source. Reduced root growth can be alleviated by application of the 1O2 scavenger histidine (HIS). Here, we examined the possibility that 1O2 production involves Russell reactions occurring among the enzymatic products of lipoxygenases (LOXs), the fatty acid hydroperoxides. LOX activity was measured for purified soybean (Glycine max) LOX1 and in crude Arabidopsis root extracts using linoleic acid as substrate. Formation of the 13(S)-Hydroperoxy-9(Z),11(E)-octadecadienoic acid product was inhibited by salicylhdroxamic acid, which is a LOX inhibitor, but not by HIS, whereas 1O2 production was inhibited by both. D2O, which specifically extends the half-life of 1O2, augmented the LOX-dependent generation of 1O2, as expected from a Russell-type reaction. The addition of linoleic acid to roots stimulated 1O2 production and inhibited growth, suggesting that the availability of LOX substrate is a rate-limiting step. Indeed, water stress rapidly increased linoleic and linolenic acids by 2.5-fold in roots. Mutants with root-specific microRNA repression of LOXs showed downregulation of LOX protein and activity. The lines with downregulated LOX displayed significantly less 1O2 formation, improved root growth in osmotic stress, and an altered transcriptome response compared with wild type. The results show that LOXs can serve as an enzymatic source of “dark” 1O2 during osmotic stress and demonstrate a role for 1O2 in defining the physiological response.
Real-Life Management Pathways for Chronic Peripheral Neuropathic Pain at Tertiary Pain Clinics in France
Authors: Perrot Serge , Pickering Gisèle , Lantéri-Minet Michel , Attal, MD, PhD Nadine
Published: January 2021

Objective

Peripheral neuropathic pain (PNP) represents a major public health issue. Severe or refractory cases warrant tertiary multidisciplinary management, but little information is available about real-life care pathways. The primary objective of this cross-sectional, observational study was to investigate the pathways of patients with PNP consulting for the first time or followed for less than 1 year in French tertiary specialized pain clinics.

Methods

PNP was diagnosed with the NeuPSIG algorithm. Data collected included demographics, pain characteristics, and details of management before and after the study visit (e.g., drug and non-drug treatment, nature of medical visits), as well as time to referral to a pain clinic and time to a diagnosis of PNP. Factors associated with delayed referral or diagnosis were analyzed with multivariate analysis.

Results

A total of 404 patients with PNP (age 55.8 ± 15.6 years, 60.3% females, 78.3% retired or unemployed, pain duration 43.4 ± 68.9 months) were enrolled by 84 pain specialists. Pain affected mainly the lower limbs (53.5%) and was predominantly related to surgery or trauma (59.4%). Primary care management was characterized by a high proportion of conventional analgesics (60.7%). Time to referral to a pain clinic was 43.4 ± 68.9 months since pain onset and 20.1 ± 39.4 months since the diagnosis of PNP. Delayed referral to a pain clinic was independently predicted by the clinical specialty of the referring doctor and by male gender.

Conclusions

This study highlights the need for accessible guidance for non–pain specialists to improve their diagnostic and management skills and for faster referral of patients with PNP to tertiary pain clinics.
Opioid Tapering/Detoxification Protocols, A Compendium: Narrative Review
Authors: Fishbain David A
Published: January 2021

Objectives

The opioid epidemic has put pressure on clinicians to taper their chronic pain patients (CPPs) from opioids. This has resulted in rapid or forced tapers and opioid discontinuation. Partially responsible is lack of information on how to taper (tapering protocols).The objectives of this narrative review were then the following: compile all the published opioid tapering/detoxification protocols from the pain/drug rehabilitation/psychiatric literature whether for inpatient or outpatient use; organize these into general types; compare the types for advantages/disadvantages for use by a clinician in an outpatient setting; and answer some commonly asked questions relating to opioid tapering.

Methods

Relevant references were identified by a search strategy utilizing the terms tapering, tapering protocols, detoxification, detoxification protocols, withdrawal, dependence, addiction, and drug rehabilitation. These were explored with the term opioids. Identified abstract were reviewed for any study relating to the objectives of this review. Those studies were then included in this review. As this is a narrative review, no quality ratings of these references were performed.

Results

Of 1,922 abstracts identified by this search strategy, 301 were reviewed in detail for potential inclusion. Of these, 104 were utilized in this review. Nine types of opioid tapering protocols were identified and compared in tabular form. Twenty-two questions in reference to opioid tapering were addressed.

Conclusions

Based on this review, the protocol utilizing the opioid of current use is the simplest to use as it requires no rotation to another opioid and thereby avoids rotation errors. It also has behavior advantages.
Similar biologic drug response regardless of radiographic status in axial spondyloarthritis: data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis registry
Authors: Michelena Xabier , Zhao Sizheng Steven , Dubash Sayam , Dean Linda E , Jones Gareth T , Marzo-Ortega Helena
Published: January 2021

Objective

To describe the baseline characteristics, biologic DMARD (bDMARD) response and drug survival of axial SpA (axSpA) patients in the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) according to radiographic status.

Methods

The BSRBR-AS is a national prospective cohort including axSpA participants classified according to the Assessment of SpondyloArthritis international Society criteria. In this analysis, baseline data of patients starting bDMARDs were compared. Ankylosing Spondylitis Disease Activity Scores (ASDASs) for low disease status, clinically important improvement (CII) and major improvement (MI) at 1 year were used to assess treatment response. Cox proportional hazards analysis was performed after adjusting for clinically relevant confounders.

Results

A total of 1145 axSpA patients were included. Higher male prevalence, older age and longer disease duration were seen in the radiographic axSpA (r-axSpA) subgroup. Based on a complete case analysis (290 patients), two-thirds of patients achieved an ASDAS low disease state at 1 year regardless of radiographic status [non-radiographic axSpA (nr-axSpA) 64.2% vs r-axSpA 66.1]. No statistically significant differences were seen between the subgroups in attaining ASDAS CII (nr-axSpA 50.7% vs r-axSpA 44.7%) or MI (nr-axSpA 20% vs r-axSpA 18.7%). Drug survival probability curves were similar for both subgroups and the hazard ratio for nr-axSpA/axSpA was 0.94 (95% CI 0.69, 1.28) when adjusted for sex, age, baseline ASDAS with CRP, smoking status, disease duration, HLA-B27 and prescribed biologic.

Conclusions

Although there appeared to be some differences in the baseline characteristics when exploring this cohort according to radiographic status, which are likely related to the natural history of the disease, the level of biologic response and drug survival was comparable between nr-axSpA and r-axSpA.
Association of venous thromboembolic events with skin, pulmonary and kidney involvement in ANCA-associated vasculitis: a multinational study
Authors: Moiseev Sergey , Kronbichler Andreas , Makarov Egor , Bulanov Nikolay , Crnogorac Matija , Direskeneli Haner , Galesic Kresimir , Gazel Ummugulsum , Geetha Duvuru , Guillevin Loic , Hrušková Zdenka , Little Mark A , Ahmed Adeel , McAdoo Stephen P , Mohammad Aladdin J , Moran Sarah , Novikov Pavel , Pusey Charles D , Rahmattulla Chinar , Satrapová Veronika , Silva Joana , Terrier Benjamin , Tesař Vladimír , Westman Kerstin , Jayne David R W
Published: January 2021

Objective

To investigate the occurrence of venous thromboembolic events (VTE) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, Turkey, Russia, UK and North America.

Methods

Patients with a definite diagnosis of AAV who were followed for at least 3 months and had sufficient documentation were included. Data on VTE, including either deep vein thrombosis or pulmonary embolism, were collected retrospectively from tertiary vasculitis centres. Univariate and multivariate regression models were used to estimate odds ratios (ORs) and 95% CIs.

Results

Over a median follow-up of 63 (interquartile range: 29, 101) months, VTE occurred in 278 (9.7%) of 2869 AAV patients with a similar frequency across different countries (from 6.3% to 13.7%), and AAV subtype [granulomatosis with polyangiitis: 9.8% (95% CI: 8.3, 11.6%); microscopic polyangiitis: 9.6% (95% CI: 7.9, 11.4%); and eosinophilic granulomatosis with polyangiitis: 9.8% (95% CI: 7.0, 13.3%)]. Most VTE (65.6%) were reported in the first-year post-diagnosis. Multiple factor logistic regression analysis adjusted for sex and age showed that skin (OR 1.71, 95% CI: 1.01, 2.92), pulmonary (OR 1.78, 95% CI: 1.04, 3.14) and kidney [eGFR 15–60 ml/min/1.73 m2, OR 2.86 (95% CI: 1.27, 6.47); eGFR <15 ml/min/1.73 m2, OR 6.71 (95% CI: 2.94, 15.33)] involvement were independent variables associated with a higher occurrence of VTE.

Conclusion

Two-thirds of VTE occurred during the initial phase of active disease. We confirmed previous findings from smaller studies that a decrease in kidney function, skin involvement and pulmonary disease are independently associated with VTE.
Cysteine sulfinic acid decarboxylase activity of Aedes aegypti aspartate 1‐decarboxylase: the structural basis of its substrate selectivity
Authors: Liu Pingyang , Ding Haizhen , Christensen Bruce M , Li Jianyong
Published: January 2021

This work aimed at characterizing biochemical properties of insect aspartate 1‐decarboxylase and studied its structure regarding to its substrate selectivity. Aspartate 1‐decarboxylase from Aedes aegypti was expressed, purified and screened for substrate specificity. Results showed that this enzyme has high activity to cysteine sulfinic acid as well as aspartate, with the specific activity to cysteine sulfinic acid being higher than that to aspartate under the same condition. In addition, this mosquito enzyme showed activity to cysteic acid, thereby making it an enzyme with both aspartate‐L‐decarboxylase and cysteine sulfinic acid decarboxylase activities. This represents the first report of an enzyme with cysteine sulfinic acid decarboxylase activity from any invertebrate species. It is also the first enzyme identified with both aspartate 1‐decarboxylase and cysteine sulfinic acid decarboxylase activities. Docking experiments suggests that Q377 plays a role in the broad substrate specificity of mosquito aspartate‐L‐decarboxylase.
3D-Printed Ostomy Flange Stabilizer
Authors: Cosman Ilan E. , Guillou Daniel T. , Cosman Bard C.
Published: January 2021

BACKGROUND:

One of the coauthors with tetraplegia (quadriplegia) and a colostomy invented an ostomy flange stabilizer to act as a temporary backplate and aid in pouch changes.

DEVICE DEVELOPMENT:

In an interactive design process, a 3D-printed ostomy flange stabilizer device was created. The resulting device can be adapted to 3 standard stoma appliance sizes. The stabilizer is reversible, allowing right- and left-handed people to use it on right- or left-sided stomas. Anyone with a 3D printer can print this device from an open-access Web site.

CONCLUSION:

This device may be of use to many with ostomies and especially those with impaired dexterity.

A 3D-printed ostomy flange stabilizer is described. 3D printing allows patient inventions to be disseminated without commercialization.
Heterozygous mutation ofVegfr3decreases renal lymphatics but is dispensable for renal function
Authors: Liu Hao , Hiremath Chitkale , Patterson Quinten , Vora Saumya , Shang Zhiguo , Jamieson Andrew R. , Fiolka Reto , Dean Kevin M. , Dellinger Michael T. , Marciano Denise K.
Published: January 2021

Background

Lymphatic abnormalities are observed in several types of kidney disease, but the relationship between the renal lymphatic system and renal function is unclear. The discovery of lymphatic-specific proteins, advances in microscopy, and available genetic mouse models provide the tools to help elucidate the role of renal lymphatics in physiology and disease.

Methods

We utilized a mouse model containing a missense mutation inVegfr3(dubbedChy) that abrogates its kinase ability.Vegfr3Chy/+mice were examined for developmental abnormalities and kidney-specific outcomes. Control andVegfr3Chy/+mice were subjected to cisplatin-mediated injury. We characterized renal lymphatics using a combination of tissue clearing, light-sheet microscopy and computational analyses.

Results

In the kidney, we found Vegfr3 is expressed not only in lymphatic vessels, but also various blood vessels.Vegfr3Chy/+mice had severely reduced renal lymphatics with 100% penetrance, but we found no abnormalities in blood pressure, renal function and histology. Similarly, there was no difference in the degree of renal injury after cisplatin, althoughVegfr3Chy/+mice developed more perivascular inflammation by histology. Control mice treated with cisplatin had a measurable increase in cortical lymphatic density despite no change in cortical lymphatic volume and length.

Conclusions

We demonstrate that Vegfr3 is required for development of renal lymphatics, but a reduction in lymphatic density does not alter renal function and induces only modest histological changes after injury. Our data suggests that an increase in lymphatic density after cisplatin injury may reflect the loss of cortical volume associated with chronic kidney disease rather than growth of lymphatic vessels.

SIGNIFICANCE STATEMENT

Defects in renal lymphatics occur in various kidney diseases, but their role in maintaining kidney structure and function is unknown. We combine tissue clearing, light-sheet microscopy and computational analysis to characterize lymphatics and find that mice with a heterozygous mutation inVegfr3(Vegfr3Chy/+) have severely reduced renal lymphatics. Strikingly, these mice have indistinguishable renal function and histology compared with controls. Even after cisplatin injury, there are no differences in renal function, althoughVegfr3Chy/+mice developed more perivascular inflammation. Our data present a novel method of lymphatic quantification and suggest that a normal complement of renal lymphatics is dispensable for renal structure and function.
Imaging-based patient inclusion model improves clinical trial performance
Authors: Tomaszewski Michal R. , Fan Shuxuan , Garcia Alberto , Qi Jin , Kim Youngchul , Gatenby Robert A. , Schabath Matthew B. , Tap William D. , Reinke Denise K. , Makanji Rikesh J , Reed Damon R. , Gillies Robert J.
Published: January 2021

Purpose

Success of new cancer therapies relies strongly on effective selection of the target patient populations. We hypothesize that computational analysis of imaging data can be used for patient enrichment in clinical trials and hence aimed to establish the appropriate framework for this analysis.

Methods

This was tested among soft-tissue sarcoma (STS) patients accrued into a randomized clinical trial (SARC021) that evaluated the efficacy of evofosfamide (Evo), a hypoxia activated prodrug, in combination with doxorubicin (Dox). Notably, SARC021 failed to meet its overall survival (OS) objective. We tested whether a radiomic biomarker-driven inclusion/exclusion criterion could have been used to result in a significant treatment benefit of the Evo+Dox combination compared to Dox monotherapy. 164 radiomics features were extracted from 303 SARC021 patients with lung metastases, divided into training and test sets.

Results

A single radiomics feature, Short Run Emphasis, was identified as the most informative. Combined into a model along with histological classification and smoking history, an enriched subset (42%) of patients had longer OS in Evo+Dox vs. Dox groups [p=0.01, Hazard Ratio (HR) =0.57 (0.36-0.90)]. Applying the same model and threshold value in an independent test set confirmed the significant survival difference [p=0.002, HR=0.29 (0.13-0.63)], identifying patients most likely to benefit from doxorubicin alone.

Conclusion

The study presents a first of its kind clinical-radiomic approach for patient enrichment in clinical trials. We show that, had an appropriate model been used for selective patient inclusion, SARC021 trial could have met its primary survival objective for patients with metastatic STS.
NanoMethViz: an R/Bioconductor package for visualizing long-read methylation data
Authors: Su Shian , Gouil Quentin , Blewitt Marnie E. , Cook Dianne , Hickey Peter F. , Ritchie Matthew E.
Published: January 2021

Motivation

A key benefit of long-read nanopore sequencing technology is the ability to detect modified DNA bases, such as 5-methylcytosine. Tools for effective visualization of data generated by this platform to assess changes in methylation profiles between samples from different experimental groups remains a challenge.

Results

To make visualization of methylation changes more straightforward, we developed the R/Bioconductor packageNanoMethViz. Our software can handle methylation calls generated from a range of different methylation callers and manages large datasets using a compressed data format. To fully explore the methylation patterns in a dataset,NanoMethVizallows plotting of data at various resolutions. At the sample-level, we use multidimensional scaling to look at the relationships between methylation profiles in an unsupervised way. We visualize methylation profiles of classes of features such as genes or CpG islands by scaling them to relative positions and aggregating their profiles. At the finest resolution, we visualize methylation patterns across individual reads along the genome using thespaghetti plot,allowing users to explore particular genes or genomic regions of interest.

In summary, our software makes the handling of methylation signal more convenient, expands upon the visualization options for nanopore data and works seamlessly with existing methylation analysis tools available in the Bioconductor project. Our software is available athttps://bioconductor.org/packages/NanoMethViz.
Homo-and heterofermentative lactobacilli are differently affected by lignocellulosic inhibitory compounds
Authors: Giacon Thamiris Guerra , de Gois e Cunha Gabriel Caetano , Eliodório Kevy Pontes , de Souza Oliveira Ricardo Pinheiro , Basso Thiago Olitta
Published: January 2021

Second generation (2G) ethanol is produced through the use of lignocellulosic biomass. However, the pretreatment processes generates a variety of molecules (furan derivatives, phenolic compounds and organic acids) that act as inhibitors of microbial metabolism, and thus reduce the efficiency of the fermentation step in this process. In this context, the present study aimed to investigate the effect of furan derivatives on the physiology of lactic acid bacteria (LAB) strains that are potential contaminants of ethanol production. Homofermentative and heterofermentative strains of laboratory LAB and isolated from first generation ethanol fermentation were used. LAB strains were challenge to grow in the presence of furfural and hydroxymethyylfurfural (HMF). We found that the effect of HMF and furfural on the growth rate of LAB is dependent of the metabolic type, and growth kinetics in the presence of these compounds is enhanced for heterofermentative LAB, whereas is inhibitory to homofermentative LAB. Sugar consumption and product formation were also enhanced in the presence of furaldehydes in heterofermentative LAB, that displayed an effective detoxification kinetics when compared to the homofermentative LAB. This knowledge is important because LAB can be explored both within the scope of bio-detoxification, being applied before the fermentation.

Key points

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Heterofermentative LAB presented the ability to decrease the concentrations of furfural and HMF

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LAB can be used in the bio-detoxification to remove the inhibitors before fermentations

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The presence of furan derivatives had a growth stimulus observed in heterofermentative LAB
“Less is more”: a dose-response account of intranasal oxytocin pharmacodynamics in the human brain
Authors: Martins Daniel , Broadmann Katja , Veronese Mattia , Dipasquale Ottavia , Mazibuko Ndaba , Schuschnig Uwe , Zelaya Fernando , Fotopoulou Aikaterini , Paloyelis Yannis
Published: January 2021

Intranasal oxytocin is receiving increasing research attention as a potential treatment for several brain disorders due to promising preclinical results. However, translating these findings to humans has been hampered by remaining uncertainties about its pharmacodynamics and the methods used to probe its effects in the human brain. Using a dose-response design (9, 18 and 36 IU) and a novel administration device, we demonstrate that oxytocin-induced physiological changes in the amygdala at rest, a key-hub of the brain oxytocin system, follow a dose-response curve with maximal effects for lower doses. Yet, the effects of oxytocin vary by amygdala subdivision, highlighting the need to qualify dose-response curves within subregion. We further link physiological changes with the density of the oxytocin receptor gene mRNA across brain regions, strengthening our confidence in intranasal oxytocin as a valid approach to engage central targets. Finally, we demonstrate that intranasal oxytocin does not disrupt cerebrovascular reactivity; the absence of major vascular confounds corroborates the validity of haemodynamic neuroimaging to probe the effects of intranasal oxytocin in the human brain.
Forebrain Shh overexpression improves cognitive function in a Down syndrome mouse model and euploid littermates
Authors: Gao Feng J. , Klinedinst Donna , Fernandez Fabian-Xosé , Cheng Bei , Savonenko Alena , Devenney Benjamin , Li Yicong , Wu Dan , Pomper Martin G. , Reeves Roger H.
Published: January 2021

People with Down syndrome (DS) have intellectual disability, early-onset dementia, and cerebellar hypoplasia. Trisomic cerebellar granule cell precursors from Ts65Dn, a mouse model of DS, had a deficit in mitogenic response to Sonic hedgehog (Shh)in vitro, and newborn Ts65Dn mice received a single subcutaneous injection of the Shh signaling agonist SAG had normalized cerebellar morphology and improved spatial learning and hippocampal synaptic plasticity at adult. However, cognitive effects of Shh overexpressionin vivoand where SAG acts to improve cognitive outcomes of trisomy are unknown. Here, we created an inducible human Shh (hShh) knock-in mouse, TRE-bi-hShh-Zsgreen1 (TRE-hShh), expressing dually-lipidated Shh-Np in the presence of transactivator (tTA). Double transgenic mice, Camk2a-tTA;TRE-hShh (Camk2a-hShh) and Pcp2-tTA;TRE-hShh (Pcp2-hShh), increased Shh signaling in forebrain and cerebellum, respectively. Forebrain Shh overexpression normalized hyperactivity, and spatial learning and memory deficits in 3-month-old Ts65Dn, while Shh overexpression in cerebellum had no effect. Further, Camk2a-hShh delayed early-onset severe cognitive impairment in 7-month-old Ts65Dn and enhanced spatial cognition in euploid (Eu) and showed no effect on the longevity of Eu or Ts65Dn, and MRI demonstrated that Pcp2-hShh mitigated disproportionately small cerebellum in Ts65Dn. Finally, Ts65Dn at postnatal day 6 had reduced Gli1 levels in hippocampus and cerebellum, which could be at least partially rescued by Camk2a-hShh and Pcp2-hShh, respectively. Our findings suggest restoration of impaired Shh signaling in forebrain from the perinatal and early postnatal period improves cognitive function.
The paradox of accounting for cultural heritage: a longitudinal study on the financial reporting of heritage assets of major Australian public cultural institutions (1992–2019)
Authors: Ferri Paolo , Sidaway Shannon I.L. , Carnegie Garry D.
Published: January 2021

Purpose

The monetary valuation of cultural heritage of a selection of 16 major public, not-for-profit Australian cultural institutions is examined over a period of almost three decades (1992–2019) to understand how they have responded to the paradoxical tensions of heritage valuation for financial reporting purposes.

Design/methodology/approach

Accounting for cultural heritage is an intrinsically paradoxical practice; it involves a conflict of two opposite ways of attributing value: the traditional accounting and the heritage professionals (or curatorial) approaches. In analysing the annual reports and other documentary sources through qualitative content analysis, the study explores how different actors responded to the conceptual and technical contradictions posed by the monetary valuation of “heritage assets”, the accounting phraseology of accounting standards.

Findings

Four phases emerge from the analysis undertaken of the empirical material, each characterised by a distinctive nature of the paradox, the institutional responses discerned and the outcomes. Although a persisting heterogeneity in the practice of accounting for cultural heritage is evident, responses by cultural institutions are shown to have minimised, so far, the negative impacts of monetary valuation in terms of commercialisation of deaccessioning decisions and distorted accountability.

Originality/value

In applying the theoretical lens of paradox theory in the context of the financial reporting of heritage, as assets, the study enhances an understanding of the challenges and responses by major public cultural institutions in a country that has led this development globally, providing insights to accounting standard setters arising from the accounting practices observed.
Management practices and the financial performance of farms
Authors: Vanhuyse Fedra , Bailey Alison , Tranter Richard
Published: January 2021

Purpose

Farm businesses in England are under pressure to intensify production sustainably while managing costs and meeting market demands. Commodity prices and support from Common Agricultural Policy (CAP) payments are important determinants of profitability. With the United Kingdom (UK) leaving the European Union (EU), revised policy will see farming more exposed to fluctuating commodity prices and financial support from Government more focused on encouraging environmental land management. The research reported here, investigated whether business management practices of farmers influences financial performance, and how policy could be tailored to better meet the needs of farm businesses.

Design/methodology/approach

Regression models were estimated for 862 Cereals, Dairy and Livestock farms in England using official data for 2011–2012, in order to assess whether different farm characteristics, business management practices (identified from a systematic review of 102 studies), knowledge acquisition indicators and manager experience had an effect on four different financial performance ratios. The financial performance of the top 25% of the sample was also compared to the bottom 25% in terms of use of business management practices.

Findings

The results show that business planning and benchmarking had a positive, statistically significant, effect on financial performance, as do business size and knowledge acquisition, albeit to a lesser extent.

Originality/value

The research reported here is the most extensive examination, to date, of the impact of management practices on the financial performance of farms. Thus, it sends strong policy recommendations.