bluuebunny/crossref_metadata_2025 huggingface dataset:
A rarefaction approach for measuring population differences in rare and common variation
Authors: Cotter Daniel J , Hofgard Elyssa F , Novembre John , Szpiech Zachary A , Rosenberg Noah A
Published: April 2023

In studying allele-frequency variation across populations, it is often convenient to classify an allelic type as “rare,” with nonzero frequency less than or equal to a specified threshold, “common,” with a frequency above the threshold, or entirely unobserved in a population. When sample sizes differ across populations, however, especially if the threshold separating “rare” and “common” corresponds to a small number of observed copies of an allelic type, discreteness effects can lead a sample from one population to possess substantially more rare allelic types than a sample from another population, even if the two populations have extremely similar underlying allele-frequency distributions across loci. We introduce a rarefaction-based sample-size correction for use in comparing rare and common variation across multiple populations whose sample sizes potentially differ. We use our approach to examine rare and common variation in worldwide human populations, finding that the sample-size correction introduces subtle differences relative to analyses that use the full available sample sizes. We introduce several ways in which the rarefaction approach can be applied: we explore the dependence of allele classifications on subsample sizes, we permit more than two classes of allelic types of nonzero frequency, and we analyze rare and common variation in sliding windows along the genome. The results can assist in clarifying similarities and differences in allele-frequency patterns across populations.
Risk governance in the response to global health emergencies: understanding the governance of chaos in Brazil’s handling of the Covid-19 pandemic
Authors: Di Giulio Gabriela Marques , Mendes Ione Maria , Campos Felipe Dos Reis , Nunes João
Published: April 2023

The Covid-19 caused by the SARS-CoV-2 virus has shown how inadequate institutional strategies interact with, and exacerbate, social inequalities, thus impacting upon the intensity of the harm produced and amplifying negative consequences. One of the lessons from this pandemic, which happens against the background of other, interconnected systemic crises, is the urgency of adopting a ‘whole-of-society’ approach to determining what does and what does not work in the context of a health emergency response. However, how can institutional performance in health emergency response be assessed? How to make sense of success or failure? We argue that the adoption of a risk governance approach sheds light on institutional performance in the response to health emergencies. Risk governance is particularly pertinent in situations where the potential for extreme consequences is considered high, where there are enormous uncertainties regarding the consequences and where different values are present and in dispute. Based on a documentary evidence review, we analyse the Brazilian response to Covid-19 by considering: (1) how the Brazilian federal government performed on its central role of managing the national response, (2) the reactions from other actors prompted by this performance and (3) the main observed effects emerging from this scenario. We argue that the Brazilian federal government response was weak in five risk governance parameters that are essential in a health crisis response: risk communication, transparency and accessibility of data, negotiation between actors, social cohesion and public participation and decisions based on technical and scientific evidence, resources and contexts. The neglect of risk governance parameters, combined with an attempt to spread doubt, confusion and disinformation—which could be termed a ‘governance by chaos’—is an important element for making sense of the effects and controversies surrounding Covid-19 in Brazil.
Time to Diagnosis and Birth Outcomes of Pregnancy-onset IBD
Authors: Vestergaard Thea , Røsok Julie , Julsgaard Mette , Bek Helmig Rikke , Friedman Sonia , Kelsen Jens
Published: April 2023

Background

Pregnancy-onset inflammatory bowel disease (PO-IBD) may pose a clinical challenge. We investigated the clinical course of PO-IBD, including time to diagnosis, medical treatment, and the impact on birth outcomes.

Methods

All pregnancies in women with IBD at a tertiary IBD center in Denmark were identified from 2008 to 2021. Maternal and offspring outcome data, retrieved from medical records of women with new onset IBD during pregnancy, were compared with the outcomes of women with IBD diagnosed prior to pregnancy (controls). Outcomes included subtype of IBD, disease location, medical treatment, birth weight, intrauterine growth retardation (IUGR), gestational age at birth, caesarean section, stillbirth, congenital malformations, and time elapsed from onset of symptoms to diagnosis.

Results

In total, 378 women contributed with 583 pregnancies. Pregnancy-onset IBD affected 34 (9.0%) women. Ulcerative colitis (UC; n = 32) was more prevalent than Chron’s disease (CD; n = 2). Birth outcomes in pregnancies affected by PO-IBD were comparable to that of the 549 controls. Women with PO-IBD received more corticosteroids and biologics following their diagnosis than did the controls (5 [14.7%] vs 2 [2.9%]; P = .07; and 14 [41.2%] vs 9 [13.2%]; P = .003, respectively). Concerning time to IBD diagnosis, there was no statistically significant difference between the 2 groups (PO-IBD, 2.5 months, interquartile range [2-6] vs controls 2 months [1-4.5]; P = .27).

Conclusion

Although we observed a trend towards a diagnostic delay, PO-IBD was not associated with a significantly increased time to diagnosis. Birth outcomes in women with PO-IBD were comparable to those diagnosed with IBD prior to pregnancy.
Socioeconomic dimensions of the Buccoo Reef Marine Park, an assessment of stakeholder perceptions towards enhanced management through MSP
Authors: Peters S M , Guppy R , Ramsewak D , Potts A
Published: April 2023

The effective management of marine protected areas (MPAs) requires an in-depth understanding and assessment of the varying socioeconomic uses and users of the physical space. However, in some localities, little research is conducted on this aspect and in particular user perceptions on current and proposed management strategies for MPAs. Such site-specific evaluations are imperative to developing context-dependent management measures. The aim of this study was to identify the spatial extent of socioeconomic activities, assess stakeholders’ awareness of the varying socioeconomic activities that take place in the Buccoo Reef Marine Park, Tobago, and gauge stakeholder support for proposed management mechanisms, namely marine spatial planning (MSP). Targeted surveys were conducted over a six-month period, to obtain perspectives from key Marine Park stakeholder groups, namely marine resource managers, visitors, and tour operators. The results indicated over ten main socioeconomic activities occurring within the Marine Park, with multiple activities taking place in the same location. Results also suggest that stakeholders are aware of the conflicts that occur between various users of the space with jet skis operation identified as the primary contributor. Finally, using a Likert scale, stakeholder groups predominantly rated the need for a marine spatial plan as “necessary.” This research, therefore, documents existing socioeconomic activities in the Buccoo Reef Marine Park and highlights the importance of stakeholder engagement in future management strategies.
Mathematical modelling of mission-abort policies: a review
Authors: da Silva Rodrigues Augusto José , Cavalcante Cristiano Alexandre Virgínio , Alberti Alexandre Ramalho , Scarf Phil , Alotaibi Naif Mohammed
Published: April 2023

This paper reviews works that consider the mathematical modelling of mission-abort policies (MAPs). In a MAP, a valuable, and perhaps, vulnerable system performs a mission with two, sometimes conflicting objectives, mission success and system survival; and the purpose of modelling is to determine the conditions under which a mission should be aborted. Such problems are important in defence and are emerging in transportation and health management. We classify models by the nature of the mission and the system, the nature of the return or rescue, type of deterioration model and the decision objectives. We show that the majority of works consider a model of a one system, one target mission in which the mission is aborted once the hazard of failure reaches a critical level, and the operating environment is the same for the outbound and inbound parts of the mission. Typically, the hazard of failure depends on the number of shocks received so far. Our analysis indicates that there has been little modelling development for multiple systems that can multi-task and for dependent systems with common-cause failures, for example. We find no evidence that MAPs are used in practice and no works reviewed develop software demonstrators. We think there is considerable scope for modelling applications in transportation (e.g. dynamic train re-scheduling and last-mile logistics) and medical treatments, and MAPs may be more general than the literature that we have reviewed suggests.
Metamorphosis Imposes Variable Constraints on Genome Expansion through Effects on Development
Authors: Mueller R Lockridge , Cressler C E , Schwartz R S , Chong R A , Butler M A
Published: April 2023

Synopsis

Genome size varies ∼100,000-fold across eukaryotes and has long been hypothesized to be influenced by metamorphosis in animals. Transposable element accumulation has been identified as a major driver of increase, but the nature of constraints limiting the size of genomes has remained unclear, even as traits such as cell size and rate of development co-vary strongly with genome size. Salamanders, which possess diverse metamorphic and non-metamorphic life histories, join the lungfish in having the largest vertebrate genomes—3 to 40 times that of humans—as well as the largest range of variation in genome size. We tested 13 biologically-inspired hypotheses exploring how the form of metamorphosis imposes varying constraints on genome expansion in a broadly representative phylogeny containing 118 species of salamanders. We show that metamorphosis during which animals undergo the most extensive and synchronous remodeling imposes the most severe constraint against genome expansion, with the severity of constraint decreasing with reduced extent and synchronicity of remodeling. More generally, our work demonstrates the potential for broader interpretation of phylogenetic comparative analysis in exploring the balance of multiple evolutionary pressures shaping phenotypic evolution.
Empirical use of temocillin in hospitalized patients: results from a retrospective audit
Authors: Kandil Hala , Gray Robert M , El-Hamad Rakan , Vidwans Madhuri , Vaghela Tejal , Naji Omar , Van De Velde Sebastien
Published: April 2023

Background

Following a global shortage of piperacillin/tazobactam in 2017, a formulary decision was taken at a large District General Hospital in the East of England to partly replace piperacillin/tazobactam with either temocillin as monotherapy or as part of a combination regimen. A retrospective audit was then conducted to assess the clinical effectiveness of temocillin therapy.

Methods

Data from patients admitted to Watford General Hospital between May and August 2017 and treated with temocillin were reviewed retrospectively. Clinical characteristics of patients, data related to the episode of infection, clinical success, tolerance and mortality were analysed.

Results

Temocillin was used in 126 patients with median age of 73 years. Infection episodes mostly originated from the abdomen (n = 46), the lung (n = 40) and the urinary tract (n = 21). Seventy-seven patients received temocillin as first-line therapy and 106 received it empirically, with temocillin prescribed in combination with another antibiotic in 82% of the empirically treated cases. Clinical success was observed in 88.9% of cases with no difference between patients treated empirically and others (89.6% versus 85%) or in efficacy among abdominal (91%), pulmonary (87.5%) and urinary (81%) infections. One case of Clostridioides difficile infection was reported in a patient treated with four different antibiotics. During the shortage period, the hospital’s standardized mortality ratio was significantly lower when compared with the same period of the preceding year (85 versus 96).

Conclusions

Using temocillin as part of an empirical strategy is feasible and safe as long as appropriate antibiotic combination is recommended based upon the indication and the likely bacterial pathogen.
Robust full-waveform inversion based on automatic differentiation and differentiable dynamic time warping
Authors: Liu Yingchang , Tang Jie , Tang Zhengwei , Sun Chengyu
Published: April 2023

Full waveform inversion is a methodology that determines high-resolution parameters. The widely used L2-norm misfit function has local minima if the low wavenumber components are not accurate. Suffering from a cycle skipping problem, the solution of waveform inversion will be trapped in the local minima. Dynamic time warping aims to find an optimal alignment between two signals, which is a more robust measure to avoid cycle-skipping challenges. However, the discontinuity makes the conventional dynamic time warping distance unsuitable for waveform inversion. We introduce a soft dynamic time warping distance as the misfit function, which is differentiable in that the inverted solution can converge to the accurate global minimum. We compare the convexity of the L2-norm and soft dynamic time warping distance and show that the soft dynamic time warping distance has a wider convexity range with different time shift and amplitudes. It can alleviate the half-wavelength limitation of the conventional L2-norm. We calculate the gradient using the automatic differentiation technique and the minibatch strategy and then analyse the alignment paths of different smooth parameters. A significant smooth parameter γ makes the Soft-DTW distance tending to the L2-norm, which generates new local minima. We recommend a small smooth parameter to ensure the convexity of the Soft-DTW distance. Numerical examples show that the soft dynamic time warping can effectively reconstruct the deep velocity parameters of the BG Compass and Marmousi models with noise robustness and lower dependence on the initial model.
3D pole-pole responses of buried anisotropic targets and various anisotropic backgrounds in direct-current resistivity survey
Authors: Ma Fengqun , Tan Handong , Kong Wenxin , Zhu Depeng
Published: April 2023

Many rocks often have the electrical anisotropy property that produces quite different responses from the electrical isotropic rocks. We applied an advanced modeling method to calculate the apparent resistivity responses over an anisotropic target in a homogenous isotropic backgound and an isotropic target embedded in different anisotropic host rocks. We demonstrated comprehensive modeling experiments to characterize the responses of surface pole-pole surveys to the buried targets in different geological backgrounds, which vary in the principal resistivities and Euler angles of the targets or the host rocks. Our modeling results show that: (i) the location of current injection controls the apparent resistivity images in value and shape; (ii) almost circle-contours or more or less elongated contours appear in the apparent resistivity images for the anisotropic targets; (iii) the isotropic target embedded in the anisotropic host rock generates some radial patterns from the current injection point; (iv) the anisotropy strike angles can be obtained from the symmetry axis of the apparent resistivity contours; and (v) multiple locations of current injections throughout the detection region are necessary for the surface pole-pole survey to avoid misleading data interpretation.
Isolation and characterization of gut bacteria associated with the degradation of host-specific terpenoids in Pagiophloeus tsushimanus (Coleoptera: Curculionidae) larvae
Authors: Qiao Heng , Zhu Han , Li Hui , Chen Hongjian , Li Shouyin , Chen Cong , Hao Dejun
Published: April 2023

Insect intestinal bacteria play an important role in resisting defensive substances of host plants. Pagiophloeus tsushimanus (Coleoptera: Curculionidae) feeds exclusively on camphor trees (Cinnamomum camphora, Laurales: Lauraceae) in China, causing substantial economic and ecological losses. It is unclear how the larvae of P. tsushimanus outcome the main secondary metabolites of C. camphora such as D-camphor, eucalyptol, and linalool. In this study, we isolated terpenoid-degrading bacteria from the gut of P. tsushimanus larvae by using selective culture medium. Maximum likelihood phylogenetic analyses were performed with 16S rDNA sequences to identify the bacteria, and results showed ten strains belonged to four genera, including Pseudomonas, Enterobacter, Serratia, and Corynebacterium. Then, gas chromatography was employed to determine the degradability of D-camphor, eucalyptol, and linalool by the isolated strains, results showed that Z5 strain (i.e., Corynebacterium variabile, Actinomycetales: Corynebacteriaceae), F1 strain (i.e., Pseudomonas aeruginosa, Pseudomonadales: Pseudomonaceae), and A3 strain (i.e., Serratia marcescens, Enterobacterales: Enterobacteriaceae) had the highest degradation rates of D-camphor, linalool, and eucalyptol, respectively. The intestinal bacteria were capable of terpenoid degradation in vitro, which suggested that these gut bacteria associated with P. tsushimanus play an important role in overcoming host plant secondary metabolite defense, thereby facilitating the host specialization of this pest.
Kidney function in patients with ovarian cancer treated with poly (ADP-ribose) polymerase (PARP) inhibitors
Authors: Gupta Shruti , Hanna Paul E , Ouyang Tianqi , Yamada Karla Sofia , Sawtell Rani , Wang Qiyu , Katz-Agranov Nurit , Feghali Lea , Krasner Carolyn N , Bouberhan Sara , Castro Cesar M , Sise Meghan E
Published: April 2023

Background

Poly (ADP-ribose) polymerase inhibitors (PARPi) have revolutionized the treatment of ovarian cancer; however, real-world data on kidney function among patients treated with PARPi are lacking.

Methods

We identified adults treated with olaparib or niraparib between 2015 and 2021 at a major cancer center in Boston, MA, USA. We determined the incidence of any acute kidney injury (AKI), defined as at least a 1.5-fold rise in serum creatinine from baseline in the first 12 months following PARPi initiation. We calculated the percentage of patients with any AKI and sustained AKI and adjudicated the etiologies by manual chart review. We compared trajectories in estimated glomerular filtration rate (eGFR) among PARPi-treated and carboplatin and paclitaxel-treated patients with ovarian cancer, matched by baseline eGFR.

Results

Of 269 patients, 60 (22.3%) developed AKI, including 43 of 194 (22.1%) olaparib-treated patients and 17 of 75 (22.7%) niraparib-treated patients. Only 9 of 269 (3.3%) had AKI attributable to the PARPi. Of the 60 patients with AKI, 21 (35%) had sustained AKI, of whom 6 had AKI attributable to the PARPi (2.2% of the whole cohort). eGFR declined within 30 days post-PARPi initiation by 9.61 (SD = 11.017)  mL/min per 1.73 m2 but recovered by 8.39 (SD = 14.05)  mL/min per 1.73 m2 within 90 days after therapy cessation. There was no difference in eGFR at 12 months post-therapy initiation in patients receiving PARPi or controls receiving carboplatin and paclitaxel (P = .29).

Conclusions

AKI is common following PARPi initiation as is a transient decline in eGFR; however, sustained AKI directly attributable to the PARPi and long-term eGFR decline are uncommon.
Dermacentor-borne necrosis erythema lymphadenopathy (DEBONEL) due to Rickettsia raoultii in a patient with erythema migrans
Authors: Norman Francesca F , Sánchez-Martín Jesús , Rodríguez-Domínguez Mario , Escudero Raquel , Martín Oihane
Published: April 2023

Erythema migrans is usually associated with infections/co-infections with Borrelia spp. DEBONEL and other localized diseases caused by Rickettsia spp. following a tick bite usually respond to therapy with doxycycline but possible co-infections with Borrelia spp should be excluded. In this case, PCR in the tick was positive for Rickettsia raoultii.
Characterization of a salt-resistant isocitrate lyase gene from mangrove wetland using shotgun metagenomic sequencing
Authors: Xu Bo , Zhang Wenfei , Li Dongming , Jin Yinghong , Rong Xianzi , Xu Yuquan , Wang Ruiping
Published: April 2023

Isocitrate lyase (ICL), as the key enzyme in the glyoxylate metabolic pathway, plays an important role in metabolic adaptation to environmental changes. In this study, metagenomic DNA from the soil and water microorganism collected from the Dongzhai Harbor Mangroves (DHM) reserve, in Haikou City, China, was high-throughput sequenced using an Illumina HiSeq 4000 platform. The icl121 gene, encoding an ICL with the highly conserved catalytic pattern IENQVSDEKQCGHQD was identified. Then, this gene was subcloned into the pET-30a vector and overexpressed in Escherichia coli BL21 (DE3) cells. The maximum enzymatic activity of the recombinant ICL121 protein is 9.47 × 102 U/mg occurring at pH 7.5 and 37°C. Furthermore, as a metalo-enzyme, ICL121 can utilize the appropriate concentrations of Mg2+, Mn2+, and Na+ ion as cofactors to exhibit high enzymatic activity. In particular, the novel metagenomic-derived icl121 gene displayed distinct salt tolerance (NaCl) and might be useful for generating salt-tolerant crops in the future.
Improvement of solubility of phospholipase D fromStreptomyces antibioticusin recombinantEscherichia coliand its application for the enzymatic synthesis of a non-natural plasmalogen
Authors: Yamaguchi Riko , Akter Shamoli , Kanehama Aki , Iwamoto Takahiro , Hasegawa Meme , Ito Akeno , Nishimukai Megumi , Yamada Miwa , Kashiwagi Akiko
Published: April 2023

Plasmalogens are a subclass of glycerophospholipids that have a vinyl-ether bond at the sn-1 position and are thought to have several physiological functions. The creation of non-natural plasmalogens with functional groups is desired for the establishment of the prevention of diseases caused by the depletion of plasmalogens. Phospholipase D (PLD) has both hydrolysis and transphosphatidylation activities. In particular, PLD from Streptomyces antibioticus has been investigated extensively due to its high transphosphatidylation activity. However, it has been difficult to stably express recombinant PLD in Escherichia coli and to express it as a soluble protein. In this study, we used the E. coli strain, SoluBL21™, and achieved stable PLD expression from the T7 promoter and increased soluble fraction in the cell. We also improved the purification method of PLD using His-tag at the C terminus. We obtained PLD with ∼730 mU mg−1 protein of specific activity, and the yield was ∼420 mU l−1 culture, corresponding to 76 mU per gram of wet cells. Finally, we synthesized a non-natural plasmalogen with 1,4-cyclohexanediol bound to the phosphate group at the sn-3 position by transphosphatidylation of the purified PLD. This method will contribute to the expansion of the chemical structure library of non-natural plasmalogens.
Counterfactual Decision Theory
Authors: Hedden Brian
Published: April 2023

I defend counterfactual decision theory, which says that you should evaluate an action in terms of which outcomes would likely obtain were you to perform it. Counterfactual decision theory has traditionally been subsumed under causal decision theory as a particular formulation of the latter. This is a mistake. Counterfactual decision theory is importantly different from, and superior to, causal decision theory, properly so called. Causation and counterfactuals come apart in three kinds of cases. In cases of overdetermination, an action can cause a good outcome without the latter counterfactually depending on the former. In cases of constitution, an action can constitute a good outcome rather than causing it. And in cases of determinism, either the laws or the past counterfactually depend on your action, even though your action cannot cause the laws or the past to be different. In each of these cases, it is counterfactual decision theory which gives the right verdict, and for the right reasons.
Optimizing the observation of optical kilonovae with medium-size telescopes
Authors: Camisasca A E , Steele I A , Bulla M , Guidorzi C , Shrestha M
Published: April 2023

We consider the optimization of the observing strategy (cadence, exposure time, and filter choice) using medium-size (2-m-class) optical telescopes in the follow-up of kilonovae localized with arcminute accuracy to be able to distinguish among various kilonova models and viewing angles. To develop an efficient observation plan, we made use of the synthetic light curves obtained with the Monte Carlo radiative transfer code POlarization Spectral Synthesis In Supernovae for different kilonova models and as a function of different viewing angles and distances. By adding the appropriate photon counting noise to the synthetic light curves, we analysed four alternative sequences having the same total time exposure of 8 h, with different time windows (0.5, 1, 2, and 4 h), each with i, r, and u filters, to determine the observing sequence that maximizes the chance of a correct identification of the model parameters. We suggest to avoid u filter and to avoid the use of colour curves. We also found that, if the error on distance is ≤$2~{{\ \rm per\ cent}}$, 0.5, 1, and 2-h time window sequences are equivalent, so we suggest to use 2-h one, because it has 1-d cadence, so it can be easily realized. When the distance of the source is unknown, 0.5-h time window sequence is preferable.
Two-temperature GRMHD simulations of black hole accretion flows with multiple magnetic loops
Authors: Jiang Hong-Xuan , Mizuno Yosuke , Fromm Christian M , Nathanail Antonios
Published: April 2023

We have performed a series of two-dimensional two-temperature general relativistic magnetohydrodynamic simulations of magnetized accretion flows initiated from tori with different sizes and poloidal magnetic loop polarities. In these two-temperature simulations, we trace the process of heating electrons through turbulence and reconnection, most of the time these electrons are trapped in plasmoids. We found that the accretion process strongly depends on the size of the magnetic loops. The accretion flows never reach the magnetically arrested (MAD) regime in small loop cases. Interaction between magnetic field with different polarities dissipates and decreases the efficiency of magnetorotational instability. The dependence on the wavelength of the loops places a lower limit on the loop size. In the large loop cases, after reaching a quasi-steady phase, a transition from standard and normal evolution flow to MAD flow is observed. The transition of the accretion state and the transition time depends on the initial loop wavelength. The formation of plasmoids strongly depends on the size of the magnetic loops. The frequent magnetic reconnection between the magnetic loops is responsible for the formation of most of the plasmoids. For some plasmoids, Kelvin–Helmholtz and tearing instabilities are coexisting, showing another channel of plasmoid formation. The simulations present that electrons in the plasmoids are well-heated up by turbulent and magnetic reconnection. Different properties of plasmoid formation in different magnetic field configurations provide new insights for the understanding of flaring activity and electron thermodynamics in Sagittarius A*.
Wasserstein distance as a new tool for discriminating cosmologies through the topology of large-scale structure
Authors: Tsizh Maksym , Tymchyshyn Vitalii , Vazza Franco
Published: April 2023

In this work, we test Wasserstein distance in conjunction with persistent homology as a tool for discriminating large-scale structures of simulated universes with different values of σ8 cosmological parameter (present root-mean-square matter fluctuation averaged over a sphere of radius 8 Mpc comoving). The Wasserstein distance (a.k.a. the pair-matching distance) was proposed to measure the difference between two networks in terms of persistent homology. The advantage of this approach consists in its non-parametric way of probing the topology of the cosmic web, in contrast to graph-theoretical approach depending on linking length. By treating the haloes of the cosmic web as points in a point cloud, we calculate persistent homologies, build persistence (birth–death) diagrams, and evaluate Wasserstein distance between them. The latter showed itself as a convenient tool to compare simulated cosmic webs. We show that one can discern two cosmic webs (simulated or real) with different σ8 parameter. It turns out that Wasserstein distance’s discrimination ability depends on redshift z, as well as on the dimensionality of considered homology features. We find that the highest discriminating power this tool obtains is at z = 2 snapshots, among the considered z = 2, 1, and 0.1 ones.
Measuring the ICM velocity structure in the Ophiuchus cluster
Authors: Gatuzz Efrain , Sanders J S , Dennerl K , Liu A , Fabian A C , Pinto C , Eckert D , Russell H , Tamura T , Walker S A , ZuHone J
Published: April 2023

We have found evidence of bulk velocities following active galactic nucleus (AGN) bubbles in the Virgo cluster and galaxy motions in the Centaurus cluster. In order to increase the sample and improve our understanding of the intracluster medium (ICM), we present the results of a detailed mapping of the Ophiuchus cluster with XMM–Newton to measure bulk flows through very accurate Fe-K measurements. To measure the gas velocities, we use a novel EPIC-pn energy-scale calibration, which uses the Cu Kα instrumental line as reference for the line emission. We created 2D spectral maps for the velocity, metallicity, temperature, density, entropy, and pressure with a spatial resolution of 0.25 arcmin (∼26 kpc). The ICM velocities in the central regions where AGN feedback is most important are similar to the velocity of the brightest cluster galaxy. We have found a large interface region where the velocity changes abruptly from blueshifted to redshifted gas that follows a sharp surface brightness discontinuity. We also found that the metallicities and temperatures do not change as we move outwards from the giant radio fossil previously identified in radio observations of the cluster. Finally, we have found a contribution from the kinetic component of $\lt 25{{\ \rm per\ cent}}$ to the total energy budget for large distances.
On the anticorrelation between pericentric distance and inner dark matter density of Milky Way’s dwarf spheroidal galaxies
Authors: Cardona-Barrero Salvador , Battaglia Giuseppina , Nipoti Carlo , Di Cintio Arianna
Published: April 2023

An anticorrelation between the central density of the dark matter (DM) halo (ρ150, DM) and the pericentric distances (rp) of the Milky Way’s (MW’s) dwarf spheroidal galaxies (dSphs) has been reported in the literature. The existence and origin of such anticorrelation are, however, controversial, one possibility being that only the densest dSphs can survive the tidal field towards the centre of our Galaxy. In this work, we place particular emphasis on quantifying the statistical significance of such anticorrelation, by using available literature data in order to explore its robustness under different assumptions on the MW gravitational potential, and for various derivations of ρ150 and rp. We consider models in which the MW is isolated and has low ($8.8\times 10^{11}\, {\rm M}_{\odot }$ ) and high ($1.6\times 10^{12}\, {\rm M}_{\odot }$ ) halo masses, respectively, as well as configurations in which the MW’s potential is perturbed by a Large Magellanic Cloud (LMC) infall. We find that, while data generally support models in which the dSphs’ central DM density decreases as a function of their pericentric radius, this anticorrelation is statistically significant at 3σ level only in ${\sim} 12~{{ \rm per\ cent}}$ of the combinations of ρ150 and rp explored. Moreover, including the impact of the LMC’s infall on to the MW weakens or even washes away this anticorrelation, with respect to models in which the MW is isolated. Our results suggest that the strength and existence of such anticorrelation are still debatable: exploring it with high-resolution simulations including baryonic physics and different DM flavours will help us to understand its emergence.
Spectroscopic and photometric studies on four solar-type short-period contact binaries in the triple stellar systems
Authors: Yang Yuangui , Michel Raúl , Yuan Huiyu , Wang Shuang , Tamayo Francisco
Published: April 2023

We reported new spectroscopy and photometry for four short-period binaries, which were acquired by several small telescopes in China from 2020 to 2022. From new spectrum and Large Sky Area Multiobject Fiber Spectroscopic Telescope data, we determined their spectral types of G8V for PZ UMa, G7 for MM Com, and V0685 Peg and G3 for V1055 Her. When compared to the Transiting Exoplanet Survey Satellite (TESS) light curve (LC) with a 2-min cadence, the difference between two light maxima for V1055 Her displays a 29.7-d oscillation. Utilizing the Wilson–Devinney program, we deduced 10 photometric solutions from our new and TESS data. Four binaries are W-type ones with variable O’Connell effects. For LC2022.1 (MM Com) and LC2022.9 (V1055 Her), Δmmax=Max.I–Max.II is as large as $15{{\ \rm per\ cent}}$ of variable light amplitude, which may be attributed to the spot’s migration and evolution. From the mass-luminosity diagram, the more massive components aref somewhat evolved main-sequence stars, whereas the less massive ones are overluminous as a result of energy exchange. Based on all eclipse timing residuals, the orbital period variations are preferably described by the light-travel time effects via the presence of additional companions. Their modulation periods range from 10 to 20 yr for four binaries, corresponding the companion’s mass ranging from M3 = 0.11 to 0.34 M⊙. Therefore, four solar-type short-period contact binaries (i.e. MM Com, PZ UMa, V0685 Peg, and V1055 Her) may be triple stellar systems.
Deletion of the mRNA stability factor ELAVL1 (HuR) in pancreatic cancer cells disrupts the tumor microenvironment integrity
Authors: McCarthy Grace A , Di Niro Roberto , Finan Jennifer M , Jain Aditi , Guo Yifei , Wyatt Cory R , Guimaraes Alexander R , Waugh Trent A , Keith Dove , Morgan Terry K , Sears Rosalie C , Brody Jonathan R
Published: April 2023

Stromal cells promote extensive fibrosis in pancreatic ductal adenocarcinoma (PDAC), which is associated with poor prognosis and therapeutic resistance. We report here for the first time that loss of the RNA-binding protein human antigen R (HuR, ELAVL1) in PDAC cells leads to reprogramming of the tumor microenvironment. In multiple in vivo models, CRISPR deletion of ELAVL1 in PDAC cells resulted in a decrease of collagen deposition, accompanied by a decrease of stromal markers (i.e. podoplanin, α-smooth muscle actin, desmin). RNA-sequencing data showed that HuR plays a role in cell–cell communication. Accordingly, cytokine arrays identified that HuR regulates the secretion of signaling molecules involved in stromal activation and extracellular matrix organization [i.e. platelet-derived growth factor AA (PDGFAA) and pentraxin 3]. Ribonucleoprotein immunoprecipitation analysis and transcription inhibition studies validated PDGFA mRNA as a novel HuR target. These data suggest that tumor-intrinsic HuR supports extrinsic activation of the stroma to produce collagen and desmoplasia through regulating signaling molecules (e.g. PDGFAA). HuR-deficient PDAC in vivo tumors with an altered tumor microenvironment are more sensitive to the standard of care gemcitabine, as compared to HuR-proficient tumors. Taken together, we identified a novel role of tumor-intrinsic HuR in its ability to modify the surrounding tumor microenvironment and regulate PDGFAA.
HiTAIC: hierarchical tumor artificial intelligence classifier traces tissue of origin and tumor type in primary and metastasized tumors using DNA methylation
Authors: Zhang Ze , Lu Yunrui , Vosoughi Soroush , Levy Joshua J , Christensen Brock C , Salas Lucas A
Published: April 2023

Human cancers are heterogenous by their cell composition and origination site. Cancer metastasis generates the conundrum of the unknown origin of migrated tumor cells. Tracing tissue of origin and tumor type in primary and metastasized cancer is vital for clinical significance. DNA methylation alterations play a crucial role in carcinogenesis and mark cell fate differentiation, thus can be used to trace tumor tissue of origin. In this study, we employed a novel tumor-type-specific hierarchical model using genome-scale DNA methylation data to develop a multilayer perceptron model, HiTAIC, to trace tissue of origin and tumor type in 27 cancers from 23 tissue sites in data from 7735 tumors with high resolution, accuracy, and specificity. In tracing primary cancer origin, HiTAIC accuracy was 99% in the test set and 93% in the external validation data set. Metastatic cancers were identified with a 96% accuracy in the external data set. HiTAIC is a user-friendly web-based application through https://sites.dartmouth.edu/salaslabhitaic/. In conclusion, we developed HiTAIC, a DNA methylation-based algorithm, to trace tumor tissue of origin in primary and metastasized cancers. The high accuracy and resolution of tumor tracing using HiTAIC holds promise for clinical assistance in identifying cancer of unknown origin.
Stem-like signatures in human meningioma cells are under the control of CXCL11/CXCL12 chemokine activity
Authors: Barbieri Federica , Bajetto Adriana , Dellacasagrande Irene , Solari Agnese , Würth Roberto , Fernandez Virginia , Rancati Silvia , Ceresa Davide , Appolloni Irene , De Luca Giuseppa , Dono Mariella , Nozza Paolo , Schiapparelli Piero , Gambaro Monica , Fiaschi Pietro , Gaggero Gabriele , Costanzo Nicolò , Thellung Stefano , Malatesta Paolo , Pagano Aldo , Zona Gianluigi , De Pietri Tonelli Davide , Florio Tullio
Published: April 2023

Background

Meningiomas are mainly benign brain tumors, although about 20% of histologically benign cases are clinically aggressive and recur after resection. We hypothesize that meningioma brain invasiveness and recurrence may be related to the presence of cancer stem cells and their high responsiveness to the CXCL12-CXCR4/CXCR7 chemokine axis. The aim of this study was to isolate meningioma stem cells from human samples, characterize them for biological features related to malignant behavior, and to identify the role of CXCR4/CXCR7 in these processes.

Methods

Meningioma stem cells were isolated from patient-derived primary cultures in stem cell-permissive conditions, and characterized for phenotype, self-renewal, proliferation and migration rates, vasculogenic mimicry (VM), and in vivo tumorigenesis, in comparison with differentiated meningioma cells and stem-like cells isolated from normal meninges. These cell populations were challenged with CXCL12 and CXCL11 and receptor antagonists to define the chemokine role in stem cell-related functions.

Results

Stem-like cells isolated from meningioma cultures display higher proliferation and migration rates, and VM, as compared to meningioma non-stem cells or cells isolated from normal meninges and were the only tumorigenic population in vivo. In meningioma cells, these stem-like functions were under the control of the CXCR4/CXCR7 chemokine axis.

Conclusions

We report a role for CXCL11 and CXCL12 in the control of malignant features in stem-like cells isolated from human meningioma, providing a possible basis for the aggressive clinical behavior observed in subsets of these tumors. CXCR4/CXCR7 antagonists might represent a useful approach for meningioma at high risk of recurrence and malignant progression.
Predicting methylation class from diffusely infiltrating adult gliomas using multimodality MRI data
Authors: Alom Zahangir , Tran Quynh T , Bag Asim K , Lucas John T , Orr Brent A
Published: April 2023

Background

Radiogenomic studies of adult-type diffuse gliomas have used magnetic resonance imaging (MRI) data to infer tumor attributes, including abnormalities such as IDH-mutation status and 1p19q deletion. This approach is effective but does not generalize to tumor types that lack highly recurrent alterations. Tumors have intrinsic DNA methylation patterns and can be grouped into stable methylation classes even when lacking recurrent mutations or copy number changes. The purpose of this study was to prove the principle that a tumor’s DNA-methylation class could be used as a predictive feature for radiogenomic modeling.

Methods

Using a custom DNA methylation-based classification model, molecular classes were assigned to diffuse gliomas in The Cancer Genome Atlas (TCGA) dataset. We then constructed and validated machine learning models to predict a tumor’s methylation family or subclass from matched multisequence MRI data using either extracted radiomic features or directly from MRI images.

Results

For models using extracted radiomic features, we demonstrated top accuracies above 90% for predicting IDH-glioma and GBM-IDHwt methylation families, IDH-mutant tumor methylation subclasses, or GBM-IDHwt molecular subclasses. Classification models utilizing MRI images directly demonstrated average accuracies of 80.6% for predicting methylation families, compared to 87.2% and 89.0% for differentiating IDH-mutated astrocytomas from oligodendrogliomas and glioblastoma molecular subclasses, respectively.

Conclusions

These findings demonstrate that MRI-based machine learning models can effectively predict the methylation class of brain tumors. Given appropriate datasets, this approach could generalize to most brain tumor types, expanding the number and types of tumors that could be used to develop radiomic or radiogenomic models.
Diffuse leptomeningeal glioneuronal tumor in a child masquerading as an intramedullary spinal pilocytic astrocytoma
Authors: Madsen Peter J , Hollawell Madison L , Santi Mariarita , Surrey Lea F , Vossough Arastoo , Orr Brent A , Hill-Kayser Christine , Tucker Alexander M , Storm Phillip B , Foster Jessica B
Published: April 2023

Diffuse leptomeningeal glioneuronal tumor (DLGNT) occurs predominantly in children and is typically characterized by diffuse leptomeningeal lesions throughout the neuroaxis with focal segments of parenchymal involvement. Recent reports have identified cases without diffuse leptomeningeal involvement that retain classic glioneuronal features on histology. In this report, we present a case of a 4-year-old boy with a large cystic-solid intramedullary spinal cord lesion that on surgical biopsy revealed a biphasic astrocytic tumor with sparsely distributed eosinophilic granular bodies and Rosenthal fibers. Next-generation sequencing revealed a KIAA1549-BRAF fusion, 1p/19q codeletion, and lack of an IDH1 mutation. Methylation profiling demonstrated a calibrated class score of 0.98 for DLGNT and copy number loss of 1p. Despite the morphologic similarities to pilocytic astrocytoma and the lack of oligodendroglial/neuronal components or leptomeningeal dissemination, the molecular profile was definitive in classifying the tumor as DLGNT. This case highlights the importance of molecular and genetic testing in the characterization of pediatric central nervous system tumors.
Persistence of Human Immunodeficiency Virus–Associated Cerebral Toxoplasmosis Lesions in Successfully Treated Patients Receiving Combination Antiretroviral Therapy
Authors: Coleman Benjamin , Smith Bryan R , Kapoor Rama , Proschan Michael A , Sereti Irini , Hammoud Dima A , Kovacs Joseph A
Published: April 2023

Background

Toxoplasmic encephalitis (TE) is a life-threatening complication of people with human immunodeficiency virus (PWH) with severe immunodeficiency, especially those with a CD4+ T-cell count <100 cells/µL. Following a clinical response to anti-Toxoplasma therapy, and immune reconstitution after initiation of combination antiretroviral therapy (ART), anti-Toxoplasma therapy can be discontinued with a low risk of relapse.

Methods

To better understand the evolution of magnetic resonance imaging (MRI)–defined TE lesions in PWH receiving ART, we undertook a retrospective study of PWH initially seen at the National Institutes of Health between 2001 and 2012, who had at least 2 serial MRI scans. Lesion size and change over time were calculated and correlated with clinical parameters.

Results

Among 24 PWH with TE and serial MRI scans, only 4 had complete clearance of lesions at the last MRI (follow-up, 0.09–5.8 years). Of 10 PWH off all anti-Toxoplasma therapy (median, 3.2 years after TE diagnosis), 6 had persistent MRI enhancement. In contrast, all 5 PWH seen in a pre–ART era study who were followed for >6 months had complete clearance of lesions. TE lesion area at diagnosis was associated with the absolute change in area (P < .0001).

Conclusions

Contrast enhancement can persist even when TE has been successfully treated and anti-Toxoplasma therapy has been stopped, highlighting the need to consider diagnostic alternatives in successfully treated patients with immune reconstitution presenting with new neurologic symptoms.
Hormone-regulated expansins: Expression, localization, and cell wall biomechanics in Arabidopsis root growth
Authors: Samalova Marketa , Melnikava Alesia , Elsayad Kareem , Peaucelle Alexis , Gahurova Evelina , Gumulec Jaromir , Spyroglou Ioannis , Zemlyanskaya Elena V , Ubogoeva Elena V , Balkova Darina , Demko Martin , Blavet Nicolas , Alexiou Panagiotis , Benes Vladimir , Mouille Gregory , Hejatko Jan
Published: April 2023

Expansins facilitate cell expansion by mediating pH-dependent cell wall (CW) loosening. However, the role of expansins in controlling CW biomechanical properties in specific tissues and organs remains elusive. We monitored hormonal responsiveness and spatial specificity of expression and localization of expansins predicted to be the direct targets of cytokinin signaling in Arabidopsis (Arabidopsis thaliana). We found EXPANSIN1 (EXPA1) homogenously distributed throughout the CW of columella/lateral root cap, while EXPA10 and EXPA14 localized predominantly at 3-cell boundaries in the epidermis/cortex in various root zones. EXPA15 revealed cell-type-specific combination of homogenous vs. 3-cell boundaries localization. By comparing Brillouin frequency shift and AFM-measured Young's modulus, we demonstrated Brillouin light scattering (BLS) as a tool suitable for non-invasive in vivo quantitative assessment of CW viscoelasticity. Using both BLS and AFM, we showed that EXPA1 overexpression upregulated CW stiffness in the root transition zone (TZ). The dexamethasone-controlled EXPA1 overexpression induced fast changes in the transcription of numerous CW-associated genes, including several EXPAs and XYLOGLUCAN:XYLOGLUCOSYL TRANSFERASEs (XTHs), and associated with rapid pectin methylesterification determined by in situ Fourier-transform infrared spectroscopy in the root TZ. The EXPA1-induced CW remodeling is associated with the shortening of the root apical meristem, leading to root growth arrest. Based on our results, we propose that expansins control root growth by a delicate orchestration of CW biomechanical properties, possibly regulating both CW loosening and CW remodeling.