bluuebunny/crossref_metadata_2025 huggingface dataset:
Probabilistic fair behaviors spark its boost in the Ultimatum game: the strength of good Samaritans
Authors: Zheng Guozhong , Zhang Jiqiang , Liang Rizhou , Ma Lin , Chen Li
Published: August 2022

Behavioral experiments on the Ultimatum game have shown that we human beings have a remarkable preference in fair play, contradicting the predictions by the game theory. Most of the existing models seeking for explanations, however, strictly follow the assumption of Homo economicus in orthodox economics that people are self-interested and fully rational to maximize their earnings. Here we relax this assumption by allowing that people probabilistically choose to be ‘good Samaritans’, acting as fair players from time to time. For well-mixed and homogeneously structured populations, we numerically show that as this probability increases the level of fairness undergoes from the low scenario abruptly to the full fairness state, where occasional fair behaviors

(

∼
5
%

)

are sufficient to drive the whole population to behave in the half–half split manner. We also develop a mean-field theory, which correctly reproduces the first-order phase transition and points out the reason. Heterogeneously structured populations, however, display continuous fairness transition; surprisingly, very few hub nodes acting as fair players are able to entrain the whole population to the full fairness state. Our results thus reveal the unexpected strength of ‘good Samaritans’, which may constitute a new explanation for the emergence of fairness in our society.
Existence and uniqueness theorems for some semi-linear equations on locally finite graphs
Authors: Pinamonti Andrea , Stefani Giorgio
Published: August 2022

We study some semi-linear equations for the

(
m
,
p
)

(m,p)

-Laplacian operator on locally finite weighted graphs. We prove existence of weak solutions for all

m
∈

N

m\in \mathbb {N}

and

p
∈
(
1
,
+
∞
)

p\in (1,+\infty )

via a variational method already known in the literature by exploiting the continuity properties of the energy functionals involved. When

m
=
1

m=1

, we also establish a uniqueness result in the spirit of the Brezis–Strauss Theorem. We finally provide some applications of our main results by dealing with some Yamabe-type and Kazdan–Warner-type equations on locally finite weighted graphs.
A class of weighted isoperimetric inequalities in hyperbolic space
Authors: Li Haizhong , Xu Botong
Published: August 2022

In this paper, we prove a class of weighted isoperimetric inequalities for bounded domains in hyperbolic space by using the isoperimetric inequality with log-convex density in Euclidean space. As a consequence, we remove the horo-convex assumption of domains in a weighted isoperimetric inequality proved by Scheuer-Xia [Trans. Amer. Math. Soc. 372 (2019), pp. 6771–6803]. Furthermore, we prove weighted isoperimetric inequalities for star-shaped domains in warped product manifolds. Particularly, we obtain a weighted isoperimetric inequality for star-shaped hypersurfaces lying outside a certain radial coordinate slice in the anti-de Sitter-Schwarzschild manifold.
Decompositions of quasirandom hypergraphs into hypergraphs of bounded degree
Authors: Ehard Stefan , Joos Felix
Published: August 2022

We prove that any quasirandom uniform hypergraph

H
H

can be approximately decomposed into any collection of bounded degree hypergraphs with almost as many edges. In fact, our results also apply to multipartite hypergraphs and even to the sparse setting when the density of 

H
H

quickly tends to

0
0

in terms of the number of vertices of

H
H

. Our results answer and address questions of Kim, Kühn, Osthus and Tyomkyn; and Glock, Kühn and Osthus as well as Keevash.

The provided approximate decompositions exhibit strong quasirandom properties which are very useful for forthcoming applications. Our results also imply approximate solutions to natural hypergraph versions of long-standing graph decomposition problems, as well as several decomposition results for (quasi)random simplicial complexes into various more elementary simplicial complexes such as triangulations of spheres and other manifolds.
Is the Product Method More Efficient Than the Difference Method for Assessing Mediation?
Authors: Cheng Chao , Spiegelman Donna , Li Fan
Published: August 2022

Mediation analysis is widely used in biomedical research to quantify the extent to which the effect from an exposure on a health outcome is through a mediator and the extent to which the effect is direct. A traditional approach for quantifying mediation is through the difference method. The other popular approach uses a counterfactual framework from which the product method arises. However, there is little prior work to articulate which method is more efficient for estimating 2 key quantities in mediation analysis, the natural indirect effect and mediation proportion. To fill in this gap, we investigated the asymptotic relative efficiency for mediation measure estimators given by the product method and the difference method. We considered 4 data types characterized by continuous and binary mediators and outcomes. Under certain conditions, we show analytically that the product method is equally efficient to the difference method, or more efficient. However, our numerical studies demonstrate that the difference method is usually at least 90% as efficient as the product method under realistic scenarios in epidemiologic research, especially for estimating the mediation proportion. We demonstrate the efficiency results by analyzing the MaxART study (Eswatini, 2014–2017), which aimed to evaluate the effectiveness of the early access to antiretroviral therapy among human immunodeficiency virus–positive patients.
Overcoming Language Barriers in Academia: Machine Translation Tools and a Vision for a Multilingual Future
Authors: Steigerwald Emma , Ramírez-Castañeda Valeria , Brandt Débora Y C , Báldi András , Shapiro Julie Teresa , Bowker Lynne , Tarvin Rebecca D
Published: August 2022

abstract

Having a central scientific language remains crucial for advancing and globally sharing science. Nevertheless, maintaining one dominant language also creates barriers to accessing scientific careers and knowledge. From an interdisciplinary perspective, we describe how, when, and why to make scientific literature more readily available in multiple languages through the practice of translation. We broadly review the advantages and limitations of neural machine translation systems and propose that translation can serve as both a short- and a long-term solution for making science more resilient, accessible, globally representative, and impactful beyond the academy. We outline actions that individuals and institutions can take to support multilingual science and scientists, including structural changes that encourage and value translating scientific literature. In the long term, improvements to machine translation technologies and collective efforts to change academic norms can transform a monolingual scientific hub into a multilingual scientific network. Translations are available in the supplemental material.
Warm acclimation alters antioxidant defences but not metabolic capacities in the Antarctic fish, Notothenia coriiceps
Authors: O’Brien Kristin M , Oldham Corey A , Sarrimanolis Jon , Fish Autumn , Castellini Luke , Vance Jenna , Lekanof Hayley , Crockett Elizabeth L
Published: August 2022

The Southern Ocean surrounding the Western Antarctic Peninsula region is rapidly warming. Survival of members of the dominant suborder of Antarctic fishes, the Notothenioidei, will likely require thermal plasticity and adaptive capacity in key traits delimiting thermal tolerance. Herein, we have assessed the thermal plasticity of several cellular and biochemical pathways, many of which are known to be associated with thermal tolerance in notothenioids, including mitochondrial function, activities of aerobic and anaerobic enzymes, antioxidant defences, protein ubiquitination and degradation in cardiac, oxidative skeletal muscles and gill of Notothenia coriiceps warm acclimated to 4°C for 22 days or 5°C for 42 days. Levels of triacylglycerol (TAG) were measured in liver and oxidative and glycolytic skeletal muscles, and glycogen in liver and glycolytic muscle to assess changes in energy stores. Metabolic pathways displayed minimal thermal plasticity, yet antioxidant defences were lower in heart and oxidative skeletal muscles of warm-acclimated animals compared with animals held at ambient temperature. Despite higher metabolic rates at elevated temperature, energy storage depots of TAG and glycogen increase in liver and remain unchanged in muscle with warm acclimation. Overall, our studies reveal that N. coriiceps displays thermal plasticity in some key traits that may contribute to their survival as the Southern Ocean continues to warm.
Low molecular weight heparin is associated with better outcomes than unfractionated heparin for thromboprophylaxis in hospitalized COVID-19 patients: a meta-analysis
Authors: Alsagaff Mochamad Yusuf , Mulia Eka Prasetya Budi , Maghfirah Irma , Azmi Yusuf , Rachmi Dita Aulia , Yutha Alqi , Andira Luqman Hakim , Semedi Bambang Pujo
Published: August 2022

Aims

This study aimed to compare the outcomes of the administration of LMWH and UFH in hospitalized COVID-19 patients.

Methods and results

We systematically searched several databases and included observational studies or clinical trials that compared the outcomes of the administration of LMWH and UFH in hospitalized COVID-19 patients. A total of nine studies comprising 9637 patients were included. Metanalysis showed that LMWH administration was associated with a lower in-hospital mortality and 28/30-day mortality compared with UFH administration {[relative risk (RR) 0.44; 95% confidence interval (95% CI) 0.32–0.61; I2: 87.9%] and (RR 0.45; 95% CI 0.24–0.86; I2: 78.4%), respectively}. Patient with LMWH had shorter duration of hospital and ICU length of stay compared with UFH {[weighted mean difference (WMD) −2.20; 95% CI −3.01 to −1.40; I2:0%] and (WMD −1.41; 95% CI −2.20 to −0.63; I2: 0%), respectively}. The risk of ICU admission or mechanical ventilation was lower in patients who received LMWH than in those who received UFH (RR 0.67; 95% CI 0.55–0.81; I2: 67.3%). However, there was no difference in the incidence of bleeding with LMWH compared with UFH (RR 0.27; 95% CI 0.07–1.01; I2: 64.6%).

Conclusion

Our meta-analysis showed that administration of LMWH was associated with better outcomes compared with UFH in hospitalized COVID-19 patients. Prospective cohorts and RCTs are urgently needed to explore the definitive effect of LMWH to provide direct high-certainty evidence.

PROSPERO registration number: CRD42021271977
Robust W-GAN-based estimation under Wasserstein contamination
Authors: Liu Zheng , Loh Po-Ling
Published: August 2022

Robust estimation is an important problem in statistics which aims at providing a reasonable estimator when the data-generating distribution lies within an appropriately defined ball around an uncontaminated distribution. Although minimax rates of estimation have been established in recent years, many existing robust estimators with provably optimal convergence rates are also computationally intractable. In this paper, we study several estimation problems under a Wasserstein contamination model and present computationally tractable estimators motivated by generative adversarial networks (GANs). Specifically, we analyze the properties of Wasserstein GAN-based estimators for location estimation, covariance matrix estimation and linear regression and show that our proposed estimators are minimax optimal in many scenarios. Finally, we present numerical results which demonstrate the effectiveness of our estimators.
SARS-CoV-2 Evolution and Patient Immunological History Shape the Breadth and Potency of Antibody-Mediated Immunity
Authors: Manali Maria , Bissett Laura A , Amat Julien A R , Logan Nicola , Scott Sam , Hughes Ellen C , Harvey William T , Orton Richard , Thomson Emma C , Gunson Rory N , Viana Mafalda , Willett Brian , Murcia Pablo R
Published: August 2022

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), humans have been exposed to distinct SARS-CoV-2 antigens, either by infection with different variants, and/or vaccination. Population immunity is thus highly heterogeneous, but the impact of such heterogeneity on the effectiveness and breadth of the antibody-mediated response is unclear. We measured antibody-mediated neutralization responses against SARS-CoV-2Wuhan, SARS-CoV-2α, SARS-CoV-2δ, and SARS-CoV-2ο pseudoviruses using sera from patients with distinct immunological histories, including naive, vaccinated, infected with SARS-CoV-2Wuhan, SARS-CoV-2α, or SARS-CoV-2δ, and vaccinated/infected individuals. We show that the breadth and potency of the antibody-mediated response is influenced by the number, the variant, and the nature (infection or vaccination) of exposures, and that individuals with mixed immunity acquired by vaccination and natural exposure exhibit the broadest and most potent responses. Our results suggest that the interplay between host immunity and SARS-CoV-2 evolution will shape the antigenicity and subsequent transmission dynamics of SARS-CoV-2, with important implications for future vaccine design.
Hyperimmune Globulin for Severely Immunocompromised Patients Hospitalized With Coronavirus Disease 2019: A Randomized, Controlled Trial
Authors: Huygens Sammy , Hofsink Quincy , Nijhof Inger S , Goorhuis Abraham , Kater Arnon P , te Boekhorst Peter A W , Swaneveld Francis , Novotný Věra M J , Bogers Susanne , Welkers Matthijs R A , Papageorgiou Grigorios , Rijnders Bart J , Heijmans Jarom
Published: August 2022

Background

The aim of this randomized, controlled trial is to determine whether antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin (COVIG) protects against severe coronavirus disease 2019 (COVID-19) in severely immunocompromised, hospitalized, COVID-19 patients.

Methods

Patients were randomly assigned to receive COVIG or intravenous immunoglobulin (IVIG) without SARS-CoV-2 antibodies.

Results

Severe COVID-19 was observed in 2 of 10 (20%) patients treated with COVIG compared to 7 of 8 (88%) in the IVIG control group (P = .015, Fisher’s exact test).

Conclusions

Antisevere acute respiratory syndrome coronavirus 2 hyperimmune globulin may be a valuable treatment in severely immunocompromised, hospitalized, COVID-19 patients and should be considered when no monoclonal antibody therapies are available.
In with the old, in with the new: machine learning for time to event biomedical research
Authors: Danciu Ioana , Agasthya Greeshma , Tate Janet P , Chandra-Shekar Mayanka , Goethert Ian , Ovchinnikova Olga S , McMahon Benjamin H , Justice Amy C
Published: August 2022

The predictive modeling literature for biomedical applications is dominated by biostatistical methods for survival analysis, and more recently some out of the box machine learning approaches. In this article, we show a presentation of a machine learning method appropriate for time-to-event modeling in the area of prostate cancer long-term disease progression. Using XGBoost adapted to long-term disease progression, we developed a predictive model for 118 788 patients with localized prostate cancer at diagnosis from the Department of Veterans Affairs (VA). Our model accounted for patient censoring. Harrell’s c-index for our model using only features available at the time of diagnosis was 0.757 95% confidence interval [0.756, 0.757]. Our results show that machine learning methods like XGBoost can be adapted to use accelerated failure time (AFT) with censoring to model long-term risk of disease progression. The long median survival justifies and requires censoring. Overall, we show that an existing machine learning approach can be used for AFT outcome modeling in prostate cancer, and more generally for other chronic diseases with long observation times.
Overdose of the HIV Medicine Genvoya® in Two Auto-Intoxications
Authors: Gys Celine , Mortelé Olivier , van Rafelghem Babette , Berry Eleanor , van Nuijs Alexander L N , Lambert Willy , Jacobs Werner , Schouwers Sofie , Meskal Anissa , Van Hemeldonck Ellen , Heytens Luc , Neels Hugo , Covaci Adrian
Published: August 2022

Toxicological data on overdose with human immunodeficiency virus inhibitors are scarce. We present a case report of two independent suicide attempts by self-administered overdose with the same antiretroviral medicine Genvoya® (emtricitabine/elvitegravir/tenofovir alafenamide/cobicistat). Both patients were admitted to the hospital and presented with a loss of consciousness, lactic acidosis, elevated hepatic transaminase levels and hemodynamic instability. While one patient survived with advanced supportive measures, the other passed away. Emtricitabine levels were measured in vivo in various consecutive serum samples and postmortem urine, peripheral and cardiac serum samples and confirmed excessive use in both cases. This is the first time that emtricitabine levels following overdose are reported. Although measured concentrations for emtricitabine were quite similar in these cases, metabolic acidosis was more pronounced in the fatal case. The difference in outcomes between the two could be due to a difference in physiological status, susceptibility to accumulation and adverse effects, and perhaps a varying interval between ingestion and the start of supportive measures.
Advanced orthogonal learning and Gaussian barebone hunger games for engineering design
Authors: Zhou Xinsen , Gui Wenyong , Heidari Ali Asghar , Cai Zhennao , Elmannai Hela , Hamdi Monia , Liang Guoxi , Chen Huiling
Published: August 2022

The hunger games search (HGS) algorithm is a recently proposed population-based optimization algorithm that mimics a common phenomenon of animals searching for food due to hunger stimuli and has a simple and easy-to- understand structure. However, the original HGS still suffers from shortcomings, such as low population diversity and the tendency to fall into local optima. To remedy these shortcomings, an improved HGS, called OCBHGS, is proposed, which introduces three main strategies, namely the chaotic initialization strategy, the Gaussian barebone mechanism, and the orthogonal learning strategy. Firstly, chaotic mapping is used for initialization to improve the quality of the initialized population. Secondly, the embedding of the Gaussian barebone mechanism effectively improves the diversity of the population, facilitates the communication between members, and helps the population avoid falling into local optima. Finally, the orthogonal learning strategy can extend the domain exploration and improve the solution accuracy of the algorithm. We conducted extensive experiments in the CEC2014 competition benchmark function, comparing OCBHGS with nine other metaheuristics and 12 improved algorithms. Also, the experimental results were evaluated using Wilcoxon signed-rank tests to analyze the experimental results comprehensively. In addition, OCBHGS was used to solve three constrained real-world engineering problems. The experimental results show that OCBHGS has a significant advantage in convergence speed and accuracy. As a result, OCBHGS ranks first in overall performance compared to other optimizers.
Assessing genomic and ecological differentiation among subspecies of the rough-footed mud turtle,Kinosternon hirtipes
Authors: Weaver Sam , McGaugh Suzanne E , Kono Thomas J Y , Macip-Rios Rodrigo , Gluesenkamp Andrew G
Published: August 2022

Combining genetic and ecological measures of differentiation can provide compelling evidence for ecological and genetic divergence among lineages. The rough-footed mud turtle, Kinosternon hirtipes, is distributed from the Trans-Pecos region of Texas to the highlands of Central Mexico and contains 6 described subspecies, 5 of which are extant. We use ddRAD sequencing and species distribution models to assess levels of ecological and genetic differentiation among these subspecies. We also predict changes in climatically suitable habitat under different climate change scenarios and assess levels of genetic diversity and inbreeding within each lineage. Our results show that there is strong genetic and ecological differentiation among multiple lineages within K. hirtipes, and that this differentiation appears to be the result of vicariance associated with the Trans-Mexican Volcanic Belt. We propose changes to subspecies designations to more accurately reflect the evolutionary relationships among populations and assess threats to each subspecies.
Political Agency and Implementation Subsidies with Imperfect Monitoring
Authors: Blumenthal Benjamin
Published: August 2022

Voters are frequently ill-equipped to monitor politicians’ actions. Politicians are expected to implement projects, whose benefits sometimes partially accrue to interest groups (IGs) and not entirely to voters. IGs thus have an incentive to affect which projects politicians implement by providing implementation subsidies to lower the cost of policymaking that politicians incur. This article shows how these considerations interact in a two-period political agency model with moral hazard and adverse selection. I study how the involvement of IGs in the policymaking process can affect voters’ welfare and show why voters might rationally not perfectly monitor politicians in the presence of IGs that might capture projects’ benefits and affect policymaking.
Field Evaluations of Three Botanically Inspired Repellents Against the Blacklegged Tick,Ixodes scapularis(Acari: Ixodidae)
Authors: Lee Xia , Wong Colin , Coats Joel , Paskewitz Susan
Published: August 2022

Three compounds synthetically-derived from botanicals sources, ethyl perillyl carbonate, geranyl isovalerate, and citronellyl cyclobutane carboxylate, were tested for repellent activity against Ixodes scapularis Say in a field trial. Tick drags were treated with the compounds or with N, N-diethyl-m-toluamide (DEET) at high (0.25 mg/cm2) or low (0.16 mg/cm2) concentrations. Negative controls included untreated drags and drags treated with acetone, the carrier for all repellents. Freshly treated drags (within 20 min) were used to collect I. scapularis ticks at a county park in Wisconsin. To assess effectiveness, we measured tick encounter rates, detachment rate, and time to detachment. None of the repellent treatments, including DEET, resulted in significantly fewer encounters compared to both control treatments. However, the percentage of ticks that detached within 3 min was significantly higher on drags treated with repellents compared to controls. DEET was the most effective, repelling 69.7–87% of ticks by 3 min, but the effectiveness of the three test compounds was still high, with 42–87% of ticks detaching by 3 min. For time to detachment, there were no significant differences between DEET and the three test compounds. We conclude that these synthetically-derived repellents were effective against I. scapularis in a field trial and could be viable alternatives to DEET.
Exploration of the origin of the 2020 X-ray outburst in OJ 287
Authors: Huang Shifeng , Hu Shaoming , Yin Hongxing , Chen Xu , Alexeeva Sofya , Jiang Yunguo
Published: August 2022

Research into OJ 287 has been ongoing for many years. In 2020 April–June, this source underwent the second highest X-ray outburst (second only to the 2016–2017 outburst) and the mechanism of this outburst is still under debate. In this paper, we discuss two scenarios to explore the origin of the outburst: an after-effect of a black hole–disc impact and a tidal disruption event (TDE). We present the weak correlations of the spectral index versus X-ray flux and the hardness ratio (HR) versus the soft X-ray flux during the outburst, and these features are different from the case in the quiescent state. The correlations are compared with those of the 2016–2017 outburst with the highest X-ray flux in monitoring history. Analysis of the outbursts in 2016–2017 and 2020 shows that the expected time of the X-ray outburst, based on the theory of the after-effect of the black hole–disc impact and the estimation of available data, is inconsistent with historical observations. The soft X-ray spectra, the barely temporal evolution of colour, and the evolution of the HR mean that the 2020 outburst shares similar features with the 2016–2017 outburst, which was considered as a possible candidate for a TDE. Additionally, we find that the predictions of full TDEs (t−5/3) and partial TDEs (t−9/4) for the soft X-ray decay light curve are well fitted. Our analysis suggests that the 2020 outburst in OJ 287 is probably related to the TDE candidate.
Galaxies and haloes on graph neural networks: Deep generative modelling scalar and vector quantities for intrinsic alignment
Authors: Jagvaral Yesukhei , Lanusse François , Singh Sukhdeep , Mandelbaum Rachel , Ravanbakhsh Siamak , Campbell Duncan
Published: August 2022

In order to prepare for the upcoming wide-field cosmological surveys, large simulations of the Universe with realistic galaxy populations are required. In particular, the tendency of galaxies to naturally align towards overdensities, an effect called intrinsic alignments (IA), can be a major source of systematics in the weak lensing analysis. As the details of galaxy formation and evolution relevant to IA cannot be simulated in practice on such volumes, we propose as an alternative a Deep Generative Model. This model is trained on the IllustrisTNG-100 simulation and is capable of sampling the orientations of a population of galaxies so as to recover the correct alignments. In our approach, we model the cosmic web as a set of graphs, where the graphs are constructed for each halo, and galaxy orientations as a signal on those graphs. The generative model is implemented on a Generative Adversarial Network architecture and uses specifically designed Graph-Convolutional Networks sensitive to the relative 3D positions of the vertices. Given (sub)halo masses and tidal fields, the model is able to learn and predict scalar features such as galaxy and dark matter subhalo shapes; and more importantly, vector features such as the 3D orientation of the major axis of the ellipsoid and the complex 2D ellipticities. For correlations of 3D orientations the model is in good quantitative agreement with the measured values from the simulation, except for at very small and transition scales. For correlations of 2D ellipticities, the model is in good quantitative agreement with the measured values from the simulation on all scales. Additionally, the model is able to capture the dependence of IA on mass, morphological type, and central/satellite type.
A spectroscopic study of 14 structures behind Holm15A: detecting a galaxy group candidate at z = 0.58
Authors: Ibarra-Medel H
Published: August 2022

Holm15A hosts one of the most massive back holes ever known. Hence, it is important to characterize any structure within its core to avoid any wrong association with its central black hole and therefore bias any future study. In this work, we present the first identification and characterization of 14 structures hidden behind the surface brightness of Holm15A. We model and subtract the spectral contribution of Holm15A to obtain the spectral information of these structures. We spectroscopically confirm that the 14 objects found are not associated with Holm15A. 10 objects have a well-defined galaxy spectrum from which we implement a fossil record analysis to reconstruct their past evolution. Nine objects are candidates members to be part of a compact galaxy group at redshift 0.5814. We find past mutual interaction among the group candidates that support the scenario of mutual crossings. Furthermore, the fossil reconstruction of the group candidates brings evidence that at least three different merger trees could assemble the galaxy group. We characterize the properties of the galaxy group from which we estimate a lower limit of the scale and mass of this group. We obtain a scale of >146 ± 3 kpc with a dispersion velocity of 622 ± 300 km s−1. These estimations consider the lensing effects of the gravitational potential of Holm15A. The other five objects were studied individually. We use public archive data of integral field spectroscopic observations from the Multi-Unit Spectroscopic Explorer instrument.
CMB spectral distortions from continuous large energy release
Authors: Acharya Sandeep Kumar , Chluba Jens
Published: August 2022

Accurate computations of spectral distortions of the cosmic microwave background (CMB) are required for constraining energy release scenarios at redshifts z ≳ 103. The existing literature focuses on distortions that are small perturbations to the background blackbody spectrum. At high redshifts (z ≳ 106), this assumption can be violated, and the CMB spectrum can be significantly distorted at least during part of its cosmic evolution. In this paper, we carry out accurate thermalization computations, evolving the distorted CMB spectrum in a general, fully non-linear way, consistently accounting for the time-dependence of the injection process, modifications to the Hubble expansion rate and relativistic Compton scattering. Specifically, we study single energy injection and decaying particle scenarios, discussing constraints on these cases. We solve the thermalization problem using two independent numerical approaches that are now available in CosmoTherm as dedicated setups for computing CMB spectral distortions in the large distortion regime. New non-linear effects at low frequencies are furthermore highlighted, showing that these warrant a more rigorous study. This work eliminates one of the long-standing simplifications in CMB spectral distortion computations, which also opens the way to more rigorous treatments of distortions induced by high-energy particle cascade, soft photon injection, and in the vicinity of primordial black holes.
XMM–Newton observations of PSR J0554+3107: pulsing thermal emission from a cooling high-mass neutron star
Authors: Tanashkin A S , Karpova A V , Potekhin A Y , Shibanov Y A , Zyuzin D A
Published: August 2022

XMM–Newton observations of the middle-aged radio-quiet γ-ray pulsar J0554+3107 allowed us, for the first time, firmly identify it in X-rays by detection of pulsations with the pulsar period. In the 0.2–2 keV band, the pulse profile shows two peaks separated by about a half of the rotation phase with the pulsed fraction of 25 ± 6 per cent. The profile and spectrum in this band can be mainly described by thermal emission from the neutron star with the hydrogen atmosphere, dipole magnetic field of ∼1013 G, and non-uniform surface temperature. Non-thermal emission from the pulsar magnetosphere is marginally detected at higher photon energies. The spectral fit with the atmosphere+power-law model implies that J0554+3107 is a rather heavy and cool neutron star with the mass of 1.6–2.1 M⊙, the radius of ≈13 km, and the redshifted effective temperature of ≈50 eV. The spectrum shows an absorption line of unknown nature at ≈350 eV. Given the extinction–distance relation, the pulsar is located at ≈2 kpc and has the redshifted bolometric thermal luminosity of ≈2 × 1032 erg s−1. We discuss cooling scenarios for J0554+3107 considering plausible equations of state of superdense matter inside the star, different compositions of the heat-blanketing envelope, and various ages.
Safety and efficacy of filgotinib for Japanese patients with RA and inadequate response to MTX: FINCH 1 52-week results and FINCH 4 48-week results
Authors: Tanaka Yoshiya , Matsubara Tsukasa , Atsumi Tatsuya , Amano Koichi , Ishiguro Naoki , Sugiyama Eiji , Yamaoka Kunihiro , Combe Bernard G , Kivitz Alan J , Bae Sang-Cheol , Keystone Edward C , Nash Peter , Genovese Mark , Matzkies Franziska , Bartok Beatrix , Pechonkina Alena , Kondo Akira , Ye Lei , Gong Qi , Tasset Chantal , Takeuchi Tsutomu
Published: August 2022

Objectives

To present safety and efficacy of the JAK1 preferential inhibitor filgotinib in Japanese patients with prior inadequate response (IR) to methotrexate (MTX) from a 52-week randomised controlled parent study (PS) and long-term extension (LTE) through June 2020.

Methods

The PS (NCT02889796) randomised MTX-IR patients to filgotinib 200 (FIL200) or 100 mg (FIL100), adalimumab (ADA) 40 mg, or placebo; all took stable background MTX. At week (W) 24, placebo patients were rerandomised to FIL200 or FIL100. The primary endpoint was W12 American College of Rheumatology 20% improvement; safety was assessed by adverse event (AE) reporting. For the LTE (NCT03025308), eligible filgotinib patients continued FIL200/FIL100; ADA patients were rerandomised (blinded) to FIL200 or FIL100; all continued MTX.

Results

In all, 114/147 Japanese patients completed the PS, 115 enrolled in LTE, and 103 remained on study in June 2020. In the PS, AEs were consistent with the overall population, and W24 efficacy was maintained or improved through W52, comparable with the overall population. LTE AE incidences were similar between doses; filgotinib efficacy was consistent from baseline to W48 and similar between PS ADA and filgotinib patients.

Conclusions

Among MTX-IR Japanese patients, filgotinib maintained efficacy over 1 year; LTE safety was consistent with the PS.
Robust counterselection and advanced λRed recombineering enable markerless chromosomal integration of large heterologous constructs
Authors: Bubnov Dmitrii M , Yuzbashev Tigran V , Khozov Andrey A , Melkina Olga E , Vybornaya Tatiana V , Stan Guy-Bart , Sineoky Sergey P
Published: August 2022

Despite advances in bacterial genome engineering, delivery of large synthetic constructs remains challenging in practice. In this study, we propose a straightforward and robust approach for the markerless integration of DNA fragments encoding whole metabolic pathways into the genome. This approach relies on the replacement of a counterselection marker with cargo DNA cassettes via λRed recombineering. We employed a counterselection strategy involving a genetic circuit based on the CI repressor of λ phage. Our design ensures elimination of most spontaneous mutants, and thus provides a counterselection stringency close to the maximum possible. We improved the efficiency of integrating long PCR-generated cassettes by exploiting the Ocr antirestriction function of T7 phage, which completely prevents degradation of unmethylated DNA by restriction endonucleases in wild-type bacteria. The employment of highly restrictive counterselection and ocr-assisted λRed recombineering allowed markerless integration of operon-sized cassettes into arbitrary genomic loci of four enterobacterial species with an efficiency of 50–100%. In the case of Escherichia coli, our strategy ensures simple combination of markerless mutations in a single strain via P1 transduction. Overall, the proposed approach can serve as a general tool for synthetic biology and metabolic engineering in a range of bacterial hosts.
Molecular basis of anti-CRISPR operon repression by Aca10
Authors: Lee So Yeon , Birkholz Nils , Fineran Peter C , Park Hyun Ho
Published: August 2022

CRISPR-Cas systems are bacterial defense systems for fighting against invaders such as bacteriophages and mobile genetic elements. To escape destruction by these bacterial immune systems, phages have co-evolved multiple anti-CRISPR (Acr) proteins, which inhibit CRISPR-Cas function. Many acr genes form an operon with genes encoding transcriptional regulators, called anti-CRISPR-associated (Aca) proteins. Aca10 is the most recently discovered Aca family that is encoded within an operon containing acrIC7 and acrIC6 in Pseudomonas citronellolis. Here, we report the high-resolution crystal structure of an Aca10 protein to unveil the molecular basis of transcriptional repressor role of Aca10 in the acrIC7-acrIC6-aca10 operon. We identified that Aca10 forms a dimer in solution, which is critical for binding specific DNA. We also showed that Aca10 directly recognizes a 21 bp palindromic sequence in the promoter of the acr operon. Finally, we revealed that R44 of Aca10 is a critical residue involved in the DNA binding, which likely results in a high degree of DNA bending.
Mining bacterial NGS data vastly expands the complete genomes of temperate phages
Authors: Zhang Xianglilan , Wang Ruohan , Xie Xiangcheng , Hu Yunjia , Wang Jianping , Sun Qiang , Feng Xikang , Lin Wei , Tong Shanwei , Yan Wei , Wen Huiqi , Wang Mengyao , Zhai Shixiang , Sun Cheng , Wang Fangyi , Niu Qi , Kropinski Andrew M , Cui Yujun , Jiang Xiaofang , Peng Shaoliang , Li Shuaicheng , Tong Yigang
Published: August 2022

Temperate phages (active prophages induced from bacteria) help control pathogenicity, modulate community structure, and maintain gut homeostasis. Complete phage genome sequences are indispensable for understanding phage biology. Traditional plaque techniques are inapplicable to temperate phages due to their lysogenicity, curbing their identification and characterization. Existing bioinformatics tools for prophage prediction usually fail to detect accurate and complete temperate phage genomes. This study proposes a novel computational temperate phage detection method (TemPhD) mining both the integrated active prophages and their spontaneously induced forms (temperate phages) from next-generation sequencing raw data. Applying the method to the available dataset resulted in 192 326 complete temperate phage genomes with different host species, expanding the existing number of complete temperate phage genomes by more than 100-fold. The wet-lab experiments demonstrated that TemPhD can accurately determine the complete genome sequences of the temperate phages, with exact flanking sites, outperforming other state-of-the-art prophage prediction methods. Our analysis indicates that temperate phages are likely to function in the microbial evolution by (i) cross-infecting different bacterial host species; (ii) transferring antibiotic resistance and virulence genes and (iii) interacting with hosts through restriction-modification and CRISPR/anti-CRISPR systems. This work provides a comprehensively complete temperate phage genome database and relevant information, which can serve as a valuable resource for phage research.
Incidence and survival of choroid plexus tumors in the United States
Authors: Takaoka Kailey , Cioffi Gino , Waite Kristin A , Finlay Jonathan L , Landi Daniel , Greppin Kaitlyn , Kruchko Carol , Ostrom Quinn T , Barnholtz-Sloan Jill S
Published: August 2022

Background

There are limited data available on incidence and survival of patients with choroid plexus tumors (CPT). This study provides the most current epidemiological analysis of choroid plexus tumors from 2004 to 2017 in the United States.

Methods

Data on 2013 patients with CPT were acquired from the Central Brain Tumor Registry of the United States in collaboration with the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute, from 2004 to 2017. CPT cases were classified by the following pathological subtypes: choroid plexus papilloma (CPP), atypical choroid plexus papilloma (aCPP), and choroid plexus carcinoma (CPC). Frequencies and age-adjusted incidence rates (AAIR) per 100 000 and rate ratios per 100 000 (IRR) were reported for age, sex, race, and ethnicity for each pathological subtype with 95% confidence intervals (95% CI). Using CDC’s National Program of Cancer Registries survival database, survival curves and hazard ratios (HRs) evaluated overall survival from 2001 to 2016.

Results

CPP had the highest overall incidence (AAIR: 0.034, 95% CI: 0.033–0.036), followed by CPC (AAIR: 0.008, 95% CI: 0.008–0.009) and aCPP (AAIR: 0.005, 95% CI: 0.005–0.006). Incidence was highest among children less than one year old among all subtypes (CPP AAIR: 0.278; aCPP AAIR: 0.140; CPC AAIR: 0.195), reducing as patients aged. Overall survival was worse among patients with CPC, being five times more likely to die compared to patients with CPP (HR: 5.23, 95% CI: 4.05–7.54, P < .001).

Conclusions

This analysis is the most current and comprehensive study in the US on the incidence and survival for CPT. Population based statistics provide critical information in understanding disease characteristics, which impact patient care and prognosis.
Prevalence of Medical Contraindications to Nirmatrelvir/Ritonavir in a Cohort of Hospitalized and Nonhospitalized Patients With COVID-19
Authors: Lim Sarah , Tignanelli Christopher J , Hoertel Nicolas , Boulware David R , Usher Michael G
Published: August 2022

This analysis describes the prevalence of contraindications to nirmatrelvir/ritonavir among 66 007 patients with coronavirus disease 2019 in a large health care system. A possible contradiction was present in 9830 patients (14.8%), with the prevalence of contraindications increasing with higher acuity of illness.
Current Role of Prospective Monitoring and Preemptive and Prophylactic Therapy for Human Herpesvirus 6 After Allogeneic Stem Cell Transplantation
Authors: Handley Guy
Published: August 2022

Human herpesvirus 6 (HHV-6) frequently reactivates after allogeneic stem cell transplantation (SCT). Most patients are asymptomatic and viremia often resolves without therapy; however, transplant-related complications may be associated with reactivation. Multiple presentations have been attributed to HHV-6 reactivation after SCT including encephalitis. Several strategies have been trialed to reduce such risks or complications. Challenges exist with prospective monitoring strategies, and established thresholds of high-level reactivation may be limited. Three published guidelines and extensive trials focusing on preemptive and prophylactic strategies are reviewed. Future areas of investigation and high-risk populations are described. Existing trials and testing platforms have significant limitations, and to date no clear benefit for a preemptive or prophylactic intervention has been demonstrated.
Estimating the impact of menstrual poverty on adolescents in Nova Scotia
Authors: Lukindo Mary , Price Victoria , Pike Meghan
Published: August 2022

Background

Menstrual poverty is defined as the inability of people who menstruate to obtain menstrual products due to financial burden. The impact of menstrual poverty is not well studied in developed countries.

Objectives

This study aims to estimate the impact of menstrual poverty on adolescents who reside in Nova Scotia (NS), Canada.

Methods

A web-based, 25-item questionnaire, the adolescent Menstrual Poverty Questionnaire (aMPQ), was developed and distributed via social media. Adolescents less than 18 years of age, English-speaking and living in NS were eligible to complete the questionnaire. Data were analysed using descriptive analysis.

Results

Four hundred and twenty adolescents completed the questionnaire, with a mean age of 16.1 years (14.4–17.9 years). Results revealed that 65% of respondents do not always have enough money to buy menstrual products. This led to unsafe menstrual hygiene practices including using alternatives for menstrual products (e.g., rags), washing disposable menstrual products, and/or wearing products for longer than intended. Forty percent of respondents reported lack of affordability of menstrual products as a cause for school absenteeism and lack of participation in sport/social activities. Seventy percent of respondents felt embarrassed to ask for products even when they are provided for free, and almost all supported the idea of having freely available menstrual products in public washrooms.

Conclusions

This study determined that menstrual poverty impacts adolescents in Nova Scotia. To address menstrual poverty, menstrual products should be freely available in all public washrooms, as this will provide unrestricted access to menstruators and promote their full participation in society.
Food insecurity in households of children receiving care at a paediatric obesity management clinic in Montreal: Overall prevalence and changes associated with the COVID-19 pandemic
Authors: Cyrenne-Dussault Marie , Sirois Maude , St-Pierre Julie , Drouin-Chartier Jean-Philippe
Published: August 2022

Objectives

Food insecurity and paediatric obesity are two major public health issues in Canada that may have been exacerbated by the COVID-19 pandemic. We assessed food insecurity and its correlates among households of children receiving care at a paediatric obesity management clinic in Montreal. We also assessed whether the prevalence of food insecurity among households of children who received care during the COVID-19 pandemic differed from those who received care before it.

Methods

This is a retrospective, cross-sectional analysis of medical records of children (2 to 17 years) who received care at a paediatric obesity management clinic in Montreal (Maison de santé prévention – Approche 180 [MSP-180]). Children’s household food security status was assessed using Health Canada’s Household Food Security Survey Module.

Results

Among the 253 children included in the study, 102 (40.3%) lived in households with moderate (n=89; 35.2%) or severe food insecurity (n=13; 5.1%). Food insecurity was more prevalent in households of children who were first- or second-generation immigrants compared with those who were third generation or more (48.3% versus 30.1%; P=0.03). Prevalence of food insecurity among households of children who received care during the COVID-19 pandemic was 5.5% higher than among those who received care before the pandemic, but the difference was not statistically significant (39.6% versus 45.1%; P=0.65).

Conclusions

Forty per cent of children treated at this paediatric obesity clinic lived in a food insecure household. This prevalence may have increased during the first year of the COVID-19 pandemic, but statistical power was insufficient to confirm it.
Effectiveness of the BNT162b2 mRNA COVID-19 vaccine among adolescents with juvenile-onset inflammatory rheumatic diseases
Authors: Ziv Amit , Heshin-Bekenstein Merav , Haviv Ruby , Kivity Shaye , Netzer Doron , Yaron Shlomit , Schur Yoav , Egert Tsipi , Egert Yona , Sela Yaron , Hashkes Philip J , Uziel Yosef
Published: August 2022

Objectives

The effectiveness of the BNT162b2 mRNA COVID-19 vaccine for adolescents with juvenile-onset inflammatory or immune rheumatic diseases (IRDs) is unknown. Several studies have suggested attenuated immunogenicity in patients with IRD. This study evaluated the effectiveness of the BNT162b2 mRNA COVID-19 vaccine in preventing COVID-19 infection in adolescents with juvenile-onset IRD compared with controls without immune rheumatic disease.

Methods

We used data from Clalit Health Services, the largest health-care organization in Israel, to conduct an observational cohort study from February to December 2021, involving 12–18 year-old adolescents diagnosed with IRD. Study outcomes included documented COVID-19 infection in relation to vaccination status and immunomodulatory therapy. We estimated vaccine effectiveness as one minus the risk ratio. Adolescents aged 12–18 years without immune rheumatic disease served as controls.

Results

A total of 1639 adolescents with IRD (juvenile idiopathic arthritis, SLE, or familial Mediterranean fever) were included and compared with 524 471 adolescents in the same age range without IRD. There was no difference in COVID-19 infection rates after the second dose of vaccine between those with IRD and controls (2.1% vs 2.1% respectively, P = 0.99). The estimated vaccine effectiveness for adolescents with IRD was 76.3% after the first dose, 94.8% after the second and 99.2% after the third dose.

Conclusion

We found that the BNT162b2 mRNA vaccine was similarly effective against COVID-19 infection in adolescents with and without IRD. Immunomodulatory therapy did not affect its effectiveness. These results can encourage adolescents with IRD to get vaccinated against COVID-19.