bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeat-associated non-AUG translation induces cytoplasmic aggregation of CAG repeat-containing RNAs
Authors: Das Michael R. , Chang Yeonji , Anderson Rachel , Saunders Reuben A. , Zhang Nan , Tomberlin Colson P. , Vale Ronald D. , Jain Ankur
Published: January 2023

CAG trinucleotide repeat expansions cause several neurodegenerative diseases, including Huntington's disease and spinocerebellar ataxia. RNAs with expanded CAG repeats contribute to disease in two unusual ways. First, these repeat-containing RNAs may agglomerate in the nucleus as foci that sequester several RNA-binding proteins. Second, these RNAs may undergo aberrant repeat-associated non-AUG (RAN) translation in multiple frames and produce aggregation-prone proteins. The relationship between RAN translation and RNA foci, and their relative contributions to cellular dysfunction, are unclear. Here, we show that CAG repeat-containing RNAs that undergo RAN translation first accumulate at nuclear foci and, over time, are exported to the cytoplasm. In the cytoplasm, these RNAs are initially dispersed but, upon RAN translation, aggregate with the RAN translation products. These RNA–RAN protein agglomerates sequester various RNA-binding proteins and are associated with the disruption of nucleocytoplasmic transport and cell death. In contrast, RNA accumulation at nuclear foci alone does not produce discernable defects in nucleocytoplasmic transport or cell viability. Inhibition of RAN translation prevents cytoplasmic RNA aggregation and alleviates cell toxicity. Our findings demonstrate that RAN translation-induced RNA-protein aggregation correlates with the key pathological hallmarks observed in disease and suggest that cytoplasmic RNA aggregation may be an underappreciated phenomenon in CAG trinucleotide repeat expansion disorders.
High-performance reality of 55SiCrV spring steel processed by the rapid-induction heat treatment
Authors: Dai Qilei , Jin Lei , Chen Wen , Wu Jingzhou , Fang Zhou , Yang Tianbao , Ma Ruijin , Li Kun
Published: January 2023

Heat treatment methodology is vital to achieve high performance of advanced spring steel. The present study has investigated the microstructure and mechanical properties of the 55SiCrV spring steel processed by a novel online rapid-induction heat treatment. The results showed that rapid heating refines the prior austenite grain size of the 55SiCrV spring steel, and the vanadium mainly exists as the solid solution in the matrix instead of the dispersive precipitation of the V-containing secondary phase under the rapid induction heat treatment condition. An optimal combination of mechanical properties simultaneously with ultrahigh strength and high plasticity was obtained and the properties of the steel are mainly enhanced by the hardenability and tempering resistance of solute V in the material.
Dynamic compression behaviour and microstructural evolution of the Mg–6Zn–2Ce–0.6Zr alloy
Authors: Xu Chenkun , Wang Zhi , Wang Feng , Zhou Le , Mao Pingli , Wei Ziqi , Liu Zheng
Published: January 2023

Herein, an Mg–6Zn–2Ce–0.6Zr alloy was prepared via the extrusion–shear process. The dynamic compression mechanical performance and mechanism of microstructural evolution of the alloy in a strain rate range from 500 to 2500 s−1 were investigated. The dynamic compression performance of the alloy increased with the strain rate. The electron backscatter diffraction analyses revealed that the angle between the c-axis and the extrusion direction of most grains changed from 90° to 180° after dynamic compression. The deformation can be attributed to the extension twining, basal slip, and prismatic slip. The dynamic deformation mechanism was studied and the fracture mechanism under a high strain rate was determined by analysing the temperature rise and absorbed energy density.
Cardiorespiratory fitness and targeted proteomics involved in brain and cardiovascular health in children with overweight/obesity
Authors: Plaza‐Florido Abel , Rodriguez‐Ayllon Maria , Altmäe Signe , Ortega Francisco B. , Esteban‐Cornejo Irene
Published: January 2023

Cardiorespiratory fitness (CRF) is inversely associated with cardiovascular disease (CVD) risk factors and brain health impairments. However, the molecular mechanisms linking CRF to health in children are poorly understood. We aimed to examine protein levels related to brain health and CVD in plasma of fit compared to unfit children with overweight/obesity (OW/OB). Eighty‐seven children with OW/OB (10.08 ± 1.1 years, 59% boys) from the ActiveBrains project were included. CRF was measured by performing a treadmill test, and children were categorized into fit or unfit. Targeted proteomics in plasma was performed using Olink's proximity extension assay technology of Neurology panel in the whole sample and of Cardiovascular panel in a subsample. Sixteen proteins (PLXNB3, sFRP3, CLEC1B, RSPO1, Gal8, CLEC10A, GCP5, MDGA1, CTSC, LAT, IL4RA, PRSS27, CXCL1, Gal9, MERTK, and GT) were differentially expressed between fit and unfit children with OW/OB after adjusting for sex, maturational status, and body mass index. However, statistically significant differences disappeared after applying FDR correction. Potential candidate proteins related to CRF levels in children with OW/OB were detected, being involved in several biological processes such as neurogenesis, immune/inflammatory response, signal transduction, platelet activation. Nevertheless, these preliminary findings should be confirmed or contrasted in future studies using larger sample sizes, longitudinal and experimental designs.
Meiotic resetting of the cellular Sod1 pool is driven by protein aggregation, degradation, and transient LUTI-mediated repression
Authors: Vander Wende Helen M. , Gopi Mounika , Onyundo Megan , Medrano Claudia , Adanlawo Temiloluwa , Brar Gloria Ann
Published: January 2023

Gametogenesis requires packaging of the cellular components needed for the next generation. In budding yeast, this process includes degradation of many mitotically stable proteins, followed by their resynthesis. Here, we show that one such case—Superoxide dismutase 1 (Sod1), a protein that commonly aggregates in human ALS patients—is regulated by an integrated set of events, beginning with the formation of pre-meiotic Sod1 aggregates. This is followed by degradation of a subset of the prior Sod1 pool and clearance of Sod1 aggregates. As degradation progresses, Sod1 protein production is transiently blocked during mid-meiotic stages by transcription of an extended and poorly translated SOD1 mRNA isoform, SOD1LUTI. Expression of SOD1LUTI is induced by the Unfolded Protein Response, and it acts to repress canonical SOD1 mRNA expression. SOD1LUTI is no longer expressed following the meiotic divisions, enabling a resurgence of canonical mRNA and synthesis of new Sod1 protein such that gametes inherit a full complement of Sod1 protein. Failure to aggregate and degrade Sod1 results in reduced gamete fitness in the presence of oxidants, highlighting the importance of this regulation. Investigation of Sod1 during yeast gametogenesis, an unusual cellular context in which Sod1 levels are tightly regulated, could shed light on conserved aspects of its aggregation and degradation, with relevance to understanding Sod1’s role in human disease.
Carrollian hydrodynamics from symmetries
Authors: Freidel Laurent , Jai-akson Puttarak
Published: January 2023

In this work, we revisit Carrollian hydrodynamics, a type of non-Lorentzian hydrodynamics which has recently gained increasing attentions due to its underlying connection with dynamics of spacetime near null boundaries, and we aim at exploring symmetries associated with conservation laws of Carrollian fluids. With an elaborate construction of Carroll geometries, we generalize the Randers–Papapetrou metric by incorporating the fluid velocity field and the sub-leading components of the metric into our considerations and we argue that these two additional fields are compulsory phase space variables in the derivation of Carrollian hydrodynamics from symmetries. We then present a new notion of symmetry, called the near-Carrollian diffeomorphism, and demonstrate that this symmetry consistently yields a complete set of Carrollian hydrodynamic equations. Furthermore, due to the presence of the new phase space fields, our results thus generalize those already presented in the previous literatures. Lastly, the Noether charges associated with the near-Carrollian diffeomorphism and their time evolutions are also discussed.
Evaluation method for the design results of space gravitational-wave telescopes
Authors: Li Jiancong , Lin Hongan , Huang Yaozhang , Yu Miao , Luo Jiaxiong , Xiao Zihao , Wang Zhi , Wu Yanxiong
Published: January 2023

Unlike traditional imaging telescopes, space gravitational-wave telescope has higher requirements for wavefront error and must meet the stability requirement of tilt-to-length (TTL). The tolerance analysis results of current telescopes can judge whether the wavefront error meets the requirements, but they cannot be used as the judgment result of the TTL noise coupling coefficient of the telescope. To analyze the influence of manufacturing errors of the telescope on the coupling coefficient of TTL noise, based on the error amount and the Zernike polynomial first-order sensitivity matrix, we established the sensitivity matrix of the mapping relationship between telescope manufacturing errors and coupling coefficients. For example, consider the design results of an off-axis four-mirror space gravitational-wave telescope. If the wavefront error was used as the judgment result to determine the tolerance distribution, the cumulative probability of the coupling coefficient meeting the requirements would be 66.7%. Furthermore, using the coupling coefficient as the control requirement and determining the tolerance allocation results according to the coupling coefficient sensitivity matrix, the cumulative probability increased to 93.8%. The necessity of using the coupling coefficient as an evaluation method for the design results of gravitational-wave telescopes was verified. This evaluation method can provide meaningful guidance for the design results of gravitational-wave telescopes.
Improved PPP-RTK positioning performance by using the elevation-dependent weighting model for the atmospheric delay corrections
Authors: Liu Min , Yin Xiao , Xiang Minzhi
Published: January 2023

With satellite phase bias products, integer ambiguity resolution (AR) enabled precise point positioning (PPP) can be achieved, that is, PPP-real-time kinematic (RTK). However, PPP-AR still requires minutes to converge to centimeter-level accuracy, as atmospheric delay parameters need to be estimated in the user un-combined (UC) model. To shorten the convergence time, reference-network-derived atmospheric delay corrections are often directly corrected for raw code/phase observables, without considering their uncertainties, thereby causing model errors. In this study, we propose a new ionosphere-weighted model, in which an elevation-dependent weight is adopted. To evaluate the proposed model, on-board kinematic experiments were conducted based on GPS/Galileo/BDS2/ BDS3 dual-frequency measurements. Compared with the positioning results of the traditional determined variance weight, the proportion of horizontal errors less than 5 cm is increased from 70% to 80%, and horizontal accuracy is improved by 22% and 9.8% at the 68th and 95th percentile, respectively, indicating that the proposed model can improve the PPP-RTK performance.
Estimation of the melting threshold of Ti supersaturated Si using time resolved reflectometry and haze measurements
Authors: Montero D , Caudevilla D , Algaidy S , Garcia-Hernansanz R , Suler A , Acosta-Alba P , Kerdiles S , Pastor D , Garcia-Hemme E , Roy F , Olea J
Published: January 2023

Hyperdoped or supersaturated semiconductors are gathering the attention of industry and research institutions due to their sub-bandgap photon absorption properties. In this study, two fast and non-invasive techniques, time-resolved reflectometry (TRR) and Haze Measurements, are applied to infer the melt and solidification regimes of Ti supersaturated 300 mm silicon wafers, aiming to ease the characterization process towards high volume manufacturing of supersaturated materials. Ti supersaturation is attained by using an ion implantation process with a dose 3 × 1015 cm−2, which amorphizes the surface. Crystalline quality is then recovered by means of a XeCl UV nanosecond laser annealing process. TRR technique is used to determine two different melting and solidification processes of the laser annealed implanted surface. A first brief, low temperature peak (α peak) is associated with the melting process of the amorphized surface, followed by a longer peak/plateau (β
1 peak/plateau), linked to the melting process of the crystalline phase below the amorphized layer, at sufficiently high laser fluences. Haze technique is used to indirectly measure the crystalline quality after the solidification process of the laser-annealed surface. Atomic force microscopy measurements are used to obtain the surface roughness value and cross-section high resolution transmission electron microscopy micrographs to check crystalline quality.
Comprehensive study on fatigue degradation of road piezoelectric energy harvesters under thermal-mechanical coupling effect
Authors: Liu Zhiming , Duan Wei , Wang Jun , Cai Guojun , He Huan , Qin Xiangzhen , Ye Feilong
Published: January 2023

Recent years have seen significant advancements in the field of road vibration energy harvesting using piezoelectric technology, including the watt-level road piezoelectric energy harvesters (RPEHs). However, research on the fatigue life of RPEH under thermal-mechanical coupling effect is lacking. In this study, six lead zirconate titanate (PZT) block piezoelectric transducers with distinct properties were fabricated, and five transducer structures were compared. The effects of piezoelectric material properties, pavement temperature, and transducer structure on RPEH fatigue degradation were investigated using approximately 23 million mechanical loads. The findings revealed that the output power of the soft PZT was significantly greater than that of the hard PZT under low-frequency cyclic loading. However, the Curie temperature decreased with an increasing piezoelectric constant of the soft PZT. Therefore, the stability of the output voltage worsened as the ambient temperature approached half the Curie temperature. Specifically, when the ambient temperature was 50 °C, the output failure phenomenon readily occurred during the initial stage of fatigue loading. By optimizing the transducer structure, the fatigue characteristics and high-temperature failure phenomenon of RPEH could be effectively improved. The coupling output modes of d
33 and d
31 were superior to that of the d
33 mode. Among these, the drum transducer exhibited the highest output performance and operational stability across different ambient temperatures, excitation frequencies, and displacements. After six million intermittent loads over 15 d (equivalent to two years of traffic load), the output power decreased from 6.51 to 6.02 mW with a degradation rate of merely 7.53%, indicating a promising application prospect. The results provide an crucial design foundation for the entire life cycle operation of RPEH in road engineering.
Experimental study of stability, quench propagation and detection methods on 15 kA sub-scale HTS fusion conductors in SULTAN
Authors: Bykovskiy N , Bajas H , Dicuonzo O , Bruzzone P , Sedlak K
Published: January 2023

High-temperature superconductors (HTSs) enable exclusive operating conditions for fusion magnets, boosting their performance up to 20 T generated magnetic fields in the temperature range from 4 K to 20 K. One of the main technological issues of HTS conductors is focused on their protection in the case of thermal runaway (quench). In spite of the extremely high thermal stability of HTS materials, quenching is still possible due to local defects along the conductor length or insufficient cooling. In such cases, the high stability results in the slow propagation of a resistive zone. Thereby, a risky hot-spot temperature (>200 K) can be reached if applying conventional quench detection methods at a voltage threshold of 0.1–0.5 V, typical for fusion magnets. Aiming at an experimental study of the phenomenon, a series of sub-scale 15 kA 3.6 m long conductors based on stacks of tapes soldered in copper profiles are manufactured at the Swiss Plasma Center, including twisted rare earth barium copper oxide (ReBCO) and bismuth strontium calcium copper oxide (BISCCO) triplets, non-twisted and solder-filled ReBCO triplets, as well as indirectly cooled non-twisted ReBCO single strands. Applying either an increasing helium inlet temperature, overcurrent operation or energy deposited by embedded cartridge heaters, critical values of the electric field and temperature are evaluated for a given operating current (up to 15 kA) and background magnetic field (up to 10.9 T). Once quenching is actually triggered, the quench propagation is studied using distributed voltage taps and temperature sensors able to monitor the external temperature of the jacket and the internal temperature of the conductor (helium or copper). Thanks to the recent upgrade of the Supraleiter Test Anlage (SULTAN) test facility, quench propagation in the conductors is measured up to a total voltage of 2 V and a peak temperature of 320 K. Furthermore, advanced quench detection methods based on superconducting insulated wires and fiber optics are also instrumented and studied. A summary of the test samples, their instrumentation and corresponding test results are presented in this work.
Techniques for Measuring Parallax and Proper Motion with VLBI
Authors: Reid M. J.
Published: January 2023

Astrometry at centimeter wavelengths using Very Long Baseline Interferometry is approaching accuracies of ∼1 μas for the angle between a target and a calibrator source separated by ≲1° on the sky. The BeSSeL Survey and the Japanese VERA project are using this to map the spiral structure of the Milky Way by measuring trigonometric parallaxes of hundreds of maser sources associated with massive, young stars. This paper outlines how μas astrometry is done, including details regarding the scheduling of observations, calibration of data, and measuring positions.
Global Extinction: Gemini North and South GMOS Combined Photometry Relative to the Gaia Catalog, and Long-term Atmospheric Change
Authors: Steinbring Eric
Published: January 2023

Effects of long-term atmospheric change were looked for in photometry employing Gemini North and South twin Multi-Object Spectrograph (GMOS-N and GMOS-S) archival data. The whole GMOS imaging database, beginning from 2003, was compared against the all-sky Gaia object catalog, yielding ∼106 Sloan

r
′

-filter samples, ending in 2021. These were combined with reported sky and meteorological conditions, and versus a simple model of the atmosphere plus cloud together with simulated throughputs. One exceptionally extincted episode in 2009 is seen, as is a trend (similar at both sites) of about 2 mmag worsening attenuation per decade. This is consistent with solar-radiance transmissivity records going back over six decades, aerosol density measurements, and more than 0.2°C/decade rise in air temperature, which has implications for the calibration of historic data sets or future surveys.
Extending the VDPC+BCS formalism by including three-body forces*
Authors: Xia Zi-Yu
Published: January 2023

Recently, Jia proposed a formalism to apply the variational principle to a coherent-pair condensate for a two-body Hamiltonian. The present study extends this formalism by including three-body forces. The result is the same as the so-called variation after particle-number projection in the BCS case, but now, the particle number is always conserved, and the time-consuming projection is avoided. Specifically, analytical formulas of the average energy are derived along with its gradient for a three-body Hamiltonian in terms of the coherent-pair structure. Gradient vanishment is required to obtain analytical expressions for the pair structure at the energy minimum. The new algorithm iterates on these pair-structure expressions to minimize energy for a three-body Hamiltonian. The new code is numerically demonstrated when applied to realistic two-body forces and random three-body forces in large model spaces. The average energy can be minimized to practically any arbitrary precision.
Variable energy X-ray fluorescence source
Authors: Elliott S.R. , Bond E.M. , Dodson B. , Rusev G. , Massarczyk R. , Meijer S.J. , Stortini M. , Wiseman C.
Published: January 2023

We detail the design of a variable energy, x-ray fluorescence source using a low activity (1.8×106 dpm) 99Tc β source that irradiates thin foils. By rotating the source among foils of Ti, Zn, Nb, Ag, and Au, the device produces x rays between 4 and 70 keV at a rate near 1 Hz. When the source is placed in a storage position, the external radiation is non-detectable. The design of the shielding and rotation mechanism permits use in vacuum and at liquid nitrogen temperature. The design is intended for the study of the low energy response to radiation impinging upon Ge detector surfaces. The source will be useful for understanding the detector response in large-scale Ge arrays such as Majorana and LEGEND.
Determination of the radial position of zero density for profile reflectometry on experimental advanced superconducting tokamak
Authors: Zhang J. , Liu A.D. , Zhou C. , Zhuang G. , Ding W.X. , Hu G.H. , Xu G.S. , Ding B.J. , Li M.H. , Zou X.L. , Zhang S.B. , Hu L.Q. , Feng X. , Wang S.F. , Wang M.Y. , Li H. , Lan T. , Mao W.Z. , Liu Z.X. , Xie J.L. , Liu W.D.
Published: January 2023

The Experimental Advanced Superconducting Tokamak (EAST) reflectometry is a Frequency-Modulated Continuous-Wave monostatic system with the transmission lines similar to the ITER reflectometer design. One of the most significant and common problems for reflectometry to reconstruct the density profile is the determination of initialization, i.e. zero density position (R
start), which could be determined by the extraordinary mode (X-mode) reflectometry. The main source of noise still comes from the wave scattering of plasmas despite the sweeping period of around 10 microseconds. It is found that to reduce the random noise of R
start, averaging on 25 periods is the optimal solution. During the L-mode discharges with only lower hybrid wave (LHW) heating, R
start would move outwards and its fluctuation and the high frequency components of turbulence around R
start would be obviously increased when the 2.45 GHz system is switched on, while no obvious change is observed in the 4.6 GHz case. These phenomena are consistent with that 2.45 GHz LHW has less current drive ability than 4.6 GHz LHW on EAST. During ELMy H-mode, the peak of R
start is consistent with Deuterium signal and the maximum displacement is about 3 cm. The comparison of density profiles from reflectometry and Lithium beam emission spectroscopy (Li-BES) suggests that setting the density at R
start to (4 ± 2)× 1017 m-3 is much better than zero, while this value is somewhat empirical and closely related to the amplitude threshold for determining the first probing frequency corresponding to R
start.
The ‘conflict trap’ reduces economic growth in the shared socioeconomic pathways
Authors: Petrova Kristina , Olafsdottir Gudlaug , Hegre Håvard , Gilmore Elisabeth A
Published: January 2023

Armed conflict and economic growth are inherently coupled; armed conflict substantially reduces economic growth, while economic growth is strongly correlated with a reduction in the propensity of armed conflict. Here, we simulate the incidence of armed conflict and its effect on economic growth simultaneously along the economic pathways defined by the shared socioeconomic pathways (SSPs). We argue that gross domestic product per capita projections through the 21st century currently in use are too optimistic since they disregard the harm to growth caused by conflict. Our analysis indicates that the correction required to account for this is substantial—expected income is 25% lower on average across countries when taking conflict into account. The correction is particularly strong for the more pessimistic SSP3 and SSP4 where expected future incidence of armed conflict is high. There are strong regional patterns with countries with contemporaneous conflicts experiencing much higher conflict burdens and reduced economic growth by the end of the century. The implications of this research indicate that today’s most marginalized societies will be substantially more vulnerable to the impact of climate change than indicated by existing income projections.
Diversity of sharp restart
Authors: Eliazar Iddo , Reuveni Shlomi
Published: January 2023

When applied to a stochastic process of interest, a restart protocol alters the overall statistical distribution of the process’ completion time; thus, the completion-time’s mean and randomness change. The explicit effect of restart on the mean is well understood, and it is known that: from a mean perspective, deterministic restart protocols—termed sharp restart—can out-perform any other restart protocol. However, little is known on the explicit effect of restart on randomness. This paper is the second in a duo exploring the effect of sharp restart on randomness: via a Shannon-entropy analysis in the first part, and via a diversity analysis in this part. Specifically, gauging randomness via diversity—a measure that is intimately related to the Renyi entropy—this paper establishes a set of universal criteria that determine: (A) precisely when a sharp-restart protocol decreases/increases the diversity of completion times; (B) the very existence of sharp-restart protocols that decrease/increase the diversity of completion times. Moreover, addressing jointly mean-behavior and randomness, this paper asserts and demonstrates when sharp restart has an aligned effect on the two (decreasing/increasing both), and when the effect is antithetical (decreasing one while increasing the other). The joint mean-diversity results require remarkably little information regarding the (original) statistical distributions of completion times, and are remarkably practical and easy to implement.
DC active power filter based on model predictive control for DC bus overvoltage suppression of accelerator grid power supply
Authors: ZHANG Hongqi , ZHU Bangyou , MA Shaoxiang , LI Zhiheng , ZHANG Ming , PAN Yuan
Published: January 2023

The China Fusion Engineering Test Reactor plans to build a 200 kV/25 A acceleration grid power supply (AGPS) for the negative-ion-based neutral beam injector prototype system. The AGPS uses a rectifier-inverter-isolated step-up structure. There is a DC bus between the rectifier and the inverter. In order to limit DC bus voltage ripple and transient fluctuations, a large number of capacitors are used, which degrades the reliability of the power supply and occupies a large amount of space. This work finds that due to the difference in the turn-off time of the rectifier and the inverter, the capacitance mainly depends on the rectifier current when the inverter is turned off. On this basis, an active power filter (APF) scheme is proposed to absorb the current. To enhance the dynamic response ability of the APF, model predictive control is adopted. In this paper, the circuit structure of the APF is introduced, the prediction model is deduced, the corresponding control strategy and signal detection method are proposed, and the simulation and experimental results show that APF can track the transient current of the DC bus and reduce the voltage fluctuation significantly.
A Demonstration of Modified Treatment Policies to Evaluate Shifts in Mobility and COVID-19 Case Rates in US Counties
Authors: Nugent Joshua R , Balzer Laura B
Published: January 2023

Mixed evidence exists of associations between mobility data and coronavirus disease 2019 (COVID-19) case rates. We aimed to evaluate the county-level impact of reducing mobility on new COVID-19 cases in summer/fall of 2020 in the United States and to demonstrate modified treatment policies to define causal effects with continuous exposures. Specifically, we investigated the impact of shifting the distribution of 10 mobility indexes on the number of newly reported cases per 100,000 residents 2 weeks ahead. Primary analyses used targeted minimum loss-based estimation with Super Learner to avoid parametric modeling assumptions during statistical estimation and flexibly adjust for a wide range of confounders, including recent case rates. We also implemented unadjusted analyses. For most weeks, unadjusted analyses suggested strong associations between mobility indexes and subsequent new case rates. However, after confounder adjustment, none of the indexes showed consistent associations under mobility reduction. Our analysis demonstrates the utility of this novel distribution-shift approach to defining and estimating causal effects with continuous exposures in epidemiology and public health.
Co-Design with People with Lived Experience: Designing Resources to Communicate with Children and Young People in Care about their Family Time Contact Visits
Authors: Black Billy , Hendry Bobby , Wright Amy Conley , Collings Susan
Published: January 2023

Contact visits, or family time, enable children in out-of-home care to sustain relationships with their birth families. In Australia, direct contact including face-to-face visits is typical for children on long-term orders, including guardianship and open adoption. Caseworkers are charged with supporting relationships between children’s birth family members and carers and ensuring contact is safe and child-centred. This article describes how people with lived experience of family time in out-of-home care have collaborated with researchers to co-design practical resources, in the context of an action research study aimed at changing caseworker practice. These resources include a book for young children and a book for older children and adolescents, which both use trauma-informed language and empower their audiences to know their rights and ask for what they need. Additional resources include co-designed tip sheets for family members and carers. People who have personally experienced the care system have unique insights into the experience of family time in out-of-home care and how it can be improved. In partnership, researchers and people with lived experience can identify the gaps in knowledge and practice resources, and co-design resources that integrate lived experience and research findings, underpinned by theory.
Atrichia with papular lesions in a 1-year-old girl resulting from a new homozygous nonsense pathogenic variant in the hairless gene
Authors: Segovia Jen-Christina , Lin Yu-Chen , Aala Wilson , Dolendo Mae Concepcion J , McGrath John A , Hsu Chao-Kai , Guevara Bryan Edgar K
Published: January 2023

Congenital atrichia is a rare disorder featuring the gradual shedding of hair at birth with near total hair loss in succeeding weeks or months. When accompanied by milia-like papules on the face or body it is called atrichia with papular lesions (APL), caused by germline pathogenic variants in the hairless (HR) gene and some somatic variants in HR are implicated in various malignancies. We report a case of a patient harbouring a germline homozygous nonsense variant in the HR gene presenting as APL with concomitant liver cancer.
Cortical speech tracking is related to individual prediction tendencies
Authors: Schubert Juliane , Schmidt Fabian , Gehmacher Quirin , Bresgen Annika , Weisz Nathan
Published: January 2023

Listening can be conceptualized as a process of active inference, in which the brain forms internal models to integrate auditory information in a complex interaction of bottom-up and top-down processes. We propose that individuals vary in their “prediction tendency” and that this variation contributes to experiential differences in everyday listening situations and shapes the cortical processing of acoustic input such as speech. Here, we presented tone sequences of varying entropy level, to independently quantify auditory prediction tendency (as the tendency to anticipate low-level acoustic features) for each individual. This measure was then used to predict cortical speech tracking in a multi speaker listening task, where participants listened to audiobooks narrated by a target speaker in isolation or interfered by 1 or 2 distractors. Furthermore, semantic violations were introduced into the story, to also examine effects of word surprisal during speech processing. Our results show that cortical speech tracking is related to prediction tendency. In addition, we find interactions between prediction tendency and background noise as well as word surprisal in disparate brain regions. Our findings suggest that individual prediction tendencies are generalizable across different listening situations and may serve as a valuable element to explain interindividual differences in natural listening situations.
Pharmacokinetics of Afatinib after Intravenous and Oral Administrations in Rats Using Validated UPLC MS/MS Assay
Authors: Almurshedi Alanood S , Radwan Mahasen A , Al Quadeib Bushra , Aldosari Basmah , Alfagih Iman M , Almarshidy Salma S
Published: January 2023

Afatinib is designated as the first-line management therapy for patients with advanced non-small cell lung cancer, and metastatic head and neck cancer. LC coupled to MS/MS can be utilised in therapeutic drug monitoring to ensure optimal use of Afatinib with the reduction of its possible adverse reactions. The aim of this investigation was to determine the pharmacokinetics of Afatinib in rats after single IV (2 mg/kg) and oral (8 mg/kg) doses. Therefore, a selective, sensitive and precise UPLC MS/MS assay thru electrospray ionisation basis with positive ionisation approach was established to measure Afatinib concentrations in the rat. The precision and accuracy of the developed assay method in the concentration range of 10–1000 ng/ml show no significant difference among inter- and-intra-day analysis (P > 0.05). Linearity was detected over the studied range with correlation coefficient, r > 0.995 (n = 6/day). The pharmacokinetics of Afatinib in the rat after a single IV dose showed a mean terminal half-life of 4.6 ± 0.97 h, and a mean clearance 480 ± 80 ml/h/kg. After PO administration, a short absorption phase with a mean Tmax of 1.3 ± 0.6 h with the highest concentration of 513.9 ± 281.1 ng/ml, and the lowest concentration detected after 24 h was 18.8 ± 10.7 ng/ml.
Discordant Clinical and Microbiological Outcomes Are Associated With Late Clinical Relapse in Clinical Trials for Complicated Urinary Tract Infections
Authors: Kadry Nadia , Natarajan Mukil , Bein Edward , Kim Peter , Farley John
Published: January 2023

Background

Current US Food and Drug Administration guidance recommends that the primary endpoint for complicated urinary tract infection clinical trials be a composite of the clinical and microbiological responses, assessed at a fixed point after therapy. Although some participants meet the criteria for clinical success, they do not meet the criteria for microbiological eradication and are classified as treatment failures. These discordant outcomes have raised questions about the utility of the microbiological endpoint.

Methods

We analyzed participant data from 13 phase 3 clinical trials submitted to the US Food and Drug Administration (N = 4842). Outcomes were determined at the test of cure (TOC) visit, recommended to occur at least 5 days after therapy and at the late follow-up visit, recommended to occur 21 to 28 days after randomization. Clinical and microbiological success were defined as the resolution of complicated urinary tract infection symptoms present at study entry, with no new symptoms (clinical cure), and a reduction in density of the original pathogen to <103 CFU/mL on urine culture (microbiological eradication).

Results

Among included participants, 70.7% were concordant successes at the TOC visit, 18.0% were discordant failures (clinical cure/microbiological persistence), and 6.7% were concordant failures (clinical failure/microbiological persistence). Discordant participants were at an increased risk for clinical failure at the late follow-up visit, and the risk of late clinical failure increased with time.

Conclusions

Discordant clinical and microbiological outcomes at the TOC visit were associated with an increased risk of late clinical failure. Microbiological outcomes appear to be an important component of the endpoint.
Genome-wide DNA methylation predicts environmentally driven life history variation in a marine fish
Authors: Venney Clare J , Cayuela Hugo , Rougeux Clément , Laporte Martin , Mérot Claire , Normandeau Eric , Leitwein Maëva , Dorant Yann , Præbel Kim , Kenchington Ellen , Clément Marie , Sirois Pascal , Bernatchez Louis
Published: January 2023

Epigenetic modifications are thought to be one of the molecular mechanisms involved in plastic adaptive responses to environmental variation. However, studies reporting associations between genome-wide epigenetic changes and habitat-specific variations in life history traits (e.g., lifespan, reproduction) are still scarce, likely due to the recent application of methylome resequencing methods to non-model species. In this study, we examined associations between whole genome DNA methylation and environmentally driven life history variation in 2 lineages of a marine fish, the capelin (Mallotus villosus), from North America and Europe. In both lineages, capelin harbor 2 contrasting life history tactics (demersal vs. beach-spawning). Performing whole genome and methylome sequencing, we showed that life history tactics are associated with epigenetic changes in both lineages, though the effect was stronger in European capelin. Genetic differentiation between the capelin harboring different life history tactics was negligible, but we found genome-wide methylation changes in both lineages. We identified 9,125 European and 199 North American differentially methylated regions (DMRs) due to life history. Gene ontology (GO) enrichment analysis for both lineages revealed an excess of terms related to neural function. Our results suggest that environmental variation causes important epigenetic changes that are associated with contrasting life history tactics in lineages with divergent genetic backgrounds, with variable importance of genetic variation in driving epigenetic variation. Our study emphasizes the potential role of genome-wide epigenetic variation in adaptation to environmental variation.
Chromosome-Level Genome Assembly of the Cape Cliff Lizard (Hemicordylus capensis)
Authors: Leitão Henrique G , Diedericks Genevieve , Broeckhoven Chris , Baeckens Simon , Svardal Hannes
Published: January 2023

Squamates represent a highly diverse and species-rich vertebrate group that is remarkably understudied from a genomic perspective. A scarcity of genomic data is particularly evident for scincomorph lizards, which encompass over 10% of all living squamates, and for which high-quality genomic resources are currently lacking. To address this knowledge gap, we present the first chromosome-level reference genome for this group, generated from a male Cape cliff lizard (Hemicordylus capensis), using highly accurate PacBio HiFi long-read sequencing data, long-range Omni-C chromosomal conformation capture data and transcriptomic data for annotation. The rHemCap1.1 genome assembly spans 2.29 Gb, with a scaffold N50 of 359.65 Mb, and includes 25,300 protein-coding genes, with a BUSCO completeness score of 95.5% (sauropsida_odb10). We have generated the most contiguous and complete chromosome-level squamate reference genome assembly publicly available to date. Furthermore, we used short-read resequencing of 35 males and females and applied a differential coverage approach to infer the sex-determination system of the species, which was previously unknown. Our results suggest this species has XX/XY sex chromosomes, representing the first evidence of sex determination in the family Cordylidae. This reference genome will help to establish this species as an evolutionary model for studying variation in body armor, a key trait in cordylids and other squamate groups. Lastly, this is the first squamate reference genome from a continental African species and, as such, represents a valuable resource not only for further evolutionary research in cordylids but also in closely related groups.
Intergenerational Relationships Across Multiple Children and Older Parents’ Depressive Symptoms in China—A Resource Contingency Perspective
Authors: Li Ting , Zhang Yang
Published: January 2023

Objectives

The multidimensional features of intergenerational relationships and the mixed feelings among parents with multiple children complicate how intergenerational relationships shape mental health among older parents. This study explores the patterns of intergenerational relationships among Chinese families with multiple children and their associations with older parents’ depressive symptoms.

Methods

Through 3 waves (2014, 2016, and 2018) of nationally representative longitudinal data obtained from the China Longitudinal Aging Social Survey (CLASS), we used the k-means clustering method and fixed-effects models to address the research questions.

Results

The findings revealed that over 41.64% of older parents had different types of intergenerational relationships with their different children. The closest parent–child relationship type was associated with the lowest levels of depressive symptoms among older parents, whereas the most estranged parent–child relationship type was associated with the highest levels of depressive symptoms. The most estranged parent–child relationship type (i.e., the alienated type) involving one child could reduce the psychological benefits gained through the closest type (i.e., the tight-knit type) involving another child. However, this moderation effect only manifested among socioeconomically privileged older parents.

Discussion

These findings highlight the importance of adopting a systematic view for studies regarding intergenerational relationships. The impacts of a single parent–child relationship on parents can be influenced by other parent–child relationships. Moreover, in the context of the dramatic and uneven social changes throughout China, the interactive features of intergenerational relationships have revealed an emerging strong preference for all-round relational harmony across multiple children, particularly among privileged Chinese families.
Patterns of populist mobilization: comparing narratives on COVID-19 in the global South
Authors: Belder F , Destradi S , Gurol J , Rodríguez C Heras , Kölük M , Martins J , Rogel S , Swarati S
Published: January 2023

This article explores the narratives shaping the official discourse on COVID-19 in five countries governed by populists in different world regions. It is based on the assumption that a crisis like the pandemic constitutes a perfect occasion for populist mobilization, allowing populist leaders to construct reality in their favour by deliberately promoting own narratives about the pandemic, its origin and management. Analyzing 357 original-language speeches and statements by representatives of the populist governments of Brazil, Israel, India, Mexico and Turkey, the article shows that populists in power use crises to mobilize support in very different ways. Surprisingly, most populist governments neither resorted to anti-scientific claims or conspiratorial discourses attributing the crisis to obscure elites, nor blamed minorities not belonging to the ‘true people’. By contrast, except for Bolsonaro in Brazil, all other populist governments tried to mobilize support by emphasizing the strength of the ‘people’ or even by promoting an inclusive discourse of national unity, leaving aside the more divisive elements of their general populist discourse. Based on the cases analysed, the article concludes by developing hypotheses on the possible drivers of such variations in patterns of populist mobilization.
Order, justice and inequality: the curious case of jihadist divine justice
Authors: Mendelsohn Barak
Published: January 2023

Many calls for a just world order discussed in this special section emphasize demands for equality in the name of an underprivileged group. The focus on these equality claims and claimants could create a false impression that justice is an objective term and that justice is necessarily made in the name of equality. In reality, the equation of justice with equality is a very recent development. Throughout history, numerous actors viewed order and justice in regimes of unequal entitlement. Even the weak and disadvantaged often envisioned justice not in equality, but in an order that would place them in a position of superiority. Using evidence from the views of al-Qaeda and the Islamic State on the relation between order, justice and equality, this article shows that for some a just order does not have to be based on equality, and in fact, depends on inequalities. Those who take for granted the idea that a just order requires equality should, thus, recognize that who is deserving and deprived of equality is not the only contested question; the disagreement over whether justice requires equality, or is manifest in inequality, has yet to be settled.
Contesting global justice from the South: redistribution in the international order
Authors: Lorca Arnulf Becker
Published: January 2023

The climate and refugee crises, and of course a global pandemic, attest to the limits that an international order based on sovereign coexistence imposes on efforts to tackle global problems. Not only members of the global civil society, but also states invoke justice to overcome the limits imposed by sovereignty and to enable multilateral cooperation. But what counts as a just solution to global problems? This article shows a sharp North–South divide emerging when the South demands just and equitable solutions that are redistributive from North to South. As the North opposes redistribution, international lawyers and diplomats from the global South have devised legal strategies to circumvent opposition. Rather than appealing only to common goals and cosmopolitan theories demanding deep commitments from states to change the international order, developing countries have sought redistributive opportunities within existing international law. Using their sovereign entitlements, developing countries pursue a combative solidarity to obtain redistribution.