bluuebunny/crossref_metadata_2025 huggingface dataset:
Idiosyncratic media exposures during a pandemic and their link to well-being, cognition, and behavior over time
Authors: Jones Nickolas M. , Thompson Rebecca R. , Holman E. Alison , Silver Roxane Cohen
Published: June 2023

Over the past two decades of research, increased media consumption in the context of collective traumas has been cross-sectionally and longitudinally linked to negative psychological outcomes. However, little is known about the specific information channels that may drive these patterns of response. The current longitudinal investigation uses a probability-based sample of 5,661 Americans measured at the onset of the COVID-19 pandemic to identify a) distinct patterns of information-channel use (i.e., dimensions) for COVID-related information, b) demographic correlates of these patterns, and c) prospective associations of these information channel dimensions with distress (i.e., worry, global distress, and emotional exhaustion), cognition (e.g., beliefs about the seriousness of COVID-19, response efficacy, and dismissive attitudes), and behavior (e.g., engaging in health-protective behaviors and risk-taking behaviors) 6 mo later. Four distinct information-channel dimensions emerged: journalistic complexity; ideologically focused news; domestically focused news; and nonnews. Results indicate that journalistic complexity was prospectively associated with more emotional exhaustion, belief in the seriousness of the coronavirus, response efficacy, engaging in health-protective behaviors, and less dismissiveness of the pandemic. A reliance on conservative-leaning media was prospectively associated with less psychological distress, taking the pandemic less seriously, and engaging in more risk-taking behaviors. We discuss the implications of this work for the public, policy makers, and future research.
Sexual anti-languages on social media
Authors: Lu Chao , Zhang Jingyuan , Zhang Ke
Published: June 2023

The past decades have witnessed a growing preoccupation with gay languages across the world. However, little attention has been devoted to gay language in the Chinese context. To address the gap, this article examined the case of gay language used on a Chinese social media. Specifically speaking, we conducted a corpus-based analysis of sexual anti-languages (SA) on Blued, by following Halliday’s concept of anti-language defined as an extreme case of social dialects and the language of an anti-society. Using a total of 1,744 text-headlines collected from Blued users’ profiles, we identified and grouped Chinese SA into six categorizations. The findings reveal that Blued abounds with SA, each of which has undergone a unique formation process. In the end, we concluded by providing several directions for future research.
Polydom/SVEP1 binds to Tie1 and promotes migration of lymphatic endothelial cells
Authors: Sato-Nishiuchi Ryoko , Doiguchi Masamichi , Morooka Nanami , Sekiguchi Kiyotoshi
Published: June 2023

Polydom is an extracellular matrix protein involved in lymphatic vessel development. Polydom-deficient mice die immediately after birth due to defects in lymphatic vessel remodeling, but the mechanism involved is poorly understood. Here, we report that Polydom directly binds to Tie1, an orphan receptor in the Angiopoietin–Tie axis, and facilitates migration of lymphatic endothelial cells (LECs) in a Tie1-dependent manner. Polydom-induced LEC migration is diminished by PI3K inhibitors but not by an ERK inhibitor, suggesting that the PI3K/Akt signaling pathway is involved in Polydom-induced LEC migration. In line with this possibility, Akt phosphorylation in LECs is enhanced by Polydom although no significant Tie1 phosphorylation is induced by Polydom. LECs also exhibited nuclear exclusion of Foxo1, a signaling event downstream of Akt activation, which was impaired in Polydom-deficient mice. These findings indicate that Polydom is a physiological ligand for Tie1 and participates in lymphatic vessel development through activation of the PI3K/Akt pathway.
Spin Hall effects in the sky
Authors: Andersson Lars , Oancea Marius A
Published: June 2023

In many areas of physics, the propagation of wave packets carrying intrinsic angular momentum is generally influenced by spin–orbit interactions. This is the main mechanism behind spin Hall effects, which result in wave packets following spin-dependent trajectories. Spin Hall effects have been observed in several experiments for electrons in condensed matter systems and for light propagating in inhomogeneous optical media. Similar effects have also been predicted for wave packets propagating in inhomogeneous gravitational fields. We give a brief introduction to gravitational spin Hall effects, emphasizing the analogies with the spin Hall effect of light in optics. Furthermore, we review the most promising astrophysical avenues that could lead to experimental observations of the gravitational spin Hall effect.
Physical properties of the swept arc channel in the context of lightning strikes to aircraft
Authors: Andraud V , Martins R Sousa , Zaepffel C , Landfried R , Testé P , Lalande P
Published: June 2023

During an in-flight lightning strike, the relative motion between the arc channel and the aircraft causes a sweeping of the attachment point on the aircraft skin. To predict the behaviour of the arc channel and therefore the potential locations for further restrikes, this study aims at investigating the phenomenon with an innovative method for producing sweeping arcs based on a stationary arc and an electromagnetic launcher propelling aeronautical samples. This article focuses on characterisation of the arc channel, aiming at establishing the evolution of its physical properties during swept-stroke for various experimental conditions. Firstly, the experimental coupling of the lightning generator with the electromagnetic launcher and with a wind tunnel is described with a discussion on the representativeness of the experiment. Then, high-speed cameras and voltage and current probes are used to measure the electrical and geometrical behaviour of the electric arc channel during a swept-stroke. The shape, the length, the voltage and the power evolution of the arc channel are evaluated for different input parameters such as speed, polarity, arc current and sample length. Furthermore, the influence of these parameters on the temperature of the arc channel is studied, resorting to an optical emission spectroscopy technique. The results are presented and discussed with the objective of providing a physical insight into arc elongation phenomenology during a swept-stroke.
Effect of atomic anti-site disorder on the anisotropic magnetoresistance in Fe50Co50 alloys
Authors: Zhang Mingsong , Peng Bin , Zhang Wanli , Zhang Wenxu
Published: June 2023

In order to understand the anti-site disorder effect on the anisotropic magnetoresistance (AMR) of alloys,

Fe

50

C
o

50

alloys were studied in this work using the fully relativistic spin-polarized Korringa–Kohn–Rostoker method. The anti-site disorder was modeled by interchanging Fe and Co atoms and treated by the coherent potential approximation. It is found that the anti-site disorder broadens the spectral function and decreases the conductivity. Our work emphasizes that the absolute variations of resistivity under magnetic moment rotation are less affected by atomic disorder. The annealing procedure improves the AMR by reduction of the total resistivity. At the same time, we also find that the fourth-order term in the angular dependent resistivity becomes weaker when the disorder increases, resulting from increased scattering of the states around the band-crossing.
Stability and mixing behavior of vanadium-iron oxide monolayers on Pt(111) and Ru(0001) substrates
Authors: Goniakowski J , Wemhoff P I , Nilius N , Noguera C
Published: June 2023

Cation mixing is a well-recognized means to obtain oxides of desired functionality with predetermined structure and stoichiometry, which yet has been only little analyzed at the nanoscale. In this context, we present a comparative analysis of the stability and mixing properties of O-poor and O-rich two-dimensional V–Fe oxides grown on Pt(111) and Ru(0001) surfaces, with the aim of gaining an insight into the role of substrate and oxygen conditions on the accessible Fe contents. We find that due to the high oxygen affinity of the Ru substrate, the mixed O-rich layers are highly stable while the stability of O-poor layers is limited to inaccessibly oxygen-poor environments. In contrast, on the Pt surface, O-poor and O-rich layers coexist with, however, a much lower Fe content in the O-rich phase. We show that cationic mixing (formation of mixed V–Fe pairs) is favored in all considered systems. It results from local cation–cation interactions, reinforced by a site effect in O-rich layers on the Ru substrate. In O-rich layers on Pt, Fe–Fe repulsion is so large that it precludes the possibility of substantial Fe content. These findings highlight the subtle interplay between structural effects, oxygen chemical potential, and substrate characteristics (work function and affinity towards oxygen), which governs the mixing of complex 2D oxide phases on metallic substrates.
The scientific basis for the use of the linear no-threshold (LNT) model at low doses and dose rates in radiological protection
Authors: Laurier Dominique , Billarand Yann , Klokov Dmitry , Leuraud Klervi
Published: June 2023

The linear no-threshold (LNT) model was introduced into the radiological protection system about 60 years ago, but this model and its use in radiation protection are still debated today. This article presents an overview of results on effects of exposure to low linear-energy-transfer radiation in radiobiology and epidemiology accumulated over the last decade and discusses their impact on the use of the LNT model in the assessment of radiation-related cancer risks at low doses. The knowledge acquired over the past 10 years, both in radiobiology and epidemiology, has reinforced scientific knowledge about cancer risks at low doses. In radiobiology, although certain mechanisms do not support linearity, the early stages of carcinogenesis comprised of mutational events, which are assumed to play a key role in carcinogenesis, show linear responses to doses from as low as 10 mGy. The impact of non-mutational mechanisms on the risk of radiation-related cancer at low doses is currently difficult to assess. In epidemiology, the results show excess cancer risks at dose levels of 100 mGy or less. While some recent results indicate non-linear dose relationships for some cancers, overall, the LNT model does not substantially overestimate the risks at low doses. Recent results, in radiobiology or in epidemiology, suggest that a dose threshold, if any, could not be greater than a few tens of mGy. The scientific knowledge currently available does not contradict the use of the LNT model for the assessment of radiation-related cancer risks within the radiological protection system, and no other dose-risk relationship seems more appropriate for radiological protection purposes.
A heterogeneous hardware scheme for accelerating the image reconstruction process of electrical tomography
Authors: Cui Ziqiang , Sun Can , Yang Pengyu , Wang Huaxiang
Published: June 2023

Currently, most of the electrical tomography measurement systems are developed on microcontroller units, digital signal processors, or field programmable gate arrays, whereas image reconstruction and display functions are implemented in a separate host computer. Therefore, the complete hardware usually comprises a measurement system and an image reconstruction computer. The current trend is to develop industrial standard electrical tomography systems, which can implement the image reconstruction and measurement functions into an integrated processor/chip. However, most of the above mentioned processors do not provide the necessary computational resources as required by the computationally intensive image reconstruction function. This paper describes a hardware scheme for implementing image reconstruction functions on a heterogeneous hardware platform, wherein the processor system and programmable logics (PLs) are tightly coupled and can achieve better resource utilization and overall system performance. By adopting a high-level synthesis method, the image reconstruction algorithms can be realized jointly by the PLs and processor system. In this hardware scheme, the algorithms are properly optimized to achieve better data throughput and execution efficiency, that is, by utilizing parallel computation in PLs. Details of the hardware scheme and method of accelerating the image reconstruction process are presented in this paper. Implementation results show that the proposed heterogeneous hardware scheme can achieve the image reconstruction rates of 24 and 1700 frames per second while employing the iterative and non-iterative algorithms, respectively.
MST resistive wall tearing mode simulations
Authors: Strauss H R , Chapman B E , Hurst N C
Published: June 2023

The Madison Symmetric Torus (MST) is a toroidal device that, when operated as a standard tokamak, does not have major disruptions. Unlike most tokamaks, the MST plasma is surrounded by a close fitting highly conducting wall, with a resistive wall penetration time two orders of magnitude longer than in JET or DIII-D, and three times longer than in ITER. The MST can operate with edge

q
a

⩽
2

, unlike standard tokamaks. Simulations presented here indicate that the MST is unstable to resistive wall tearing modes (RWTMs) and resistive wall modes (RWMs). They could in principle cause disruptions, but the predicted thermal quench (TQ) time is much longer than the experimental pulse time. If the MST TQ time were comparable to measurements in JET and DIII-D, theory and simulations predict that disruptions would have been observed in MST. This is consistent with the modeling herein, predicting that disruptions are caused by RWTMs and RWMs. In the low

q
a

∼
2

regime of MST, the RWTM asymptotically satisfies the RWM dispersion relation. The transition from RWTM to RWM occurs smoothly at

q
a

=
m

/

n

, where

m
,
n

are poloidal and toroidal mode numbers.
Periodic orbits in a near Yang-Mills potential
Authors: Contopoulos G , Harsoula M
Published: June 2023

We study numerically the orbits in the Yang-Mills (YM) potential

V
=

1

2

x

2

y

2

and in the potentials of the general form

V
=

1

2

[
α
(

x

2

+

y

2

)
+

x

2

y

2

]

. We found that the stable period-9 periodic orbit of the YM potential belongs to a family of orbits that bifurcates from a basic period-9 family of the general form of the potential V, when α is slightly above zero. This basic period-9 family and its bifurcations exist only up to a maximum value of

α
=

α

max

. We calculate the Hénon stability index of these orbits. The pattern of the stability diagram is the same for all the symmetric orbits of odd periods 3,5,7,9 and 11, that we have found. We also found the stability diagrams for asymmetric orbits of period 2,3,4,5 which have again the same pattern. All these orbits are unstable for α=0 (YM potential) except for the stable orbits of period-9 and some orbits with multiples of 9 periods.
Demonstration of indirectly driven implosion experiments with cryogenic pure deuterium layered capsules on the Shenguang Laser Facility
Authors: Ge Fengjun , Pu Yudong , Wang Kai , Huang Tianxuan , Sun Chuankui , Qi Xiaobo , Wu Changshu , Gu Jianfa , Chen Zhongjin , Yan Ji , Jiang Wei , Yang Dong , Dong Yunsong , Wang Feng , Zhou Shiyang , Ding Yongkun
Published: June 2023

To achieve ignition in a laboratory via inertial confinement fusion, a spherical capsule containing a frozen layer of deuterium and tritium (DT) fuel will be imploded on an MJ-class laser facility. However, if pure deuterium fuel can be used in place of DT fuel for tuning shots, we may speed up the process of ignition experiments while maintaining the surrogacy by significantly reducing the level of radioactivity. Unfortunately, it has long been assumed that neither the approach of symmetrical infrared irradiation used in the Omega direct-drive experiments nor the method of beta-layering used in the NIF experiments can be used to smooth the D layered capsule in cylindrical hohlraums. The difficulty in smoothing the D ice layer prevents us from taking advantage of cryogenic D-layered capsules in indirect-drive experiments. In this work, we established a procedure to form a uniform D-ice layer for capsules held in cylindrical hohlraums and carried out indirect-drive cryogenic D-layered implosion experiments using a squared laser pulse on the Shenguang Laser Facility in China. The quality of the D ice layer is characterized by phase-contrast imaging. The root-mean-square of the power spectrum in modes 2–100 is about 2.2 μm. The implosion performance of the D-layered capsules is close to the prediction of one-dimensional simulations. The measured neutron yield and areal fuel density are 1.2 × 1011 and 80 mg cm−2, respectively.
Impacts of green rating systems on the economy and society
Authors: Doan Dat Tien , Qin Lang
Published: June 2023

This study examines the impact of green rating systems on the construction industry in sustainable development. Five widely used green rating systems, BREEAM, LEED, Green Star, Green Mark and CASBEE, were examined to identify their effectiveness in promoting sustainable construction practices, specifically in the economic and social aspects. Results revealed that all rating systems offer a comprehensive environmental performance assessment but have varying degrees of success in the rest pillars of sustainability. The rating systems have notably influenced the construction sector, motivating developers and designers to integrate sustainable elements into their structures. The advantages of such rating systems extend beyond singular buildings, benefiting society as well by decreasing environmental harm, advancing the health and well-being of occupants, and stimulating economic progress. Furthermore, the study suggests that construction companies that design and build green-certified buildings have a competitive advantage in the market. Overall, the study highlights the benefits of using green rating systems to promote their wider adoption in the construction industry.
A non-invasive computational method to determine the directionality of skin tension lines
Authors: Roy Ashutosh , Vemaganti Kumar
Published: June 2023

The topography of human skin surface has cutaneous lines or skin tension lines whose orientation depends on factors like age, cosmetic use, environmental conditions, etc. Characterizing the orientation of these lines is of immense importance for the cosmetics industry, medical technology and applications like haptics. In this study we propose a simple method based on the ratio of the correlation length to the root mean square roughness along several profiles to characterize the directionality of these lines. This ratio is then normalized across all the profiles leading to a polar plot that varies between 0 and 1, with the major orientation appearing at a value of 1. Our results show that this non-invasive computational approach can be applied to skin roughness data or image intensities. As a practical application of the approach, we demonstrate its ability to capture changes in skin tension line orientation with age, using roughness data from the literature.
In-vitro experiments on bio-functional calcium phosphate based coatings on titanium dental implant
Authors: Balamurugan P , Selvakumar N
Published: June 2023

Dental implants are a revolution in dentistry, but certain deficiencies still need to be addressed. One of the most severe threats to the success of dental implants is peri-implant infection. Existing coatings on titanium (Ti-6Al-4V) alloy surfaces rapidly lose antibacterial efficacy, reducing their ability to prevent peri-implant infectious disease. The objective of this paper was to investigate the dissolution capabilities and film properties of calcium phosphate (CaP) based layers on a titanium (Ti-6Al-4V) alloy surface produced with the radiofrequency magnetron sputtering method. These coatings have demonstrated good osseointegration capability due to their similarity to bone mineral matter. The bioactive coating materials are calcium phosphate, zinc chloride, and silver nitrate. Microstructural investigations of coated components were assessed using Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), Energy Dispersive (EDX) analysis, and Atomic Force Microscopy (AFM). Bacterial adhesion to biomaterials is still a major issue when it comes to medical equipment. Antimicrobial peptides have generated interest due to the rise in antibiotic-resistant bacteria. The fact that there are concerns regarding the development of antibiotic resistance due to the development of traditional antibiotics to prevent illness reflects the complexity of the matter.

The coated titanium samples were inoculated in nutrient broth and incubated at 37 °C for 24 h. The samples were tested against Staphylococcus aureus and Staphylococcus epidermidis for 72 h. A standard row containing between 1 * 105 CFU ml−1 and 1 * 107 CFU ml−1of fresh exponential culture was prepared. The plates were cultured at 37 °C and shaken (100 rpm) while the OD600 was monitored every 30 min. After 24 h, Staphylococcus aureus inhibition was higher than 70% in S4, and Staphylococcus epidermidis inhibition ranged from 60 to 70% in S4. Antimicrobial activity was found in the calcium phosphate coated samples (S4) against gram-positive Staphylococcus epidermidis and Staphylococcus aureus bacteria. The antimicrobial evaluation showed that titanium made with bioactive coating inhibited bacterial growth and biofilm formation.
Effect of precipitates evolution on mechanical properties of Al 7050 alloy during secondary aging
Authors: Zhao Wei , Wang Longxiang , Ren Yonghai , He Bing , Han Senlin , Xu Pingwei , Liang Yu
Published: June 2023

The microstructure and mechanical properties were investigated in Al 7050 alloy after aging treatments. Results showed that refining the η′ precipitates and increasing the proportion of the η′ precipitates significantly improved its mechanical properties. High density dislocations created by cold deformation promoted the nucleation of the main strengthening η′ phase during aging. High-density fine precipitates was created, which increases the yield strength. However, the strength of the deformed sample decreased by ∼31.6% after the secondary aging at 157 °C, with more degradation than other samples. Microstructure study presented that some precipitates were composed of two distinctive areas. An in situ transformation from a simple triclinic Mg2Zn3 to the η phase (MgZn2) was observed during the secondary aging. The loss in strength after secondary aging at 157 °C proved that the η′ precipitates transformed into the η precipitates by absorbing solute atoms at a temperature lower than equilibrium precipitation temperature of η precipitates. The residual high-density dislocations in the cold-deformed samples promoted the diffusion of solute atoms, which accelerated the η′ → η transformation during the secondary aging. Significant reduction in the volume of η′ precipitations led to the rapid deterioration of mechanical properties.
Modification of PVDF membrane for harvesting of Nannochloropsis sp. and its cleaning results
Authors: Romadiansyah Taufik Qodar , Ali Badrut Tamam Ibnu , Lestari Widi Citra , Permatasari Marisa , Ermavitalini Dini , Widiastuti Nurul
Published: June 2023

One of the biggest challenges in implementing microalgae-based biofuels is the effective harvesting process. Filtration membrane has become one of the flexible methods in microalgae harvesting. This study investigated the harvesting of Nannochloropsis sp. using a modified PVDF membrane at various LiCl as an additive with N-methyl-2-pyrrolidone (NMP) solvent. Harvesting of Nannochloropsis sp. with PVDF membrane has never been reported before. The addition of LiCl can improve the performance of PVDF membrane due to LiCl has a great affinity for water, resulted in inducing the formation of the pore structure of membrane. The optimum membrane composition was determined at various LiCl additive from 1% to 3% (w/w). The hydrophilicity of the membrane increased as indicated by the increasing of water permeance, which were 516, 546, 660, and 614 l m−2h−1 bar−1 for neat PVDF, PVDF/LiCl-1, PVDF/LiCl-2, and PVDF/LiCl-3 membrane, respectively. PVDF/LiCl-2 membrane showed the highest water permeance and the highest total average permeance (150 l m−2h−1 bar−1) with 100% rejection of Nannochloropsis sp. harvesting. The membranes was cleaned using sodium hypochlorite, citric acid, and nitric acid. The SEM results showed that the membrane after cleaning appears the algae particles in the membrane pore. Furthermore, algae particles were almost not visible on cleaned membrane. The FTIR results showed an absorption at 3401 cm−1, which was a characteristic of the hydrogen N–H bond, also including a typical amide uptake (C=O) at 1648 cm−1 indicating protein appearance. Moreover, the cleaned membrane did not appear any absorption that indicates the foulant.
Different healing characteristics of thiol-bearing molecules on CVD-grown MoS2
Authors: Feraco Giovanna , Luca Oreste De , Syari’ati Ali , Hameed Sardar , El Yumin Abdurrahman Ali , Ye Jianting , Agostino Raffaele G , Rudolf Petra
Published: June 2023

Vacancies in atomically thin molybdenum disulphide play an essential role in controlling its optical and electronic properties, which are crucial for applications in sensorics, catalysis or electronics. For this reason, defect engineering employing thiol-terminated molecules is used to heal and/or functionalise defective nanosheets. In this work, chemical vapour deposition-grown MoS2 with different defect densities was functionalised with three molecules: 4-aminothiophenol (ATP), biphenyl-4-thiol (BPT) and 4-nitrothiophenol (NTP). The molecules’ efficacy in functionalising MoS2 was probed by x-ray photoelectron, Raman and photoluminescence (PL) spectroscopy. The results show that exposing a defective single layer of MoS2 to either ATP, BPT or NTP molecules heals the defects, however the chemical structure of these molecules affects the optical response and only for BPT the PL intensity increases.
AiiDA-defects: an automated and fully reproducible workflow for the complete characterization of defect chemistry in functional materials
Authors: Muy Sokseiha , Johnston Conrad , Marzari Nicola
Published: June 2023

Functional materials that enable many technological applications in our everyday lives owe their unique properties to defects that are carefully engineered and incorporated into these materials during processing. However, optimizing and characterizing these defects is very challenging in practice, making computational modelling an indispensable complementary tool. We have developed an automated workflow and code to accelerate these calculations (AiiDA-defects), which utilises the AiiDA framework, a robust open-source high-throughput materials informatics infrastructure that provides workflow automation while simultaneously preserving and storing the full data provenance in a relational database that is queryable and traversable. This paper describes the design and implementation details of AiiDA-defects, the models and algorithms used, and demonstrates its use in an application to fully characterize the defect chemistry of the well known solid-state Li-ion conductors LiZnPS4. We anticipate that AiiDA-defects will be useful as a tool for fully automated and reproducible defect calculations, allowing detailed defect chemistry to be obtained in a reliable and high-throughput way, and paving the way toward the generation of defects databases for accelerated materials design and discovery.
Efficacy and Safety of Tapencarium (RZL-012) in Submental Fat Reduction
Authors: Shridharani Sachin M , Dayan Steven , Biesman Brian , Cohen Joel , Downie Jeanine , Jones Derek , Shamban Ava , Fabi Sabrina , Yoelin Steve , Fagien Steven , Ablon Glynis , Gold Michael , Gueta Racheli , Walker Patricia
Published: June 2023

Background

Tapencarium (RZL-012) (5-(3.6-dibromo-9H-carbazol-9-yl)-N, N, N-trimethylpentan-1-aminium chloride) is a novel injectable synthetic molecule with cytolytic properties, capable of reducing subcutaneous fat volume.

Objectives

The goal of this 3-armed, randomized, double-blind, placebo-controlled phase 2b study was to determine the safety and efficacy of low- and high-dose RZL-012 vs placebo on submental fat (SMF) reduction.

Methods

Patients (n = 151, age 18-65 years) with excess SMF received a single treatment session of RZL-012 or placebo in the submental area, after which they were monitored for 84 days. SMF was assessed at baseline and after dosing with newly developed scales, namely the Clinician Chin Assessment Tool (C-CAT) and Subject Chin Assessment Tool (S-CAT). SMF was also assessed by magnetic resonance imaging (MRI) at screening and on Day 84 after treatment.

Results

The proportion of patients who had a 1-grade or 2-grade improvement in C-CAT and/or S-CAT on Day 84 vs baseline was significantly higher in the high-dose RZL-012 group vs the placebo group (P < .002). The relative percentage reduction in MRI-measured SMF volume (Day 84 vs screening) was significantly greater in the high-dose RZL-012 group vs the low-dose RZL-012 or the placebo group (P < .0001). Local injection site reactions were the most common adverse events (AEs).

Conclusions

A single administration of RZL-012 into SMF resulted in significant improvement in submental appearance as assessed by clinicians, patients, and MRI. From a safety perspective, there were no serious AEs and no clinically significant changes in vital signs or laboratory tests over the course of the study.

Level of Evidence: 1
UNRES-GPU for physics-based coarse-grained simulations of protein systems at biological time- and size-scales
Authors: Ocetkiewicz Krzysztof M , Czaplewski Cezary , Krawczyk Henryk , Lipska Agnieszka G , Liwo Adam , Proficz Jerzy , Sieradzan Adam K , Czarnul Paweł
Published: June 2023

The UNited RESisdue (UNRES) package for coarse-grained simulations, which has recently been optimized to treat large protein systems, has been implemented on Graphical Processor Units (GPUs). An over 100-time speed-up of the GPU code (run on an NVIDIA A100) with respect to the sequential code and an 8.5 speed-up with respect to the parallel Open Multi-Processing (OpenMP) code (run on 32 cores of 2 AMD EPYC 7313 Central Processor Units (CPUs)) has been achieved for large proteins (with size over 10 000 residues). Due to the averaging over the fine-grain degrees of freedom, 1 time unit of UNRES simulations is equivalent to about 1000 time units of laboratory time; therefore, millisecond time scale of large protein systems can be reached with the UNRES-GPU code.

Availability and implementation

The source code of UNRES-GPU along with the benchmarks used for tests is available at https://projects.task.gda.pl/eurohpcpl-public/unres.
BBmix: a Bayesian beta-binomial mixture model for accurate genotyping from RNA-sequencing
Authors: Vigorito Elena , Barton Anne , Pitzalis Costantino , Lewis Myles J , Wallace Chris
Published: June 2023

Motivation

While many pipelines have been developed for calling genotypes using RNA-sequencing (RNA-Seq) data, they all have adapted DNA genotype callers that do not model biases specific to RNA-Seq such as allele-specific expression (ASE).

Results

Here, we present Bayesian beta-binomial mixture model (BBmix), a Bayesian beta-binomial mixture model that first learns the expected distribution of read counts for each genotype, and then deploys those learned parameters to call genotypes probabilistically. We benchmarked our model on a wide variety of datasets and showed that our method generally performed better than competitors, mainly due to an increase of up to 1.4% in the accuracy of heterozygous calls, which may have a big impact in reducing false positive rate in applications sensitive to genotyping error such as ASE. Moreover, BBmix can be easily incorporated into standard pipelines for calling genotypes. We further show that parameters are generally transferable within datasets, such that a single learning run of less than 1 h is sufficient to call genotypes in a large number of samples.

Availability and implementation

We implemented BBmix as an R package that is available for free under a GPL-2 licence at https://gitlab.com/evigorito/bbmix and https://cran.r-project.org/package=bbmix with accompanying pipeline at https://gitlab.com/evigorito/bbmix_pipeline.
410 Dupilumab treatment reduces total IgE levels in patients 6 months and older with moderate-to-severe atopic dermatitis
Authors: Siegfried Elaine C , Cork Michael J , Boguniewicz Mark  , Deleuran Mette , Simpson Eric L   , Chen Zhen , Clearfield Drew , Shah Parul , Marco Ainara Rodríguez
Published: June 2023

Atopic dermatitis (AD) is a type 2 inflammatory disease characterized by elevations in several biomarkers including serum IgE—a key downstream mediator in the type 2 adaptive immune response. Patients with moderate-to-severe AD were enrolled for 16 weeks in any of six randomized, placebo-controlled, phase 3 studies: in LIBERTY AD PRESCHOOL, (NCT03346434 part B) patients aged 6 months to 5 years were treated with dupilumab 200/300 mg every 4 weeks (q4w) + topical corticosteroids (TCS; n = 83) or placebo + TCS (n = 79); in LIBERTY AD PEDS (NCT03345914), patients aged 6–11 years were treated with dupilumab + TCS [100/200 mg q2w (n = 122), 300 mg q4w (n = 122)] or placebo + TCS (n = 123); in LIBERTY AD ADOL (NCT03054428), patients aged 12–17 years were treated with dupilumab [200/300 mg q2w (n = 82), 300 mg q4w (n = 83)] or placebo (n = 85); and in LIBERTY AD CHRONOS/SOLO1/SOLO2 (NCT02260986/NCT02277743/NCT02277769, pooled), patients aged ≥18 years were treated with dupilumab [300 mg q2w (n = 563),300 mg qw (n = 781) ] or placebo (n = 775). The TCS were allowed in CHRONOS only. At Week 16, dupilumab treatment significantly (P < 0.0001) reduced median total serum IgE levels [kU/L (IQR)] compared with placebo in patients aged 6 months to 5 years [843 (207–3300) vs. 3625 (540.5–8585)], 6–11 years [1519 (532–3808) vs. 3862 (1166–9999)], 12–17 years [1391 (436–2842) vs. 4569 (800.5–10000)] and ≥18 years [1340 (229–4360) vs. 3722 (555–10000)]. Dupilumab treatment reduced total serum IgE levels in patients aged 6 months and older with moderate-to-severe AD. Overall safety was consistent with the known dupilumab safety profile.
431 Assessment of racial and ethnic differences of atopic dermatitis severity and treatment patterns in a diverse outpatient cohort in the United States
Authors: Sanfilippo Eric , Iyer Sneha , Patel Nisha , Silverberg Jonathan I
Published: June 2023

Previous population-based studies in the USA found racial and ethnic differences of atopic dermatitis (AD) severity and treatment patterns. It is unclear whether these differences are from differences of disease characteristics or disparities. This study aims to examine racial and ethnic differences in severity and treatment patterns in a diverse outpatient patient cohort of patients with AD (n = 833). A retrospective observational study was performed of patients with physician-diagnosed atopic AD from a large metropolitan tertiary care medical center. Medical records were reviewed for race, ethnicity, disease severity and use of therapies from 10/01/2015-10/1/2021. Atopic dermatitis cases were identified using Hanifin–Rajka criteria. Chi-square or Fisher’s exact tests or were used to assess associations of race and ethnicity with AD severity. Generalized linear models were used to assess interactions of race or ethnicity with gender or age as predictors of individual treatments. There were no significant associations of body surface area (BSA; Fisher’s exact test, P = 0.19 and P = 0.44) or physician’s global assessment (PGA; P = 0.63 and P = 0.57) with race or ethnicity; nor interactions of race/ethnicity with gender or age as predictors of BSA or PGA. Asian and multiracial/other patients were more likely than White or Black patients to use topical calcineurin inhibitors (Chi-square, P = 0.01). Dupilumab use differed by race (Multiracial/other = 35.0%; White = 20.1%; Asian = 15.7%; Black = 13.6%; Chi-square, P = 0.03), but not ethnicity (P = 0.88). Use of oral corticosteroids (Chi-square, P = 0.74), immunosuppressants (P = 0.98) or GABAergics (P = 0.16), or NBUVB (P = 0.42) did not differ by race. There were no statistical interactions of race or ethnicity with gender or age as predictors of treatment use. This study demonstrates that AD severity and specific treatments did not differ overall between racial and ethnic groups in this diverse urban academic cohort.
Social Care Responses to Children who Experience Criminal Exploitation and Violence: The Conditions for a Welfare Response
Authors: Lloyd Jenny , Manister Molly , Wroe Lauren
Published: June 2023

This article explores social care responses to children experiencing criminal exploitation and violence. The article draws on data from two children’s social care departments in England applying a Contextual Safeguarding framework to extra-familial harm. Using evidence from interviews, focus groups, meeting observations and two peer assessments, the article explores factors that facilitate welfare approaches when children commit crimes and those conditions that undermine welfare approaches. The findings outline five conditions which facilitate or inhibit welfare responses including: whether legal rights promote the best interests of the child, if harm reduction prioritises a child’s needs, if language is underpinned by caring intention, the extent that systems harm is recognised and addressed and how practitioners gain knowledge of young people. The discussion introduces a welfare framework for social workers to define and describe what the conditions for welfare responses can constitute.
Efficacy and safety of MAS825 (anti-IL-1β/IL-18) in COVID-19 patients with pneumonia and impaired respiratory function
Authors: Hakim Alex D , Awili Mustafa , O’Neal Hollis R , Siddiqi Omar , Jaffrani Naseem , Lee Richard , Overcash Jeffrey S , Chauffe Ann , Hammond Terese C , Patel Bela , Waters Michael , Criner Gerard J , Pachori Alok , Junge Guido , Levitch Rafael , Watts Jen , Koo Philip , Sengupta Tirtha , Yu Lili , Kiffe Michael , Pinck Anne , Stein Richard R , Bendrick-Peart Jamie , Jenkins Janet , Rowlands Marianna , Waldron-Lynch Frank , Matthews Jesse
Published: June 2023

MAS825, a bispecific IL-1β/IL-18 monoclonal antibody, could improve clinical outcomes in COVID-19 pneumonia by reducing inflammasome-mediated inflammation. Hospitalized non-ventilated patients with COVID-19 pneumonia (n = 138) were randomized (1:1) to receive MAS825 (10 mg/kg single i.v.) or placebo in addition to standard of care (SoC). The primary endpoint was the composite Acute Physiology and Chronic Health Evaluation II (APACHE II) score on Day 15 or on the day of discharge (whichever was earlier) with worst-case imputation for death. Other study endpoints included safety, C-reactive protein (CRP), SARS-CoV-2 presence, and inflammatory markers. On Day 15, the APACHE II score was 14.5 ± 1.87 and 13.5 ± 1.8 in the MAS825 and placebo groups, respectively (P = 0.33). MAS825 + SoC led to 33% relative reduction in intensive care unit (ICU) admissions, ~1 day reduction in ICU stay, reduction in mean duration of oxygen support (13.5 versus 14.3 days), and earlier clearance of virus on Day 15 versus placebo + SoC group. On Day 15, compared with placebo group, patients treated with MAS825 + SoC showed a 51% decrease in CRP levels, 42% lower IL-6 levels, 19% decrease in neutrophil levels, and 16% lower interferon-γ levels, indicative of IL-1β and IL-18 pathway engagement. MAS825 + SoC did not improve APACHE II score in hospitalized patients with severe COVID-19 pneumonia; however, it inhibited relevant clinical and inflammatory pathway biomarkers and resulted in faster virus clearance versus placebo + SoC. MAS825 used in conjunction with SoC was well tolerated. None of the adverse events (AEs) or serious AEs were treatment-related.
Loss of a Loved One: An Empirical Study of Pain and Suffering Awards in Wrongful Death Cases in China
Authors: Ding Chunyan , Zhi Pei
Published: June 2023

This article presents the first empirical evidence on the Chinese judicial assessment of pain and suffering damages for wrongful death. Drawing upon 1,225 Chinese judicial decisions of medical negligence resulting in a patient’s wrongful death, it investigates the empirical effects of various guiding factors that the Supreme People’s Court requires lower courts to consider when awarding the pain and suffering damages, and further tests the deep pockets theory and the anchoring effect theory in the real-life setting of Chinese wrongful death litigation. Based on regression analysis, this study finds that the awarded economic damages, the causal contribution of the defendant’s negligence, and the living standard of the court’s locality positively correlate with the amount of pain and suffering damages in wrongful death cases. It also finds empirical evidence supporting the deep pockets effect and the anchoring effect in Chinese courts’ awarding pain and suffering damages for wrongful death.
A body composition model with multiple storage compartments for polar bears (Ursus maritimus)
Authors: Penk Stephanie R , Sadana Pranav , Archer Louise C , Pagano Anthony M , Cattet Marc R L , Lunn Nicholas J , Thiemann Gregory W , Molnár Péter K
Published: June 2023

Climate warming is rapidly altering Arctic ecosystems. Polar bears (Ursus maritimus) need sea ice as a platform from which to hunt seals, but increased sea-ice loss is lengthening periods when bears are without access to primary hunting habitat. During periods of food scarcity, survival depends on the energy that a bear has stored in body reserves, termed storage energy, making this a key metric in predictive models assessing climate change impacts on polar bears. Here, we developed a body composition model for polar bears that estimates storage energy while accounting for changes in storage tissue composition. We used data of dissected polar bears (n = 31) to link routinely collected field measures of total body mass and straight-line body length to the body composition of individual bears, described in terms of structural mass and two storage compartments, adipose and muscle. We then estimated the masses of metabolizable proteins and lipids within these storage compartments, giving total storage energy. We tested this multi-storage model by using it to predict changes in the lipid stores from an independent dataset of wild polar bears (n = 36) that were recaptured 8–200 days later. Using length and mass measurements, our model successfully predicted direct measurements of lipid changes via isotopic dilutions (root mean squared error of 14.5 kg). Separating storage into two compartments, and allowing the molecular composition of storage to vary, provides new avenues for quantifying energy stores of individuals across their life cycle. The multi-storage body composition model thus provides a basis for further exploring energetic costs of physiological processes that contribute to individual survival and reproductive success. Given bioenergetic models are increasingly used as a tool to predict individual fitness and population dynamics, our approach for estimating individual energy stores could be applicable to a wide range of species.
Influence of cusp morphology and sex on quantitative valve composition in severe aortic stenosis
Authors: Patel Kush P , Lin Andrew , Kumar Niraj , Esposito Giulia , Grodecki Kajetan , Lloyd Guy , Mathur Anthony , Baumbach Andreas , Mullen Michael J , Williams Michelle C , Newby David E , Treibel Thomas A , Dweck Marc R , Dey Damini
Published: June 2023

Aims

Aortic stenosis is characterized by fibrosis and calcification of the valve, with a higher proportion of fibrosis observed in women. Stenotic bicuspid aortic valves progress more rapidly than tricuspid valves, which may also influence the relative composition of the valve. We aimed to investigate the influence of cusp morphology on quantitative aortic valve composition quantified from contrast-enhanced computed tomography angiography in severe aortic stenosis.

Methods and results

Patients undergoing transcatheter aortic valve implantation with bicuspid and tricuspid valves were propensity matched 1:1 by age, sex, and comorbidities. Computed tomography angiograms were analysed using semi-automated software to quantify the fibrotic and calcific scores (volume/valve annular area) and the fibro-calcific ratio (fibrotic score/calcific score). The study population (n = 140) was elderly (76 ± 10 years, 62% male) and had a peak aortic jet velocity of 4.1 ± 0.7 m/s. Compared with those with tricuspid valves (n = 70), patients with bicuspid valves (n = 70) had higher fibrotic scores [204 (interquartile range 118–267) vs. 144 (99–208) mm3/cm2, P = 0.006] with similar calcific scores (P = 0.614). Women had greater fibrotic scores than men in bicuspid [224 (181–307) vs. 169 (109–247) mm3/cm2, P = 0.042] but not tricuspid valves (P = 0.232). Men had greater calcific scores than women in both bicuspid [203 (124–355) vs. 130 (70–182) mm3/cm2, P = 0.008] and tricuspid [177 (136–249) vs. 100 (62–150) mm3/cm2, P = 0.004] valves. Among both valve types, women had a greater fibro-calcific ratio compared with men [tricuspid 1.86 (0.94–2.56) vs. 0.86 (0.54–1.24), P = 0.001 and bicuspid 1.78 (1.21–2.90) vs. 0.74 (0.44–1.53), P = 0.001].

Conclusions

In severe aortic stenosis, bicuspid valves have proportionately more fibrosis than tricuspid valves, especially in women.
The relevance of competing risk adjustment in cardiovascular risk prediction models for clinical practice
Authors: Hageman Steven H J , Dorresteijn Jannick A N , Pennells Lisa , van Smeden Maarten , Bots Michiel L , Di Angelantonio Emanuele , Visseren Frank L J
Published: June 2023

Background

Many models developed for predicting the risk of cardiovascular disease (CVD) are adjusted for the competing risk of non-CVD mortality, which has been suggested to reduce potential overestimation of cumulative incidence in populations where the risk of competing events is high. The objective was to evaluate and illustrate the clinical impact of competing risk adjustment when deriving a CVD prediction model in a high-risk population.

Methods and results

Individuals with established atherosclerotic CVD were included from the Utrecht Cardiovascular Cohort—Secondary Manifestations of ARTerial disease (UCC-SMART). In 8355 individuals, followed for a median of 8.2 years (IQR 4.2–12.5), two similar prediction models for the estimation of 10-year residual CVD risk were derived: with competing risk adjustment using a Fine and Gray model and without competing risk adjustment using a Cox proportional hazards model. On average, predictions were higher from the Cox model. The Cox model predictions overestimated the cumulative incidence [predicted–observed ratio 1.14 (95% CI 1.09–1.20)], which was most apparent in the highest risk quartiles and in older persons. Discrimination of both models was similar. When determining treatment eligibility on thresholds of predicted risks, more individuals would be treated based on the Cox model predictions. If, for example, individuals with a predicted risk > 20% were considered eligible for treatment, 34% of the population would be treated according to the Fine and Gray model predictions and 44% according to the Cox model predictions.

Interpretation

Individual predictions from the model unadjusted for competing risks were higher, reflecting the different interpretations of both models. For models aiming to accurately predict absolute risks, especially in high-risk populations, competing risk adjustment must be considered.