bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulation of a floating solar farm in waves with a novel sun-tracking system
Authors: Wei Yujia , Ou Binjian , Wang Junxian , Yang Liang , Luo Zhenhua , Jain Sagar , Hetharia Wolter , Riyadi Soegeng , Utama IKAP , Huang Luofeng
Published: August 2023

The awareness of the energy and climate crisis has accelerated the development of renewable energy sources. Photovoltaic (PV) solar power plants harvest clean solar energy and convert it to electricity, which will be one of the most promising alternatives to the power industry in the context of a low-carbon society. Due to its low power density, the traditional deployment of PV systems on land or inland rivers requires much space. Therefore, industries are increasingly interested in expanding offshore Floating PhotoVoltaics (FPV) to oceans, where FPV has less influence on the marine environment and does not occupy precious space for land resources and human activities. This study performs a hydrodynamics-based structural response analysis for a novel FPV system in OpenFOAM. The wave-proof FPV platform is newly designed for this work, which integrated breakwater technologies to sustain the system’s survivability in harsh ocean-wave environments. Firstly, the rational mooring types for FPVs installed close to the island are studied considering seabed effects. Subsequently, extensive parametric studies have been conducted to determine a rational design strategy for the mitigation of wave impact. Several potential effects of the proposed platforms on the hydrodynamics in a coastal sea are evaluated for the first time.
Adaptive grid deformation method for CFD application to hull optimization
Authors: Wang Shuguang , Kim Yonghwan
Published: August 2023

This work introduces a new grid deformation method for an efficient CFD-based optimization of ship hull forms. The method uses a two-level point transformation technique to manipulate grid points with a small number of design points. At the first level, generic B-spline is employed to transfer grid points based on movements of control points sampled inside a control box, ensuring accuracy and smoothness of surface modification. At the second level, Radial Basis Function with Wendland’s C2 continuity is adopted to interpolate movements of control points based on relatively few design points. It is shown to be effective in preserving good mesh quality and efficiency. The method is applied to the deformation of hull surfaces for ship models KVLCC2 and KCS, and to investigate the effects of bulbous bow on calm-water resistance with fixed Lpp. A regression model is proposed for ship length, location of buoyancy, wet surface area, and displacement. Numerical results show that the present method is well-suited for CFD-based hull form optimization with better efficiency.
The use of Ctrl+Z in ship design: removing a bulbous bow
Authors: Arribas F P , Oyuela S , Otero A D , Sosa R , Diaz-Ojeda H R
Published: August 2023

A bulbous bow is a widely employed feature to enhance the hydrodynamic resistance of ships. More than 95% of the merchant fleet incorporates various types of bulbous bows to reduce wave-making resistance and wave breaking. Bulbous bow is also utilized in smaller vessels like fishing vessels. In certain cases, the initial ship design includes the addition of a bulbous bow by default. In this study, which focuses on a typical Argentinian trawler fishing vessel, we investigate the impact of the bulbous bow on resistance. Taking a reverse approach, we modify the fishing vessel by removing the bulbous bow and we evaluate its hydrodynamics. This research aims to assess the reduction in ship resistance achieved by the bulbous bow under different load conditions and speeds, comparing the vessel with and without the bulbous bow. The numerical analysis uses OpenFOAM, and the results are validated through towing tank experiments. The research demonstrates that the performance of the bulbous bow varies across different conditions, indicating that not always the vessel with a bulbous bow is better.
Experimental and numerical Investigation on drag reduction using polymer coatings
Authors: Du Xinru , Mutsuda Hidemi , Wasada Yuya , Nakashima Takuji
Published: August 2023

The phenomenon of polymer drag reduction (DR) has primarily been investigated in the context of internal flows featuring mixed solutions. However, research on non-uniform polymer DR in external flows, such as polymer coatings on the surfaces of marine applications, remains scarce. To address this gap, experimental and numerical investigations were conducted in this research to find out the DR and turbulence performance. Firstly, the experimental results are shown to demonstrate the effectiveness of polymer DR. Specifically, the drag reduction performance of a silicon polymer coating is tested under different Reynolds numbers. Then, the mesoscopic dissipative particle dynamics (DPD) method is coupled with DNS and LES methods, and the finitely extensible nonlinear elastic approach is used to validate the results obtained using this DNS/LES-DPD method. Additionally, the model is used to investigate the influence of the height of the polymer region on non-uniform polymer DR and turbulence behaviour is also investigated. The model also reveals that the polymer DR efficiency is significant even when the polymer region does not extend across the entire fluid area such as the application of polymer coating.
A CFD-based evaluation of ship speed at EEXI draft
Authors: Yuan Shuai , Shi Lei , Hu Fan , Yu Hai , Xiong Xiaoqing
Published: August 2023

This paper presents a simulation of ship speed for an existing containership at EEXI draft using Computational Fluid Dynamics (CFD). The simulation is divided into two steps namely (a) the numerical prediction of ship performance at model scale, and (b) the extrapolation of results to full scale. Model scale numerical simulations of ship resistance, open-water propeller and ship-propeller-rudder interactions at demonstrated. The method is at first validated by comparing against available experiments and at second stage full-scale ship performance is assessed by an extrapolation method. Comparison of the ship speed predicted by CFD against experiments demonstrates a difference of 0.05 knots when the same extrapolation coefficients are applied.
On suitable CFD setups for cavitation dynamics
Authors: Wang Youjiang
Published: August 2023

In the current work, cavitating simulations were carried out with different setups including different mesh resolutions, time steps, RANS and IDDES turbulence models to investigate their influence on cavitation dynamics. The simulations were conducted for the Delft Twist hydrofoil, for which comprehensive experimental data is available. The open-source CFD solver OpenFoam is adopted because further model improvement is straightforward. The hydrodynamics, cavity volume, and cavitation shedding frequency are compared between different simulations. It is found that a good mesh for hydrodynamics is by far not enough to obtain appropriate cavitation dynamics. The turbulence model plays a prominent role on cavitation dynamics. The current work provides a valuable reference for choosing suitable setups to simulate cavitation dynamics.
Numerical simulations of submarine self-propulsion flows near the free surface
Authors: Guo Enkai , Cao Liushuai , Shen Zhiben , Wang Yun
Published: August 2023

Submarine needs to complete more tasks near the free-surface area in modern war. When sailing near the free surface, the self-propelled characteristics of the submarine and its nearby flow field will be affected by the free surface. This paper presents the research on the self-propulsion submarine near the free surface with computational fluid dynamics (CFD) method. We take the generic Joubert BB2 submarine and Marine 7371R propeller models as the research objects. The RANS method and SST k-ω turbulence model are selected to solve the turbulent flows. The volume of fluid (VOF) method is used to capture the free surface. Grid convergence study is performed based on three sets of grids with different resolution. Numerical simulations are performed under the self-propulsion cases with different submergence depths and velocities. The proportional integral (PI) controller method is proposed to obtain the self-propulsion point. The results are more accurate compared with the traditional one. It is found that with the decrease of the submergence depths, the rotating speed of the self-propelled point and the corresponding thrust increase. The study also explores the free surface effect on flow field characteristics, wave-making characteristics and vortex structures. The scientific findings provide some useful results for the self-propulsion submarines near the free surface and support the further research in the future.
Analysis of the Hydrodynamic Performance of a Gate Rudder System
Authors: Turkmen Serkan , Wang Li , Raftopoulos Stefanos , Li Chang , Norman Rose
Published: August 2023

An alternative twin rudder system known as the Gate Rudder© has been applied to newbuild vessels and an existing ship with the aim to improve their hydrodynamic performance and reduce greenhouse gas emissions. The system consists of two asymmetric cross-sections and L-shaped blades located either side of a propeller. The blades generate thrust (duct effect) from the propeller and ship-included flow. Initially, forces and moments of a single blade were measured using a 6-axis strain gauge sensor in the towing tank without a propeller. An alternative measuring device, consisting of a Piezoelectric Macro-Fiber Composite Actuator, was then attached to the blade to investigate flow-induced forces. Finally, Computational Fluid Dynamic (CFD) simulations were compared with the experimental results to identify the source of the oscillating forces. The results show that flow-induced vibrations may occur on the gate rudder blades at both shedding frequencies and the structure’s natural frequency.
Estimation of the entrained water effect of tandem propellers based on numerical method
Authors: Wang Jianzheng , Zhou Ruiping , Guo Yukuo , Luo Xiaoyuan
Published: August 2023

The objective of the paper is to propose the empirical formulas of the entrained water effect based on numerical method to estimate the virtual mass and the virtual moment of inertia for tandem propellers. The fluid-solid interaction of combined propellers in the flow field has been taken into consideration in the calculation. The axial added mass and the added moment of inertia of the entrained water are calculated for a single propeller using the finite element method and the existing empirical formulas to verify the feasibility and accuracy of numerical method. Consequently, the numerical calculation of tandem propellers is conducted to obtain the novel empirical formulas of entrained water properties, which are available to evaluate the influence of the blade diameter, the expanded area ratio and the pitch/diameter ratio. The corresponding correction coefficients in the empirical formulas considering the entrained water effect of tandem propellers are given. The empirical formulas are beneficial to relevant practical engineering calculation of entrained water properties for combined propellers.
Predicting inkjet jetting behavior for viscoelastic inks using machine learning
Authors: Kim Seongju , Wenger Raphaël , Bürgy Olivier , Balestra Gioele , Jeong Unyong , Jung Sungjune
Published: August 2023

Inkjet printing offers significant potential for additive manufacturing technology. However, predicting jetting behavior is challenging because the rheological properties of functional inks commonly used in the industry are overlooked in printability maps that rely on the Ohnesorge and Weber numbers. We present a machine learning-based predictive model for jetting behavior that incorporates the Deborah number, the Ohnesorge number, and the waveform parameters. Ten viscoelastic inks have been prepared and their storage modulus and loss modulus measured, showing good agreement with those obtained by the theoretical Maxwell model. With the relaxation time of the viscoelastic ink obtained by analyzing the Maxwell model equations, the Deborah number could be calculated. We collected a large data set of jetting behaviors of each ink with various waveforms using drop watching system. Three distinct machine learning models were employed to build predictive models. After comparing the prediction accuracy of the machine learning models, we found that multilayer perceptron showed outstanding prediction accuracy. The final predictive model exhibited remarkable accuracy for an unknown ink based on waveform parameters, and the correlation between jetting behavior and ink properties was reasonable. Finally, we developed a printability map characterized by the Ohnesorge and Deborah numbers through the proposed predictive model for viscoelastic fluids and the chosen industrial printhead.
High performance composite Pr4Ni3O 10±δ
—Ce0.75Gd0.1Pr0.15O
2−δ
solid oxide cell air electrode
Authors: Xie Zheng , Jang Inyoung , Ouyang Mengzheng , Hankin Anna , Skinner Stephen J
Published: August 2023

A composite electrode composed of Pr4Ni3O

10
±
δ

—Ce0.75Gd0.1Pr0.15O

2
−
δ

(50 wt.%–50 wt.%) was thoroughly investigated in terms of the electrochemical performance as a function of microstructure. The electrochemical performance was characterized by electrochemical impedance spectroscopy and the microstructures, characterized by focused ion beam-scanning electron microscopy and 3D reconstructions, were modified by changing the particle size of Pr4Ni3O

10
±
δ

and the electrode thickness. The distribution of relaxation time method was applied to help resolve electrochemical processes occurring in the electrodes. It was found that an appropriate increase in electrode thickness and an appropriate decrease in particle size enhanced the oxygen reduction reaction (ORR) kinetics. The lowest area specific resistance obtained in this study at 670 ∘C under pO
2 of 0.21 atm was 0.055 Ω cm2. Finally, a comparison to the Adler-Lane-Steele (ALS) model was made and the main active site for the ORR was concluded to be triple phase boundaries. A fuel cell made of the composite material as the cathode was fabricated and tested. The peak power density was 1 W cm−2 at 800 ∘C, which demonstrates that this composite material is promising for solid oxide fuel cell cathodes.
Experimental and analytical investigation of bio-inspired lattice structures under compressive loading
Authors: Doodi Ramakrishna , Balamurali Gunji
Published: August 2023

The main objective of this study is to fabricate a Novel bio-inspired lattice structure for energy absorption. A lattice structure design was proposed based on the microstructure of one of the various butterfly species Papilio Xuthus. Two major parameters are chosen from the structure to make multiple designs which may cause changes in the behavior of the structure among all available parameters. The parametric values required for the designs were calculated with the help of Response Surface Methodology (RSM) using Minitab software. The proposed designs are modeled in Autodesk Fusion 360 and 3D printed specimens of size 40 × 40 × 40 (all are in mm) are fabricated by Stereolithography (SLA) process based on the chosen parameters. The 3D-printed specimens are tested under quasi-static compressive loading using Instron 8801 Universal testing machine (UTM). The test results obtained from the testing are used to construct regression equations for energy absorption (EA) and specific energy absorption (SEA). The developed equations can be used to find out EA and SEA values for any combination of the proposed parameters (x and d) for suitable energy absorption applications.
Normal vector centering method for probe correction in cylindrical worm tooth profile measurement
Authors: Jie Tang , Hui Wan , Zhaoyao Shi , Guangcai Zhou
Published: August 2023

The measurement results of cylindrical worms vary greatly under different probe tip diameters on the Gear Measuring Centre (GMC). Considering toroidal enveloping cylindrical worm (ZC1 worm) as an instance, after analysing the worm grinding coordinate system, the probe correction method based on normal vector centreing (NVC) is established. The theoretical coordinate values of the points on the normal equidistant line which is rotated into the axial section are used as the probe tip centre trajectory. Experiments were carried out with probe tip diameters of 1.0 mm, 1.5 mm and 2.0 mm for the worm tooth profile measurement on a GMC. Compared with the traditional method, the variation between the profile deviations results using the proposed method become smaller and the variation of ‘profile deviation, total’ is reduced from 8.3 μm to 0.5 μm, the profile slope deviation variation is reduced from 8.6 μm to 0.5 μm. The proposed method in ZC1 worm tooth profile measurement can effectively reduce the variation between the measurement results under different GMC probe tip diameters, and also the methodology can be applied to other kinds of cylindrical worms. The method has significance for other curved profiles measurement on coordinate measurements.
Foundations of attribution in climate-change science
Authors: Lloyd Elisabeth A , Shepherd Theodore G
Published: August 2023

Attribution—the explanation of an observed change in terms of multiple causal factors—is the cornerstone of climate-change science. For anthropogenic climate change (ACC), the central causal factor is evidently ACC itself, and one of the primary tools used to reveal ACC is aggregation, or grouping together, of data, e.g. global mean surface temperature. Whilst this approach has served climate-change science well, the landscape is changing rapidly. First, there is an increasing focus on regional or local aspects of climate change, and on singular or unprecedented events, which require varying degrees of disaggregation. Relatedly, climate change is increasingly apparent in observations at the local scale, which is challenging the primacy of climate model simulations. Finally, the explosion of climate data is leading to more phenomena-laden methodologies such as machine learning. All this demands a re-think of how attribution is performed and causal explanations are constructed. Here we use Lloyd’s ‘Logic of Research Questions’ framework to show how the way in which the attribution question is framed can strongly constrain its possible and responsive answers. To address the Research Question ‘What was the effect of ACC on X?’ (RQ1), scientists generally consider the question ‘What were the causal factors leading to X, and was ACC among them?’. If the causal factors include only external forcing and internal variability (RQ2), then answering RQ2 also answers RQ1. However, this unconditional attribution is not always possible. In such cases, allowing the causal factors to include elements of the climate system itself (RQ3)—the conditional, storyline approach—is shown to allow for a wider range of possible and responsive answers than RQ2, including that of singular causation. This flexibility is important when uncertainties are high. As a result, the conditional RQ3 mitigates against the sort of epistemic injustice that can arise from the unconditional RQ2.
Inductive limits of noncommutative Cartan inclusions
Authors: Meyer Ralf , Raad Ali , Taylor Jonathan
Published: August 2023

We prove that an inductive limit of aperiodic noncommutative Cartan inclusions is a noncommutative Cartan inclusion whenever the connecting maps are injective, preserve normalisers and entwine conditional expectations. We show that under the additional assumption that the inductive limit Cartan subalgebra is either essentially separable, essentially simple or essentially of Type I we get an aperiodic inclusion in the limit. Consequently, we subsume the case where the building block Cartan subalgebras are commutative and provide a proof of a theorem of Xin Li without passing to twisted étale groupoids.
Operators taking values into Köthe-Bochner spaces
Authors: Randrianantoanina Narcisse
Published: August 2023

It is known that for

0
>
p
≤
1

0>p\leq 1

, every linear operator

T
:

L
p

(
μ
)
→

L
p

(
λ
)

T: L_p( \mu ) \to L_p(\lambda )

is norm-bounded if and only if it is regular. Recently, this has been generalized to operators from

L
1

(
μ
)

L_1(\mu )

into the Lebesgue-Bochner space

L
1

(
λ
;
X
)

L_1(\lambda ;X)

in the form of dominated operators: every linear operator

T
:

L
1

(
μ
)
→

L
1

(
λ
;
X
)

T: L_1( \mu ) \to L_1(\lambda ;X)

is norm-bounded if and only if it is dominated. Using another method of proof, we generalize this result to all indices

0
>
p
≤
1

0>p\leq 1

. Our result asserts that if

X
X

is a

p
p

-Banach space, then every linear operator

T
:

L
p

(
μ
)
→

L
p

(
λ
;
X
)

T: L_p( \mu ) \to L_p(\lambda ;X)

is norm-bounded if and only if there is a positive operator

S
:

L
1

(
μ
)
→

L
1

(
λ
)

S:L_1(\mu ) \to L_1(\lambda )

satisfying for every

f
∈

L
p

(
μ
)

f\in L_p(\mu )

,
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="double-vertical-bar upper T f left-parenthesis omega right-parenthesis double-vertical-bar Subscript upper X Superscript p Baseline less-than-or-equal-to upper S left-parenthesis StartAbsoluteValue f EndAbsoluteValue Superscript p Baseline right-parenthesis left-parenthesis omega right-parenthesis comma lamda hyphen a period e period">

‖
T
f
(
ω
)

‖
X
p

≤
S
(

|

f

|

p

)
(
ω
)
,

λ

-a.e

.

\|Tf(\omega )\|_X^p \leq S(|f|^p)(\omega ), \quad \text {$\lambda $-a.e}.

\]
We also obtain as a consequence, a version of Grothendieck inequality for bounded linear operators from

L
p

(
μ
)

L_p(\mu )

into

L
p

(
λ
;
X
)

L_p(\lambda ;X)

for

0
>
p
≤
1

0>p\leq 1

.
Associations of Early-Life Adversity With Later-Life Epigenetic Aging Profiles in the Multi-Ethnic Study of Atherosclerosis
Authors: Schmitz Lauren L , Duffie Elizabeth , Zhao Wei , Ratliff Scott M , Ding Jingzhong , Liu Yongmei , Merkin Sharon Stein , Smith Jennifer A , Seeman Teresa
Published: August 2023

Epigenetic biomarkers of accelerated aging have been widely used to predict disease risk and may enhance our understanding of biological mechanisms between early-life adversity and disparities in aging. With respect to childhood adversity, most studies have used parental education or childhood disadvantage and/or have not examined the role played by socioemotional or physical abuse and trauma in epigenetic profiles at older ages. This study leveraged data from the Multi-Ethnic Study of Atherosclerosis (MESA) on experiences of threat and deprivation in participants’ early lives (i.e., before the age of 18 years) to examine whether exposure to specific dimensions of early-life adversity is associated with epigenetic profiles at older ages that are indicative of accelerated biological aging. The sample included 842 MESA respondents with DNA methylation data collected between 2010 and 2012 who answered questions on early-life adversities in a 2018–2019 telephone follow-up. We found that experiences of deprivation, but not threat, were associated with later-life GrimAge epigenetic aging signatures that were developed to predict mortality risk. Results indicated that smoking behavior partially mediates this association, which suggests that lifestyle behaviors may act as downstream mechanisms between parental deprivation in early life and accelerated epigenetic aging in later life.
PhenoDriver: interpretable framework for studying personalized phenotype-associated driver genes in breast cancer
Authors: Li Yan , Zhang Shao-Wu , Xie Ming-Yu , Zhang Tong
Published: August 2023

Identifying personalized cancer driver genes and further revealing their oncogenic mechanisms is critical for understanding the mechanisms of cell transformation and aiding clinical diagnosis. Almost all existing methods primarily focus on identifying driver genes at the cohort or individual level but fail to further uncover their underlying oncogenic mechanisms. To fill this gap, we present an interpretable framework, PhenoDriver, to identify personalized cancer driver genes, elucidate their roles in cancer development and uncover the association between driver genes and clinical phenotypic alterations. By analyzing 988 breast cancer patients, we demonstrate the outstanding performance of PhenoDriver in identifying breast cancer driver genes at the cohort level compared to other state-of-the-art methods. Otherwise, our PhenoDriver can also effectively identify driver genes with both recurrent and rare mutations in individual patients. We further explore and reveal the oncogenic mechanisms of some known and unknown breast cancer driver genes (e.g. TP53, MAP3K1, HTT, etc.) identified by PhenoDriver, and construct their subnetworks for regulating clinical abnormal phenotypes. Notably, most of our findings are consistent with existing biological knowledge. Based on the personalized driver profiles, we discover two existing and one unreported breast cancer subtypes and uncover their molecular mechanisms. These results intensify our understanding for breast cancer mechanisms, guide therapeutic decisions and assist in the development of targeted anticancer therapies.
The paralogs’ enigma of germ-cell specific genes dispensable for fertility: the case of 19 oogenesin genes
Authors: Castille Johan , Thépot Dominique , Fouchécourt Sophie , Dalbies-Tran Rozenn , Passet Bruno , Daniel-Carlier Nathalie , Vilotte Jean-Luc , Monget Philippe
Published: August 2023

Gene knockout experiments have shown that many genes are dispensable for a given biological function. In this review, we make an assessment of male and female germ cell-specific genes dispensable for the function of reproduction in mice, the inactivation of which does not affect fertility. In particular, we describe the deletion of a 1 Mb block containing nineteen paralogous genes of the oogenesin/Pramel family specifically expressed in female and/or male germ cells, which has no consequences in both sexes. We discuss this notion of dispensability and the experiments that need to be carried out to definitively conclude that a gene is dispensable for a function.
Does Policing Help or Hurt? Examining the Longitudinal Relationship Between Police Involvement and Delinquency in Norway
Authors: Andersen Synøve Nygaard
Published: August 2023

The population heterogeneity argument links criminality to time-stable individual traits and suggests that criminal justice system involvements exert no independent influence on criminal behaviour. This study directly tests this postulation by estimating the relationship between police involvement and subsequent delinquency in an individual fixed effects design. The analysis relies on five waves of longitudinal data on self-reported delinquency and administrative data on police contacts. Results show that time-stable individual traits matter, but that the frequency of police contacts is positively associated with offending also after such characteristics have been accounted for. The results are thus in line with the state dependence argument and provide tentative support for labelling theory’s postulation that criminal justice involvement increases rather than decreases criminal behaviour.
Identifying characteristics of dermal fibroblasts in skin homeostasis and disease
Authors: Chen Fang-Zhou , Tan Poh-Ching , Yang Zihan , Li Qingfeng , Zhou Shuang-Bai
Published: August 2023

Heterogeneous dermal fibroblasts are the main components that constitute the dermis. Distinct fibroblast subgroups show specific characteristics and functional plasticity that determine dermal structure during skin development and wound healing. Although researchers have described the roles of fibroblast subsets, this is not completely understood. We review recent evidence supporting understanding about the heterogeneity of fibroblasts. We summarize the origins and the identified profiles of fibroblast subpopulations. The characteristics of fibroblast subpopulations in both healthy and diseased states are highlighted, and the potential of subpopulations to be involved in wound healing in different ways was discussed. Additionally, we review the plasticity of subpopulations and the underlying signalling mechanisms. This review may provide greater insights into potential novel therapeutic targets and tissue regeneration strategies for the future.
Squamous cell carcinoma and MYH9-associated elastin aggregation (MALTA) syndrome
Authors: Fostier William , Husain Akhtar , Rajan Neil
Published: August 2023

MYH9-associated elastin aggregation (MALTA) syndrome is a rare inherited syndrome of irregular elastin aggregation and sweat duct proliferation associated with pathogenic variants in MYH9. MALTA syndrome was first proposed in 2019, unifying Nicolau–Balus and Rombo syndromes as phenotypes arising from pathogenic variants in the same gene; however, it has not been associated with cutaneous squamous cell carcinoma (cSCC). Here, we report the clinical features of a family with a novel MYH9 c.1952A>C p.(Lys651Thr) pathogenic variant, providing evidence that cSCC development may be an associated feature of MALTA syndrome.
Increased thromboinflammatory load in hereditary angioedema
Authors: Gramstad Olav Rogde , Schjalm Camilla , Mollnes Tom Eirik , Nielsen Erik Waage
Published: August 2023

C1 inhibitor (C1Inh) is a serine protease inhibitor involved in the kallikrein-kinin system, the complement system, the coagulation system, and the fibrinolytic system. In addition to the plasma leakage observed in hereditary angioedema (HAE), C1Inh deficiency may also affect these systems, which are important for thrombosis and inflammation. The aim of this study was to investigate the thromboinflammatory load in C1Inh deficiency. We measured 27 cytokines including interleukins, chemokines, interferons, growth factors, and regulators using multiplex technology. Complement activation (C4d, C3bc, and sC5b-C9/TCC), haemostatic markers (β-thromboglobulin (β-TG), thrombin-antithrombin complexes (TAT), prothrombin fragment 1 + 2 (F1 + 2), active plasminogen activator inhibitor-1 (PAI-1), and the neutrophil activation marker myeloperoxidase (MPO) were measured by enzyme immunoassays. Plasma and serum samples were collected from 20 patients with HAE type 1 or 2 in clinical remission and compared with 20 healthy age- and sex-matched controls. Compared to healthy controls, HAE patients had significantly higher levels of tumour necrosis factor (TNF), interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-7, IL-9, IL-12, and IL-17A, chemokine ligand (CXCL) 8, chemokine ligand (CCL) 3, CCL4, IL-1 receptor antagonist (IL-1RA), granulocyte-macrophage colony-stimulating factor (GM-CSF), fibroblast growth factor (FGF) 2 and platelet-derived growth factor (PDGF)-BB. HAE patients also had higher levels of TAT and F1 + 2. Although granulocyte colony-stimulating factor (G-CSF), β-TG and PAI-1 were higher in HAE patients, the differences did not reach statistical significance after correction for multiple testing. In conclusion, C1Inh deficiency is associated with an increased baseline thromboinflammatory load. These findings may reflect that HAE patients are in a subclinical attack state outside of clinically apparent oedema attacks.
Epidemiology and predictors of hyponatremia in a contemporary cohort of patients with malignancy: a retrospective cohort study
Authors: Murashima Miho , Ambe Kaori , Aoki Yuka , Kasugai Takahisa , Tomonari Tatsuya , Ono Minamo , Mizuno Masashi , Tohkin Masahiro , Hamano Takayuki
Published: August 2023

Background

Hyponatremia is associated with worse outcomes among patients with malignancy. However, contemporary cohort data on epidemiology and risk factors are lacking.

Methods

In this single-centre, retrospective cohort study, patients who received intravenous antineoplastic agents from 2018 to 2020 at Nagoya City University Hospital were enrolled. Associations of demographics, antineoplastic agents, types of malignancy and concomitant medications with hyponatremia, defined as serum sodium concentration ≤130 mmol/l, were analysed by mixed-effects logistic regression and the machine learning–based LightGBM model artificial intelligence technology.

Results

Among 2644 patients, 657 (24.8%) developed at least one episode of hyponatremia. Approximately 80% of hyponatremia was due to sodium wasting from the kidneys. Variables associated with hyponatremia both by mixed-effects logistic regression and the LightGBM model were older age, hypoalbuminemia and higher estimated glomerular filtration rate. Among antineoplastic agents, cisplatin {odds ratio [OR] 1.52 [95% confidence interval (CI) 1.18–1.96]}, pembrolizumab [OR 1.42 (95% CI 1.02–1.97)] and bortezomib [OR 3.04 (95% CI 1.96–4.71)] were associated with hyponatremia and these variables also had a positive impact on predicted hyponatremia in the LightGBM model.

Conclusions

Hyponatremia was common among patients with malignancy. In addition to older age and poor nutritional status, novel antineoplastic agents, including immune checkpoint inhibitors and bortezomib, should be recognized as risk factors for hyponatremia.
Improving mean-field network percolation models with neighbourhood information
Authors: Jones Chris , Wiesner Karoline
Published: August 2023

Mean field theory models of percolation on networks provide analytic estimates of network robustness under node or edge removal. We introduce a new mean field theory model based on generating functions that includes information about the tree-likeness of each node’s local neighbourhood. We show that our new model outperforms all other generating function models in prediction accuracy when testing their estimates on a wide range of real-world network data. We compare the new model’s performance against the recently introduced message-passing models and provide evidence that the standard version is also outperformed, while the ‘loopy’ version is only outperformed on a targeted attack strategy. As we show, however, the computational complexity of our model implementation is much lower than that of message-passing algorithms. We provide evidence that all discussed models are poor in predicting networks with highly modular structure with dispersed modules, which are also characterized by high mixing times, identifying this as a general limitation of percolation prediction models.
Hospital admissions in the last year of life of patients with heart failure
Authors: Abel Alexandra A I , Samuel Nathan A , Cuthbert Joseph J , Brown Oliver I , Pellicori Pierpaolo , Kazmi Syed , Cleland John G F , Johnson Miriam J , Clark Andrew L
Published: August 2023

Aim

To explore the frequency, causes, and pattern of hospitalisation for patients with chronic heart failure (HF) in the 12 months preceding death. We also investigated cause of death.

Methods

Patients referred to a secondary care HF clinic were routinely consented for follow-up between 2001 and 2020 and classified into three phenotypes: (i) HF with reduced ejection fraction (HFrEF), (ii) HF with preserved ejection fraction (HFpEF) with plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) 125–399 ng L−1, and (iii) HFpEF with NT-proBNP ≥400 ng L−1. Hospital admissions in the last year of life were classified as: HF, other cardiovascular (CV), or non-cardiovascular (non-CV). The cause of death was systematically adjudicated.

Results

A total of 4925 patients (38% women; median age at death 81 [75–87] years) had 9127 hospitalisations in the last year of life. The median number of hospitalisations was 2 (1–3) and total days spent in hospital was 12 (2–25). Out of the total, 83% of patients had ≥1 hospitalisation but only 20% had ≥1 HF hospitalisation; 24% had ≥1 CV hospitalisation; 70% had ≥1 non-CV hospitalisation. Heart failure hospitalisations were most common in patients with HFrEF, but in all groups, at least two thirds of admissions were for non-CV causes. There were 788 (16%) deaths due to progressive HF, of which 74% occurred in hospital.

Conclusion

For patients with chronic HF in the last year of life, most hospitalisations were for non-CV causes regardless of HF phenotype. Most patients had no HF hospitalisations in their last year of life. Most deaths were from causes other than progressive HF.
Relation between HLA and copy number variation of steroid 21-hydroxylase in a Swedish cohort of patients with autoimmune Addison's disease
Authors: Lundtoft Christian , Eriksson Daniel , Bianchi Matteo , Aranda-Guillén Maribel , Landegren Nils , Rantapää-Dahlqvist Solbritt , Söderkvist Peter , Meadows Jennifer R S ,   The DISSECT Consortium, Rönnblom Lars , Lindblad-Toh Kerstin , Wahren-Herlenius Marie , Nordmark Gunnel , Lundberg Ingrid E , Syvänen Ann-Christine , Sandling Johanna K , Kozyrev Sergey V , Eloranta Maija-Leena , Bianchi Matteo , Rantapää-Dahlqvist Solbritt , Meadows Jennifer R S , Nordin Jessika , Dahlqvist Johanna , Mathioudaki Argyri , Farias Fabiana H G , Tandre Karolina ,   The ImmunoArray Consortium, Lindblad-Toh Kerstin , Pielberg Gerli Rosengren , Lobell Anna , Karlsson Åsa , Murén Eva , Andersson Göran , Ahlgren Kerstin M , Rönnblom Lars , Landegren Nils , Kämpe Olle , Söderkvist Peter ,   The Swedish Addison Registry Study Group, Åkerman Anna-Karin , Hulting Anna-Lena , Lindberg Bengt , Lundberg Elena , Johannsson Gudmundur , Skov Jakob , Wahlberg Jeanette , Duchen Karel , Isaksson Magnus , Elfving Maria , Stenlid Maria Halldin , Landin-Olsson Mona , Nilsson Ola , Kämpe Olle , Ekwall Olov , Dahlqvist Per , Bergthorsdottir Ragnhildur , Nergårdh Ricard , Björnsdottir Sigridur , Bensing Sophie , Olsson Tommy , Bensing Sophie , Pielberg Gerli Rosengren , Lindblad-Toh Kerstin , Rönnblom Lars , Kämpe Olle
Published: August 2023

Objective

Autoantibodies against the adrenal enzyme 21-hydroxylase is a hallmark manifestation in autoimmune Addison's disease (AAD). Steroid 21-hydroxylase is encoded by CYP21A2, which is located in the human leucocyte antigen (HLA) region together with the highly similar pseudogene CYP21A1P. A high level of copy number variation is seen for the 2 genes, and therefore, we asked whether genetic variation of the CYP21 genes is associated with AAD.

Design

Case-control study on patients with AAD and healthy controls.

Methods

Using next-generation DNA sequencing, we estimated the copy number of CYP21A2 and CYP21A1P, together with HLA alleles, in 479 Swedish patients with AAD and autoantibodies against 21-hydroxylase and in 1393 healthy controls.

Results

With 95% of individuals carrying 2 functional 21-hydroxylase genes, no difference in CYP21A2 copy number was found when comparing patients and controls. In contrast, we discovered a lower copy number of the pseudogene CYP21A1P among AAD patients (P = 5 × 10−44), together with associations of additional nucleotide variants, in the CYP21 region. However, the strongest association was found for HLA-DQB1*02:01 (P = 9 × 10−63), which, in combination with the DRB1*04:04-DQB1*03:02 haplotype, imposed the greatest risk of AAD.

Conclusions

We identified strong associations between copy number variants in the CYP21 region and risk of AAD, although these associations most likely are due to linkage disequilibrium with disease-associated HLA class II alleles.
Arrhythmic mitral valve prolapse and mitral annular disjunction: pathophysiology, risk stratification, and management
Authors: Essayagh Benjamin , Sabbag Avi , El-Am Edward , Cavalcante João L , Michelena Hector I , Enriquez-Sarano Maurice
Published: August 2023

Mitral valve prolapse (MVP) is the most frequent valve condition but remains a conundrum in many aspects, particularly in regard to the existence and frequency of an arrhythmic form (AMVP) and its link to sudden cardiac death. Furthermore, the presence, frequency, and significance of the anatomic functional feature called mitral annular disjunction (MAD) have remained widely disputed. Recent case series and cohorts have shattered the concept that MVP is most generally benign and have emphasized the various phenotypes associated with clinically significant ventricular arrhythmias, including AMVP. The definition, evaluation, follow-up, and management of AMVP represent the focus of the present review, strengthened by recent coherent studies defining an arrhythmic MVP phenotypic that would affect a small subset of patients with MVP at concentrated high risk. The role of MAD in this context is of particular importance, and this review highlights the characteristics of AMVP phenotypes and MAD, their clinical, multimodality imaging, and rhythmic evaluation. These seminal facts lead to proposing a risk stratification clinical pathway with consideration of medical, rhythmologic, and surgical management and have been objects of recent expert consensus statements and of proposals for new research directions.
De novo genome assembly and comparative genomics for the colonial ascidian Botrylloides violaceus
Authors: Sumner Jack T , Andrasz Cassidy L , Johnson Christine A , Wax Sarah , Anderson Paul , Keeling Elena L , Davidson Jean M
Published: August 2023

Ascidians have the potential to reveal fundamental biological insights related to coloniality, regeneration, immune function, and the evolution of these traits. This study implements a hybrid assembly technique to produce a genome assembly and annotation for the botryllid ascidian, Botrylloides violaceus. A hybrid genome assembly was produced using Illumina, Inc. short and Oxford Nanopore Technologies long-read sequencing technologies. The resulting assembly is comprised of 831 contigs, has a total length of 121 Mbp, N50 of 1 Mbp, and a BUSCO score of 96.1%. Genome annotation identified 13 K protein-coding genes. Comparative genomic analysis with other tunicates reveals patterns of conservation and divergence within orthologous gene families even among closely related species. Characterization of the Wnt gene family, encoding signaling ligands involved in development and regeneration, reveals conserved patterns of subfamily presence and gene copy number among botryllids. This supports the use of genomic data from nonmodel organisms in the investigation of biological phenomena.
Counteracting Age-Related Netrin-1 Signaling Insufficiency Ameliorates Endothelial Cell Senescence and Angiogenesis Impairment
Authors: Yang Zhen , Li Han , Yan Dan , Luo Pengcheng , Guan Yuqi , Luo Mandi , Nie Hao , Huang Yi , Zhang Le , Ruan Lei , Yan Jinhua , Zhang Cuntai
Published: August 2023

Senescent cells that accumulate are regarded as promising therapeutic targets. However, senolytic therapy failed to achieve satisfactory results. We previously discovered that young human plasma improved vascular endothelial cell senescence, and UNC5B might be a novel intervention target. Netrin-1, as a natural ligand of UNC5B, plays roles in multiple age-related vascular disorders, but its involvement in aging is still unclear. Here, we observed a significant decrease in plasma Netrin-1 levels in old healthy subjects compared to the young. In vivo, adeno-associated-virus-mediated delivery of Netrin-1 into aged mice significantly improved functional recovery in a model of hindlimb ischemia, promoted angiogenesis in ischemic tissues, and activated the endothelial nitric oxide synthase. Furthermore, we revealed that low-dose Netrin-1 recombinant protein significantly reduced senescence-associated-β-galactosidase-positive cells, inhibited the P53 pathway, promoted cell migration, increased tubule formation, and elevated nitric oxide production in senescent endothelial cells. However, UNC5B inhibition blocked the pro-angiogenesis effect of low-dose Netrin-1 on senescent cells or aortic rings. In summary, this study depicts that modulating Netrin-1 signaling can result in improved vascular health and Netrin-1 may have therapeutic potential for age-related ischemic diseases.
An electrical resistivity image of the Hikurangi subduction margin
Authors: Heise Wiebke , Bertrand Edward A , Caldwell T Grant , Ogawa Yasuo , Bannister Stephen , Bennie Stewart L , Hart Rory , Palmer Neville , Tseng Kuo Hsuen , Fukai Masato , Ishikawa Masaki , Seki Kaori , Nishizawa Tatsuji , McGrath Jack
Published: August 2023

Along the Hikurangi subduction margin, on the east coast of New Zealand's North Island, the interplate coupling changes from locked in the south to weakly coupled in the north. New magnetotelluric (MT) data from 151 locations linking previous MT surveys into a single contiguous data set that encompasses the weakly coupled part of the margin are analysed. By inverting the combined data we have constructed a 3-D image of the electrical resistivity of the subduction interface shear zone along a 300-km-long segment of the margin. Our results show that the electrical resistivity of the subduction interface shear zone is heterogenous; the degree of heterogeneity decreasing from north to south. The resistivity heterogeneities correlate well with the distribution of near-plate interface seismicity, Vp/Vs values and the pattern of areal strain rate derived from GPS data. These correlations are consistent with variations in the fluid content of the subduction interface shear zone. In the northern part of this segment, conductive areas adjacent to the interface are interpreted to be fluid rich areas where seismicity is sparse, Vp/Vs ratios are high and the areal strain rate is extensional. In contrast, where the areal strain rate is compressional the plate interface is more resistive, and seismicity is more abundant consistent with greater interplate friction. In the south, the resistivity of the plate interface is more homogenous, and the overlying plate is more resistive at shallower levels than in the north. Our results support the hypothesis that the fluid and/or hydrated clay content of the subduction interface shear zone are an important control on interplate coupling.
Structure and dynamics of the Ecuador Fracture Zone, Panama Basin
Authors: Peirce C , Tedd J C , Hobbs R W
Published: August 2023

In this study, multiple geophysical data types are used to investigate the structure and dynamics of the Ecuador Fracture Zone—a complex multistranded strike-slip fault system located in the Panama Basin. Gravity modelling reveals a 25–30-km-wide region of ∼3-km-thick, low-density crust beneath this system and an anomalously low-density region in the uppermost mantle. Along both edges, the transition to the ‘normal’ structure and thickness oceanic crust formed at both the Ecuador and Costa Rica Rifts is abrupt. Within the Ecuador Fracture Zone itself, normal faults bound the median ridges. These faults traverse the entire thickness of accumulated sediment and offset the seabed, while sediment layer geometries document multiple phases of relative uplift, with the most recent phase still ongoing. Active extensional faulting, with an approximately spreading ridge-parallel strike, is also observed in 6–7 Ma Costa Rica Rift crust. The median ridges and the transverse ridge at the eastern edge of the Ecuador Fracture Zone also have contrasting crustal density structures. Both median ridges have a lower density crust than between the intervening valleys, while the transverse ridge crust has an equivalent thickness and density structure to that formed at the Costa Rica Rift. The active median valley basement-cutting normal faults allow seawater ingress and alternation of the crustal footwall, and also flow to mantle depth where, based on gravity modelling, 30–50 per cent serpentinization of mantle peridotite occurs. The resulting serpentinite-driven buoyancy acts as the primary control on the observed median ridge relative vertical tectonism. In contrast, the relative uplift of the transverse ridge results from lithospheric flexure in response to a change in spreading direction between the Ecuador and Costa Rica Rifts. Contrary to the widely accepted assumption that fracture zones are tectonically inactive systems, the Ecuador Fracture Zone provides evidence of extension, serpentinization due to ongoing hydrothermal circulation and relative uplift.