bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic significance of liver stiffness in patients with primary biliary cholangitis: validation of Baveno VII criteria
Authors: Ding Dawei , Guo Guanya , Cui Lina , Jia Gui , Wang Xiufang , Zhang Miao , Tian Siyuan , Zheng Linhua , Liu Yansheng , Hu Yinan , Xuan Guoyun , Yang Jiaqi , Yang Chunmei , Sun Ruiqing , Deng Juan , Guo Changcun , Chen Yu , Shang Yulong , Han Ying
Published: September 2023

Background

The role of liver stiffness measurements (LSM) in patients with primary biliary cholangitis (PBC) remains to be further elucidated.

Aims

To clarify the prognostic role of LSM and to validate the “novel concepts” proposed by the Baveno VII Working Group.

Methods

An analysis of the prognostic significance of LSM was performed involving 672 patients.

Results

LSM and ΔLSM/ΔT were independent risk factors for liver decompensation, liver transplantation, or liver-related death (primary outcomes, p < 0.001, both). A rule of 5 kPa for LSM (10–15–20 kPa) could be used to denote progressively higher relative risks of primary outcomes. Patients with LSM < 10 kPa have a negligible 3-year risk of primary outcomes (< 1%). Cut-off values of 10 and 15 kPa can be used to classify PBC patients into low-, medium-, and high-risk groups. A clinically significant decrease in LSM, evaluated at 6, 12, or 24 months elastography tests, was associated with a substantially reduced risk of primary outcomes (p < 0.05, all), which can be defined as a decrease in LSM of >  − 20% associated with LSM < 20 kPa or any decrease to LSM < 10 kPa. A clinically significant increase in LSM, evaluated at 6, 12, or 24 months elastography tests, was associated with a substantially raised risk of primary outcomes (p < 0.05, all), which can be defined as an increase in LSM of ≥  + 20% or any increase to LSM ≥ 15 kPa.

Conclusions

LSM can be used to monitor disease progression and predict long-term prognosis in patients with PBC.
Investigation of Dynamic-Mechanical-Thermal Analysis of Innovative Hybrid Carbon/Glass Fibers Reinforced by GNPs and Al2O3 for Marine Structures
Authors: Abu-Okail Mohamed , Ghafaar Metwally Abdel , Elshalakany Abou Bakr , Shiba Mohamed S. , Abu-Oqail Ahmed , Gamil Mohammed
Published: September 2023

Marine structural applications face numerous challenges related to environmental load, corrosion, and fatigue under varying time and temperature conditions. One of the major challenges faced by marine structural applications is dynamic mechanical thermal analysis (DMTA). In this study, innovative hybrid carbon/glass fibers (CGF) reinforced with different contents (1.5 wt. % and 3 wt. %) of dual nano-powders, including graphene nanoplatelets (GNPs) and aluminium oxide (Al2O3), were developed as reinforcements inside the epoxy matrix. The nanocomposites were fabricated using a hand lay-up technique, resulting in a nanocomposite sheet with dimensions of 300 mm length, 200 mm width, and 2.3 mm thickness. DMTA test specimens were prepared with dimensions of 50 mm length, 10 mm width, and 2.3 mm thickness. To ensure accuracy, three replicates were conducted for each condition, and the average values were calculated for analysis. Before DMTA, the prepared nanocomposites were analyzed using optical microscopy (OM), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDAX) to compare the influence of incorporating dual nano-powders. DMTA was carried out at different temperature values (ranging from 10 °C to 105 °C) and times (ranging from 5 to 575 min) at 1 Hz frequency with a heating rate of 4 °C/min and a nitrogen flow rate of 20 ml/min. The main objective of this study was to investigate the influence of incorporating dual nano-powders such as GNPs and Al2O3on various dynamic mechanical properties including storage modulus, loss modulus, damping factor (DF), and glass transition temperature (Tg) of the hybrid carbon/glass fiber-reinforced epoxy composites. The fabricated hybrid CGF composite with 1.5% wt. GA nanoparticles exhibited higher values for the DF of 0.68 and the Tg of 73.4 °C. However, increasing the nanoparticle content to 3% wt. GA led to a deterioration in the DF (0.54) and a reduction in Tg (27.8 °C) due to decreased bonding between the carbon fibers (CF) and glass fibers (GF) caused by the higher nanoparticle concentration. The complex modulus (E*) values demonstrated expected trends with temperature and time for the CGF-1.5% wt. GA composite, indicating acceptable behaviour. In contrast, the CGF-3% wt. GA composite exhibited lower E* values, indicating a decrease in stiffness and mechanical properties compared to the CGF-1.5% wt. GA composite. Microstructural observations after DMTA revealed a uniform scattering of nanoparticles in the CGF-1.5% wt. GA sample, while the CGF-3% wt. GA sample demonstrated improved scattering of Al2O3nanoparticles on the surface. The microstructural analysis further indicated a brittle nature with high resistance to crack initiation and propagation in the CGF-1.5% wt. GA composite.
Ontology learning from relational database: a review
Authors: Mosca Rosalba , De Santo Massimo , Gaeta Rosario
Published: September 2023

A relational database (RDB) is a digital database that uses components (such as constraints, tables, keys, etc.) to manage data in a structured manner. Because of these components, RDBs are considered ’poor’ from a semantic point of view, precisely because of the structure-oriented nature of the components used. One way to eliminate this limitation is to transform the RDB into an ontology. The purpose of this article is to review the different approaches existing in the literature to extract data from an RDB and convert it into ontology instances. Two approaches are used to integrate the mapping between RDBs and ontologies. The first allows ontologies to be extracted from an RDB, the second consists of a mapping of the relational database to an existing ontology. Our proposed review focuses on methods for creating a specific ontology from an RDB. The proposed review examines this field, classifying the methods that will be analyzed according to their inputs and outputs. Such classification may be useful for understanding the usability of methods. The aim is to critically review existing studies to help outline this research topic’s progress and identify methods’ gaps and functionalities.
Fuzzy cellular automaton with slow-to-start property
Authors: Higashi Kohei
Published: September 2023

We propose a nonlinear discrete model which incorporates the effects of slow-to-start property into rule 184 fuzzy CA as a mathematical traffic flow model. The exact solutions corresponding to free-flow and congested states are given for the new model. The exact average fluxes of both states are also given. By studying the stability of the uniform solution corresponding to the congested state, the critical point at which congestion does not occur is obtained analytically. This may be the first analytical result on stability of congested states of the models with slow-to-start property. The stability of some typical free-flow states are also discussed analytically.
Hilbert-type operator induced by radial weight on Hardy spaces
Authors: Merchán Noel , Peláez José Ángel , de la Rosa Elena
Published: September 2023

We consider the Hilbert-type operator defined by $$\begin{aligned} H_{\omega }(f)(z)=\int _0^1 f(t)\left( \frac{1}{z}\int _0^z B^{\omega }_t(u)\,du\right) \,\omega (t)dt, \end{aligned}$$

H
ω

(
f
)

(
z
)

=

∫
0
1

f

(
t
)

1
z

∫
0
z

B
t
ω

(
u
)

d
u

ω

(
t
)

d
t
,

where $$\{B^{\omega }_\zeta \}_{\zeta \in \mathbb {D}}$$

{

B
ζ
ω

}

ζ
∈
D

are the reproducing kernels of the Bergman space $$A^2_\omega $$

A
ω
2

induced by a radial weight $$\omega $$
ω
in the unit disc $$\mathbb {D}$$
D
. We prove that $$H_{\omega }$$

H
ω

is bounded on the Hardy space $$H^p$$

H
p

, $$1<p<\infty $$

1
<
p
<
∞

, if and only if $$\begin{aligned} \sup _{0\le r<1} \frac{\widehat{\omega }(r)}{\widehat{\omega }\left( \frac{1+r}{2}\right) }<\infty , (\dag )\end{aligned}$$

sup

0
≤
r
<
1

ω
^

(
r
)

ω
^

1
+
r

2

<
∞
,

(
†
)

and $$\begin{aligned} \sup \limits _{0<r<1}\left( \int _0^r \frac{1}{\widehat{\omega }(t)^p} dt\right) ^{\frac{1}{p}} \left( \int _r^1 \left( \frac{\widehat{\omega }(t)}{1-t}\right) ^{p'}\,dt\right) ^{\frac{1}{p'}} <\infty , \end{aligned}$$

sup

0
<
r
<
1

∫
0
r

1

ω
^

(
t
)

p

d
t

1
p

∫
r
1

ω
^

(
t
)

1
-
t

p
′

d
t

1

p
′

<
∞
,

where $$\widehat{\omega }(r)=\int _r^1 \omega (s)\,ds$$

ω
^

(
r
)

=

∫
r
1

ω

(
s
)

d
s

. We also prove that $$H_\omega : H^1\rightarrow H^1$$

H
ω

:

H
1

→

H
1

is bounded if and only if ($$\dag $$
†
) holds and $$\begin{aligned} \sup \limits _{r \in [0,1)} \frac{\widehat{\omega }(r)}{1-r} \left( \int _0^r \frac{ds}{\widehat{\omega }(s)}\right) <\infty . \end{aligned}$$

sup

r
∈
[
0
,
1
)

ω
^

(
r
)

1
-
r

∫
0
r

ds

ω
^

(
s
)

<
∞
.

As for the case $$p=\infty $$

p
=
∞

, $$H_\omega $$

H
ω

is bounded from $$H^\infty $$

H
∞

to $$\mathord \textrm{BMOA}$$
BMOA
, or to the Bloch space, if and only if ($$\dag $$
†
) holds. In addition, we prove that there does not exist radial weights $$\omega $$
ω
such that $$H_{\omega }: H^p \rightarrow H^p $$

H
ω

:

H
p

→

H
p

, $$1\le p<\infty $$

1
≤
p
<
∞

, is compact and we consider the action of $$H_{\omega }$$

H
ω

on some spaces of analytic functions closely related to Hardy spaces.
TTOBench—an Open-Source Library for Train Trajectory Optimization
Authors: Kouzoupis Dimitris , Pendharkar Ishan , Corman Francesco
Published: September 2023

Over the past few years, the field of train trajectory optimization has been enriched with numerous publications proposing novel solution algorithms, solving known practical problems or applying existing methods to academic and industrial applications. However, the data that were used in the numerical experiments - especially those related to the railway infrastructure - are rarely public, making the comparison of different algorithms or the reproduction of any results difficult if not impossible. In this work, we try to bridge this gap by introducing a library of track data with slope and speed limit information as a first step towards an open-source benchmark suite for train trajectory optimization. The collected items were either publicly available in some form or acquired by the digitalization of published figures. We encourage authors in the field to contribute to this library for the common benefit of the community.
Surgeon-Stratified Periprosthetic Fracture Risk in a Single-Hospital Cohort of 1531 Uncemented ABG-II Femoral Stems at Primary Total Hip Arthroplasty
Authors: Kropivšek Luka , Antolič Vane , Mavčič Blaž
Published: September 2023

Purpose

Late periprosthetic fracture risk with uncemented ABG-II femoral stems at primary total hip arthroplasty (THA) has been reported before, but single-hospital surgeon-stratified reports of this implant have never been published. We asked whether periprosthetic fracture rates of ABG-II femoral stems implanted at a single tertiary hospital depended on patients’ age, gender and the operating surgeon.

Methods

The study included 1531 consecutive primary ABG-II femoral stems implanted at a single tertiary hospital between January 1, 2012 and December 31, 2018. The Kaplan–Meier and Cox regression analyses were performed after 3.6–10.6 years of follow-up.

Results

In the cohort, we recorded 8 intraoperative, 22 early postoperative (within 90 days of implantation) and 26 late periprosthetic fractures (over 90 days postoperatively). The revision rate of ABG-II femoral stems was 5.1/100 component-years for early and 0.3/100 component-years for late periprosthetic fractures. The Kaplan–Meier cumulative probability of periprosthetic fracture was 2.1% at one, 2.3% at 2, 3.2% at 5, and 6.5% at 10 years after the implantation. Higher patient's age at operation was an independent risk factor of subsequent periprosthetic fracture (hazard ratio 1.07, 95% confidence interval 1.03–1.10; p < 0.01), regardless of the operating surgeon. Most of the fractured femora were Dorr type C (stovepipe).

Conclusion

The study presents the largest published ABG-II femoral stem cohort from a single hospital so far with 9291 component-years of observation. Periprosthetic fracture risk of ABG-II increased with patients’ age, had no variability between different surgeons, and was considerably higher from other uncemented femoral stems used at the same hospital.

Level of Evidence

III.
Multilingualism in Early Medieval Britain
Authors: Brady Lindy
Published: September 2023

In the words of its own historians, pre-Norman Britain held five languages and four peoples. Yet in modern scholarship, Old English is too often studied separately from the other languages that surrounded it. This Element offers a comprehensive synthesis of the evidence from the pre-Norman period that situates Old English as one of several living languages that together formed the basis of a vibrant oral and written literary culture in early medieval Britain. Each section centres around a key thematic topic and is illustrated through a series of memorable case studies that encapsulate the extent to which multilingualism appeared in every facet of life in early medieval Britain: religious and scholarly; political and military; economic and cultural; intellectual and artistic. The Element makes an overall argument for the dynamic extent of transcultural literary and linguistic culture in early medieval Britain before the arrival of the Normans.
On a multi-parameter variant of the Bellow–Furstenberg problem
Authors: Bourgain Jean , Mirek Mariusz , Stein Elias M. , Wright James
Published: September 2023

We prove convergence in norm and pointwise almost everywhere on

$L^p$

,

$p\in (1,\infty )$

, for certain multi-parameter polynomial ergodic averages by establishing the corresponding multi-parameter maximal and oscillation inequalities. Our result, in particular, gives an affirmative answer to a multi-parameter variant of the Bellow–Furstenberg problem. This paper is also the first systematic treatment of multi-parameter oscillation semi-norms which allows an efficient handling of multi-parameter pointwise convergence problems with arithmetic features. The methods of proof of our main result develop estimates for multi-parameter exponential sums, as well as introduce new ideas from the so-called multi-parameter circle method in the context of the geometry of backwards Newton diagrams that are dictated by the shape of the polynomials defining our ergodic averages.
Self-sustained azimuthal aeroacoustic modes. Part 2. Effect of a swirling mean flow on the modal dynamics
Authors: Faure-Beaulieu Abel , Pedergnana Tiemo , Noiray Nicolas
Published: September 2023

The whistling induced by a low-Mach turbulent flow through a deep axisymmetric cavity in a duct is investigated theoretically and experimentally. The experiments include acoustic measurements and stereoscopic particle image velocimetry (PIV). The paper focuses on the effect of a mean swirl on the dynamics of the azimuthal aeroacoustic modes. The mean swirl in the cavity has two origins: one component is imposed by a controlled tangential air injection upstream of the cavity, and the other component spontaneously arises under the action of the self-sustained azimuthal aeroacoustic mode, as explained in the companion paper, Part 1 (Faure-Beaulieu, Xiong, Pedergnana & Noiray, J. Fluid Mech., vol. 971, 2023, A21). Experiments show that the dynamics of the aeroacoustic wave is influenced by the imposed swirl. In particular, the spinning wave propagating against the swirl is promoted. To explain this, a linear perturbation analysis is performed around an incompressible mean swirling flow obtained from RANS simulations. It reveals that the dominant shear layer modes of azimuthal order 1 and −1 involved in the whistling phenomenon are helical modes winding respectively with and against the swirl, and spinning respectively in counterswirl and co-swirl directions. The counterswirl hydrodynamic mode is the least damped of the two, which is in agreement with the experimental observations. Finally, a low-order model based on the wave equation is derived. With only a few parameters, it fully reproduces the experimental observations for a wide range of imposed swirl intensity in the duct flow, and it allows us to disentangle the mechanisms responsible for this complex aeroacoustic instability.
Pore-resolved investigation of turbulent open channel flow over a randomly packed permeable sediment bed
Authors: Karra Shashank K. , Apte Sourabh V. , He Xiaoliang , Scheibe Timothy D.
Published: September 2023

Pore-resolved direct numerical simulations are performed to investigate the interactions between streamflow turbulence and groundwater flow through a randomly packed porous sediment bed for three permeability Reynolds numbers,

$Re_K=2.56$

, 5.17 and 8.94, representative of natural stream or river systems. Time–space averaging is used to quantify the Reynolds stress, form-induced stress, mean flow and shear penetration depths, and mixing length at the sediment–water interface (SWI). The mean flow and shear penetration depths increase with

$Re_K$

and are found to be nonlinear functions of non-dimensional permeability. The peaks and significant values of the Reynolds stresses, form-induced stresses, and pressure variations are shown to occur in the top layer of the bed, which is also confirmed by conducting simulations of just the top layer as roughness elements over an impermeable wall. The probability distribution functions (p.d.f.s) of normalized local bed stress are found to collapse for all Reynolds numbers, and their root-mean-square fluctuations are assumed to follow logarithmic correlations. The fluctuations in local bed stress and resultant drag and lift forces on sediment grains are mainly a result of the top layer; their p.d.f.s are symmetric with heavy tails, and can be well represented by a non-Gaussian model fit. The bed stress statistics and the pressure data at the SWI potentially can be used in providing better boundary conditions in modelling of incipient motion and reach-scale transport in the hyporheic zone.
Electrostatic Waves Around a Magnetopause Reconnection Secondary Electron Diffusion Region Modulated by Whistler and Lower‐Hybrid Waves
Authors: Wang Shan , Graham Daniel B. , An Xin , Li Li , Zong Qiu‐Gang , Zhou Xu‐Zhi , Li Wen‐Ya , Liu Zhi‐Yang
Published: September 2023

We investigate electrostatic waves in a magnetopause reconnection event around a secondary electron diffusion region. Near the current sheet mid‐plane, parallel electron beam‐mode waves are modulated by whistler waves. We conclude that the anisotropy of energized electrons in the reconnection exhaust excites whistler waves, which produce spatially modulated electron beams through nonlinear Landau resonance, and these beams excite beam‐mode electrostatic waves. In the separatrix region, parallel propagating electrostatic waves associated with field‐aligned electron beams and perpendicular propagating electron cyclotron harmonic waves with loss cone distributions exhibit modulation frequencies in the lower‐hybrid wave (LHW) frequency range. We infer that LHWs scatter electrons to produce beams and alter loss cones to modulate electrostatic waves. The results advance our understanding about the regimes and mechanisms of electrostatic waves in reconnection, with an emphasis on their coupling with lower‐frequency electromagnetic waves.
Enhanced Solar Wind Dynamic Pressure as a Driver of Low‐Energy Proton Temperature Anisotropies and High‐Frequency EMIC Waves
Authors: Xue Zuxiang , Yuan Zhigang , Yu Xiongdong , Huang Zheng , Deng Dan
Published: September 2023

Typical and high‐frequency electromagnetic ion cyclotron (EMIC) waves were simultaneously registered by satellites in the afternoon sector of the inner magnetosphere during enhanced solar wind dynamic pressure (Pdyn) on 3 November 2015. The compression of the dayside magnetosphere leads to amplified field intensities and squeezed field lines, which causes adiabatic accelerations of both hot (10s keV) and low‐energy (10s–100s eV) protons at the equatorial region. Temperature anisotropies of low‐energy protons enhance in immediate response to Pdyn impact accompanied by the generation of EMIC waves with frequencies close to proton gyrofrequencies. The low‐energy protons with enhanced fluxes are found to resonate with the high‐frequency EMIC waves, indicating their potential contributions to wave excitation. The comprehensive analysis of this work provides a new physical scenario describing the evolution of low‐energy protons and the generation of high‐frequency EMIC waves, reflecting the critical role of Pdyn in magnetospheric plasma dynamics.
Budyko Framework Based Analysis of the Effect of Climate Change on Watershed Evaporation Efficiency and Its Impact on Discharge Over Europe
Authors: Collignan Julie , Polcher Jan , Bastin Sophie , Quintana‐Segui Pere
Published: September 2023

In the context of climate change, the stakes surrounding water availability are rapidly intensifying. Decomposing and quantifying the effects of climate on discharge allows us to understand their impact on water resources better. We propose a methodology to separate the effect of change in the annual mean of climate variables from the effect of the intra‐annual distribution of precipitation. It combines the Budyko framework with land surface model (LSM) outputs. The LSM is used to reproduce the behavior of 2,134 reconstructed watersheds across Europe between 1902 and 2010, with climate inputs as the only source of change. We fit a one‐parameter approximation of the Budyko framework to the LSM outputs. It accounts for the evolution of the annual mean in precipitation (P) and potential evapotranspiration (PET). We introduce a varying parameter in the equation, representing the effect of long‐term variations in the intra‐annual distribution of P and PET. To better assess the effects of changes in annual means or intra‐annual distribution of P, we construct synthetic forcings fixing one or the other. European results show that the trends in the annual averages of P dominate the trends in discharge due to climate. The second main climate driver is PET, except over the Mediterranean area, where changes in intra‐annual variations of P have a higher impact on discharge than trends in PET. Therefore, the effects of changes in the intra‐annual distribution of climate variables are to be addressed when looking at changes in annual discharge.
The singularities of light: intensity, phase, polarisation
Authors: Berry Michael V.
Published: September 2023

In modern optics, light can be described at different levels: as rays, as scalar waves, as vector fields, and as quantum fields. In the first three levels, there are singularities—characteristic features, useful in interpreting phenomena at that level. In geometrical optics, the singularities are ray caustics; in scalar wave optics, they are phase singularities (=wave dislocations= wave vortices = nodal manifolds); in vector waves, they are singularities where the polarisation of light is purely linear or purely circular. The singularities at each level are dissolved at the next level. Similar singularities occur in all waves, not just light.
Perceptual learning deficits mediated by somatostatin releasing inhibitory interneurons of olfactory bulb in an early life stress mouse model
Authors: Pardasani Meenakshi , Ramakrishnan Anantha Maharasi , Mahajan Sarang , Kantroo Meher , McGowan Eleanor , Das Susobhan , Srikanth Priyadharshini , Pandey Sanyukta , Abraham Nixon M.
Published: September 2023

Early life adversity (ELA) causes aberrant functioning of neural circuits affecting the health of an individual. While ELA-induced behavioural disorders resulting from sensory and cognitive disabilities can be assessed clinically, the neural mechanisms need to be probed using animal models by employing multi-pronged experimental approaches. As ELA can alter sensory perception, we investigated the effect of early weaning on murine olfaction. By implementing go/no-go odour discrimination paradigm, we observed olfactory learning and memory impairments in early life stressed (ELS) male mice. As olfactory bulb (OB) circuitry plays a critical role in odour learning, we studied the plausible changes in the OB of ELS mice. Lowered c-Fos activity in the external plexiform layer and a reduction in the number of dendritic processes of somatostatin-releasing, GABAergic interneurons (SOM-INs) in the ELS mice led us to hypothesise the underlying circuit. We recorded reduced synaptic inhibitory feedback on mitral/tufted (M/T) cells, in the OB slices from ELS mice, explaining the learning deficiency caused by compromised refinement of OB output. The reduction in synaptic inhibition was nullified by the photo-activation of ChR2-expressing SOM-INs in ELS mice. The role of SOM-INs was revealed by learning-dependent refinement of Ca2+dynamics quantified by GCaMP6f signals, which was absent in ELS mice. Further, the causal role of SOM-INs involving circuitry was investigated by optogenetic modulation during the odour discrimination learning. Photo-activating these neurons rescued the ELA-induced learning deficits. Conversely, photo-inhibition caused learning deficiency in control animals, while it completely abolished the learning in ELS mice, confirming the adverse effects mediated by SOM-INs. Our results thus establish the role of specific inhibitory circuit in pre-cortical sensory area in orchestrating ELA-dependent changes.
Relative importance of speech and voice features in the classification of schizophrenia and depression
Authors: Berardi Mark , Brosch Katharina , Pfarr Julia-Katharina , Schneider Katharina , Sültmann Angela , Thomas-Odenthal Florian , Wroblewski Adrian , Usemann Paula , Philipsen Alexandra , Dannlowski Udo , Nenadić Igor , Kircher Tilo , Krug Axel , Stein Frederike , Dietrich Maria
Published: September 2023

Speech is a promising biomarker for schizophrenia spectrum disorder (SSD) and major depressive disorder (MDD). This proof of principle study investigates previously studied speech acoustics in combination with a novel application of voice pathology features as objective and reproducible classifiers for depression, schizophrenia, and healthy controls (HC). Speech and voice features for classification were calculated from recordings of picture descriptions from 240 speech samples (20 participants with SSD, 20 with MDD, and 20 HC each with 4 samples). Binary classification support vector machine (SVM) models classified the disorder groups and HC. For each feature, the permutation feature importance was calculated, and the top 25% most important features were used to compare differences between the disorder groups and HC including correlations between the important features and symptom severity scores. Multiple kernels for SVM were tested and the pairwise models with the best performing kernel (3-degree polynomial) were highly accurate for each classification: 0.947 for HC vs. SSD, 0.920 for HC vs. MDD, and 0.932 for SSD vs. MDD. The relatively most important features were measures of articulation coordination, number of pauses per minute, and speech variability. There were moderate correlations between important features and positive symptoms for SSD. The important features suggest that speech characteristics relating to psychomotor slowing, alogia, and flat affect differ between HC, SSD, and MDD.
A spectroscopic liquid biopsy for the earlier detection of multiple cancer types
Authors: Cameron James M. , Sala Alexandra , Antoniou Georgios , Brennan Paul M. , Butler Holly J. , Conn Justin J. A. , Connal Siobhan , Curran Tom , Hegarty Mark G. , McHardy Rose G. , Orringer Daniel , Palmer David S. , Smith Benjamin R. , Baker Matthew J.
Published: September 2023

Background

A rapid, low-cost blood test that can be applied to reliably detect multiple different cancer types would be transformational.

Methods

In this large-scale discovery study (n = 2092 patients) we applied the Dxcover® Cancer Liquid Biopsy to examine eight different cancers. The test uses Fourier transform infrared (FTIR) spectroscopy and machine-learning algorithms to detect cancer.

Results

Area under the receiver operating characteristic curve (ROC) values were calculated for eight cancer types versus symptomatic non-cancer controls: brain (0.90), breast (0.76), colorectal (0.91), kidney (0.91), lung (0.91), ovarian (0.86), pancreatic (0.84) and prostate (0.86). We assessed the test performance when all eight cancer types were pooled to classify ‘any cancer’ against non-cancer patients. The cancer versus asymptomatic non-cancer classification detected 64% of Stage I cancers when specificity was 99% (overall sensitivity 57%). When tuned for higher sensitivity, this model identified 99% of Stage I cancers (with specificity 59%).

Conclusions

This spectroscopic blood test can effectively detect early-stage disease and can be fine-tuned to maximise either sensitivity or specificity depending on the requirements from different healthcare systems and cancer diagnostic pathways. This low-cost strategy could facilitate the requisite earlier diagnosis, when cancer treatment can be more effective, or less toxic.

Statement of translational relevance

The earlier diagnosis of cancer is of paramount importance to improve patient survival. Current liquid biopsies are mainly focused on single tumour-derived biomarkers, which limits test sensitivity, especially for early-stage cancers that do not shed enough genetic material. This pan-omic liquid biopsy analyses the full complement of tumour and immune-derived markers present within blood derivatives and could facilitate the earlier detection of multiple cancer types. There is a low barrier to integrating this blood test into existing diagnostic pathways since the technology is rapid, simple to use, only minute sample volumes are required, and sample preparation is minimal. In addition, the spectroscopic liquid biopsy described in this study has the potential to be combined with other orthogonal tests, such as cell-free DNA, which could provide an efficient route to diagnosis. Cancer treatment can be more effective when given earlier, and this low-cost strategy has the potential to improve patient prognosis.
CSE reduces OTUD4 triggering lung epithelial cell apoptosis via PAI-1 degradation
Authors: Luo Lijuan , Li Tiao , Zeng Zihang , Li Herui , He Xue , Chen Yan
Published: September 2023

Ovarian tumor family deubiquitinase 4 (OTUD4), a member of the OTU deubiquitinating enzyme, is implicated to decrease in cancer to regulate cell apoptosis. However, the role of OTUD4 in cigarette smoke induced epithelial cell apoptosis and its mechanism have not been elucidated. In this study, we showed that OTUD4 protein reduced in CSE treated mice and airway epithelial cells. OTUD4 silence aggravated cell apoptosis and emphysematous change in the lung tissue of cigarette smoke extract (CSE) treated mice. Additionally, restoration of OTUD4 in the lung of mice alleviated CSE induced apoptosis and emphysematous morphology change. The effect of OTUD4 on cell apoptosis was also confirmed in vitro. Through protein profile screening, we identified that OTUD4 may interact with plasminogen activator inhibitor 1(PAI-1). We further confirmed that OTUD4 interacted with PAI-1 for de-ubiquitination and inhibiting CSE induced PAI-1 degradation. Furthermore, the protective role of OTUD4 in airway epithelial cells apoptosis was blocked by PAI-1 deactivation. Taken together, our data suggest that OTUD4 regulates cigarette smoke (CS)-triggered airway epithelial cell apoptosis via modulating PAI-1 degradation. Targeting OUTD4/PAI-1 signaling might potentially provide a therapeutic target against the lung cell apoptosis in cigarette smoke (CS)-induced emphysema.
Inhibition of cGAS–STING pathway alleviates neuroinflammation-induced retinal ganglion cell death after ischemia/reperfusion injury
Authors: Wu Xingdi , Yu Naiji , Ye Zifan , Gu Yuxiang , Zhang Chengshou , Chen Min , Wang Kaijun
Published: September 2023

Acute glaucoma is a vision-threatening disease characterized by a sudden elevation in intraocular pressure (IOP), followed by retinal ganglion cell (RGC) death. Cytosolic double-stranded DNA (dsDNA)—a damage-associated molecular pattern (DAMP) that triggers inflammation and immune responses—has been implicated in the pathogenesis of IOP-induced RGC death, but the underlying mechanism is not entirely clear. In this study, we investigated the effect of the inflammatory cascade on dsDNA recognition and examined the neuroprotective effect of the cyclic GMP-AMP (cGAMP) synthase (cGAS) antagonist A151 on a retinal ischemia/reperfusion (RIR) mouse model. Our findings reveal a novel mechanism of microglia-induced neuroinflammation-mediated RGC death associated with glaucomatous vision loss. We found that RIR injury facilitated the release of dsDNA, which initiated inflammatory responses by activating cGAS–stimulator of interferon genes (STING) pathway. Correspondingly, elevated expressions of cGAS and STING were found in retinal samples from human glaucoma donors. Furthermore, we found that deletion or inhibition of cGAS or STING in microglia transfected with poly(dA:dT) specifically decreased microglia activation and inflammation response. We also observed that A151 treatment promoted poly(dA:dT)--stimulated changes in polarization from the M1 to the M2 phenotype in microglia. Subsequently, A151 administered to mice effectively inhibited the cGAS–STING pathway, absent in melanoma 2 (AIM2) inflammasome and pyroptosis-related molecules. Furthermore, A151 administration significantly reduced neuroinflammation, ameliorated RGC death and RGC-related reductions in visual function. These findings provide a unique perspective on glaucomatous neuropathogenesis and suggest cGAS as an underlying target of retinal inflammation to provide a potential therapeutic for acute glaucoma.
Low glucose metabolite 3-phosphoglycerate switches PHGDH from serine synthesis to p53 activation to control cell fate
Authors: Wu Yu-Qing , Zhang Chen-Song , Xiong Jinye , Cai Dong-Qi , Wang Chen-Zhe , Wang Yu , Liu Yan-Hui , Wang Yu , Li Yiming , Wu Jian , Wu Jianfeng , Lan Bin , Wang Xuefeng , Chen Siwei , Cao Xianglei , Wei Xiaoyan , Hu Hui-Hui , Guo Huiling , Yu Yaxin , Ghafoor Abdul , Xie Changchuan , Wu Yaying , Xu Zheni , Zhang Cixiong , Zhu Mingxia , Huang Xi , Sun Xiufeng , Lin Shu-Yong , Piao Hai-Long , Zhou Jianyin , Lin Sheng-Cai
Published: September 2023

Glycolytic intermediary metabolites such as fructose-1,6-bisphosphate can serve as signals, controlling metabolic states beyond energy metabolism. However, whether glycolytic metabolites also play a role in controlling cell fate remains unexplored. Here, we find that low levels of glycolytic metabolite 3-phosphoglycerate (3-PGA) can switch phosphoglycerate dehydrogenase (PHGDH) from cataplerosis serine synthesis to pro-apoptotic activation of p53. PHGDH is a p53-binding protein, and when unoccupied by 3-PGA interacts with the scaffold protein AXIN in complex with the kinase HIPK2, both of which are also p53-binding proteins. This leads to the formation of a multivalent p53-binding complex that allows HIPK2 to specifically phosphorylate p53-Ser46 and thereby promote apoptosis. Furthermore, we show that PHGDH mutants (R135W and V261M) that are constitutively bound to 3-PGA abolish p53 activation even under low glucose conditions, while the mutants (T57A and T78A) unable to bind 3-PGA cause constitutive p53 activation and apoptosis in hepatocellular carcinoma (HCC) cells, even in the presence of high glucose. In vivo, PHGDH-T57A induces apoptosis and inhibits the growth of diethylnitrosamine-induced mouse HCC, whereas PHGDH-R135W prevents apoptosis and promotes HCC growth, and knockout of Trp53 abolishes these effects above. Importantly, caloric restriction that lowers whole-body glucose levels can impede HCC growth dependent on PHGDH. Together, these results unveil a mechanism by which glucose availability autonomously controls p53 activity, providing a new paradigm of cell fate control by metabolic substrate availability.
Device-independent certification of indefinite causal order in the quantum switch
Authors: van der Lugt Tein , Barrett Jonathan , Chiribella Giulio
Published: September 2023

Quantum theory is compatible with scenarios in which the order of operations is indefinite. Experimental investigations of such scenarios, all of which have been based on a process known as the quantum switch, have provided demonstrations of indefinite causal order conditioned on assumptions on the devices used in the laboratory. But is a device-independent certification possible, similar to the certification of Bell nonlocality through the violation of Bell inequalities? Previous results have shown that the answer is negative if the switch is considered in isolation. Here, however, we present an inequality that can be used to device-independently certify indefinite causal order in the quantum switch in the presence of an additional spacelike-separated observer under an assumption asserting the impossibility of superluminal and retrocausal influences.
Emplacement of the Argyle diamond deposit into an ancient rift zone triggered by supercontinent breakup
Authors: Olierook Hugo K. H. , Fougerouse Denis , Doucet Luc S. , Liu Yebo , Rayner Murray J. , Danišík Martin , Condon Daniel J. , McInnes Brent I. A. , Jaques A. Lynton , Evans Noreen J. , McDonald Bradley J. , Li Zheng-Xiang , Kirkland Christopher L. , Mayers Celia , Wingate Michael T. D.
Published: September 2023

Argyle is the world’s largest source of natural diamonds, yet one of only a few economic deposits hosted in a Paleoproterozoic orogen. The geodynamic triggers responsible for its alkaline ultramafic volcanic host are unknown. Here we show, using U-Pb and (U-Th)/He geochronology of detrital apatite and detrital zircon, and U-Pb dating of hydrothermal titanite, that emplacement of the Argyle lamproite is bracketed between 1311 ± 9 Ma and 1257 ± 15 Ma (2σ), older than previously known. To form the Argyle lamproite diatreme complex, emplacement was likely driven by lithospheric extension related to the breakup of the supercontinent Nuna. Extension facilitated production of low-degree partial melts and their migration through transcrustal corridors in the Paleoproterozoic Halls Creek Orogen, a rheologically-weak rift zone adjacent to the Kimberley Craton. Diamondiferous diatreme emplacement during (super)continental breakup may be prevalent but hitherto under-recognized in rift zones at the edges of ancient continental blocks.
Auxin-producing bacteria promote barley rhizosheath formation
Authors: Xu Feiyun , Liao Hanpeng , Yang Jinyong , Zhang Yingjiao , Yu Peng , Cao Yiying , Fang Ju , Chen Shu , Li Liang , Sun Leyun , Du Chongxuan , Wang Ke , Dang Xiaolin , Feng Zhiwei , Cao Yifan , Li Ying , Zhang Jianhua , Xu Weifeng
Published: September 2023

The rhizosheath, or the layer of soil closely adhering to roots, can help plants to tolerate drought under moderate soil drying conditions. Rhizosheath formation is the result of poorly understood interactions between root exudates, microbes, and soil conditions. Here, we study the roles played by the soil microbiota in rhizosheath formation in barley (a dry crop). We show that barley rhizosheath formation is greater in acid soil than in alkaline soil, and inoculation with microbiota from acid soil enhances rhizosheath formation in alkaline soil. The rhizosheath-promoting activity is associated with the presence of Flavobacteriaceae and Paenibacillaceae bacteria that express genes for biosynthesis of indole-3-acetic acid (IAA, a common auxin), as determined by metagenomics and metatranscriptomics. Two bacterial strains isolated from rhizosheath (Chryseobacterium culicis and Paenibacillus polymyxa) produce IAA and enhance barley rhizosheath formation, while their IAA-defective mutants are unable to promote rhizosheath formation. Co-inoculation with the IAA-producing strains enhances barley grain yield in field experiments through an increase in spike number. Our findings contribute to our understanding of barley rhizosheath formation, and suggest potential strategies for crop improvement.
Translating genomic tools to Raman spectroscopy analysis enables high-dimensional tissue characterization on molecular resolution
Authors: Sigle Manuel , Rohlfing Anne-Katrin , Kenny Martin , Scheuermann Sophia , Sun Na , Graeßner Ulla , Haug Verena , Sudmann Jessica , Seitz Christian M. , Heinzmann David , Schenke-Layland Katja , Maguire Patricia B. , Walch Axel , Marzi Julia , Gawaz Meinrad Paul
Published: September 2023

Spatial transcriptomics of histological sections have revolutionized research in life sciences and enabled unprecedented insights into genetic processes involved in tissue reorganization. However, in contrast to genomic analysis, the actual biomolecular composition of the sample has fallen behind, leaving a gap of potentially highly valuable information. Raman microspectroscopy provides untargeted spatiomolecular information at high resolution, capable of filling this gap. In this study we demonstrate spatially resolved Raman “spectromics” to reveal homogeneity, heterogeneity and dynamics of cell matrix on molecular levels by repurposing state-of-the-art bioinformatic analysis tools commonly used for transcriptomic analyses. By exploring sections of murine myocardial infarction and cardiac hypertrophy, we identify myocardial subclusters when spatially approaching the pathology, and define the surrounding metabolic and cellular (immune-) landscape. Our innovative, label-free, non-invasive “spectromics” approach could therefore open perspectives for a profound characterization of histological samples, while additionally allowing the combination with consecutive downstream analyses of the very same specimen.
A molecular pyroelectric enabling broadband photo-pyroelectric effect towards self-driven wide spectral photodetection
Authors: Zeng Xi , Liu Yi , Weng Wen , Hua Lina , Tang Liwei , Guo Wuqian , Chen Yaoyao , Yang Tian , Xu Haojie , Luo Junhua , Sun Zhihua
Published: September 2023

Broadband spectral photoresponse has shown bright prospects for various optoelectronic devices, while fulfilling high photoactivity beyond the material bandgap is a great challenge. Here, we present a molecular pyroelectric, N-isopropylbenzylaminium trifluoroacetate (N-IBATFA), of which the broadband photo-pyroelectric effects allow for self-driven wide spectral photodetection. As a simple organic binary salt, N-IBATFA possesses a large polarization (~9.5 μC cm−2), high pyroelectric coefficient (~6.9 μC cm−2 K−1) and figures-of-merits (FV = 187.9 × 10−2 cm2 μC−1; FD = 881.5 × 10−5 Pa−0.5) comparable to the state-of-art pyroelectric materials. Particularly, such intriguing attributes endow broadband photo-pyroelectric effect, namely, transient currents covering ultraviolet (UV, 266 nm) to near-infrared (NIR, 1950 nm) spectral regime, which breaks the restriction of its optical absorption and thus allows wide UV-NIR spectral photodetection. Our finding highlights the potential of molecular system as high-performance candidates toward self-powered wide spectral photodetection.
Composition of cetacean communities worldwide shapes their contribution to ocean nutrient cycling
Authors: Gilbert Lola , Jeanniard-du-Dot Tiphaine , Authier Matthieu , Chouvelon Tiphaine , Spitz Jérôme
Published: September 2023

Defecation by large whales is known to fertilise oceans with nutrients, stimulating phytoplankton and ecosystem productivity. However, our current understanding of these processes is limited to a few species, nutrients and ecosystems. Here, we investigate the role of cetacean communities in the worldwide biological cycling of two major nutrients and six trace nutrients. We show that cetaceans release more nutrients in mesotrophic to eutrophic temperate waters than in oligotrophic tropical waters, mirroring patterns of ecosystem productivity. The released nutrient cocktails also vary geographically, driven by the composition of cetacean communities. The roles of small cetaceans, deep diving cetaceans and baleen whales differ quantitatively and functionally, with contributions of small cetaceans and deep divers exceeding those of large whales in some areas. The functional diversity of cetacean communities expands beyond their role as top predators to include their role as active nutrient vectors, which might be equally important to local ecosystem dynamics.
Nongenetic surface engineering of mesenchymal stromal cells with polyvalent antibodies to enhance targeting efficiency
Authors: Ye Tenghui , Liu Xi , Zhong Xianghua , Yan Ran , Shi Peng
Published: September 2023

Systemic infusion is a prevalent administration method for mesenchymal stromal cells (MSCs) in clinical trials. However, the inability to deliver a large number of therapeutic cells to diseased tissue is a substantial barrier. Here, we demonstrate that surface engineering of MSCs with polyvalent antibodies can effectively improve the targeting efficiency of MSCs to diseased tissue. The polyvalent antibody is directly synthesized on the cell surface via DNA template-directed biomolecule assembly. The data show that engineered MSCs exhibit superior adhesion to inflamed endothelium in vitro and in vivo. In female mouse models of acute inflammation and inflammatory bowel disease, engineered MSCs show enhanced targeting efficiency and therapeutic efficacy in damaged tissues. Notably, the entire procedure for polyvalent functionalization only requires the simple mixing of cells and solutions under physiological conditions within a few hours, which significantly reduces preparation processes and manufacturing costs and minimizes the impact on the cells. Thus, our study provides a strategy for improved MSC-based regenerative medicine.
Selecting cardiac magnetic resonance images suitable for annotation of pulmonary arteries using an active-learning based deep learning model
Authors: van der Veen Werner , Benjamins Jan-Walter , Yeung Ming Wai , van der Harst Pim
Published: September 2023

An increasing and aging patient population poses a growing burden on healthcare professionals. Automation of medical imaging diagnostics holds promise for enhancing patient care and reducing manpower required to accommodate an increasing patient-population. Deep learning, a subset of machine learning, has the potential to facilitate automated diagnostics, but commonly requires large-scaled labeled datasets. In medical domains, data is often abundant but labeling is a laborious and costly task. Active learning provides a method to optimize the selection of unlabeled samples that are most suitable for improvement of the model and incorporate them into the model training process. This approach proves beneficial when only a small number of labeled samples are available. Various selection methods currently exist, but most of them employ fixed querying schedules. There is limited research on how the timing of a query can impact performance in relation to the number of queried samples. This paper proposes a novel approach called dynamic querying, which aims to optimize the timing of queries to enhance model development while utilizing as few labeled images as possible. The performance of the proposed model is compared to a model trained utilizing a fully-supervised training method, and its effectiveness is assessed based on dataset size requirements and loss rates. Dynamic querying demonstrates a considerably faster learning curve in relation to the number of labeled samples used, achieving an accuracy of 70% using only 24 samples, compared to 82% for a fully-supervised model trained on the complete training dataset of 1017 images.