bluuebunny/crossref_metadata_2025 huggingface dataset:
A concept of “materials” diffraction and imaging beamline for SKIF: Siberian circular photon source
Authors: Chernov Vladimir A. , Bataev Ivan A. , Rakshun Yakov V. , Khomyakov Yuri V. , Gorbachev Maksim V. , Trebushinin Andrei E. , Chkhalo Nikolay I. , Krasnorutskiy Dmitry A. , Naumkin Viktor S. , Sklyarov Artem N. , Mezentsev Nikolay A. , Korsunsky Alexander M. , Dolbnya Igor P.
Published: January 2023

Over the next decade, the extremely brilliant fourth generation synchrotron radiation sources are set to become a key driving force in materials characterization and technology development. In this study, we present a conceptual design of a versatile “Materia” diffraction and imaging beamline for a low-emittance synchrotron radiation facility. The beamline was optimized for operation with three main principal delivery regimes: parallel collimated beam ∼1 mm beam size, micro-focus regime with ∼10 μm beam spot size on the sample, and nano-focus regime with <100 nm focus. All regimes will operate in the photon energy range of 10–30 keV with the key feature of the beamline being fast switching between them, as well as between the various realizations of diffraction and imaging operation modes while maintaining the target beam position at the sample, and with both spectrally narrow and spectrally broad beams up to the energy band ΔE/E of 5 × 10−2. The manuscript presents the details of the principal characteristics selected for the insertion device and beamline optics, the materials characterization techniques, including the simulations of thermal load impact on the critical beamline optics components. Significant efforts were made to design the monochromators to mitigate the very high beam power load produced by a superconducting undulator source. The manuscript will be of interest to research groups involved in the design of new synchrotron beamlines.
Effect of the E × B drift on the redistribution of the divertor particle flux in the HL-2A ECRH plasmas
Authors: Wu N. , Cheng J. , Du H. L. , Huang Z. H. , Yan L. W. , Wang W. C. , Yi K. Y. , Miao X. Q. , Gao J. M. , Xu J. Q. , Shi Z. B. , Liu Y. , Yang Q. W. , Dong J. Q. , Zhong W. L. , Xu M.
Published: January 2023

Double-peaked distribution (DPD) of particle flux has only been observed on the outer divertor target in electron cyclotron resonance heating deuterium plasmas with B×∇B toward the X-point in the HL-2A tokamak using high spatiotemporal Langmuir probe arrays. The experimental results demonstrate that the formation of the DPD is mainly due to the enhanced poloidal E×B drift flow stimulated in the divertor region, which is dependent on the plasma density, heating power, and divertor structure. The experimental results are qualitatively consistent with the SOLPS simulation. The experiment also shows that the formation of the DPD might be related to the enhanced cross field transport in the far scrape-off layer. This experimental findings presented here reveal the crucial role played by the synergistic effect of poloidal E × B drift flow and the closed divertor structure in the redistribution of the particle flux, which provides a potential way for the control of high heat flux in future fusion devices.
Experimental investigation of film reversal evolution characteristics in gas–liquid annular flow
Authors: Wang Li-song , Yang Meng , Hou Lin-tong , Liu Shuo , Zhang Jian , Xu Jing-yu
Published: January 2023

In natural gas wells, liquid loading is a severe problem threatening production safety. Published studies have verified that liquid loading is closely related to film reversal in gas–liquid annular flow, but the evolution of the film reversal is still unclear. This article reports on experiments conducted to reveal the film reversal evolution characteristics. Experiments were conducted in a 50-mm-diameter vertical pipe with superficial gas velocities ranging from 5.66 to 22.64 m/s and superficial liquid velocities ranging from 0.014 to 0.170 m/s. A camera and electrical resistance tomography were used to obtain qualitative and quantitative results, and an error analysis verified the experiments’ repeatability and reliability. The evolution process is divided objectively into three stages to clarify the film reversal: no film reversal (No-FR), the onset of film reversal (Onset-FR), and complete film reversal (Complete-FR). The three stages occur successively with decreasing gas velocity. The characteristics of the individual stages are elaborated, including the interfacial structures, morphological features, and motion trajectories. The void fractions are analyzed in both the time and frequency domains, where the statistical parameters of the probability density function, average value, and standard deviation are presented. The results show that the Onset-FR stage exhibits characteristics similar to both the No-FR and Complete-FR stages, indicating that it plays an intermediate role in the gradual evolutionary process. The current experimental results also achieve excellent agreement with published datasets and correlations.
Spirits quality classification based on machine vision technology and expert knowledge
Authors: Chen Mengchi , Liu Hao , Zhang Suyi , Liu Zhiyong , Mi Junpeng , Huang Wenjun , Li Delin
Published: January 2023

By combining machine vision technology and expert knowledge, this paper proposes an online intelligent classification solution for Chinese spirits, which effectively improves the classification accuracy and production efficiency of spirits. Specifically, an intelligent spirits quality classification system is first designed, including spirits collectors, image sampling cameras, and computing devices. According to the principle that the size and shape of the bubbles in the spirits collector will change with the alcohol content in the spirits, a classification method of spirits quality based on the convolutional neural network (CNN) and bubble region of interest (ROI) selection is proposed. Furthermore, a post-processing method based on expert knowledge is proposed to improve the accuracy of the classification algorithm. A spirits quality classification dataset containing 139 119 images is created, and 15 CNNs are tested. Test results show that the highest spirits quality classification accuracy is 98.62% after using the bubble ROI selection method, and the highest classification accuracy reached 99.82% after adopting the post-processing method. Furthermore, practical application tests show that the solution proposed in this paper can improve spirits’ production quality and efficiency.
Minimization of image lag in polycrystalline mercuric iodide converters through incorporation of Frisch grid structures for digital breast tomosynthesis
Authors: Shen Liuxing , Antonuk Larry E , El-Mohri Youcef , Zhao Qihua
Published: January 2023

Objective. Polycrystalline mercuric iodide photoconductive converters fabricated using particle-in-binder techniques (PIB HgI2) provide significantly more detected charge per x-ray interaction than from a-Se and CsI:Tl converters commonly used with active matrix flat-panel imagers (AMFPIs). This enhanced sensitivity makes PIB HgI2 an interesting candidate for applications involving low x-ray exposures—since the relatively high levels of additive electronic noise exhibited by AMFPIs incorporating a-Se and CsI:Tl reduce detective quantum efficiency (DQE) performance under such conditions. A theoretical study is reported on an approach for addressing a major challenge impeding practical use of PIB HgI2 converters—the high lag exhibited by the material (over 10%) which would lead to undesirable image artifacts in applications involving acquisition of consecutive images such as digital breast tomosynthesis. Approach. Charge transport modeling accounting for the trapping and release of holes (thought to be the primary contributor to lag) was used to examine signal properties, including lag, of pillar-supported Frisch grids embedded in the photoconductor for 100 μm pitch AMFPI pixels. Performance was examined as a function of electrode voltage, grid pitch (center-to-center distance between neighboring grid wires) and the ratio of grid wire width to grid pitch. Main results. Optimum grid designs maximizing suppression of signal generated by hole transport, without significantly affecting the total signal due to electron and hole transport, were identified and MTF was determined. For the most favorable designs, additional modeling was used to determine DQE. The results indicate that, through judicious choice of grid design and operational conditions, first frame lag can be significantly reduced to below 1%—less than the low levels exhibited by a-Se. DQE performance is shown to be largely maintained as exposure decreases—which should help to maintain good image quality. Significance. Substantial reduction of lag in PIB HgI2 converters via incorporation of Frisch grids has been demonstrated through modeling.
Improving generalization performance of electrocardiogram classification models
Authors: Han Hyeongrok , Park Seongjae , Min Seonwoo , Kim Eunji , Kim HyunGi , Park Sangha , Kim Jin-Kook , Park Junsang , An Junho , Lee Kwanglo , Jeong Wonsun , Chon Sangil , Ha Kwon-Woo , Han Myungkyu , Choi Hyun-Soo , Yoon Sungroh
Published: January 2023

Objective. Recently, many electrocardiogram (ECG) classification algorithms using deep learning have been proposed. Because the ECG characteristics vary across datasets owing to variations in factors such as recorded hospitals and the race of participants, the model needs to have a consistently high generalization performance across datasets. In this study, as part of the PhysioNet/Computing in Cardiology Challenge (PhysioNet Challenge) 2021, we present a model to classify cardiac abnormalities from the 12- and the reduced-lead ECGs. Approach. To improve the generalization performance of our earlier proposed model, we adopted a practical suite of techniques, i.e. constant-weighted cross-entropy loss, additional features, mixup augmentation, squeeze/excitation block, and OneCycle learning rate scheduler. We evaluated its generalization performance using the leave-one-dataset-out cross-validation setting. Furthermore, we demonstrate that the knowledge distillation from the 12-lead and large-teacher models improved the performance of the reduced-lead and small-student models. Main results. With the proposed model, our DSAIL SNU team has received Challenge scores of 0.55, 0.58, 0.58, 0.57, and 0.57 (ranked 2nd, 1st, 1st, 2nd, and 2nd of 39 teams) for the 12-, 6-, 4-, 3-, and 2-lead versions of the hidden test set, respectively. Significance. The proposed model achieved a higher generalization performance over six different hidden test datasets than the one we submitted to the PhysioNet Challenge 2020.
Confinement of self-generated Mg(BH4)2 particles for simultaneously enhanced flux pinning and grain connectivity in polycrystalline H-doped MgB2
Authors: Cui Ganggang , Cai Qi , Li Yanmo , Yu Qilin
Published: January 2023

The present study reports a simple quenching method to simultaneously improve flux pinning and grain connectivity in polycrystalline H-doped MgB2, which was ex-situ synthesized at 350 °C under the H2 pressure of 3 MPa. Quenching prevented the phase transformation of β-Mg(BH4)2→α-Mg(BH4)2 upon cooling, and the dominant point-pinning effects originated from the self-generated nano-sized β-Mg(BH4)2 particles that were confined within the MgB2 grains. A semi-coherent relationship was found between MgB2(100) and Mg(BH4)2(

1
ˉ

1

4
ˉ

) planes. Meanwhile, the precipitation-induced expansion of the MgB2 grains remained at room temperature, leading to an increasing number of contact points as well as grain connectivity. Compared with the un-doped MgB2, the quenched H-doped one exhibited enhanced critical current density over the entire field. These results are expected to guide the design of flux pinning centers for improving the J
c performance of standard type II superconductors.
Investigation of the generalized Euler characteristic of graphs and microwave networks split at edges and vertices
Authors: Farooq Omer , Akhshani Afshin , Białous Małgorzata , Bauch Szymon , Ławniczak Michał , Sirko Leszek
Published: January 2023

We analyze the situation when the original graph is split at edges and vertices into two disconnected subgraphs. We show that there is a relationship between the generalized Euler characteristic



o

(
∣

V

D

o

∣
)

of the original graph and the generalized Euler characteristics



i

(
∣

V

D

i

∣
)

, i = 1,2, of two disconnected subgraphs, where

∣

V

D

o

∣

and

∣

V

D

i

∣

, i = 1,2, are the numbers of vertices with the Dirichlet boundary conditions in the graphs. Theoretical predictions are verified experimentally using microwave networks which simulate quantum graphs.
Systematic study of global optical model potentials in (d, p) transfer reactions*
Authors: Gao Yonghao , Ren Zhongzhou , Jin Lei
Published: January 2023

In the T-matrix form of the transfer reaction, the optical model potentials (OMPs) are used to compute the scattering wave function and transition operator. For most cases, the elastic scattering cross sections, normally used to generate the OMPs, are not directly given in the same experiment. Then, the global OMPs, which fit the experimental data over a broad mass and energy range, are widely used in the theoretical calculations. Different sets of global OMPs with different parameter sets can reproduce the scattering cross section equally well within the uncertainty. Here, we apply different global OMPs to calculate the (differential) cross sections of

transfer reactions on the target nuclei

,

,

, and

at different energies. The results demonstrate that the effects of deuteron and nucleon global OMPs on transfer (differential) cross sections vary with energy and target mass. Furthermore, the influences of the spin-orbit coupling term of deuteron and nucleon global OMPs on the transfer cross sections are not negligible.
A novel temperature-controlled laser system to uniformly activate cutaneous thermal receptors during movable thermal stimulation
Authors: Rujoie Ahmad , Andersen Ole Kæseler , Frahm Ken Steffen
Published: January 2023

Objective. Laser stimulators have been widely used in pain studies to selectively activate Aδ and C nociceptors without coactivation of mechanoreceptors. Temperature-controlled laser systems have been implemented with low-temperature variations during stimulations, however, these systems purely enabled stationary stimulation. This study aimed to implement, test and validate a new laser stimulation system that controls skin temperature by continuously adjusting laser output during stimulus movement to allow accurate investigation of tempo-spatial mechanisms in the nociceptive system. Approach. For validation, laser stimuli were delivered to the right forearm of eight healthy subjects using a diode laser. The laser beam was displaced across the skin to deliver a moving thermal stimulation to the skin surface. To test the function and feasibility of the system, different stimulation parameters were investigated involving two control modes (open-loop and closed-loop), three displacement velocities (5, 10 and 12 mm s−1 ), two intensities (high 46 °C and low 42 °C), two stimulus lengths (20 and 100 mm) and two directions (distal and proximal). Main results. During closed-loop control, the stimulation error and variation of stimulation temperatures were significantly smaller than during open-loop control. The standard deviation of stimulation temperatures increased significantly with stimulation intensity and displacement length. Significance. This study showed that more accurate, less variable laser stimulations were delivered to the skin using closed-loop control during a movable stimulus. The more uniform skin temperature during stimuli is likely to ensure a more uniform nociceptor activation.
Insulation State Assessment of Cable Intermediate Joint based on the Combination of Variable Weight and TOPSIS
Authors: Liu Shaohui , Liang Nianbai , Chen Jiayang , Li Lei , Liu Song , Qiu Haorong , Deng Baixi
Published: January 2023

In order to understand the insulation operation state of cable joint in real time, an evaluation method of cable joint insulation state based on improved TOPSIS with variable weight is proposed. Taking the partial discharge(PD) data monitored online as an example, the representative PD characteristic parameters is selected. Furthermore, Sen + Mann-Kendall test method is used to quantitatively calculate the trend change of corresponding PD characteristic parameters. Then the deterioration degree is introduced to normalize the PD characteristic parameters. Considering the change of weight under extreme deterioration, a variable weight function is constructed to optimize the constant weight. Finally, an improved TOPSIS method is applied to construct the cable intermediate joint state evaluation model. The case analysis shows that this model is more accurately than the traditional model in assessing the insulation condition of cable intermediate joint.
Mimicry API Gateway Decision Algorithm Based on Trust Distribution
Authors: Pan Yunfei , Jia Hongyong , Liu Wenhe , Sun He , Xu Mingyang , Chen Cen
Published: January 2023

Aiming at the lack of dynamic and comprehensiveness of trust evaluation methods in current adjudication algorithms, an adjudication algorithm for mimic API gateway based on trust distribution is proposed. The algorithm comprehensively considers the direct and indirect trust relationships between equipment executives from the perspective of trust distribution, and on this basis introduces a dynamic penalty strategy, which greatly improves the dynamics and effectiveness of the algorithm. In addition, the algorithm is simulated and tested in the simulated API gateway environment, and the simulation results show that the proposed algorithm has significantly improved the reliability and security of trust evaluation compared with the previous adjudication algorithms.
Jacking Construction and Measures for Jacking-up of Large Gradient Bridge
Authors: Wang Shouqiang , Zhou Wenbo , Ge Yiheng , Hu Jiaping , Wang Zhuoying , Cheng Ye
Published: January 2023

Nowadays, more and more bridges are difficult to meet the traffic needs because of the limitations on bridge clearance height while bridge demolition and reconstruction will lengthen the construction cycle, waste a lot of resources, increase the construction cost, etc. By solving these problems and using the original bridge effectively, the bridge jacking-up construction technology is widely used. With the construction of urban road network, the original ramp bridge needs to be elevated to the new main road in the process of viaduct construction in Shanghai, which involves the slope adjustment of large gradient bridge. The jacking section of the bridge with 16.5m width deck and the total length 220.51m is divided into two sections with 19.51+24×3+19m and 19+24×3+19m span combinations. A series of measures are put forward for the bridge jacking construction: the ball-head Jacks are installed to offset Jack deflection, the sliding steel plate is used to ensure vertical and horizontal displacement of the Jack, the push-pull devices are installed to ensure the width of expansion joint while jacking-up and the fast-hardening concrete is proposed to use in the process of pier heightening.
First Principles Study on Photocatalytic Properties of TiO2 (101) @ MoO3 Material
Authors: Yu Zhiqing , Li Xiaotao , Ma Zhenning , Wang Xun , Li Xing
Published: January 2023

The structural stability, energy band, density of states images and absorption spectra of TiO2 (101) surface and TiO2 (101) @ MoO3 system were calculated and analyzed by the first principle method. The results show that MoO3 clusters can form Mo-O-Ti bridge structure on TiO2 (101) surface, which has good stability and is beneficial to practical use. Compared with the pure TiO2 (101) surface, the adsorption of MoO3 clusters on the TiO2 (101) surface can generate empty energy levels in the intrinsic band gap, which is conducive to reducing the energy requirements for electronic transitions, and thus conducive to electronic transitions between band gaps. The absorption spectrum analysis also proves that the TiO2 (101) @ MoO3 absorption spectrum has an absorption peak at the wavelength of 420nm, and the absorption spectrum is highly higher than the TiO2 (101) surface. The corresponding wavelength of the absorption peak in this region has entered the visible light region, which can greatly enhance the utilization of visible photons, and is of great significance for photocatalysis.
Improved Image Style Transfer Based on VGG-16 Convolutional Neural Network Model
Authors: Shu Chenhao , Hu Xichuan
Published: January 2023

In the field of computer vision, image style transfer is an important research direction. With the promotion of artificial intelligence, this technology is becoming more and more popular. Compared with the current image style transfer technology based on artificial intelligence, the traditional technology appears to be complex, time-consuming and inefficient. Migration technology is mainly based on images of the current mainstream style VGG - 16 convolution neural network model, adopts TensorFlow framework, in this article to a picture before the smart migration style photo style, texture features such as the methods of improvement, by modifying the style loss function, makes the image content images can transfer a variety of style, Finally, it is verified by relevant experiments.
On Hadamard powers of positive semi-definite matrices
Authors: Baslingker Jnaneshwar , Dan Biltu
Published: January 2023

Consider the set of scalars

α
\alpha

for which the

α
\alpha

th Hadamard power of any

n
×
n

n\times n

positive semi-definite (p.s.d.) matrix with non-negative entries is p.s.d. It is known that this set is of the form

{
0
,
1
,
…
,
n
−
3
}
∪
[
n
−
2
,
∞
)

\{0, 1, \dots , n-3\}\cup [n-2, \infty )

. A natural question is “what is the possible form of the set of such

α
\alpha

for a fixed p.s.d. matrix with non-negative entries?”. In all examples appearing in the literature, the set turns out to be union of a finite set and a semi-infinite interval. In this article, examples of matrices are given for which the set consists of a finite set and more than one disjoint interval of positive length. In fact, it is proved that the number of such disjoint intervals can be made arbitrarily large, by giving explicit examples of matrices.

The case when the entries of the matrices are not necessarily non-negative is also considered.
Automatic continuity of separating and biseparating isomorphisms
Authors: Lo Ching-on , Loh Anthony
Published: January 2023

Let

p
p

be a fixed number with

1
≤
p
>
∞

1 \leq p > \infty

. It is shown that every surjective and biseparating linear map between

L
p

L^p

-spaces is continuous when the underlying measure space is non-atomic. We also prove that a separating isomorphism on

l
p

l^p

is both continuous and biseparating. Furthermore, these (bi-)separating maps take the form of a weighted composition operator. Our proofs are direct, elementary and do not invoke deep results about Riesz spaces or Banach lattices.
Modeling and analyzing single-cell multimodal data with deep parametric inference
Authors: Hu Huan , Feng Zhen , Lin Hai , Zhao Junjie , Zhang Yaru , Xu Fei , Chen Lingling , Chen Feng , Ma Yunlong , Su Jianzhong , Zhao Qi , Shuai Jianwei
Published: January 2023

The proliferation of single-cell multimodal sequencing technologies has enabled us to understand cellular heterogeneity with multiple views, providing novel and actionable biological insights into the disease-driving mechanisms. Here, we propose a comprehensive end-to-end single-cell multimodal analysis framework named Deep Parametric Inference (DPI). DPI transforms single-cell multimodal data into a multimodal parameter space by inferring individual modal parameters. Analysis of cord blood mononuclear cells (CBMC) reveals that the multimodal parameter space can characterize the heterogeneity of cells more comprehensively than individual modalities. Furthermore, comparisons with the state-of-the-art methods on multiple datasets show that DPI has superior performance. Additionally, DPI can reference and query cell types without batch effects. As a result, DPI can successfully analyze the progression of COVID-19 disease in peripheral blood mononuclear cells (PBMC). Notably, we further propose a cell state vector field and analyze the transformation pattern of bone marrow cells (BMC) states. In conclusion, DPI is a powerful single-cell multimodal analysis framework that can provide new biological insights into biomedical researchers. The python packages, datasets and user-friendly manuals of DPI are freely available at https://github.com/studentiz/dpi.
A real-world prospective cohort study of immunogenicity and reactogenicity of ChAdOx1-S[recombinant] among patients with immune-mediated dermatological diseases
Authors: Chanprapaph Kumutnart , Seree-aphinan Chutima , Rattanakaemakorn Ploysyne , Pomsoong Cherrin , Ratanapokasatit Yanisa , Setthaudom Chavachol , Thitithanyanont Arunee , Suriyo Aphinyaphiwat , Suangtamai Thanitta , Suchonwanit P ,   the COVIDVAC-DERM study group
Published: January 2023

Background

Immunogenicity and reactogenicity of COVID-19 vaccines have been established in various groups of immunosuppressed patients; however, studies involving patients with immune-mediated dermatological diseases (IMDDs) are scarce.

Objectives

To investigate the influence of IMDDs on the development of SARS-CoV-2-specific immunity and side-effects following ChAdOx1-S[recombinant] vaccination.

Methods

This prospective cohort study included 127 patients with IMDDs and 97 participants without immune-mediated diseases who received ChAdOx1-S[recombinant]. SARS-CoV-2-specific immunity and side-effect profiles were assessed at 1 month postvaccination and compared between groups. Immunological (primary) outcomes were the percentages of participants who tested positive for neutralizing antibodies [seroconversion rate (SR)] and those who developed T-cell-mediated immunity demonstrated by an interferon-γ-releasing assay (IGRA) [positive IGRA rate (+IGRA)]. Reactogenicity-related (secondary) outcomes were the unsolicited adverse reactions and worsening of IMDD activity reflected by the uptitration of immunosuppressants during and within 1 month of vaccination.

Results

Overall, the SR for the IMDD group was similar to that of participants without immune-mediated conditions (75·6 vs. 84·5, P = 0·101), whereas + IGRA was lower (72·4 vs. 88·7, P = 0·003). Reactogenicity was similar between groups. No severe adverse reaction was reported. By stratifying the participants in the IMDD group according to individual disease, the immunogenicity of the vaccine was lowest in patients with autoimmune bullous diseases (AIBD) (SR 64·5%, +IGRA 62·9%) and highest in patients with psoriasis (SR 87·7%, +IGRA 80·7%). The reverse trend was found for vaccine-related reactions. Immunosuppressants were uptitrated in 15·8% of cases; 75% of these were patients with AIBD.

Conclusions

Among participants with IMDDs, ChAdOx1-S[recombinant] showed good immunogenicity among patients with psoriasis, but demonstrated lower levels of immunogenicity for patients with AIBD. Some patients, especially patients with AIBD, should be closely monitored as they may require treatment escalation within 1 month postvaccination.
Exploring disease comorbidities and temporal disease progression of psoriasis: an observational, retrospective, multi-database, cohort study
Authors: Rosenø Nana A L , Lørup Erik Hillo , Richardson Craig , Alarcon Ivette , Egeberg Alexander 
Published: January 2023

Background

Comorbidities associated with psoriasis are well documented. However, few studies have explored the comorbidity trajectories that patients with psoriasis commonly experience over time. This study reports the 5-year comorbidity trajectories of patients with psoriasis.

Objectives

To determine the long-term comorbidity trajectories of patients with psoriasis in Denmark.

Methods

This observational cohort study explored the Danish National Patient Registry (DNPR) between 1999 and 2013 to identify comorbidities diagnosed 5 years prior to or after a psoriasis diagnosis. Comorbidity occurrence in patients with psoriasis (psoriasis cohort) was compared with patients without psoriasis (the N group). Comparison groups, each the same size as the psoriasis cohort, were created by selecting random patients from the N group. If a comorbidity occurrence was higher in more than nine comparison groups than in the psoriasis cohort, it was not analysed and only comorbidities that occurred in ≥ 0·8% of the psoriasis cohort were analysed. The strength of association between a psoriasis diagnosis and a comorbidity diagnosis was measured using relative risk (RR). All psoriasis and comorbidity pairs that achieved RR > 1 (P < 0·001) (known as a Diagnosed Pair) were tested for directionality to identify the sequence of diagnoses using a binomial test. Diagnosed Pairs with a statistically significant direction (Bonferroni corrected P-value < 0·025) were then used to create comorbidity trajectory clusters 5 years before and after a psoriasis diagnosis.

Results

A total of 17 683 patients with psoriasis were compared with 10 000 comparison groups. A total of 121 comorbidities met the minimum criteria that ≥ 0·8% of the psoriasis cohort were diagnosed with the comorbidity within 5 years (before or after) of their psoriasis diagnosis. Thirty-eight of these comorbidities achieved RR > 1 (P < 0·001) with psoriasis, of which 19 achieved a significant direction from psoriasis to a comorbidity (including psoriasis to hypothyroidism), and four achieved a significant direction from a comorbidity diagnosis to a psoriasis diagnosis (including Crohn disease to psoriasis); four of five comorbidity trajectories with three sequential diagnoses achieved an RR > 1 (P < 0·001) and a significant direction from psoriasis to the first comorbidity to the second comorbidity (including psoriasis to hypertension to atrial fibrillation and flutter).

Conclusions

Comorbidity trajectories may support clinicians in conducting disease risk analyses of patients with psoriasis and help plan optimal treatment to prevent future high-risk comorbidities.
Heritability of cognitive abilities and regional brain structures in middle-aged to elderly East Asians
Authors: Lee Younghwa , Park Jun Young , Lee Jang Jae , Gim Jungsoo , Do Ah Ra , Jo Jinyeon , Park Juhong , Kim Kangjin , Park Kyungtaek , Jin Heejin , Choi Kyu Yeong , Kang Sarang , Kim Hoowon , Kim SangYun , Moon Seung Hwan , Farrer Lindsay A , Lee Kun Ho , Won Sungho
Published: January 2023

This study examined the single-nucleotide polymorphism heritability and genetic correlations of cognitive abilities and brain structural measures (regional subcortical volume and cortical thickness) in middle-aged and elderly East Asians (Korean) from the Gwangju Alzheimer’s and Related Dementias cohort study. Significant heritability was found in memory function, caudate volume, thickness of the entorhinal cortices, pars opercularis, superior frontal gyri, and transverse temporal gyri. There were 3 significant genetic correlations between (i) the caudate volume and the thickness of the entorhinal cortices, (ii) the thickness of the superior frontal gyri and pars opercularis, and (iii) the thickness of the superior frontal and transverse temporal gyri. This is the first study to describe the heritability and genetic correlations of cognitive and neuroanatomical traits in middle-aged to elderly East Asians. Our results support the previous findings showing that genetic factors play a substantial role in the cognitive and neuroanatomical traits in middle to advanced age. Moreover, by demonstrating shared genetic effects on different brain regions, it gives us a genetic insight into understanding cognitive and brain changes with age, such as aging-related cognitive decline, cortical atrophy, and neural compensation.
Age-dependent changes in the dynamic functional organization of the brain at rest: a cross-cultural replication approach
Authors: Yang Xi , Zhou Xinqi , Xin Fei , Becker Benjamin , Linden David , Hernaus Dennis
Published: January 2023

Age-associated changes in brain function play an important role in the development of neurodegenerative diseases. Although previous work has examined age-related changes in static functional connectivity, accumulating evidence suggests that advancing age is especially associated with alterations in the dynamic interactions and transitions between different brain states, which hitherto have received less attention. Conclusions of previous studies in this domain are moreover limited by suboptimal replicability of resting-state functional magnetic resonance imaging (fMRI) and culturally homogenous cohorts. Here, we investigate the robustness of age-associated changes in dynamic functional connectivity (dFC) by capitalizing on the availability of fMRI cohorts from two cultures (Western European and Chinese). In both the LEMON (Western European) and SALD (Chinese) cohorts, we consistently identify two distinct states: a more frequent segregated within-network connectivity state (state I) and a less frequent integrated between-network connectivity state (state II). Moreover, in both these cohorts, older (55–80 years) compared to younger participants (20–35 years) exhibited lower occurrence of and spent less time in state I. Older participants also tended to exhibit more transitions between networks and greater variance in global efficiency. Overall, our cross-cultural replication of age-associated changes in dFC metrics implies that advancing age is robustly associated with a reorganization of dynamic brain activation that favors the use of less functionally specific networks.
Peripheral and Portal VenousKRASctDNA Detection as Independent Prognostic Markers of Early Tumor Recurrence in Pancreatic Ductal Adenocarcinoma
Authors: Nitschke Christine , Markmann Benedikt , Walter Philipp , Badbaran Anita , Tölle Marie , Kropidlowski Jolanthe , Belloum Yassine , Goetz Mara R , Bardenhagen Jan , Stern Louisa , Tintelnot Joseph , Schönlein Martin , Sinn Marianne , van der Leest Paul , Simon Ronald , Heumann Asmus , Izbicki Jakob R , Pantel Klaus , Wikman Harriet , Uzunoglu Faik G
Published: January 2023

Background

KRAS circulating tumor DNA (ctDNA) has shown biomarker potential for pancreatic ductal adenocarcinoma (PDAC) but has not been applied in clinical routine yet. We aim to improve clinical applicability of ctDNA detection in PDAC and to study the impact of blood-draw site and time point on the detectability and prognostic role of KRAS mutations.

Methods

221 blood samples from 108 PDAC patients (65 curative, 43 palliative) were analyzed. Baseline peripheral and tumor-draining portal venous (PV), postoperative, and follow-up blood were analyzed and correlated with prognosis.

Results

Significantly higher KRAS mutant detection rates and copy numbers were observed in palliative compared to curative patients baseline blood (58.1% vs 24.6%; P = 0.002; and P < 0.001). Significantly higher KRAS mutant copies were found in PV blood compared to baseline (P < 0.05) samples. KRAS detection in pre- and postoperative and PV blood were significantly associated with shorter recurrence-free survival (all P < 0.015) and identified as independent prognostic markers. KRAS ctDNA status was also an independent unfavorable prognostic factor for shorter overall survival in both palliative and curative cohorts (hazard ratio [HR] 4.9, P = 0.011; HR 6.9, P = 0.008).

Conclusions

KRAS ctDNA detection is an independent adverse prognostic marker in curative and palliative PDAC patients—at all sites of blood draw and a strong follow-up marker. The most substantial prognostic impact was seen for PV blood, which could be an effective novel tool for identifying prognostic borderline patients—guiding future decision-making on neoadjuvant treatment despite anatomical resectability. In addition, higher PV mutant copy numbers contribute to an improved technical feasibility.
How Not To Design An Efficient FHE-Friendly Block Cipher: Seljuk
Authors: Ashur Tomer , Mahzoun Mohammad , Toprakhisar Dilara
Published: January 2023

With the rapid increase in the practical applications of secure computation protocols, increasingly more research is focused on the efficiency of the symmetric-key primitives underlying them. Whereas traditional block ciphers have evolved to be efficient with respect to certain performance metrics, secure computation protocols call for a different efficiency metric: arithmetic complexity. Arithmetic complexity is viewed through the number and layout of nonlinear operations in the circuit implemented by the protocol. Symmetric-key algorithms that are optimized for this metric are said to be algebraic ciphers. It has been shown that recently proposed algebraic ciphers are greatly efficient in ZK and MPC protocols. However, there has not been many algebraic ciphers proposed targeting Fully Homomorphic Encryption (FHE). In this paper, we evaluate the behavior of Vision when implemented as a circuit in an FHE protocol. To this end, we present a state-of-the-art comparison of AES and Vision implemented using HElib. Counterintuitively, Vision does not deliver a better performance than AES in this setting. Then, by attempting to improve a bottleneck of the FHE implementation evaluating Vision we present a new cipher: Seljuk. Despite the improvement with respect to Vision, Seljuk does not deliver the expected performance.
A chromosome-level genome assembly of theHenosepilachna vigintioctomaculataprovides insights into the evolution of ladybird beetles
Authors: Zhu Wenbo , Chi Shengqi , Wang Yanchun , Li Haorong , Wang Zhongkai , Gu Songdong , Sun Ting , Xiang Hui , You Ping , Ren Yandong
Published: January 2023

The ladybird beetle Henosepilachna vigintioctomaculata is an economically significant oligophagous pest that induces damage to many Solanaceae crops. An increasing number of studies have examined the population and phenotype diversity of ladybird beetles. However, few comparative genome analyses of ladybird beetle species have been conducted. Here, we obtained a high-quality chromosome-level genome assembly of H. vigintioctomaculata using various sequencing technologies, and the chromosome-level genome assembly was ~581.63 Mb, with 11 chromosomes successfully assembled. The phylogenetic analysis showed that H. vigintioctomaculata is a more ancient lineage than the other three sequenced ladybird beetles, Harmonia axyridis, Propylea japonica, and Coccinella septempunctata. We also compared positively selected genes (PSGs), transposable elements (TEs) ratios and insertion times, and key gene families associated with environmental adaptation among these ladybird beetles. The pattern of TEs evolution of H. vigintioctomaculata differs from the other three ladybird beetles. The PSGs were associated with ladybird beetles development. However, the key gene families associated with environmental adaptation in ladybird beetles varied. Overall, the high-quality draft genome sequence of H. vigintioctomaculata provides a useful resource for studies of beetle biology, especially for the invasive biology of ladybird beetles.
GIP reduces osteoclast activity and improves osteoblast survival in primary human bone cells
Authors: Hansen Morten S , Søe Kent , Christensen Line L , Fernandez-Guerra Paula , Hansen Nina W , Wyatt Rachael A , Martin Claire , Hardy Rowan S , Andersen Thomas L , Olesen Jacob B , Hartmann Bolette , Rosenkilde Mette M , Kassem Moustapha , Rauch Alexander , Gorvin Caroline M , Frost Morten
Published: January 2023

Objective

Drugs targeting the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) are emerging as treatments for type-2 diabetes and obesity. GIP acutely decreases serum markers of bone resorption and transiently increases bone formation markers in short-term clinical investigations. However, it is unknown whether GIP acts directly on bone cells to mediate these effects. Using a GIPR-specific antagonist, we aimed to assess whether GIP acts directly on primary human osteoclasts and osteoblasts.

Methods

Osteoclasts were differentiated from human CD14+ monocytes and osteoblasts from human bone. GIPR expression was determined using RNA-seq in primary human osteoclasts and in situ hybridization in human femoral bone. Osteoclastic resorptive activity was assessed using microscopy. GIPR signaling pathways in osteoclasts and osteoblasts were assessed using LANCE cAMP and AlphaLISA phosphorylation assays, intracellular calcium imaging and confocal microscopy. The bioenergetic profile of osteoclasts was evaluated using Seahorse XF-96.

Results

GIPR is robustly expressed in mature human osteoclasts. GIP inhibits osteoclastogenesis, delays bone resorption, and increases osteoclast apoptosis by acting upon multiple signaling pathways (Src, cAMP, Akt, p38, Akt, NFκB) to impair nuclear translocation of nuclear factor of activated T cells-1 (NFATc1) and nuclear factor-κB (NFκB). Osteoblasts also expressed GIPR, and GIP improved osteoblast survival. Decreased bone resorption and improved osteoblast survival were also observed after GIP treatment of osteoclast–osteoblast co-cultures. Antagonizing GIPR with GIP(3–30)NH2 abolished the effects of GIP on osteoclasts and osteoblasts.

Conclusions

GIP inhibits bone resorption and improves survival of human osteoblasts, indicating that drugs targeting GIPR may impair bone resorption, whilst preserving bone formation.
Real-time detection of acromegaly from facial images with artificial intelligence
Authors: Kizilgul Muhammed , Karakis Rukiye , Dogan Nurettin , Bostan Hayri , Yapici Muhammed Mutlu , Gul Umran , Ucan Bekir , Duman Elvan , Duger Hakan , Cakal Erman , Akin Omer
Published: January 2023

Objective

Despite improvements in diagnostic methods, acromegaly is still a late-diagnosed disease. In this study, it was aimed to automatically recognize acromegaly disease from facial images by using deep learning methods and to facilitate the detection of the disease.

Design

Cross-sectional, single-centre study

Methods

The study included 77 acromegaly (52.56 ± 11.74, 34 males/43 females) patients and 71 healthy controls (48.47 ± 8.91, 39 males/32 females), considering gender and age compatibility. At the time of the photography, 56/77 (73%) of the acromegaly patients were in remission. Normalized images were obtained by scaling, aligning, and cropping video frames. Three architectures named ResNet50, DenseNet121, and InceptionV3 were used for the transfer learning-based convolutional neural network (CNN) model developed to classify face images as “Healthy” or “Acromegaly”. Additionally, we trained and integrated these CNN machine learning methods to create an Ensemble Method (EM) for facial detection of acromegaly.

Results

The positive predictive values obtained for acromegaly with the ResNet50, DenseNet121, InceptionV3, and EM were calculated as 0.958, 0.965, 0.962, and 0.997, respectively. The average sensitivity, specificity, precision, and correlation coefficient values calculated for each of the ResNet50, DenseNet121, and InceptionV3 models are quite close. On the other hand, EM outperformed these three CNN architectures and provided the best overall performance in terms of sensitivity, specificity, accuracy, and precision as 0.997, 0.997, 0.997, and 0.998, respectively.

Conclusions

The present study provided evidence that the proposed AcroEnsemble Model might detect acromegaly from facial images with high performance. This highlights that artificial intelligence programs are promising methods for detecting acromegaly in the future.
Involvement of mTOR pathway in neurodegeneration in NSF-related developmental and epileptic encephalopathy
Authors: Hayashi Takahiro , Yano Naoko , Kora Kengo , Yokoyama Atsushi , Maizuru Kanako , Kayaki Taisei , Nishikawa Kinuko , Osawa Mitsujiro , Niwa Akira , Takenouchi Toshiki , Hijikata Atsushi , Shirai Tsuyoshi , Suzuki Hisato , Kosaki Kenjiro , Saito Megumu K , Takita Junko , Yoshida Takeshi
Published: January 2023

Membrane fusion is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. During neurotransmitter exocytosis, SNARE proteins on a synaptic vesicle and the target membrane form a complex, resulting in neurotransmitter release. N-ethylmaleimide-sensitive factor (NSF), a homohexameric ATPase, disassembles the complex, allowing individual SNARE proteins to be recycled. Recently, the association between pathogenic NSF variants and developmental and epileptic encephalopathy (DEE) was reported; however, the molecular pathomechanism of NSF-related DEE remains unclear. Here, three patients with de novo heterozygous NSF variants were presented, of which two were associated with DEE and one with a very mild phenotype. One of the DEE patients also had hypocalcemia from parathyroid hormone deficiency and neuromuscular junction impairment. Using PC12 cells, a neurosecretion model, we show that NSF with DEE-associated variants impaired the recycling of vesicular membrane proteins and vesicle enlargement in response to exocytotic stimulation. In addition, DEE-associated variants caused neurodegenerative change and defective autophagy through overactivation of the mammalian/mechanistic target of rapamycin (mTOR) pathway. Treatment with rapamycin, an mTOR inhibitor or overexpression of wild-type NSF ameliorated these phenotypes. Furthermore, neurons differentiated from patient-derived induced pluripotent stem cells showed neurite degeneration, which was also alleviated by rapamycin treatment or gene correction using genome editing. Protein structure analysis of NSF revealed that DEE-associated variants might disrupt the transmission of the conformational change of NSF monomers and consequently halt the rotation of ATP hydrolysis, indicating a dominant negative mechanism. In conclusion, this study elucidates the pathomechanism underlying NSF-related DEE and identifies a potential therapeutic approach.
Induction and Maintenance Treatment With Upadacitinib Improves Health-Related Quality of Life in Patients With Moderately to Severely Active Ulcerative Colitis: Phase 3 Study Results
Authors: Panés Julian , Loftus Edward V , Higgins Peter D R , Lindsay James O , Zhou Wen , Yao, Xuan , Ilo Dapo , Phillips Charles , Tran Jacinda , Sanchez Gonzalez Yuri , Vermeire Séverine
Published: January 2023

Background

We evaluated the health-related quality of life (HRQoL) benefits of upadacitinib (UPA) induction and maintenance treatment in a phase 3 study of patients with ulcerative colitis (UC) across a broad range of patient-centered outcomes.

Methods

Patients received UPA 45 mg once daily or placebo as induction treatment for 8 weeks. Patients who achieved clinical response were rerandomized to receive once daily UPA 15 mg, 30 mg, or placebo as maintenance treatment for 52 weeks. The percentages of patients reporting a clinically meaningful within-person change from baseline in the Ulcerative Colitis Symptoms Questionnaire, Inflammatory Bowel Disease Questionnaire, Work Productivity and Impairment Questionnaire, 36-Item Short Form Survey, and European Quality of Life-5 Dimension 5 Levels were evaluated at weeks 2 and 8 of induction and at weeks 0 and 52 of maintenance.

Results

Significant improvements from baseline in all HRQoL measures except the Work Productivity and Impairment Questionnaire–absenteeism were achieved with UPA (P < .001) vs placebo as early as week 2 of induction. These improvements were sustained at week 52 with significantly more patients treated with either 15 mg or 30 mg UPA vs placebo achieving meaningful within-person change in the Ulcerative Colitis Symptoms Questionnaire; Inflammatory Bowel Disease Questionnaire; overall work impairment, presenteeism, and activity impairment; both 36-Item Short Form Survey Physical and Mental Component Summaries; and European Quality of Life-5 Dimension 5 Levels (P < .001).

Conclusions

Induction treatment with UPA 45 mg significantly improved HRQoL measures. A significantly higher percentage of patients who responded to induction treatment with UPA maintained clinically meaningful improvements consistently across a wide range of HRQoL outcomes after 52 weeks of maintenance therapy with UPA (15 mg and 30 mg) compared with placebo. (ClinicalTrials.gov, Numbers: NCT02819635, NCT03653026).