bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential therapies for immune-related adverse events associated with immune checkpoint inhibition: from monoclonal antibodies to kinase inhibition
Authors: Henderson Berg Meagan-Helen , del Rincón Sonia Victoria , Miller Wilson H
Published: January 2022

The therapeutic benefits of immune checkpoint inhibitors (ICIs), which enable antitumor immune responses, can be tempered by unwanted immune-related adverse events (irAEs). Treatment recommendations stratified by irAE phenotype and immunohistopathological findings have only recently been proposed and are often based on those used in primary autoimmune diseases, including targeting of specific proinflammatory cytokines with monoclonal antibodies. Increasing evidence supports the use of such antibody-based strategies as effective steroid-sparing treatments, although the therapies themselves may be associated with additional drug toxicities and reduced ICI efficacy. Kinases are key contributors to the adaptive and innate responses that drive primary autoimmune diseases and irAEs. The janus kinase/signal transducer and activator of transcription, Bruton’s tyrosine kinase, and mitogen-activated protein kinase-interacting serine/threonine protein kinases 1 and 2 pathways are also critical to tumor progression and have important roles in cells of the tumor microenvironment. Herein, we review the histopathological, biological, and clinical evidence to support specific monoclonal antibodies and kinase inhibition as management strategies for irAEs.
Overcoming tumor heterogeneity by ex vivo arming of T cells using multiple bispecific antibodies
Authors: Park Jeong A , Cheung Nai-Kong V
Published: January 2022

Background

Tumorous heterogeneity is a hallmark of tumor evolution and cancer progression, being a longstanding challenge to targeted immunotherapy. Ex vivo armed T cells (EATs) using IgG-(L)-scFv bispecific antibodies (BsAbs) are potent tumor-specific cytotoxic effectors. To improve the anti-tumor efficacy of EATs against heterogeneous solid tumors, we explored multi-antigen targeting approaches.

Methods

Ex vivo expanded T cells were armed with BsAbs built on the IgG-(L)-scFv platform, where an anti-CD3 (huOKT3) scFv was attached to the carboxyl end of both light chains of a tumor specific IgG. Multispecificity was created by combining monospecific EATs, combining BsAbs on the same T cell, or combining specificities on the same antibody. Three multi-antigens targeting EAT strategies were tested: (1) pooled-EATs (EATs each with unique specificity administered simultaneously) or alternate-EATs (EATs each with unique specificity administered in an alternating schedule), (2) dual-EATs or multi-EATs (T cells simultaneously armed with ≥2 BsAbs), and (3) TriAb-EATs (T cells armed with BsAb specific for two targets besides CD3 (TriAb)). The properties and efficiencies of these three strategies were evaluated by flow cytometry, in vitro cytotoxicity, cytokine release assays, and in vivo studies performed in BALB-Rag2-/-IL-2R-γc-KO (BRG) mice xenografted with cancer cell line (CDX) or patient-derived tumor (PDX).

Results

Multi-EATs retained target antigen specificity and anti-tumor potency. Cytokine release with multi-EATs in the presence of tumor cells was substantially less than when multiple BsAbs were mixed with unarmed T cells. When tested against CDXs or PDXs, dual-EATs or multi-EATs effectively suppressed tumor growth without clinical toxicities. Most importantly, dual-EATs or multi-EATs were highly efficient in preventing clonal escape while mono-EATs or TriAb- EATs were not as effective.

Conclusions

Multi-EATs have the potential to increase potency, reduce toxicity, and overcome tumor heterogeneity without excessive cytokine release. Arming T cells with multiple BsAbs deserves further exploration to prevent or to treat cancer resistance.
Mortality in patients with psychogenic non-epileptic seizures a population-based cohort study
Authors: Zhang Le , Beghi Ettore , Tomson Torbjörn , Beghi Massimiliano , Erba Giuseppe , Chang Zheng
Published: January 2022

Objectives

To compare mortality, comorbidities and causes of death in people with psychogenic non-epileptic seizures (PNES), epilepsy and the general population.

Methods

Using linkage of multiple Swedish national registers, we identified individuals with incident diagnosis of PNES, epilepsy and conversion disorder with motor symptoms or deficits, and 10 controls for each. Main outcome was all-cause mortality. Causes of death were categorised into non-natural (eg, suicide, injuries) and natural. Conditional Cox regression models were used to estimate HRs and 95% CIs for mortality. HRs were adjusted for socioeconomic factors and psychiatric comorbidities.

Results

Included were 885 individuals with PNES, 50 663 with epilepsy and 1057 with conversion disorder and motor symptoms or deficits. We found 32 (3.6%) deaths among individuals with PNES, compared with 46 (0.5%) deaths in controls, giving an adjusted HR of 5.5 (95% CI 2.8 to 10.8). Patients with epilepsy had a 6.7 times higher risk of death (95% CI 6.4 to 7.0) compared with individuals without epilepsy. The association between conversion disorder with motor symptoms or deficits was non-significant after adjusting for psychiatric comorbidities. PNES carried a higher risk of natural (HR 8.1, 95% CI 4.0 to 16.4) and non-natural causes of death (HR 15.3, 95% CI 3.0 to 78.6). Suicide ranked high in patients with PNES (18.8%) and conversion disorder with motor symptoms and deficits. The association between PNES diagnosis and all-cause mortality varied with age and time since diagnosis.

Conclusion

Like epilepsy, PNES carries a higher than expected risk of both natural and non-natural causes of death. The high proportion of suicides requires further investigation.
Cognitive decline and diabetes: a systematic review of the neuropathological correlates accounting for cognition at death
Authors: Hadley Gina , Zhang Jiali , Harris-Skillman Eva , Alexopoulou Zoi , DeLuca Gabriele C , Pendlebury Sarah T
Published: January 2022

Given conflicting findings in epidemiologic studies, we determined the relative contributions of different neuropathologies to the excess risk of cognitive decline in diabetes mellitus (DM) through a systematic review of the literature. Included studies compared subjects with and without DM and reported neuropathological outcomes accounting for cognition at death. Data on Alzheimer’s disease (AD) pathology, cerebrovascular disease and non-vascular, non-AD pathology were extracted from each study. Eleven studies (n=6 prospective cohorts, n=5 retrospective post-mortem series, total n=6330) met inclusion criteria. All 11 studies quantified AD changes and 10/11 measured cerebrovascular disease: macroscopic lesions (n=9), microinfarcts (n=8), cerebral amyloid angiopathy (CAA, n=7), lacunes (n=6), white matter disease (n=5), haemorrhages (n=4), microbleeds (n=1), hippocampal microvasculature (n=1). Other pathology was infrequently examined. No study reported increased AD pathology in DM, three studies showed a decrease (n=872) and four (n= 4018) showed no difference, after adjustment for cognition at death. No study reported reduced cerebrovascular pathology in DM. Three studies (n=2345) reported an increase in large infarcts, lacunes and microinfarcts. One study found lower cognitive scores in DM compared to non-DM subjects despite similar cerebrovascular and AD-pathology load suggesting contributions from other neuropathological processes. In conclusion, lack of an association between DM and AD-related neuropathology was consistent across studies, irrespective of methodology. In contrast to AD, DM was associated with increased large and small vessel disease. Data on other pathologies such as non-AD neurodegeneration, and blood-brain-barrier breakdown were lacking. Further studies evaluating relative contributions of different neuropathologies to the excess risk of DM are needed.
A new cosmological model based on quantization of the zero-point field
Authors: Dikshit Biswaranjan
Published: January 2022

Inflation has presented solutions for a number of important cosmological problems while leaving some unanswered. In this paper, we present a new cosmological model based on the quantization of the zero-point field, which is consistent with empirical data, requires fewer assumptions, and presents answers to some of those unanswered questions. A comparison between standard cosmology and the theory presented in this paper is given herein. Vacuum energy density: The standard inflationary model needs both Hubble’s constant and matter density to estimate the vacuum energy density, but new cosmological model needs only Hubble’s constant. Non-vacuum energy density: The standard model cannot predict the non-vacuum energy density, but the new model can predict it using only Hubble’s constant. Ratio of vacuum energy to total energy: The standard model cannot predict the ratio of vacuum energy to total energy, but the new model can predict it, without using Hubble’s constant. Energy conservation: In the standard model, total energy is not conserved before inflation and at the time of the creation of the universe, but in the new model total energy is mathematically proved to be conserved from the beginning of the universe as net energy (including gravitational potential energy) is always zero. Flatness and homogeneity: The standard model requires an inflaton field with a specific potential energy distribution to explain it, but the new model does not need any such hypothetical field; the zero-point field is sufficient.
Influence of torsion charge on shadow and observation signature of black hole surrounded by various profiles of accretions
Authors: He Ke-Jian , Tan Shuang-Cheng , Li Guo-Ping
Published: January 2022

In this paper, we carefully study the shadow and observational signature of the black hole with torsion charge for a distant observer, and further compare the results with that gotten in Schwarzschild spacetime. For thin disk accretion cases, the result shows that there are not only dark areas in the observed image of black hole, but also photon rings and lensing rings, which are closely associated with the torsion charge. The change of torsion charge will directly affect the range of photon ring and lens ring, and the contribution proportion of these rings to the observed intensity. In addition, the total flux of observed intensity is mainly provided by direct emission, and the lensing ring and photon ring contribute only a small part. By further considering the static and infalling cases of spherically symmetric accretion, one can find that the observed image is much darker for the falling accretion matters, but the shadow radius does not change. However, both the observed intensity and shadow size are significantly different when the torsion charge changes. That is, the size of the observed shadow is related to the spacetime geometry. In addition, based on the shadow of M87, we also constraint the torsion charge of black hole by using the diameter of shadow approximately. Finally, by comparing our results and that in Schwarzschild spacetime, it shows that black hole shadow can provide a feasible method for distinguishing those two spacetime.
Shadows and precession of orbits in rotating Janis–Newman–Winicour spacetime
Authors: Solanki Divyesh N. , Bambhaniya Parth , Dey Dipanjan , Joshi Pankaj S. , Pathak Kamlesh N.
Published: January 2022

In this paper, we construct the rotating Janis–Newman–Winicour (JNW) naked singularity spacetime using Newman–Janis Algorithm (NJA). We analyse NJA with and without complexification methods and find that the energy conditions do satisfied when we skip the complexification step. We study the shadows cast by rotating JNW naked singularity and compare them with the shadows cast by the Kerr black hole. We find that the shadow of the rotating naked singularity can be distinguished from the shadow of the Kerr black hole. While we analyse the precession of timelike bound orbits in rotating JNW spacetime, we find that it can have a negative (or opposite) precession, which is not present in the Kerr black hole case. These novel signatures of the shadow and orbital precession in rotating JNW naked singularity spacetime could be important in the context of the recent observation of the shadow of the M87 galactic center and the stellar dynamics of ‘S-stars’ around Milkyway galactic center.
Wormholes in Poincarè gauge theory of gravity
Authors: Ziaie Amir Hadi , Corda Christian
Published: January 2022

In this work, we study static spherically symmetric solutions representing wormhole configurations in Poincarè gauge theory ( PGT ). The gravitational sector of the Lagrangian is chosen as a subclass of PGT Lagrangians for which the spin-[Formula: see text] is the only propagating torsion mode. The spacetime torsion in PGT has a dynamical nature even in the absence of intrinsic angular momentum (spin) of matter, hence torsion can play a principal role in the case of usual spin-less gravitating systems. We therefore consider a spin-less matter distribution with an anisotropic energy–momentum tensor ( EMT ) as the supporting source for wormhole structure to obtain a class of zero tidal force wormhole solutions. It is seen that the matter distribution obeys the physical reasonability conditions, i.e. the weak ( WEC ) and null ( NEC ) energy conditions either at the throat and throughout the spacetime. We further consider varying equations of state in radial and tangential directions via definitions [Formula: see text] and [Formula: see text] and investigate the behavior of state parameters at the throat of wormhole. We observe that our solutions allow for wormhole configurations without the need of exotic matter. Observational features of the wormhole solutions are also discussed utilizing gravitational lensing effects. It is found that the light deflection angle diverges at the throat (which indeed, effectively acts as a photon sphere) and can get zero and negative values depending on the model parameters.
Strong rates of convergence of space-time discretization schemes for the 2D Navier–Stokes equations with additive noise
Authors: Bessaih Hakima , Millet Annie
Published: January 2022

We consider the strong solution of the 2D Navier–Stokes equations in a torus subject to an additive noise. We implement a fully implicit time numerical scheme and a finite element method in space. We prove that the space-time rate of convergence is the “optimal” one, namely, [Formula: see text] in time and 1 in space. Let us mention that the coefficient [Formula: see text] is equal to the time regularity of the solution with values in [Formula: see text]. Our method relies on the existence of finite exponential moments for both the solution and its time approximation. Unlike previous results, our main new idea is the use of a discrete Grönwall lemma for the error estimate without any localization.
Stochastic 2D rotating Euler flows with bounded vorticity or white noise initial conditions
Authors: Gao Hongjun , Gao Xiancheng
Published: January 2022

In this paper, we consider the stochastic two-dimensional (2D) rotating Euler equations with [Formula: see text] initial conditions and white noise initial conditions, respectively. The existence and uniqueness of the equations with [Formula: see text] vorticity are proved. The stability of [Formula: see text] tending to 0 for [Formula: see text] initial conditions will be proved. At last, the case of white noise initial conditions is considered.
Improving Seeding Growth Method for Preparing Densely Attached Spherical Gold Nanoparticles on Solid Substrate
Authors: Nouneh K. , Khaaissa Y. , Talbi A. , Taghzouti O. K. , Belahmar A. , El Mabrouk K. , Zekriti M. , El Mouakibi A. , Oyama M.
Published: January 2022

In this paper, a modified seed-mediated growth approach to produce gold nanoparticles through HAuCl4 chemical reduction in water fabricated by growth process on indium tin oxide (ITO) was proposed. Particular attention was devoted to exploring the seeding and growth number cycle process in the formation of Au nanoparticles on the ITO surface. In agreement with the assumed analytical model, we have found that the absorbance maximum intensity [Formula: see text] depends substantially on the metal nanoparticles’ sizes, shape and density on the ITO surface. The deposited nanoparticles’ synthesized parameters were evaluated by the surface images obtained using field emission scanning electron microscopy (FE-SEM), UV-Vis spectroscopy and electrochemical measurements. The results show that the electrochemical responses of the as-prepared sample were significantly improved, in particular for the 2-cycle seeded particles followed by one-cycle growth.
Effects of peripheral substituents on epimerization kinetics of formylated chlorophylls
Authors: Tanaka Masayuki , Tanaka Aiko , Saga Yoshitaka
Published: January 2022

C132-[Formula: see text]-epimers of chlorophyll (Chl) molecules are important cofactors in the photosystem I reaction centers in oxygenic photosynthetic organisms; however, their production mechanism is still unclear. The reaction properties of Chl epimerization are helpful for a better understanding of the molecular mechanism of the in vivo formation of Chl C132-[Formula: see text]-epimers. We report herein the kinetic properties of the epimerization of formylated Chl molecules, Chl [Formula: see text] and Chl [Formula: see text], by use of triethylamine. Both Chl [Formula: see text] and Chl [Formula: see text] performed faster epimerization kinetics than Chl [Formula: see text], indicating that the electron-withdrawing ability of the formyl groups directly linked to the chlorin macrocycle is responsible for acceleration of the epimerization. Comparing the rate constants of the two mono-formylated Chl molecules indicated that the epimerization of Chl [Formula: see text] was faster than that of Chl [Formula: see text]. This difference is rationalized by invoking a combination of the inductive effects of the C3- and C7-substituents in Chls; the sums of Hammett [Formula: see text] parameters of the C3- and C7-substituents exhibited high correlations with the epimerization rate constants of Chls [Formula: see text], [Formula: see text], and [Formula: see text].
Diversely-Supervised Visual Product Search
Authors: Thong William , Snoek Cees G. M.
Published: January 2022

This article strives for a diversely supervised visual product search, where queries specify a diverse set of labels to search for. Where previous works have focused on representing attribute, instance, or category labels individually, we consider them together to create a diverse set of labels for visually describing products. We learn an embedding from the supervisory signal provided by every label to encode their interrelationships. Once trained, every label has a corresponding visual representation in the embedding space, which is an aggregation of selected items from the training set. At search time, composite query representations retrieve images that match a specific set of diverse labels. We form composite query representations by averaging over the aggregated representations of each diverse label in the specific set. For evaluation, we extend existing product datasets of cars and clothes with a diverse set of labels. Experiments show the benefits of our embedding for diversely supervised visual product search in seen and unseen product combinations and for discovering product design styles.
LogoDet-3K: A Large-scale Image Dataset for Logo Detection
Authors: Wang Jing , Min Weiqing , Hou Sujuan , Ma Shengnan , Zheng Yuanjie , Jiang Shuqiang
Published: January 2022

Logo detection has been gaining considerable attention because of its wide range of applications in the multimedia field, such as copyright infringement detection, brand visibility monitoring, and product brand management on social media. In this article, we introduce LogoDet-3K, the largest logo detection dataset with full annotation, which has 3,000 logo categories, about 200,000 manually annotated logo objects, and 158,652 images. LogoDet-3K creates a more challenging benchmark for logo detection, for its higher comprehensive coverage and wider variety in both logo categories and annotated objects compared with existing datasets. We describe the collection and annotation process of our dataset and analyze its scale and diversity in comparison to other datasets for logo detection. We further propose a strong baseline method Logo-Yolo, which incorporates Focal loss and CIoU loss into the basic YOLOv3 framework for large-scale logo detection. It obtains about 4% improvement on the average performance compared with YOLOv3, and greater improvements compared with reported several deep detection models on LogoDet-3K. We perform extensive evaluation on three other existing datasets to further verify on both logo detection and retrieval tasks, and we demonstrate better generalization ability of LogoDet-3K on logo detection and retrieval tasks. The LogoDet-3K dataset is used to promote large-scale logo-related research. The code and LogoDet-3K can be found at https://github.com/Wangjing1551/LogoDet-3K-Dataset.
Learning Hierarchical Video Graph Networks for One-Stop Video Delivery
Authors: Song Yaguang , Gao Junyu , Yang Xiaoshan , Xu Changsheng
Published: January 2022

The explosive growth of video data has brought great challenges to video retrieval, which aims to find out related videos from a video collection. Most users are usually not interested in all the content of retrieved videos but have a more fine-grained need. In the meantime, most existing methods can only return a ranked list of retrieved videos lacking a proper way to present the video content. In this paper, we introduce a distinctively new task, namely
One-Stop Video Delivery (OSVD)
aiming to realize a comprehensive retrieval system with the following merits: it not only retrieves the relevant videos but also filters out irrelevant information and presents compact video content to users, given a natural language query and video collection. To solve this task, we propose an end-to-end
Hierarchical Video Graph Reasoning framework (HVGR)
, which considers relations of different video levels and jointly accomplishes the one-stop delivery task. Specifically, we decompose the video into three levels, namely the video-level, moment-level, and the clip-level in a coarse-to-fine manner, and apply
Graph Neural Networks (GNNs)
on the hierarchical graph to model the relations. Furthermore, a pairwise ranking loss named Progressively Refined Loss is proposed based on prior knowledge that there is a relative order of the similarity of query-video, query-moment, and query-clip due to the different granularity of matched information. Extensive experimental results on benchmark datasets demonstrate that the proposed method achieves superior performance compared with baseline methods.
An Empirical Method for Causal Inference of Constructs for QoE in Haptic–Audiovisual Communications
Authors: Tasaka Shuji
Published: January 2022

This article proposes an empirical method for inferring causal directions in multidimensional Quality of Experience (QoE) in multimedia communications, noting that causation in QoE is perceptual. As an example for modeling framework, we pick up a Bayesian structural equation model (SEM) previously built for haptic audiovisual interactive communications. The SEM includes three constructs (Audiovisual quality, Haptic quality, and User experience quality), which are latent variables each representing a group of observed variables with similar characteristics. In the SEM, the causal directions of the constructs were assumed by resorting to the domain knowledge. This article aims at proposing a methodology for inferring causal directions of constructs in general by verifying the assumption of causal directions in the SEM through their observed data alone. For that purpose, we compare six SEMs each with different causal directions of constructs, one of which is the one from the domain knowledge. The proposed method is based on QoE prediction by a Bayesian approach with Markov chain Monte Carlo (MCMC) simulation. Setting observed scores to the indicators of exogenous variables in each SEM, we predict values of all the indicators; we then assess the mean square error (MSE) between predicted QoE and mean opinion score (MOS) from observed scores and estimate the probability distribution of the MSE in each SEM. We can compare any two SEMs to find which is more plausible by examining the probability that the MSE for one SEM is smaller than or equal to that for the other. These probabilities are estimated with MCMC simulation. The method indicates that the causal directions thus inferred for the haptic audiovisual interactive communications adequately support the original ones drawn from the domain knowledge. In addition, we demonstrate that QoE can behave like the “impact-perceive-adapt” model of the effects of delayed haptic and visual feedback on performance in a collaborative environment, which Jay, Glencross, and Hubbold proposed in 2007, and that it accompanies reversal of plausible causal directions like a flip–flop.
What Has the Undiagnosed Diseases Network Taught Us About the Clinical Applications of Genomic Testing?
Authors: Murdock David R. , Rosenfeld Jill A. , Lee Brendan
Published: January 2022

Genetic testing has undergone a revolution in the last decade, particularly with the advent of next-generation sequencing and its associated reductions in costs and increases in efficiencies. The Undiagnosed Diseases Network (UDN) has been a leader in the application of such genomic testing for rare disease diagnosis. This review discusses the current state of genomic testing performed within the UDN, with a focus on the strengths and limitations of whole-exome and whole-genome sequencing in clinical diagnostics and the importance of ongoing data reanalysis. The role of emerging technologies such as RNA and long-read sequencing to further improve diagnostic rates in the UDN is also described. This review concludes with a discussion of the challenges faced in insurance coverage of comprehensive genomic testing as well as the opportunities for a larger role of testing in clinical medicine.
Corrosion Mechanism of Microporous Nickel-Chromium Coatings: Part I. Impact of Cupric Ions on Nickel Layers
Authors: Ganborena Larraitz , Özkaya Berkem , García Marta , Grande Hans-Jürgen , García-Lecina Eva , Vega Jesús Manuel
Published: January 2022

The effect of Cu2+ ions in the corrosion behaviour of microporous nickel-chromium multilayer coatings was investigated by means of electrochemical measurements such as open circuit potential and potentiodynamic polarisation. Data was obtained under exposure to acidified chloride-based electrolytes, varying the content (presence or absence) of cupric ions and the aeration conditions. A field emission scanning electronic microscope was used to obtain micrographs of the cross-section after exposure to different electrolytes whilst an optical microscope was used to characterise the surface appearance. Results have shown that Cu2+ cations are governing the reduction reaction independently of the presence of oxygen according to the polarisation curves. Samples exposed under this electrolyte have shown that the corrosion front was only located into the bright nickel layer. In contrast, the corrosion mechanism was modified in absence of Cu2+ ions. In fact, not only the bright nickel layer was corroded but also the microporous nickel one. It implies a different aesthetic impact on the surface depending on the type of active sites formed in each electrolyte.
Role of linkage between cerebral activity and baroreflex control of heart rate via central vasopressin V1a receptors in food-deprived mice
Authors: Sumiyoshi Eri , Masuki Shizue , Nose Hiroshi
Published: January 2022

Motivated behaviors, characterized by goal-directed and persistent movements, are indispensable for living. However, how cerebro-cardiovascular adjustment occurs during such behaviors remains unknown. By focusing on food-seeking behavior in a food-deprived condition using free-moving mice, we found that this condition enhanced the linkage between cerebral activation and suppression of baroreflex control of heart rate through central vasopressin V1a receptors, making it easier to start motivated behaviors by enhancing pressor response.
Experimental validation of a mean systemic pressure analog against zero-flow measurements in porcine VA-ECMO
Authors: Werner-Moller Per , Heinisch Paul Philipp , Hana Anisa , Bachmann Kaspar F. , Sondergaard Soren , Jakob Stephan M. , Takala Jukka , Berger David
Published: January 2022

This is the first study ever to validate the mean systemic pressure analog (Pmsa) against the reference mean systemic filling pressure (MSFP) determined at full arterio-venous pressure equilibrium. Using a porcine ECMO model with clinically relevant levels of vasoconstriction and volume expansion, we showed that Pmsa accurately estimated absolute and changing values of MSFP, with a poor between-method precision. The within-method precision of Pmsa was excellent.
A New Bivariate Extended Generalized Inverted Kumaraswamy Weibull Distribution
Authors: Ragab Mahmoud , Elhassanein Ahmed
Published: January 2022

This article presents a new bivariate extended generalized inverted Kumaraswamy Weibull (BIEGIKw-Weibull) distribution with nine parameters. Statistical properties of the new distribution are discussed. Forms of copulas, moments, conditional moments, bivariate reliability function, and bivariate hazard rate function are derived. Maximum likelihood estimators are formulated. Simulation is conducted for three different sets of parameters to verify the theoretical results and to discuss the new distribution properties. The performance of the maximum likelihood method is investigated via Monte Carlo simulation depending on the bias and the standard error. Simulated lifetime data is used as an application of the new model.
Role of Cholinergic Anti-Inflammatory Pathway in Protecting Sepsis-Induced Acute Lung Injury through Regulation of the Conventional Dendritic Cells
Authors: Li Ruiting , Hu Xuemei , Chen Huibin , Zhao Yue , Gao Xuehui , Yuan Yin , Guo Huiling , Huang Haiyan , Zou Xiaojing , Qi Hong , Liu Hong , Shang You
Published: January 2022

Background. The cholinergic anti-inflammatory pathway connects the immune response system and the nervous system via the vagus nerve. The key regulatory receptor is the α7-subtype of the nicotinic acetylcholine receptor (α7nAChR). Cholinergic anti-inflammatory pathway has been proved to be effective in suppressing the inflammation responses in acute lung injury (ALI). Dendritic cells (DCs), the important antigen-presenting cells, also express the α7nAChR. Past studies have indicated that reducing the quantity of mature conventional DCs and inhibiting the maturation of pulmonary DCs may prove effective for the treatment of ALI. However, the effects of cholinergic anti-inflammatory pathway on maturation, function, and quantity of DCs and conventional DCs in ALI remain unclear. Objective. It was hypothesized that cholinergic anti-inflammatory pathway may inhibit the inflammatory response of ALI by regulating maturation, phenotype, and quantity of DCs and conventional DCs. Methods. GTS-21 (GTS-21 dihydrochloride), an α7nAchR agonist, was prophylactically administered in sepsis-induced ALI mouse model and LPS-primed bone marrow-derived dendritic cells. The effects of GTS-21 were observed with respect to maturation, phenotype, and quantity of DCs, conventional DCs, and conventional DCs2 (type 2 conventional DCs) and the release of DC-related proinflammatory cytokines in vivo and in vitro. Results. The results of the present study revealed that GTS-21 treatment decreased the maturation of DCs and the production of DC-related proinflammatory cytokines in vitro and in sepsis-induced ALI mouse model; it reduced the quantity of CD11c+MHCII+ conventional DCs and CD11c+CD11b+ conventional DCs2 in vivo experiment. Conclusions. Cholinergic anti-inflammatory pathway contributes to the reduction in the inflammatory response in ALI by regulating maturation, phenotype, and quantity of DCs, conventional DCs, and conventional DCs2.
Evaluation of Cardiac Function before and after PAD Regimen in Patients with Multiple Myeloma by Three-Dimensional Speckle Tracking Imaging
Authors: Chen Dongliang , Yan Zining , Fan Li , Rui Yifei
Published: January 2022

In this manuscript, we have evaluated numerous changes of cardiac function in patients with multiple myeloma before and after PAD chemotherapy with 3D speck tracking imaging (3D-STI). For this purpose, 39 patients with multiple myeloma, from July 2019 to December 2020, who received the PAD regimen (bortezomib + doxorubicin liposome + dexamethasone, a course of 12 days) were selected as subjects. A comparison of two-dimensional conventional echocardiographic parameters before and after chemotherapy and 3D-STI related parameters was carried out. After 6 cycles of chemotherapy, the levels of TAPSE, RVFAC, and LVEF were significantly lower than those before chemotherapy (

P
<
0.05

). There was no significant difference in the results of left and right ventricle two-dimensional conventional echocardiography before chemotherapy and 2 or 4 cycles after chemotherapy (

P
>
0.05

). There were significant differences in the levels of RVGCS, RVGLS, RVGRS, LVGLS, and LVGRS before and after chemotherapy (

P
<
0.05

). Specifically, RVGCS: after 6 cycles of chemotherapy < after 4 cycles of chemotherapy < before chemotherapy; RVGLS: after 6 cycles of chemotherapy < after 4 cycles of chemotherapy < after 2 cycles of chemotherapy < before chemotherapy; RVGRS: after 6 cycles of chemotherapy < after 4 cycles of chemotherapy < before chemotherapy; LVGLS: after 6 cycles of chemotherapy < after 4 cycles of chemotherapy < before chemotherapy; and LVGRS: after 6 cycles of chemotherapy < before chemotherapy. The results of Pearson correlation analysis showed that the dose of doxorubicin was negatively correlated with RVGCS, RVGLS, RVGRS, and LVGLS, but not with TAPSE, RVFAC, LVEF, and LVGRS. 3D-STI is helpful for early detection of the changes of left and right ventricular myocardial function after PAD chemotherapy in patients with multiple myeloma. And the early screening value of the RVGLS parameter is higher.
Distribution and Risk Factors of Multidrug-Resistant Bacteria Infection in Orthopedic Patients
Authors: Liang Maohua , Liu Qiang
Published: January 2022

Objective. To study the distribution and risk factors of multidrug-resistant bacteria (MDROS) infection in orthopedic patients and to provide reference for clinical prevention and control measures. Methods. The data of 239 inpatients with orthopedic trauma from June 2019 to December 2020 were selected as the research objects, and the distribution characteristics of MDROS infection were analyzed through the real-time monitoring system of nosocomial infection. Logistic regression analysis was used to screen out the risk factors causing MDROS infection, and the preventive measures were put forward. Results. 178 strains of pathogens were isolated from 239 patients, including 53 strains of MDROS, and the detection rate was 29.78%. The main pathogenic bacteria were ESBLs, MRSA, CRAB, CRE, and MDR/PDRPA. The main infection sites of MDROS in orthopedic patients were the respiratory tract and wound. No CRE1 was detected, and 64.39%, 17.42%, and 14.39% of ESBL-producing bacteria, MRSA, and MDR/PDRPA, respectively, were detected. Logistic multivariate analysis showed that the length of hospital stay, antibiotic use time, open injury, and serum albumin level were independent risk factors of MDROS infection in orthopedic trauma patients. Conclusion. To prevent MDROS infection in orthopedic patients, we should start from many aspects, focusing on reducing unnecessary hospitalization days, rationally preventing the use of antibacterial drugs, effectively treating basic diseases, etc., timely and effective thorough debridement, strengthening functional training, reducing bed rest, and strengthening targeted monitoring of related infections which are the keys to reduce MDROS infection in orthopedic patients.
Comparative Study on Clear Specimen Strength and Member Strength of Side‐Pressure Laminated Bamboo
Authors: Gao Danping , Chen Bowang , Wang Liu , Tang Chunan , Yuan Ping
Published: January 2022

Side‐pressure laminated bamboo (LB) made from heat‐modified, fast‐growing bamboo is introduced in this document. As a relatively new type of bamboo composite fabricated by bamboo strips, side‐pressure LB has some favorable mechanical properties, such as thermal insulation, light mass, high strength, and earthquake resistance. To promote the application of side‐pressure LB in structural engineering, according to the test standards for timber, the mechanical properties of bamboo, including tensile strength parallel to the grain, compressive strength parallel to the grain, bending strength and bending modulus, and shear strength parallel to the grain, were obtained by testing clear bamboo. Meanwhile, the bending and shear tests were performed on full‐sized beams of side‐pressure LB. Comparing the strength of clear bamboo and full‐sized bamboo beams under bending and shear, explore the effect of size on bending and shear strength. The results demonstrate that the size effect has a significant influence on the bending strength, and the bending strength decreases clearly with the increase of the span of member; the shear strength is mainly affected by the shear area and decreases with the increase of the shear area. Based on the measured indicators of shear strength, a formula suitable for converting the shear strength of clear bamboo to full‐sized bamboo beam is proposed. And the recommended design strengths of bamboo are given by using the limit state method, which provides a design basis for the engineering application of bamboo.
PGF2α-FP Receptor Ameliorates Senescence of VSMCs in Vascular Remodeling by Src/PAI-1 Signal Pathway
Authors: Hu Bo-ang , Sai Wen-wen , Yuan Jun , Lan Hong-tao , Qi Jia , Wang Di , Zhang Wei , Wang Zhi-hao , Zhong Ming , Shang Yuan-yuan
Published: January 2022

Senescence in vascular smooth muscle cells (VSMCs) is involved in vascular remodeling of aged mice. ProstaglandinF2α- (PGF2α-) FP receptor plays a critical role in cardiovascular diseases (CVDs), hypertension, and cardiac fibrosis. However, its role in senescence-induced arteriosclerosis is yet to be fully elucidated. In this study, we found that FP receptor expression increased in aged mouse aortas and senescence VSMCs. FP receptor gene silencing can ameliorate vascular aging and inhibit oxidative stress, thereby reducing the expression of PAI-1, inhibiting the activation of MMPs, and ultimately improving the excessive deposition of ECM and delaying the process of vascular fibrosis. FP receptor could promote VSMC senescence by upregulated Src/PAI-1 signal pathway, and inhibited FP receptor/Src/PAI-1 pathway could ameliorate VSMCs aging in vitro, evidenced by the decrease of senescence-related proteins P16, P21, P53, and GLB1 expressions. These results suggested that FP receptor is a promoter of vascular aging, by inducing cellular aging, oxidative stress, and vascular remodeling via Src and PAI-1 upregulation.
MiroRNA-31-3p Promotes the Invasion and Metastasis of Non-Small-Cell Lung Cancer Cells by Targeting Forkhead Box 1 (FOXO1)
Authors: Zeng Xiaoyuan , Liu Da , Peng Ganlin , Liu Jun , Yang Hongzhong
Published: January 2022

Objective. To explore the possibility of microRNA miR-31-3p as a biomarker for bone metastasis of non-small-cell lung cancer (NSCLC) and its molecular mechanism to the invasion and metastasis of NSCLC cells. Methods. Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of miR-31-3p and forkhead box 1 (FOXO1) in NSCLC tissues, serum, and cells to analyze the correlation between the expression levels of miR-31-3p and the clinicopathology of NSCLC. After interference with or overexpressing miR-31-3p, NSCLC cell proliferation, apoptosis, invasion ability, and migration ability were detected by MTT, flow cytometry, Transwell, and scratch experiment, respectively. The interaction between miR-31-3p and FOXO1 was further verified by the dual-luciferase reporter experiment. Western blot was performed to detect the protein expression of FOXO1 in tissues and FOXO1, RhoA, p-RhoA, ROCK-2, and p-ROCK-2 in cells. Results. In tissues, serum, and NSCLC cell line A549 of the NSCLC patients, the expression of FOXO1 was notably lower, and the miR-31-3p expression was significantly higher. Overexpression of miR-31-3p could distinctly improve the proliferation, invasion, and migration of A549 cells, meanwhile inhibit cell apoptosis, and activate the RhoA/ROCK-2 signaling pathway, while interfering with the expression of miR-31-3p has the opposite function. Besides, bioinformatics analysis and luciferase reporter assay confirmed that FOXO1 was a target gene of miR-31-3p. Overexpressing FOXO1 could inhibit the proliferation and metastasis of A549 cells, but overexpressing miR-31-3p reverses the results. Conclusion. This study confirmed that miR-31-3p promotes the proliferation, invasion, and migration of NSCLC cells and inhibits apoptosis through targeted regulating FOXO1 and be a potential therapeutic targets for the treatment of NSCLC.
Design of Intelligent Customer Service Questioning and Answering a System for Power Business Scenario Based on AI Technology
Authors: Wu Shisong
Published: January 2022

In order to solve the problems of large demand for power business and small number of customer service, an intelligent customer service questioning and answering a system for power business scenario based on AI technology is designed. The approach first uses the particle swarm optimization algorithm to automatically classify the question attributes and then uses the fuzzy c-means clustering algorithm to match the answers with the highest similarity to the questions and return to the customers. The system collects the questions raised by customers through the acquisition module, uploads the question work order to the knowledge base through the information assistance module, and stores the preprocessed questions to the knowledge base. After completing the problem attribute classification through the particle swarm clustering algorithm classification model in the batch analysis and calculation module, the question answers are matched through fuzzy c-means clustering. At the same time, the similarity of different keywords is calculated to find a series of related questions. After the obtained data are analyzed in real time through the self-service customer service module, the answer is extracted and fed back to the customer, and the question answer is presented to the customer in the system interface. The experimental results show that the designed system has low worst-case time complexity, which is up to 0.35 only. The reason is that the system in this paper can use priority information to deal with the problems raised by customers, which is different from the past work where dealing with customers request via priority information is not used. The system can give the corresponding answers according to the customer’s options. It has convenient operation, high integrated control ability, and good information management performance. Compared with the traditional approach which could waste a lot of resource and data, the proposed approach can reduce the differences between problem data, eliminate invalid data, and simplify the data classification process. The application of the system can effectively accelerate the information transmission efficiency of the power company and can be used for power exchange platform automation in the future.
[Retracted] Prediction and Risk Assessment Models for Subarachnoid Hemorrhage: A Systematic Review on Case Studies
Authors: Sengupta Jewel , Alzbutas Robertas
Published: January 2022

Subarachnoid hemorrhage (SAH) is one of the major health issues known to society and has a higher mortality rate. The clinical factors with computed tomography (CT), magnetic resonance image (MRI), and electroencephalography (EEG) data were used to evaluate the performance of the developed method. In this paper, various methods such as statistical analysis, logistic regression, machine learning, and deep learning methods were used in the prediction and detection of SAH which are reviewed. The advantages and limitations of SAH prediction and risk assessment methods are also being reviewed. Most of the existing methods were evaluated on the collected dataset for the SAH prediction. In some researches, deep learning methods were applied, which resulted in higher performance in the prediction process. EEG data were applied in the existing methods for the prediction process, and these methods demonstrated higher performance. However, the existing methods have the limitations of overfitting problems, imbalance data problems, and lower efficiency in feature analysis. The artificial neural network (ANN) and support vector machine (SVM) methods have been applied for the prediction process, and considerably higher performance is achieved by using this method.
Research on Seismic Vulnerability of High-Pier and Long-Span Bridges Based on Improved IMK Resilience Model
Authors: Wang Yifan , Yin Lihui
Published: January 2022

After the fragility curve is established, the probability of structural damage reaching each level of damage under the action of the ground motion can be determined according to the ground motion parameters, so as to calculate the direct and indirect loss caused by the structural damage and complete the earthquake damage prediction. This paper combines the improved IMK resilience model to study the seismic vulnerability of high-pier and long-span bridges. Moreover, this paper obtains the parameter calculation model based on the regression analysis of PEER’s 255 column specimen data. The improved IMK model needs to modify the elastic stiffness and strain hardening rate of the rotating spring to ensure the accuracy of the lateral stiffness of the component. The experimental research shows that the seismic vulnerability research model of high-pier and long-span bridges based on the improved IMK restoring force model has a certain analytical effect.
Novel Artificial Biofilm Equivalent for Denture Surfaces: A Pilot Study
Authors: Kunze Jan-Philipp , Boening Klaus , Meissner Heike , Kresse-Walczak Katarzyna
Published: January 2022

The microbial population of the dental biofilm is embedded in an extracellular matrix that contains organic polymers such as polysaccharides. The extracellular matrix promotes biofilm adhesion on surfaces of dental prostheses and acts as a protective barrier. Thus, a breakdown of the extracellular matrix is crucial for an effective mechanical biofilm removal by brushing. The purpose of this study was to develop an artificial biofilm equivalent (ABE) that is able to mimic the mechanical properties of a natural biofilm concerning abrasion resistance. It contains the two polysaccharides chitosan (ChS) and methylcellulose (MC). Polymethylmethacrylate (PMMA) cylinders (

n
=
80

) were manufactured and coated with the ABE with varying concentration ratios of ChS and MC. Eight test series (

n
=
8

each) with different mixing ratios of ChS/MC were tested for their abrasion resistance to brushing in a toothbrush simulator. For the ABE, a total of 2.0 g of polysaccharides were added to 100 ml of 2% acetic acid: 0.3–1.0 g ChS and 1.0–1.7 MC, respectively. Furthermore, two control series (

n
=
8

each) with 2.0 g of ChS only or 2.0 g of MC only were performed. Coated specimens were subjected to an increasing number of brushing strokes from 5 to 45 via abrasion test. The specimens were photographed, and a computerized planimetric method (CPM) was used to calculate the percentage of remaining ABE on the brushed areas of the PMMA cylinders. The abrasion resistance of the ABE to brushing decreased with an increasing ratio of MC in the mixture. The abrasion resistance of the ABE can be adjusted by changing the ratio of ChS and MC.