bluuebunny/crossref_metadata_2025 huggingface dataset:
FINANCIAL LITERACY AND FINANCIAL INCLUSION EFFECTS ON STABILITY AND COMPETITIVENESS INDICATORS IN THE BANKING SECTOR: CROSS COUNTRY EVIDENCE FOR AFRICA AND THE WORLD
Authors: JUNGO JOÃO , MADALENO MARA , BOTELHO ANABELA
Published: September 2021

Financial inclusion has allowed financial products with very high-interest rates and complex conditions to become increasingly affordable. Financial inclusion programs, which aim to reach all social strata, strongly expose financial institutions to risk and particularly credit risk. That said, additional interventions such as financial education of those included are needed. We aim to examine the impact of financial literacy and financial inclusion of households on bank performance. Specifically, we want to examine the impact of financial literacy on credit risk, competitiveness among banks and financial stability. The FGLS estimation results suggest that financial literacy and financial inclusion reduce credit risk and enhance the stability of banks, and regarding competitiveness, our results were inconclusive as they show different effects for each competitiveness indicator, although they point to improved competitiveness in some cases. This research allows policymakers to understand that individual financial attitudes can be reflected in the general welfare of financial institutions and encourages the intensification of programs aimed at improving household financial literacy.
Reflective Nested Simulations Supporting Optimizations within Sequential Railway Traffic Simulators
Authors: Diviš Roman , Kavička Antonín
Published: September 2021

This article describes and discusses railway-traffic simulators that use reflective nested simulations. Such simulations support optimizations (decision-making) with a focus on the selection of the most suitable solution where selected types of traffic problems are present.

This approach allows suspension of the ongoing main simulation at a given moment and, by using supportive nested simulations (working with an appropriate lookahead), assessment of the different acceptable solution variants for the problem encountered—that is, a what-if analysis is carried out. The variant that provides the best predicted operational results (based on a specific criterion) is then selected for continuing the suspended main simulation. The proposed procedures are associated, in particular, with the use of sequential simulators specifically developed for railway traffic simulations. Special attention is paid to parallel computations of replications both of the main simulation and of supportive nested simulations.

The concept proposed, applicable to railway traffic modelling, has the following advantages. First, the solution variants for the existing traffic situation are analyzed with respect to the feasibility of direct monitoring and evaluation of the natural traffic indicators or the appropriate (multi-criterial) function. The indicator values compare the results obtained from the variants being tested. Second, the supporting nested simulations, which potentially use additional hierarchic nesting, can also include future occurrences of random effects (such as train delay), thereby enabling us to realistically assess future traffic in stochastic conditions.

The guidelines presented (for exploiting nested simulations within application projects with time constraints) are illustrated on a simulation case study focusing on traffic assessment related to the track infrastructure of a passenger railway station. Nested simulations support decisions linked with dynamic assignments of platform tracks to delayed trains.

The use of reflective nested simulations is appropriate particularly in situations in which a reasonable number of admissible variants are to be analyzed within decision-making problem solution. This method is applicable especially to the support of medium-term (tactical) and long-term (strategic) planning. Because of rather high computational and time demands, nested simulations are not recommended for solving short-term (operative) planning/control problems.
Three Dimensional Reconstruction of Botanical Trees with Simulatable Geometry
Authors: Quigley Ed , Lin Winnie , Zhu Yilin , Fedkiw Ronald
Published: September 2021

We tackle the challenging problem of creating full and accurate three dimensional reconstructions of botanical trees with the topological and geometric accuracy required for subsequent physical simulation, e.g. in response to wind forces. Although certain aspects of our approach would benefit from various improvements, our results exceed the state of the art especially in geometric and topological complexity and accuracy. Starting with two dimensional RGB image data acquired from cameras attached to drones, we create point clouds, textured triangle meshes, and a simulatable and skinned cylindrical articulated rigid body model. We discuss the pros and cons of each step of our pipeline, and in order to stimulate future research we make the raw and processed data from every step of the pipeline as well as the final geometric reconstructions publicly available.
Methods for Robot Behavior Adaptation for Cognitive Neurorehabilitation
Authors: Kubota Alyssa , Riek Laurel D.
Published: September 2021

An estimated 11% of adults report experiencing some form of cognitive decline, which may be associated with conditions such as stroke or dementia and can impact their memory, cognition, behavior, and physical abilities. While there are no known pharmacological treatments for many of these conditions, behavioral treatments such as cognitive training can prolong the independence of people with cognitive impairments. These treatments teach metacognitive strategies to compensate for memory difficulties in their everyday lives. Personalizing these treatments to suit the preferences and goals of an individual is critical to improving their engagement and sustainment, as well as maximizing the treatment's effectiveness. Robots have great potential to facilitate these training regimens and support people with cognitive impairments, their caregivers, and clinicians. This article examines how robots can adapt their behavior to be personalized to an individual in the context of cognitive neurorehabilitation. We provide an overview of existing robots being used to support neurorehabilitation and identify key principles for working in this space. We then examine state-of-the-art technical approaches for enabling longitudinal behavioral adaptation. To conclude, we discuss our recent work on enabling social robots to automatically adapt their behavior and explore open challenges for longitudinal behavior adaptation. This work will help guide the robotics community as it continues to provide more engaging, effective, and personalized interactions between people and robots.
Physiology labs during a pandemic: What did we learn?
Authors: Chen Xinnian , Kirn-Safran Catherine B. , van der Meulen Talitha , Myhr Karen L. , Savitzky Alan H. , Fleegal-DeMotta Melissa A.
Published: September 2021

This article captures a collective reflection on the successes and challenges we experienced when teaching physiology laboratories online during the COVID-19 pandemic. Physiology instructors from six institutions discussed their own efforts to redesign meaningful physiology laboratories that could be taught remotely, as the nation scrambled to respond to the sudden shift out of the classroom. Despite the complexity of this task, clear themes emerged as our courses transitioned to an online format in spring 2020 and were solidified in the fall of 2020. This article reflects on the history, features, benefits, and challenges of current laboratory teaching when applying a scientific teaching approach to facilitate the redesign process. We believe online networks like ours can facilitate information sharing, promote innovations, and provide support for instructors. The insights we gained through this collaboration will influence our thinking about the future of the physiology lab, whether online or in person.
Application of 3D Image Technology in Motor and Sensory Nerve Classification
Authors: Liu Na
Published: September 2021

Objective. To explore the application of 3D image technology in motor and sensory nerve classification. Methods. A total of 200 sections of the 5cm-long popliteal fossa peroneal nerve from adult volunteers were cut and frozen. The slices were 10 m thick, and the interval between the slices was 0.25 mm. Acetylcholinesterase histochemical staining was used to observe the changes of nerve bundles under the microscope. The stained sections were transformed into digital images by the digital camera system, and the images were stitched to obtain a two-dimensional panoramic image 100 times magnified. The properties of the functional bundles were manually judged. Using Amira 3.1 three‐dimensional reconstruction software to realize the three-dimensional reconstruction and visualization of nerve can not only accurately perceive the complex three-dimensional surface structure of nerve, but also arbitrarily display, rotate, scale, and segment the three-dimensional structure inside nerve, and carry out three-dimensional measurement in time. It has made preliminary achievements in brachial plexus, lumbosacral plexus, neural stem functional bundle (group), and intramuscular nerve routing and distribution, including the regeneration process of sensory nerve and three-dimensional reconstruction and visualization of composite tissue containing sensory nerve. Conclusion. Based on histology and computer technology, the functional band of short peroneal nerve can be reconstructed in 3D, which provides a feasible basis for the three-dimensional reconstruction of the functional band of the long peripheral nerve.
Research on Optimization of Blockchain Network and Data Communication in the Ecological Structure of Sports Industry
Authors: Li Yupeng , Kim Kitak , Ding Yu
Published: September 2021

Problems such as excessive centralization of sports industry operations, unclear value, and lack of IP protection hinder the benign interaction between various formats of the sports industry and the healthy operation of the industrial ecosystem. This article is aimed at studying the use of the decentralization, openness and transparency, smart contracts, copyright traceability, and other characteristics of the BT to construct a PCMR model, which can solve the pain points faced by the sports industry ecosystem in a targeted manner, and forming a way to reconstruct trust, the specific implementation path of the integration of BT and sports industry with mechanism as the core. This paper proposes blockchain network and data communication algorithms such as consensus algorithm, signature core algorithm, and practical Byzantine fault‐tolerant algorithm to provide technical support for the application of blockchain technology in the sports industry ecosystem and, at the same time, provide technical support for blockchain network and data communication. The feasibility analysis of the application of the sports industry ecosystem is proposed, and the implementation path of the blockchain network and data communication to reconstruct the sports industry ecosystem is analyzed. Finally, the empirical test of the support of blockchain sports to the sports industry is carried out. By analyzing the panel data of 240 observations of 48 listed companies in 5 years as a sample of the sports industry, the experimental results show that the dominant modulus of the sample does not have other differences, and the leftovers all pass significance test at the 10% level at least, denoting that the fundamental sample is more rational.
Cooperation‐Based Modeling of Sustainable Development: An Approach from Filippov’s Systems
Authors: Amador Jorge A. , Redondo Johan Manuel , Olivar‐Tost Gerard , Erazo Christian
Published: September 2021

The concept of Sustainable Development has given rise to multiple interpretations. In this article, it is proposed that Sustainable Development should be interpreted as the capacity of territory, community, or landscape to conserve the notion of well‐being that its population has agreed upon. To see the implications of this interpretation, a Brander and Taylor model, to evaluate the implications that extractivist policies have over an isolated community and cooperating communities, is proposed. For an isolated community and through a bifurcation analysis in which the Hopf bifurcation and the heteroclinic cycle bifurcation are detected, 4 prospective scenarios are found, but only one is sustainable under different extraction policies. In the case of cooperation, the exchange between communities is considered by coupling two models such as the one defined for the isolated community, with the condition that their transfers of renewable resources involve conservation policies. Since human decisions do not occur in a continuum, but rather through jumps, the mathematical model of cooperation used is a Filippov System, in which the dynamics could involve two switching manifolds of codimension one and one switching manifold of codimension two. The exchange in the cooperation model, for specific parameter arrangements, exhibits n‐periodic orbits and chaos. It is notable that, in the cases in which the system shows sliding, it could be interpreted as a recovery delay related to the time needed by the deficit community to recover, until its dependence on the other community stops. It is concluded (1) that a sustainability analysis depends on the way well‐being is defined because every definition of well‐being is not necessarily sustainable, (2) that sustainability can be visualized as invariant sets in the nonzero region of the space of states (equilibrium points, n‐periodic orbits, and strange attractors), and (3) that exchange is key to the prevalence of the human being in time. The results question us on whether Sustainable Development is only to keep us alive or if it also implies doing it with dignity.
Analysis of Load Optimization in Solid Rocket Motor Propellant Grain with Pressure Cure
Authors: Cui Zhanxin , Li Haiyang , Shen Zhibin , Cui Huiru
Published: September 2021

At present, the casting of large-size motors often adopts pressure cure. This technology can effectively reduce the risk of damage to the structural integrity of the grain in the case-bonded casting solid rocket motor. In this paper, ABAQUS is used to establish a finite element model of star-shaped grains. The whole process of pressure cure was simulated and modeled, and the Python script was redeveloped. The Evol evolutionary algorithm was used in ISIGHT to optimize the load parameters such as pressure value, attenuation coefficient of the relief curve, and the attenuation coefficient of the cooling curve. The effects of different pressure values and different cooling and depressurizing rates on the residual stress and strain were analyzed. The optimization results show that the closer the pressure value is to the theoretical pressure, the more significant the effect of pressure cure. However, the effect of stress and strain reduction in different directions is slightly different. The different cooling and pressure relief rates have a great influence on the process quantity. Pressure cure works best when the pressure attenuation coefficient is equal to 6850, and the temperature attenuation coefficient is equal to 8650. The optimization analysis of pressure curing provides a reference for engineering practice.
Autoimmune Regulator Gene Polymorphisms in Egyptian Systemic Lupus Erythematosus Patients: Preliminary Results
Authors: Attia Doaa HS , Dorgham Dalia AH , El Maghraby Ahmed A. , Alkaffas Marwa , Abdel Kawy Mahitab A. , Sherif Mai M. , Abdel Halim Radwa M.
Published: September 2021

Background. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease. The autoimmune regulator (AIRE) is a master regulator of self-tolerance development. AIRE mutations lead to the development of autoimmune polyglandular syndrome type 1 while AIRE polymorphisms have been linked to organ-specific autoimmunity. The study is aimed at addressing the association between AIRE polymorphisms, rs2075876 (G > A) and rs760426 (A > G), and SLE susceptibility and expression in Egyptian patients. Methods. Ninety-nine patients were included. One hundred and ten, and 123 control subjects were genotyped for rs2075876 and rs760426, respectively. Lupus severity was assessed using the Lupus Severity of Disease Index and Lupus Severity Index (LSI). Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) damage index was considered. Genotyping was done using StepOne Real-Time PCR. Results. AIRE rs760426 GG was more frequent in the patients under the genotype level (14.1% vs. 4.9%,

p
=
0.032

) and recessive model (14.1% vs. 4.9%,

p
=
0.017

,

OR
=
3.2

(1.2-8.7)). Musculoskeletal involvement and nephritis were associated with AIRE rs2075876 under the dominant (97.9% vs. 80.8%,

p
=
0.009

,

OR
=
11

(1.3-89.2)) and recessive models (100% vs. 69.3%,

p
=
0.032

), respectively; and both were linked to AIRE rs2075876 at the allelic level: 98.3% vs. 85%,

p
=
0.005

,

OR
=
10.1

(1.3-76.6) and 82.8% vs. 68.6,

p
=
0.041

,

OR
=
2.2

(1-4.7), respectively. Patients with AIRE rs2075876 A alleles had a higher damage index ( 1 ± 1.3 vs. 0.6 ± 1.1,

p
=
0.045

) while the LSI was greater in patients with AIRE rs2075876 (8.5 ± 0.5 vs. 7.8 ± 1.3,

p
=
0.002

) and rs760426 (8.6 ± 11 vs. 7.8 ± 1.2,

p
=
0.031

) under the recessive models. Conclusion. AIRE rs760426 could share in SLE susceptibility while AIRE rs2075876 could influence the disease expression and burden in Egyptian patients.
Paeoniflorin Effect of Schwann Cell-Derived Exosomes Ameliorates Dorsal Root Ganglion Neurons Apoptosis through IRE1α Pathway
Authors: Zhu Yanbo , Han Shuo , Li Xiao , Gao Yingying , Zhu Jiayue , Yang Xinwei , Xu Liping
Published: September 2021

Background. Diabetic peripheral neuropathy (DPN) is a common complication of diabetes but its pathogenesis is not fully clarified. Endoplasmic reticulum (ER) stress has been confirmed to be involved in the development of DPN. Dorsal root ganglion neuron (DRGn) is the target cell of DPN injure in the peripheral neurons system. Schwann cell (SCs)-derived exosomes (SC-EXOs) can carry IRE1α signal transduction factors in ER stress to DRGn. The aim of this study is to investigate the effect of SC-EXOs treated with paeoniflorin (PF) on DRGn stimulated by high glucose. Methods. SCs were divided into Control group (Control), 150 mM glucose group (HG), high osmotic pressure group (HOP), and low, middle, and high dose PF group (PF1, PF10, and PF100). Exosomes were obtained from SCs by ultracentrifugation and identified according to marker proteins, including CD63, Alix, Hsp70, and TSG101. ER stress initiating factor GRP78, the IRE1α pathway information transmission factor IRE1α, and the phosphorylation level of IRE1α were detected by Western blot, DRGn is divided into Control group (Control), 50 mM glucose group + Control exosomes group (HG + EXOs Control), 50 mM glucose group (HG), and 50 mM glucose group + administration exosomes group (HG + EXOs PF1, HG + EXOs PF10, and HG + EXOs PF100); ER morphology of primary DRGn was observed by using the transmission electron microscope, the level of DRGn apoptosis was analyzed by TUNEL, and the downstream proteins of ER stress including CHOP, XBP1S, JNK, and p-JNK in DRG and the expression of apoptosis-related proteins Bcl-2, Bax, Caspase-3, and Caspase-12 were measured by Western blot. Results. Compared with the exosomes in the HG group, the exosomes after the intervention of PF can significantly reduce the expression of GRP78, IRE1α, and the phosphorylation level of IRE1αP<0.05; compared with the DRGn in the HG group, the SC-EXOs treated with PF could regulate the expression of proteins downstream of IRE1α pathway in ER stress (P<0.05orP<0.01), improve the morphological integrity of ER, and reduce apoptosis in DRGn (P<0.05orP<0.01). Conclusion. PF regulates the information of ER stress carried by SC-EXOs and further affects downstream of IRE1α pathway in DRGn, thus reducing ER stress-induced apoptosis. PF can interfere with DPN through affecting information communication carried by EXOs between SCs and DRGn.
A Study on the Volatile Compounds in Elaeagnus angustifolia L. Flowers during Flowering Season by Gas Chromatography-Mass Spectrometry Coupled with Advanced Chemometrics
Authors: Liu Zhijing , Ding Degang , Cui Huapeng , Wang Chuanchuan , Liu Juntao , Chen Li , Fan Meijuan , Geng Guangwei
Published: September 2021

The flowers of Elaeagnus angustifolia L. have been used as a homologous variety in China, whose quality seriously relies on the compositions during the flowering period. Unfortunately, studies on the variations of volatile compounds during the flowering season are rarely reported. Herein, a gas chromatography-mass spectrometry-based untargeted metabolomic methodology was proposed for the comprehensive analysis of volatile compounds in E. angustifolia flowers to classify various flowering stages. Samples from four flowering stages were collected, including the initial bloom stage, pre-full bloom stage (70–80% of flowers), full bloom stage, and ending of the bloom stage. Simultaneous distillation extraction was used for the extraction of volatile compounds in the flowers, which was then analyzed by a newly developed chemometric data analysis tool, autoGCMSDataAnal. An advantage of the developed methodology is that compounds can be accurately screened and identified. Finally, 59 compounds that showed significant difference among four flowering stages were screened and 31 compounds were identified. Sample clustering results from principal component analysis and hierarchical clustering analysis suggested that flowers from the pre-full bloom stage and full bloom stage may be more suitable when used as raw materials for industrial products.
Generalized Reich–Ćirić–Rus-Type and Kannan-Type Contractions in Cone
b
-Metric Spaces over Banach Algebras
Authors: Han Yan , Xu Shaoyuan
Published: September 2021

In this paper, we firstly introduce the generalized Reich‐Ćirić‐Rus-type and Kannan-type contractions in cone

b

-metric spaces over Banach algebras and then obtain some fixed point theorems satisfying these generalized contractive conditions, without appealing to the compactness of

X

. Secondly, we prove the existence and uniqueness results for fixed points of asymptotically regular mappings with generalized Lipschitz constants. The continuity of the mappings is deleted or relaxed. At last, we prove that the completeness of cone

b

-metric spaces over Banach algebras is necessary if the generalized Kannan-type contraction has a fixed point in

X

. Our results greatly extend several important results in the literature. Moreover, we present some nontrivial examples to support the new concepts and our fixed point theorems.
Wenshen Shengjing Decoction Improves Early Embryo Development by Maintaining Low H3K27me3 Levels in Sperm and Pronuclear Embryos of Spermatogenesis Impaired Mice
Authors: Sun Yanmei , Gao Fan , Xu Da , Lu Lei , Chen Qianggen , Yang Zheqing , Wang Xuenan , Pan Xiaoyan
Published: September 2021

Many ingredients in Wenshen Shengjing Decoction (WSSJD) can cause epigenetic changes in the development of different types of cells. It is not yet known whether they can cause epigenetic changes in sperms or early embryos. Here, we investigated the role of WSSJD in epigenetic modifications of sperms or early embryos and early embryo development. A mouse model with spermatogenesis disorders was established with cyclophosphamide (CPA). WSSJD was administrated for 30 days. The male model mice after the treatment were mated with the female mice treated with superovulation. The embryo development rate of each stage was calculated. Immunofluorescence staining was used to detect the expression of H3K27me3 in sperm, pronuclear embryos, and 2-cell embryos. Western blotting was used to detect the expression of histone demethylase KDM6A and methyltransferase EZH2 in 2-cell embryos with developmental arrest. The expressions of zygotic genome activation genes (ZSCAN4, E1F1AX, HSPA1A, ERV4-2, and MYC) in 2-cell embryos with developmental arrest were analyzed with qRT-PCR. Comparing with the control group, CPA destroyed the development of seminiferous epithelium, significantly increased the expression level of H3K27me3 in sperm, reduced the expression ratio of H3K27me3 in female and male pronuclei, delayed the development of 2-cell embryos, and increased the developmental arrest rate and degeneration rate of 2-cell embryos. Moreover, the expressions of EZH2 and H3K27me3 were significantly increased in the 2-cell embryos with developmental arrest, and the expression of zygotic genome activation genes (ZSCAN4, E1F1AX, HSPA1A, ERV4-2, and MYC) was significantly decreased. Compared with the CPA group, WSSJD promoted the development of seminiferous epithelium, maintained a low level of H3K27me3 modification in sperm and male pronucleus, significantly increased the development rate of 2-cell embryos and 3-4 cell embryos, and reduced the developmental arrest rate and degeneration rate of 2-cell embryos. WSSJD may promote early embryonic development by maintaining a low level of H3K27me3 modification in sperm and male pronucleus and regulating the zygotic genome activation in mice with spermatogenesis disorders induced by CPA.
A Survey on Transmission Schemes on Large‐Scale Internet of Things with Nonorthogonal Multiple Access
Authors: Zhou Wenyu , Zhao Rui , Zhu Fusheng , Lai Lijia , Li Xutao
Published: September 2021

This paper performs a comprehensive survey on transmission schemes for the large‐scale Internet of things (IoT) networks with nonorthogonal multiple access (NOMA). By solving the interference among users, NOMA can significantly improve the frequency reuse efficiency and support multiple users to use the same frequency resources. It is considered to be one of the most effective technologies for the next‐generation wireless communication. However, there are still many challenges on the transmission schemes for the large‐scale NOMA system, including the short‐data packet transmission, active user detection, channel estimation, and data detection. In order to meet these challenges, this paper first reviews the short‐packet transmission in the large‐scale NOMA systems and then reviews the active user detection and channel estimation technologies of the considered systems.
Biomimetic Rotary Tillage Blade Design for Reduced Torque and Energy Requirement
Authors: Yang Yuwan , Tong Jin , Huang Yuxiang , Li Jinguang , Jiang Xiaohu
Published: September 2021

A rotary cultivator is a primary cultivating machine in many countries. However, it is always challenged by high operating torque and power requirement. To address this issue, biomimetic rotary tillage blades were designed in this study for reduced torque and energy requirement based on the geometric characteristics (GC) of five fore claws of mole rats, including the contour curves of the five claw tips (GC-1) and the structural characteristics of the multiclaw combination (GC-2). Herein, the optimal blade was selected by considering three factors: (1) the ratio (

r

) of claw width to lateral spacing, (2) the inclined angle (

θ

) of the multiclaw combination, and (3) the rotary speed (

n

) through the soil bin tests. The results showed that the order of influence of factors on torque was

n

,

r

, and

θ

; the optimal combination of factors with the minimal torque was

r
=
1.25

,

θ
=

60

°

, and

n
=
240
 
rpm

. Furthermore, the torque of the optimal blade (BB-1) was studied by comparing with a conventional (CB) and a reported optimal biomimetic blade (BB-2) in the soil bin at the rotary speed from 160 to 320 rpm. Results showed that BB-1 and BB-2 averagely reduced the torque by 13.99% and 3.74% compared with CB, respectively. The field experiment results also showed the excellent soil-cutting performance of BB-1 whose average torques were largely reduced by 17.00%, 16.88%, and 21.80% compared with CB at different rotary speeds, forward velocities, and tillage depths, respectively. It was found that the geometric structure of the five claws of mole rats could not only enhance the penetrating and sliding cutting performance of the cutting edge of BB-1 but also diminish the soil failure wedge for minimizing soil shear resistance of BB-1. Therefore, the GC of five fore claws of mole rats could inspire the development of efficient tillage or digging tools for reducing soil resistance and energy consumption.
Influencing Factors of e‐Commerce Enterprise Development Based on Mobile Computing Big Data Analysis
Authors: Zhu Yixue , Chai Boyue
Published: September 2021

With the development of increasingly advanced information technology and electronic technology, especially with regard to physical information systems, cloud computing systems, and social services, big data will be widely visible, creating benefits for people and at the same time facing huge challenges. In addition, with the advent of the era of big data, the scale of data sets is getting larger and larger. Traditional data analysis methods can no longer solve the problem of large‐scale data sets, and the hidden information behind big data is digging out, especially in the field of e‐commerce. We have become a key factor in competition among enterprises. We use a support vector machine method based on parallel computing to analyze the data. First, the training samples are divided into several working subsets through the SOM self‐organizing neural network classification method. Compared with the ever‐increasing progress of information technology and electronic equipment, especially the related physical information system finally merges the training results of each working set, so as to quickly deal with the problem of massive data prediction and analysis. This paper proposes that big data has the flexibility of expansion and quality assessment system, so it is meaningful to replace the double‐sidedness of quality assessment with big data. Finally, considering the excellent performance of parallel support vector machines in data mining and analysis, we apply this method to the big data analysis of e‐commerce. The research results show that parallel support vector machines can solve the problem of processing large‐scale data sets. The emergence of data dirty problems has increased the effective rate by at least 70%.
Dietary Advanced Glycation End-Products and Mortality after Breast Cancer in the Women's Health Initiative
Authors: Omofuma Omonefe O. , Peterson Lindsay L. , Turner David P. , Merchant Anwar T. , Zhang Jiajia , Thomson Cynthia A. , Neuhouser Marian L. , Snetselaar Linda G. , Caan Bette J. , Shadyab Aladdin H. , Saquib Nazmus , Banack Hailey R. , Uribarri Jaime , Steck Susan E.
Published: September 2021

Background:

Advanced glycation end-products (AGE) are formed through nonenzymatic glycation of free amino groups in proteins or lipid. They are associated with inflammation and oxidative stress, and their accumulation in the body is implicated in chronic disease morbidity and mortality. We examined the association between postdiagnosis dietary Nϵ-carboxymethyl-lysine (CML)–AGE intake and mortality among women diagnosed with breast cancer.

Methods:

Postmenopausal women aged 50 to 79 years were enrolled in the Women's Health Initiative (WHI) between 1993 and 1998 and followed up until death or censoring through March 2018. We included 2,023 women diagnosed with first primary invasive breast cancer during follow-up who completed a food frequency questionnaire (FFQ) after diagnosis. Cox proportional hazards (PH) regression models estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) of association between tertiles of postdiagnosis CML-AGE intake and mortality risk from all causes, breast cancer, and cardiovascular disease.

Results:

After a median 15.1 years of follow-up, 630 deaths from all causes were reported (193 were breast cancer–related, and 129 were cardiovascular disease–related). Postdiagnosis CML-AGE intake was associated with all-cause (HRT3vsT1, 1.37; 95% CI, 1.09–1.74), breast cancer (HRT3vsT1, 1.49; 95% CI, 0.98–2.24), and cardiovascular disease (HRT3vsT1, 1.91; 95% CI, 1.09–3.32) mortality.

Conclusions:

Higher intake of AGEs was associated with higher risk of major causes of mortality among postmenopausal women diagnosed with breast cancer.

Impact:

Our findings suggest that dietary AGEs may contribute to the risk of mortality after breast cancer diagnosis. Further prospective studies examining dietary AGEs in breast cancer outcomes and intervention studies targeting dietary AGE reduction are needed to confirm our findings.
Immunogenicity and Safety of COVID-19 Vaccine BNT162b2 for Patients with Solid Cancer: A Large Cohort Prospective Study from a Single Institution
Authors: Di Noia Vincenzo , Pimpinelli Fulvia , Renna Davide , Barberi Vittoria , Maccallini Maria Teresa , Gariazzo Ludovica , Pontone Martina , Monti Alessandro , Campo Flaminia , Taraborelli Emanuela , Di Santo Maria , Petrone Fabrizio , Mandoj Chiara , Ferraresi Virginia , Ferretti Gianluigi , Carlini Paolo , Di Bella Ornella , Conti Laura , La Malfa Antonia Marina , Pellini Raul , Bracco Domenico , Giannarelli Diana , Morrone Aldo , Cognetti Francesco
Published: September 2021

Purpose:

We assessed the immunogenicity and safety of the BNT162b2 vaccine in a large cohort of patients with cancer (CP).

Experimental Design:

From March 1, 2021 to March 20, 2021, this prospective cohort study included 816 CP afferent to our institution and eligible for the vaccination. A cohort of 274 health care workers (HCW) was used as age- and sex-matched control group. BNT162b2 was administered as a two-dose regimen given 21 days apart. Blood samples to analyze anti-Spike (S) IgG antibodies (Ab) were collected prevaccination [timepoint (TP) 0], and at 3 weeks (TP1) and 7 weeks (TP2) after the first dose.

Results:

Patients characteristics: median age 62 (range, 21–97); breast/lung cancer/others (31/21/48%); active treatment/follow-up (90/10%). In the whole CP cohort, the serologic response rate (RR) and the titre of anti-S IgG significantly increased across the TPs; at TP2, the responders (IgG >15 AU/mL) were 94.2%. Active chemotherapy and chronic use of steroids were independent predictors of lower RR. Adverse events (AE) after the booster predicted higher likelihood of response (OR, 4.04; 95% confidence interval, 1.63–9.99; P = 0.003). Comparing the matched cohorts, the responders were significantly lower in CP than in HCW at TP1 (61.2% vs. 93.2%) and TP2 (93.3% vs. 100%), while the geometric mean concentration of IgG did not significantly differ at TP2 being significantly lower in CP (23.3) than in HCW (52.1) at TP1. BNT162b2 was well tolerated in CP; severe-grade AEs were 3.5% and 1.3% after the first and second doses, respectively.

Conclusions:

BNT162b2 assures serologic immunization without clinically significant toxicity in CP. The second dose is needed to reach a satisfactory humoral response.
Novel Mitochondria-Based Targeting Restores Responsiveness in Therapeutically Resistant Human Lung Cancer Cells
Authors: Yin Liyuan , Zhang Yi , Yin Lijuan , Ou Yan , Lewis Michael S. , Wang Ruoxiang , Zhau Haiyen E. , Zhou Qinghua , Chung Leland W.K.
Published: September 2021

Cisplatin and tyrosine kinase inhibitors (TKI) are recommended to treat non–small cell lung cancer (NSCLC). However, ubiquitously acquired drug resistance in patients with NSCLC diminishes their therapeutic efficacy. Strategies for overcoming cisplatin and TKI resistance are an unmet medical need. We previously described a group of near-infrared heptamethine carbocyanine fluorescent dyes, referred to as DZ, with tumor-homing properties via differentially expressed organic anion-transporting polypeptides on cancer cells. This group of organic dyes can deliver therapeutic payloads specifically to tumor cells in the form of a chemical conjugate. We synthesized DZ-simvastatin (DZ-SIM) initially to target cholesterol biosynthesis in lung cancer cells. DZ-SIM killed both cisplatin-sensitive and cisplatin-resistant as well as EGFR-TKI–sensitive and EGFR-TKI–resistant lung cancer cells. This conjugate specifically accumulated in and effectively inhibited the growth of xenograft tumors formed by NSCLC cells resistant to first-generation (H1650) and third-generation (PC9AR) EGFR TKIs. DZ-SIM induced cell death by targeting mitochondrial structure and function. We concluded that DZ-SIM could be a promising novel therapy for overcoming drug resistance in patients with NSCLC.
Paclitaxel Induces Micronucleation and Activates Pro-Inflammatory cGAS–STING Signaling in Triple-Negative Breast Cancer
Authors: Hu Yang , Manasrah Baraa K. , McGregor Stephanie M. , Lera Robert F. , Norman Roshan X. , Tucker John B. , Scribano Christina M. , Yan Rachel E. , Humayun Mouhita , Wisinski Kari B. , Tevaarwerk Amye J. , O'Regan Ruth M. , Wilke Lee G. , Weaver Beth A. , Beebe David J. , Jin Ning , Burkard Mark E.
Published: September 2021

Taxanes remain one of the most effective medical treatments for breast cancer. Clinical trials have coupled taxanes with immune checkpoint inhibitors in patients with triple-negative breast cancer (TNBC) with promising results. However, the mechanism linking taxanes to immune activation is unclear. To determine if paclitaxel could elicit an antitumoral immune response, we sampled tumor tissues from patients with TNBC receiving weekly paclitaxel (80 mg/m2) and found increased stromal tumor-infiltrating lymphocytes and micronucleation over baseline in three of six samples. At clinically relevant concentrations, paclitaxel can induce chromosome missegregation on multipolar spindles during mitosis. Consequently, post-mitotic cells are multinucleated and contain micronuclei, which often activate cyclic GMP-AMP synthase (cGAS) and may induce a type I IFN response reliant on the stimulator of IFN genes (STING) pathway. Other microtubule-targeting agents, eribulin and vinorelbine, recapitulate this cGAS/STING response and increased the expression of immune checkpoint molecule, PD-L1, in TNBC cell lines. To test the possibility that microtubule-targeting agents sensitize tumors that express cGAS to immune checkpoint inhibitors, we identified 10 patients with TNBC treated with PD-L1 or PD-1, seven of whom also received microtubule-targeting agents. Elevated baseline cGAS expression significantly correlated with treatment response in patients receiving microtubule-targeting agents in combination with immune checkpoint inhibitors. Our study identifies a mechanism by which microtubule-targeting agents can potentiate an immune response in TNBC. Further, baseline cGAS expression may predict patient treatment response to therapies combining microtubule-targeting agents and immune checkpoint inhibitors.
Glypican-1 Is a Novel Target for Stroma and Tumor Cell Dual-Targeting Antibody–Drug Conjugates in Pancreatic Cancer
Authors: Tsujii Shigehiro , Serada Satoshi , Fujimoto Minoru , Uemura Sunao , Namikawa Tsutomu , Nomura Taisei , Murakami Ichiro , Hanazaki Kazuhiro , Naka Tetsuji
Published: September 2021

Pancreatic ductal adenocarcinoma (PDAC) is a stroma-rich cancer. Extracellular matrix proteins produced by cancer-associated fibroblasts (CAFs) found in tumor stroma that impedes effective delivery of chemotherapeutic agents results in poor response in patients with PDAC. Previously, our group reported that glypican-1 (GPC1) was overexpressed in human PDAC and negatively correlated with patient survival. Immunohistochemical analysis of 25 patients with PDAC tumor specimens revealed elevated expression of GPC1 in stromal cells and pancreatic cancer cells in 80% of patients. Interestingly, GPC1 was expressed on CAFs in PDAC. We generated a GPC1 antibody–drug conjugate conjugated with monomethyl auristatin E [GPC1-ADC(MMAE)] and evaluated its preclinical antitumor activity by targeting GPC1-positive CAF and cancer cells in PDAC. GPC1-ADC(MMAE) inhibited the growth of GPC1-positive PDAC cell lines in vitro. Furthermore, GPC1-ADC(MMAE) showed a potent antitumor effect in the PDAC patient-derived tumor xenograft (PDX) model against GPC1-positive CAF and heterogeneous GPC1-expressing cancer cells. Notably, GPC1-ADC(MMAE) showed robust preclinical efficacy against GPC1 in a stroma-positive/cancer-negative PDAC PDX model. GPC1-ADC(MMAE) was delivered and internalized to CAFs. Although apoptosis was not observed in CAFs, the released MMAE from CAFs via MDR-1 induced apoptosis of cancer cells neighboring CAFs and efficiently inhibited PDAC tumor growth. GPC1-ADC(MMAE) exhibited potent and unique antitumor activity in GPC1-positive PDAC PDX models, which suggests that GPC1 is a novel therapeutic target in PDAC and other stromal GPC1-positive solid tumors. These findings show that targeting GPC1 on CAF using GPC1-ADC(MMAE) is a useful approach in case of stroma-rich tumors such as PDAC.
Rational Combination of CRM1 Inhibitor Selinexor and Olaparib Shows Synergy in Ovarian Cancer Cell Lines and Mouse Models
Authors: Handley Katelyn F. , Rodriguez-Aguayo Cristian , Ma Shaolin , Stur Elaine , Joseph Robiya , Bayraktar Emine , Dasari Santosh K. , Nguyen Nghi , Powell Reid T. , Sobieski Mary , Ivan Cristina , Kim Mark , Umamaheswaran Sujanitha , Glassman Deanna , Wen Yunfei , Amero Paola , Stephan Clifford , Coleman Robert L. , Landesman Yosef , Westin Shannon N. , Ram Prahlad T. , Sood Anil K.
Published: September 2021

CRM1 inhibitors have demonstrated antitumor effects in ovarian and other cancers; however, rational combinations are largely unexplored. We performed a high-throughput drug library screen to identify drugs that might combine well with selinexor in ovarian cancer. Next, we tested the combination of selinexor with the top hit from the drug screen in vitro and in vivo. Finally, we assessed for mechanisms underlying the identified synergy using reverse phase protein arrays (RPPA). The drug library screen assessing 688 drugs identified olaparib (a PARP inhibitor) as the most synergistic combination with selinexor. Synergy was further demonstrated by MTT assays. In the A2780luc ip1 mouse model, the combination of selinexor and olaparib yielded significantly lower tumor weight and fewer tumor nodules compared with the control group (P < 0.04 and P < 0.03). In the OVCAR5 mouse model, the combination yielded significantly fewer nodules (P = 0.006) and markedly lower tumor weight compared with the control group (P = 0.059). RPPA analysis indicated decreased expression of DNA damage repair proteins and increased expression of tumor suppressor proteins in the combination treatment group. Collectively, our preclinical findings indicate that combination with selinexor to expand the utility and efficacy of PARP inhibitors in ovarian cancer warrants further exploration.
Safety and Efficacy of Tivozanib in First-Line mRCC: A Multicenter Compassionate-Use Study (Meet-Uro 16)
Authors: Basso Umberto , Procopio Giuseppe , Fornarini Giuseppe , Massari Francesco , Bearz Alessandra , Fratino Lucia , Milella Michele , Bassanelli Maria , Ermacora Paola , Bimbatti Davide , Verzoni Elena , Rizzo Mimma , Porta Camillo
Published: September 2021

Introduction: Tivozanib is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR-1), VEGFR-2, and VEGFR-3, recently approved in Europe for the first-line treatment of metastatic renal cell carcinoma (mRCC). Methods: Retrospective analysis of safety and activity of tivozanib administered at 1.34 mg daily (3 weeks on, 1 week off) within a compassionate-use program to patients with mRCC with no prior systemic treatment in Italy. Results: From August 2018 to April 2019, 64 patients have started tivozanib in 9 oncology units. The median age was 67.5 years (range 40–85), 62.5% males. According to International Metastatic Renal Cell Carcinoma Database Consortium criteria, 27.1% of patients were good prognosis, 57.6% intermediate, and 15.3% poor. Primary tumor had been removed in 71.9% of patients. Histology was clear cell 89%, papillary 4.7%, and unclassified 6.3%. The response rate was 34.4%, stable disease 40.6%, and progression 15.6%. Grade 3–4 toxicities were 7.8% hypertension, 4.7% anemia, 3.1% mucositis, 3.1% asthenia, 1.6% diarrhea, 1.6% anorexia, 1.6% worsening of renal function, and 3.1% cardiac events. Dose reduction to 0.89 mg was applied to 17.2% of patients, and the discontinuation rate due to toxicity was 5.8%. Median progression-free survival was 12.4 months, with 68.7% of patients alive at 12 months. The developing of hypertension predicted increased progression-free survival at multivariate analysis (HR, 0.128; 95% CI, 0.03–0.59; p = 0.008). Conclusions: Tivozanib showed good activity and favorable safety profile in a real-world cohort of unselected patients with mRCC. Predictive biomarkers of response to antiangiogenic therapy are urgently needed in order to identify RCC patients who could still receive a monotherapy with VEGFR inhibitors in the first line.
Spondylometaepiphyseal Dysplasia Short Limb-Abnormal Calcification Type in Turkish Patients Reveals a Novel Mutation and New Features
Authors: Yilmaz Gulec Elif , Ali Bassam R. , John Anne , Tuysuz Beyhan
Published: September 2021

Spondylometaepiphyseal dysplasia short limb-abnormal calcification type (SMED-SL/AC) is a rare autosomal recessive disorder. It is a severe dwarfism syndrome with a characteristic feature of progressive calcification of epiphyseal and other cartilaginous tissues. It is caused by pathogenic variants in the DDR2 gene encoding the discoidin domain receptor tyrosine kinase 2. Thus far, 37 cases and 8 pathogenic variants have been reported. Most of the reported cases are of Middle Eastern and Puerto Rican origins. Only one Turkish case has been reported previously with a novel truncating variant p.(R489*). Here, we report 2 new cases, 1 with a novel variant p.(S311G) and 1 with a splice site variant c.2283+1G>A. In addition, we reviewed a previously reported case, and sequencing of stored DNA revealed the recently reported nonsense variant p.(R489*) as the underlying cause. Therefore, our data increase the number of SMED-SL/AC Turkish patients with molecular results to 4. Furthermore, we compared the features of Turkish patients with other reported cases and expanded the characteristics of the disorder with new features such as triventricular hydrocephalus, intracranial hemorrhage, hypopigmentation of hair, dry and scaly skin, arthralgia, and hypocalcemia. We also compared the pathogenic variants of Turkish patients with other variants, aiming to explain the mechanism leading to a more severe and early fatal course in Turkish patients.
Camptothecin-Induced Replication Stress Affects DNA Replication Profiling by E/L Repli-Seq
Authors: Hayakawa Takuya , Suzuki Rino , Kagotani Kazuhiro , Okumura Katsuzumi , Takebayashi Shin-ichiro
Published: September 2021

E/L Repli-seq is a powerful tool for detecting cell type-specific replication landscapes in mammalian cells, but its potential to monitor DNA replication under replication stress awaits better understanding. Here, we used E/L Repli-seq to examine the temporal order of DNA replication in human retinal pigment epithelium cells treated with the topoisomerase I inhibitor camptothecin. We found that the replication profiles by E/L Repli-seq exhibit characteristic patterns after replication-stress induction, including the loss of specific initiation zones within individual early replication timing domains. We also observed global disappearance of the replication timing domain structures in the profiles, which can be explained by checkpoint-dependent suppression of replication initiation. Thus, our results demonstrate the effectiveness of E/L Repli-seq at identifying cells with replication-stress-induced altered DNA replication programs.