bluuebunny/crossref_metadata_2025 huggingface dataset:
Approximation, characterization, and continuity of multivariate monotonic regression functions
Authors: Schmid Jochen
Published: December 2021

We deal with monotonic regression of multivariate functions [Formula: see text] on a compact rectangular domain [Formula: see text] in [Formula: see text], where monotonicity is understood in a generalized sense: as isotonicity in some coordinate directions and antitonicity in some other coordinate directions. As usual, the monotonic regression of a given function [Formula: see text] is the monotonic function [Formula: see text] that has the smallest (weighted) mean-squared distance from [Formula: see text]. We establish a simple general approach to compute monotonic regression functions: namely, we show that the monotonic regression [Formula: see text] of a given function [Formula: see text] can be approximated arbitrarily well — with simple bounds on the approximation error in both the [Formula: see text]-norm and the [Formula: see text]-norm — by the monotonic regression [Formula: see text] of grid-constant functions [Formula: see text]. monotonic regression algorithms. We also establish the continuity of the monotonic regression [Formula: see text] of a continuous function [Formula: see text] along with an explicit averaging formula for [Formula: see text]. And finally, we deal with generalized monotonic regression where the mean-squared distance from standard monotonic regression is replaced by more complex distance measures which arise, for instance, in maximum smoothed likelihood estimation. We will see that the solution of such generalized monotonic regression problems is simply given by the standard monotonic regression [Formula: see text].
Mapping the Wave of Industry Digitalization by Co-Word Analysis: An Exploration of Four Disruptive Industries
Authors: Bzhalava Levan , Hassan Sohaib S. , Kaivo-oja Jari , Köping Olsson Bengt , Imran Javed
Published: December 2021

This paper aims to identify global digital trends across industries and to map emerging business areas by co-word analysis. As the industrial landscape has become complex and dynamic due to the rapid pace of technological changes and digital transformation, identifying industrial trends can be critical for strategic planning and investment policy at the firm and regional level. For this purpose, the paper examines industry and technology profiles of top startups across four industries (i.e. education, finance, healthcare, manufacturing) using CrunchBase metadata for the period 2016–2018 and studies in which subsector early-stage firms bring digital technologies on a global level. In particular, we apply word co-occurrence analysis to reveal which subindustry and digital technology keywords/keyphrases appear together in startup company classification. We also use network analysis to visualize industry structure and to identify digitalization trends across sectors. The results obtained from the analysis show that gamification and personalization are emerging trends in the education sector. In the finance industry, digital technologies penetrate in a wide set of services such as financial transactions, payments, insurance, venture capital, stock exchange, asset and risk management. Moreover, the data analyses indicate that health diagnostics and elderly care areas are at the forefront of the healthcare industry digitalization. In the manufacturing sector, startup companies focus on automating industrial processes and creating smart interconnected manufacturing. Finally, we discuss the implications of the study for strategic planning and management.
GENDER GAPS IN ENTREPRENEURSHIP AND EDUCATION LEVELS FROM THE PERSPECTIVE OF CLUSTERS OF EUROPEAN COUNTRIES
Authors: GAWEŁ ALEKSANDRA , KRSTIĆ MILOŠ
Published: December 2021

In European countries, the gender gap in entrepreneurship is persistently observed because females make up on average 30 percent of entrepreneurs. The aim of the paper is to investigate the impact of gender gaps in education at different levels (youth, higher education, adult learning and STEM education) on the gender gap in entrepreneurship, both in all analyzed European countries and in identified clusters of countries. The research is based on the cluster analysis and regression modelling of yearly panel data for 31 European countries for the period 2013–2018. Generally speaking, to the same extent, the gender gap in entrepreneurship can be explained by the gender gap in educational outcomes at different levels, mostly in early leavers and in STEM education. However, European countries are not monolithic in these aspects, as four clusters of countries are identified. Relationships between the gender gaps strongly depend on the country’s characteristics. In countries with a relatively lower level of female entrepreneurship and their education outcomes, the gender gap in entrepreneurship is affected the most significant in comparison to other clusters, by gender gaps in early leavers, higher education and STEM education. However, in clusters of countries with relatively moderate or high levels of female entrepreneurship and education outcomes, their relationships are rather limited.
Dynamical aspects of corona virus infection
Authors: Larsen Jens Christian
Published: December 2021

In this paper, we consider five mathematical models of corona virus infection. The first model is a mathematical model of corona virus entry. The second model is a mathematical model for interactions of virus N-protein and viral RNA. Here, we prove that phosphorylated N protein increases the affinity of viral RNA. The third model is a mathematical model of virion assembly. It is a six-dimensional model. But there is an invariant three-dimensional submodel, which we can prove has a positive stable equilibrium. The fourth model is a model of an enzyme inhibitor that blocks viral replication. The fifth model is a model of a virus and a vaccine.
Path-following interior-point algorithm for monotone linear complementarity problems
Authors: Grimes Welid
Published: December 2021

This paper presents a path-following full-Newton step interior-point algorithm for solving monotone linear complementarity problems. Under new choices of the defaults of the updating barrier parameter [Formula: see text] and the threshold [Formula: see text] which defines the size of the neighborhood of the central-path, we show that the short-step algorithm has the best-known polynomial complexity, namely, [Formula: see text]. Finally, some numerical results are reported to show the efficiency of our algorithm.
Alignment of carbon nanotubes under the influences of nematic liquid crystals and electric fields — an analytical study
Authors: Sumandra Setia Budi , Mahendra Bhisma , Nugroho Fahrudin , Yusuf Yusril
Published: December 2021

Carbon nanotubes (CNTs) have benefits in various fields, they are disadvantageous due to their tendency to form aggregates and poorly controlled alignment of the CNT molecules (characterized by order parameters). These deficiencies can be overcome by dispersing the CNTs in nematic liquid crystal (LC) and placing the mixture under the influence of an electric field. In this study, Doi and Landau–de Gennes free energy density equations are used to analytically confirm that an electric field increases the order parameters of CNTs and LCs in a dispersion mixture. The anchoring strength of the nematic LC is also found to affect the order parameters of the CNTs and LC. Further, increasing the length-to-diameter ratio of the CNTs increases their alignment without affecting the LC alignment. These findings indicate that CNT molecular alignment can be controlled by adjusting the CNT length-to-diameter ratio, anchoring the LCs, and adjusting the electric field strength.
Religious, Civil, and Economic Freedoms: What’s the Chicken and What’s the Egg?
Authors: Makridis Christos Andreas
Published: December 2021

This paper studies the relationship between religious liberty and economic freedom. First, three new facts emerge: (a) religious liberty has increased since 1960, but has slipped substantially over the past decade; (b) the countries that experienced the largest declines in religious liberty tend to have greater economic freedom, especially property rights; (c) changes in religious liberty are associated with changes in the allocation of time to religious activities. Second, using a combination of vector autoregressions and dynamic panel methods, improvements in religious liberty tend to precede economic freedom. Finally, increases in religious liberty have a wide array of spillovers that are important determinants of economic freedom and explain the direction of causality. Countries cannot have long-run economic prosperity and freedom without actively allowing for and promoting religious liberty.
In Persona Christi Capitis: Agency Problems When God is the Principal
Authors: Jace Clara E. , Piano Ennio E.
Published: December 2021

The in persona Christi Capitis doctrine of the Roman Catholic Church guarantees the validity of its sacraments, irrespective of the personal morality of the priest who performs them. While this protects their value as metacredence goods, it seemingly opens the door to opportunistic behaviour by the clergy. To balance out its institutional incentives, the Roman Catholic Church must rigorously screen its candidates for the priesthood. Historical evidence supports our hypothesis that the development of the in persona Christi Capitis doctrine was accompanied by marginal increases in the screening of seminarians, which may have been an optimal response to changing historical circumstances. Also consistent with our hypothesis, a cross section of contemporary Christian denominations shows a correlation between a group’s stance on sacramental theology and the strictness of its screening of candidates to religious ministry.
On the Anonymization of Workflow Provenance without Compromising the Transparency of Lineage
Authors: Belhajjame Khalid
Published: December 2021

Workflows have been adopted in several scientific fields as a tool for the specification and execution of scientific experiments. In addition to automating the execution of experiments, workflow systems often include capabilities to record provenance information, which contains, among other things, data records used and generated by the workflow as a whole but also by its component modules. It is widely recognized that provenance information can be useful for the interpretation, verification, and re-use of workflow results, justifying its sharing and publication among scientists. However, workflow execution in some branches of science can manipulate sensitive datasets that contain information about individuals. To address this problem, we investigate, in this article, the problem of anonymizing the provenance of workflows. In doing so, we consider a popular class of workflows in which component modules use and generate collections of data records as a result of their invocation, as opposed to a single data record. The solution we propose offers guarantees of confidentiality without compromising lineage information, which provides transparency as to the relationships between the data records used and generated by the workflow modules. We provide algorithmic solutions that show how the provenance of a single module and an entire workflow can be anonymized and present the results of experiments that we conducted for their evaluation.
Knowledge-Driven Data Ecosystems Toward Data Transparency
Authors: Geisler Sandra , Vidal Maria-Esther , Cappiello Cinzia , Lóscio Bernadette Farias , Gal Avigdor , Jarke Matthias , Lenzerini Maurizio , Missier Paolo , Otto Boris , Paja Elda , Pernici Barbara , Rehof Jakob
Published: December 2021

A
data ecosystem
(DE) offers a keystone-player or alliance-driven infrastructure that enables the interaction of different stakeholders and the resolution of interoperability issues among shared data. However, despite years of research in data governance and management, trustability is still affected by the absence of transparent and traceable data-driven pipelines. In this work, we focus on requirements and challenges that DEs face when ensuring data transparency. Requirements are derived from the data and organizational management, as well as from broader legal and ethical considerations. We propose a novel knowledge-driven DE architecture, providing the pillars for satisfying the analyzed requirements. We illustrate the potential of our proposal in a real-world scenario. Last, we discuss and rate the potential of the proposed architecture in the fulfillmentof these requirements.
Validity and Rigour in Soma Design-Sketching with the Soma
Authors: Ståhl Anna , Tsaknaki Vasiliki , Balaam Madeline
Published: December 2021

We report on the design processes of two ongoing soma design projects: the Pelvic Chair and the Breathing Wings. These projects take a first-person, soma design approach, grounded in a holistic perspective of the mind and body (the soma). We contribute a reflective account of our soma design processes that deepens the field’s understanding of how soma design is achieved through first-person approaches. We show how we use our somas, our first-person experiences, to stimulate a design process, to prototype through and to use as a way of critiquing emerging designs. Grounding our analysis in new materialism, we show how our designs are in essence, “performative intra-actions”. Using our own somas, our designs open up for experiences within certain constraints, allowing for a material-discursive agency of sorts. Many different somas may be intra-acted through our designs, even if it was our somas who started them.
Concepts and Consequences of a Core Gut Microbiota for Animal Growth and Development
Authors: Perlman Daphne , Martínez-Álvaro Marina , Moraïs Sarah , Altshuler Ianina , Hagen Live H. , Jami Elie , Roehe Rainer , Pope Phillip B. , Mizrahi Itzhak
Published: December 2021

Animal microbiomes are occasionally considered as an extension of host anatomy, physiology, and even their genomic architecture. Their compositions encompass variable and constant portions when examined across multiple hosts. The latter, termed the core microbiome, is viewed as more accommodated to its host environment and suggested to benefit host fitness. Nevertheless, discrepancies in its definitions, characteristics, and importance to its hosts exist across studies. We survey studies that characterize the core microbiome, detail its current definitions and available methods to identify it, and emphasize the crucial need to upgrade and standardize the methodologies among studies. We highlight ruminants as a case study and discussthe link between the core microbiome and host physiology and genetics, as well as potential factors that shape it. We conclude with main directives of action to better understand the host–core microbiome axis and acquire the necessary insights into its controlled modulation.
CRISPR Screens to Identify Regulators of Tumor Immunity
Authors: LaFleur Martin W. , Sharpe Arlene H.
Published: December 2021

Cancer immunotherapies, such as immune checkpoint blockade (ICB), have been used in a wide range of tumor types with immense clinical benefit. However, ICB does not work in all patients, and attempts to combine ICB with other immune-based therapies have not lived up to their initial promise. Thus, there is a significant unmet need to discover new targets and combination therapies to extend the benefits of immunotherapy to more patients. Systems biology approaches are well suited for addressing this problem because these approaches enable evaluation of many gene targets simultaneously and ranking their relative importance for a phenotype of interest. As such, loss-of-function CRISPR screens are an emerging set of tools being used to prioritize gene targets for modulating pathways of interest in tumor and immune cells. This review describes the first screens performed to discover cancer immunotherapy targets and the technological advances that will enable next-generation screens.
Chemical Stability of Proteins in Foods: Oxidation and the Maillard Reaction
Authors: Poojary Mahesha M. , Lund Marianne N.
Published: December 2021

Protein is a major nutrient present in foods along with carbohydrates and lipids. Food proteins undergo a wide range of modifications during food production, processing, and storage. In this review, we discuss two major reactions, oxidation and the Maillard reaction, involved in chemical modifications of food proteins. Protein oxidation in foods is initiated by metal-, enzyme-, or light-induced processes. Food protein oxidation results in the loss of thiol groups and the formation of protein carbonyls and specific oxidation products of cysteine, tyrosine, tryptophan, phenylalanine, and methionine residues, such as disulfides, dityrosine, kynurenine, m-tyrosine, and methionine sulfoxide. The Maillard reaction involves the reaction of nucleophilic amino acid residues with reducing sugars, which yields numerous heterogeneous compounds such as α-dicarbonyls, furans, Strecker aldehydes, advanced glycation end-products, and melanoidins. Both protein oxidation and the Maillard reaction result in the loss of essential amino acids but may positively or negatively impact food structure and flavor.
Roles of Cities in Creating Healthful Food Systems
Authors: Cohen Nevin
Published: December 2021

Over the past several decades, cities worldwide have attempted to reconfigure their food systems to improve public health, advance social justice, and promote environmental resilience using diverse municipal policies, often with the support of stakeholder-led governance mechanisms such as food policy councils. This article reviews the roles that cities have played in creating healthful urban food systems and the effects of those policies on public health. It explains that despite wide-ranging policy initiatives, disparities in food insecurity and malnourishment persist. It concludes by describing several promising pathways for urban food policy: engaging in food-focused urban planning to create equitable food environments; treating policies to address inequality and social justice as upstream food policies; considering the effects of new business models such as online food retail in urban food policy making; and using food procurement as a lever to influence regional, national, and global food systems.
Blood gas analyses in hyperbaric and underwater environments: a systematic review
Authors: Paganini Matteo , Moon Richard E. , Boccalon Nicole , Melloni Giorgio E. M. , Giacon Tommaso A. , Camporesi Enrico M. , Bosco Gerardo
Published: December 2021

Pulmonary gas exchange during diving or in a dry hyperbaric environment is affected by increased breathing gas density and possibly water immersion. During free diving, there is also the effect of apnea. Few studies have published blood gas data in underwater or hyperbaric environments: this review summarizes the available literature and was used to test the hypothesis that arterial Po2 under hyperbaric conditions can be predicted from blood gas measurement at 1 atmosphere assuming a constant arterial/alveolar Po2 ratio (a:A). A systematic search was performed on traditional sources including arterial blood gases obtained on humans in hyperbaric or underwater environments. The a:A was calculated at 1 atmosphere absolute (ATA). For each condition, predicted arterial partial pressure of oxygen ([Formula: see text]) at pressure was calculated using the 1 ATA a:A, and the measured [Formula: see text] was plotted against the predicted value with Spearman correlation coefficients. Of 3,640 records reviewed, 30 studies were included: 25 were reports describing values obtained in hyperbaric chambers, and the remaining were collected while underwater. Increased inspired O2 at pressure resulted in increased [Formula: see text], although underlying lung disease in patients treated with hyperbaric oxygen attenuated the rise. [Formula: see text] generally increased only slightly. In breath-hold divers, hyperoxemia generally occurred at maximum depth, with hypoxemia after surfacing. The a:A adequately predicted the [Formula: see text] under various conditions: dry ( r = 0.993, P < 0.0001), rest versus exercise ( r = 0.999, P < 0.0001), and breathing mixtures ( r = 0.995, P < 0.0001). In conclusion, pulmonary oxygenation under hyperbaric conditions can be reliably and accurately predicted from 1 ATA a:A measurements.
Classification of All Single Traveling Wave Solutions of Fractional Coupled Boussinesq Equations via the Complete Discrimination System Method
Authors: Han Tianyong , Li Zhao
Published: December 2021

In this paper, the complete discrimination system method is used to construct the exact traveling wave solutions for fractional coupled Boussinesq equations in the sense of conformable fractional derivatives. As a result, we get the exact traveling wave solutions of fractional coupled Boussinesq equations, which include rational function solutions, Jacobian elliptic function solutions, implicit solutions, hyperbolic function solutions, and trigonometric function solutions. Finally, the obtained solution is compared with the existing literature.
Teaching Reform of “Work-Integrated Learning” in International Trade Practice from the Perspective of BDaaS
Authors: Zhu Yiting
Published: December 2021

To improve the reform performance of international trade practice, the method with perspective of big data is researched in this study. The international trade professional is developing rapidly to keep pace with social development gradually. With the further development of the society, the traditional international trade major exposed some shortcomings, such as course training target, content and teaching method, and so on, which have fallen behind the progress of society. However, the perspective BDaaS is applied in this study to solve this problem, and the experiment results show that the proposed method will effectively improve the ability of cultivating international trade professionals.
Effects of lncRNA LINC01320 on Proliferation and Migration of Pancreatic Cancer Cells through Targeted Regulation of miR-324-3p
Authors: Meng Hua , Guo Kun , Zhang Yun
Published: December 2021

Objective. LINC01320 is a new oncogenic gene. Nevertheless, the effect of LINC01320 on pancreatic cancer (PC) is still unclear. This research aimed to seek the influence of LINC01320 on PC and its possible mechanism. Methods. RT-qPCR is used to test the LINC01320 in tissues and cells. Cell viability, apoptosis, migration, and invasiveness are detected to explore the role of LINC01320 in PC, and target genes are predicted by bioinformatics methods. The mechanism of action was further explored by transfection of specific siRNA, miRNA mimetics, or miRNA inhibitors. In order to verify the effect of LINC01320 in vivo, we carried out tumor xenotransplantation. Results. We conclude that LINC01320 is highly expressed in PC tissues and cell strains. LINC01320 high expression was bound up with a poor prognosis. LINC01320 gene knockout inhibited the growth, migration, and invasiveness of PC cells. In addition, LINC01320 is expressed by miR-324-3p, which is also supported by in vivo experiments. Conclusion. LINC01320 is highly expressed in PC, and it can suppress the growth and migration of PC cells through targeted regulation of miR-324-3p, which is expected to become a latent target for clinical treatment.
Score for the Overall Survival Probability Scores of Fibrosarcoma Patients after Surgery: A Novel Nomogram-Based Risk Assessment System
Authors: Chen Yuyuan , Chi Changxing , Chen Dedian , Chen Sanjun , Yang Binbin , Huang Sijia , Zheng Zengpai
Published: December 2021

Background. The primary purpose of this study was to determine the risk factors affecting overall survival (OS) in patients with fibrosarcoma after surgery and to develop a prognostic nomogram in these patients. Methods. Data were collected from the Surveillance, Epidemiology, and End Results database on 439 postoperative patients with fibrosarcoma who underwent surgical resection from 2004 to 2015. Independent risk factors were identified by performing Cox regression analysis on the training set, and based on this, a prognostic nomogram was created. The accuracy of the prognostic model in terms of survival was demonstrated by the area under the curve (AUC) of the receiver operating characteristic curves. In addition, the prediction consistency and clinical value of the nomogram were validated by calibration curves and decision curve analysis. Results. All included patients were divided into a training set (n = 308) and a validation set (n = 131). Based on univariate and multivariate analyses, we determined that age, race, grade, and historic stage were independent risk factors for overall survival after surgery in patients with fibrosarcoma. The AUC of the receiver operating characteristic curves demonstrated the high predictive accuracy of the prognostic nomogram, while the decision curve analysis revealed the high clinical application of the model. The calibration curves showed good agreement between predicted and observed survival rates. Conclusion. We developed a new nomogram to estimate 1-year, 3-year, and 5-year OS based on the independent risk factors. The model has good discriminatory performance and calibration ability for predicting the prognosis of patients with fibrosarcoma after surgery.
Application of Ultrasound Diagnosis Technology Based on Statistical Analysis in Rehabilitation Treatment of Shoulder Sports Injuries
Authors: Duan Huiyu , Xun Shenglong , Teng Yusong , Zhang Gong
Published: December 2021

Objective. This study uses statistics to analyze the diagnostic significance of ultrasonic exploration for rotator cuff injuries. Methods. For this study, 50 patients with rotator cuff injury or shoulder impingement syndrome admitted to the hospital from September 2017 to January 2019 were selected as the targets of this discussion. The general clinical materials of the patients were retrospectively analyzed, and ultrasound was performed for them. The results of the examination and arthroscopy are compared with the final pathological results. Results. The diagnostic sensitivity of ultrasound in the diagnosis of partial rupture and complete rupture of the supraspinatus tendon was 100%, and the specificity was 55.55%. The diagnostic sensitivity of partial rupture and complete rupture of the subscapular tendon was 100%, and the specificity was 42.8%; there was no significant difference compared with the joint mirror examination, and there was no statistical significance. Conclusion. The thesis adopts ultrasound exploration for patients with rotator cuff injuries with high diagnostic sensitivity. It is a reliable and effective clinical diagnosis method, which is worthy of clinical application and promotion.
Research of Mechanical Resonance Analysis and Suppression Control Method of the Servo Drive System
Authors: Li Wenli , Liu Yongkang , Ge Shuaishuai , Liao Daming
Published: December 2021

Transmission mechanisms of the servo drive system are not a pure rigid body, and the existence of the elastic transmission mechanisms will make the system generate mechanical resonance. Aiming at mechanical resonance of the servo drive system, the resonance generation mechanism is analyzed, the four‐mass model considering the time‐varying meshing stiffness of the gear is established, and the influence of different stiffness parameters on the mechanical resonance of the system is researched in this paper. The composite controller of Model Predictive Control (MPC) with Notch Filter is used to simulate the mechanical resonance suppression of the four‐mass servo system considering time‐varying meshing stiffness, and it is compared with the mechanical resonance suppression method based on Model Predictive Control. The simulation results show that when the step speed is 200 r/min, the overshoot is reduced from 11.6 r/min to 1.1 r/min, which is reduced by 90.5%. Under the impact load condition, from 10 Nm to 30 Nm, overshoot is reduced from 34.3 r/min to 12.8 r/min, reduced by 62%, and torque oscillation is reduced by 81.5%. Therefore, the composite controller of Model Predictive Control with Notch Filter can suppress the mechanical resonance problem effectively, caused by elastic transmission, and improve the robustness of servo drive system.
Application of Smart Sensor in Underwater Weak Object Detection and Positioning
Authors: Zhang Yangmei
Published: December 2021

This paper is aimed at studying underwater object detection and positioning. Objects are detected and positioned through an underwater scene segmentation‐based weak object detection algorithm and underwater positioning technology based on the three‐dimensional (3D) omnidirectional magnetic induction smart sensor. The proposed weak object detection involves a predesigned U‐shaped network‐ (U‐Net‐) architectured image segmentation network, which has been improved before application. The key factor of underwater positioning technology based on 3D omnidirectional magnetic induction is the magnetic induction intensity. The results show that the image‐enhanced object detection method improves the accuracy of Yellow Croaker, Goldfish, and Mandarin Fish by 3.2%, 1.5%, and 1.6%, respectively. In terms of sensor positioning technology, under the positioning Signal‐to‐Noise Ratio (SNR) of 15 dB and 20 dB, the curve trends of actual distance and positioning distance are consistent, while SNR = 10 dB, the two curves deviate greatly. The research conclusions read as follows: an underwater scene segmentation‐based weak object detection method is proposed for invalid underwater object samples from poor labeling, which can effectively segment the background from underwater objects, remove the negative impact of invalid samples, and improve the precision of weak object detection. The positioning model based on a 3D coil magnetic induction sensor can obtain more accurate positioning coordinates. The effectiveness of 3D omnidirectional magnetic induction coil underwater positioning technology is verified by simulation experiments.
VDR Polymorphisms in Autoimmune Connective Tissue Diseases: Focus on Italian Population
Authors: Latini Andrea , De Benedittis Giada , Perricone Carlo , Colafrancesco Serena , Conigliaro Paola , Ceccarelli Fulvia , Chimenti Maria Sole , Novelli Lucia , Priori Roberta , Conti Fabrizio , Ciccacci Cinzia , Borgiani Paola
Published: December 2021

Vitamin D is an important hormone involved in various physiologic processes, and its activity is linked to binding with vitamin D receptor (VDR). Genetic polymorphisms in the VDR gene could modulate the expression or function of the receptor and, consequently, alter the effects of vitamin D. Variants in VDR gene have been associated with susceptibility to many illnesses sensitive to vitamin D administration and to autoimmune disorders, but no data are available regarding autoimmune connective tissue diseases in Italian population. We analyzed three VDR polymorphisms in 695 Italian patients with autoimmune connective tissue diseases (308 with systemic lupus erythematosus (SLE), 195 with primary Sjogren’s syndrome (pSS), and 192 with rheumatoid arthritis (RA)) and in 246 healthy controls with the aim to evaluate a possible association of VDR SNPs with susceptibility to these diseases in the Italian population. Genotyping of rs2228570, rs7975232, and rs731236 in VDR gene was performed by an allelic discrimination assay. A case/control association study and a genotype/phenotype correlation analysis have been performed. We observed a higher risk to develop SLE for rs2228570 TT genotype (

P
=
0.029

,

OR
=
1.79

). No association was observed between susceptibility to pSS or RA and this SNP, although this variant is significantly less present in RA patients producing autoantibodies. For rs7975232 SNP, we observed a significant association of the variant homozygous genotype with SLE (

P
=
0.009

,

OR
=
1.82

), pSS (

P
=
0.046

,

OR
=
1.66

), and RA (

P
=
0.028

,

OR
=
1.75

) susceptibility. Moreover, we reported associations of this genotype with clinical phenotypes of SLE and pSS. Lastly, the GG genotype of rs731236 was associated with a lower RA susceptibility (

P
=
0.045

,

OR
=
0.55

). Our results show that the explored VDR polymorphisms are significantly associated with autoimmune connective tissue disorders and support the hypothesis that the genetic variability of VDR gene may be involved in susceptibility to these diseases in Italian population.
Cloud-Assisted Privacy-Preserving Method for Healthcare Using Adaptive Fractional Brain Storm Integrated Whale Optimization Algorithm
Authors: Thanga Revathi S. , Gayathri A. , Kalaivani J. , Christo Mary Subaja , Pelusi Danilo , Azees M.
Published: December 2021

The security of medical data in the cloud is the key consideration of cloud customers. While publishing the medical data, the cloud distributor may suffer from data leakages and attacks such that the data may leak. In order to resolve this, this article devises the developed Adaptive Fractional Brain Storm Integrated Whale Optimization Algorithm (AFBS_WOA), which is the hybridization of Adaptive Fractional Brain Storm Optimization (AFBSO) and Whale Optimization algorithm (WOA). The developed AFBS_WOA algorithm generates the key matrix coefficient for retrieving the perturbed database in order to preserve the privacy of healthcare data in the cloud. The developed AFBS-WOA scheme utilized the fitness function involving utility and privacy measures for calculating the secret key. Here, the privacy-preserved database is obtained by multiplying the input database with a key matrix based on developed AFBS-WOA using the Tracy–Singh product. For data retrieval, the secret key is shared with the service provider in order to retrieve the database, and then the data are accessed. Moreover, the experimental result demonstrates that the developed AFBS_WOA model attained the maximum utility and privacy measure of 0.1872 and 0.8755 using the Hungarian dataset.
A Driving Simulation to Analysis and Quantitative Comparison of Driving Behavior of Guide Signs at Intersections
Authors: Wei Tianzheng , Zhu Tong , Li Chenxin , Liu Haoxue
Published: December 2021

Guide signs are an important source for drivers to obtain road information. However, the evaluation methods for the effectiveness of guide signs are not unified. The quantitative model for evaluating guide signs needs to be constructed to unify the current system of guide signs. This study aims to take the commonly used guide signs in China as the research object to explore the evaluation method of guide signs at intersections. Eight kinds of guide signs were designed and made based on the common layout (layout 1 and layout 2) and the amount of information on signs (3–6). Thirty-four drivers were recruited to organize a driving simulation based on the visual cognitive tasks. Drivers’ legibility time and driver behavior were obtained by using the driving simulator and E-Prime program. A comprehensive quantitative evaluation model of guide signs was established based on the factor analysis method and grey correlation analysis method from the perspective of safe driving. The results show that there is no significant difference in the SD of speed and the SD of acceleration under the influence of various guide signs. The average vehicle speed and acceleration decrease, and the lateral offset distance of the vehicle increases with the amount of information on guide signs increasing. The quantitative evaluation results of guide signs show that the visual security decreases with the increase of the amount of information on guide signs. And layout 2 has better performance than layout 1 when the amount of information on guide signs is the same. This study not only explores the change rule of driving behavior under the influence of guide signs, but also provides a reference for the selection of guide signs.
Intelligent Error Correction of College English Spoken Grammar Based on the GA‐MLP‐NN Algorithm
Authors: Du Yining
Published: December 2021

With the development of neural networks in deep learning, artificial intelligence machine learning has become the main focus of researchers. In College English grammar detection, oral grammar is the most error rate content. So, this paper optimizes MLP based on GA in the deep learning neural network and then studies the intelligent image correction of College English spoken grammar. The main direction is to discuss and analyze GA‐MLP‐NN algorithm technology first and then predict the error correction model of spoken language grammar by combining the optimized algorithm. The results show that GA‐MLP‐NN provides excellent accuracy for the prediction of the whole syntax error correction model. Then, the paper studies the deep learning technology to build an intelligent image error correction model of College English spoken grammar. The results show that the effect of intelligent correction of spoken grammar is very fast and accurate.
Polymorphisms CYP2R1 rs10766197 and CYP27B1 rs10877012 in Multiple Sclerosis: A Case-Control Study
Authors: Martinez-Hernandez A. , Perez-Guerrero E. E. , Macias-Islas M. A. , Nava-Valdivia C. A. , Villagomez-Vega A. , Contreras-Haro B. , Garcia-Ortega Y. E. , Esparza-Guerrero Y. , Gallardo-Moya S. G. , Gamez-Nava J. I. , Gonzalez-Lopez L. , Oliva-Flores E. , Rodriguez-Jimenez N. A. , Cortes-Enriquez F. , Saldaña-Cruz A. M.
Published: December 2021

Background. Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Low vitamin D levels have been reported to be a risk factor for MS, and genetic variances could be implicated. The aim of this study was to evaluate the association of MS with rs10766197 polymorphism of CYP2R1 gene and rs10877012 polymorphism of CYP27B1 gene. The second aim was to analyse whether these polymorphisms are associated with the severity of the progression of MS. Material and Methods. In a case-control study, we included 116 MS patients and 226 controls, all of whom were Mexican Mestizo. MS was diagnosed by McDonald criteria (2017). A complete neurological evaluation was performed to evaluate the severity of disease progression. Serum 25-hydroxyvitamin D [25(OH) vitamin D] levels were measured by ELISA. Single nucleotide polymorphisms rs10766197 of CYP2R1 gene and rs10877012 SNP of CYP27B1 gene were genotyped by real-time PCR. Results. Serum 25(OH) vitamin D levels were lower in MS patients than in controls (

p
=
0.009

). No differences were observed between serum 25(OH) vitamin D levels of MS patients with severe progression compared to low progression (

p
=
0.88

). A higher frequency of the A allele of CYP2R1 rs10766197 was observed between MS patients and controls (

p
=
0.05

). No differences were observed in the frequency of T allele of CYP27B1 rs10877012 (

p
=
0.65

). In subanalysis, patients with

GA
+
AA

genotypes of CYP2R1 rs10766197 had an increased risk of MS compared to controls (

p
=
0.03

). No increased risk was observed in

GT
+
TT

genotypes of CYP27B1 rs10877012 (

p
=
0.63

). No differences were observed in allele frequencies of either polymorphism between patients with severe vs. low disease progression. Conclusion. Lower serum 25(OH) vitamin D levels were observed in MS patients than in controls, although these levels were not associated with disease progression. Carriers of

GA
+
AA

genotypes of CYP2R1 rs10766197 had an increased risk of MS. None of these polymorphisms was associated with severe progression of MS.
Stable and Holomorphic Implementation of Complex Functions Using a Unit Circle-Based Transform
Authors: Thankappan Binesh
Published: December 2021

A stable and holomorphic implementation of complex functions in

ℂ

plane making use of a unit circle-based transform is presented in this paper. In this method, any complex number or function can be represented as an infinite series sum of progressive products of a base complex unit and its conjugate only, where both are defined inside the unit circle. With each term in the infinite progression lying inside the unit circle, the sum ultimately converges to the complex function under consideration. Since infinitely large number of terms are present in the progression, the first element of which may be deemed as the base unit of the given complex number, it is addressed as complex baselet so that the complex number or function is termed as the complex baselet transform. Using this approach, various fundamental operations applied on the original complex number in

ℂ

are mapped to equivalent operations on the complex baselet inside the unit circle, and results are presented. This implementation has unique properties due to the fact that the constituent elements are all lying inside the unit circle. Out of numerous applications, two cases are presented: one of a stable implementation of an otherwise unstable system and the second case of functions not satisfying Cauchy–Riemann equations thereby not holomorphic in

ℂ

plane, which are made complex differentiable using the proposed transform-based implementation. Various lemmas and theorems related to this approach are also included with proofs.
Cancer-Causative Mutations Occurring in Early Embryogenesis
Authors: Pareja Fresia , Ptashkin Ryan N. , Brown David N. , Derakhshan Fatemeh , Selenica Pier , da Silva Edaise M. , Gazzo Andrea M. , Da Cruz Paula Arnaud , Breen Kelsey , Shen Ronglai , Marra Antonio , Zehir Ahmet , Benayed Ryma , Berger Michael F. , Ceyhan-Birsoy Ozge , Jairam Sowmya , Sheehan Margaret , Patel Utsav , Kemel Yelena , Casanova-Murphy Jacklyn , Schwartz Christopher J. , Vahdatinia Mahsa , Comen Elizabeth , Borsu Laetitia , Pei Xin , Riaz Nadeem , Abramson David H. , Weigelt Britta , Walsh Michael F. , Hadjantonakis Anna-Katerina , Ladanyi Marc , Offit Kenneth , Stadler Zsofia K. , Robson Mark E. , Reis-Filho Jorge S. , Mandelker Diana
Published: December 2021

Mosaic mutations in normal tissues can occur early in embryogenesis and be associated with hereditary cancer syndromes when affecting cancer susceptibility genes (CSG). Their contribution to apparently sporadic cancers is currently unknown. Analysis of paired tumor/blood sequencing data of 35,310 patients with cancer revealed 36 pathogenic mosaic variants affecting CSGs, most of which were not detected by prior clinical genetic testing. These CSG mosaic variants were consistently detected at varying variant allelic fractions in microdissected normal tissues (n = 48) from distinct embryonic lineages in all individuals tested, indicating their early embryonic origin, likely prior to gastrulation, and likely asymmetrical propagation. Tumor-specific biallelic inactivation of the CSG affected by a mosaic variant was observed in 91.7% (33/36) of cases, and tumors displayed the hallmark pathologic and/or genomic features of inactivation of the respective CSGs, establishing a causal link between CSG mosaic variants arising in early embryogenesis and the development of apparently sporadic cancers.

Significance:

Here, we demonstrate that mosaic variants in CSGs arising in early embryogenesis contribute to the oncogenesis of seemingly sporadic cancers. These variants can be systematically detected through the analysis of tumor/normal sequencing data, and their detection may affect therapeutic decisions as well as prophylactic measures for patients and their offspring.

See related commentary by Liggett and Sankaran, p. 889.

This article is highlighted in the In This Issue feature, p. 873
Concurrent Paraneoplastic Dermatomyositis and Acquired C1 Esterase Inhibitor Deficiency in Primary Laryngeal Small Cell Carcinoma
Authors: Nindra Udit , Nguyen Katie , Hong JunHee , Bray Victoria , Moylan Eugene
Published: December 2021

Small cell carcinoma is associated with a number of paraneoplastic syndromes. We report a case of a 42-year-old female who presented with primary laryngeal small cell carcinoma associated with concurrent paraneoplastic dermatomyositis and paraneoplastic angioedema secondary to acquired C1 esterase inhibitor deficiency. The patient required extensive treatment for her dermatomyositis including high-dose corticosteroid therapy and intravenous immunoglobulin followed by steroid-sparing disease-modifying immunosuppression. Her angioedema also required multiple lines of therapy including bradykinin inhibitors and human recombinant C1 esterase. We believe this is the first reported case of either of these paraneoplastic syndromes arising from an extrapulmonary small cell carcinoma and highlights the difficulty of its initial diagnosis as well as concurrent management.
Giant Adrenal Lipoma with Hemorrhage Requiring Extended Surgical Resection
Authors: Otsubo Kanji , Kobayashi Shinjiro , Ida Keisuke , Katayama Masafumi , Koizumi Satoshi , Koike Junki , Otsubo Takehito , Tsuchihashi Atsuhito
Published: December 2021

Adrenal lipoma is a rare, benign tumor, reported to account for 0.7% of primary adrenal tumors. A 69-year-old man presented with left lateral abdominal pain. Computed tomography (CT) was performed, and a huge, irregularly shaped retroperitoneal tumor of uneven internal density was identified, with the border between the tumor and the pancreas and kidney being unclear. Active hemorrhage was also depicted. The tumor consisted mainly of fat, with the exception of the hematoma; it measured 200 mm; and the boundary between it and nearby organs, such as the pancreas, was unclear. Despite angiography being performed twice, the responsible vessel was not identified. Thus, for the purpose of both diagnosis and treatment, we resected the tumor, and considering the possibility of a malignancy, such as liposarcoma, we also resected the pancreatic body and tail and the spleen. The final histopathologic diagnosis was benign adrenal lipoma with hemorrhage, with no invasion to surrounding tissue. Hemorrhage within an adrenal tumor is rare. Most adrenal lipomas are small “incidentalomas” and asymptomatic. With development of a large adrenal lipoma comes the possibility of hemorrhage along with the possibility of features suggestive of malignancy. We encountered a giant adrenal lipoma with hemorrhage and, because of the aforementioned features, performed extended surgical resection, seen in retrospect as oversurgery. The widespread use of CT has led to an increased number of reported cases of adrenal lipoma. We anticipate an accumulation of case reports, which will allow for development of an appropriate treatment algorithm.
Upregulation of NADPH Oxidase 2 Contributes to Renal Fibrosis in pcy Mice: An Experimental Model of Nephronophthisis
Authors: Hoshino Yuya , Sonoda Hiroko , Mikoda Nobuyuki , Ikeda Masahiro
Published: December 2021

Background: DBA/2FG-pcy (pcy) mice harbor a homozygous Nphp3 missense mutation and develop nephronophthisis with renal interstitial fibrosis. Previous studies have shown that aberrant oxygen homeostasis contributes to the renal pathology in pcy mice, but the underlying molecular mechanism remains largely unknown. Methods: pcy mice and a control strain, DBA/2N (DBA) mice, were used. Renal levels of 62 mRNAs involved in oxygen homeostasis were investigated by real-time PCR, and the resulting data were used for extraction of pathological pathways. On the basis of the genes found to be upregulated and pathway analysis, further studies were performed using immunoblotting, immunohistochemistry, and pharmacological intervention. Results: In comparison with DBA mice, the levels of 18 mRNAs were altered by >2-fold in pcy mice. Pathway analysis extracted molecular pathways related to oxidative stress, inflammation, and cell adhesion. As the levels of mRNAs relevant to the NADPH oxidase 2 (NOX2) pathway were prominently (4 genes >5-fold) increased in pcy mice, we further analyzed the molecules related to this pathway. A time course study suggested that the pathway was gradually activated in pcy mice from at least 5 weeks of age. Immunohistochemistry study revealed that NOX2 protein was colocalized with a macrophage marker protein in the renal interstitium. Moreover, treatment of pcy mice with apocynin, an inhibitor of the NOX2 pathway, ameliorated the renal fibrosis. Conclusion: Our findings suggest that the activation of the NOX2 pathway, possibly mediated by macrophage infiltration, plays a pivotal role in progressive renal fibrosis in pcy mice.