bluuebunny/crossref_metadata_2025 huggingface dataset:
Digital Twin Technology: The Future of Predicting Neurological Complications of Pediatric Cancers and Their Treatment
Authors: Thiong’o Grace M. , Rutka James T.
Published: January 2022

Healthcare technologies have seen a surge in utilization during the COVID 19 pandemic. Remote patient care, virtual follow-up and other forms of futurism will likely see further adaptation both as a preparational strategy for future pandemics and due to the inevitable evolution of artificial intelligence. This manuscript theorizes the healthcare applications of digital twin technology. Digital twin is a triune concept that involves a physical model, a virtual counterpart, and the interplay between the two constructs. This interface between computer science and medicine is a new frontier with broad potential applications. We propose that digital twin technology can exhaustively and methodologically analyze the associations between a physical cancer patient and a corresponding digital counterpart with the goal of isolating predictors of neurological sequalae of disease. This proposition stems from the premise that data science can complement clinical acumen to scientifically inform the diagnostics, treatment planning and prognostication of cancer care. Specifically, digital twin could predict neurological complications through its utilization in precision medicine, modelling cancer care and treatment, predictive analytics and machine learning, and in consolidating various spectra of clinician opinions.
Cutaneous Toxicity Associated With Enfortumab Vedotin: A Real-Word Study Leveraging U.S. Food and Drug Administration Adverse Event Reporting System
Authors: Yang Hui , Yu Xiaojia , An Zhuoling
Published: January 2022

Introduction

Enfortumab vedotin (EV) has been demonstrated to have a significant response rate in early phase trials and is known for its tolerable side-effect profile. Emerging case reports have raised awareness of cutaneous toxicities, which may be a potentially fatal complication.

Objective

To assess the potential relevance between EV and cutaneous toxicities reports through data mining of the U.S. Food and Drug Administration (FDA) adverse event reporting system (FAERS).

Methods

Data from January 1, 2019, to November 4, 2021, in the FAERS database were retrieved. Information component (IC) and reporting odds ratio (ROR) were used to evaluate the association between EV and cutaneous toxicities events.

Results

EV was significantly associated with cutaneous toxicities in the database compared with both all other drugs (ROR 12.90 [10.62–15.66], IC 2.76 [2.52–3.01], middle signal) and platinum-based therapy (ROR 15.11 [12.43–18.37], IC 2.91 [2.66–3.15], middle signal) in the FAERS database. A significant association was detected between EV and all the cutaneous adverse effects (AEs) except erythema, palmar–plantar erythrodysesthesia syndrome, and dermatitis allergic. Both Stevens–Johnson syndrome and toxic epidermal necrolysis occurred 15 times as frequently for EV compared with all other drugs (ROR = 15.20; ROR = 15.52), while Stevens–Johnson syndrome occurred 18 times and toxic epidermal necrolysis occurred 7 times as frequently for EV compared with platinum-based therapy in the database (ROR = 18.74; ROR = 7.80). All groups that limited the gender and age showed a significant association between EV and cutaneous toxicities.

Conclusions

A significant signal was detected between EV use and cutaneous toxicities. It is worth noting that Stevens–Johnson syndrome and toxic epidermal necrolysis were significantly associated with EV use.
Interprofessional Consensus Regarding Design Requirements for Liquid-Based Perinatal Life Support (PLS) Technology
Authors: van der Hout-van der Jagt M. Beatrijs , Verweij E. J. T. , Andriessen Peter , de Boode Willem P. , Bos Arend F. , Delbressine Frank L. M. , Eggink Alex J. , Erwich Jan Jaap H. M. , Feijs Loe M. G. , Groenendaal Floris , Kramer Boris W. W. , Lely A. Titia , Loop Rachel F. A. M. , Neukamp Franziska , Onland Wes , Oudijk Martijn A. , te Pas Arjan B. , Reiss Irwin K. M. , Schoberer Mark , Scholten Ralph R. , Spaanderman Marc E. A. , van der Ven Myrthe , Vermeulen Marijn J. , van de Vosse Frans N. , Oei S. Guid
Published: January 2022

Liquid-based perinatal life support (PLS) technology will probably be applied in a first-in-human study within the next decade. Research and development of PLS technology should not only address technical issues, but also consider socio-ethical and legal aspects, its application area, and the corresponding design implications. This paper represents the consensus opinion of a group of healthcare professionals, designers, ethicists, researchers and patient representatives, who have expertise in tertiary obstetric and neonatal care, bio-ethics, experimental perinatal animal models for physiologic research, biomedical modeling, monitoring, and design. The aim of this paper is to provide a framework for research and development of PLS technology. These requirements are considering the possible respective user perspectives, with the aim to co-create a PLS system that facilitates physiological growth and development for extremely preterm born infants.
To Lighten the Burden of Cure: Thyroid Disease in Long-Term Survivors After TBI Conditioning for Paediatric ALL
Authors: Zubarovskaya Natalia , Bauer Dorothea , Ronceray Leila , Poetschger Ulrike , Kurzmann Paulina , Lender Carina , Kuzmina Zoya , Lawitschka Anita
Published: January 2022

Thyroid disorders are well-studied after allogeneic haematopoietic stem cell transplantation (HSCT) following total body irradiation (TBI)-based conditioning, occurring in 15–30% of paediatric survivors. The toxic effect of TBI is known but data on the role of immunological dysregulation (ID) and chronic graft-versus-host-disease (cGvHD) are scarce. We studied functional and structural thyroid disorders in 97 paediatric ALL patients after TBI-based HSCT, assessing their correlation with patient/transplant characteristics including cGvHD, prolonged immunosuppression and ID. The 10- and 15-year cumulative incidence (CI) of functional disorders was 50 and 60%. Univariate analysis revealed TBI in 6 vs. 8 fractions (p = 0.01), an interval between ALL diagnosis and HSCT <1 year (p = 0.038), and the application of ATG (p = 0.044) as risk factors. The 10- and 15-year CI of structural disorders was 60 and 80%. No correlation between patient/transplant characteristics and structural disorders was observed. cGvHD, prolonged immunosuppression and additional radiotherapy were not associated with any thyroid disease. We observed a significant correlation between ID and the development of thyroid dysfunction in patients with structural changes (10-year CI: 77% for patients with ID vs. 56% without ID, p = 0.02). The impact of our results on thyroid follow-up evaluations and the significance of hormonal replacement therapy are discussed.
The Gene Expression Analysis of Peripheral Blood Monocytes From Psoriasis Vulgaris Patients With Different Traditional Chinese Medicine Syndromes
Authors: Lu Yue , Qi Yao , Li Li , Yan Yuhong , Wei Jianan , Yao Danni , Wu Jingjing , Deng Hao , Deng Jingwen , Ye Shuyan , Chen Haiming , Chen Qubo , Gao Hengjun , Han Ling , Lu Chuanjian
Published: January 2022

Psoriasis is chronic skin disease and an important health concern. Traditional Chinese Medicine (TCM) has shown great promise in the treatment of psoriasis. However, the correlation between TCM Syndromes and genomics of psoriasis has not been evaluated. Here, we analyzed gene expression profiling of monocytes from psoriasis vulgaris patients with different TCM syndrome types to reveal the molecular basis of different psoriasis syndromes. Of the 62 cases of psoriasis vulgaris recruited, 16, 23, and 23 cases were of blood-heat syndrome, blood stasis syndrome, and blood-dryness syndrome, respectively; 10 healthy controls were recruited as controls. Affymertix’s Gene Chip ®clariom D gene chip was used to detect the gene expression profile of peripheral blood monocytes collected from recruited individuals. Compared with the healthy control group, 1570 genes were up-regulated and 977 genes were down-regulated in the psoriasis vulgaris patients group; 798 genes and 108 genes were up- and down-regulated in the blood-heat syndrome group respectively; 319 and 433 genes were up- and down-regulated in the blood-dryness syndrome group, respectively; and 502 and 179 genes were up-and down-regulated in the blood-stasis syndrome group. Our analyses indicated not only common differential genes and pathways between psoriasis syndrome groups and healthy controls, but also syndrome-specific genes and pathways. The results of this study link the three syndromes at the gene level and will be useful for clarifying the molecular basis of TCM syndromes of psoriasis.

Clinical Trial Registration: (http://www.chictr.org.cn/showproj.aspx?proj=4390), identifier (ChiCTR-TRC-14005185).
Fenofibrate Improves Insulin Resistance and Hepatic Steatosis and Regulates the Let-7/SERCA2b Axis in High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice
Authors: Zhang Dan , Niu Shanzhuang , Ma Yicheng , Chen Hang , Wen Yu , Li Mingke , Zhou Bo , Deng Yi , Shi Chunjing , Pu Guangyu , Yang Meng , Wang Xianmei , Zou Chenggang , Chen Yuanli , Ma Lanqing
Published: January 2022

Fenofibrate is widely used in clinical therapy to effectively ameliorate the development of non-alcoholic fatty liver disease (NAFLD); however, its specific molecular mechanism of action remains largely unknown. MicroRNAs (miRNAs) are key mediators in regulating endoplasmic reticulum (ER) stress during NAFLD, and the deregulation of miRNAs has been demonstrated in NAFLD pathophysiology. The present study aimed to identify whether fenofibrate could influence miRNA expression in NAFLD and investigate the specific mechanism of action of fenofibrate in lipid metabolism disorder-associated diseases. We found that fenofibrate alleviated ER stress and increased the levels of SERCA2b, which serves as a regulator of ER stress. Additionally, the levels of let-7 miRNA were regulated by fenofibrate; let-7 was found to target the 3′ untranslated region of SERCA2b. The present data suggest that the protective effects of fenofibrate against insulin resistance and its suppressive activity against excessive hepatic lipid accumulation may be related to the alteration of the let-7/SERCA2b axis and alleviation of ER stress.
Multifactoriality of Parkinson’s Disease as Explored Through Human Neural Stem Cells and Their Transplantation in Middle-Aged Parkinsonian Mice
Authors: Nelke Anna , García-López Silvia , Martínez-Serrano Alberto , Pereira Marta P.
Published: January 2022

Parkinson’s disease (PD) is an age-associated neurodegenerative disorder for which there is currently no cure. Cell replacement therapy is a potential treatment for PD; however, this therapy has more clinically beneficial outcomes in younger patients with less advanced PD. In this study, hVM1 clone 32 cells, a line of human neural stem cells, were characterized and subsequently transplanted in middle-aged Parkinsonian mice in order to examine cell replacement therapy as a treatment for PD. In vitro analyses revealed that these cells express standard dopamine-centered markers as well as others associated with mitochondrial and peroxisome function, as well as glucose and lipid metabolism. Four months after the transplantation of the hVM1 clone 32 cells, striatal expression of tyrosine hydroxylase was minimally reduced in all Parkinsonian mice but that of dopamine transporter was decreased to a greater extent in buffer compared to cell-treated mice. Behavioral tests showed marked differences between experimental groups, and cell transplant improved hyperactivity and gait alterations, while in the striatum, astroglial populations were increased in all groups due to age and a higher amount of microglia were found in Parkinsonian mice. In the motor cortex, nonphosphorylated neurofilament heavy was increased in all Parkinsonian mice. Overall, these findings demonstrate that hVM1 clone 32 cell transplant prevented motor and non-motor impairments and that PD is a complex disorder with many influencing factors, thus reinforcing the idea of novel targets for PD treatment that tend to be focused on dopamine and nigrostriatal damage.
Deciphering the Effective Constituents and Mechanisms of Portulaca oleracea L. for Treating NASH via Integrating Bioinformatics Analysis and Experimental Pharmacology
Authors: He Xiaoli , Hu Yiren , Liu Wei , Zhu Guanghao , Zhang Ruoxi , You Jiawen , Shao Yanting , Li Yunhao , Zhang Zeng , Cui Jingang , He Yanming , Ge Guangbo , Yang Hongjie
Published: January 2022

Nonalcoholic steatohepatitis (NASH) is a highly prevalent metabolic disorder. Currently, there are no effective pharmacotherapeutic options for preventing and treating NASH. Portulaca oleracea L. (POL) is an edible herb that has been used for preventing and treating some metabolic disorders in China, but the bioactive constituents in POL and the related mechanisms for treating NASH are still unclear. Here, a comprehensive research strategy was used to identify the core genes and the key constituents in POL for treating NASH, via integrating bioinformatics analysis and experimental pharmacology both in vitro and in vivo. The phenotypes and mechanisms of POL were carefully investigated by performing a set of in vivo and in vitro experiments. Bioinformatics analysis suggested that prostaglandin-endoperoxide synthase 2 (PTGS2) was the core target and myricetin (Myr) was the key constituent in POL for treating NASH. In NASH mice model induced by methionine choline deficiency diet, POL significantly alleviated hepatic steatosis and liver injury. In free fatty acids-induced hepatocytes, POL and Myr significantly down-regulated the expression of PTGS2, decreased the number of lipid droplets, and regulated the mRNA expression of lipid synthesis and homeostasis genes, including FASN, CPT1a, SERBP1c, ACC1, and SCD1. In lipopolysaccharide-induced macrophages, POL and Myr significantly reduced the expression of PTGS2 and blocked the secretion of inflammatory mediators TNF-α, IL-6, and IL-1β. Further investigations demonstrate that Myr acts as both suppressor and inhibitor of PTGS2. Collectively, POL and its major component Myr can ameliorate NASH via down-regulating and inhibiting PTGS2, suggesting that POL and Myr can be developed as novel medicines for treating NASH.
Speckle Noise Suppression Algorithm of Holographic Display Based on Spatial Light Modulator
Authors: Li Nan-Nan , Chen Chun , Lee Byoungho , Wang Di , Wang Qiong-Hua
Published: January 2022

Holography has emerged as one of the most attractive three-dimensional display technologies. With the technological development of computer science and coherent light source, the computer-generated holography has been applied in many fields. However, the speckle noise of the holographic reconstructed image seriously affects the viewing experience. In this paper, the cause of speckle noise generation in holographic display is introduced. Then, discussions about the speckle noise suppression methods are provided. The discussions are categorized into iterative and non-iterative approaches. Besides, we also introduce other speckle noise suppression techniques which are proposed from the perspective of light coherence, human visual system and optical system. Finally, the prospects of different types of approaches are summarized.
Polarization and Accountability in Covid Times
Authors: Beramendi Pablo , Rodden Jonathan
Published: January 2022

We analyze the relationship between accountability and polarization in the context of the COVID crisis. We make three points. First, when voters perceive the out-party to be ideologically extreme, they are less likely to hold incumbents accountable for poor outcomes via competence-based evaluations. Knowing this, even in the context of major crises, incumbents face weaker incentives to take politically costly measures that would minimize deaths. Second, there is a partisan asymmetry whereby the additional government intrusion associated with effective COVID response can be more politically costly for the right than for the left, because it undercuts the ideological distinctiveness that drives the base-mobilization strategy of the right. Third, this asymmetry generates incentives for politicization of COVID mitigation policies that ultimately lead to partisan differences in mitigation behavior and outcomes. To illustrate this logic, we provide preliminary evidence that COVID death rates are higher in more polarized democracies, and that in one of the most polarized democracies—the United States—COVID deaths have become increasingly correlated with partisanship.
Affective Cognition of Students’ Autonomous Learning in College English Teaching Based on Deep Learning
Authors: Zhang Dian
Published: January 2022

Emotions can influence and regulate learners’ attention, memory, thinking, and other cognitive activities. The similarities and differences between English and non-English majors in terms of English classroom learning engagement were compared, and the significant factors affecting the emotional, cognitive, and behavioral engagement of the two groups of students in the English classroom were different. English majors’ affective engagement in the classroom was not significant, which was largely related to their time and frequency of English learning. Traditional methods of learner emotion recognition suffer from low recognition rate, complex algorithms, poor robustness, and easy to lose key information about facial expression features. The paper proposes a convolutional neural network-based learner emotion recognition method, which includes three convolutional layers, three pooling layers, and one fully connected layer. In the future, the method will can be applied to the construction of smart learning environments, providing technical support for improving learner models, realizing emotional interactions, and mining learning behaviors, etc.
Towards Computational Modeling of Human Goal Recognition
Authors: Treger Shify , Kaminka Gal A.
Published: January 2022

Recently, we are seeing the emergence of plan- and goal-recognition algorithms which are based on the principle ofrationality. These avoid the use of a plan library that compactly encodes all possible observable plans, and instead generate plans dynamically to match the observations. However, recent experiments by Berkovitz (Berkovitz, The effect of spatial cognition and context on robot movement legibility in human-robot collaboration, 2018) show that in many cases, humans seem to have reached quick (correct) decisions when observing motions which were far from rational (optimal), while optimal motions were slower to be recognized. Intrigued by these findings, we experimented with a variety of rationality-based recognition algorithms on the same data. The results clearly show that none of the algorithms reported in the literature accounts for human subject decisions, even in this simple task. This is our first contribution. We hypothesize that humans utilize plan-recognition in service of goal recognition, i.e., match observations to known plans, and use the set of recognized plans to conclude as to the likely goals. To test this hypothesis, a second contribution in this paper is the introduction of a novel offline recognition algorithm. While preliminary, the algorithm accounts for the results reported by Berkovitz significantly better than the existing algorithms. Moreover, the proposed algorithm marries rationality-based and plan-library based methods seamlessly.
Virtual Reality and EEG-Based Intelligent Agent in Older Adults With Subjective Cognitive Decline: A Feasibility Study for Effects on Emotion and Cognition
Authors: Cuesta Marc , Verty Lynn Valeyry , Ben Abdessalem Hamdi , Byrns Alexie , Bruneau Marie-Andrée , Frasson Claude , Belleville Sylvie
Published: January 2022

Objectives: Immersive virtual reality has tremendous potential to improve cognition in populations with cognitive impairment. We conducted a feasibility and proof-of-concept study to assess the potential of virtual reality and electroencephalography, with or without an intelligent agent, that adapts the presented material to the emotions elicited by the environment.

Method: Older adults with subjective cognitive decline recruited from the community received a virtual reality-based intervention taking place in one of two virtual environments, a train (Part 1, N = 19) or a music theatre, complemented by the intelligent agent (Part 2, N = 19). A comparative control group (N = 19) receiving no intervention was also included. All participants completed measures of affect and cognition before and after the intervention. The intervention groups completed measures of cybersickness and user experience after the intervention.

Results: Participants did not suffer from increased cybersickness following either intervention. They also reported a positive to highly positive user experience concerning the following aspects: attractivity, hedonic quality-identity and hedonic quality-stimulation. The measures of affect showed no pre-post change when comparing either intervention to the control condition. However, a reduction of negative affect was observed following the train intervention for participants with a high self-reported negative affect at baseline. Finally, there was a significant improvement in working memory when comparing either intervention group to the control condition.

Conclusion: Our results support the feasibility and tolerability of the technology, and a positive impact on cognition, paving the way for a larger-scale randomized clinical trial to confirm efficacy.
Toward Accurate Formation Routes of Complex Organic Molecules in the Interstellar Medium: The Paradigmatic Cases of Acrylonitrile and Cyanomethanimine
Authors: Barone Vincenzo , Puzzarini Cristina
Published: January 2022

The investigation of reaction mechanisms in the interstellar medium requires the evaluation of reaction rates and branching ratios, which can be effectively obtained in the framework of the ab-initio transition state/master equation formalism. However, the reliability of this approach relies on the computation of accurate reaction enthalpies and activation energies for all the paths characterizing the potential energy surface under investigation. Two effective yet reliable parameter-free model chemistries are introduced to obtain accurate energies of all stationary points, with structural determination performed using double-hybrid density functionals. After their validation, these model chemistries have been employed to analyze the competition between hydrogen abstraction and addition/elimination in the reaction between the CN radical and ethylene or methanimine. The energetics has then been complemented by a kinetic study. The results provide new information about important reactive channels operative in different regions of the interstellar medium and in the atmospheres of exoplanets. These further extend the recent general addition/elimination mechanism for the formation of “complex imines” from the reaction of methanimine with a small radical species.
Jednostki gramatyczne pochodne od liczebników i wyrażeń
liczebnikowych .
Authors: Sobotka Piotr
Published: January 2022

This paper discusses the notion of quantity and related notions from the
perspective of their lexicalisation in the area of the so-called (functional, auxiliary)
grammatical expressions. Such units, founded on the notion of quantity, create
a microsystem composed of the following semantic and functional classes:
interrogative pronouns, relators, prepositions, metapredicative operators (of
gradation, limitation, approximation), conjunctions, particles, metatextual
commentaries, and modifi er of declarativity. The semantic relationships between
these units are similar to the ones noticeable between expressions from the
relevant level of language; apart from that, they form pairs based on such
relationships with units from outside the examined lexical and conceptual fi eld.
The paper also discusses the variant groups among the analysed expressions
and units that are formally similar yet functionally different.
Algorithms for Detecting and Refining the Area of Intangible Continuous Objects for Mobile Wireless Sensor Networks
Authors: Huang Shih-Chang , Huang Cong-Han
Published: January 2022

Detecting the intangible continuous object (ICO) is a significant task, especially when the ICO is harmful as a toxic gas. Many studies used steady sensors to sketch the contour and find the area of the ICO. Applying the mobile sensors can further improve the precision of the detected ICO by efficiently adjusting the positions of a subset of the deployed sensors. This paper proposed two methods to figure out the area of the ICO, named Delaunay triangulation with moving sensors (MDT) and convex hull with moving sensors (MCH). First, the proposed methods divide the sensors into ICO-covered and ICO-uncovered sensors. Next, the convex hull algorithm and the Delaunay triangulation geometric architecture are applied to figure out the rough boundary of the ICO. Then, the area of the ICO is further refined by the proposed sensor moving algorithm. Simulation results show that the figured out area sizes of MDT and MCH are 135% and 102% of the actual ICO. The results are better than the planarization algorithms Gabriel Graph (GG) and Delaunay triangulation without moving sensors, that amount to 137% and 145% of the actual ICO. The simulation also evaluates the impact of the sensors’ moving step size to find the compromise between the accuracy of the area and the convergence time of area refinement.
Management Accounting and Control in Higher Education Institutions: A Systematic Literature Review
Authors: Vale José , Amaral Joana , Abrantes Luís , Leal Carmem , Silva Rui
Published: January 2022

The new public management reforms have led to significant changes in higher education institutions (HEIs) regarding the management accounting and control (MAC) of these organizations. Therefore, this paper provides an overview of the main studies on MAC in these types of organizations through a systematic literature review (SLR). The PRISMA guidelines were followed, and data were collected from the Web of Science and Scopus databases. The final sample encompassed 50 articles, published between 1981 and 2020. The results show that MAC research tends to focus on management control systems and performance evaluation systems. They also suggest that, although the development and implementation of various MAC tools are crucial for HEIs, such implementation often is partial. This is due to the stakeholders’ perceptions/attitudes regarding the importance of such tools. The results also indicate that institutional theory is the most addressed one. Most of the time, HEIs implement MAC tools due to external pressures. By synthesizing the main trends in MAC, this SLR intends to provide a theoretical contribution to the literature in this research field. Several themes for further research are suggested, such as assessing the relationship between MAC and the management of “knowledge” and intellectual capital in these institutions, and addressing sustainability issues. From a practical viewpoint, HEI managers can obtain important insights to apply the most appropriate tools to their institutions.
Effects of DARSI Intervention Program on Adolescents’ Perceptions of Love, Tolerance toward Abuse and Dating Violence Perpetration
Authors: Cava María-Jesús , Carrascosa Laura , Buelga Sofía
Published: January 2022

Teen dating violence is a serious problem and intervention programs aimed at reducing this violence and helping adolescents to develop healthier romantic relationships are needed. The objective of this study was to assess the effects of the DARSI program on the development of a more adequate perception of love, the reduction of tolerance toward abuse in romantic relationships, and the reduction of the perpetration of dating violence in adolescents. The sample consisted of 129 adolescents, aged 12 to 17 years (M = 14.05, SD = 1.08). A repeated measures (pre-test and post-test) quasi-experimental design with an intervention group and a control group was used to assess the effects of the program. The results showed significant decreases in unhealthy perceptions of love (linking love with control and dependence), tolerance toward abuse in romantic relationships, and dating violence perpetration in the intervention group. Healthier perceptions of love (linking love with respect and communication) were observed in the intervention group after the implementation of this program. These findings support the implementation in educational contexts of programs focused on the development of non-violent and healthy romantic relationships in adolescents.
An End-to-End UAV Simulation Platform for Visual SLAM and Navigation
Authors: Chen Shengyang , Zhou Weifeng , Yang An-Shik , Chen Han , Li Boyang , Wen Chih-Yung
Published: January 2022

Visual simultaneous localization and mapping (v-SLAM) and navigation of unmanned aerial vehicles (UAVs) are receiving increasing attention in both research and education. However, extensive physical testing can be expensive and time-consuming due to safety precautions, battery constraints, and the complexity of hardware setups. For the efficient development of navigation algorithms and autonomous systems, as well as for education purposes, the ROS-Gazebo-PX4 simulator was customized in-depth, integrated into our previous released research works, and provided as an end-to-end simulation (E2ES) solution for UAV, v-SLAM, and navigation applications. Unlike most other similar works, which can only stimulate certain parts of the navigation algorithms, the E2ES platform simulates all of the localization, mapping, and path-planning kits in one simulator. The navigation stack performs well in the E2ES test bench with the absolute pose errors of 0.3 m (translation) and 0.9 degree (rotation), respectively, for an 83 m length trajectory. Moreover, the E2ES provides an out-of-box, click-and-fly autonomy in UAV navigation. The project source code is opened for the benefit of the research community.
Hemostatic Analysis of Simulated Gloydius ussuriensis Envenomation Using Canine Blood: A Comparison of Thromboelastography and Classical Coagulation Tests
Authors: Lee Jong-Sun , Kim Jung-Hyun
Published: January 2022

Snake envenomation may lead to venom-induced consumptive coagulopathy (VICC), usually diagnosed by classical coagulation tests (CCTs), such as prothrombin time (PT) and activated partial thromboplastin time (aPTT). However, the results of CCTs are frequently normal in the initial stages, which may delay anti-venom treatments. Thromboelastography (TEG) is a point-of-care and real-time diagnostic tool that enables a comprehensive assessment of the coagulation process. This in vitro study aimed to determine concentration-dependent changes in canine blood caused by Gloydius ussuriensis (G. ussuriensis) envenomation using TEG and CCTs. Lyophilized G. ussuriensis venom was reconstructed using mouse intravenous lethal dose 50 (LD50iv) and serially diluted to 25% LD50iv, 50% LD50iv, and 75% LD50iv to reproduce VICC at different concentrations. Normal saline was used for the control. We compared TEG values of the reaction time (R), kinetic time (K), rate of clot formation (α-angle), maximum amplitude (MA), fibrinolysis at 30 min (LY30), and global strength of the clot (G) with those of PT, aPTT, fibrinogen, and platelet counts (PLTs). Most TEG parameters, except R and LY30, demonstrated statistically significant changes compared with the control at all concentrations. CCTs, except PLTs, revealed significant changes at ≥50% LD50iv. Thus, TEG could be a useful diagnostic strategy for early VICC and preventing treatment delay.
Error Features in Predicting Typhoon Winds: A Case Study Comparing Simulated and Measured Data
Authors: Peng Shaoyuan , Liu Yichao , Li Renge , Wei Ying , Chan Pak-Wai , Li Sunwei
Published: January 2022

Simulating a typhoon’s wind field via mesoscale models is important in terms of providing not only the guidelines for urban planning and onshore/offshore constructions, but also the provision of insight into the dynamics and thermodynamics of tropical cyclone systems. Therefore, the errors that are contained in simulation results were investigated in the present study, in association with large-scale meteorological patterns and localized wind conditions in the typhoon boundary layer. In detail, the full-set three-dimensional simulations of three typhoon cases were carried out in order to provide the typhoon wind fields that were required to compare with the observations that were obtained through land weather stations and offshore buoys. Although the reliability of typhoon simulations has been thoroughly investigated, the previous works mostly concentrated on the configurations and dynamic core of the model. The present study reveals, however, the influences of the characteristics of the specific weather system on the simulation’s results, which provides the foundation for the proposition of empirical corrections to improve the mesoscale simulation results of typhoon wind fields without updating the model’s algorithm.
Elastic and Inelastic Cross Sections for Low-Energy Electron Collisions with ClF Molecule Using the R-Matrix Method
Authors: Bassi Monika , Bharadvaja Anand , Baluja Kasturi Lal
Published: January 2022

The ClF molecule belongs to an interhalogen family and is important in laser physics and condensed phase molecular dynamics. The elastic and excitation scattering cross sections are obtained in a fixed nuclei approximation using the UKRmol+ codes based on R-matrix formalism. The scattering calculations were performed in the static-exchange (SE), static-exchange-plus-polarisation (SEP), and close-coupling (CC) models. Three CC models with different target states were employed, namely, the 1-state, 5-states, and 12-states. In the CC model, the target states were represented by configuration interaction (CI) wavefunctions. A good agreement of dipole and quadrupole moments of the ground state was obtained with the experimental values, which indicates a good representation of the target modelling. The study predicted the existence of a shape resonance in the SE, SEP, and 5-states CC models. This resonance vanished in the 12-states CC model. The excitation cross sections from ground to the lowest two excited states were also reported. The elastic differential and momentum transfer cross sections were obtained in the 12-states CC models. The contribution of long-range interactions to elastic scattering was included via Born closure approach. The quantities like collision frequencies and rate coefficients were also presented over a wide range of electron temperatures. The ionization cross sections were computed using the binary-encounter-Bethe (BEB) model. The results were reported in C2v point group representation.
Adrenomedullin: Not Just Another Gastrointestinal Peptide
Authors: Martínez-Herrero Sonia , Martínez Alfredo
Published: January 2022

Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are two bioactive peptides derived from the same precursor with several biological functions including vasodilation, angiogenesis, or anti-inflammation, among others. AM and PAMP are widely expressed throughout the gastrointestinal (GI) tract where they behave as GI hormones, regulating numerous physiological processes such as gastric emptying, gastric acid release, insulin secretion, bowel movements, or intestinal barrier function. Furthermore, it has been recently demonstrated that AM/PAMP have an impact on gut microbiome composition, inhibiting the growth of bacteria related with disease and increasing the number of beneficial bacteria such as Lactobacillus or Bifidobacterium. Due to their wide functions in the GI tract, AM and PAMP are involved in several digestive pathologies such as peptic ulcer, diabetes, colon cancer, or inflammatory bowel disease (IBD). AM is a key protective factor in IBD onset and development, as it regulates cytokine production in the intestinal mucosa, improves vascular and lymphatic regeneration and function and mucosal epithelial repair, and promotes a beneficial gut microbiome composition. AM and PAMP are relevant GI hormones that can be targeted to develop novel therapeutic agents for IBD, other GI disorders, or microbiome-related pathologies.
Label-Free Physical Techniques and Methodologies for Proteins Detection in Microfluidic Biosensor Structures
Authors: Konoplev Georgii , Agafonova Darina , Bakhchova Liubov , Mukhin Nikolay , Kurachkina Marharyta , Schmidt Marc-Peter , Verlov Nikolay , Sidorov Alexander , Oseev Aleksandr , Stepanova Oksana , Kozyrev Andrey , Dmitriev Alexander , Hirsch Soeren
Published: January 2022

Proteins in biological fluids (blood, urine, cerebrospinal fluid) are important biomarkers of various pathological conditions. Protein biomarkers detection and quantification have been proven to be an indispensable diagnostic tool in clinical practice. There is a growing tendency towards using portable diagnostic biosensor devices for point-of-care (POC) analysis based on microfluidic technology as an alternative to conventional laboratory protein assays. In contrast to universally accepted analytical methods involving protein labeling, label-free approaches often allow the development of biosensors with minimal requirements for sample preparation by omitting expensive labelling reagents. The aim of the present work is to review the variety of physical label-free techniques of protein detection and characterization which are suitable for application in micro-fluidic structures and analyze the technological and material aspects of label-free biosensors that implement these methods. The most widely used optical and impedance spectroscopy techniques: absorption, fluorescence, surface plasmon resonance, Raman scattering, and interferometry, as well as new trends in photonics are reviewed. The challenges of materials selection, surfaces tailoring in microfluidic structures, and enhancement of the sensitivity and miniaturization of biosensor systems are discussed. The review provides an overview for current advances and future trends in microfluidics integrated technologies for label-free protein biomarkers detection and discusses existing challenges and a way towards novel solutions.
The Cytogenetic Profile of Primary and Secondary Plasma Cell Leukemia: Etiopathogenetic Perspectives, Prognostic Impact and Clinical Relevance to Newly Diagnosed Multiple Myeloma with Differential Circulating Clonal Plasma Cells
Authors: Papadhimitriou Stefanos I. , Terpos Evangelos , Liapis Konstantinos , Pavlidis Dimitrios , Marinakis Theodoros , Kastritis Efstathios , Dimopoulos Meletios-Athanasios , Tsitsilonis Ourania E. , Kostopoulos Ioannis V.
Published: January 2022

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell dyscrasia that may appear as de-novo leukemia (pPCL) or on the basis of a pre-existing multiple myeloma (MM), called secondary plasma cell leukemia (sPCL). In this prospective study, we have applied a broad panel of FISH probes in 965 newly diagnosed MM (NDMM) and 44 PCL cases of both types to reveal the particular cytogenetic differences among the three plasma cell dyscrasias. In order to evaluate the frequency and patterns of clonal evolution, the same FISH panel was applied both at diagnosis and at the time of first relapse for 81 relapsed MM patients and both at MM diagnosis and during sPCL transformation for the 19 sPCL cases described here. pPCL was characterized by frequent MYC translocations and t(11;14) with a 11q13 breakpoint centered on the MYEOV gene, not commonly seen in MM. sPCL had a higher number of FISH abnormalities and was strongly associated with the presence of del(17p13), either acquired at the initial MM stage or as a newly acquired lesion upon leukemogenesis in the context of the apparent clonal evolution observed in sPCL. In clinical terms, sPCL showed a shorter overall survival than pPCL with either standard or high-risk (t(4;14) and/or t(14;16) and/or del(17p13) and/or ≥3 concomitant aberrations) abnormalities (median 5 months vs. 21 and 11 months respectively, p < 0.001), suggesting a prognostic stratification based on cytogenetic background. These observations proved relevant in the NDMM setting, where higher levels of circulating plasma cells (CPCs) were strongly associated with high-risk cytogenetics (median frequency of CPCs: 0.11% of peripheral blood nucleated cells for high-risk vs. 0.007% for standard-risk NDMM, p < 0.0001). Most importantly, the combined evaluation of CPCs (higher or lower than a cut-off of 0.03%), together with patients’ cytogenetic status, could be used for an improved prognostic stratification of NDMM patients.
Pd2Spermine Complex Shows Cancer Selectivity and Efficacy to Inhibit Growth of Triple-Negative Breast Tumors in Mice
Authors: Vojtek Martin , Gonçalves-Monteiro Salomé , Šeminská Patrícia , Valová Katarína , Bellón Loreto , Dias-Pereira Patrícia , Marques Franklim , Marques Maria P. M. , Batista de Carvalho Ana L. M. , Mota-Filipe Helder , Ferreira Isabel M. P. L. V. O. , Diniz Carmen
Published: January 2022

Pd2Spm is a dinuclear palladium(II)-spermine chelate with promising anticancer properties against triple-negative breast cancer (TNBC), a breast carcinoma subset with poor prognosis and limited treatment options. The present study evaluated the in vitro and in vivo anticancer effects of Pd2Spm compared to the reference metal-based drug cisplatin. Triple-negative breast cancer MDA-MB-231 cells, non-cancerous MCF-12A breast cells and chorioallantoic membrane (CAM) assay were used for antiproliferative, antimigratory and antiangiogenic studies. For an in vivo efficacy study, female CBA nude mice with subcutaneously implanted MDA-MB-231 breast tumors were treated with Pd2Spm (5 mg/kg/day) or cisplatin (2 mg/kg/day) administered intraperitoneally during 5 consecutive days. Promising selective antiproliferative activity of Pd2Spm was observed in MDA-MB-231 cells (IC50 values of 7.3–8.3 µM), with at least 10-fold lower activity in MCF-12A cells (IC50 values of 89.5–228.9 µM). Pd2Spm inhibited the migration of MDA-MB-231 cells, suppressed angiogenesis in CAM and decreased VEGF secretion from MDA-MB-231 cells with similar potency as cisplatin. Pd2Spm-treated mice showed a significant reduction in tumor growth progression, and tumors evidenced a reduction in the Ki-67 proliferation index and number of mitotic figures, as well as increased DNA damage, similar to cisplatin-treated animals. Encouragingly, systemic toxicity (hematotoxicity and weight loss) observed in cisplatin-treated animals was not observed in Pd2Spm-treated mice. The present study reports, for the first time, promising cancer selectivity, in vivo antitumor activity towards TNBC and a low systemic toxicity of Pd2Spm. Thus, this agent may be viewed as a promising Pd(II) drug candidate for the treatment of this type of low-prognosis neoplasia.
State-of-the-Art Explainability Methods with Focus on Visual Analytics Showcased by Glioma Classification
Authors: Gashi Milot , Vuković Matej , Jekic Nikolina , Thalmann Stefan , Holzinger Andreas , Jean-Quartier Claire , Jeanquartier Fleur
Published: January 2022

This study aims to reflect on a list of libraries providing decision support to AI models. The goal is to assist in finding suitable libraries that support visual explainability and interpretability of the output of their AI model. Especially in sensitive application areas, such as medicine, this is crucial for understanding the decision-making process and for a safe application. Therefore, we use a glioma classification model’s reasoning as an underlying case. We present a comparison of 11 identified Python libraries that provide an addition to the better known SHAP and LIME libraries for visualizing explainability. The libraries are selected based on certain attributes, such as being implemented in Python, supporting visual analysis, thorough documentation, and active maintenance. We showcase and compare four libraries for global interpretations (ELI5, Dalex, InterpretML, and SHAP) and three libraries for local interpretations (Lime, Dalex, and InterpretML). As use case, we process a combination of openly available data sets on glioma for the task of studying feature importance when classifying the grade II, III, and IV brain tumor subtypes glioblastoma multiforme (GBM), anaplastic astrocytoma (AASTR), and oligodendroglioma (ODG), out of 1276 samples and 252 attributes. The exemplified model confirms known variations and studying local explainability contributes to revealing less known variations as putative biomarkers. The full comparison spreadsheet and implementation examples can be found in the appendix.
Molecular Targets of Triple-Negative Breast Cancer: Where Do We Stand?
Authors: Newton Emma E. , Mueller Lauren E. , Treadwell Scout M. , Morris Cindy A. , Machado Heather L.
Published: January 2022

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer. Due to its heterogeneity and lack of hormone receptor expression, this subtype is more likely to metastasize and resist treatment attempts than are other forms of breast cancer. Due to the absence of targetable receptors, chemotherapy and breast conserving surgery have been the predominant treatment options for patients. However, resistance to chemotherapy and local recurrence of the tumors is frequent. Emerging immunotherapies have begun to change treatment plans for patients diagnosed with TNBC. In this review, we discuss the various immune pathways identified in TNBC and the role they play as targets for new potential treatment choices. Various therapeutic options that inhibit key pathways in cellular growth cycles, DNA repair mechanisms, epithelial mesenchymal transition, and immunosuppression have been shown to improve survival in patients with this disease. With promising results thus far, continued studies of immunotherapy and neoadjuvant therapy options for TNBC are likely to alter the treatment course for these diagnoses in the future.
ITIH5-Derived Polypeptides Covering the VIT Domain Suppress the Growth of Human Cancer Cells In Vitro
Authors: Rose Michael , Huth Sebastian , Wiesehöfer Marc , Ehling Josef , Henkel Corinna , Steitz Julia , Lammers Twan , Kistermann Jennifer , Klaas Oliver , Koch Maximilian , Rushrush Sandra , Knüchel Ruth , Dahl Edgar
Published: January 2022

Oncogenic drivers such as mutated EGFR are the preferred targets in modern drug development. However, restoring the lost function of tumor suppressor proteins could also be a valid approach to combatting cancer. ITIH5 has been revealed as a potent metastasis suppressor in both breast and pancreatic cancer. Here, we show that ITIH5 overexpression in MDA-MB-231 breast cancer cells can also locally suppress tumor growth by 85%, when transplanted into the mammary fat pad of nude mice. For a potential drug development approach, we further aimed to define downsized ITIH5 polypeptides that still are capable of mediating growth inhibitory effects. By cloning truncated and His-tagged ITIH5 fragments, we synthesized two recombinant N-terminal polypeptides (ITIH5681aa and ITIH5161aa), both covering the ITI heavy chain specific “vault protein inter-alpha-trypsin” (VIT) domain. Truncated ITIH5 variants caused dose-dependent cell growth inhibition by up to 50% when applied to various cancer cell lines (e.g., MDA-MB-231, SCaBER, A549) reflecting breast, bladder and lung cancer in vitro. Thus, our data suggest the substantial role of the ITIH5-specific VIT domain in ITIH5-mediated suppression of tumor cell proliferation. As extracellularly administered ITIH5 peptides mimic the growth-inhibitory effects of the full-length ITIH5 tumor suppressor protein, they may constitute the basis for developing anticancer drugs in the future.