bluuebunny/crossref_metadata_2025 huggingface dataset:
State of the Art and Future Directions of Digital Twins for Production Logistics: A Systematic Literature Review
Authors: Kaiblinger Alexander , Woschank Manuel
Published: January 2022

Digital Twins (DTs) are widely discussed in the context of the Industry 4.0 paradigm as one of the main opportunities to strengthen the overall competitiveness of manufacturing enterprises. Despite a substantial scientific discussion, there is still no unified understanding regarding the constitution and subsequent usage of DTs within production logistics systems. Therefore, this paper focuses on the application of DTs in production logistics. The authors discuss common definitions, characteristics, and functionalities of DTs and outline current developments and implications from state-of-the-art implementation approaches, by using a systematic literature review. Moreover, based on the research findings, the authors evaluate a set of DT case studies, identify current research gaps, and present potential directions for future research initiatives regarding the field of production logistics in manufacturing enterprises.
Developments on Perovskite Solar Cells (PSCs): A Critical Review
Authors: Lekesi Lehlohonolo P. , Koao Lehlohonolo F. , Motloung Setumo V. , Motaung Tshwafo E. , Malevu Thembinkosi
Published: January 2022

This review provides detailed information on perovskite solar cell device background and monitors stepwise scientific efforts applied to improve device performance with time. The work reviews previous studies and the latest developments in the perovskite crystal structure, electronic structure, device architecture, fabrication methods, and challenges. Advantages, such as easy bandgap tunability, low charge recombination rates, and low fabrication cost, are among the topics discussed. Some of the most important elements highlighted in this review are concerns regarding commercialization and prototyping. Perovskite solar cells are generally still lab-based devices suffering from drawbacks such as device intrinsic and extrinsic instabilities and rising environmental concerns due to the use of the toxic inorganic lead (Pb) element in the perovskite (ABX3) light-active material. Some interesting recommendations and possible future perspectives are well articulated.
Molecular Dynamics Simulation of Nanoscale Elastic Properties of Hydrated Na-, Cs-, and Ca-Montmorillonite
Authors: Kuang Lianfei , Zhu Qiyin , Shang Xiangyu , Zhao Xiaodong
Published: January 2022

The knowledge of nanoscale mechanical properties of montmorillonite (MMT) with various compensation cations upon hydration is essential for many environmental engineering-related applications. This paper uses a Molecular Dynamics (MD) method to simulate nanoscale elastic properties of hydrated Na-, Cs-, and Ca-MMT with unconstrained system atoms. The variation of basal spacing of MMT shows step characteristics in the initial crystalline swelling stage followed by an approximately linear change in the subsequent osmotic swelling stage as the increasing of interlayer water content. The water content of MMT in the thermodynamic stable-state conditions during hydration is determined by comparing the immersion energy and hydration energy. Under this stable hydration state, the nanoscale elastic properties are further simulated by the constant strain method. Since the non-bonding strength between MMT lamellae is much lower than the boning strength within the mineral structure, the in-plane and out-of-plane strength of MMT has strong anisotropy. Simulated results including the stiffness tensor and linear elastic constants based on the assumption of orthotropic symmetry are all in good agreement with results from the literature. Furthermore, the out-of-plane stiffness tensor components of C33, C44, and C55 all fluctuate with the increase of interlayer water content, which is related to the formation of interlayer H-bonds and atom-free volume ratio. The in-plane stiffness tensor components C11, C22, and C12 decrease nonlinearly with the increase of water content, and these components are mainly controlled by the bonding strength of mineral atoms and the geometry of the hydrated MMT system. Young’s modulus in all three directions exhibits a nonlinear decrease with increasing water content.
Density Estimates as Representations of Agricultural Fields for Remote Sensing-Based Monitoring of Tillage and Vegetation Cover
Authors: Luotamo Markku , Yli-Heikkilä Maria , Klami Arto
Published: January 2022

We consider the use of remote sensing for large-scale monitoring of agricultural land use, focusing on classification of tillage and vegetation cover for individual field parcels across large spatial areas. From the perspective of remote sensing and modelling, field parcels are challenging as objects of interest due to highly varying shape and size but relatively uniform pixel content and texture. To model such areas we need representations that can be reliably estimated already for small parcels and that are invariant to the size of the parcel. We propose representing the parcels using density estimates of remote imaging pixels and provide a computational pipeline that combines the representation with arbitrary supervised learning algorithms, while allowing easy integration of multiple imaging sources. We demonstrate the method in the task of the automatic monitoring of autumn tillage method and vegetation cover of Finnish crop fields, based on the integrated analysis of intensity of Synthetic Aperture Radar (SAR) polarity bands of the Sentinel-1 satellite and spectral indices calculated from Sentinel-2 multispectral image data. We use a collection of 127,757 field parcels monitored in April 2018 and annotated to six tillage method and vegetation cover classes, reaching 70% classification accuracy for test parcels when using both SAR and multispectral data. Besides this task, the method could also directly be applied for other agricultural monitoring tasks, such as crop yield prediction.
Deep Learning for Orthopedic Disease Based on Medical Image Analysis: Present and Future
Authors: Lee JiHwan , Chung Seok Won
Published: January 2022

Since its development, deep learning has been quickly incorporated into the field of medicine and has had a profound impact. Since 2017, many studies applying deep learning-based diagnostics in the field of orthopedics have demonstrated outstanding performance. However, most published papers have focused on disease detection or classification, leaving some unsatisfactory reports in areas such as segmentation and prediction. This review introduces research published in the field of orthopedics classified according to disease from the perspective of orthopedic surgeons, and areas of future research are discussed. This paper provides orthopedic surgeons with an overall understanding of artificial intelligence-based image analysis and the information that medical data should be treated with low prejudice, providing developers and researchers with insight into the real-world context in which clinicians are embracing medical artificial intelligence.
Large Deformation Characteristics of Surrounding Rock and Support Technology of Shallow-Buried Soft Rock Roadway: A Case Study
Authors: Zhu Liu , Yao Qiangling , Xu Qiang , Yu Liqiang , Qu Qundi
Published: January 2022

The coal resources in the coal-rich area of western China are mostly located in the late diagenetic Cretaceous and Jurassic strata. In this paper, a study on the support of soft rock roadways was carried out in the background of the soft rock track roadway in the Jiebangou coal mine. The field investigation showed that the surrounding rocks of the roadway were weak, soft, and broken, and the surrounding rocks were cemented, with the roadway local deformation exceeding 1 m. The borehole television results showed that the surrounding rocks were mainly weak sandy mudstone and yellow mudstone. The average uniaxial compressive strength of the surrounding rock was 15.49 MPa. The roadway is a shallow buried soft rock roadway; site investigation revealed that the original U-shaped steel shed had an extremely low resistance to slip, the filling body behind the U-shaped steel shed fell off, the interaction between the U-shaped steel shed and the surrounding rock was poor, the U-shaped steel shed could not provide sufficient timely support resistance, and the bearing capacity of the U-shaped steel shed was far from consideration. The floor was not effectively supported. The floor had different degrees of the bottom drum, and frequent undercover caused new stress disturbances, which loosened the bottom corners of both rock types and made the shed legs move continuously inward, reducing the bearing capacity and actual support resistance of the bracket. Numerical calculations were performed to study the deformation characteristics of the surrounding rock of the tunnel and the yielding damage characteristics of the brace. The results showed that the current U-shack support strength was insufficient, the two sides were deformed by 950 mm, the bottom of the roadway bulged by 540 mm, and the surrounding rock was mainly shear damaged. The fall of the filler behind the shed caused damage to the U-shaped steel shed spire. Through site investigation results and numerical calculations, the deformation and damage characteristics of the soft rock roadway and its damage causes were analyzed, and the support technology system of ‘strengthening support for weak structural parts’ was proposed. This improved the mechanical properties of the weak structural support body, the stress state of the local surrounding rock, and the bearing capacity of the support structure, and effectively controlled the deformation, damage, and instability of the surrounding rock of the roadway, and deformation, damage, and destabilization of the roadway, thereby achieving overall stability for the surrounding rock of the roadway.
A Low-Cost Global Navigation Satellite System Positioning Accuracy Assessment Method for Agricultural Machinery
Authors: Radočaj Dorijan , Plaščak Ivan , Heffer Goran , Jurišić Mladen
Published: January 2022

The high-precision positioning and navigation of agricultural machinery represent a backbone for precision agriculture, while its worldwide implementation is in rapid growth. Previous studies improved low-cost global navigation satellite system (GNSS) hardware solutions and fused GNSS data with complementary sources, but there is still no affordable and flexible framework for positioning accuracy assessment of agricultural machinery. Such a low-cost method was proposed in this study, simulating the actual movement of the agricultural machinery during agrotechnical operations. Four of the most commonly used GNSS corrections in Croatia were evaluated in two repetitions: Croatian Positioning System (CROPOS), individual base station, Satellite-based Augmentation Systems (SBASs), and an absolute positioning method using a smartphone. CROPOS and base station produced the highest mean GNSS positioning accuracy of 2.4 and 2.9 cm, respectively, but both of these corrections produced lower accuracy than declared. All evaluated corrections produced significantly different median values in two repetitions, representing inconsistency of the positioning accuracy regarding field conditions. While the proposed method allowed flexible and effective application in the field, future studies will be directed towards the reduction of the operator’s subjective impact, mainly by implementing autosteering solutions in agricultural machinery.
Stochastic Approach to Hosting Limit of Transmission System and Improving Method Utilizing HVDC
Authors: Lee Dongyeong , Lee Junghun , Jang Gilsoo
Published: January 2022

According to the global de-carbonization trends, renewable energy integration has become an increasingly important issue in power systems. To achieve 100% renewable energy integration and operate a system with these resources, it is necessary to appropriately evaluate the system hosting capability and prepare appropriate planning and operation strategies using the evaluation result. So far, these interests have focused particularly on distribution-level systems. However, although the hosting limit in transmission-level systems requires further consideration, previous study is limited. This study introduces the constraints on the transmission-level hosting limit. In addition, a stochastic estimation of the hosting limit methodology in the transmission system and the use of a high voltage direct current system to improve hosting capacity are proposed and evaluated. Moreover, these methodology-based simulations are conducted using possible scenarios on the IEEE 39 bus system with some constraints, and the simulation results are presented herein. The results showed that the HVDC location selection and operation using the proposed method and optimization technique is appropriate. The strategy can be used to integrate more renewable energy. Furthermore, the proposed methodology can be applied to renewable energy integration scenario establishing a plan.
Clinical Comparison of the Glomerular Filtration Rate Calculated from Different Renal Depths and Formulae
Authors: Hsu Wen-Ling , Chang Shu-Min , Chang Chin-Chuan
Published: January 2022

A camera-based method using Technetium-99m diethylenetriaminepentaacetic acid (Tc-99m DTPA) is commonly used to calculate glomerular filtration rate (GFR), especially, as it can easily calculate split renal function. Renal depth is the main factor affecting the measurement of GFR accuracy. This study aimed to compare the difference of renal depths between three formulae and a CT scan, and, additionally, to calculate the GFRs by four methods. We retrospectively reviewed the medical records of patients receiving a renal dynamic scan. All patients underwent a laboratory test within one month, and a computed tomography (CT) scan within two months, before or after the renal dynamic scan. The GFRs were calculated by employing a renal dynamic scan using renal depth measured in three formulae (Tonnesen’s, Itoh K’s, and Taylor’s), and a CT scan. The renal depths measured by the above four methods were compared, and the GFRs were compared to the modified estimated GFR (eGFR). Fifty-one patients were enrolled in the study. The mean modified eGFR was 60.5 ± 42.7 mL/min. The mean GFRs calculated by three formulae and CT were 45.3 ± 23.3, 54.7 ± 27.5, 56.5 ± 26.3, and 63.7 ± 30.0, respectively. All of them correlated well with the modified eGFR (r = 0.87, 0.87, 0.87, and 0.84, respectively). The Bland–Altman plot revealed good consistency between the calculated GFR by Tonnesen’s and the modified eGFR. The renal depths measured using the three formulae were smaller than those measured using the CT scan, and the right renal depth was always larger than the left. In patients with modified eGFR > 60 mL/min, the GFR calculated by CT was the closest to the modified eGFR. The Renal depth measured by CT scan is deeper than that using formula, and it influences the GFR calculated by Gate’s method. The GFR calculated by CT is more closely related to modified eGFR when modified eGFR > 60 mL/min.
Achieving Electrochemical-Sustainable-Based Solutions for Monitoring and Treating Hydroxychloroquine in Real Water Matrix
Authors: Medeiros de Araújo Danyelle , Dos Santos Elisama V. , Martínez-Huitle Carlos A. , De Battisti Achille
Published: January 2022

Hydroxychloroquine (HCQ) has been extensively consumed due to the Coronavirus (COVID-19) pandemic. Therefore, it is increasingly found in different water matrices. For this reason, the concentration of HCQ in water should be monitored and the treatment of contaminated water matrices with HCQ is a key issue to overcome immediately. Thus, in this study, the development of technologies and smart water solutions to reach the Sustainable Development Goal 6 (SDG6) is the main objective. To do that, the integration of electrochemical technologies for their environmental application on HCQ detection, quantification and degradation was performed. Firstly, an electrochemical cork-graphite sensor was prepared to identify/quantify HCQ in river water matrices by differential pulse voltammetric (DPV) method. Subsequently, an HCQ-polluted river water sample was electrochemically treated with BDD electrode by applying 15, 30 and 45 mA cm−2. The HCQ decay and organic matter removal was monitored by DPV with composite sensor and chemical oxygen demand (COD) measurements, respectively. Results clearly confirmed that, on the one hand, the cork-graphite sensor exhibited good current response to quantify of HCQ in the river water matrix, with limit of detection and quantification of 1.46 mg L−1 (≈3.36 µM) and 4.42 mg L−1 (≈10.19 µM), respectively. On the other hand, the electrochemical oxidation (EO) efficiently removed HCQ from real river water sample using BDD electrodes. Complete HCQ removal was achieved at all applied current densities; whereas in terms of COD, significant removals (68%, 71% and 84% at 15, 30 and 45 mA cm−2, respectively) were achieved. Based on the achieved results, the offline integration of electrochemical SDG6 technologies in order to monitor and remove HCQ is an efficient and effective strategy.
Visibility Assessment of New Photovoltaic Power Plants in Areas with Special Landscape Value
Authors: Zorzano-Alba Enrique , Fernandez-Jimenez Luis Alfredo , Garcia-Garrido Eduardo , Lara-Santillan Pedro M. , Falces Alberto , Zorzano-Santamaria Pedro J. , Capellan-Villacian Candido , Mendoza-Villena Montserrat
Published: January 2022

Power plants based on renewable sources offer environmental, technical and economic advantages. Of particular importance is the reduction in greenhouse gas emissions compared to conventional power plants. Despite the advantages, people are often opposed to the construction of these facilities due to their high visual impact, particularly if they are close to places with a great cultural and/or landscape value. This paper proposes a new methodology for identifying the most suitable geographical areas for the construction of new photovoltaic (PV) power plants in zones of special scenic or cultural interest, helping to keep the environment free from the visual intrusions caused by these facilities. From several repeated analyses, the degree of visibility of the new PV plant, the potential observation time of passing visitors, considering the route they follow and their speed, and the increase in visibility of the plants when seen totally or partially with the sky as background, are determined. The result obtained is a map showing the ranking of the geographical areas based on a variable calculated in such analyses: the Global Accumulated Perception Time (GAPT). The application of this methodology can help the different agents involved in the decision-making process for the installation of new PV plant by providing them with an objective visibility criterion.
Understanding Query Combination Behavior in Exploratory Searches
Authors: Li Pengfei , Zhang Yin , Zhang Bin
Published: January 2022

In exploratory search, users sometimes combine two or more issued queries into new queries. We present such a kind of search behavior as query combination behavior. We find that the queries after combination usually can better meet users’ information needs. We also observe that users combine queries for different motivations, which leads to different types of query combination behaviors. Previous work on understanding user exploratory search behaviors has focused on how people reformulate queries, but not on how and why they combine queries. Being able to answer these questions is important for exploring how users search and learn during information retrieval processes and further developing support to assist searchers. In this paper, we first describe a two-layer hierarchical structure for understanding the space of query combination behavior types. We manually classify query combination behavior sessions from AOL and Sogou search engines and explain the relationship from combining queries to success. We then characterize some key aspects of this behavior and propose a classifier that can automatically classify types of query combination behavior using behavioral features. Finally, we summarize our findings and show how search engines can better assist searchers.
DNA Flow-Stretch Assays for Studies of Protein-DNA Interactions at the Single-Molecule Level
Authors: Kopūstas Aurimas , Zaremba Mindaugas , Tutkus Marijonas
Published: January 2022

Protein-DNA interactions are the core of the cell’s molecular machinery. For a long time, conventional biochemical methods served as a powerful investigatory basis of protein-DNA interactions and target search mechanisms. Currently single-molecule (SM) techniques have emerged as a complementary tool for studying these interactions and have revealed plenty of previously obscured mechanistic details. In comparison to the traditional ones, SM methods allow direct monitoring of individual biomolecules. Therefore, SM methods reveal reactions that are otherwise hidden by the ensemble averaging observed in conventional bulk-type methods. SM biophysical techniques employing various nanobiotechnology methods for immobilization of studied molecules grant the possibility to monitor individual reaction trajectories of biomolecules. Next-generation in vitro SM biophysics approaches enabling high-throughput studies are characterized by much greater complexity than the ones developed previously. Currently, several high-throughput DNA flow-stretch assays have been published and have shown many benefits for mechanistic target search studies of various DNA-binding proteins, such as CRISPR-Cas, Argonaute, various ATP-fueled helicases and translocases, and others. This review focuses on SM techniques employing surface-immobilized and relatively long DNA molecules for studying protein-DNA interaction mechanisms.
Speech- and Language-Based Classification of Alzheimer’s Disease: A Systematic Review
Authors: Vigo Inês , Coelho Luis , Reis Sara
Published: January 2022

Background: Alzheimer’s disease (AD) has paramount importance due to its rising prevalence, the impact on the patient and society, and the related healthcare costs. However, current diagnostic techniques are not designed for frequent mass screening, delaying therapeutic intervention and worsening prognoses. To be able to detect AD at an early stage, ideally at a pre-clinical stage, speech analysis emerges as a simple low-cost non-invasive procedure. Objectives: In this work it is our objective to do a systematic review about speech-based detection and classification of Alzheimer’s Disease with the purpose of identifying the most effective algorithms and best practices. Methods: A systematic literature search was performed from Jan 2015 up to May 2020 using ScienceDirect, PubMed and DBLP. Articles were screened by title, abstract and full text as needed. A manual complementary search among the references of the included papers was also performed. Inclusion criteria and search strategies were defined a priori. Results: We were able: to identify the main resources that can support the development of decision support systems for AD, to list speech features that are correlated with the linguistic and acoustic footprint of the disease, to recognize the data models that can provide robust results and to observe the performance indicators that were reported. Discussion: A computational system with the adequate elements combination, based on the identified best-practices, can point to a whole new diagnostic approach, leading to better insights about AD symptoms and its disease patterns, creating conditions to promote a longer life span as well as an improvement in patient quality of life. The clinically relevant results that were identified can be used to establish a reference system and help to define research guidelines for future developments.
Organ on Chip Technology to Model Cancer Growth and Metastasis
Authors: Imparato Giorgia , Urciuolo Francesco , Netti Paolo Antonio
Published: January 2022

Organ on chip (OOC) has emerged as a major technological breakthrough and distinct model system revolutionizing biomedical research and drug discovery by recapitulating the crucial structural and functional complexity of human organs in vitro. OOC are rapidly emerging as powerful tools for oncology research. Indeed, Cancer on chip (COC) can ideally reproduce certain key aspects of the tumor microenvironment (TME), such as biochemical gradients and niche factors, dynamic cell–cell and cell–matrix interactions, and complex tissue structures composed of tumor and stromal cells. Here, we review the state of the art in COC models with a focus on the microphysiological systems that host multicellular 3D tissue engineering models and can help elucidate the complex biology of TME and cancer growth and progression. Finally, some examples of microengineered tumor models integrated with multi-organ microdevices to study disease progression in different tissues will be presented.
Functional and Kinetic Comparison of Alanine Cysteine Serine Transporters ASCT1 and ASCT2
Authors: Wang Jiali , Dong Yang , Grewer Christof
Published: January 2022

Neutral amino acid transporters ASCT1 and ASCT2 are two SLC1 (solute carrier 1) family subtypes, which are specific for neutral amino acids. The other members of the SLC1 family are acidic amino acid transporters (EAATs 1–5). While the functional similarities and differences between the EAATs have been well studied, less is known about how the subtypes ASCT1 and 2 differ in kinetics and function. Here, by performing comprehensive electrophysiological analysis, we identified similarities and differences between these subtypes, as well as novel functional properties, such as apparent substrate affinities of the inward-facing conformation (in the range of 70 μM for L-serine as the substrate). Key findings were: ASCT1 has a higher apparent affinity for Na+, as well as a larger [Na+] dependence of substrate affinity compared to ASCT2. However, the general sequential Na+/substrate binding mechanism with at least one Na+ binding first, followed by amino acid substrate, followed by at least one more Na+ ion, appears to be conserved between the two subtypes. In addition, the first Na+ binding step, presumably to the Na3 site, occurs with high apparent affinity (<1 mM) in both transporters. In addition, ASCT1 and 2 show different substrate selectivities, where ASCT1 does not respond to extracellular glutamine. Finally, in both transporters, we measured rapid, capacitive charge movements upon application and removal of amino acid, due to rearrangement of the translocation equilibrium. This charge movement decays rapidly, with a time constant of 4–5 ms and recovers with a time constant in the 15 ms range after substrate removal. This places a lower limit on the turnover rate of amino acid exchange by these two transporters of 60–80 s−1.
Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and Functions
Authors: Klaihmon Phatchanat , Lorthongpanich Chanchao , Kheolamai Pakpoom , Luanpitpong Sudjit , Issaragrisil Surapol
Published: January 2022

The hippo signaling pathway plays an essential role in controlling organ size and balancing tissue homeostasis. Its two main effectors, yes-associated protein (YAP) and WW domain-containing transcription regulator 1, WWTR1 or TAZ, have also been shown to regulate endothelial cell functions and angiogenesis. In this study, the functions of YAP and TAZ in human endothelial progenitor cells (EPCs) were investigated by a loss-of-function study using CRISPR/Cas9-mediated gene knockdown (KD). Depletion of either YAP or TAZ reduced EPC survival and impaired many of their critical functions, including migration, invasion, vessel-formation, and expression of pro-angiogenic genes. Notably, TAZ-KD EPCs exhibited more severe phenotypes in comparison to YAP-KD EPCs. Moreover, the conditioned medium derived from TAZ-KD EPCs reduced the survivability of human lung cancer cells and increased their sensitivity to chemotherapeutic agents. The overexpression of either wild-type or constitutively active TAZ rescued the impaired phenotypes of TAZ-KD EPCs and restored the expression of pro-angiogenic genes in those EPCs. In summary, we demonstrate the crucial role of Hippo signaling components, YAP and TAZ, in controlling several aspects of EPC functions that can potentially be used as a drug target to enhance EPC functions in patients.
Identification of Thrombosis-Related Genes in Patients with Advanced Gastric Cancer: Data from AGAMENON-SEOM Registry
Authors: Zaragoza-Huesca David , Garrido-Rodríguez Pedro , Jiménez-Fonseca Paula , Martínez de Castro Eva , Sánchez-Cánovas Manuel , Visa Laura , Custodio Ana , Fernández-Montes Ana , Peñas-Martínez Julia , Morales del Burgo Patricia , Gallego Javier , Luengo-Gil Ginés , Vicente Vicente , Martínez-Martínez Irene , Carmona-Bayonas Alberto
Published: January 2022

Advanced gastric cancer is one of the most thrombogenic neoplasms. However, genetic mechanisms underlying this complication remain obscure, and the molecular and histological heterogeneity of this neoplasm hinder the identification of thrombotic biomarkers. Therefore, our main objective was to identify genes related to thrombosis regardless of Lauren subtypes. Furthermore, in a secondary exploratory study, we seek to discover thrombosis-associated genes that were specific to each TCGA molecular subtype. We designed a nested case-control study using the cohort of the AGAMENON national advanced gastric cancer registry. Ninety-seven patients were selected—48 with and 49 without venous thromboembolism (using propensity score matching to adjust for confounding factors)—and a differential gene expression array stratified by Lauren histopathological subtypes was carried out in primary tumor samples. For the secondary objective, the aforementioned differential expression analysis was conducted for each TCGA group. Fifteen genes were determined to be associated with thrombosis with the same expression trend in both the intestinal and diffuse subtypes. In thrombotic subjects, CRELD1, KCNH8, CRYGN, MAGEB16, SAA1, ARL11, CCDC169, TRMT61A, RIPPLY3 and PLA2G6 were underexpressed (adjusted-p < 0.05), while PRKD3, MIR5683, SDCBP, EPS8 and CDC45 were overexpressed (adjusted-p < 0.05), and correlated, by logistic regression, with lower or higher thrombotic risk, respectively, in the overall cohort. In each TCGA molecular subtype, we identified a series of genes differentially expressed in thrombosis that appear to be subtype-specific. We have identified several genes associated with venous thromboembolism in advanced gastric cancer that are common to Lauren intestinal and diffuse subtypes. Should these genetic factors be validated in the future, they could be complemented with existing clinical models to bolster the ability to predict thrombotic risk in individuals with advanced gastric adenocarcinoma.
Anorectal and Genital Mucosal Melanoma: Diagnostic Challenges, Current Knowledge and Therapeutic Opportunities of Rare Melanomas
Authors: Ottaviano Margaret , Giunta Emilio Francesco , Marandino Laura , Tortora Marianna , Attademo Laura , Bosso Davide , Cardalesi Cinzia , Fabbrocini Antonietta , Rosanova Mario , Silvestri Antonia , Montella Liliana , Tammaro Pasquale , Marra Ester , Trojaniello Claudia , Vitale Maria Grazia , Simeone Ester , Troiani Teresa , Daniele Bruno , Ascierto Paolo Antonio
Published: January 2022

Mucosal melanomas (MM) are rare tumors, being less than 2% of all diagnosed melanomas, comprising a variegated group of malignancies arising from melanocytes in virtually all mucosal epithelia, even if more frequently found in oral and sino-nasal cavities, ano-rectum and female genitalia (vulva and vagina). To date, there is no consensus about the optimal management strategy of MM. Furthermore, the clinical rationale of molecular tumor characterization regarding BRAF, KIT or NRAS, as well as the therapeutic value of immunotherapy, chemotherapy and targeted therapy, has not yet been deeply explored and clearly established in MM. In this overview, focused on anorectal and genital MM as models of rare melanomas deserving of a multidisciplinary approach, we highlight the need of referring these patients to centers with experts in melanoma, anorectal and uro-genital cancers treatments. Taking into account the rarity, the poor outcomes and the lack of effective treatment options for MM, tailored research needs to be promptly promoted.
Numerical Training Videos and Early Numerical Achievement: A Study on 3-Year-Old Preschoolers
Authors: Cuder Alessandro , Vidoz Marta , De Vita Chiara , Pellizzoni Sandra , Passolunghi Maria Chiara
Published: January 2022

Early numerical abilities predict later math achievement and could be improved in children by using various training methods. As the literature on the use of training videos to develop numerical abilities is still surprisingly scant, the aim of the present study was to test the efficacy of a numerical training video on the development of counting and number line knowledge in 3-year-old preschoolers. Far transfer effects to cardinality and working memory were also examined. The study involved 86 children randomly assigned to two intervention groups: a numerical training group exposed to videos on counting and number lines; and a control group exposed to videos on colors and animal names in a foreign language. After the video training, there was an improvement in the numerical training group’s counting skills, but not in their number line knowledge, and this improvement persisted six months later. The numerical training group also showed a far-transfer enhancement of cardinality six months after the intervention. Based on our results, numerical training videos could be effective in helping to enhance early numeracy skills in very young preschoolers.
Confirmation Bias in the Course of Instructed Reinforcement Learning in Schizophrenia-Spectrum Disorders
Authors: Frydecka Dorota , Piotrowski Patryk , Bielawski Tomasz , Pawlak Edyta , Kłosińska Ewa , Krefft Maja , Al Noaimy Kamila , Rymaszewska Joanna , Moustafa Ahmed A. , Drapała Jarosław , Misiak Błażej
Published: January 2022

A large body of research attributes learning deficits in schizophrenia (SZ) to the systems involved in value representation (prefrontal cortex, PFC) and reinforcement learning (basal ganglia, BG) as well as to the compromised connectivity of these regions. In this study, we employed learning tasks hypothesized to probe the function and interaction of the PFC and BG in patients with SZ-spectrum disorders in comparison to healthy control (HC) subjects. In the Instructed Probabilistic Selection task (IPST), participants received false instruction about one of the stimuli used in the course of probabilistic learning which creates confirmation bias, whereby the instructed stimulus is overvalued in comparison to its real experienced value. The IPST was administered to 102 patients with SZ and 120 HC subjects. We have shown that SZ patients and HC subjects were equally influenced by false instruction in reinforcement learning (RL) probabilistic task (IPST) (p-value = 0.441); however, HC subjects had significantly higher learning rates associated with the process of overcoming cognitive bias in comparison to SZ patients (p-value = 0.018). The behavioral results of our study could be hypothesized to provide further evidence for impairments in the SZ-BG circuitry; however, this should be verified by neurofunctional imaging studies.
Optimization of the Curved Metal Damper to Improve Structural Energy Dissipation Capacity
Authors: Kim Young-Chan , Mortazavi Seyed , Farzampour Alireza , Hu Jong-Wan , Mansouri Iman , Awoyera Paul
Published: January 2022

Structural curved metal dampers are implemented in various applications to mitigate the damages at a specific area efficiently. A stable and saturated hysteretic behavior for the in-plane direction is dependent on the shape of a curved-shaped damper. However, it has been experimentally shown that the hysteretic behavior in the conventional curved-shaped damper is unstable, mainly as a result of bi-directional deformations. Therefore, it is necessary to conduct shape optimization for curved dampers to enhance their hysteretic behavior and energy dissipation capability. In this study, the finite element (FE) model built in ABAQUS, is utilized to obtain optimal shape for the curved-shaped damper. The effectiveness of the model is checked by comparisons of the FE model and experimental results. The parameters for the optimization include the curved length and shape of the damper, and the improved approach is conducted by investigating the curved sections. In addition, the design parameters are represented by B-spline curves (to ensure enhanced system performance), regression analysis is implemented to derive optimization formulations considering energy dissipation, constitutive material model, and cumulative plastic strain. Results determine that the energy dissipation capacity of the curved steel damper could be improved by 32% using shape optimization techniques compared to the conventional dampers. Ultimately, the study proposes simple optimal shapes for further implementations in practical designs.
The Role of Stereotactic Radiosurgery in the Management of Foramen Magnum Meningiomas—A Multicenter Analysis and Review of the Literature
Authors: Ehret Felix , Kufeld Markus , Fürweger Christoph , Haidenberger Alfred , Fichte Susanne , Lehrke Ralph , Senger Carolin , Kaul David , Bleif Martin , Becker Gerd , Rueß Daniel , Ruge Maximilian , Schichor Christian , Tonn Jörg-Christian , Muacevic Alexander
Published: January 2022

Background: Foramen magnum meningiomas (FMMs) represent a considerable neurosurgical challenge given their location and potential morbidity. Stereotactic radiosurgery (SRS) is an established non-invasive treatment modality for various benign and malignant brain tumors. However, reports on single-session or multisession SRS for the management and treatment of FMMs are exceedingly rare. We report the largest FMM SRS series to date and describe our multicenter treatment experience utilizing robotic radiosurgery. Methods: Patients who underwent SRS between 2005 and 2020 as a treatment for a FMM at six different centers were eligible for analysis. Results: Sixty-two patients met the inclusion criteria. The median follow-up was 28.9 months. The median prescription dose and isodose line were 14 Gy and 70%, respectively. Single-session SRS accounted for 81% of treatments. The remaining patients received three to five fractions, with doses ranging from 19.5 to 25 Gy. Ten (16%) patients were treated for a tumor recurrence after surgery, and thirteen (21%) underwent adjuvant treatment. The remaining 39 FMMs (63%) received SRS as their primary treatment. For patients with an upfront surgical resection, histopathological examination revealed 22 World Health Organization grade I tumors and one grade II FMM. The median tumor volume was 2.6 cubic centimeters. No local failures were observed throughout the available follow-up, including patients with a follow-up ≥ five years (16 patients), leading to an overall local control of 100%. Tumor volume significantly decreased after treatment, with a median volume reduction of 21% at the last available follow-up (p < 0.01). The one-, three-, and five-year progression-free survival were 100%, 96.6%, and 93.0%, respectively. Most patients showed stable (47%) or improved (21%) neurological deficits at the last follow-up. No high-grade adverse events were observed. Conclusions: SRS is an effective and safe treatment modality for FMMs. Despite the paucity of available data and previous reports, SRS should be considered for selected patients, especially those with subtotal tumor resections, recurrences, and patients not suitable for surgery.
Skeletal Muscle Depletion and Major Postoperative Complications in Locally-Advanced Head and Neck Cancer: A Comparison between Ultrasound of Rectus Femoris Muscle and Neck Cross-Sectional Imaging
Authors: Galli Andrea , Colombo Michele , Prizio Carmine , Carrara Giulia , Lira Luce Francesca , Paesano Pier Luigi , Della Vecchia Giovanna , Giordano Leone , Bondi Stefano , Tulli Michele , Di Santo Davide , Mirabile Aurora , De Cobelli Francesco , Bussi Mario
Published: January 2022

Skeletal muscle mass (SMM) depletion has been validated in many surgical fields as independent predictor of complications through cross-sectional imaging. We evaluated SMM depletion in a stage III-IV head and neck cancer cohort, comparing the accuracy of CT/MRI at C3 level with ultrasound (US) of rectus femoris muscle (RF) in terms of prediction of major complications. Patients submitted to surgery were recruited from 2016 to 2021. SMM was estimated on CT/MRI by calculating the sum of the cross-sectional area (CSA) of the sternocleidomastoid and paravertebral muscles at C3 level and its height-indexed value (cervical skeletal muscle index, CSMI) and on US by computing the CSA of RF. Specific thresholds were defined for both US and CT/MRI according to ROC curve in terms of best prediction of 30-day major complications to detect sarcopenic subjects (40–53%). Sixty-five patients completed the study. At univariate analysis, major complications were associated to lower RF CSA, lower CSA at C3 level and lower CSMI, together with previous radiotherapy, higher ASA score and higher modified frailty index (mFI). At multivariate analysis RF CSA (OR 7.07, p = 0.004), CSA at C3 level (OR 6.74, p = 0.005) and CSMI (OR 4.02, p = 0.025) were confirmed as independent predictors in three different models including radiotherapy, ASA score and mFI. This analysis proved the value of SMM depletion as predictor of major complications in a head and neck cancer cohort, either defined on cross-sectional imaging at C3 or on US of RF.
Sustainable Electrochemical NO Capture and Storage System Based on the Reversible Fe2+/Fe3+-EDTA Redox Reaction
Authors: Eum Heesung , Cheong Seokhyeon , Kim Jiyun , Han Seo-Jung , Cheong Minserk , Lee Hyunjoo , Lee Hae-Seok , Lee Dong Ki
Published: January 2022

The removal of nitric oxide (NO), which is an aggregation agent for fine dust that causes air pollution, from exhaust gas has been considered an important treatment in the context of environmental conservation. Herein, we propose a sustainable electrochemical NO removal system based on the reversible Fe2+/Fe3+-ethylenediamine tetraacetic acid (EDTA) redox reaction, which enables continuous NO capture and storage at ambient temperature without the addition of any sacrificial agents. We have designed a flow-type reaction system in which the NO absorption and emission can be separately conducted in the individual reservoirs of the catholyte and anolyte with the continuous regeneration of Fe2+-EDTA by the electrochemical reduction in Fe3+-EDTA. A continuous flow reaction using a silver cathode and glassy carbon anode showed that the concentrations of Fe2+ and Fe3+-EDTA in the electrolyte were successfully maintained at a 1:1 ratio, which demonstrates that the proposed system can be applied for continuous NO capture and storage.
Analysis of 5-Azacytidine Resistance Models Reveals a Set of Targetable Pathways
Authors: Minařík Lubomír , Pimková Kristýna , Kokavec Juraj , Schaffartziková Adéla , Vellieux Fréderic , Kulvait Vojtěch , Daumová Lenka , Dusilková Nina , Jonášová Anna , Vargová Karina Savvulidi , Králová Viziová Petra , Sedláček Radislav , Zemanová Zuzana , Stopka Tomáš
Published: January 2022

The mechanisms by which myelodysplastic syndrome (MDS) cells resist the effects of hypomethylating agents (HMA) are currently the subject of intensive research. A better understanding of mechanisms by which the MDS cell becomes to tolerate HMA and progresses to acute myeloid leukemia (AML) requires the development of new cellular models. From MDS/AML cell lines we developed a model of 5-azacytidine (AZA) resistance whose stability was validated by a transplantation approach into immunocompromised mice. When investigating mRNA expression and DNA variants of the AZA resistant phenotype we observed deregulation of several cancer-related pathways including the phosphatidylinosito-3 kinase signaling. We have further shown that these pathways can be modulated by specific inhibitors that, while blocking the proliferation of AZA resistant cells, are unable to increase their sensitivity to AZA. Our data reveal a set of molecular mechanisms that can be targeted to expand therapeutic options during progression on AZA therapy.
Effects of Formyl Peptide Receptor Agonists Ac9-12 and WKYMV in In Vivo and In Vitro Acute Inflammatory Experimental Models
Authors: Lice Izabella , Sanches José Marcos , Correia-Silva Rebeca D. , Corrêa Mab P. , Icimoto Marcelo Y. , Silva Alex A. R. , Sánchez-Vinces Salvador , Porcari Andreia M. , Moreira Vanessa , Gil Cristiane D.
Published: January 2022

Formyl peptide receptors (Fprs) are a G-protein-coupled receptor family mainly expressed on leukocytes. The activation of Fpr1 and Fpr2 triggers a cascade of signaling events, leading to leukocyte migration, cytokine release, and increased phagocytosis. In this study, we evaluate the effects of the Fpr1 and Fpr2 agonists Ac9-12 and WKYMV, respectively, in carrageenan-induced acute peritonitis and LPS-stimulated macrophages. Peritonitis was induced in male C57BL/6 mice through the intraperitoneal injection of 1 mL of 3% carrageenan solution or saline (control). Pre-treatments with Ac9-12 and WKYMV reduced leukocyte influx to the peritoneal cavity, particularly neutrophils and monocytes, and the release of IL-1β. The addition of the Fpr2 antagonist WRW4 reversed only the anti-inflammatory actions of WKYMV. In vitro, the administration of Boc2 and WRW4 reversed the effects of Ac9-12 and WKYMV, respectively, in the production of IL-6 by LPS-stimulated macrophages. These biological effects of peptides were differently regulated by ERK and p38 signaling pathways. Lipidomic analysis evidenced that Ac9-12 and WKYMV altered the intracellular lipid profile of LPS-stimulated macrophages, revealing an increased concentration of several glycerophospholipids, suggesting regulation of inflammatory pathways triggered by LPS. Overall, our data indicate the therapeutic potential of Ac9-12 and WKYMV via Fpr1 or Fpr2-activation in the inflammatory response and macrophage activation.
Combination Therapy of Placenta-Derived Mesenchymal Stem Cells with WKYMVm Promotes Hepatic Function in a Rat Model with Hepatic Disease via Vascular Remodeling
Authors: Jun Ji Hye , Park Sohae , Kim Jae Yeon , Lim Ja-Yun , Park Gyu Tae , Kim Jae Ho , Kim Gi Jin
Published: January 2022

Changes in the structure and function of blood vessels are important factors that play a primary role in regeneration of injured organs. WKYMVm has been reported as a therapeutic factor that promotes the migration and proliferation of angiogenic cells. Additionally, we previously demonstrated that placenta-derived mesenchymal stem cells (PD-MSCs) induce hepatic regeneration in hepatic failure via antifibrotic effects. Therefore, our objectives were to analyze the combination effect of PD-MSCs and WKYMVm in a rat model with bile duct ligation (BDL) and evaluate their therapeutic mechanism. To analyze the anti-fibrotic and angiogenic effects on liver regeneration, it was analyzed using ELISA, qRT-PCR, Western blot, immunofluorescence, and immunohistochemistry. Collagen accumulation was significantly decreased in PD-MSCs with the WKYMVm combination (Tx+WK) group compared with the nontransplantation (NTx) and PD-MSC-transplanted (Tx) group (p < 0.05). Furthermore, the combination of PD-MSCs with WKYMVm significantly promoted hepatic function by increasing hepatocyte proliferation and albumin as well as angiogenesis by activated FPR2 signaling (p < 0.05). The combination therapy of PD-MSCs with WKYMVm could be an efficient treatment in hepatic diseases via vascular remodeling. Therefore, the combination therapy of PD-MSCs with WKYMVm could be a new therapeutic strategy in degenerative medicine.