bluuebunny/crossref_metadata_2025 huggingface dataset:
A Layered KNN-SVM Approach to Predict Missing Values of Functional Requirements in Product Customization
Authors: Gu Ye , Zhang Shuyou , Qiu Lemiao , Wang Zili , Zhang Lichun
Published: March 2021

The conversion from functional requirements (FRs) to design parameters is the foundation of product customization. However, original customer needs usually result in incomplete FRs, limited by customers’ incomprehension on the design requirements of these products. As the incomplete FRs may undermine the design activities afterwards, managers need to develop an effective approach to predict the missing values of the FR. This study proposes an integrative approach to obtain the complete FR. The k nearest neighbor (KNN) algorithm is employed to predict the missing continuous variables in FR, using the improved distance formula for two incomplete FRs. Support vector machine (SVM) classifiers are adopted to classify the missing categorical variables in FR, combined with directed acyclic graph for multi-class classification. KNN and SVM are then integrated into a multi-layer framework to predict the missing values of FR, where categorical and continuous variables both exist. A case study on the elevator customization is conducted to verify that KNN-SVM is feasible in accurate prediction of elevator FR values. Furthermore, KNN-SVM outperforms other five single and five composite methods, with average reduction in root mean squared error (RMSE) of 39% and 21% against KNN and KNN-Tree, respectively.
Phenolic Profiling of Five Different Australian Grown Apples
Authors: Li Heng , Subbiah Vigasini , Barrow Colin J. , Dunshea Frank R. , Suleria Hafiz A. R.
Published: March 2021

Apples (Malus domestica) are one of the most widely grown and consumed fruits in the world that contain abundant phenolic compounds that possess remarkable antioxidant potential. The current study characterised phenolic compounds from five different varieties of Australian grown apples (Royal Gala, Pink Lady, Red Delicious, Fuji and Smitten) using LC-ESI-QTOF-MS/MS and quantified through HPLC-PDA. The phenolic content and antioxidant potential were determined using various assays. Red Delicious had the highest total phenolic (121.78 ± 3.45 mg/g fw) and total flavonoid content (101.23 ± 3.75 mg/g fw) among the five apple samples. In LC-ESI-QTOF-MS/MS analysis, a total of 97 different phenolic compounds were characterised in five apple samples, including Royal Gala (37), Pink Lady (54), Red Delicious (17), Fuji (67) and Smitten (46). In the HPLC quantification, phenolic acid (chlorogenic acid, 15.69 ± 0.09 mg/g fw) and flavonoid (quercetin, 18.96 ± 0.08 mg/g fw) were most abundant in Royal Gala. The obtained results highlight the importance of Australian apple varieties as a rich source of functional compounds with potential bioactivity.
Method for Select Best AIS Data in Prediction Vessel Movements and Route Estimation
Authors: Bautista-Sánchez Rogelio , Barbosa-Santillan Liliana Ibeth , Sánchez-Escobar Juan Jaime
Published: March 2021

The prediction of vessel maritime navigation has become an exciting topic in the last years, especially considering economics, commercial exchange, and security. In addition, vessel monitoring requires better systems and techniques that help enterprises and governments to protect their interests. Specifically, the prediction of vessel movements is essential for safety and tracking. However, the applications of prediction techniques have a high cost related to computational efficiency and low resource saving. This article presents a sample method to select historical data on vessel-specific routes to optimize the computational performance of the prediction of vessel positions and route estimation in real-time. These historical navigation data can help to estimate a complete path and perform vessel position predictions through time. This Select Best AIS Data in Prediction Vessel Movements and Route Estimation (PreMovEst) method works in a Vessel Traffic Service database to save computational resources when predictions or route estimations are executed. This article discusses AIS data and the artificial neural network. This work aims to present a prediction model that correctly predicts the physical movement in the route. It supports path planning for the Vessel Traffic Service. After testing the method, the results obtained for route estimation have a precision of 76.15%, and those for vessel position predictions through time have an accuracy of 81.043%.
Drivers’ Psychomotor Reaction Times Tested with a Test Station Method
Authors: Szydłowski Tomasz , Surmiński Krzysztof , Batory Damian
Published: March 2021

The article presents the standard method of the evaluation of car drivers’ psychomotor reaction times. A characteristic feature of this method is the ability to conduct tests using real vehicles equipped with mobile measuring apparatus. Measurements are carried out on people whose task is to initiate specific maneuvers (such as: a braking or turning maneuver, a combined braking and turning maneuver, as well as e.g., the use of an audio signal) in response to external stimuli coming from different directions. The sources of the stimuli are light signals emitted by variable message signs placed around the vehicle. The developed control and measurement equipment allows us to realize various and complex test scenarios. It generates stimulus sequences, assesses the correctness of the driver’s response and measures its time. This method allows us to obtain sets of results from tests carried out under different conditions and variable test durations. The possibility of testing a large number of participants in a relatively short time and in repetitive conditions allows for reliable statistical inference. The paper presents examples of research results obtained on the basis of few thousand tests carried out on a large group of respondents. The registered data was statistically processed and referred to the literature. A high degree of correlation between the analyzed results and the literature reports proves that the presented method may be a source of data for the analysis of phenomena related to the time of the driver’s response, especially the influence of various factors affecting its values.
Anti-Inflammatory and Antioxidant Properties of Ethanol Extracts of Raw, Blanched, Steamed, and Sous-Vide Cooked Okra (Abelmoschus esculentus L.) in LPS or H2O2-Treated RAW264.7 Cells
Authors: Lee Taenam , Joo Nami
Published: March 2021

Okra (Abelmoschus esculentus L.) is a plant belonging to the Malvaceae family. All parts of okra, including the pod, leaf, and branch, are edible, with the pod being especially enriched with sugars, dietary fibers, minerals, vitamins, and antioxidants. It has beneficial effect against colitis, hepatitis, and gastric ulcer. However, studies on okra’s anti-inflammatory effects remain limited. It is known that cooking methods change nutrition and functional compounds in foods. In this study, we prepared ethanolic extracts of okra using four different cooking methods (raw, blanching, steaming, and sous-vide), and analyzed anti-inflammatory and antioxidant effects on lipopolysaccharide- (LPS) or hydrogen peroxide (H2O2)-treated RAW264.7 macrophages. Cell viability was similar between all four cooking methods, confirming that okra extracts (≤200 μg/mL) were not cytotoxic. All cooking methods inhibited nitric oxide production (indicator of inflammatory responses). Sous-vide cooking showed low inhibitory effect at 100–200 μg/mL of okra extract. Moreover, examining the mRNA expression of inducible cycloxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and inflammatory cytokines (tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1-beta (IL-1β)) showed inhibitory effects by all cooking methods. Reactive oxygen species (ROS) levels were also reduced for all cooking methods, with sous-vide cooking showing the highest rate of reduction. These results confirm the anti-inflammatory and antioxidant effects of raw and multimethod cooked okra. Notably, sous-vide cooking showed the greatest potential to improve okra’s therapeutic effects.
Facial Paralysis Detection on Images Using Key Point Analysis
Authors: Parra-Dominguez Gemma S. , Sanchez-Yanez Raul E. , Garcia-Capulin Carlos H.
Published: March 2021

The inability to move the muscles of the face on one or both sides is known as facial paralysis, which may affect the ability of the patient to speak, blink, swallow saliva, eat, or communicate through natural facial expressions. The well-being of the patient could also be negatively affected. Computer-based systems as a means to detect facial paralysis are important in the development of standardized tools for medical assessment, treatment, and monitoring; additionally, they are expected to provide user-friendly tools for patient monitoring at home. In this work, a methodology to detect facial paralysis in a face photograph is proposed. A system consisting of three modules—facial landmark extraction, facial measure computation, and facial paralysis classification—was designed. Our facial measures aim to identify asymmetry levels within the face elements using facial landmarks, and a binary classifier based on a multi-layer perceptron approach provides an output label. The Weka suite was selected to design the classifier and implement the learning algorithm. Tests on publicly available databases reveal outstanding classification results on images, showing that our methodology that was used to design a binary classifier can be expanded to other databases with great results, even if the participants do not execute similar facial expressions.
Statistical Analysis of Nanofiber Mat AFM Images by Gray-Scale-Resolved Hurst Exponent Distributions
Authors: Blachowicz Tomasz , Domino Krzysztof , Koruszowic Michał , Grzybowski Jacek , Böhm Tobias , Ehrmann Andrea
Published: March 2021

Two-dimensional structures, either periodic or random, can be classified by diverse mathematical methods. Quantitative descriptions of such surfaces, however, are scarce since bijective definitions must be found to measure unique dependency between described structures and the chosen quantitative parameters. To solve this problem, we use statistical analysis of periodic fibrous structures by Hurst exponent distributions. Although such a Hurst exponent approach was suggested some years ago, the quantitative analysis of atomic force microscopy (AFM) images of nanofiber mats in such a way was described only recently. In this paper, we discuss the influence of typical AFM image post-processing steps on the gray-scale-resolved Hurst exponent distribution. Examples of these steps are polynomial background subtraction, aligning rows, deleting horizontal errors and sharpening. Our results show that while characteristic features of these false-color images may be shifted in terms of gray-channel and Hurst exponent, they can still be used to identify AFM images and, in the next step, to quantitatively describe AFM images of nanofibrous surfaces. Such a gray-channel approach can be regarded as a simple way to include some information about the 3D structure of the image.
Integrated Design of a Morphing Winglet for Active Load Control and Alleviation of Turboprop Regional Aircraft
Authors: Dimino Ignazio , Andreutti Giovanni , Moens Frédéric , Fonte Federico , Pecora Rosario , Concilio Antonio
Published: March 2021

Aircraft winglets are well-established devices that improve aircraft fuel efficiency by enabling a higher lift over drag ratios and lower induced drag. Retrofitting winglets to existing aircraft also increases aircraft payload/range by the same order of the fuel burn savings, although the additional loads and moments imparted to the wing may impact structural interfaces, adding more weight to the wing. Winglet installation on aircraft wing influences numerous design parameters and requires a proper balance between aerodynamics and weight efficiency. Advanced dynamic aeroelastic analyses of the wing/winglet structure are also crucial for this assessment. Within the scope of the Clean Sky 2 REG IADP Airgreen 2 project, targeting novel technologies for next-generation regional aircraft, this paper deals with the integrated design of a full-scale morphing winglet for the purpose of improving aircraft aerodynamic efficiency in off-design flight conditions, lowering wing-bending moments due to maneuvers and increasing aircraft flight stability through morphing technology. A fault-tolerant morphing winglet architecture, based on two independent and asynchronous control surfaces with variable camber and differential settings, is presented. The system is designed to face different flight situations by a proper action on the movable control tabs. The potential for reducing wing and winglet loads by means of the winglet control surfaces is numerically assessed, along with the expected aerodynamic performance and the actuation systems’ integration in the winglet surface geometry. Such a device was designed by CIRA for regional aircraft installation, whereas the aerodynamic benefits and performance were estimated by ONERA on the natural laminar flow wing. An active load controller was developed by PoliMI and UniNA performed aeroelastic trade-offs and flutter calculations due to the coupling of winglet movable harmonics and aircraft wing bending and torsion.
A Study on the Microstructure and Corrosion Characteristics of Early Iron Age Bronze Mirrors Excavated from the Korean Peninsula
Authors: Cho Nam Chul , Jang Min Kyeong , Huh Il Kwon
Published: March 2021

Bronze mirrors, considered important grave goods, were widely used before glass mirrors in ancient times. Most excavated bronze artifacts are covered with corrosive materials and lose their original colors. More importantly, identifying corrosion characteristics and the manufacturing techniques used for these artifacts are essential for proper artifact preservation. In this study, Early Iron Age bronze mirrors excavated from the Korean Peninsula were examined to determine their microstructures, corrosion characteristics, and production techniques using various analytical methods, such as Micro-Raman spectroscopy and field emission electron probe microanalysis. As a result, sulfides containing iron suggested chalcopyrite use during production or that the sulfides originated from copper, iron, and sulfur residual matte. The analysis also detected corrosion layers with high tin oxide (SnO2) levels and selective corrosion in the α + δ eutectoid phase on the artifact’s surface. In the corrosive layer, cuprite, malachite, and cassiterite corrosion products were detected, and nanocrystalline SnO2 was identified as a characteristic of long-term soil erosion. Identifying these artifacts’ corrosion characteristics and manufacturing techniques is essential and can greatly contribute to proper artifact preservation.
Thermo-Economic Comparisons of Environmentally Friendly Solar Assisted Absorption Air Conditioning Systems
Authors: Al-Falahi Adil , Alobaid Falah , Epple Bernd
Published: March 2021

Absorption refrigeration cycle is considered a vital option for thermal cooling processes. Designing new systems is needed to meet the increasing communities’ demands of space cooling. This should be given more attention especially with the increasing conventional fossil fuel energy costs and CO2 emission. This work presents the thermo-economic analysis to compare between different solar absorption cooling system configurations. The proposed system combines a solar field, flashing tank and absorption chiller: two types of absorption cycle H2O-LiBr and NH3-H2O have been compared to each other by parabolic trough collectors and evacuated tube collectors under the same operating conditions. A case study of 200 TR total cooling load is also presented. Results reveal that parabolic trough collector combined with H2O-LiBr (PTC/H2O-LiBr) gives lower design aspects and minimum rates of hourly costs (5.2 $/h) followed by ETC/H2O-LiBr configuration (5.6 $/h). H2O-LiBr gives lower thermo-economic product cost (0.14 $/GJ) compared to the NH3-H2O (0.16 $/GJ). The absorption refrigeration cycle coefficient of performance ranged between 0.5 and 0.9.
Optical Coherence Tomography Angiography Monitors Cutaneous Wound Healing under Angiogenesis-Promoting Treatment in Diabetic and Non-Diabetic Mice
Authors: Pfister Martin , Schützenberger Kornelia , Schäfer Bhavapriya J. , Puchner Stefan , Stegmann Hannes , Hohenadl Christine , Mildner Michael , Garhöfer Gerhard , Schmetterer Leopold , Werkmeister René M.
Published: March 2021

During wound healing, the rapid re-establishment of a functional microcirculation in the wounded tissue is of utmost importance. We applied optical coherence tomography (OCT) angiography to evaluate vascular remodeling in an excisional wound model in the pinnae of C57BL/6 and db/db mice receiving different proangiogenic topical treatments. Analysis of the high-resolution OCT angiograms, including the four quantitative parameters vessel density, vessel length, number of bifurcations, and vessel tortuosity, revealed changes of the microvasculature and allowed identification of the overlapping wound healing phases hemostasis, inflammation, proliferation, and remodeling. Angiograms acquired in the inflammatory phase in the first days showed a dilation of vessels and recruitment of pre-existing capillaries. In the proliferative phase, angiogenesis with the sprouting of new capillaries into the wound tissue led to an increase of the OCT angiography parameters vessel density, normalized vessel length, number of bifurcations, and vessel tortuosity by 28–47%, 39–52%, 33–48%, and 3–8% versus baseline, respectively. After the peak observed on study days four to seven, the parameters slowly decreased but remained still elevated 18 days after wounding, indicating a continuing remodeling phase. Our study suggests that OCT angiography has the potential to serve as a valuable preclinical research tool in studies investigating impaired vascular remodeling during wound healing and potential new treatment strategies.
Lag Effects of Ozone, PM2.5, and Meteorological Factors on COVID-19 New Cases at the Disease Epicenter in Queens, New York
Authors: Adhikari Atin , Yin Jingjing
Published: March 2021

The influences of environmental factors on COVID-19 may not be immediate and could be lagged for days to weeks. This study investigated the choice of lag days for calculating cumulative lag effects of ozone, PM2.5, and five meteorological factors (wind speed, temperature, relative humidity, absolute humidity, and cloud percentages) on COVID-19 new cases at the epicenter of Queens County, New York, before the governor’s executive order on wearing of masks in public places (1 March to 11 April 2020). Daily data for selected air pollutants and meteorological factors were collected from the US EPA Air Quality System, weather observation station of the NOAA National Centers for Environmental Information at John F. Kennedy Airport, and World Weather Online. Negative binomial regression models were applied, including the autocorrelations and trend of the time series, as well as the effective reproductive number as confounders. The effects of ozone, PM2.5, and five meteorological factors were significant on COVID-19 new cases with lag9-lag13 days. Incidence rate ratios (IRRs) were consistent for any lag day choice between lag0 and lag14 days and started fluctuating after lag15 days. Considering moving averages >14 days yielded less reliable variables for summarizing the cumulative lag effects of environmental factors on COVID-19 new cases and considering lag days from 9 to 13 would yield significant findings. Future studies should consider this approach of lag day checks concerning the modeling of COVID-19 progression in relation to meteorological factors and ambient air pollutants.
The First Record and Classification of Planktonic Radiolarian (Phylum Retaria) and Phaeodarian (Phylum Cercozoa) in the Eastern Indian Ocean
Authors: Munir Sonia , Sun Jun , Morton Steve L.
Published: March 2021

Siliceous planktonic species of the phyla Retaria and Cercozoa were investigated from the surface to a 200 m depth around the eastern Indian Ocean (80.00°–96.10° E, 10.08° N–6.00° S) during a 2-month cruise (10 April–13 May 2014). These species are commonly referred to as Radiolarians and are found in all of the world’s oceans; however, this is a detailed investigation of the species’ diversity in the eastern Indian Ocean. Samples were collected from the eastern Indian Ocean using a plankton towing net during a vertical haul from 44 sampling stations, which resulted in 168 taxa, including 60 species that were newly recorded in the study area. The main purpose of this work was to identify members of the phyla Retaria and Cercozoa and their distribution in the eastern Indian Ocean. The species’ morphology, identification, notes, and new geographical records are briefly described.
Lysosomal Functions in Glia Associated with Neurodegeneration
Authors: Kreher Conlan , Favret Jacob , Maulik Malabika , Shin Daesung
Published: March 2021

Lysosomes are cellular organelles that contain various acidic digestive enzymes. Despite their small size, they have multiple functions. Lysosomes remove or recycle unnecessary cell parts. They repair damaged cellular membranes by exocytosis. Lysosomes also sense cellular energy status and transmit signals to the nucleus. Glial cells are non-neuronal cells in the nervous system and have an active role in homeostatic support for neurons. In response to dynamic cues, glia use lysosomal pathways for the secretion and uptake of regulatory molecules, which affect the physiology of neighboring neurons. Therefore, functional aberration of glial lysosomes can trigger neuronal degeneration. Here, we review lysosomal functions in oligodendrocytes, astrocytes, and microglia, with emphasis on neurodegeneration.
Cyclodextrins, Natural Compounds, and Plant Bioactives—A Nutritional Perspective
Authors: Wüpper Svenja , Lüersen Kai , Rimbach Gerald
Published: March 2021

Cyclodextrins (CDs) are a group of cyclic oligosaccharides produced from starch or starch derivatives. They contain six (αCD), seven (βCD), eight (γCD), or more glucopyranose monomers linked via α-1,4-glycosidic bonds. CDs have a truncated cone shape with a hydrophilic outer wall and a less hydrophilic inner wall, the latter forming a more apolar internal cavity. Because of this special architecture, CDs are soluble in water and can simultaneously host lipophilic guest molecules. The major advantage of inclusion into CDs is increased aqueous solubility of such lipophilic substances. Accordingly, we present studies where the complexation of natural compounds such as propolis and dietary plant bioactives (e.g., tocotrienol, pentacyclic triterpenoids, curcumin) with γCD resulted in improved stability, bioavailability, and bioactivity in various laboratory model organisms and in humans. We also address safety aspects that may arise from increased bioavailability of plant extracts or natural compounds owing to CD complexation. When orally administered, α- and βCD—which are inert to intestinal digestion—are fermented by the human intestinal flora, while γCD is almost completely degraded to glucose units by α-amylase. Hence, recent reports indicate that empty γCD supplementation exhibits metabolic activity on its own, which may provide opportunities for new applications.
SCRIB Is Involved in the Progression of Ovarian Carcinomas in Association with the Factors Linked to Epithelial-to-Mesenchymal Transition and Predicts Shorter Survival of Diagnosed Patients
Authors: Hussein Usama Khamis , Ahmed Asmaa Gamal , Choi Won Ku , Kim Kyoung Min , Park See-Hyoung , Park Ho Sung , Noh Sang Jae , Lee Ho , Chung Myoung Ja , Moon Woo Sung , Kang Myoung Jae , Cho Dong Hyu , Jang Kyu Yun
Published: March 2021

SCRIB is a polarity protein important in maintaining cell junctions. However, recent reports have raised the possibility that SCRIB might have a role in human cancers. Thus, this study evaluated the roles of SCRIB in ovarian cancers. In 102 human ovarian carcinomas, nuclear expression of SCRIB predicted shorter survival of ovarian carcinoma patients, especially in the patients who received post-operative chemotherapy. In SKOV3 and SNU119 ovarian cancer cells, overexpression of SCRIB stimulated the proliferation and invasion of cells. Knockout of SCRIB inhibited in vivo tumor growth of SKOV3 cells and overexpression of SCRIB promoted tumor growth. Overexpression of SCRIB stimulated epithelial-to-mesenchymal transition by increasing the expression of N-cadherin, snail, TGF-β1, and smad2/3, and decreasing the expression of E-cadherin; the converse was observed with inhibition of SCRIB. In conclusion, this study presents the nuclear expression of SCRIB as a prognostic marker of ovarian carcinomas and suggests that SCRIB is involved in the progression of ovarian carcinomas by stimulating proliferation and epithelial-to-mesenchymal transition-related invasiveness.
Effects of Increasing Stimulated Area in Spatiotemporally Congruent Unisensory and Multisensory Conditions
Authors: Martolini Chiara , Cappagli Giulia , Signorini Sabrina , Gori Monica
Published: March 2021

Research has shown that the ability to integrate complementary sensory inputs into a unique and coherent percept based on spatiotemporal coincidence can improve perceptual precision, namely multisensory integration. Despite the extensive research on multisensory integration, very little is known about the principal mechanisms responsible for the spatial interaction of multiple sensory stimuli. Furthermore, it is not clear whether the size of spatialized stimulation can affect unisensory and multisensory perception. The present study aims to unravel whether the stimulated area’s increase has a detrimental or beneficial effect on sensory threshold. Sixteen typical adults were asked to discriminate unimodal (visual, auditory, tactile), bimodal (audio-visual, audio-tactile, visuo-tactile) and trimodal (audio-visual-tactile) stimulation produced by one, two, three or four devices positioned on the forearm. Results related to unisensory conditions indicate that the increase of the stimulated area has a detrimental effect on auditory and tactile accuracy and visual reaction times, suggesting that the size of stimulated areas affects these perceptual stimulations. Concerning multisensory stimulation, our findings indicate that integrating auditory and tactile information improves sensory precision only when the stimulation area is augmented to four devices, suggesting that multisensory interaction is occurring for expanded spatial areas.
Neuroimaging Correlates of Cognitive Dysfunction in Adults with Multiple Sclerosis
Authors: Petracca Maria , Pontillo Giuseppe , Moccia Marcello , Carotenuto Antonio , Cocozza Sirio , Lanzillo Roberta , Brunetti Arturo , Brescia Morra Vincenzo
Published: March 2021

Cognitive impairment is a frequent and meaningful symptom in multiple sclerosis (MS), caused by the accrual of brain structural damage only partially counteracted by effective functional reorganization. As both these aspects can be successfully investigated through the application of advanced neuroimaging, here, we offer an up-to-date overview of the latest findings on structural, functional and metabolic correlates of cognitive impairment in adults with MS, focusing on the mechanisms sustaining damage accrual and on the identification of useful imaging markers of cognitive decline.
Diagnosis and Assessment of Deep Pile Cap Foundation of a Tall Building Affected by Internal Expansion Reactions
Authors: Silva Fernando A. N. , Delgado João M. P. Q. , Azevedo António C. , Mahfoud Tahlaiti , Khelidj Abdelhafid , Nascimento Nicole , Lima António G. B.
Published: March 2021

Early deterioration of reinforced concrete foundations has been often reported in recent years. This process is usually characterized by an extensive mapping cracking process on concrete surfaces that results from several types of Internal Swelling Reaction (ISR). In this paper, a real case study of a tall reinforced concrete building with a severe deterioration process installed in its deep foundations is discussed. Laboratory tests were performed in concrete drilled cores extracted from a deep pile cap block 19 years after the beginning of construction. Tests to assess the compressive strength, the static and the dynamic modulus of elasticity, the gas permeability, and electron microscopy scanning to find out the primary mechanism responsible for the deterioration observed during in situ inspections. Chemical alterations of materials were observed in concrete cores, mainly due to Delayed Ettringite Formation (DEF), which significantly affected the integrity and durability of the structure. Dynamic modulus of elasticity showed to be a better indicator of damage induced by ISR in concrete than compressive strength. Procedures to strengthen the deteriorated elements using prestressing proved to be an efficient strategy to recover the structural integrity of pile caps deteriorated due to expansions due to ISR.
Actuation Characteristics of Basic Body Plans for Soft Modular Pneubotics in Architecture
Authors: Andrić Davor , Galić Josip , Šerman Karin
Published: March 2021

The article examines the actuation characteristics of different basic structural schemes—basic body plans—for soft modular pneubotics in architecture are investigated. Eight basic body plans are translated from abstract expressions into their corresponding modular structures and (re)constructed in their physical form using up to 12 soft unit elements in the shape of a cube. Reconstructed basic body plans are then examined through a qualitative analysis of their ability to actuate and change the shape of the structure. Through adaptive manual inflation of an individual element, a group of elements, or all elements at once, motions and transformations are produced and evaluated. The results show that five out of eight basic body plans have higher actuation capacity while three show a less pronounced capacity to change shape. Based on the most pronounced characteristics of the examined basic body plans, design opportunities for potential architectural applications are proposed. These include structures that can self-erect, lift, tilt, bend, change thickness, curvature, etc. What is also shown is that basic body plans could be combined into one complex structural body.
Variability in Breast Cancer Biomarker Assessment and the Effect on Oncological Treatment Decisions: A Nationwide 5-Year Population-Based Study
Authors: Acs Balazs , Fredriksson Irma , Rönnlund Caroline , Hagerling Catharina , Ehinger Anna , Kovács Anikó , Røge Rasmus , Bergh Jonas , Hartman Johan
Published: March 2021

We compared estrogen receptor (ER), progesterone receptor (PR), human epidermal growth-factor receptor 2 (HER2), Ki67, and grade scores among the pathology departments in Sweden. We investigated how ER and HER2 positivity rates affect the distribution of endocrine and HER2-targeted treatments among oncology departments. All breast cancer patients diagnosed between 2013 and 2018 in Sweden were identified in the National Quality Register for Breast Cancer. Cases with data on ER, PR, HER2, Ki67, grade, and treatment were selected (43,261 cases from 29 departments following the guidelines for biomarker testing). The ER positivity rates ranged from 84.2% to 97.6% with 6/29 labs out of the overall confidence intervals (CIs), while PR rates varied between 64.8% and 86.6% with 7/29 labs out of the CIs. HER2 positivity rates ranged from 9.4% to 16.3%, with 3/29 labs out of the overall CIs. Median Ki67 varied between 15% and 30%, where 19/29 labs showed significant intra-laboratory variability. The proportion of grade-II cases varied between 42.9% and 57.1%, and 13/29 labs were outside of the CI. Adjusting for patient characteristics, the proportion of endocrine and anti-HER2 treatments followed the rate of ER and HER2 positivity, illustrating the clinical effect of inter- and intra-laboratory variability. There was limited variability among departments in ER, PR, and HER2 testing. However, even a few outlier pathology labs affected endocrine and HER2-targeted treatment rates in a clinically relevant proportion, suggesting the need for improvement. High variability was found in grading and Ki67 assessment, illustrating the need for the adoption of new technologies in practice.
Relevance of 2′-O-Methylation and Pseudouridylation for the Malignant Melanoma
Authors: Jasinski-Bergner Simon , Blümke Juliane , Wickenhauser Claudia , Seliger Barbara
Published: March 2021

The two RNA modifications 2′-O-methylation and pseudouridylation occur on several RNA species including ribosomal RNAs leading to an increased translation as well as cell proliferation associated with distinct functions. Using malignant melanoma (MM) as a model system the proteins mediating these RNA modifications were for the first time analyzed by different bioinformatics tools and public available databases regarding their expression and histological localization. Next to this, the impact of these RNA-modifying factors on prognostic relevant processes and marker genes of malignant melanoma was investigated and correlated to immune surveillance and evasion strategies. The RNA modifying factors exerted statistically significant positive correlations to the expression of genes involved in cell proliferation and were statistically significant negative correlated to the expression of human leukocyte antigen class I genes as well as of components of the antigen processing machinery in malignant melanoma. Upregulation of the RNA modifying proteins was of prognostic relevance in this tumor disease with a negative impact on the overall survival of melanoma patients. Furthermore, the expression of known oncogenic miRs, which are induced in malignant melanoma, directly correlated to the expression of factors involved in these two RNA modifications.
Expanding the Spectrum of Pancreatic Cancers Responsive to Vesicular Stomatitis Virus-Based Oncolytic Virotherapy: Challenges and Solutions
Authors: Holbrook Molly C. , Goad Dakota W. , Grdzelishvili Valery Z.
Published: March 2021

Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with poor prognosis and a dismal survival rate, expected to become the second leading cause of cancer-related deaths in the United States. Oncolytic virus (OV) is an anticancer approach that utilizes replication-competent viruses to preferentially infect and kill tumor cells. Vesicular stomatitis virus (VSV), one such OV, is already in several phase I clinical trials against different malignancies. VSV-based recombinant viruses are effective OVs against a majority of tested PDAC cell lines. However, some PDAC cell lines are resistant to VSV. Upregulated type I IFN signaling and constitutive expression of a subset of interferon-simulated genes (ISGs) play a major role in such resistance, while other mechanisms, such as inefficient viral attachment and resistance to VSV-mediated apoptosis, also play a role in some PDACs. Several alternative approaches have been shown to break the resistance of PDACs to VSV without compromising VSV oncoselectivity, including (i) combinations of VSV with JAK1/2 inhibitors (such as ruxolitinib); (ii) triple combinations of VSV with ruxolitinib and polycations improving both VSV replication and attachment; (iii) combinations of VSV with chemotherapeutic drugs (such as paclitaxel) arresting cells in the G2/M phase; (iv) arming VSV with p53 transgenes; (v) directed evolution approach producing more effective OVs. The latter study demonstrated impressive long-term genomic stability of complex VSV recombinants encoding large transgenes, supporting further clinical development of VSV as safe therapeutics for PDAC.
Cancer-Associated Fibroblast-Induced Resistance to Chemotherapy and Radiotherapy in Gastrointestinal Cancers
Authors: Ham In-Hye , Lee Dagyeong , Hur Hoon
Published: March 2021

In the past few decades, the role of cancer-associated fibroblasts (CAFs) in resistance to therapies for gastrointestinal (GI) cancers has emerged. Clinical studies focusing on GI cancers have revealed that the high expression of CAF-related molecules within tumors is significantly correlated with unfavorable therapeutic outcomes; however, the exact mechanisms whereby CAFs enhance resistance to chemotherapy and radiotherapy in GI cancers remain unclear. The cells of origin of CAFs in GI cancers include normal resident fibroblasts, mesenchymal stem cells, endothelial cells, pericytes, and even epithelial cells. CAFs accumulated within GI cancers produce cytokines, chemokines, and growth factors involved in resistance to therapies. CAF-derived exosomes can be engaged in stroma-related resistance to treatments, and several non-coding RNAs, such as miR-92a, miR-106b, CCAL, and H19, are present in CAF-derived exosomes and transferred to GI cancer cells. The CAF-induced desmoplastic reaction interferes with drug delivery to GI cancer cells, evoking resistance to chemotherapy. However, due to the heterogeneity of CAFs in GI cancers, identifying the exact mechanism underlying CAF-induced resistance may be difficult. Recent advancements in single-cell “omics” technologies could offer clues for revealing the specific subtypes and biomarkers related to resistance.
The Role of circRNAs in Human Papillomavirus (HPV)-Associated Cancers
Authors: Bonelli Patrizia , Borrelli Antonella , Tuccillo Franca Maria , Buonaguro Franco Maria , Tornesello Maria Lina
Published: March 2021

Circular RNAs (circRNAs) are a new class of “non-coding RNAs” that originate from non-sequential back-splicing of exons and/or introns of precursor messenger RNAs (pre-mRNAs). These molecules are generally produced at low levels in a cell-type-specific manner in mammalian tissues, but due to their circular conformation they are unaffected by the cell mRNA decay machinery. circRNAs can sponge multiple microRNAs or RNA-binding proteins and play a crucial role in the regulation of gene expression and protein translation. Many circRNAs have been shown to be aberrantly expressed in several cancer types, and to sustain specific oncogenic processes. Particularly, in virus-associated malignancies such as human papillomavirus (HPV)-associated anogenital carcinoma and oropharyngeal and oral cancers, circRNAs have been shown to be involved in tumorigenesis and cancer progression, as well as in drug resistance, and some are useful diagnostic and prognostic markers. HPV-derived circRNAs, encompassing the HPV E7 oncogene, have been shown to be expressed and to serve as transcript for synthesis of the E7 oncoprotein, thus reinforcing the virus oncogenic activity in HPV-associated cancers. In this review, we summarize research advances in the biogenesis of cell and viral circRNAs, their features and functions in the pathophysiology of HPV-associated tumors, and their importance as diagnostic, prognostic, and therapeutic targets in anogenital and oropharyngeal and oral cancers.
Carbonic Anhydrase IX Promotes Human Cervical Cancer Cell Motility by Regulating PFKFB4 Expression
Authors: Hsin Min-Chieh , Hsieh Yi-Hsien , Hsiao Yi-Hsuan , Chen Pei-Ni , Wang Po-Hui , Yang Shun-Fa
Published: March 2021

Carbonic anhydrase IX (CAIX) is a hypoxia-induced protein that is highly expressed in numerous human cancers. However, the molecular mechanisms involved in CAIX and human cervical cancer metastasis remain poorly understood. In this study, CAIX overexpression in SiHa cells increased cell migration and epithelial-to-mesenchymal transition (EMT). Silencing CAIX in the Caski cell line decreased the motility of cells and EMT. Furthermore, the RNA-sequencing analysis identified a target gene, bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB4), which is influenced by CAIX overexpression and knockdown. A positive correlation was found between CAIX expression and PFKFB4 levels in the cervical cancer of the TCGA database. Mechanistically, CAIX overexpression activated the phosphorylation of extracellular signal-regulated kinases (ERKs) to induce EMT and promote cell migration. In clinical results, human cervical cancer patients with CAIXhigh/PFKFB4high expression in the late stage had higher rates of lymph node metastasis and the shortest survival time. Our study found that CAIX overexpression increases PFKFB4 expression and EMT, promoting cervical cancer cell migration. CAIX could contribute to cervical cancer cell metastasis and its inhibition could be a cervical cancer treatment strategy.
CD11c-CD8 Spatial Cross Presentation: A Novel Approach to Link Immune Surveillance and Patient Survival in Soft Tissue Sarcoma
Authors: Su Yanhong , Tsagkozis Panagiotis , Papakonstantinou Andri , Tobin Nicholas P. , Gultekin Okan , Malmerfelt Anna , Ingelshed Katrine , Neo Shi Yong , Lundquist Johanna , Chaabane Wiem , Nisancioglu Maya H. , Leiss Lina W. , Östman Arne , Bergh Jonas , Sedimbi Saikiran , Lehti Kaisa , Lundqvist Andreas , Stragliotto Christina L. , Haglund Felix , Ehnman Monika
Published: March 2021

Checkpoint inhibitors are slowly being introduced in the care of specific sarcoma subtypes such as undifferentiated pleomorphic sarcoma, alveolar soft part sarcoma, and angiosarcoma even though formal indication is lacking. Proper biomarkers to unravel potential immune reactivity in the tumor microenvironment are therefore expected to be highly warranted. In this study, intratumoral spatial cross presentation was investigated as a novel concept where immune cell composition in the tumor microenvironment was suggested to act as a proxy for immune surveillance. Double immunohistochemistry revealed a prognostic role of direct spatial interactions between CD11c+ antigen-presenting cells (APCs) and CD8+ cells in contrast to each marker alone in a soft tissue sarcoma (STS) cohort of 177 patients from the Karolinska University Hospital (MFS p = 0.048, OS p = 0.025). The survival benefit was verified in multivariable analysis (MFS p = 0.012, OS p = 0.004). Transcriptomics performed in the TCGA sarcoma cohort confirmed the prognostic value of combining CD11c with CD8 (259 patients, p = 0.005), irrespective of FOXP3 levels and in a CD274 (PD-LI)-rich tumor microenvironment. Altogether, this study presents a histopathological approach to link immune surveillance and patient survival in STS. Notably, spatial cross presentation as a prognostic marker is distinct from therapy response-predictive biomarkers such as immune checkpoint molecules of the PD-L1/PD1 pathway.
Conversion Therapy of Intrahepatic Cholangiocarcinoma Is Associated with Improved Prognosis and Verified by a Case of Patient-Derived Organoid
Authors: Wang Zhiwei , Jin Yun , Guo Yinghao , Tan Zhenhua , Zhang Xiaoxiao , Ye Dan , Yu Yuanquan , Peng Shuyou , Zheng Lei , Li Jiangtao
Published: March 2021

This study was performed to determine the efficacy of conversion therapy in intrahepatic cholangiocarcinoma (IHCC) and explore the feasibility of cancer organoid to direct the conversion therapy of IHCC. Patient data were retrospectively reviewed in this study and cancer organoids were established using tissues obtained from two patients. A total of 42 patients with IHCC received conversion therapy, 9 of whom were downstaged successfully, and another 157 patients were initially resectable. Kaplan–Meier curves showed that the successfully downstaged patients had a significantly improved overall survival compared to those in whom downstaging was unsuccessful (p = 0.017), and had a similar overall survival to that of initially resectable patients (p = 0.965). The IHCC organoid was successfully established from one of two obtained tissues. Routine hematoxylin and eosin staining and immunohistological staining found the organoid retained the histopathological characteristics of the original tissues. Whole exome sequencing results indicated the IHCC organoid retained appropriately 87% of the variants in the original tissue. Gemcitabine and paclitaxel exhibited the strongest inhibitory effects on the cancer organoid as determined using drug screening tests, consistent with the levels of efficacy observed in the patient from whom it was derived. This study indicates that conversion therapy could improve the survival of patients with IHCC despite its low success rate, and it may be directed by cancer organoids though this is merely a proof of feasibility.
Concurrent Cetuximab and Nivolumab as a Second-Line or beyond Treatment of Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results of Phase I/II Study
Authors: Chung Christine H. , Bonomi Marcelo , Steuer Conor E. , Li Jiannong , Bhateja Priyanka , Johnson Matthew , Masannat Jude , Song Feifei , Hernandez-Prera Juan C. , Wenig Bruce M. , Molina Helen , Farinhas Joaquim M. , McMullen Caitlin P. , Wadsworth J. Trad , Patel Krupal B. , Kish Julie A. , Muzaffar Jameel , Kirtane Kedar , Rocco James W. , Schell Michael J. , Saba Nabil F.
Published: March 2021

We hypothesized the combination of cetuximab and nivolumab would improve survival in recurrent and/or metastatic (R/M) HNSCC by providing synergy in cancer control and evaluated toxicities and efficacy of the combination. Effects of sequential administration of cetuximab and anti-Programmed Cell Death-1 checkpoint inhibitors (CPI) were also explored. Patients who failed at least one line of palliative treatment for incurable HNSCC were treated with cetuximab 500 mg/m2 IV on Day (D)-14 as a lead-in followed by cetuximab 500 mg/m2 IV and nivolumab 240 mg/m2 IV on D1 and D15 every 28-D cycle. Electronic health record-derived real-world data (RWD) were used to explore sequential treatment effects of CPI and cetuximab. A total of 45 evaluable patients were analyzed, and 31/45 (69%) patients had prior exposure to either CPI or cetuximab. The only grade 4 treatment-related adverse event was cetuximab infusion reaction in one patient. The 1-year progression-free survival (PFS) and overall survival (OS) rates were 19% and 44%, respectively. Although patients with no prior CPI (23/45, 51%) showed a trend for more favorable PFS relative to patients with prior CPI (22/45, 49%), the improvement in the 1-year OS did not reach the statistical threshold. For evaluation of sequential CPI and cetuximab treatment effects, we selected RWD-cetuximab cohort with 173 patients and RWD-CPI cohort with 658 patients from 6862 R/M HNSCC. Our result suggested patients treated with RWD-cetuximab after RWD-CPI had worse OS compared to no prior RWD-CPI (HR 1.81, 95% CI 1.02–3.16). Our data suggest the combination of cetuximab and nivolumab is well tolerated. Optimal sequencing of cetuximab and CPI may have an impact in prognosis and requires further evaluation.